Christopher R. Kelsey, Junzo P. Chino, Jared D. Christensen, and Lawrence B. Marks
This chapter addresses two topics central to the management of patients with cancer: oncologic anatomy and oncologic imaging. Although these topics are relevant for all specialties involved in the treatment of cancer, they are particularly germane for radiation oncologists. A sound understanding of anatomy, especially pertaining to malignant processes, facilitates interpretation of imaging studies. Likewise, understanding the advantages and limitations of individual imaging modalities assists in defining rational clinical target volumes (CTVs) that maximize the therapeutic ratio.
Advances in diagnostic imaging have increased our ability to visualize macroscopic disease, referred to as gross tumor volume (GTV). Imaging is currently unable to identify microscopic tumor extension around a primary tumor or occult nodal involvement. A CTV is created to account for both of these uncertainties (Table 30.1). A rational definition of the CTV should reflect the clinician’s knowledge regarding the patterns of spread for each particular cancer. This involves both local spread around the primary site and patterns of lymphatic drainage. Appropriate expansion of a GTV to a CTV minimizes the risk of local failure (i.e., marginal miss), while reducing the risk of complications by avoiding regions at low risk of involvement (Fig. 30.1).
Radiation treatment planning has undergone considerable evolution during the past 20 years. With conventional planning, the physician conceives of beam orientations and aperture shapes based on the interpretation of available clinical and diagnostic information, including three-dimensional (3D) imaging data such as computed tomography (CT) or magnetic resonance imaging (MRI). The beam is then applied to the patient using a fluoroscopy-based conventional simulator, relying on an understanding of tumor and normal tissue anatomy and its association with fluoroscopic bony anatomy and surface anatomy. Relatively generous margins are used to account for inherent uncertainties of the process.
With 3D treatment planning, anatomic information from a planning CT scan is transferred to a computer where the images are segmented to define the tumor and normal tissues. Software allows this 3D information to be displayed and viewed from any orientation. Beam orientation and shape are chosen to encompass the target, yet minimize, as much as possible, normal tissue exposure. Thus, 3D planning tools allow the 3D anatomy to be more accurately incorporated into the planning process than with conventional techniques. The computer allows the planner to use beam orientations that are nonstandard (e.g., nonaxial beams). Beam apertures are typically smaller than with conventional simulation due to reduced uncertainty in the entire process. Current technology also allows data from other imaging modalities (MRI, positron emission tomography [PET], etc.) to be fused with the planning CT dataset and hence considered in the planning process. It is advantageous to position the patient similarly during the imaging and treatment planning scans to facilitate accurate image correlation.
Intensity modulated radiation therapy (IMRT) requires the clinician to explicitly delineate target volumes, including elective nodal basins and avoidance structures. The introduction of IMRT has revolutionized radiation treatment planning, and in the process, has required clinicians to become more proficient in 3D anatomy and malignant patterns of spread. Several groups have published guidelines demarcating elective nodal stations on axial CT images, including head and neck cancer,1,2 lung cancer,3 anorectal cancer,4 and others. These stations are somewhat artificial but facilitate rational demarcation of nodal stations at risk, reporting of patterns of spread and failure, and communication with surgical colleagues.
One of the risks of 3D and IMRT is a false sense of security in the accuracy of imaging to portray the in vivo extent of disease. Further, imaging obtained at the time of initial treatment planning may not be representative of the in vivo anatomy throughout a multiweek course of therapy. Indeed, there have been several published examples of inferior outcomes with highly conformal treatment planning.5,6 Modern imaging tools are clearly not perfect. The rapid embrace of newer technologies to visualize gross tumor and to address uncertainties related to organ motion and setup errors may be counterproductive if relied on too heavily in the treatment planning process. It is likely that we have, in the past, been able to sterilize microscopic tumor at the edge of radiotherapy fields that were expanded to account for setup errors and organ motion (i.e., not expanded with the intent of covering the microscopic disease). Furthermore, the clinical history or examination and imaging can be discordant, and one needs to be careful not to be overly reliant on imaging when defining target volumes. For example, in a patient with cancer of the nasopharynx with cranial nerve deficits, the target volume should include the corresponding anatomic site of likely extension, even in the absence of an abnormality on imaging. Thus, a sound understanding of oncologic anatomy and imaging modalities is vital in the treatment planning process.
FIGURE 30.1. Gross disease identified with imaging is depicted, along with appropriate expansions to encompass surrounding microscopic disease (CTV) and setup/motion uncertainties (PTV).
TABLE 30.1 VOLUME DEFINITIONS FOR RADIATION THERAPY PLANNING
IMAGING MODALITIES
Radiologic imaging is an integral component in the management of cancer patients. Imaging is utilized in the diagnosis and initial staging of disease, treatment planning, and posttreatment surveillance. Radiation oncologists must be familiar with the available imaging modalities and understand the appropriate utilization and limitations of each, which often varies based on the tumor site and study indication. In particular, a general sense of the sensitivity, specificity, and positive and negative predictive values of an imaging study helps the clinician assimilate and interpret imaging information that can be misleading or even contradictory. A detailed review of each imaging modality and its associated physics is beyond the scope of this chapter. However a general overview of the imaging modalities most frequently utilized in clinical practice is provided, with disease-specific applications addressed in the systems-based anatomy sections.
Radiography
Conventional radiography creates a two-dimensional gray-scale image produced by the differential attenuation of x-rays that pass through soft tissues of varying density. Tissues that are very dense, such as bone, will absorb more x-rays than tissues that are less dense, such as lung. Radiographs are therefore best suited to detect pathology when a lesion differs greatly in density from adjacent structures, such as a soft tissue mass surrounded by aerated lung or a lytic lesion surrounded by dense bone. Radiographs have excellent spatial resolution: the ability to detect a small object within a given volume. However, they are suboptimal when there are only subtle differences in tissue density. Therefore, even large lesions can be missed if they are of similar density to surrounding structures. Given this and other limitations, additional imaging modalities are often obtained to supplement plain radiographs. In addition, although conventional radiography has limited utility in oncologic imaging, the basic principles underlie more advanced imaging modalities such as CT.
Cross-Sectional Imaging
CT, MRI, and ultrasound (US) generate two-dimensional cross-sectional images. The benefits of cross-sectional imaging include visualization of superimposed structures obscured on planar images, improved anatomic detail of individual organs and their precise relationship to adjacent structures, and the ability to perform multiplanar reconstructions. Furthermore, some applications provide functional in addition to morphologic information and can be acquired in real time, permitting image guidance for procedures. For these reasons, cross-sectional modalities are the mainstay of oncologic imaging.
Computed Tomography
CT generates cross-sectional images from the transmission of radiation through tissue. A patient lies on the scanner table within a gantry that houses an x-ray generator opposite multiple rows of detectors, hence the term multidetector CT (MDCT). Current generation scanners (e.g., 64 or 128 MDCT) are able to acquire high-resolution image data much faster due to improvements in the number of detectors and computer processing. As the gantry rotates, the detectors measure x-ray transmission through the rotation, or slice. The patient is moved through the scanner as the gantry rotates, resulting in a helical or spiral course at a very thin slice thickness, typically 0.625 mm. The spatial and temporal data from multiple projections are then processed by a Fourier transform mechanism generating two-dimensional axial images. The thin-slice volume dataset is isotropic, meaning that images can be reconstructed in orthogonal and oblique planes without a loss in image quality. Furthermore, thin-slice acquisition improves contrast resolution and decreases partial volume artifacts, thereby improving imaging quality and accuracy.
Images are displayed within a matrix composed of voxels, each representing a volume of radiodensity that is quantified by a linear attenuation value called a Hounsfield unit (HU). Each voxel is assigned a HU in the range of –1,000 to 1,000 corresponding to a shade of gray to represent the attenuation difference between a given material and water. By convention, air is the least dense material with a HU value of –1,000, while water has a HU value of 0. Soft tissues have a range of attenuation with typical HU values as follows: fat (–120), blood (30), muscle (40), bone (>300). HU analysis is more accurate than visual assessment of tissue composition and is particularly useful in characterizing enhancement postcontrast administration, a feature critical in the assessment of many solid organ lesions.
Both intravenous (IV) and oral contrast agents may be utilized to improve spatial resolution. Oral contrast agents are routinely used for abdominal and pelvic imaging to distinguish bowel from adjacent organs, lymph nodes, and tumors. The use of an intravascular contrast agent during CT depends on the study indication, target organ, and patient status. IV contrast agents contain variable concentrations of iodine compounds that attenuate, or absorb, x-rays, which allows for enhanced detection of vascular structures. Administration of IV contrast media is required for thorough assessment of vessels (e.g., aorta, pulmonary arteries), solid organs (e.g., liver, kidneys), and characterization of lesion vascularity. Contrast-enhanced CT is often necessary to detect solid organ metastases (e.g., liver, adrenal gland, brain). Contrast is usually not necessary for routine pulmonary imaging due to the inherent contrast of solid lesions within a background of aerated lung, although it does improve the characterization of hilar lymph nodes.
Given that the administration of contrast media can alter tissue attenuation, the HU value of a lesion or tissue may differ depending on whether the study was performed with or without contrast and based on the timing of image acquisition (e.g., arterial vs. portal venous phase). HUs are used during radiation treatment planning dose calculations; therefore, contrast can affect these calculations. If indicated, the HU within a structure enhanced by contrast (e.g., the bladder when planning for prostate cancer treatment) can be set to an alternate value prior to dose calculations. A similar phenomenon often occurs when materials with a high atomic number are within the scanned volume. These materials (e.g., dental fillings, hip prostheses) can cause artifacts that can make it challenging to accurately segment the image or affect dose calculations. The latter can also be corrected by setting the HU within the affected area to the desired value.
IV contrast agents are excreted through the kidneys, are nephrotoxic, and are not typically administered to patients with impaired renal function (glomerular filtration rate [GFR] <60, creatine [Cr] <1.8) unless on dialysis or out of emergent medical necessity. IV contrast media should also not be given to patients with a known contrast allergy resulting in anaphylaxis or laryngeal edema. More minor reactions, such as pruritus, are not an absolute contraindications and contrast may be administered following a proper steroid pretreatment protocol. Alternative imaging modalities should be considered if a contrast-enhanced study is required in the setting of a severe contrast allergy. An allergy to shellfish is no longer considered a contraindication to iodinated contrast administration.7
In part due to its availability, rapid acquisition, and high-yield anatomic data, CT has become one of the most widely used medical imaging modalities in the United States, with over 70 million scans performed annually, and it serves as the core modality for oncologic imaging.8 Although CT is noninvasive, it is not entirely benign. CT utilizes radiation to generate images, and although dose modulation and optimal scanning parameters can significantly reduce patient radiation exposure, the cumulative effects of CT radiation are of clinical concern. Alternative imaging modalities should always be considered and performed in lieu of CT when appropriate.
