APPENDIX 2
CHAPTER 1
1. E. This patient likely has HPV-associated oropharynx cancer, which tends to occur at a slightly younger age than smoking- and alcohol-related cancers. He is expected to have a 30% to 50% better prognosis compared to patients with the same site and stage of cancer who have a history of smoking and alcohol abuse. Because of the stage of disease, considerations for cure include definitive chemoradiation, and surgery followed by adjuvant radiation (with concomitant chemotherapy if positive margins or extracapsular spread). He could also be entered into clinical trials evaluating less toxic therapies in this group of patients.
2. E. This is a young patient with little or no smoking history and an oral cancer. Consideration should be given to inheritable abnormalities in DNA repair, such as Fanconi anemia in this patient, especially given the history of leukemia in a sibling. She is at risk for second primaries, particularly in the oral cavity and should be monitored carefully for this. The limited stage of disease and the risk of more primaries in the oral cavity make surgery (in this case, wide local excision or partial glossectomy) the best choice of treatment. Because of the size of the primary tumor, she should have elective neck dissection, because the risk of microscopic nodal involvement is at least 30% even with negative physical examination and CT.
3. C. This is a patient who emigrated from a region where nasopharyngeal carcinoma is endemic. Supraclavicular lymph node-positive nasopharyngeal carcinoma qualifies as locally advanced disease (stage IVB in this case). Nasopharyngeal carcinoma does have a strong association with EBV, unlike other head and neck malignancies, some of which are associated with HPV infection. The recommended treatment for locally advanced nasopharyngeal carcinoma is concurrent cisplatin chemotherapy and radiation with adjuvant chemotherapy with cisplatin and 5-FU; 5-year overall survival near 50% to 60% is seen in modern series. Surgery is rarely indicated for nasopharyngeal carcinoma.
4. D. This is a relatively typical course for a patient receiving concurrent chemoradiation for an oropharyngeal squamous cell carcinoma. Oral candidiasis is not uncommon in this setting, and is treated with antifungal medications at the time it is discovered; prophylactic treatment is not generally indicated. Percutaneous feeding tube removal is not scheduled for a specific time frame, but is only done once a patient can demonstrate a sustained ability to take adequate nutrition orally. A thorough dental evaluation and any procedures, particularly extractions, should be done before initiating chemoradiation. Healing ability will be impaired after chemoradiation, and extractions pose a risk for the development of osteoradionecrosis. Cholinergic agonists can be considered for xerostomia that persists for 1 to 2 years after chemoradiation and is troublesome. For large (>6 cm, N3) adenopathy, a planned neck dissection after definitive chemoradiation is standard at many institutions.
5. E. In locally advanced carcinoma of the larynx, cisplatin and concurrent radiation results in improved larynx preservation and similar survival compared to surgery followed by radiation and compared with chemotherapy followed by radiation or radiation alone. However, adding cetuximab to the combination of cisplatin and radiation has not been shown to improve outcomes over those achieved with just concurrent cisplatin and radiation. Postoperative cisplatin and radiation do improve local control and progression-free survival in patients with nodal extracapsular extension and positive margins. The choice of treatment will depend on the patient’s overall condition, the likelihood that voice can be preserved with nonoperative primary treatment, and the patient’s preference. Radiation alone could be considered for a patient that cannot tolerate combined chemoradiation or surgery followed by combined chemoradiation, but this patient has a good performance status and medical condition, as well as family support.
CHAPTER 2
1. A. The patient with good performance status with newly diagnosed metastatic squamous cell lung cancer would benefit from systemic chemotherapy. Histology of NSCLC is important in treatment selection. Patients with squamous histology have shown showed improved survival with cisplatin/gemcitabine as initial chemotherapy treatment compared with pemetrexed/cisplatin (B is incorrect). Bevacizumab is not recommended in patients who are at increased risk of bleeding: squamous histology, tumor location close to major blood vessels, tumor necrosis, cavitation or pre-existing hemoptysis (C and D are incorrect).
2. E. Randomized trials of screening with chest radiography with or without sputum cytology have shown no reduction in lung-cancer mortality (C and D are incorrect). The National Lung Screening Trial (NLST), a randomized trial compared annual screening by low dose chest CT scanning with chest x-ray for three years found a reduction in lung cancer related mortality and all cause mortality in high-risk patients screened with low dose CT scan. However the high-risk population was defined by NLST as individuals between 55 and 74 years of age with at least 30 pack-year cigarette smoking, and former smokers who had quit within the previous 15 years. There is no data to support lung cancer screening in a person with the risk- profile described in the question (A and B are incorrect).
3. B. The patient has stage IIIB disease (T2N3). Stage IIIB lung cancers are not amenable to curative surgical resection unless they are highly selected (A and C are incorrect). For patients with stage IIIB disease with good performance status, combined modality therapy with chemotherapy and radiation is recommended. Concurrent chemotherapy and radiation is superior to sequential therapy (D is incorrect).
CHAPTER 3
1. A. Small cell carcinomas express TTF1 and epithelial markers (CK7 and keratin) most commonly. Neuroendocrine markers (chromogranin and synaptophysin) are often positive in this disease, but can be negative in 10% of small cell carcinoma cases.
2. B. 10% to 14% of patients with small cell carcinoma have brain metastases at diagnosis. Therefore some form of brain imaging (CT or MRI) is indicated. The role of PET/CT in SCLC is debatable. Mediastinoscopy is an invasive investigation used in the staging of locally advanced non–small cell lung cancer. A bone marrow examination is not routinely recommended in this disease.
3. C. This patient has limited stage disease, as he has disease that can be confined to one radiation field. Limited and extensive stages are part of the Veteran’s Association Classification system. Stage I disease would not involve ipsilateral mediastinal lymph nodes, and stage IV disease would include distant metastases. The TNM staging system is not commonly used in SCLC, but should be encouraged.
This patient’s comorbidities include a history of head trauma 20 years ago which has impaired his short-term memory. He is otherwise fit and independent, with a PS of 1.
4. C. Phase III data support the treatment of LS SCLC with combined chemoradiotherapy. Concurrent chemotherapy has been shown to be superior to sequential therapy. Chemotherapy alone (options A and B) would be more appropriate treatment options for extensive stage disease.
5. C. Prophylactic cranial irradiation has been shown to improve both morbidity and mortality in limited and ES SCLC that demonstrates a response to chemotherapy. However, there is a significant incidence of neurocognitive decline as a long-term toxicity of this treatment. Therefore, in this patient, a discussion would have to take place regarding the pros and cons of this prophylactic treatment in a patient with known neurocognitive impairment.
CHAPTER 4
1. B. Endoscopic ultrasound (EUS) provides the most staging information on a patient with apparently localized esophageal cancer. In the absence of distant metastatic disease, establishing T and N stages is the primary concern, as this will guide his treatment plan. While PET/CT has greater sensitivity for metastatic disease than CT alone, it does not have the same sensitivity for nodal staging.
2. D. SCC is more common in the upper esophagus than the lower, and is more strongly associated with alcohol intake and cigarette smoking. The prognosis for patients with SCC has not been shown to differ from those with adenocarcinoma, but it appears to be a more chemo- and radiosensitive disease. In addition to this, the operative approach for resection of tumors in the upper esophagus can result in more operative morbidity. In light of this, there is a rationale for treating with definitive chemoradiotherapy. Standard chemotherapy protocols in this treatment include cisplatin combined with fluorouracil, or oxaliplatin combined with fluorouracil. Although this approach has not been compared directly to a surgical approach, the outcomes from studies are similar, and the potential operative morbidity is avoided.
3. D. Patients diagnosed with metastatic esophageal adenocarcinoma have been shown to benefit from palliative chemotherapy from a number of studies, and the cisplatin/fluorouracil regimen is one of the most widely studied. Recent advances in understanding the molecular biology of cancer have led to targeted therapies being developed in a number of diseases. The HER2 oncogene is overexpressed in approximately 15% of esophagogastric cancers, and a recent study has shown that the addition of trastuzumab, a monoclonal antibody directed against the HER2 receptor, to cisplatin and fluorouracil chemotherapy results in improved tumor response and survival. VEGFR is implicated in tumor angiogenesis, and studies evaluating antiangiogenic agents such as bevacizumab are ongoing. The EGF receptor is also overexpressed in many esophagogastric cancers, but studies investigating the use of agents targeting this receptor have failed to show a benefit. ERCC1 levels appear to be associated with sensitivity to platinum chemotherapy in esophageal cancer, but their use in clinical practice is currently not recommended outside of a clinical trial.
CHAPTER 5
1. D. This patient has an early-stage primary gastric lymphoma localized to GI tract. Pathology is consistent with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue tumor (MALT lymphoma) which is typically associated with Helicobacter pylori infection. Primary gastric lymphoma accounts for 3% of gastric neoplasms and 10% of lymphomas. H. pylori-induced gastritis leads to the accumulation of CD4+ lymphocytes and mature B cells in the gastric lamina propria resulting in the activation of T cells with B-cell proliferation and lymphoid follicle formation which eventually evolve into a monoclonal lymphoma. The treatment of choice for H. pylori-positive early-stage disease (stagey/IIE) is eradication of H. pylori. This would provide 50% to 80% histologic complete response and long-term remission. However, patients with t(11:18) translocation are typically not responsive to H. pyloritherapy and external beam radiation (RT) is recommended. Local RT (total dose of 25 to 30 Gy) results in high rates of overall and complete responses (100% and 98%, respectively) and 5-year disease-free and overall survival rates of 98% and 77%, respectively. Bone scans are not routinely recommended for MALT lymphoma. Surgery is reserved for patients with obstructive symptoms or bleeding and chemotherapy is reserved for higher grade gastric lymphomas.
2. B. The risk of gastric cancer increases 15 to 20 years after partial gastrectomy surgery with the relative risk of 1.5 to 3. The mechanism is thought to be due to gastric production of N-nitroso carcinogens in the gastric remnant. These compounds are generated from nitrate and nitrite by gastric bacteria, which have overgrown from postoperative hypochlorhydria. In addition, gastric reflux of bile with increased level of bile acids may play a role. The increasing risk of gastric stump cancer with duration of postoperative period suggests a dose–response relationship and supports this mechanism of carcinogenesis. There are no sufficient data to support routine endoscopic surveillance for patients with previous partial gastrectomy for peptic ulcer disease. However, the threshold should be low to endoscopically evaluate upper GI symptoms. If surveillance is considered, it should be initiated 15 to 20 years postgastrectomy. Routine screening for gastric cancer is not recommended in the United States, where the overall gastric cancer burden is low. Periodic upper endoscopy can be offered to patients who are considered to be at increased risk; however, the benefits and risks are unclear.
3. C. The patient has metastatic gastric adenocarcinoma and the goal of treatment is palliation. He has a reasonable performance status with no major comorbidities. Therefore, the standard of care is to screen for HER2 expression status by immunohistochemistry (IHC) and gene amplification by florescence in situ hybridization (FISH) if IHC is equivocal. If HER2 is positive, chemotherapy with trastuzumab is recommended as a first-line treatment. Data from the randomized phase III ToGA study showed that the addition of the monoclonal antibody against HER2 (trastuzumab) to cisplatin/fluoropyrimidine provided significantly higher objective response rates (47% vs. 35%) and improved median overall survival compared to chemotherapy alone (13.8 vs. 11.1 months; p= 0.0046). Since EGD did not show active bleeding and the patient did not have uncontrolled pain from the tumor, RT is not indicated at this point. There is no role for concurrent or sequential chemoradiation for metastatic gastric cancer. Bevacizumab with chemotherapy in metastatic gastric cancer did not show a survival advantage in the phase III trial and should not be offered outside of a clinical trial, particularly given the patient’s recent bleeding event.
4. D. The adjuvant treatment options for R0 resected gastric tumor are chemoradiation and potentially chemotherapy if D2 resection is achieved. At least 16 lymph nodes need to be examined for adequate sampling. D2 resection involves removal of extensive lymph nodes including perigastric, hepatic, left gastric, celiac, and splenic arteries; splenic hilar nodes; +/– splenectomy. D2 resection is not routinely performed in the United States and only performed in the experienced centers because of the significant postoperative morbidity and mortality. Subjecting the patient to a repeat surgical intervention is not justified given the negative margins and adequate node sampling. The INT-0116 trial demonstrated a survival benefit with adjuvant chemoradiation (5-FU/leucovorin before, during, and after radiation therapy) compared to surgery alone in patients who received less than a D2 resection. Oral fluropyrimidine (S-1) for 1 year adjuvant after D2 resection showed improvement in overall survival and relapse-free survival and is approved for adjuvant therapy in Japan. S-1 is not commercially available in the United States. Perioperative (pre- and postoperative) polychemotherapy using ECF (epirubicin, cisplatin, and infusional 5-FU) is an acceptable standard of care, but the patient did not receive preoperative chemotherapy. Therefore, chemoRT would be the best option to improve relapse-free and overall survival.
5. C. The patient has a resectable gastric cancer, likely T2N1-2M0 disease. A randomized phase III (MAGIC) trial showed that perioperative chemotherapy with ECF (epirubicin, cisplatin, 5FU) given for 3 months before and after surgery resulted in significantly improved 5-year progression-free survival (HR 0.66; 95% CI 0.53 to 0.81; p < 0.001) and overall survival (36% vs. 23%) compared to surgery alone. After perioperative polychemotherapy, the resected tumors were significantly smaller and less advanced with similar postoperative complications or deaths between two arms. Neoadjuvant concurrent chemoRT is more commonly used for esophageal, GEJ, and gastric cardia cancers than for potentially resectable noncardia gastric adenocarcinomas. There are no randomized trials addressing the benefit of preoperative chemoRT in noncardia gastric cancer. No survival benefit was observed with adjuvant radiation alone after surgery. Preoperative chemotherapy in combination with bevacizumab is still under investigation and should not be used outside the context of a clinical trial.
CHAPTER 6
1. B. This patient has been diagnosed with a stage I (T1a N0 M0) well-differentiated gallbladder adenocarcinoma, which was incidentally found postsurgical resection. Among patients with T1a lesions with negative tumor margins, survival rates approach 100% with simple cholecystectomy alone. These patients may be observed postcholecystectomy. Extended cholecystectomy is recommended for patients with T1b or greater lesions. If the malignancy was an incidental finding similar to the patient above, preoperative restaging should be considered first to rule out metastatic disease. Chemotherapy is recommended in patients with T1b or greater disease with an unresectable lesion. If chemotherapy were the preferred option, gemcitabine and cisplatin combination therapy would be the recommended route. Hospice discussion is not relevant in this patient population as survival rates approach 100% with cholecystectomy for T1a lesions.
2. C. The patient discussed above appears to have a stage III (T4 N1 MO) poorly differentiated extrahepatic cholangiocarcinoma. Surgical resection (R0) remains the only possibility for cure; however, due to tumor involvement of the blood vessels, the surgical team determined this patient’s tumor to be unresectable. In patients with unresectable disease, combination chemotherapy with gemcitabine and cisplatin is the current standard of care for upfront therapy. A 2010 New England Journal of Medicine article demonstrated that gemcitabine and cisplatin in combination improved overall survival and progression-free survival compared to gemcitabine alone. Chemoradiation can be used as first-line treatment in patients with locally advanced disease; however, chemotherapy of choice would be a fluoropyrimidine instead of gemcitabine. Surveillance would not be an option for this patient due to the aggressive nature of this disease.
CHAPTER 7
1. D. This patient has advanced cirrhosis and a new liver lesion that is confirmed as HCC based on radiographic and biochemical criteria. According to the American Association for the Study of Liver Disease (AASLD) guidelines, no tissue confirmation of HCC is required when these criteria are met. In fact, percutaneous biopsy has been linked with the potential for cancer seeding along the biopsy track, which could limit the patient’s eligibility for liver transplant. PET scanning is generally not helpful in the workup and management of localized HCC. Up to half of HCC lesions are not FDG-avid on PET scan, so the modality is not indicated, except in the workup of potential metastatic sites. Liver resection and liver transplant are both considered potentially curative treatment modalities for a patient with a solitary HCC, but in this case, the advanced underlying cirrhosis suggested by thrombocytopenia, portal hypertension, and decreased synthetic function (low albumin) means that resection is contraindicated. The patient would be at extremely high risk for perioperative mortality and would likely progress to fulminant liver failure shortly after a major hepatectomy. Liver transplant is the most appropriate treatment plan in this case, pending formal review by a multidisciplinary group and the timely availability of a donor organ.
2. B. This patient has metastatic HCC, so there is no indication for curative intent therapy. There is no role for debulking surgery in patients with HCC, as it will not impact survival. Liver transplant is not indicated here, as the tumor burden is clearly outside the Milano/Mazzaferro criteria, with the presence of extrahepatic disease (we do not have details on the extent of the liver masses, only that they are multifocal). Since no transplant is on offer, there is no indication for bridging therapy with TACE. He has BCLC stage C disease, for which TACE is not recommended as primary therapy, in this case due to the significant extrahepatic disease burden. The fact that the patient has retained a reasonable performance status of ECOG 1 indicates that he is still a candidate for some form of therapy—there are options to consider before hospice referral. Sorafenib is the only approved systemic agent for the first-line treatment of advanced HCC and is the appropriate choice in this case. Therapy is palliative in nature, but improved PFS has been shown in a number of randomized clinical trials comparing sorafenib with best supportive care. An alternative option here may be to consider enrolling on a first-line clinical trial, if one were available at this tertiary care center.
3. B. This woman has developed HCC arising from NAFLD (nonalcoholic fatty liver disease) and has BCLC stage B disease (intermediate stage). The extent of liver disease in this case means that surgical resection is not an option, but the typical recommendation would be for some form of liver-directed therapy. There are no obvious contraindications to TACE in this scenario. A number of meta-analyses have suggested PFS and OS benefit from intra-arterial therapy, and most centers would offer this patient TACE or TAE (bland embolization, with no chemotherapeutic component). While sorafenib is an approved agent for advanced HCC, not amenable to curative intent therapy, the PFS benefit is not as great as that seen with TACE/TAE in this clinical setting (BCLC stage B). Similarly, a chemotherapy-based clinical trial would not be appropriate to offer a patient who is a candidate for liver-directed therapy, as in this case.
4. C. This patient underwent appropriate up-front therapy for solitary HCC in a noncirrhotic liver. He was not a candidate for liver transplant, as his tumor was greater than 5 cm in maximal diameter, but he was an excellent candidate for surgical resection due to his preserved liver function. Despite this good surgical outcome, he still has a high risk of tumor recurrence, especially in light of the vascular invasion seen on the pathology specimen. However, there is no evidence to suggest that adjuvant therapy, either radiation or systemic chemotherapy, will impact this risk of recurrence in patients with HCC. As such, the recommendation here is for interval surveillance with imaging and laboratory data (AFP). The most common site for recurrence remains the liver remnant, and other potential sites include lymph nodes, lung, adrenal gland, and bone. Treatment options at the time of recurrence will depend on the extent and location of that recurrence. Liver transplant workup is not appropriate in this case, as the original tumor was clearly outside the Milano/Mazzaferro criteria.
CHAPTER 8
1. C. This patient’s presentation, symptoms, and complete blood count are consistent with iron deficiency anemia (IDA). Although she reports possible hemorrhoidal bleeding, a microcytic anemia in a nonmenstruating female should raise concern for occult blood loss from the gastrointestinal tract (large polyp, cancer, etc.). Given her history of bright red blood per rectum and evidence of IDA, colonoscopy is the next best test to order. FOBT or FIT tests are excellent screening tests for a colorectal malignancy, but should only be used in a screening, not in a diagnostic setting. A PET scan is not indicated at this time, even if a colorectal malignancy is confirmed, as a more appropriate imaging study in that setting would include a contrasted CT scan. In addition, primary colon cancers or large polyps can be difficult to identify with PET scan due to the normal biologic uptake of fluorodeoxyglucose by the surrounding bowel. Although mammograms are age-appropriate screening tests for breast cancer, they are not a priority currently for this scenario.
2. E. Hereditary nonpolyposis colon cancer (HNPCC or Lynch syndrome) is an autosomal dominant genetic condition which increases the risk of cancers of the GI tract including colon, pancreatic, gastric, hepatobiliary, and small bowel, as well as ovary, endometrium, and genitourinary tract. It is caused by a germline mutation occurring in the DNA mismatch–repair genes (e.g., hMSH2, hMLH1, hPMS1, and hPMS2), which can be assayed directly or indirectly reflected by MSI. The inheritance pattern follows the Amsterdam criteria including three or more relatives with an associated cancer, two or more successive generations affected, one or more relatives diagnosed before the age of 50 years, and one should be a first-degree relative of the other two. It commonly presents with poorly differentiated tumors or mucinous histology in the right side of the colon. The APC gene is involved in FAP, which presents with hundreds of colonic polyps. The BRCA1 gene is most commonly involved in breast and ovarian carcinomas. The STK11 tumor suppressor gene is mutated in Peutz–Jeghers Syndrome. The CHD1 gene encodes for the E-cadherin protein with loss resulting in hereditary diffuse gastric and lobular breast cancers.
3. C. This patient has a completely resected stage IIIB (pT2N2aM0) sigmoid colon cancer. Adjuvant chemotherapy for 6 months is the standard of care treatment for stage III colon cancers to improve OS. There are multiple acceptable regimens available, all of which include a fluoropyrimidine (e.g., 5-FU or capecitabine) with or without oxaliplatin. There is no role for irinotecan or biologic agents in the adjuvant setting. Additional resection is not warranted given the specimen had negative margins, and at least 12 lymph nodes were removed indicating adequate sampling. Radiation therapy has a limited role and is not recommended routinely in colon cancer due to bowel mobility, risk of small bowel toxicity, and risk of damage to anastomotic sites.
4. B. Bevacizumab is a monoclonal antibody that inhibits VEGFA. It is approved in combination with fluoropyrimidine-based therapy as first-line treatment of metastatic colon cancer and has been shown to improve response rates and OS. Cetuximab and pmab are both monoclonal antibodies that target EGFR and are effective only in patients with metastatic CRC harboring wild-type K-ras. Cetuximab is approved for use in disease refractory to treatment with irinotecan and for first-line treatment in combination with FOLFIRI chemotherapy. Panitumumab is approved as a single agent to improve progression-free survival in heavily pretreated patients. Regorafenib is the first and currently only small molecule tyrosine multikinase inhibitor approved for heavily pretreated patients with advanced CRC. Rituximab is an anti-CD20 monoclonal antibody highly effective in B-cell neoplasms and autoimmune conditions. It does not have a role in colon cancer.
5. D. Her rectal cancer clinical stage is IIIB (cT2N2aM0). Based on randomized controlled trials, neoadjuvant chemotherapy concurrent with radiation (chemoRT), followed by surgical resection and additional 4 months of postoperative systemic chemotherapy is considered the standard of care for patients with stage II and III rectal cancers. The German Rectal Cancer Group compared neoadjuvant chemoRT followed by adjuvant systemic chemotherapy to initial surgical resection followed by adjuvant chemoRT and systemic chemotherapy. Patients in the neoadjuvant group had significantly less local recurrence rates, better tolerance of the therapy, and no increased surgical complications. However, OS was not impacted. This sequence represents the standard of care for patients with stage II and III rectal cancers who are candidates for trimodality therapy. Transanal mucosal resections are not an appropriate surgical procedure for this patient who most likely will require a low anterior resection with total mesorectal excision.
CHAPTER 9
1. C. Adjuvant chemotherapy has been shown by the CONKO and ESPAC studies to result in a small survival benefit compared to control. While lymph node positivity does have prognostic relevance, it does not influence the decision about whether to administer adjuvant therapy, perhaps because the vast majority of node-negative patients will still experience disease recurrence.
2. D. While Folfirinox has become the new standard of care for this situation there may be other factors (e.g., comorbid conditions or contraindications such as biliary obstruction) which may preclude this intensive regimen. Single-agent gemcitabine is defensible based on the relative lack of randomized studies in support of combination treatment. Erlotinib is also an FDA-approved option for this indication.
3. D. Ca-199 is nonspecific and insensitive for the detection of early onset disease. Therefore it has no value as a screening test. Jaundice itself can result in Ca-199 elevations; therefore, if it is to be used to follow therapy (as an adjunct to, rather than in place of, imaging), the baseline measurement should be poststent placement. Ca-199 has been shown to have prognostic value in both the pre- and postoperative settings.
CHAPTER 10
1. B. The updated RTOG shows that concurrent 5-FU + MMC with RT was superior to neoadjuvant CDDP + 5-FU followed by concurrent CDDP + 5-FU with RT in terms of overall survival (78% vs. 70%) and DFS (57.8% vs. 67.8%). Thus, answer “A” cannot be correct. The ACT II trial demonstrated that MMC/5-FU + RT was equivalent to concurrent 5-FU + MMC with RT + maintenance chemotherapy. Maintenance therapy did not impact overall survival or DFS. Thus, answer “C” would not be correct. Finally, answer “D” is not correct as 5-FU/MMC + concurrent RT was superior to 5-FU + concurrent RT as demonstrated in RTOG 87-04 in terms of DFS, CFS, and local-regional control.
2. C. The National Cancer Database has provided 5-year survival of anal canal carcinoma patients by stage for both squamous and nonsquamous histologies. The database is based on cases diagnosed from 1998 to 1999 and included 3,598 cases.
For squamous cell histology, the 5-year survival is as follows: stage I = 71.4%, stage II = 63.5%, stage IIIA = 48.1%, stage IIIB = 43.2%, and stage IV = 20.9%. For nonsquamous histology, the 5-year survival is as follows: stage I = 59.1%, stage II = 52.9%, stage IIIA = 37.7%, stage IIIB = 24.4%, and stage IV = 7.4%. The prognosis shows a statistically worst survival stage for stage between squamous and nonsquamous cell histologies, except for stage IIIA.
3. C. Early reports indicated that some HIV-positive patients were receiving less than optimal therapy due to concerns for treatment toxicity. However, patients with a CD4 count of ≥200 can have excellent control of their disease with acceptable morbidity. Those with CD4 counts of <200, however, may require a modification in their treatment regimen such as omission of MMC or a reduction in the RT field and/or dose. UCSF analyzed 17 HIV-positive patients and documented CD4 counts. All nine patients with a CD4 count ≥200 had control of their disease. Four patients did require a treatment break of 2 weeks, but no hospitalizations occurred. Among the eight patients with CD4 counts <200, four experienced lowered blood counts, intractable diarrhea, or moist desquamation. Four of eight ultimately required colostomies for either treatment-related toxicity or for salvage for disease. Disease, though, was controlled in seven of eight patients. Thus, based on the UCSF experience with HIV-positive patients, one should consider modifying the treatment regimen particularly if CD4 counts are less than 200. Thus, for this patient with a CD4 count >200, he should receive full dose chemotherapy with 5-FU and MMC and full dose radiation therapy.