Magnetic Resonance Imaging
MRI generates cross-sectional images without ionizing radiation. MRI utilizes strong magnets, typically 1.5 or 3.0 T for clinical applications. A 3.0 T magnet is 60,000 times greater than the earth’s magnetic field. The magnetic field uniformly aligns the nuclei of hydrogen protons within tissue. Applying a radiofrequency (RF) pulse sequence and gradient to the magnetic field disrupts this alignment and equilibrium. When the RF pulse is removed, the protons realign, or relax, within the field and emit a measurable resonance radio signal. The detected radio signals, referred to as echoes or spin echoes, are then used to generate an image. The most important tissue properties for image generation are the proton density, the spin-lattice relaxation time (T1) and the spin-spin relaxation time (T2). Different tissues have different proton density and relaxation times, absorbing and releasing radio wave energy at different rates, which in part accounts for the high tissue contrast obtained by MRI.
Different RF pulse sequences can accentuate different tissue characteristics by varying parameters such as the repetition time (TR)—the time between RF pulses in the sequence, which determines how much time protons have to realign within the magnetic field—and the echo time (TE)—the time between the RF pulse and the peak returning signal. TR and TE dramatically affect image contrast and determine which tissue properties are selected. T1-weighted images, in which fluid is dark and fat is bright, are generally good at depicting anatomy; T1-weighted images are generated by selecting short TR (typically ≤800 ms) and short TE values (≤30 ms). T2-weighted images, in which fluid is bright and fat is dark, are fluid-sensitive and can depict areas of pathology; T2-weighted images are generated by selecting long TR (≥2,000 ms) and long TE values (≥60 ms) (Table 30.2). Scan sequences are composed of variations in RF pulses and TR and TE settings. Although these vary by MRI scanner manufacturer using proprietary names, the underlying principles are similar. Common sequence techniques include:
Spin-echo (SE) sequences produce standard T1- and T2-weighted images.
Multiple spin-echo (MSE) sequences allow for faster image acquisition and are also referred to as turbo spin echo, fast spin echo, or rapid-acquisition relaxation-enhanced imaging. The signal intensity and image quality is less than that of conventional SE sequences. Furthermore, fat is bright on MSE T2-weighted images, which can limit sensitivity for detecting pathology. Fat-suppression techniques can be used to offset this limitation. Fast low-angle acquisition with relaxation enhancement and half-Fourier acquisition single-shot turbo spin-echo sequences are MSE variations.
Inversion recovery (IR) pulse sequences emphasize differences in T1 properties of tissues. A time of inversion (TI) is added to the sequence that can be set to target specific tissues. Short time of inversion recovery sequences suppress tissues with short T1 relaxation times, such as fat, and enhance tissues with high T2 properties, such as fluid, resulting in added tissue contrast. The opposite effect may be achieved with fluid-attenuation inversion recovery sequences. In addition to IR, tissue suppression may be achieved with fat or fluid saturation and opposed-imaging techniques.
Gradient-recalled echo (GRE) pulse sequences are used for rapid image acquisition, which minimizes motion artifact associated with breathing, the cardiac cycle, vessel pulsation, and bowel peristalsis. GRE sequences have low tissue contrast, with the exception of flowing blood, which is bright in signal, and are therefore ideal for cardiac and vascular applications. Fast low-angle shot (FLASH) and true fast imaging with steady-state precession (FISP) are examples of this technique.
Although the inherent tissue contrast with MRI is excellent, the administration of contrast media can further improve the detection of pathology and subtle differences in tissue properties. Gadolinium chelates are the most commonly used MRI contrast agents, which, like the iodinated CT equivalents, are confined to the vasculature and do not cross an intact blood–brain barrier. Gadolinium is a heavy metal ion with paramagnetic effects that shorten T1 and T2 relaxation times. Although there are flow-related techniques for vascular imaging that do not require contrast media (e.g., time of flight imaging), the use of a contrast agent is essential for characterizing tissue perfusion. Once considered safe for patients with impaired renal function, the use of gadolinium-based contrast agents have now been associated with nephrogenic systemic fibrosis (NSF), a debilitating and potentially fatal condition of fibrin deposition within the skin and other organs.9 Although the precise mechanism is not understood, patients with severe renal dysfunction (GFR <30) who receive gadolinium-based contrast media are at increased risk of developing NSF.
One of the advantages of MRI over CT is that it can provide functional in addition to anatomic information. This is particularly beneficial in oncologic imaging. MRI techniques allow for tissue diffusion and perfusion imaging, quantification of blood flow by velocity phase encoding, and magnetic resonance proton spectroscopy, which provides biochemical quantification of tissues.
As with other imaging techniques, MRI has modality-specific artifacts that can limit image quality. Motion artifact can be problematic with MRI due to long scan times. Chemical shift artifact results in a loss of signal at the interface of tissues with highly variable contrast properties. MRI is also highly sensitive to magnetic field distortions that can produce artifacts. Susceptibility artifact is one of the most common problems with MRI and is frequently attributable to objects that alter the magnetic field, resulting in signal voids or distortion of MRI images, such as metallic hardware or devices. The magnetization of such objects also presents a safety hazard as items can overheat or become displaced, resulting in serious harm or injury. Patients must be carefully screened to ensure that any medical devices or surgical hardware are MRI compliant.
TABLE 30.2 MAGNETIC RESONANCE IMAGING SIGNAL INTENSITIES (SPIN-ECHO IMAGING)
Ultrasonography
US is an imaging modality utilizing pulse-echo techniques rather than radiation to produce an image. The US transducer coverts electrical energy into a high-frequency pulse that is transmitted through tissues. The pulse interacts at tissue interfaces, generating a reflected echo signal that is detected by the transducer. The returning sound waves are transformed into a gray scale image in real time. Image quality is, in large part, determined by the pulse frequency. High-frequency transducers (5–12 MHz) produce high-resolution images but have limited ability to penetrate. Therefore, they are best suited to imaging superficial structures such as the breast or thyroid. Low-frequency transducers (1–3.5 MHz) generate lower quality images but have better tissue penetration and are most often used for imaging abdominal and pelvic organs. The degree to which tissues are visualized by US is called echogenicity. Fat is highly echogenic (bright), whereas fluid-containing structures, such as simple cysts, are anechoic (dark).
The quality of US images is highly dependent on the sonographer. Variability in user experience can be problematic in the performance, reproducibility, and interpretation of US exams. Furthermore, US is prone to artifacts. Bone almost completely absorbs sound waves, resulting in acoustic shadowing that completely obscures tissues located beyond the bone. Air is also problematic as it almost completely reflects sound waves, leaving little pulse energy to penetrate tissues deep to the air. The application of a water-soluble gel between the transducer and the patient’s skin eliminates air at the skin surface and ensures transmission of the US beam. Artifacts secondary to air markedly limit evaluation of lesions near the lung or bowel. In contrast to air, fluid readily transmits sound and makes an excellent “acoustic window” for imaging. This is the reason that patients are encouraged to drink plenty of fluids prior to a pelvic US examination—so that the bladder is fully distended.
TABLE 30.3 ENDOSCOPIC ULTRASOUND WALL LAYERS OF THE ESOPHAGUS
FIGURE 30.2. Axial endoscopic ultrasound image (right) and histologic specimen (left) from a normal esophagus. The endoscopic ultrasound layers and histologic layers of the esophagus are correlated (see Table 30.3). (Endoscopic ultrasound image courtesy of Dr. Frank Gress. Histologic image courtesy of Dr. Daniel Goodenough.)
Color Doppler US is an important adjunct to conventional gray-scale sonography. The Doppler effect is a change in frequency of returning sound waves reflected by a moving object, such as flowing blood. If blood flows away from the transducer, the echo frequency decreases; whereas if blood flows toward the transducer, the echo frequency increases. The change in frequency is directly proportional to the flow velocity and produces a color overlay in areas of flow on the standard gray-scale US image. Color Doppler US is useful in characterizing blood flow within lesions and assisting in image-guided procedures.
Endoscopic ultrasound (EUS) was introduced in the early 1980 s and has become a tool important in oncologic staging. It allows for high-resolution images of internal structures not typically accessible by high-frequency transducers by passing the probe through bowel or airways. It is most widely applied in the setting of gastrointestinal (GI) malignancies, especially esophageal and rectal carcinomas. A 5 to 12 MHz transducer can readily identify five of the layers of the gastrointestinal tract (Table 30.3 and Fig. 30.2).10 Higher frequency transducers can identify additional layers, such as the muscularis mucosa and lamina propria of the esophagus, which has important staging implications. EUS is also utilized for characterization and image-guided sampling of regional lymph nodes in GI or bronchopulmonary disease. The ability of EUS to predict the tumor (T) stage is generally superior to its ability to predict the node (N) stage, although some imaging patterns of nodal involvement are recognized. Normal lymph nodes are usually ovoid, <10 mm in short axis, and have a homogeneous but variable echogenic appearance that may be isoechoic, hyperechoic, or hypoechoic to surrounding tissues. An echogenic (bright) center is common and represents the normal fatty hilum. Suspicious lymph nodes are typically round, >10 mm in short axis, have distinct margins, and are typically hypoechoic. If all four features are present, the likelihood of malignancy is 80% to 100%.11 There is, however, considerable overlap between benign and malignant features of lymph nodes on EUS in addition to wide interobserver variability. Tissue sampling is therefore recommended for accurate staging. When describing clinical T and N staging by EUS, the prefix u should be utilized (e.g., uT3N1).
Nuclear Imaging
Although radiographic and cross-sectional studies provide important anatomic information regarding pathologic processes, nuclear radiology provides physiologic information based on the distribution of an injected or ingested radiopharmaceutical. Radiopharmaceuticals consist of a radioactive substrate (radionuclide, radioisotope, or radiotracer) that is coupled with a physiologically active compound or analog. For example, technetium-99 m is a radioisotope that is coupled to pertechnetate, an iodine analog, which can enter thyroid follicular cells. The timing of imaging depends on the kinetics of absorption, metabolism, and half-life of the radionuclide. Gamma rays emitted by nuclear decay of the radionuclide are then detected using a γ-camera corresponding to radiotracer activity that is described in terms of uptake.