4. C. After patients have completed definitive chemoradiation therapy, patients should be followed up clinically in 8 to 12 weeks after therapy. Cummings demonstrated that mean time for tumor regression was 3 months but regression of a tumor could occur up to 12 months. Thus, if there is persistent disease at 8 to 12 weeks, patients should be followed up closely (every month) to document regression. As long as there is documented regression on serial examinations, patients may continue to be monitored. However, at any point if there is progression, then biopsy followed by salvage APR should be considered. Thus, answer “C” is correct and “A” is incorrect and immediate APR should not be considered. Answer “B” also is incorrect as chemotherapy alone has not been shown of benefit in this situation. Finally, although option “D” could be considered, as salvage radiation has been attempted, typically salvage APR would be considered in the future if the patient later progresses on future serial examination.
5. B. Toxic deaths from CMT have ranged from 0% to 5%. In the UKCCCR study, 6/116 (2%) experienced toxic death, mostly due to septicemia. The EORTC trial reported on 1 toxic death out of 110 patients. In RTOG 8704 study, four patients (3%) experienced death in the MMC arm. More recently, there were no reported toxic deaths in both RTOG 98-11 and ACT II trials. The ACCORD 03 trial, a four-arm randomized trial, showed similar toxic deaths across all four arms (A = 1 [1%], B = 2 [2.6%], C = 3 [3%], D = 1 [1%]).
CHAPTER 11
1. E. Adjuvant imatinib for 3 years. The size and mitotic rate of this patient’s tumor fall in the high risk of recurrence category warranting 3 years of adjuvant therapy with imatinib based on the phase III clinical trial reported by Joensuu et al. in 2012. There is no role for adjuvant therapy with either radiation therapy or cytotoxic chemotherapy in GIST.
2. A. Increase the dose of imatinib to 400 mg twice daily. Patients with exon 9 mutations have a higher likelihood of resistance to imatinib. The Meta-GIST trial showed improved progression-free survival with the 800 mg daily dose of imatinib for patients with exon 9 mutations. The current recommendation is to increase the dose of imatinib to 800 mg daily if patients are not responding to the standard initial dose of 400 mg daily.
3. E. Systemic therapy with a fluoropyrimidine and oxaliplatin. Chemotherapy for metastatic SBA improves survival over no treatment. The most promising survival data from multiple retrospective studies involves the combination of a fluoropyrimidine with oxaliplatin in the first-line treatment for patients with metastatic SBA. There is no clear role for radiation therapy to liver lesions located in bilateral liver lobes.
CHAPTER 12
1. E. The patient is an unaffected family member with a strong family history. Her family history includes breast cancer, ovarian cancer, and pancreatic cancer. She has a high risk of having a BRCA2 mutation. The next step is to do genetic counseling and testing. Bilateral mastectomy and prophylactic salpingo-oophorectomy are not recommended for every patient with a mutation. It should be decided case by case. CT/PET scan is not studied for screening in high-risk patients and it should not be used. Breast MRI and pelvic ultrasound can be considered, if she has a mutation. The role of serum markers in mutation carriers is debated. CA-125 may be used in addition to the vaginal ultrasound in patients with a BRCA mutation.
2. C. This patient will meet the inclusion criteria for ACOSOG Z 0011. In that study, patients with sentinel lymph node-positive (one to two nodes) disease were randomized between complete axillary node dissections and no further axillary surgery; no further axillary surgery arm had similar PFS and OS compared to complete axillary node dissection. Lymph node positive, by itself, is not a criterion for receiving chemotherapy. She could be in the luminal type A breast cancer and may very well be treated with endocrine therapy only. The SWOG study showed that Oncotype can be done in patients with node-positive disease also.
3. B. She has a IIB cancer and in the conventional sense she should receive chemotherapy. But many luminal type A patients (ER/PR positive and Ki-67 less than 14 as per St. Galen criteria) can be treated with only endocrine therapy, and not chemotherapy. She does not meet the criteria for radiation therapy after mastectomy (tumor more than 5 cm, four or more lymph nodes or other poor prognostic features). Even patients older than 65 will benefit from chemotherapy, if that is indicated.
4. D. Ado-trastuzumab emtansine is an antibody−drug conjugate composed of trastuzumab linked to a highly potent cytotoxic derivative of maytansine (DM1) by a stable linker. DM1 is a microtubule inhibitor. Ado-trastuzumab emtansine has been found to be active in trastuzumab- and lapatinib-resistant metastatic breast cancer, as well as in trastuzumab-naïve tumors. Results of the phase 3 EMILIA trial that compared trastuzumab emtansine with capecitabine + lapatinib in advanced HER2-positive breast cancer showed a substantial improvement in progression-free survival (PFS) and OS with the conjugate. This patient does not meet the criteria for the CLEOPATRA study and pertuzumab is approved in first-line metastatic breast cancer.
5. C. About 10% of patients receiving everolimus can develop pneumonitis. In a majority of patients, after ruling out an infectious cause, the patient can be managed with corticosteroid, discontinuation of the therapy until it is resolved. In grade 1 to 3 pneumonitis, everolimus can be restarted after appropriate supportive therapy and once the symptoms have resolved to grade 1 with a dose reduction.
CHAPTER 13
1. A. Cytoreductive nephrectomy is most likely to benefit patients who are good surgical candidates as well as candidates for postnephrectomy systemic therapy, such as those with a good performance status, a relatively slow rate of disease progression, and those with relatively low metastatic burden (as demonstrated in a randomized phase 3 study where interferon was offered postnephrectomy). Patients described in B to D are less likely to benefit from this approach as they do not satisfy one or more of the above criteria.
2. D. Complete responses are seen in 7% to 9% of metastatic clear cell RCC patients receiving high-dose IL-2, with the majority of these remaining disease-free for long periods. The efficacy of IL-2 has not been adequately evaluated in patients with non–clear cell histologies and the use of this agent is largely restricted to clear cell RCC patients. There are no randomized phase 3 studies demonstrating survival benefit with IL-2.
3. B. This patient appears to have “standard” risk metachronous metastatic clear cell RCC. Sunitinib has been shown to prolong progression-free survival compared to IFN-α in a randomized phase 3 trial in patients with previously untreated metastatic clear cell RCC. Axitinib and everolimus have both shown clinical benefit in previously treated patients, while temsirolimus is associated with improved OS compared to IFN-α in “poor risk” patients. While high-dose IL-2 may be a reasonable option for this patient, there are no randomized studies demonstrating benefit for this agent over other available therapies.
4. D. There are no standard systemic therapy options of proven benefit at this time for most patients with advanced RCC patients with non–clear cell histologies. While foretinib, a MET inhibitor, as well as inhibitors of the VEGF and mTOR pathways have activity in small subsets of these patients, their utility in the majority of patients with non–clear cell RCC remains to be established.
5. C. A renal mass in a young man with skin findings suggestive of cutaneous leiomyomata, a family history of kidney cancer, and uterine fibroids should arouse suspicion for hereditary leiomyomatosis and renal cell cancer (HLRCC), a familial kidney cancer syndrome characterized by germ-line mutations in the gene encoding the Krebs cycle enzyme, FH.
CHAPTER 14
1. B. The indications of adjuvant radiation after RP include T3 disease (such as extracapsular extension or seminal vesicle involvement) or positive surgical margins. The finding of lymph node-positive disease during prostatectomy is not an indication for radiotherapy, although limited data support the use of ADT in such patients.
2. D. This patient has a rising PSA after a 12-month response to bicalutamide, an ARA. ARAs including flutamide, nilutamide, and bicalutamide all can have agonistic properties over time in 10% to 15% of patients who respond to such treatments. Therefore, in an asymptomatic patient, the best approach is to withdraw the bicalutamide and reevaluate the patient in 6 weeks (or 4 weeks if the patient was on flutamide or nilutamide). There is no indication for chemotherapy or abiraterone in a patient without confirmed metastatic disease. While imaging is not inappropriate in this patient, a bone scan with a CT scan would be more appropriate than an MRI alone. Nonetheless, given the lack of symptoms, this could be done after the evaluation for a withdrawal response. Unless there is concern that the patient does not have castrate levels of testosterone, switching from a GnRH agonist to a GnRH agonist will provide no benefit.
3. D. Clinical trials have demonstrated a survival benefit for sipuleucel-T in patients with metastatic, CRPC with minimal symptoms. There is no current indication for patients with castration-sensitive disease.
4. B. A phase 3 study in non-mCRPC patients with high risk of bone metastasis demonstrated that denosumab can delay bone metastasis in this population. It is important to note that this is not an FDA indication for this treatment; however, the study demonstrates the growing ability to target CaP in the bone microenvironment. Zoledronic acid has been shown to delay skeletal-related events in castration-resistant, metastatic disease. Calcium/vitamin D is indicated in all men with castration levels of testosterone to delay osteopenia. Cabozantinib has shown promising preliminary results in resolving bone metastasis and is currently in phase 3 trials in CaP.
5. C. Although new therapies have increased options for treating metastatic CaP, docetaxel with prednisone remains the most appropriate therapies for moderate or higher levels of symptoms related to metastatic, CRPC. There are no definitive data to support the use of docetaxel with radiation or surgery in newly diagnosed CaP.
CHAPTER 15
1. D. Radical cystectomy and pelvic lymphadenectomy are the “gold standard” therapeutic modalities for locoregional, muscle-invasive bladder cancer. In men, this includes removal of the prostate gland, seminal vesicles, and proximal urethra. In women, it includes removal of the urethra, uterus, fallopian tubes, anterior vaginal wall, and surrounding fascia. Almost one of four patients have unsuspected nodal metastases (24%) found with pelvic lymph node dissection, despite negative preoperative staging. This extensive surgery ensures a low rate of pelvic recurrence even in lymph node-positive patients and 25% of these lymph node-positive patients experienced long-term survival. A proper lymph node dissection is important. In addition, the number of lymph nodes examined in cystectomy specimens has been reported to impact patient outcome.
2. D. Bladder cancer is common around the world. Cigarette smoking is thought to account for more than half of all cases of TCCs of the bladder in the United States. There is a marked male predominance and it is predominantly a neoplasm that occurs in patients aged >50 years. In addition, numerous specific chemicals have been identified as bladder carcinogens in humans, some relating to specific occupational exposures to arylamines (found in cigarette smoke, permanent hair dyes, and other environmental sources). Treatment with cytostatic drugs, especially cyclophosphamide, is associated with increased risk of bladder cancer, as is treatment with radiotherapy. In developing countries, especially in the Middle East and parts of Africa (Nile River Valley), bladder cancer occurs most commonly secondary to schistosomiasis, which is frequently associated with the development of squamous cell carcinoma similar to that of other chronic inflammatory processes of the lower urinary tract. Arsenic has been indicated as a bladder carcinogen in Argentina, Chile, and Taiwan.
3. A. The presence of carcinoma in situ is an indication for intravesical BCG therapy. It is important to note that there is muscle present in the biopsy; this allows the correct assessment of the invasiveness of the tumor. Cystectomy would be indicated for recurrent or persistent disease only. Other indications for the use of intravesical BCG include treatment of the residual non–muscle-invasive papillary tumor, and prophylaxis against recurrence of superficial tumors and against progression after resection of a tumor.
4. D. The most common presenting symptom for patients with bladder cancer is hematuria. Patients may also have urinary symptoms such as frequency and discomfort. In the absence of a urinary tract infection, patients over 50 years of age should be evaluated with cystoscopy and urine cytology. A CT scan of the abdomen and pelvis should be done only if the lesions seen on cystoscopy appear high grade, or suggestive of muscle invasion. CT of the chest is premature in this patient with hematuria.
5. B. Neoadjuvant chemotherapy with cisplatin combination chemotherapy improves survival in patients with muscle-invasive bladder cancer and good renal function. However, a large proportion of patients are ineligible for cisplatin chemotherapy based on renal function or functional status. There are limited data as to the efficacy and survival benefit of non–cisplatin-based regimens in the neoadjuvant or adjuvant setting. Therefore, patients with muscle-invasive bladder cancer who are intolerant/ ineligible for cisplatin-based chemotherapy should proceed to cystectomy.
CHAPTER 16
1. B. This is a nonseminoma germ cell tumor in the anterior mediastinum because of the elevated HCG and AFP. Patients with Klinefelter syndrome have an increased risk of developing mediastinal germ cell tumor. This is not the case with Down syndrome. Seminoma is unlikely because of the elevated AFP. Primary mediastinal B-cell lymphoma and thymoma are both unlikely because of the elevated tumor markers.
2. C. Elevated levels of HCG without AFP are suggestive of a seminoma. CD30 and cytokeratin are positive in embryonal carcinoma. NANOG and OCT4 may be expressed in seminoma, but the expression of SOX2 is indicative of a nonseminomatous (embryonal) component. C117 (c-kit) is expressed by seminoma but not by embryonal carcinoma or yolk sac tumor.
3. E. This is an intermediate-risk stage III seminoma. Surveillance is recommended for lymph node mass that is ≤3 cm after chemotherapy.
4. E. Bleomycin is not recommended for patients with signs of pulmonary compromise especially if the DLCO has declined by more than 40% from baseline. Hence, BEP is not acceptable. Four cycles of EP is not sufficient for this case of poor risk nonseminoma and carboplatin-based regimen are not as effective as ciplatin-containing regimen. VeIP is a salvage therapy for relapsed or refractory disease.
5. C. Based on the International Consensus Risk Classification, the 5-year OS for poor risk nonseminoma is 48%.
6. B. All patients should be counseled on sperm banking prior to therapy for testicular germ cell tumor.
7. C. Increased copy number of 12p is seen in nearly all cases of testicular germ cell tumor. It may be one or more copies of i(12p) or tandem duplication of 12p.
8. B. Residual mass with yolk sac element requires two additional cycles of chemotherapy. More than two cycles will likely be an overtreatment. Surveillance is not an adequate option.
CHAPTER 17
1. A. After initially achieving a clinical complete remission as a result of management of her advanced ovarian carcinoma with the minimum standard of care, this patient presents with a rising CA-125 (based on three successive rising CA-125 with the last value above 100) and no other evidence of disease. She is asymptomatic. This situation was studied in a large phase 3 trial in Europe. Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomized trial; Rustin et al. (2010). There was no difference in survival (HR = 1.00) and thus no benefit from earlier initiation of therapy for only a rising CA-125. Furthermore, deterioration of quality of life began a median of 3 months earlier in the early treatment group. These data support not treating for only a rising CA-125. When this patient ultimately develops tissue evidence of recurrence, she should be classified as potentially platinum sensitive due to her treatment-free interval of >18 months, substantially greater than the 6 months required for definition, and treated with a carboplatin-based doublet. She should be evaluated for secondary surgical cytoreduction, which should be done if the surgeon feels that he/she can remove all gross disease. This is a controversial conclusion in the United States, where many use the Rustin CA-125 criteria (at least doubled and over 100) as an indicator for therapy, even when evaluable disease is observed on examination and/or imaging.
2. D. RRSO has been shown to reduce risk of ovarian/tubal/peritoneal cancer to 5% and is recommended for all women who are at high risk and who have completed childbearing. Optimal time for surgery is upon completion of child-bearing and 10 years prior to the youngest age at cancer presentation in the family. Screening with transvaginal sonography, CA-125, or pelvic examination has not been shown to reduce ovarian carcinoma mortality or lead to early detection in the general population or the high-risk population. It is, however, recommended for women who have not completed childbearing or who do not wish RRSO. Oral contraceptives can reduce the risk of ovarian cancer by as much as 50% in the general population; they have not been conclusively shown to be safe and effective in the mutation-carrier population. Oral contraceptives also have a 1.6 RR for the risk of breast cancer.
3. B. This patient has stage IIIC optimally debulked ovarian carcinoma and should receive chemotherapy following surgery. According to the consensus of all cooperative groups worldwide dealing with ovarian carcinoma, the minimum treatment of choice is six cycles of paclitaxel plus carboplatin. The National Cancer Institute issued a clinical alert in January of 2006 declaring IP therapy to be the treatment of patients with small-volume residual disease (optimal cytoreduction), but the alert also noted that there was no clear benefit of any one IP regimen because of toxicity (GOG 172). More recently, the GOG 218 showed that the addition of bevacizumab to paclitaxel/carboplatin plus bevacizumab maintenance produces a superior progression-free survival with the data too early to determine whether there will be a survival difference, but this is not for optimally debulked ovarian cancer patients and bevacizumab is not FDA approved for any ovarian cancer indication in the United States.
CHAPTER 18
1. C. Hormonal therapy is preferred as first-line intervention for recurrent or metastatic endometrial cancer due to its lower toxicity profile and response rate similar to chemotherapy. Hormonal therapy produces responses in 15% to 30% of patients and is associated with survival twice as long as in nonresponders. On average, responses last for 1 year. TAM is reserved for second-line hormone therapy. Currently, NCCN guidelines recommend the use of bevacizumab only after progression on prior cytotoxic chemotherapy. External beam radiotherapy is used in the metastatic setting if it can be directed to a particular tumor site. In this case the patient has bilateral lung nodules so systemic therapy is preferred.
2. D. There is currently insufficient evidence to recommend routine surveillance with MRI, ultrasound or hysteroscopy for detection of endometrial cancer in patients on TAM. Women taking TAM should have a gynecologic evaluation according to the same guidelines for women not taking TAM. The presence of symptoms such as abnormal vaginal bleeding should trigger prompt investigation.
3. E. The patient’s strong family history of colon cancer diagnosed in family members at a young age is strongly suggestive of HNPCC also known as Lynch syndrome. Lynch syndrome is caused by an autosomal dominant disorder characterized by a germline mutation in mismatch repair genes and is associated with tumors exhibiting microsatellite instability. Lynch syndrome is associated with increased risk of cancers of the colon, endometrium, ovary, stomach, small intestine, hepatobiliary tract, urinary tract, brain, and skin. The ACS recommends that women with HNPCC undergo annual endometrial biopsy after age 35, since the lifetime risk of endometrial cancer in patients with HNPCC is 40% to 60%. Prophylactic hysterectomy and BSO is a risk-reducing option that should be considered by women who have completed childbearing, since the lifetime risk of ovarian cancer in patients with Lynch syndrome is 10% to 20%.
4. A. In stage III and IV metastatic papillary serous endometrial cancer referral for clinical trials is strongly recommended as there is no FDA-approved standard of care. A reasonable first-line treatment is chemotherapy, for example, with a triplet regimen such as cisplatin, doxorubicin, and paclitaxel, or carboplatin and paclitaxel doublet. Hormone therapy with medroxyprogesterone acetate is only recommended for endometrioid subtype and is not recommended for papillary serous and clear cell subtype. Vaginal brachytherapy alone is generally reserved for localized disease (stage I disease and stage II grade 1).
CHAPTER 19
1. B. Cervical cancer is caused by exposure to high-risk strains of HPV not HSV. Greater than 99% of cervical cancers harbor HPV DNA and HPV types 16 and 18 account for 70% of those cervical cancers. The rest of the epidemiologic information is correct. The higher incidence of cervical cancer among minorities in the United States is thought to be due to barriers in screening secondary to lack of insurance, low income, and immigration from low screening countries.
2. A. Major prognostic factors are stage, nodal involvement, tumor size, depth of cervical stroma invasion, LVSI, and to a lesser extent histologic type and grade. Spread is usually orderly starting from the cervix to the pelvic nodes, along lymphovascular planes to the iliac (pelvic) lymph nodes and finally to the para-aortic lymph nodes. Hematogenous spread is typically a late occurrence but most commonly involves lung, liver, and bone. Patients with microinvasive cervical cancer have minimal risk (1% or less) of metastatic disease and are adequately treated with a cervical conization or simple hysterectomy.
3. D. Because the global burden of cervical cancer is in low-resource countries where abilities to surgically stage may be limited, cervical cancer is clinically staged. Imaging may include CT or combined PET/CT and MRI when available, for treatment planning purposes only. Hydronephrosis seen on intravenous pyelogram represents stage IIIB disease. If hydronephrosis is noted on CT scan or CT-IVP, this is also acceptable to determine stage IIIB disease, because the same finding would likely be apparent on traditional IVP.
4. B. Although chemoradiation is superior to surgical therapy for advanced disease, both treatments have comparable survival for early-stage disease. Chemoradiation avoids a surgical procedure, while the benefits of radical hysterectomy include preservation of ovarian function, avoidance of acute and chronic radiation–induced changes to the genitourinary and gastrointestinal systems, and obtaining a surgical specimen for prognostic purposes. Cervical conization or simple hysterectomy would not be appropriate for this patient, since she has visible disease. If future fertility is desired, radical trachelectomy with pelvic lymph node dissection can be considered. Since this patient is near or at menopause, a fertility-sparing procedure would not be appropriate.
5. D. The patient has an isolated central pelvic recurrence after chemoradiotherapy. Since she has already likely received the maximum dose of pelvic radiation, additional radiation would not be appropriate. Any chemotherapeutic regimen would only be palliative; however, pelvic exenteration performed for a centrally recurrent disease provides a 5-year survival of approximately 50%.
CHAPTER 20
1. C. The patient has stage IVB disease. Pelvic exenteration is a radical surgery with significant morbidity and uncertain survival benefit. Chemoradiation may allow less extensive resection. There are no data for tamoxifen in the management of SCC of the vulva. Brachytherapy would be inadequate treatment for stage IVB disease.
2. B. There is no proven standard of care for relapsed stage IV SCC of the vulva. Since the patient appears to have a good performance status, referral for a clinical trial is appropriate. Repeat radiation to the pelvis would not be recommended given that the treatment was <2 years ago and is unlikely to give benefit.
3. E. In patients in whom invasive disease is not suspected or seen on biopsy, laser ablation is an appropriate therapy. Radical vulvectomy is reserved for invasive disease. Observation is not appropriate since invasive disease may develop.
CHAPTER 21
1. A. More than 85% of patients with Ewing sarcoma carry the characteristic EWS-FLI translocation. RMS is a small blue round cell tumor as well, which in the alveolar RMS subtype may carry the PAX7/FKHR translocation. The recommended treatment for Ewing sarcoma is multimodality therapy including surgery, radiation, and multiagent chemotherapy.
2. E. Osteosarcoma occurs in children and adolescents and older adults. The treatment of choice is neoadjuvant chemotherapy followed by surgical resection. Oligometastatic disease is curable with surgical resection. There is no characteristic chromosomal translocation for osteosarcoma.
3. F. RMS is a tumor primarily of the soft tissues, but may also grow in bone. The standard treatment involves 8 to 12 cycles of chemotherapy with VAC in addition to radiation and surgical resection if feasible. RMS occurs in infants, where it carries a better prognosis and may present as a primary bladder rumor.
CHAPTER 22
1. A. The tumor is thin (less than 1 mm deep) without ulceration or mitosis, and hence has a very low risk of harboring occult metastasis in the regional lymph nodes (AJCC stage IA). Sentinel lymph node biopsy is not recommended in tumors 1 mm or lower unless the tumor has ulceration or mitosis. High-dose interferon is recommended in patients at high risk of recurrence in tumor that is deeply invading with ulceration or that with lymph node metastasis and ulcerated primary.
2. C. The independent factors of prognosis in patients with cutaneous melanoma are depth of invasion, age more than 65 years, ulceration, tumor stage, and mitosis more than 0/mm2.
3. D. The patient has an isolated metastatic tumor to the lung. He has no other signs of tumor metastasis and a surgical treatment could render a durable complete remission in about 25% of instances. He will need to be closely followed clinically and with imaging studies.
4. D. This young patient is very sick and requires a treatment that will work relatively quickly. High-dose IL-2 is not an option since it does not work quickly and the patient is too sick to tolerate this agent. Single-agent dacarbazine has a low response rate of about 7% to 12% and is not likely to help in this patient, while infusion of ipilimumab is not the appropriate option at this time, since its onset of action is very slow. This patient’s tumor is positive for BRAF mutation and prompt administration of vemurafenib is likely to prevent rapid progression of this tumor and result in clinical benefit.
5. C. Polyoma viral DNA is found integrated in more than 90% of Merkel cell tumors raising a possibility of association with a viral etiology in this tumor.
CHAPTER 23
1. B. Patients with t(8;21) or inv(16) have a favorable prognosis and benefit most from HDAC consolidation. These patients do not seem to benefit from autologous or allogeneic transplant in first remission.
2. D. This patient has a very high suspicion of APL considering she is young, female, and appears to have disseminated intravascular coagulopathy (DIC). This is an oncologic emergency and ATRA therapy should be started as soon as APL is suspected. APL is a very curable disease, but unfortunately 10% of patients die early in the treatment course, typically from DIC and bleeding complications. Hydration and allopurinol are part of the initial therapy of acute leukemias, but are not the most important aspect for this patient. A bone marrow examination will need to be performed, but ATRA therapy should be started regardless. If the patient is found to have APL, she should be treated with anthracycline-based chemotherapy.
3. B. Approximately 25% to 30% of patients with ALL will have t(9;22). These patients are considered a very poor prognostic group. The addition of imatinib to standard ALL treatment regimens has been shown to be well tolerated with profound improvements in remission rates and survival. Rituximab and ofatumumab would not benefit this patient considering his disease does not express CD20. There are very limited data on the use of Alemtuzumab in patients will ALL.
CHAPTER 24
1. D. Del 13q is the most common cytogenetic abnormality in CLL, occurring in 50% of cases as either alone or in combination with other genetic mutations. Patients who have del 13q as their only abnormality have a more favorable prognosis. Their disease follows a more indolent course and their survival is similar to age-matched controls. The expression of CD38 and unmutated IgVH is associated with a poorer prognosis. They have a shorter overall survival and higher risk of relapse following treatment. Trisomy 12 is associated with an intermediate prognosis.