There are numerous available nuclear imaging studies that take advantage of differing radiopharmaceuticals for oncologic imaging. Many of these play a primary role in the management of oncology patients with specific malignancies. For example, indium-111 capromab pendetide (ProstaScint) can be utilized for prostate cancer and gallium-67 can be used for lymphomas—both of which will be discussed in greater detail later in the chapter. However, the primary nuclear imaging studies relevant to general oncologic imaging are PET and bone scintigraphy. These studies have broad application for many malignant processes in the diagnosis, staging, and surveillance of disease.
Positron Emission Tomography
Although several radionuclides for PET are available, the most common is 18-fluorodeoxyglucose (FDG). FDG is a glucose analog that concentrates in areas of high metabolic activity. Tumor cells are often highly metabolic, with rapid cell division and an increased number of glucose transporters. However, FDG uptake is not specific for malignancy and accumulates in any cell with increased metabolic activity, including myocardium, gastric mucosa, brain tissue, thyroid, and salivary glands, which limits evaluation of these organs. Furthermore, FDG tracer is excreted within the urinary system; therefore, activity within the kidneys, collecting system, and bladder can obscure malignancy of these structures. Notwithstanding these limitations, PET-CT has become the preferred imaging modality for clinical staging, facilitating the characterization of benign versus malignant pathology, detecting sites of unsuspected disease, identifying optimal sites for tissue sampling, assessing treatment response, and monitoring for recurrence for multiple malignancies.
Initially performed in isolation, PET is now routinely obtained in conjunction with CT. PET-CT combines the physiologic assessment of PET with the anatomic assessment of CT, resulting in improved diagnostic accuracy.12 PET and CT may be obtained independently on the same day but is more commonly performed on a combined PET-CT scanner, which more precisely aligns the two imaging datasets for fusion as the patient does not have to move between examinations. Patients must fast for 4 to 6 hours prior to scanning in order to limit metabolic activity within the GI tract. Blood glucose levels should be well controlled (<150 mg/dL) to limit glucose receptor competition with FDG, as high glucose levels can result in a false-negative scan. Speech and motion should be restricted to minimize muscle uptake, which could obscure pathology. Approximately 1 hour following FDG administration, a CT scan is performed immediately followed by PET imaging, which can take up to 60 minutes. CT and PET datasets are then reconstructed in separate axial, coronal, and sagittal series as well as fused PET-CT images.
FDG uptake is nonspecific, localizing to any tissue with increased metabolic activity. Although most malignant tumors are hypermetabolic relative to normal tissues, nonmalignant processes also concentrate FDG, including foci of infection, inflammation, and benign neoplasms. FDG uptake is quantified by the standard uptake value (SUV). Most malignant tumors have a maximum SUV >2.5, while physiologic uptake is typically <2.5. SUVs are not absolute and can be affected by the timing of imaging, improper attenuation correction, partial volume affects, patient weight, FDG dose, and factors affecting FDG uptake, as previously described. It is therefore difficult to accurately compare SUVs between scans. However, if care is taken to ensure that variables between studies are similar, such as performing the examination on the same scanner with similar patient preparation, FDG dosing, and image timing, comparing SUVs between studies may be reliable. Clinical studies to date have documented that under such uniform conditions, changes in SUV have prognostic value, indicating that most tumors responding to therapy show a 20% to 40% decrease in SUV early in course of treatment.13–15
Bone Scintigraphy
Normal bone undergoes continuous remodeling, maintaining a delicate balance between osteoblastic and osteoclastic activity. Most bone metastases originate as intramedullary lesions, having gained access to the bone through the vasculature. As the lesions enlarge, reactive osteoblastic and osteoclastic changes result in characteristic radiographic changes indicative of bone metastases (sclerotic, lytic, or mixed lesions). Rapidly growing metastases tend to produce lytic lesions, while more slowly growing metastases typically produce sclerotic (or blastic) lesions. Metastases from multiple myeloma, thyroid cancer, and renal cell carcinoma are predominantly lytic, while blastic lesions are associated with breast and prostate cancers. The primary utility of bone scintigraphy in oncologic imaging is the detection of osseous metastatic disease.
Bone scintigraphy or bone scan imaging utilizes radiopharmaceuticals composed of bisphosphonates; the most common of which is the radionuclide technetium-99 m methylene diphosphonate (99mTc-MDP). 99mTc-MDP localizes to areas of new bone mineralization, which occurs in a wide array of bone pathology and is therefore highly sensitive to osseous disease, but is not very specific. Although a 30% to 50% reduction in bone density must occur before bone metastases are detected on radiographs, as little as 5% to 10% change is required to detect such on a bone scan.16,17 Furthermore, bone scans are relatively inexpensive, convenient, and visualize the entire skeleton, including sites that are difficult to assess on plain films (e.g., ribs, sternum, scapula, sacrum). Reported sensitivities range from 62% to 100% with similar specificity rates (78% to 100%).18
Two primary patterns of radiotracer activity can be associated with malignancy: increased or decreased activity. Increased uptake occurs in areas of increased blood flow and osteoblastic activity; this is a common finding in metabolically active tumors and small sclerotic metastatic foci. Decreased radiotracer activity occurs as a “cold” area on bone scan and is associated with lytic bone disease and aggressive tumors that outgrow their blood supply. Rapidly progressing and purely lytic disease are the main causes of false-negative findings on bone scintigraphy, while false-positive findings can be related to trauma, healing, benign bone tumors, or arthritic changes.
Bone metastases are considered “nonmeasurable” using the Response Evaluation Criteria in Solid Tumors.19 Although a decrease in the intensity of radionuclide uptake is often ascribed to a response to treatment and an increase is attributed to progressive disease, several points must be considered. First, tumor response may cause a “flare phenomenon,” resulting from increased activity secondary to new osteoblastic activity concomitant with new bone formation. This may be falsely attributed to progressive disease. Similarly, lytic lesions that were previously “cold” on bone scan can transform into “hot” spots (areas of uptake) after treatment. Second, rapidly progressive disease with overwhelming bone destruction without new bone formation can be misinterpreted as stable or responding disease on bone scan.
Many patients are at low risk of harboring occult osseous metastatic disease and, in the absence of symptoms, a bone scan can be omitted from the staging workup. In prostate cancer, only approximately 1% of patients with a prostate-specific antigen (PSA) <10 will have a positive bone scan.20,21 Patients with a Gleason score ≤7 and a PSA of 10 to 20 have a similar low risk of bone metastases.22 In these patients, a bone scan should be omitted in the absence of symptoms. Similarly, a bone scan may be omitted in asymptomatic patients with node-negative breast cancer and lung cancer. Although studies have shown that MRI may be more sensitive than bone scans, especially for vertebral metastases, whole-body MRI is impractical and bone scintigraphy is considered sufficiently sensitive that MRI should be reserved for equivocal bone scans in the context of high clinical suspicion or for patients with positive bone scans but low clinical suspicion. Like MRI, PET has been shown to be more sensitive than scintigraphy for the diagnosis of osseous metastatic disease with sensitivity of 91% and 75%, and specificity values of 96% and 95%, respectively.23 FDG-PET also provides earlier detection of metastases than bone scans, attributable to the fact that increased glucose metabolism in neoplastic cells occurs prior to increased osteogenesis (required for bone scintigraphy uptake). PET also has the advantage of providing more comprehensive imaging in that it can detect soft tissue metastases in addition to bone disease, whereas scintigraphy only evaluates osseous structures. As a general rule, patients with isolated osteoblastic metastases may be monitored by serial bone scans, while other clinical scenarios are likely best suited for PET.
BRAIN AND SPINE
Oncologic Anatomy
The Brain
The central nervous system consists of the brain and spinal cord. Both are covered with three meningeal layers—the dura mater, arachnoid mater, and pia mater. Meningiomas are the most common tumors arising from the meninges. They arise from arachnoid cells but are typically affixed to the underside of the dura mater. They are well-circumscribed tumors that do not typically invade the underlying brain parenchyma. Thus, when planning a course of radiation therapy, only minimal margins are required to account for surrounding microscopic disease extent in the direction of the brain parenchyma. Many meningiomas will have a linear area of enhancement on MRI, extending from the tumor along the dura. This so-called dural tail is generally not felt to represent direct extension of tumor but rather vascular congestion within the dura, leading to the characteristic enhancement.24,25 Thus, enlarging the target volumes to include this linear area of enhancement is probably unnecessary unless other imaging abnormalities are apparent (e.g., nodularity).
The arachnoid mater and pia mater are considered the leptomeninges with the intervening space (subarachnoid space) filled with cerebrospinal fluid (CSF). Cancer can breach the CSF space through several routes, including hematogenous spread (via the Batson venous plexus or the arterial system) or by direct extension. Once cancer breaches the subarachnoid space, the entire craniospinal axis is at risk, and tumor deposits can lead to increased intracranial pressure, cranial nerve deficits, radiculopathies, and seizures. Leptomeningeal involvement occurs most frequently with pediatric brain tumors (e.g., medulloblastoma), acute lymphoblastic leukemia, and some solid cancers (e.g., breast cancer, melanoma, and lung cancer in particular).26
The major units of the brain include the cerebral hemispheres, diencephalon, cerebellum, and brainstem. The cerebral hemispheres consist of the frontal, parietal, temporal, and occipital lobes, basal ganglia, and lateral ventricles. The diencephalon includes the thalamus, hypothalamus, and third ventricle. The brainstem consists of the midbrain, the pons, and the medulla oblongata. The fourth ventricle lies between the pons and the cerebellum. Although more than half of pediatric brain tumors arise in the posterior fossa (cerebellum and brainstem), the vast majority of primary brain tumors in adults arise in the cerebral hemispheres or diencephalon.
Cranial Nerves
The cranial nerves consist of 12 paired nerves whose nuclei (with the exception of CN I) are located in the brainstem and upper spinal cord. They are termed cranial nerves because they exit the cranium through foramina in the base of skull and are encased by sheaths formed from the meninges. Nerve pathways connecting the cerebral cortex with the cranial nerves are complex. Although spinal motor neurons are innervated by the corticospinal tracts, many of the lower motor neurons in the brainstem are innervated by the corticobulbar tracts. These upper motor neurons innervate the cranial motor nuclei bilaterally (with some exceptions), in contrast to the nerves within the corticospinal tracts, which largely cross in the medulla leading to contralateral innervation.
Multiple tumors, both benign and malignant, commonly involve the cranial nerves, leading to serious neurologic deficits. Some of the more common include meningiomas involving the optic nerves (CN II), vestibular schwannomas (CN VIII), parotid gland tumors (CN VII), nasopharyngeal carcinoma (multiple), and brainstem gliomas (multiple).