2. C. This patient most likely has AIHA, a known hematologic complication of CLL. Further evaluation may be notable for spherocytes on peripheral blood smear and a positive direct antiglobulin test, but neither is always present with AIHA. Other labs suggestive of hemolysis include an elevated indirect bilirubin, elevated LDH, and a low haptoglobin. Prednisone dosed at 1 mg/kg/day is the typical initial therapy for AIHA. Improvement in hemoglobin can be seen within a couple of weeks. Prednisone should be tapered off slowly once the hemoglobin and hemolysis labs normalize. This patient is hemodynamically stable with no history of cardiovascular disease, so a blood transfusion is not necessary at this time. Chemotherapy would only be indicated in this patient if corticosteroids were unsuccessful in controlling her AIHA. If corticosteroids were unsuccessful, fludarabine would not be the treatment of choice as it can potentiate AIHA. A bendamustine-based regimen would be more appropriate. Although rituximab can be used for AIHA, it is not typically used as a front-line option in part because of its cost relative to steroids.
3. B. Cyclophosphamide is an alkylating agent that has been demonstrated to cause myeloid neoplasias 3 to 8 years after exposure. These myeloid neoplasias, including MDS and AML, are typically associated with abnormalities of chromosomes 5 and 7. Fludarabine has been associated with a small risk of MDS and AML, but this is typically in patients who have received other chemotherapeutics as well. Rituximab has been associated with a delayed neutropenia a few months after exposure, but is not associated with secondary malignancies when administered by itself. CLL is associated with other malignancies such as colon and skin cancer. There are rare case reports of CLL transforming to AML in previously untreated patients, but no clear evidence of transformation to MDS.
CHAPTER 25
1. C. Based on the Baccarani score this would be termed a failure to TKI therapy. An optimal response would be at least a partial cytogenetic response, with the Ph clone being less than 35%. A suboptimal response would be minor cytogenetic response, with the Ph clone being between 36% and 65%. This would be termed a failure due to no cytogenetic response and evidence of a new mutation.
2. C. Cytogenetic clonal evolution portends for a poor prognosis as well as is more commonly found in AP and BP. This patient does not have any cytogenetic response, as well as clonal evolution; therefore he is a candidate for an allogeneic stem cell transplant if a donor is found. Due to his T315I mutation the optimal TKI for him would be ponatinib. There are no data for doubling the dasatinib dose. Changing to ponatinib alone would not address his clonal evolution. Cytotoxic chemotherapy is not necessary at this point as he is still in CP, but could be indicated if he was in BP.
CHAPTER 26
1. E. The myeloid neoplasms have overlapping clinical characteristics, because after all, many of the causative mutations can occur in the different categories of MPNs or MDS. Mr. Jones’ demographic and constellation of symptoms, signs, and investigation observations thus far: shortness of breath, bruises, splenomegaly, macrocytic anemia, and thrombocytopenia are compatible with any of the above diagnoses. Other less likely differential diagnoses include portal hypertension from liver cirrhosis or portal vein thrombosis, since there were no suggestions of chronic liver disease risk factors, symptoms or signs in the history, and physical examination. Although he has had foreign travel to compel consideration of unusual protozoal illnesses such as malaria during the history and physical examination, this was sufficient to indicate that this diagnosis, or other protozoal illnesses, is highly unlikely. Determining the specific diagnosis, and Mr. Jones’ risks for complications, will require further evaluation.
2. E. The reticulocyte count and lactate dehydrogenase are of course routine components in the evaluation of anemia, to better understand if the cause is from decreased production or increased destruction. Although the observations thus far do not place hemolytic anemia high on the differential diagnoses list, these parameters are nonetheless highly valuable baseline measures in the evaluation and management of myeloid malignancies, since they can be followed over time to confirm that therapy is changing things in the right direction, with decreasing LDH and increasing functional marrow as represented by appropriate reticulocyte count levels for the degree of anemia. The JAK2 V617F mutation is part of the diagnostic criteria for the MPNs, because of its highly recurrent association with these conditions. Bone marrow aspirate for morphologic evaluation and karyotype analysis are invaluable in classifying an MPN and in evaluating risk, a very pertinent consideration in Mr. Jones who is a potential candidate for allogeneic stem cell transplant. Although the clinical picture suggests that chronic myeloid leukemia is a less likely MPN, the treatment implications of this diagnosis are profound, and there is a need to rule out this diagnosis. It can be legitimately argued, however, that the clinical picture of Mr. Jones does not compel urgent evaluation to rule out CML, and that instead of FISH analysis, Dr. Brown can wait for the results of standard metaphase karyotyping of the bone marrow.
3. A. The diagnostic evaluation suggests that the diagnosis is primary MF, although an MDS/MPN overlap neoplasm remains in the differential diagnosis. The clinical features and observations suggest that Mr. Jones is at least in an intermediate risk or even in a high-risk category (e.g., by the DIPSS plus risk classification system) of MF. Furthermore, he is relatively young. Thus, allogeneic stem cell transplant must be considered, and at a minimum, Mr. Jones and his sibling should be HLA typed. His predominant symptom complex relates to anemia, with a possibility also of platelet dysfunction in addition to the thrombocytopenia. Thus, pending evaluation for transplant, management of anemia is indicated, including transfusion if necessary, and consideration for androgens such as danazol. If Mr. Jones does not have a sibling match, and if unrelated donor transplant is not an option, then experimental therapies should be considered; these could include DNMT1-depleting drugs such as 5-azacytidine or decitabine. Although Mr. Jones has splenomegaly, this is asymptomatic, and a JAK2 inhibitor is not indicated. For the same reasons, HU is not indicated. Erythropoietin could be considered if erythropoietin levels are inappropriately low (e.g., <200 milliunits/mL). Although it is possible that they are, since levels were not checked, it seems unlikely given Mr. Jones’ age and normal renal function tests. Iron supplements would only be indicated if Mr. Jones is iron deficient, again unlikely given the constellation of observations, the MCV, and Mr. Jones’ sex. Of course, iron studies should be performed.
CHAPTER 27
1. C. This patient has a M-protein and has >10% plasma cells in the bone marrow in the absence of any end-organ damage. A useful acronym to remember is CRAB—HyperCalcemia, Renal failure, Anemia, and Bone lesions. MGUS patients also have no evidence of end-organ damage but have an M-spike <3 g/dL and <10% clonal plasma cells in the bone marrow. Negative congo red staining points against amyloid deposition. This patient does not have MM as she has no evidence of end-organ damage. The correct answer is SMM.
2. A. The patient is progressing on thalidomide and dexamethasone therapy with worsening anemia, renal failure, and increasing urine M-spike. This patient most likely has light chain cast nephropathy. Increasing the dose of thalidomide is unlikely to induce a response and will probably increase the propensity for adverse effects. Lenalidomide and melphalan should be avoided in patients with advanced renal failure and response is seen after few weeks of therapy. Bortezomib does not need dose adjustments and can induce rapid responses and is the preferred drug for myeloma patients with renal failure.
CHAPTER 28
1. A. Although the majority of BL cases harbor t(8;14), other MYC-activating translocations can also occur in this disease. The (11;14) translocation is present in virtually all cases of mantle cell lymphoma, but is associated with overexpression of cyclin D1. The (14;18) translocation is present in most cases of follicular lymphoma, but is associated with overexpression of bcl-2. The (2;5) translocation is associated with ALK-positive anaplastic large cell lymphoma, which has a better prognosis than its ALK-negative counterpart. Lastly, 11q deletions are associated with bulky lymphadenopathy and relatively poor prognosis in CLL/SLL, although the inclusion of cyclophosphamide into the therapeutic regimen may to some extent overcome this adverse prognostic significance.
2. B. The NF-κB pathway is constitutively activated in ABC-DLBCL, leading to upregulation of multiple antiapoptotic transcription factors. Targeting of NF-κB and its downstream regulators is currently a focus of intense research, and early studies are demonstrating promising results.
3. C. The patient has stage IV DLBCL with a high/intermediate IPI and requires immediate therapy with the current standard of care regimen, R-CHOP-21. R-CHOP-14 with growth factor support has not demonstrated any advantage over R-CHOP-21, and there is a trend toward increased toxicity with the former. R-hyper-CVAD is a dose-intensive regimen used in BL. Response assessment after completion of therapy using both metabolic (FDG-PET) and anatomic (CT) imaging is appropriate for DLBCL, as the achievement of PET-negative status without complete anatomic resolution of lymphadenopathy is now considered equivalent to anatomic complete response (CR). Imaging after two to four cycles of therapy is recommended to ensure chemoresponsive disease; however, evidence of good response on interim imaging should not be used to shorten the duration of therapy. Any patient with BM involvement at diagnosis must have documented clearance by repeat BM aspirate/biopsy prior to designation of CR.
4. E. There is a high suspicion for transformation of this patient’s FL into an aggressive large cell lymphoma, given his rapidly progressive disease and the variably intense FDG uptake on PET. The approach to treating this patient may change considerably if transformation is identified, and consequently a biopsy of the most hypermetabolic and/or rapidly growing focus of disease (the site with the highest likelihood of transformation) is indicated prior to initiation of salvage therapy. Answers A, B, and C are all reasonable therapies for relapsed FL. BM biopsy is indicated for both staging and diagnostic purposes.
5. E. This patient’s clinical presentation and histologic findings are classic for PMBL. Classic Hodgkin lymphoma is characterized by the presence of Reed–Sternberg cells, and the malignant lymphocyte immunophenotype is typically CD30+, CD15+, and CD45–. T-lymphoblastic lymphoma is the nodal manifestation of T-ALL, and immunophenotype is consistent with T-cell origin (CD19/20–, CD2+, CD7+). SLL is the nodal/aleukemic manifestation of CLL, does not typically present as an isolated mediastinal mass, and consists of small malignant lymphocytes with dim CD20 expression. Mantle cell lymphoma is a variably aggressive lymphoma with a striking male predominance that typically presents with both nodal and extranodal (BM, peripheral blood, GI tract) involvement and is confirmed by the presence of t(11;14).
CHAPTER 29
1. C. In young HL patients, measures to ensure fertility preservation before starting chemotherapy are of paramount importance. While infertility due to ABVD chemotherapy is uncommon, sperm banking (which is relatively inexpensive and readily available) in a male patient before starting treatment is important for two reasons: (1) To document normal sperm count and motility at baseline, since suboptimal sperm count and quality is not uncommon in HL patients even before initiating chemotherapy. (2) Sperm banking is often not feasible in patients, who have refractory disease after ABVD chemotherapy before starting salvage regimens associated with high probability of causing infertility. Bone marrow aspiration biopsy is not required in patients with stage IA or IIA disease, and bilateral bone marrow biopsies are not needed in HL. Infuse-A-port is often inserted before starting chemotherapy, but ABVD-like regimens can be safely administered using peripheral intravenous access only.
2. B. The patient in this question has favorable risk, early-stage (IIA) HL, according to the German Hodgkin Study Group (GHSG) criteria. The HD10 trial by GHSG showed that in patients with favorable early-stage HL, two cycles of ABVD followed by 20 Gy of involved field radiation was not inferior to more aggressive options. Option A is appropriate for patients with unfavorable nonbulky early-stage HL. R-CHOP (C) is not an option of HL (at least in the front-line setting). Subtotal radiation therapy is inferior of chemotherapy combined with involved field radiation therapy and is not recommended.
3. D. HL is a highly curable hematologic malignancy; however, delays in administering chemotherapy on time (A and B) or reducing dose intensity (E) can negatively impact the probability of long-term disease control and are not recommended. Administration of growth factors (e.g., filgrastim) with ABVD has been shown to be associated with increased pulmonary toxicity and is not routinely recommended (B and C). ABVD can be safely administered to HL patients with growth factor support and regardless of ANC at the day of chemotherapy.
4. A. The patient in this question shows evidence of chemosensitive disease after second-line therapy with ICE regimen. High-dose therapy and autologous transplantation are curative for relapsed, chemosensitive patients with HL and remains the standard of care of this patient population (A). Patients with relapsed HL should be referred to a transplant center for transplant planning soon after a relapse is confirmed (ideally before starting salvage chemotherapy regimens). Chemotherapy alone (C) in this setting is inferior to chemotherapy followed by autologous transplantation. Similarly allogeneic transplantation (B) is generally not indicated in first relapse, outside the setting of a clinical trial. There is no role of brentuximab vedotin maintenance after chemotherapy (D).
CHAPTER 30
1. B. A patient with normal cytogenetics AML is treated upfront with induction and consolidation therapy followed by close observation in CR1. At the time of first relapse, apart from reinduction chemotherapy, every attempt must be made to HLA type the patient at the earliest and find a suitable donor for an allogeneic HCT in CR2. Since she does not have a sibling donor, a National Marrow Donor Program search must be initiated to locate a suitable donor. Time is vital as it takes 3 to 6 months to obtain an allograft from an URD. She has a 70% chance of finding a HLA-matched donor. Choice A is not a therapeutic option for this patient; autologous HCT is sometimes considered as consolidation therapy in CR1, ideally in a clinical trial setting; C and D are wrong as allogeneic HCT should be considered in first relapse or CR2 and deferring it will considerably worsen her prognosis.
2. D. Use of carmustine (BCNU) as part of high-dose therapy can cause delayed interstitial pneumonitis and present with typical findings as described in the question. The correct management includes obtaining a pulmonary function test including diffusion lung capacity of carbon monoxide and the use of steroids (D). BCNU can cause pulmonary fibrosis which may take years to manifest. The described symptoms, lack of productive cough, and negative chest x-ray point against bacterial pneumonia and hence choice A is not the best answer. The compliant use of trimethoprim–sulfamethoxazole effectively protects the patient against Pneumocystis pneumonia and hence switching to inhaled pentamidine (B) is not indicated.