The classic presenting symptoms of diffuse pontine gliomas illustrate the intricate anatomy of the pons. A unilateral lesion in the ventral pons with involvement of the pyramidal tracts (upper motor neurons) might cause contralateral motor weakness in the arms or legs. In addition, cranial nerves within the pons might also be affected, unilaterally, without complete paralysis because of bilateral innervation of the cranial nerves by fibers in the corticobulbar tracts. Ataxia, denoting impairment of coordination without weakness, can be caused by involvement of fibers projecting from the pons to the cerebellum within the middle cerebellar peduncle. Through this pathway, the cerebellum receives a copy of the information for muscle movement that the corticospinal tracts relay to lower motor neurons, facilitating the complicated act of coordination.
The cranial nerves should also be carefully examined when evaluating a patient with nasopharyngeal carcinoma (NPC). One-fifth of patients with NPC present with symptoms of cranial nerve involvement (Table 30.4). The most commonly involved cranial nerves are the abducent nerve (CN VI) and the trigeminal nerve (CN V). CN VI originates in the ventral aspect of the brainstem, ascends on the clivus, and crosses the internal carotid artery near the superior aspect of foramen lacerum before entering the cavernous sinus. It then exits the skull through the superior orbital fissure. The motor and sensory nerve roots of CN V exit the pons, pass underneath the free edge of the tentorium cerebelli into Meckel’s cave, forming the trigeminal (Gasserian) ganglion. From the ganglion, V1 and V2 enter the cavernous sinus and subsequently exit the skull through the superior orbital fissure and foramen rotundum, respectively. V3 exits the skull through foramen ovale.
The nasopharynx is in close proximity to foramen lacerum, rotundum, and ovale, explaining the frequent tumor involvement of CN V and VI. Invasion superiorly to the foramen lacerum and involvement of the trigeminal ganglion could lead to dysfunction in all three branches of CN V. In fact, most patients with NPC and CN V involvement have isolated deficits of V2 or V3. This occurs due to extension into foramen rotundum and ovale, respectively (Fig. 30.3). After gaining access to the middle cranial fossa, NPC may extend superiorly into the cavernous sinus. Four cranial nerves, including two branches of CN V, pass through the cavernous sinus. Within the sinus, the oculomotor nerve (CN III) is located most superiorly, while the maxillary nerve (CN V2) is located most inferiorly. One would suspect that cranial nerves located more superiorly in the cavernous sinus would be involved less frequently than those located closer to the base of skull. This is consistent with what is observed clinically (see Table 30.4).
Lower cranial nerve involvement can occur without intracranial extension. The fossa of Rosenmüller is the most common site of origin of NPC. The lateral border of the fossa of Rosenmüller is the pharyngeal space. Direct tumor extension laterally into the parapharyngeal space or lymphatic metastases to high parapharyngeal lymph nodes can affect the cranial nerves exiting the jugular foramen (CN IX, X, and XI), and hypoglossal canal (CN XII). This may result in loss of the gag reflex (CN IX), hoarseness or dysphagia (CN X), atrophy or paralysis of trapezius and sternocleidomastoid (CN XI), as well as tongue deviation (CN XII).
Spine
The vertebral column typically consists of 33 bones (7 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 4 coccygeal). The sacral and coccygeal vertebral bodies are fused. Although all individuals have seven cervical vertebral bodies, variations in the number of the other vertebral levels are occasionally observed. The spinal cord is housed within the spinal canal and encased by the meninges. Spinal cord levels do not correspond with levels of the vertebral column. In adults, the spinal cord typically ends at the L1-2 interspace (termed the conus medullaris). In an infant, the spinal cord terminates at L2 or L3. However, the spinal nerves continue to descend within the spinal canal (termed the cauda equina). The subarachnoid space, containing CSF, typically extends to the second sacral vertebral body. At this level the meninges fuse together and extend caudally as the filum terminale, which anchors the spinal cord to the coccyx. These anatomical issues have implications when evaluating a patient with spinal cord compression, designing craniospinal fields, and when setting up palliative spine fields.
TABLE 30.4 MAJOR FORAMINA AND OTHER APERTURES IN THE CRANIAL FOSSAE AND THEIR PRIMARY CONTENTS AND CLINICAL ASSOCIATION WITH NASOPHARYNGEAL CANCER
FIGURE 30.3. Coronal T1 magnetic resonance image with contrast demonstrating nasopharyngeal carcinoma extending through foramen ovale into Meckel’s cave.
FIGURE 30.4. Axial T1 magnetic resonance image with contrast demonstrating a 2.5-cm melanoma brain metastasis in the left frontal lobe. Note the prior resection cavity in the right frontal lobe.
Oncologic Imaging
Intracranial Metastases
Approximately 50% of adult intracranial neoplasms are metastatic, with lung, breast, melanoma, renal, and colon cancers being the most common, in order of decreasing frequency. Among individual primaries, melanoma is associated with the highest frequency of brain metastases.27 Most metastases gain access to the brain through the vasculature and typically arise at the junction of the gray and white matter,28 presumably because the caliber of blood vessels decreases at this point, acting as a trap for tumor emboli. Approximately 80% of brain metastases are found in the cerebral hemispheres, with less frequent involvement of the cerebellum (15%) and brainstem (5%), reflecting their smaller volume and blood flow.
The detection of brain metastases is an important part of initial staging. Furthermore, due to improved treatment strategies and overall cancer survival, the overall incidence of brain metastases is increasing. The preferred imaging modality for the diagnosis of intracranial metastasis is contrast-enhanced MRI. Brain metastases are typically well circumscribed and avidly enhance (Fig. 30.4). They are also typically associated with a disproportionate amount of surrounding edema best depicted on T2-weighted sequences. MRI is more sensitive than CT in detecting intracranial metastases, and approximately 20% of patients with solitary metastatic lesions by CT show multiple lesions on MRI.29 Furthermore, for patients with a single brain metastasis detected with a conventional single-dose MRI-contrasted study, triple-dose studies will depict additional metastases in up to 25% of patients.30 The detection of multiple lesions aids in directing appropriate treatment and helps to distinguish metastases from primary brain tumors, which are more commonly solitary.
Conventional PET-CT has limited utility in the assessment of brain metastases due to the high metabolic rate of normal brain tissue. However, delayed phase PET, performed approximately 3.5 hours following FDG injection, allows for washout of FDG from normal brain cells, while abnormal tissue retains FDG. Delayed phase PET has been shown to be beneficial in detecting both primary and metastatic brain lesions as well as differentiating between residual or recurrent tumor and radiation necrosis following treatment.31,32 The utility of delayed phase PET may be further enhanced through fusion with MRI.
Primary Brain Malignancy
Primary brain tumors account for approximately 50% of adult intracranial masses, of which half are malignant. The most common malignant primary brain tumor in adults is glioblastoma multiforme (GBM), which usually arises in the cerebral hemispheres. Compared with CT, MRI is more accurate in delineating the local gross extent of disease. In a series of 52 patients with primary brain tumors, the MRI signal abnormality was larger than that identified by CT in 62% of patients. Furthermore, 10 patients with equivocal CT scans had clear abnormalities on MRI.33 GBMs are characterized by an expansile mass that is iso- to hypointense to surrounding tissue on T1-weighted images, with central necrosis and peripheral ring enhancement postcontrast administration. T2-weighted imaging shows a heterogeneous mass with high signal of the tumor nidus and surrounding T2-signal abnormality corresponding to vasogenic edema, in which malignant cells are known to frequently reside.34 Central areas of low signal reflect a combination of blood products, necrosis, and vascular flow voids.
GBM most commonly grows along white matter tracts and does not typically involve the dura or skull. GBM is one of two entities that may spread into the contralateral cerebral hemisphere via tracts of the corpus callosum; central nervous system lymphoma is the other. Other potential routes of spread, including subependymal extension with CSF contamination or hematogenous dissemination, are possible but unusual.
Advanced imaging techniques are also beneficial in characterizing intracranial malignancy. Magnetic resonance spectroscopy (MRS) provides metabolic and biochemical information about tumors in relation to normal brain tissue by quantifying five metabolite peaks: choline (Cho)-containing compounds, Cr, N-acetylaspartate (NAA), lactate, and lipid: the Cho peak reflects cell membrane turnover, Cr is a surrogate for energy synthesis, and NAA is a marker exclusive to neuronal cells. Lactate is detected in necrotic tumors and infarcted tissue and results from anaerobic metabolism. Lipid peaks are produced by cellular and myelin breakdown products. The hallmark spectroscopic pattern of brain tumors is an increase in Cho-containing compounds and a decrease in NAA relative to normal brain tissue. MRS can also aid in the evaluation of tumor type and grade. High-grade gliomas tend to exhibit higher Cho:Cr and Cho:NAA ratios. High-grade gliomas also typically have higher lipid and lactate peaks as the result of necrosis.35 MRS can also distinguish metastatic disease from high-grade gliomas, particularly when combined with perfusion MRI.36 Differentiating radiation necrosis from tumor is also possible using MRS; however, newer techniques, such as dynamic susceptibility-weighted contrast-enhanced perfusion MRI, may be even more accurate and are currently being studied.37
Spinal Metastases
Osseous metastases are common in many malignancies, and the vertebral bodies are frequently involved due to the vascular distribution to the spine. MRI is more sensitive at detecting early vertebral body metastases than both radiographs and CT as it can image changes within the marrow space before cortical destruction occurs. Given that PET has similar sensitivity as MRI for osseous metastatic disease, is performed as part of routine staging, and can image the entire body, MRI is reserved for troubleshooting, such as determining extent of invasion into adjacent tissues. One notable exception is the use of urgent MRI for identification of cord compression in the setting of acute neurologic compromise. In this situation, it is often the T2-weighted sequences that are most useful: the high-signal CSF provides contrast to identify disease encroaching into the spinal canal. Spinal cord edema can also be identified. One should consider screening the entire spine when evaluating for cord compression.
Spinal cord compression is often considered an oncologic emergency, because the longer the duration of symptoms, the less likely the patient will regain function. Thus, therapy is often instituted emergently in these cases (e.g., with radiation, steroids, surgery, or sometimes chemotherapy in sensitive tumors). There is often discordance between the imaging and clinical examination findings. It is the clinicalfindings that determine the acuity of the situation rather than the imaging findings. A radiologic finding of cord compression certainly warrants an evaluation but does not necessarily warrant emergent intervention.
HEAD AND NECK
Oncologic Anatomy
The anatomy of the head and neck is complex, and it is important that oncologists have an intimate understanding of the location, function, and radiographic appearance of the various subsites. The potential for significant morbidity associated with local tumor progression and recurrence in the head and neck region, as well as the associated late effects of curative treatment, necessitates attention to detail. The impact of anatomy is such that the Accreditation Council for Graduate Medical Education mandates cadaver lab experience for otolaryngology residency.
Lymphatic Drainage of the Head and Neck
The lymphatics in the head and neck region largely proceed in an orderly fashion from sites in the upper aerodigestive tract into the common jugular chains, which eventually empty into systemic circulation near the junction of the internal jugular and subclavian veins. There are notable exceptions to this orderly drainage that can influence radiation treatment planning. In order to discuss this in a systematic fashion, the lymphatic basins of the neck are divided into six distinct levels, with surgical and radiographic boundaries.38
Level I is defined as both the submental basins (level IA) and the submandibular basins (level IB) and receive drainage from the oral cavity, although this basin may also be at risk from other sites in the setting of advanced nodal disease (N2b or greater). Level II contains the upper jugular nodes, extending from the C1 vertebral body to the hyoid bone, including the contents of the carotid sheath and the space deep to the sternocleidomastoid muscle (SCM). Level II is subdivided into anterior (level IIA) and posterior (level IIB) regions, as defined by the posterior border of the jugular vein. Level II contains the jugulodigastric node at the level of the jugular vein as it crosses the posterior belly of the digastric muscle, and is a common lymphatic pathway for the majority of the upper aerodigestive tract. Level III follows the carotid sheath and space posterior to the SCM from the hyoid bone to the cricoid and receives efferent lymph drainage from level II. Level IV continues to follow the same jugular chain to the level of the clavicle. Level V contains the posterior triangle of the neck, boarded by the trapezius posteriorly, the SCM anteriorly, and the clavicle inferiorly and is at particular risk for nasopharyngeal primaries. Level VI are the prelaryngeal lymph nodes (Delphian nodes), which extend from the inferior edge of the thyroid cartilage to the sternal notch, bounded laterally by the sternal heads of the SCM. Level VI is at risk in laryngeal cancers with subglottic or transglottic extension and for hypopharyngeal cancers with esophageal extension.39
In addition, there are two other regions not included in this level classification that are worthy of consideration. Just superior to level II, following the carotid sheath to the skull base are the junctional or retrostyloid nodes, which may be at risk when there is ipsilateral nodal disease. Medial to these nodes and to level II lie the retropharygeal nodes (or nodes of Rouviere), which lie in the regions anterior to the prevertebral fascia, which in turn surrounds the longus capitis and the longus colli muscles. The retropharyngeal nodes extend superiorly to the skull base and inferiorly to the hyoid bone and are at risk of cancers arising from the nasopharynx, posterior pharyngeal wall, and the pyriform sinus.40
The Oral Cavity
The oral cavity encompasses three major subsites: the oral tongue, the floor of mouth, and the buccal mucosa. Carcinomas originating from the oral tongue have potential to spread locally through the intrinsic and extrinsic muscles of the tongue, inferiorly to the floor of mouth, and posteriorly to the anterior tonsillar pillar. For the floor of mouth, the genioglossus, geniohyoid, and root muscles of the tongue are at risk for local disease spread, as well as levels IA and IB of the neck, laterally to the alveolar ridge and mandible. Tumors of the buccal mucosa may extend superiorly to the infratemporal fossa, inferiorly to the submandibular region, anteriorly to the lip commissure, and posteriorly to the retromolar trigone.40
The Oropharynx
The oropharynx anteriorly is bounded by the base of tongue, laterally by the tonsils, superiorly by the soft palate, and posteriorly by the posterior pharynx. Tumors arising from the base of tongue are often difficult to assess for extent of disease; therefore, the entire base of tongue, proximal oral tongue, and vallecula are at risk for subclinical disease. MRI may aid in delineation of the gross tumor volume for this site.41 Tonsillar cancers may involve the base of tongue, palate, and buccal mucosa, although in locally advanced cases, they may also involve the nasopharynx, parapharyngeal space, and pterygoid muscles. Soft palate tumors may extend laterally to the tonsillar pillars and superiorly to the pterygopalatine fossa.
Nasopharynx, Oropharynx, and Hypopharynx
The nasopharynx is bounded superiorly and posteriorly by the sphenoid sinus, clivus, and the prevertebral fascia of C1 and C2. The parapharyngeal space lies laterally to the nasopharynx, which in turn is bounded laterally by the medial pterygoid muscle. The parapharyngeal space offers few anatomic barriers for the direct invasion of tumors superiorly and laterally to the base of skull, resulting in cranial nerve deficits as noted above. The eustachian tube empties into the nasopharynx at the torus tubarius; just posterior to the torus is the pharyngeal recess (or fossa of Rosenmüller), a fold of mucosa that is a frequent site for primary malignancies of this region.
Carcinoma arising from the posterior and lateral pharyngeal walls may spread superiorly to the nasopharynx and inferiorly to the hypopharynx. Similarly, primaries of the hypopharynx may spread superiorly through the oropharynx and nasopharynx. Malignancies of the pyriform sinus may also place the ipsilateral larynx at risk.
Larynx
The larynx is subdivided into three anatomic regions: the supraglottis (containing the epiglottis, the arytenoid and aryepiglottic folds, and the ventricular bands or false cords), the glottis (a 1-cm plane extending inferiorly from the lateral margin of the ventricle, including the true vocal cords and commissures), and the subglottis (from the inferior border of the glottis to the inferior aspect of the cricoid). The true cords have essentially no lymphatic drainage, allowing for focal treatment of a limited primary tumor without elective nodal treatment. In contrast, the supraglottic larynx has a rich and bilateral lymphatic system, requiring either dissection or elective nodal radiotherapy for even early primary tumors. The subglottis is a rare site of primary tumors and may invade locally into soft tissue as well as metastasize to laryngeal and tracheal lymphatics.42
Oncologic Imaging
For cancer of the head and neck, staging relies on careful physical examination, fiberoptic and direct laryngoscopy, directed biopsies, and integration of imaging modalities. Contrast-enhanced CT is the standard imaging modality for carcinomas of the head and neck region (Fig. 30.5). MRI may be a superior imaging modality for evaluating the extent of primary tumors of the oral cavity, oropharynx, and nasopharynx.43 Novel approaches with MRI have shown promise in evaluating tumor responses to treatment by measuring physiologic changes within the tumor. Dynamic contrast-enhanced MRI may give insight into the vascular permeability (k-trans) in the tumor microenvironment; k-trans was found to be significantly higher in complete responders to concurrent chemoradiation therapy in one series.44 Diffusion-weighted MRI may also provide information about the cellularity of a tumor mass or involved lymph node; an increase in the apparent diffusion coefficient (corresponding to a decrease in cellularity) during chemoradiation has been correlated with improved 2-year local control in another series.45
FDG-PET imaging for head and neck cancer has been useful as an adjunct to MRI and CT, particularly in clarifying the significance of intermediate lesions on MRI or CT. In one series, the addition of FDG-PET imaging improved the accuracy of tumor delineation from 40% to 70% with MRI or CT alone to 97% to 100%, altering the management of 23% of the patient under study.46 Another series found FDG-PET to have a sensitivity of 88% in determining the primary tumor and a sensitivity of 82% and specificity of 100% for lymph node metastases.47 However, in initial staging, no noninvasive imaging modality has a high enough negative predictive value to forgo appropriate dissection or elective nodal irradiation when the characteristics of the primary tumor suggest a significant risk of spread. That is in contrast to the value of FDG-PET after chemoradiation for the detection of residual nodal disease. The sensitivity for detection of persistent disease was 96% with a specificity of 72% in a posttreatment series, with a negative predictive value in some series as high as 99%, allowing for the abandonment of routine posttreatment neck dissections in patients with a complete clinical and PET response.48,49 Novel PET tracers such as Cu64-ATSM and F18-misonidasole, designed to evaluate hypoxia within the tumor, may also prove to be clinically useful.50
THE BRACHIAL PLEXUS
Oncologic Anatomy
The brachial plexus originates from the primary rami of the C5 through the T1 vertebral levels and joins to form three nerve trunks (upper, middle, and lower) in the neck. These trunks divide as they course beneath the clavicle, forming three cords (lateral, medial, and posterior) in close approximation to the axillary artery, posterior to the pectoralis minor. The cords then form the three primary terminal nerves for the arm (the median, ulnar, and radial nerves) as well as the musculocutaneous nerve. These peripheral nerves are of particular importance due to the significant morbidity associated with injury, either from tumor invasion or from treatment-related toxicity. As the plexus traverses the neck and axilla, it is of particular relevance when treating tumors of the head and neck, upper thorax, and breast.
Oncologic Imaging
Identifying the brachial plexus is difficult on CT imaging and may be most directly visualized on MRI.51 However, one may accurately contour the position of the trunks, divisions, and cords on noncontrast CT imaging based on bony, muscular, and vascular landmarks.52 The method put forward by Hall et al.52 begins contouring at the origination of the vertebral foramina of C5 through T1. The anterior and middle scalene muscles are then identified, with the trunks lying in the space between these muscles. The middle scalene will end at the superior aspect of the first rib just as the divisions of the plexus will be joining with the axillary artery as a neurovascular bundle. The artery then can be followed laterally as a surrogate for the remainder of the cords into the upper arm. Of interest to breast treatment, the course of the plexus will be brought superior and lateral with the upper arm with abduction, though still constrained by its course underneath the clavicle (Fig. 30.6).
FIGURE 30.5. Axial computed tomography image demonstrating a squamous cell carcinoma involving the right aryepiglottic fold with anterior extension into the pre-epiglottic space.
THE THORAX
Oncologic Anatomy
The thorax consists of the superior part of the trunk and contains several important structures, including the heart, lungs, esophagus, and pleura. Primary tumors of the heart are extremely rare. On the other hand, lung cancer is the leading cause of cancer mortality in the United States, and the incidence of esophageal carcinoma is rising. Other common malignancies that arise in the thorax include malignant pleural mesothelioma, thymic malignancies, and malignant lymphomas.
There are many clinically relevant anatomical issues when evaluating patients with cancers of the thorax. These include (a) lobe-specific patterns of lymphatic spread, (b) the complex anatomy surrounding the lung apex, (c) the extent of the pleural space, (d) esophageal landmarks, and (e) thymic architecture.
Patterns of Lymphatic Spread
Lung malignancies frequently metastasize to regional lymph nodes. A basic understanding of mediastinal lymph node stations and lobe-specific lymphatic spread is helpful when evaluating and planning treatment for patients with lung cancer. The mediastinal nodes are a complex system, and it is challenging to predict where lymph node metastases will develop. However, these basic patterns provide a framework for customizing local treatment approaches (surgery and radiation therapy).