3. C. Evaluation of the potential donor (sibling and unrelated) is an important part of pretransplant workup. Only serious or life-threatening illness that endangers the donor or history of malignancy within the past 5 years (except nonmelanoma skin cancers) are considered absolute contraindications (A). While there is a theoretical risk for AML with the use of growth factors, this has not been observed in healthy donors and family history does not pose an increased risk either (D). Subablative chemotherapy (e.g., Cy) prior to growth factor–mobilized progenitor cell collection is only considered for autotransplant. Growth factor–mobilized progenitor cell collection is very well tolerated barring minor bone pain, a rare risk of spontaneous splenic rupture, and no long-term effects (C).
4. A. The triad of findings (hyperbilirubinemia, right upper quadrant pain, and weight gain/ascites) in the first 3 weeks after myeloablative allogeneic HCT should strongly raise the suspicion of SOS. Pre-existing liver disease, conditioning regimens containing combination of Cy with Bu and higher dose TBI, and prior exposure to gemtuzumab ozogamicin are all risk factors for developing SOS. With the advent of intravenous Bu with levels followed closely and restricting the radiation dose to 12 to 13 Gy has dramatically decreased the incidence. Acute GVHD must be considered in the differential and sometimes liver biopsy is required. In this case choice B is wrong as the clinical features fit SOS. Hepatosplenic candidiasis, once common, is very effectively prevented with azole prophylaxis and thrombotic microangiopathy is unlikely with normal peripheral smear (C and D).
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1. E. The presentation of mediastinal and/or retroperitoneal nodes in men aged below 65 years places germ cell tumor high on the differential list. Therefore, CT chest, abdomen, and pelvis and tumor markers β-hCG and AFP should be obtained for both men and women. For men over 40, a PSA should also be obtained. For women, workup for breast cancer should also be performed, with ER/PR and Her-2 immunohistochemistry, mammogram and breast ultrasound, and/or MRI breast. If all workups are negative, review the case with the pathologist for further workup to differentiate testicular, ovarian, or non–small cell lung cancer.
2. D. Patients with adenocarcinoma with mediastinal nodes as the only site of disease most likely have either germ cell tumor or non–small cell lung cancer primary. Patients aged below 50 years should be treated for poor-risk germ cell tumor. However, patients aged between 40 and 50 years could also be treated for non–small cell lung cancer. Patients aged 50 years and older should be treated for non–small cell lung cancer. Testicular ultrasound should be performed if β-hCG and/or AFP levels are elevated.
3. E. A primary site in the genital or anorectal areas, including the surrounding skin, is often identified in most patients with squamous cell carcinoma involving inguinal nodes. The prognosis for these patients is good. Curative therapy is available for some of these patients. If there is no primary site found, lymphadenectomy with or without adjuvant radiation therapy can result in long-term survival.
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1. B. Age <50 (answer A) is a good prognostic factor. Answer B is a poor prognostic factor. MGMT promoter methylation is an excellent prognostic factor, but lack of methylation indicates a tumor unlikely to respond to temozolomide, which conveys prognosis at or below the median OS in the 2006 Stupp trial of XRT with temozolomide. Gross total resection (answer C) is a good prognostic indicator in GBM. A Karnofsky performance status of 90 (answer D) is excellent and places this patient in the good prognostic group (KPS >70 presurgery).
2. D. While all answers are not unreasonable, the standard of care in this patient would be D. Clinical trials have demonstrated the superiority of resection followed by WBRT when compared with surgery alone or WBRT alone. Of course, an informed discussion with the patient about the potential risks and benefits of each procedure may also end up in the patient choosing hospice care, but an informed discussion would include conveying to the patient that her length and quality of life may be significantly improved by choosing answer D.
3. D. While radiotherapy (answer A) is capable of inhibiting growth of meningiomas, it is not considered a front-line option in a patient without symptoms, especially if the lesion is surgically resectable. WBRT (answer B) is not a reasonable choice for meningioma management in any setting. Surgical resection (answer C) is a good choice for management of meningioma and would be the ideal choice in a patient with symptomatic disease. However, because this patient has no symptoms, it is probably best to recommend observation (answer D) for him with regular follow-up examinations and MRIs at fixed intervals, which would depend on the pace of growth seen with serial MRI scans. While it would not be incorrect to choose surgery, observation offers less likelihood of morbidity. There is no need for surgery followed by radiotherapy (answer E) to the resection cavity in an asymptomatic patient without evidence of progression or atypical/malignant features.
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1. B. The purpose of this question is to understand the management of patients with previously untreated metastatic PTC. Unlike most malignancies, resection of the primary tumor and lymph nodes should be performed in all patients with metastatic disease. This is because these patients are still potentially curable with subsequent radioactive iodine treatment. Complete responses are seen in approximately 45% of patients. This is particularly the case for young patients with multiple pulmonary metastases. A preoperative diagnostic radioactive iodine scan would not be useful for two reasons: all of the iodine would concentrate in the thyroid, and the patient has had a recent CT scan with IV contrast. Iodinated contrast will interfere with the diagnostic scan by increasing the circulating iodine. For this reason (and because radioactive iodine is intended for remnant ablation and metastases, not primary tumors), treatment with radioactive iodine is not an appropriate first step in this patient’s management. Doxorubicin-based chemotherapy and clinical trials with kinase inhibitors are reserved for patients with radioactive iodine refractory disease.
2. C. The purpose of this question is to recognize the appropriate time to initiate therapy with a kinase inhibitor in advanced MTC. Vandetanib and cabozantinib are tyrosine kinase inhibitors that are approved for the treatment of symptomatic or progressive MTC in patients with unresectable locally advanced or metastatic disease. Both were approved based on improvement in progression-free survival compared to placebo, but demonstrated no improvement in overall survival. Therefore, given the treatment-related risks, use in patients with indolent, asymptomatic, or slowly progressing disease is typically not recommended. Answer B is incorrect because we do not know the results of his imaging. Asymptomatic patients with elevated calcitonin and negative imaging should not receive vandetanib. If disease is present, there are several options to be considered depending on the disease burden and location. They include surgical resection if feasible, localized therapy such as radiofrequency ablation or chemoembolization, vandetanib, or cabozantinib therapy. Answers A and E are incorrect because MTC is derived from parafollicular or C cells. This cell type does not incorporate iodine or have TSH receptors. Therefore, TSH suppression and radioactive iodine are not effective therapies. Answer D is incorrect because while external beam radiation is sometimes used, it is not done empirically without imaging to assess for resectable disease. Further, MTC is not particularly radiosensitive. Answer C is the best answer. If his imaging is negative, his calcitonin should be repeated in 3 to 6 months. If it is stable, no further imaging is indicated. If it continues to rise, it rapidly increases, or he develops new symptoms, further imaging should be done.
3. D. The purpose of this question is to understand the role of mitotane for the treatment of ACC. Mitotane is an adrenocortolytic therapy with objective tumor responses seen in approximately one-third of patients with metastatic disease. Its primary benefit (achieved in approximately 75% of cases) is the reduction of symptoms related to the ectopic hormone production of these tumors. This patient has associated Cushing syndrome with weight gain, weakness, and hypertension, and is therefore particularly in need of an adrenocortolytic therapy. Both streptozocin and the combination of cisplatin, doxorubicin, and etoposide (EDP) are often used with mitotane. These two regimens, in combination with mitotane, were studied head to head in a clinical trial as first-line therapy for patients with locally advanced or metastatic disease that is not amenable to surgery. EDP with mitotane was superior to streptozocin and mitotane with regard to overall response rate and progression-free survival; however, there was no overall survival advantage.
4. B. The purpose of this question is to understand the clinical presentation and diagnosis of Zollinger–Ellison syndrome and gastrinoma. This patient’s clinical symptoms are suggestive of Zollinger–Ellison syndrome, the condition associated with a gastrinoma that is characterized by refractory peptic ulcer disease, diarrhea, and gastric hyperacidity. Patients who are suspected of gastrinoma with an elevated gastrin level should undergo a secretin stimulation test as the next step in diagnosis. Secretin stimulates secretion of gastrin from gastrinomas, but not from normal G cells. As a result, gastrin levels will rise after secretin infusion in patients with gastrinomas. A positive secretin stimulation test is generally considered a rise in gastrin of ≥200 pg/mL. After the diagnosis of gastrinoma is made, it must be localized using imaging. EUS, octreotide scan (somatostatin receptor scintigraphy), CT, and MRI are all useful imaging modalities to localize gastrinomas. 131I-MIBG is structurally similar to norepinephrine and is typically used to diagnose pheochromocytomas.
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1. A. Decrease in transfusion rates is the only benefit of ESAs consistently demonstrated in RCTs and meta-analyses. Consistent evidence does not exist for the rest of the attributes provided in the choices (especially at higher Hb levels). Strikingly, in the case of choice C, at least one meta-analysis of 53 pooled RCTs showed that the use of ESAs is significantly associated with shorter survival.
2. C. As per the current guidelines and FDA label, the ESAs are best recommended for cancer-induced anemia to decrease the need of blood transfusions when the Hb levels fall below 10 g/dL. Between 10 and 12 g/dL there is a lack of consistent evidence to say that ESAs would decrease transfusion requirement. There is also an emerging body of evidence that shows that ESAs are associated with significantly increased mortality. For the patient in choice B, the symptomatic anemia may warrant a blood transfusion instead for quick relief. Although there still lack consensus data on the use of ESA based on the intent of chemotherapy regimen, FDA labeling restricts the use to those being treated with palliative intent.
3. A. Routine adjunctive use of CSF for FN is not recommended unless the patient has risk factors for infection-associated complication, including age >65, expected prolonged neutropenia (>10 days), profound neutropenia (<100/µL), sepsis syndrome, hospitalization, pneumonia, invasive fungal infection, or uncontrolled primary disease. In a clinical scenario described in choice B, the use of G-CSF may be justified as a secondary prophylaxis. Citron et al. showed that dose-dense regimen supported by G-CSF has superior clinical outcome. The ASCO guideline recommends administering CSF to patients who had dose-limiting neutropenic event that could otherwise impact planned dose of chemotherapy from a prior cycle of chemotherapy when no CSFs were given. In a clinical scenario described in choice C, the use of G-CSF may be justified as a treatment of FN with a high-risk feature of profound neutropenia (ANC <100/µL). Likewise, a patient in choice D has FN with at least two high-risk features—age above 65 and likely a postobstructive pneumonia. Thus, the use of G-CSF is justified. In choice E, the use of G-CSF may be justified as primary prophylaxis. TPF regimen is myelosuppressive and the goal of induction therapy is curative. The patient has one high-risk feature (age above 65).
4. B. Cochrane meta-analysis reported by Bohlius et al. concluded that CSFs, when used as a prophylaxis in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, FN, and infection. No evidence exists to suggest that either G-CSF or GM-CSF provide a significant advantage in terms of complete tumor response, freedom from treatment failure, or overall survival. Choice A is false because no data exist that compared pegfilgrastim and filgrastim in this disease setting. Citron et al. reported that dose-dense regimen supported by G-CSF had superior clinical outcome compared with conventional chemotherapy in node-positive breast cancer patients. Choice C is false. The meta-analysis by Clark et al. showed the use of CSF in chemotherapy-induced FN was associated with statistically significant reduction in the hospital stay, and shorter time to neutrophil recovery. Reduction in infection-related morality or overall mortality was not statistically significant. Choice D is wrong because ASCO 2006 update guidelines recommend the use of CSFs with first- and subsequent cycle chemotherapy to prevent FN when the risk is greater than 20%. Choice E is false. Gurion et al. reported that the addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow-up or in overall survival. There was no difference in complete remission rates, relapse rates, and disease-free survival. CSFs did not decrease the occurrence of bacteremias, nor the occurrence of invasive fungal infections. CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm.
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1. D. Fever during neutropenia is a medical emergency, and antibiotics should be started without delay. AML during transplant is not a “low-risk patient” who could be considered for oral antibiotics. The recommended first-line agents for fever during neutropenia include cefepime, piperacillin–tazobactam, imipenem, and meropenem. Vancomycin is not routinely indicated as part of the starting regimen, except under one of the following circumstances: hemodynamic instability, known MRSA carrier, clinically apparent catheter infection, pneumonia, and mucositis. Mucositis has been associated with bacteremia caused by Streptococcus mitis with severe sepsis and high mortality, and this is the reason this patient should receive vancomycin. Most authorities consider that imipenem and meropenem offer enough coverage against S. mitis to be used as single agents.
2. E. This question is about when to change antibiotics during fever and neutropenia. Persistent fever alone is not an indication to change the antibiotic regimen, but hemodynamic decompensation as seen in this patient mandates antimicrobial changes. Although antifungal coverage can be considered, the patient has been febrile only for 48 hours and she is hypotensive: both details make antibacterial agent changes more important, so option A cannot be the right choice. Antibiotic coverage for known VRE colonization is very reasonable for a patient who is known to be colonized with it and is not responding to standard antibiotic therapy. However, there is no indication that the catheter is infected with VRE. The single culture bottle for coagulase-negative Staphylococcus is more suggestive of a contaminated culture or, at most, catheter colonization. Thus the suggestions regarding vancomycin and the catheter are distractors—the issue here is not catheter-associated bacteremia, but hemodynamic instability during neutropenia. There is no indication to remove the catheter. More importantly, the history of prior ESBL infection suggests the possibility of a gram-negative infection resistant to cefepime. This must be addressed with expanded gram-negative coverage. The best option is E, which addresses the known prior pathogens (ESBL and VRE) and the possibility of a Candidainfection that could break through and cause hypotension.
3. D. This question is about persistent fever during neutropenia. In this case D is the best answer, although all the other options have some merits. Answer E is wrong: antibiotics should not be discontinued during fever and neutropenia to test for drug fever, as this strategy resulted in high frequency of septic shock in a randomized trial. Daptomycin could be stopped (current guidelines support discontinuing the gram-positive coverage if no clinical specimen has shown a microorganism that requires it), but this does not address the persistent fever, so option B is not adequate. Maintaining the same coverage after 5 days of persistent fever (option A) is not the standard of practice. In this case, it is appropriate to look for a fungal infection by obtaining CT of the chest and sinuses and expand the antifungal coverage. There has been one randomized trial comparing adding amphotericin in all cases of persistent fever with adding it only when there was ancillary evidence of fungal infection (serologic markers, abnormal CT, and others), and in fact this so-called preemptive addition of amphotericin was inferior to the standard empirical management.
4. C. There is no indication to obtain PPD, galactomannan, or hepatitis C serology before chemotherapy for lymphoma. However, hepatitis B reactivation has been very well documented following CHOP-R. Individuals with evidence of chronic virus B infection (carriers or people with chronic hepatitis) who are going to receive chemotherapy for lymphoma need to be treated prophylactically with lamivudine or entecavir. It is unknown for how long after completion of treatment the antiviral medicines should be continued, as reactivation of hepatitis B post-CHOP-R has happened several months out.
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1. A. SCC most often involves the thoracic spine, followed by lumbosacral and cervical spine.
2. D. A is not correct because immediate RT is only indicated for patients with symptomatic SVC syndrome presenting with stridor or mental status changes from cerebral edema. B is not correct because without histologic diagnosis, certain malignancies may not be responsive to glucocorticoids and chemotherapy. C is not correct because thrombolytic therapy and anticoagulation should only be considered for thrombosis causing SVC syndrome. D is the correct answer. Endovascular stenting can result in rapid resolution of symptoms. Accurate histologic diagnosis of the patient’s malignancy can guide further therapy and care. RT may obscure the biopsy findings.
3. H. Zolendronic acid should only be used after adequate hydration. Densosumab is preferred in the setting of renal failure, and osteonecrosis of jaw is associated with this agent as well.
4. F.
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1. D. Delirium is an acute disturbance of consciousness with reduced ability to focus, sustain, or shift attention. Patients may demonstrate an array of symptoms including changes in cognition, memory deficits, disorientation, speech/language disturbances, delusions, and perceptual abnormalities. A medical workup is required as delirium, by definition, has an underlying medical or neurologic cause. Haloperidol would be a reasonable choice for management of agitation in a patient without contraindications such as QTc prolongation or other cardiovascular risk factors. BZDs such as lorazepam should generally be reserved for delirium related to alcohol or BZD withdrawal. The Academy of Psychosomatic Medicine has an online monograph on evidence-based management of delirium available at: http://www.apm.org/library/monographs/delirium/APM-EACLPP_DeliriumMonograph.pdf.
2. A. Differentiating between nonclinical mood changes and a clinical diagnosis of major depressive disorder (MDD) can be difficult for many cancer patients. The somatic symptoms of cancer and cancer treatment can mimic the diagnostic and statistical manual criteria for MDD. The patient in this case has many symptoms that point strongly to a diagnosis of MDD such as excessive guilt, early morning awakening, and anhedonia (a lack of interest in her normal hobbies and activities). An antidepressant would be a reasonable management choice for this individual. Tamoxifen is broken down to its active metabolite, endoxifen, by cytochrome P-450 2D6. Many antidepressants have an inhibitory effect on 2D6 substrates and therefore could potentially inhibit the conversion to endoxifen. Venlafaxine (Effexor) has minimal inhibitory effect at 2D6 and would be the best antidepressant choice in this patient. Paroxetine would be a poor choice as it is a potent inhibitor at 2D6. A medication to help sleep and/or anxiety may be a reasonable choice in this patient but would not address the core depressive symptoms. Clonazepam could be used to help address anxiety and sleep but does not address symptoms such as excessive guilt. Zolpidem is commonly used to help sleep but would not help the other symptoms this patient is experiencing.
3. B. The patient’s age and gender are major contributors to risk factors for self-harm. The strongest predictor of self-harm is a prior history of self-harm. The other issues listed such as his financial status or his medications could potentially contribute to self-harm but are not as predictive as prior history. Recent data suggest a correlation to receiving a diagnosis of cancer and suicide, with highest risk of suicide in the first 4 weeks of cancer diagnosis. Highest rates of suicide in cancer patients are seen in esophageal, pancreatic, liver, and lung cancer.
4. D. Given this girl’s admission for chemotherapy, it will be challenging to differentiate insomnia from anxiety from that of chemotherapy-related side effects and new environment (the hospital) versus preexisting anxiety without reviewing her developmental and social history. After full review of history with both patient directly and her parents, it will then be important to determine whether the patient might require an anxiolytic (BZD or antihistamine). The general rule with children is to use low doses of anxiolytics for short duration if required.
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1. D. Combination chemotherapy that includes doxorubicin (an anthracycline) and cyclophosphamide (an “AC” regimen) is categorized by current ASCO and NCCN guidelines as presenting high emetic risk. Docetaxel is also emetogenic, albeit categorized among drugs associated with low emetic risk. Guideline-driven recommendations advise prophylaxis appropriate for the most emetogenic component of treatment; therefore, antiemetic prophylaxis appropriate for treatment with high emetic risk is indicated, which includes combination of a 5- HT3receptor antagonist, dexamethasone, and aprepitant (or fosaprepitant). Option A limits glucocorticoid use to only the first day of treatment, which deviates from ASCO and NCCN recommendations for delayed-phase prophylaxis, but remains consistent with MASCC/ESMO recommendations; however, concurrent use of aprepitant (or fosaprepitant) with dexamethasone increases the steroid’s bioavailability and, therefore, a 20 mg dose of dexamethasone in combination with fosaprepitant substantially exceeds the 12 mg dose recommended by MASCC/ESMO, ASCO, and NCCN guidelines. Option B complies with the components of acute-phase prophylaxis recommended by NCCN and ASCO guidelines. Again, however, a 20 mg of dexamethasone in combination with aprepitant on day 1 exceeds the 12 mg dose recommended by all three guidelines. Delayed-phase prophylaxis follows MASCC/ESMO recommendation, but is inconsistent with ASCO and NCCN recommendations by omitting dexamethasone on days after chemotherapy. Acute-phase prophylaxis described in option C closely resembles all three guidelines’ recommendations for acute-phase prophylaxis, but the omission of aprepitant on days 2 and 3 after a 115 mg dose of fosaprepitant is inconsistent with FDA-approved labeling and all three guidelines’ recommendations for use of an NK1receptor antagonist on those days. The addition of dexamethasone on days 2 and 3, while consistent with ASCO and NCCN guidelines, is a deviation from MASCC/ESMO guidance. Option D most closely complies with all three professional guidelines by including fosaprepitant on an administration schedule appropriate for the dose administered, a 5-HT3 receptor antagonist only on day 1, and dexamethasone given at a dose appropriate for use with fosaprepitant (or aprepitant), on a schedule consistent with ASCO guidelines, and a duration of use consistent with ASCO and NCCN guidelines. Option E eliminates entirely the glucocorticoid component of prophylaxis recommended by all three guidelines for the day of treatment and describes a dose of ondansetron that exceeds the FDA warnings against intravenously administered single doses >16 mg to prevent serious adverse effects on cardiac electrophysiology.
2. E. Dexamethasone and other steroids given systemically for antiemetic prophylaxis often destabilize blood glucose control in diabetic patients, more so in patients whose blood glucose is not well controlled before receiving steroid medications. Increased lability in blood glucose control does not, however, preclude high-potency glucocorticoid use in an antiemetic regimen, but requires more intensive blood glucose monitoring and adjusting and supplementing antidiabetic medications during steroid use and withdrawing antidiabetic drugs after steroids are discontinued until blood glucose again stabilizes to within goals for glycemic control. Therefore, the prohibition described in option A is unnecessary as long as healthcare providers and patients recognize the need for more intensive blood glucose monitoring and altering antidiabetic treatment to maintain glycemic control during steroid use. Option B is correct. Paroxetine is a substrate and potent inhibitor of the CYP CYP2D6 enzyme, the primary catalyst for phase 1 metabolism of palonosetron and hydrodolasetron, dolasetron’s active metabolite. The rate at which substrates for CYP2D6 are metabolized is often described as “capacity limited” by virtue of two or more substrates in competition, or an amount of one or more substrates that overwhelm enzyme availability. Therefore, the half-life of one or more drugs competing for metabolism catalyzed by CYP2D6 may be substantially increased and, consequently, pharmacodynamic effects associated with pharmacologically active substrates may be exaggerated and persist for unpredictably lengthy periods due to protracted elimination. Ondansetron also is a substrate for CYP2D6, but like palonosetron, it is a substrate for phase 1 metabolism through alternative catalysts, including CYP3A4, a high-capacity enzyme. It is unsafe and, therefore, not possible to temporarily discontinue paroxetine during antineoplastic treatment as a means to avoid interaction with other CYP2D6 substrates. Rapid dose decreases and abrupt discontinuation of paroxetine have been associated with a withdrawal syndrome characterized by a variety of severe somatic, psychiatric, and neurologic adverse effects. With respect to option C, there is presently no evidence supporting dose or schedule modification of empirically dosed antiemetics based on extremes of body weight. Among high-potency glucocorticoids and 5-HT3 and NK1 receptor antagonists, the safest and most effective antiemetics in clinical use, recommendations for weight-based dosing appear in FDA-approved product labeling only for ondansetron and granisetron, and, with respect to intravenously administered ondansetron, labeling includes warnings against exceeding 16 mg for single doses. Option D is also correct. Paroxetine use has been associated with aberrations in cardiac electrophysiology including prolongation of ventricular repolarization and, in combination with other CYP2D6 substrate drugs with similar deleterious effects on cardiac conduction, has been implicated in causing torsades de pointes. Both dolasetron and ondansetron have been associated with cardiac QT interval prolongation, which is the basis for contraindications and warnings that appear in current labeling for both products. The potential for serious abnormal arrhythmias is increased by electrolyte abnormalities including hypokalemia and hypomagnesemia and by paroxetine’s potential for altering the elimination of 5-HT3 receptor antagonists by inhibiting CYP2D6. The patient’s healthcare providers should prudently replace magnesium and confirm achieving serum magnesium concentrations within a range of normal values before giving ondansetron intravenously or dolasetron in antiemetic prophylaxis. Option E is the best response, because it acknowledges the validity of both B and D.
3. B. Option A is an attractive choice because gastroparesis and altered GI motility are complications associated with diabetes. Compromised GI motility is a risk factor for emetic symptoms independent of the emetogenicity of treatment, but the selection is based on inference rather than evidence provided by the case history. Option B, female sex, is a well-documented risk factor for poor emetic control. With respect to C, anxiety preceding antineoplastic treatments often accompanies developing and frank anticipatory emetic symptoms. Anecdotally, anxiety during antineoplastic treatments appears to exacerbate emetic symptoms, but other behavioral disorders including clinical depression, have not been associated with emetic outcomes. With respect to options D, E, and F, predilection for motion or travel sickness and severe and persistent emetic symptoms during pregnancy, respectively, are recognized risk factors for poor emetic control during antineoplastic treatment, but the case history does not identify either condition. Likewise, constipation is included among pathologic factors associated with altered GI motility or obstruction that, when coincident with emetogenic treatment, predispose toward poor emetic control. In addition, constipation is a common side effect associated with paroxetine use, but again, the patient’s case history reveals nothing suggesting compromised or altered GI motility. Additional dialog between the patient and her healthcare providers is warranted to establish whether she has experienced difficulty with bowel movements rather than assuming an additional risk factor exists.