Both anatomical and clinical studies have shown that bronchogenic tumors frequently spread directly into mediastinal lymph nodes, bypassing intrapulmonary and hilar lymph nodes. This phenomenon appears to occur more frequently for upper lobe tumors.53 For right-sided tumors, these pathways most frequently lead to ipsilateral paratracheal and subcarinal lymph node stations. For left-sided tumors, direct spread to anterior mediastinal lymph node stations (prevascular, para-aortic, and anterior-posterior window) is more common than to other mediastinal nodal stations. Second, right lung segments drain predominantly into the ipsilateral mediastinum. Conversely, left lung tumors commonly spread to both sides of the mediastinum,54,55 especially left lower lobe tumors. Third, direct passageways to the supraclavicular fossa exist but are rare. Clinically, supraclavicular failures are uncommon and are usually associated with failure in upper paratracheal lymph node stations.56 Fourth, most clinical studies have shown that subcarinal lymph nodes are frequently involved by both upper and lower lobe tumors.
The Superior Sulcus
The superior sulcus of the lung is surrounded by multiple critical structures. The subclavian artery and vein pass anterior to the lung apex, the brachial plexus and its branches cross over the apex of the lung toward the arm, and the stellate ganglia lie posteriorly alongside the exiting nerve roots of the lower cervical and upper thoracic spine. Other structures that can be involved by superior sulcus tumors are the vertebral bodies, trachea, and esophagus. Patients with superior sulcus tumors present with a variety of presentations (arm edema, arm weakness, and sensory deficits or Horner syndrome) related to the local extent of their disease.
FIGURE 30.6. The brachial plexus (yellow contour) is delineated on axial computed tomography images on a woman undergoing treatment to the left breast. The anterior scalene (green arrow) and middle scalene (red arrow) are identified. The brachial plexus is delineated in the space between these muscles, originating at the C5-T1 roots and continuing to the axillary neurovascular bundle. The course of the plexus is contoured more distally than clinically necessary to emphasize the course and location when the arm is abducted.
FIGURE 30.7. The extent of the pleura is illustrated. Note the inferior extension of the costodiaphragmatic recess and the medial extension of the costomediastinal recesses. (Courtesy of the University of Bristol, Department of Anatomy.)
The Pleura
The lungs are enclosed within a pleural sac. The visceral pleura is adherent to all of the surfaces of the lung, including the individual lobes where the pleura extends into the fissures. The parietal pleura is adherent to the thoracic wall, mediastinum, and diaphragm. The pleural recesses are potential spaces where portions of opposed parietal pleura are in contact during quiet respiration (Fig. 30.7). The inferior extension of the costodiaphragmatic recess can be easily underestimated, as can the medial extent of the costomediastinal recess (see Fig. 30.7). The inferior aspect of the costodiaphragmatic recess often extends to the level of the midkidney. The posteromedial extent of the pleura often wraps anteriorly over the descending aorta.
Malignant mesothelioma is a rare pleural neoplasm associated with prior asbestos exposure. Pathologically, it can be categorized into epithelial, sarcomatoid, and mixed histologic subtypes. Mesothelioma initially involves the pleura and grows by contiguous spread from the pleural space into the lung, chest wall, mediastinum, pericardium, and diaphragm. The extent of the pleural spaces has implications for postoperative radiation target volumes (Fig. 30.8).
FIGURE 30.8. Digitally reconstructed coronal image from a treatment planning computed tomography scan illustrating the inferior extent of the costodiaphragmatic recess, which extends to the level of the midkidney. The patient had previously undergone an extrapleural pneumonectomy at which time metallic clips were placed, demarcating the inferior extent of the recess. The clinical target volume is illustrated in red.
TABLE 30.5 “ACCURACY” OF COMPUTED TOMOGRAPHY AND POSITRON EMISSION TOMOGRAPHY FOR MEDIASTINAL STAGING OF NON–SMALL CELL LUNG CANCER
Esophageal Anatomy
The esophagus extends from the cricopharyngeus muscle at the level of the cricoid cartilage to the gastroesophageal junction in the abdomen. The cervical esophagus extends from the cricopharyngeus muscle (approximately15 cm from the incisors) to the level of the thoracic inlet (approximately 18 cm from the incisors). The thoracic esophagus extends from the thoracic inlet to the diaphragm and is sometimes divided into upper, middle, and lower sections. The carina is located at approximately 25 cm from the incisors and the gastroesophageal junction is located at approximately 40 cm. These general numbers are helpful when planning radiation fields based on staging studies that include endoscopy, EUS, and PET.
Thymus Architecture
The thymus is an encapsulated, bilobed gland situated in the superior anterior mediastinum and is involved in adaptive immunity. Although prominent in size during infancy and early childhood, it begins to involute during adolescence. The thymus decreases significantly in size in most patients after administration of chemotherapy, but typically regrows during the recovery phase, sometimes to a larger size than at baseline.57
The thymus gland is composed of both lymphocytes and epithelial cells. Thymic neoplasms are a common cause of anterior mediastinal masses and include both benign and malignant pathologies, including thymomas from epithelial cells and leukemias or lymphomas from lymphocytes.
Thymomas are the second most common primary mediastinal neoplasm in adults following lymphoma and are classified on a histologic spectrum from benign encapsulated thymoma to malignant thymic carcinoma. Once thymomas extend through the capsule, they can invade other regional structures, including the lungs and great vessels, sometimes rendering them inoperable. The thymus gland lies within the pleural envelope. The most common pattern of spread is within the pleural and pericardial spaces. Lymphatic and hematogenous metastases are rare.
Oncologic Imaging
Non–Small Cell Lung Cancer
Treatment decisions are often predicated on the status of the mediastinum in patients with operable non–small cell lung cancer (NSCLC). Patients without mediastinal disease generally proceed directly to resection, while those with mediastinal spread often receive induction therapy or definitive chemoradiotherapy. The standard noninvasive staging tool has been CT. In general, the sensitivity and specificity of CT is less than optimal58–60 (Table 30.5). Thus, mediastinoscopy is often utilized to pathologically stage the mediastinum. Mediastinoscopy is associated with a low rate of morbidity. Nevertheless, if noninvasive studies proved highly accurate, this procedure might be avoided in some patients.
Numerous studies and meta-analyses58–62 have assessed the ability of CT, PET, and integrated PET-CT to accurately stage the mediastinum in patients with NSCLC (see Table 30.5). Although significant heterogeneity exists among the individual studies, several conclusions can be drawn. First, the positive predictive value of CT is poor (around 50%). PET and PET-CT is somewhat better (80% to 90%). Still, 10% to 20% of patients with PET abnormalities in the mediastinum will have no evidence of disease at mediastinoscopy, although insufficient sampling may be explanatory in some cases. Therefore, many still advocate mediastinoscopy in the setting of a positive PET. The negative predictive value of PET and PET-CT appears to be better, especially when there are no enlarged lymph nodes visible on CT.63 Nonetheless, most guidelines recommend mediastinoscopy prior to resection given the inherent limitations of PET.
Presently, pathology is considered the gold standard in studies that assess the accuracy of imaging. In a recent analysis in patients who had surgery for NSCLC with negative mediastinal nodes by pathology, patients with abnormalities in the mediastinal nodes on preoperative PET had worse disease outcomes than those with a negative PET in the mediastinum.64 Thus, PET may have predictive value beyond the information provided by histology.
Localization of the esophagus is important during treatment planning of lung cancer. The esophagus is often well visualized on CT. However, its course can be tortuous and its exact location is often uncertain. Having the patient swallow dilute contrast during the planning CT can assist in localization of the esophagus. The heart and spinal canal (as a surrogate for the spinal cord) are also well seen on CT. The substructures of the heart, however, are often challenging to define on CT. If one were to try to preferentially spare or consider the dose to cardiac substructures, an MRI or nuclear medicine cardiac image might provide additional information.
Esophageal Carcinoma
The most commonly used staging tools for esophageal carcinoma are barium swallow, EUS, CT, and PET. EUS, as previously discussed, is the most accurate modality to assess depth of invasion (T stage) but is less accurate in assessing nodal involvement (N stage) (Fig. 30.9). The ability to perform fine-needle aspiration biopsies of suspicious nodes, primarily disease in the celiac axis, has increased the ability of EUS to stage regional nodes. The reported accuracy of EUS for T and N stage is approximately 85% to 90% and 75%, respectively.65,66 CT is primarily used to assess for metastatic disease. It is fairly unreliable in predicting T or N stage. The optimal role of PET in esophageal cancer staging is undefined, but it is generally used to evaluate for local or regional nodal disease and distant metastases. However, the sensitivity of PET for local or regional nodal disease does not appear to be superior to EUS.67 PET may be most helpful in detecting distant metastases and differentiating patients who have residual disease after neoadjuvant chemoradiotherapy, requiring surgical resection, from those who are complete responders and may be spared the morbidity of surgery.68
Mesothelioma
CT best evaluates suspected mesothelioma for initial diagnosis and surgical planning. The characteristic CT appearance is focal or diffuse nodular pleural thickening, which demonstrates enhancement postcontrast administration.69CT is better than MRI at depicting the extent of disease; however, neither modality is particularly sensitive at detecting diaphragmatic or pericardial invasion unless it is extensive. PET is often performed for staging to detect distant and nodal metastases. However, it can also be helpful in establishing the initial diagnosis when CT findings are subtle, as even small foci of disease are typically highly FDG avid.
Superior Sulcus
Imaging plays a crucial role in the diagnosis and staging of superior sulcus tumors. Although radiographs are commonly the initial study to identify an abnormality at the lung apex, the precise location, extent of invasion, and assessment of resectability are best performed by a combination of CT, MRI, and PET. CT is best to define the primary tumor and detect rib or vertebral body invasion. CT may also identify suspicious pulmonary nodules that may be below the threshold for PET detection. Contrast-enhanced MRI using T1-weighted sequences is best for determining resectability by assessing the brachial plexus.70 The primary role of PET is to identify distant and nodal metastases.
Superior sulcus tumors are staged according to the American Joint Commission on Cancer (AJCC) guidelines for staging of NSCLC and are classified as at least stage IIB disease due to direct invasion of the chest wall.71 It is important to note that involvement of the brachial plexus or subclavian vessels is not part of the AJCC staging classification. Superior sulcus tumors, by definition, invade the chest wall; rib destruction and involvement of the lower brachial plexus roots (C8, T1) is considered T3 disease, whereas invasion of brachial plexus roots C5-7, the esophagus, vertebral body, or subclavian vessels constitutes T4 disease. Contraindications to surgery include invasion of brachial plexus roots or trunks above T1, invasion of >50% of a vertebral body, invasion of the esophagus or trachea and mediastinal (N2) or contralateral supraclavicular (N3) nodes; therefore, some T4-designated tumors may still be resectable, again highlighting the importance of accurate imaging.