4. D. Cisplatin alone or in combination with other emetogenic drugs is associated with high emetic risk. Therefore, in addition to providing antiemetic prophylaxis appropriate for the most component of combination chemotherapy with the greatest emetic risk, our strategy for prophylaxis from the second through the fifth day of treatment should include medications appropriate to provide protection against both acute- and delayed-phase symptoms. Antiemetic prophylaxis for multiple-day emetogenic treatments has been less well studied than prophylaxis for treatments given on a single day, and professional guidelines are less explicit about how some antiemetics should be used to optimally protect against emetic symptoms associated with multiple-day treatments (i.e., palonosetron and NK1 receptor antagonists). Consequently, some extrapolation and assumptions are required from what is known about the effectiveness of prophylaxis for single-day treatments leavened with knowledge about the pharmacokinetic and pharmaceutical characteristics of available antiemetics and, if known, patient-specific pharmacogenomic characteristics that may affect drug metabolism. Clinicians also must ascertain whether (1) the emetogenic risk of treatment is the same or varies among treatment days and (2) the physiologic changes that underlie acute- and delayed-phase symptoms are operative concurrently, which may require antiemetic prophylaxis appropriate for one or both phases on each treatment day. When treatment includes drugs with high and moderate emetogenic risks on different days, also consider whether antiemetic prophylaxis against delayed-phase symptoms is indicated after emetogenic treatment is completed and the duration for which prophylaxis should continue. Although the present case scenario is realistic, it is simplified by a regimen without daily variation in emetic risk and a patient without concomitant medications or conditions that could complicate antiemetic selection and use. The regimen described in option A is well designed to give protection against both acute- and delayed-phase symptoms during the days on which antineoplastic treatment is given, but omits prophylaxis against delayed-phase symptoms likely to occur during the days following treatment. In addition, a 20 mg dose of dexamethasone is excessive when given with aprepitant. Option B deviates from ASCO, MASCC/ESMO, and NCCN guidelines by omitting the antiemetic benefit obtained by combining a high-potency glucocorticoid with either or both 5-HT3 and NK1 receptor antagonists. Repeated administration of fosaprepitant at a 150 mg dose on an intermittent schedule also is not supported by FDA-approved product labeling or the three professional guidelines. Option C meets the MASCC/ESMO guidelines’ recommendations with respect to 5-HT3 receptor antagonist and high-potency glucocorticoid on days of emetogenic treatment without an NK1 receptor antagonist, and comes close to both ASCO and NCCN guidelines, but, in contrast with the last two guidelines, the regimen omits an NK1 receptor antagonist on treatment days and dexamethasone use for 2 or three days after completing emetogenic therapy. Option D includes continuous transdermal administration of granisetron from a topically applied patch, a delivery system appropriate for multiple-day emetogenic treatment. A patch delivers granisetron 3.1 mg per day percutaneously during continuous application for up to 7 days. In addition, the regimen includes a high-potency glucocorticoid during emetogenic treatment and for 3 days afterward at doses, administration schedules, and for durations of use consistent with ASCO and NCCN guidelines’ recommendations, and an NK1 receptor antagonist as suggested by both ASCO and NCCN guidelines. Option E includes a 5-HT3 receptor antagonist and dexamethasone on the days when emetogenic treatment is given consistent with all three professional guidelines’ recommendations and for 3 days after chemotherapy is completed which follows ASCO’s and NCCN’s recommendations, but deviates with respect to dexamethasone doses given on days 1 to 5. The regimen also deviates from MASCC/ESMO recommendations by including a NK1 receptor antagonist during multiday chemotherapy and from ASCO and NCCN guidelines’ suggestions with respect to the duration of aprepitant use.
5. B. All three professional antiemetic guidelines label carboplatin as presenting moderate emetic risk, but current NCCN guidelines qualify that categorization by including carboplatin among antineoplastics that may be highly emetogenic in some patients. Although NCCN guidelines do not identify patient subgroups or characterize risk factors that may predispose toward high emetic risk from carboplatin, we should recognize in the present case factors that place her at increased risk for poor emetic control during and after chemotherapy, such as female sex, and from her history, motion sickness, and pregnancy complicated by severe persistent emetic symptoms. As a result of poor emetic control during her first treatment cycle, the patient has acquired an additional risk factor that predisposes for poor emetic control during subsequent emetogenic treatments and for developing a conditioned emetic response, that is, anticipatory symptoms. Arguably, initial prophylaxis did not receive a fair trial because the patient did not complete the antiemetic regimen planned for her first treatment cycle, but the aggregate factors are both historical and acquired that predispose toward poor emetic control and carboplatin’s mutable emetogenic risk between moderate and high suggest pursuing a more aggressive approach to achieve the goal of antiemetic prophylaxis: complete emetic control with each cycle or course of treatment. Option A describes rechallenge with the antiemetic regimen previously attempted reinforced by reinstruction and encouragement to comply with the plan for self-administered medication and monitoring. A reasonable approach in a patient without risk factors for poor emetic control and receiving treatment for which emetic risk was more certain, but the mitigating risk factors noted above are arguments for antiemetic prophylaxis escalated from the previously planned regimen. Option B, escalating the aggressiveness of antiemetic prophylaxis, is suggested by the NCCN guidelines’ characterization of carboplatin-containing regimens as highly emetogenic in some patients, and, from the same resource, a caveat within “Principles for Managing Breakthrough Emesis,” specifically: “Based on the patient’s experiences, the chemotherapy regimen may actually be more emetogenic than generally classified.” Option C is an attractive adjunctive intervention, and may serve to quell what anxiety contributes toward developing and exacerbating emetic symptoms, but evidence for improvement on the effectiveness of antiemetic prophylaxis with a high-potency glucocorticoid combined with 5-HT3 and NK1 receptor antagonists is lacking. Options D and E are empiric approaches to “cover all the bases.” Acknowledging neurotransmitters are the principle mediators in initiating and propagating emetic symptoms, anticholinergic and dopaminergic (D2) receptor antagonists potentially may add preventative or therapeutic benefit. However, the more prudent course before attempting empiric replacement and supplementation would be to optimize emetic control with high-potency glucocorticoids, and 5-HT3 and NK1 receptor antagonists, which, by comparison with anticholinergic and antidopaminergic agents, are more effective and possess better therapeutic indices.
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1. D. The multifactorial causes of weight loss in patients with cancer include cellular and metabolic derangements that lead to depletion of fat and muscle stores. Historically, it was thought that patients with cancer had increased energy expenditure, but measured resting energy expenditure in those with cancer is widely variable and an association with extent of tumor and energy expenditure has not been found. Unlike simple starvation, where glucose turnover is slowed and lean body mass is preserved, there is a maladaptaion to starvation in cancer with increased glucose turnover, increase in wasteful metabolic cycles, increased protein turnover, increased muscle protein degradation, and depletion of adipose stores due to increased lipolysis.
2. D. As summarized in the ASPEN Guidelines, “Nutrition support therapy is appropriate in patients receiving active anticancer treatment who are malnourished and who are anticipated to be unable to ingest and/or absorb adequate nutrients for a prolonged period of time (7 to 14 days).” EN is preferred for patients who are unable to maintain adequate nutritional intake by mouth as it maintains the functional integrity of the gastrointestinal tract. EN via jejunostomy feeding tubes can be successful in patients postgastrectomy. PN would only be appropriate if the patient failed an EN trial with appropriate tube placement. Tracking oral intake will allow the tube feeding volume to be adjusted according to oral intake, so that adequate nutrition can be provided, with eventual weaning off of EN.
3. A. Hypercalcemia of malignancy does not respond to a low calcium diet. NCI’s PDQ cancer information summary on hypercalcemia indicates that “even though the gut has a role in normal calcium homeostasis, absorption is usually diminished in individuals with hypercalcemia, making dietary calcium restriction unnecessary.”
4. D. A patient with low albumin and prealbumin levels may or may not be malnourished. Albumin and prealbumin lack specificity and sensitivity as indicators of nutritional status. They can be reduced by nonnutritional factors such as hypervolemia and inflammation. Earlier reports associating these proteins with nutritional status did not account for the variable of inflammation. These serum hepatic transport proteins are considered negative acute-phase proteins because liver synthesis of these proteins decreases in response to chronic or acute inflammation. C-reactive protein, a positive acute-phase protein, can be measured to help clarify whether active inflammation is present. If C-reactive protein is elevated and albumin or prealbumin are reduced, then inflammation is likely. In order to diagnose a malnutrition syndrome, further information suggesting loss of body cell mass or compromised nutritional intake would be needed. In addition, the half-life of albumin is 18 to 21 days and so a 1-week period is too soon to detect changes in albumin synthesis alone.
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1. C. The patient currently is in a “pain crisis” warranting utilization of stronger analagesics. Based on DOME (daily oral morphine equivalents), 1 mg of intravenous hydormorphone is approximately four times as strong as the hydrocodone the patient had previously taken. Additionally, propoxyphene, oxycodone, and ibuprofen are not available parenterally. Meperidine has metabolites that can be epileptogenic.
2. E. When initiating a long-acting opiate after achieving control of acute pain, the long-acting opiate should be initiated at roughly 50% of the DOME. Among the choices offered, choice E the fentanyl transdermal patch provides 50 mg or roughly 50% of the required analgesia. All the other choices provide much stronger doses of opiates which could possibly result in adverse effects.
3. D. Among the choices listed, choice D is the only one that provides the 30 mg of DOME; all the other choices provide much stronger doses of opiates which could possibly result in adverse effects.
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1. B. In the setting of hypotension and the possibility of an acute GI bleed, standard PICC lines or any central venous access line other than a cordis is insufficient as a resuscitative line. In the scenario detailed above, the appropriate management of the patient is to move him to a critical care bed, send coagulation studies, establish large poor IVs (16G if possible), and type and cross the patient for 4U of packed red blood cells. Type and screen is insufficient in this setting. While blousing with a crystalloid is appropriate, it should be a temporizing intervention with plans for infusion of blood products to be initiated at the same time.
2. D. Damage to the tunica intima results in platelet aggregation and thrombosis of the vein. The end result is the loss of peripheral veins for access for not only venous infusions but also for venous sampling.
3. D. The use of peripheral IV in this setting is not ideal as the patient will be getting a year of therapy in addition to multiple doses of chemotherapy. This will lead to eventual loss of peripheral IV access. The midline catheter cannot stay in place for a year; a nontunneled catheter is too unstable in the long-term setting as it has a high likelihood of being inadvertently dislodging and the subsequent potential for hemorrhage. The tunneled catheter is a reasonable option for long-term chemotherapy, but her therapy will be every 2 to 3 weeks and so constant access to the vein is not necessary. Additionally, a tunneled catheter is much more visible, thereby potentially impeding the privacy of a young woman. The infusaport can be placed in a pocket on the chest wall in a location that can be hidden by garments and therefore from the general public.
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1. C. A contraindication to performing a LP is the presence of unequal pressures between the supratentorial and infratentorial compartments. This is usually deduced from the following characteristics on imaging of the brain: midline shift; loss of suprachiasmatic and basilar cisterns; posterior fossa mass; loss of superior cerebellar cistern; or loss of the quadrigeminal plate cistern. When a patient presents with neurologic symptoms, imaging of the brain is necessary prior to performing LP.
2. B. No, anticoagulation should be held prior to a bone marrow biopsy. The patient should hold his Enoxaparin 24 hours prior to the bone marrow. If the patient was on coumadin, he should be transitioned over to a low-molecular heparin, and this should be held 24 hours prior to the bone marrow.
3. B. In the absence of fluoroscopic guidance, a thoracentesis should be performed through the seventh or eighth intercostal space.
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1. C. Multiple types of radiation can be used to treat breast cancer as part of breast conservation, but all are directed at the breast. Brachytherapy, whole-breast RT, and partial breast RT may all be used to treat breast cancer. Systemic radionucleide therapy is not appropriate as part of breast conserving therapy but may be used as palliative therapy in patients with metastatic disease and in the management of thyroid cancer.
2. B. Most of the effects of radiation occur in the treated area. One of the most common side effects of radiation is skin irritation and redness at the treated site. Patients may also experience fatigue. Alopecia would be unlikely unless the head was treated. Similarly, nausea is unlikely unless the head or abdomen is treated.
3. B. Dividing radiation into smaller doses takes advantage several aspects of tumor biology. First, this allows more tumor cells to be exposed to radiation in a sensitive phase of the cell cycle since different cells will be cycling at different times. In addition, many normal tissues can repair better than tumors, thus giving smaller doses at different times instead of one large dose takes advantage of this by letting normal tissue repair in between. Additionally, tumors tend to be better oxygenated after a dose of radiation, likely through killing of competing tumor cells, thus increasing oxygenation and sensitivity to radiation.
4. D. Damage to DNA is the primary mechanism of lethality after exposure to radiation. Although many organelles and cellular components may be damaged by radiation, these do not typically result in lethality.
5. B. IMRT is a method that allows a highly conformal treatment. Similar doses are given compared to other external beam RT approaches so the overall treatment time, total dose, and DNA damage are similar.
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1. B. Any woman with triple negative breast cancer under the age of 60 should have testing for BRCA1/2 testing including BART. Choice A is not the correct answer because she needs genetic testing. C is not the correct answer because she should have BRCA testing first. If BRCAtesting is negative, it is recommended for all women with breast cancer under the age of 30 have p53 testing. D and E are not correct because she does not meet criteria for PTEN testing or Peutz–Jeghers syndrome.
2. D. The tumor spectrum for LFS includes sarcoma, premenopausal breast cancer, brain tumor, adrenalcorticoid tumor, leukemia, and lung bronchoalveloar cancer.
3. B. The rest of the tumors are seen commonly with Cowden syndrome.
4. C. This patient has the classic presentation of colon cancer in a family history consistent with Lynch syndrome. Colon cancer associated with Lynch syndrome is typically found in the right colon and, despite the aggressive histologic features, does not metastasize as often as sporadic cases. Lynch syndrome is caused by germline mutations of the MMR genes, of which MLH1 and MSH2 are the most common.
5. B. Von Hippel–Lindau disease is commonly associated with hemangioblastoma of the CNS, clear cell RCC, pancreatic neuroendocrine tumors, and pheochromocytomas. In this patient whose family history is highly suspicious for VHL disease, a concomitant diagnosis of pheochromocytoma must be ruled out prior to surgery to minimize perioperative complications and avoid the use of β-blockade.