Thymic Malignancy
Thymic neoplasms often go undetected until they are quite large and become symptomatic, at which time they may be depicted as a mediastinal mass on chest radiography. Contrast-enhanced CT is best for characterizing thymomas and detecting local invasion. High-grade tumors tend to be larger in size, have irregular margins, enhance heterogeneously, and have regions of necrosis; mediastinal lymphadenopathy may also be present. Direct invasion into the pleura, pericardium, and vessels is often difficult to detect by CT unless extensive. A preserved fat plane between tumor and adjacent structures is a negative predictor of invasion; however, this finding has poor positive predictive value.72 Therefore, mere contiguity of tumor with a structure or loss of normal anatomic planes is not sufficient to preclude surgical resection.
FIGURE 30.9. Endoscopic ultrasound image demonstrating a T3 esophageal tumor with an abnormal peritumoral lymph node. (Image courtesy of Dr. Frank Gress.)
TABLE 30.6 RISK OF INTERNAL MAMMARY LYMPH NODE INVOLVEMENT BASED ON STATUS OF AXILLA AND LOCATION WITHIN THE BREAST
TABLE 30.7 BREAST IMAGING REPORTING AND DATA SYSTEM (BIRADS) CATEGORIES USED FOR MAMMOGRAPHY EXAMINATIONS AND RISK OF MALIGNANCY
THE BREAST
Oncologic Anatomy
Breasts are present in both males and females, although they are only well developed in the latter with the onset of puberty. In the male, generally only a few ducts are present, which nonetheless can rarely develop into malignancy, particularly in the context of BRCA2 mutations.73 In the female, the breast originates from a roughly circular base or bed extending from the lateral border of the sternum to the midaxillary line from medial to lateral, and from the second through sixth ribs superior to inferior. The upper outer quadrant extends along the pectoralis major toward the axilla, forming the axillary tail of Spence. This is also the most frequent quadrant for primary breast cancer (approximately 40%), which may be simply due the additional breast tissue associated with the tail.74 Just posterior to the breast is the retromammary space, consisting of loose connective tissue, allowing for movement on the breast on the chest wall. Two-thirds of the breast rests on the deep pectoral fascia, which lies over the pectoralis major; the remainder rests on the fascia of the serratus anterior.
The breast tissue consists of lactiferous ducts that each drain 15 to 20 mammary gland lobules, and it is these ducts that are the origin of the majority of both noninvasive (ductal carcinoma in situ) and invasive disease (invasive ductal carcinoma). The breast is then anchored to the skin by suspensory ligaments (or Cooper’s ligaments) and interspersed with fat lobules. These ligamentous attachments to the skin become more prominent with breast edema or congestion due to tumor involving the dermal lymphatics, resulting in the characteristic appearance of peau d’orange.
The lymphatic drainage of the breast is primarily to the axilla, although the upper outer quadrant may drain to the intermediary intrapectoral nodes (or Rotter’s nodes) lying between the pectoralis major and pectoralis minor muscles, and the inner quadrants may drain to the internal mammary nodes (IMN). The axilla is divided into three sections with relation to the pectoralis minor muscle; the nodes found inferolateral to the muscle are termed level I, those beneath the muscle are termed level II, and those medial to the muscle are level III. Level I and II are generally removed in a standard axillary dissection, while the level III and the subsequent infraclavicular and supraclavicular basins are generally not considered resectable and are the target of radiotherapy if the more proximal basins have disease.
In a study of the location of sentinel nodes from various breast quadrants, the majority of drainage in all breast quadrants was to the axilla, and isolated drainage to the IMN was very rare (<6% in any quadrant).75 However, identification of an additional IMN sentinel was found in 10% to 50% of cases dependent on quadrant (the upper outer quadrant was lowest at 10%, and the lower inner quadrant was most frequent at 52%). In surgical series in which the IMNs were routinely dissected, the incidence of isolated IMN disease was limited to 5% to 15%.76–78 The risk of involvement increased when the axilla was also involved (20% to 55%), dependent on the axillary disease burden and location of the involved quadrant of the breast (Table 30.6). When IMNs were involved, the majority were located in the first three intercostal interspaces (first interspace 80%, second 75%, third 40%, and fourth 5%).77 That stated, irradiation of the IMN nodes is controversial, and randomized data have not confirmed a survival benefit to routine treatment, although the treatment is well tolerated with modern techniques.79–81
Oncologic Imaging
Mammography remains the preferred imaging modality for the diagnosis and follow-up of both invasive and noninvasive disease. Multiple randomized trials have shown that screening mammography reduces the risk of breast cancer mortality by 20% to 35% in women aged 50 to 69.82–86 The efficacy of screening in younger women (aged 40 to 49) and elderly women (aged 70 or older) is less certain. Most published guidelines suggest initiating screening at age 40. Screening mammography includes two standard views of each breast: a craniocaudal (CC) view and a mediolateral oblique (MLO) view. These images are taken at approximately 45-degree angulation to each other (i.e., they are not orthogonal). Although the CC view is oriented in the long axis of the patient (i.e., superior/inferior), the MLO is oriented in the medial-superior/lateral-inferior direction. The MLO view increases visualization of the upper outer quadrant and tail of the breast, while the CC view ensures adequate visualization of the inferior and medial aspects of the breast. Additional views, such as spot compression, can be utilized to further evaluate suspicious lesions.
The majority of women (approximately 95%) with abnormalities on a screening mammogram do not have breast cancer; thus, the positive predictive value is low. Overall, the sensitivity of screening mammography is approximately 75% (i.e., 25% of women diagnosed with breast cancer have a history of a normal mammogram 12 to 24 months prior to diagnosis). Sensitivity and specificity vary widely depending on breast density; for fatty versus dense fibroglandular breasts, reported sensitivities are 87% versus 63%, while specificities are 92% versus 68%, respectively.87–89 Furthermore, sensitivity and specificity differ between screen-film versus digital mammography, with digital systems generally having higher diagnostic accuracy in women with dense breast tissue compared to film mammography.90
Systematic interpretation and unambiguous reporting is important for any screening study. Given the prevalence of breast malignancy and its clinical implications, the Breast Imaging Reporting and Data System (BI-RADS) was developed and constitutes guidelines for standardized reporting and quality assurance of screening mammography within the United States (Table 30.7). Mammographers are ahead of their radiology colleagues in this regard as the BI-RADS system affords a clear unambiguous means of quantifying the “suspiciousness” of mammographic findings. Systems similar to BI-RADS would be helpful for other imaging modalities as a means to reduce the risks of misunderstanding and miscommunication between radiologists and other care providers.
Features of concern for malignancy at mammography include a focal mass, irregular borders, and microcalcifications. Spiculation can be due to invasion into, or reactive changes within, the surrounding breast parenchyma. However, spiculated masses can also be secondary to fat necrosis, postoperative scarring, or other nonmalignant processes. Calcifications associated with ductal carcinoma in situ or invasive carcinoma are typically pleomorphic (heterogeneous) in appearance and clustered in a localized area (Fig. 30.10). Linear, branching calcifications are suggestive of intraductal carcinoma. Round, well-circumscribed lesions, with or without coarse calcifications, are often benign.
Abnormalities on screening mammogram are generally followed with a diagnostic mammogram, in which supplemental and magnified views may be obtained to detect and characterize microcalcifications. Breast US is often performed to further characterize suspicious lesions, guide core biopsy, and assess regional lymph nodes. It is most helpful in differentiating fluid-filled cysts from solid tumors. MRI is not routinely recommended for upfront screening, except in patients with dense breast tissue and those at very high risk for primary breast malignancy, including those with BRCA mutations or women who received chest radiation therapy at a young age (typically <30 years old).91 In addition to T1 and T2 lesion characteristics, patterns of MRI enhancement and washout kinetics are beneficial in evaluating concerning lesions. MRI can also be used for biopsy image guidance. After biopsy confirmation of disease, MRI has been examined in an attempt to better diagnose multifocal or contralateral disease preoperatively. One trial found contralateral cancers on MRI in 3% of their cohort, at the cost of performing a biopsy in 12%.92 Preoperative MRI, however, did not improve the requirement for reoperation in a randomized UK trial.93 The only clinically relevant outcome that routine use of preoperative MRI appears to have changed is that more women are having mastectomies as opposed to breast conservation.94
FIGURE 30.10. Clustered, pleomorphic calcifications visualized on mammography. The patient was found to have ductal carcinoma in situ.
THE ABDOMEN
Oncologic Anatomy
Many diverse malignancies arise from abdominal structures. The most common are epithelial cancers of the stomach, pancreas, colon, liver, kidney, and biliary tract, including the gallbladder. Cancers of the kidney and colon are not often managed with radiation therapy and are not discussed further. Several relevant anatomical issues include (a) site-specific patterns of lymphatic spread for gastric cancer, (b) local disease extension of pancreatic cancer rendering a tumor inoperable, and (c) anatomy of the biliary tree.
Gastric Cancer: Patterns of Lymphatic Spread
The stomach is a distensible organ located in the left upper abdomen. It is classically divided into four parts: the gastroesophageal junction (cardia), fundus, body, and pylorus (antrum). Although the incidence of epithelial malignancies of the distal stomach has declined in Western countries over the past century, the incidence of malignancies of the gastroesophageal junction is increasing. Lymph node involvement is common in gastric cancer, likely due to the extensive submucosal and subserosal lymphatic networks. This rich lymphatic network places all lymph node regions within the abdomen at risk of harboring regional metastases, irrespective of the part of the stomach involved. However, some general patterns have been observed, which can facilitate rational radiation treatment planning for gastric cancer.
For tumors within the stomach, the perigastric region located along the greater and lesser curvatures of the stomach are typically the initial draining lymph node basin. The other primary lymph node regions are those along the three arterial branches of the celiac axis (common hepatic, left gastric, splenic). Secondary and tertiary drainage sites include lymph nodes in the hepatoduodenal, peripancreatic, para-aortic, mesenteric, and middle colic region.
A large surgical series from Japan demonstrated that the most common site of lymph node involvement was along the lesser and greater curvature (perigastrics), regardless of the part of the stomach involved (11% to 40%).95 As expected, lymph node involvement around the cardia was unusual for distal stomach tumors (0% to 7%) but common for proximal tumors (13% to 31%). Similarly, infrapyloric lymph nodes were commonly involved for distant gastric cancers (49%) but rare for proximal tumors (3%). Other common sites of lymph node involvement included those along the left gastric artery (19% to 23%), common hepatic artery (7% to 25%, greatest for distal tumors), and celiac axis (8% to 13%). The risk of splenic hilar involvement has varied among surgical series but is generally highest for proximal tumors.95–97 Based on these and other data, guidelines have been published outlining proposed radiation fields for gastric cancer based on site of involvement within the stomach.98,99
Pancreas
The pancreas is an elongated digestive gland posterior to the stomach. It is classically divided into four parts: the head, neck, body, and tail. The pancreatic head is nestled within the curve of the duodenum and this is where most pancreatic carcinomas arise. The pancreas has a rich lymphatic network and is in close proximity to multiple other abdominal organs and structures, making surgical resection difficult and negatively affecting long-term cure rates (resectability is the most important prognostic factor).
Biliary Tree
Hepatocytes within the liver secrete bile (an important agent for digestion) into bile canaliculi, the initial branches of the intrahepatic duct system. These canaliculi drain bile into larger and larger channels that eventually become the left and right hepatic ducts, draining bile from the left and right lobes of the liver, respectively. These exit the liver from the porta hepatis and join to form the common hepatic duct (approximately 4 cm in length). The cystic duct joins the common hepatic duct to form the common bile duct (approximately 10 cm in length). The common bile duct extends to, and empties into, the duodenum. It lies alongside the hepatic artery and portal vein.
Biliary tract cancers include adenocarcinomas of the gallbladder and bile ducts, the latter referred to as cholangiocarcinomas. Cholangiocarcinomas include intrahepatic, perihilar, and distant extrahepatic biliary malignancies. Klatskin tumors are perihilar tumors that involve the bifurcation of the common hepatic duct. Both resectability and prognosis increase for more distally located biliary tumors.
FIGURE 30.11. Axial computed tomography image demonstrating an adenocarcinoma of the pancreatic head with tumor abutting the superior mesenteric artery.
Oncologic Imaging
Pancreatic Cancer
The pancreas can be imaged with US, CT, and MRI. MDCT with IV contrast and thin-section reconstructions optimize pancreatic tissue characterization and allow for detection of small tumors as well as vascular and ductal invasion. CT also defines the surgical anatomy to determine resectability and can detect regional and distant metastases (Fig. 30.11).
Adenocarcinoma of the pancreas most frequently arises in the head of the gland, to the right of the superior mesenteric or portal vein. It usually appears as a hypodense mass relative to the normally enhancing pancreas. Surgical resection typically provides the only chance of cure, and CT with thin-section reconstructions and IV contrast enhancement is an important technique to assess resectability. Encasement of the superior mesenteric artery (SMA) or celiac trunk defines an unresectable T4 tumor. On the other hand, the presence of a fat plane around the celiac trunk and SMA, along with a patent superior mesenteric or portal vein, defines potentially resectable disease. Borderline cases include those with tumor abutment on the SMA, severe unilateral SMV or portal vein impingement, or adjacent organ invasion. CT does not, however, detect small volume peritoneal or surface liver metastases that can be identified with laparoscopy. Oral contrast during radiation planning scans can be helpful to define the stomach and duodenum.
Hepatic Imaging
MDCT with IV contrast allows for morphologic characterization of the liver and biliary system. The administration of IV contrast is essential as many hepatic tumors are of similar attenuation as normal liver parenchyma and are not identifiable until central necrosis is present. MDCT with contrast is performed in both arterial and portal-venous phases of enhancement. This allows for detection of both early- and late-enhancing lesions, as well as characterization of enhancement patterns that can differentiate between benign and malignant disease. For example, hemangiomas are classically low attenuating on noncontrast images, have peripheral enhancement on the arterial phase, and demonstrate central filling on portal-venous phase imaging. Hepatocellular carcinoma is the most common primary hepatic malignancy and is characteristically hypervascular with pronounced enhancement throughout the solid tumor components on arterial phase images and diminished enhancement on the portal-venous phase. Contrast-enhanced CT can also identify invasion of tumor into the portal and hepatic veins and is frequently associated with portal vein thrombosis. As with other malignancies, PET is recommended for staging and identification of extrahepatic disease.
The liver is one of the most common sites of metastatic disease for many cancers. In patients with a known extrahepatic primary malignancy, evaluation of the liver is an important part of staging. Contrast-enhanced CT has a high sensitivity (73%) and specificity (96%) for detecting hepatic metastases.100 MDCT of the liver for metastatic disease is typically performed with biphasic technique. Although most metastases are identified on the portal-venous phase, some hypervascular tumors (e.g., melanoma, renal cell carcinoma) may only be identified on arterial phase imaging. MRI has similar accuracy for the diagnosis of hepatic metastases as CT and may be performed in patients with an allergy to iodinated contrast media. However, CT outperforms MRI in detecting extrahepatic lesions, particularly within the lungs.
Biliary Imaging
US is typically the initial imaging study for patients with suspected biliary or pancreatic disease. The primary goals of evaluation include assessment for biliary and pancreatic ductal dilatation (abnormal is >3 mm), identify the presence of stones, characterize the gallbladder wall, and exclude a pancreatic head mass. US does not, however, image the entire pancreatic and biliary ductal system. In the presence of an US abnormality, further imaging is required.
Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive procedure that involves passing an endoscope into the duodenum and cannulating the main bile duct at the ampulla of Vater. Contrast is then infused to image both the biliary and pancreatic ductal system. In addition to being minimally invasive, ERCP carries risks associated with conscious sedation and can induce pancreatitis in 1.3% to 8.6% of patients.101 Any evidence of biliary obstruction in the absence of calculi typically prompts further evaluation with cross-sectional imaging to exclude malignancy. ERCP can directly visualize ampullary carcinomas and permits tissue diagnosis achieved using needle aspiration, brush cytology, or forceps biopsy. ERCP may also provide palliation via stent placement in the setting of known obstructive biliary malignancy.
Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method of imaging the intra- and extrahepatic biliary and pancreatic ducts. MRCP does not require IV contrast; imaging relies heavily on T2-weighted sequences and high-resolution techniques resulting in the pancreatic and biliary ducts appearing very bright while surrounding tissues are dark in signal.102 MRCP and ERCP have similar sensitivities and specificities in detecting ductal obstruction in the setting of malignancy, although MRCP is better at defining the anatomical extent and type of tumor involved (pancreatic vs. cholangiocarcinoma).103,104
Normal Tissue
During RT planning for cancers of the upper abdomen, consideration of the dose to the kidneys may be important. The kidneys are well visualized on CT. However, regional differences in kidney function cannot be readily assessed on CT. Nuclear medicine renal scans provide quantitative information regarding delivery of fluid into the kidneys from the bloodstream, concentration of wastes in the kidney, and excretion from the kidneys into the ureters and filling of the bladder. This information is useful when significant portions of one or both kidneys will be exposed to doses of RT expected to cause regional dysfunction. The liver, stomach, and small bowel are other organs whose location is often important to consider during RT planning. These are usually well seen on CT, although the use of oral contrast can be helpful.
THE PELVIC LYMPH NODES
Oncologic Anatomy
The lymphatic drainage of pelvic organs follows the iliac vessels throughout their branching within the pelvis. Most superiorly within the pelvis, the common iliac chains receive the majority of lymph drainage from intrapelvic organs, which then empty to the para-aortic chains superiorly in the region of the bifurcation of the abdominal aorta. The gonadal veins and arteries are notable exceptions to this orderly flow of lymph from the pelvis and are discussed separately below. Also of note, the rectum, sigmoid, and distal colon have a separate path for lymphatic metastasis via the inferior mesenteric chain to the preaortic basin.
The common iliac pathway receives lymphatic drainage from three primary routes: the external iliac chain, the internal iliac chain, and the presacral chain. The external iliac pathway begins at the point where the femoral vessels cross the inguinal ligament to become the external iliac chains, which courses more proximally to the common bifurcation. The internal iliac chain (also termed the hypogastric chain) is a more complex plexus, flowing back from the distal elaborations of the same artery. Just as these branches of the internal iliac vessels provide blood supply for the pelvic organs, the corresponding lymph node chains provide the majority of lymph drainage. The obturator nodes are part of the internal iliac system and may be found at the point in which the obturator vessels perforate the obturator internus muscle. Radiographically these nodes lay medial to the femoral head, just superior to the bony obturator foramen. The presacral chain is located just anterior to the sacrum and receives lymphatic drainage from the rectum, the cervix, and posterior vagina in the female and the prostate in the male.4,94,105
The testicles have an interesting lymphatic drainage that differs with laterality, essentially mirroring the differences in venous drainage of the two testicles. On the right, the testicle drains into the para-aortic nodes along the lower portion of the inferior vena cava at about the level of L3-L4 following the left testicular vein. On the left, the testicle drains to the renal hilar nodes following the left testicular vein.
Oncologic Imaging
CT is the current preferred means of identifying vessels within the pelvis and is an acceptable method of delineating the pelvic lymph node basins for elective radiotherapy. A 7-mm margin may be applied to the internal and external iliac vessels to arrive at a nodal CTV, with uninvolved bone, muscle (such as the psoas), and bowel excluded from the volume. The 7-mm margin was developed by investigators in London, who determined the minimum margin on CT visible vessels needed to cover 95% of all nodes identified using ultrasmall iron oxide particles (USPIO) as an MRI contrast agent.106,107 Special care, however, should be taken to include visualized lymph nodes, even if they lie outside of this margin. One centimeter of soft tissue anterior to the sacrum, bridging between the common and internal nodal CTVs, should be added when presacral coverage is desired. The Radiation Therapy Oncology Group has release several atlases to aid the clinician in the contouring of pelvic CTVs that are available at its website. With 3D CT imaging, bony landmarks may not be the ideal determinant of block or multileaf collimator shapes when treating the pelvis.108,109
THE RECTUM
Oncologic Anatomy
The rectum is the final, straight portion of the large bowel, measuring approximately 12 cm in length, beginning at the transition from the sigmoid colon with the fusion of the tenia into the circumferential longitudinal muscle. It terminates with the ampulla, leading to the anal canal and dentate (or pectinate) line. Posteriorly, the entire rectum is extraperitoneal, whereas anteriorly, the peritoneal reflection occurs at approximately 7 to 9 cm from the anal verge in males at the posterior aspect of the bladder (superior to the prostate), and 5 to 8 cm from the verge in females, forming the rectouterine pouch (or pouch of Douglas). Below this point, the distal third of the rectum is entirely extraperitoneal.
The mesorectum is the supportive mesentery of the rectum, lying in the extraperitoneal space between the rectum anteriorly and sacrum posteriorly. It is of critical importance as a potential area of both direct and lymphatic spread of rectal cancers. High-quality total mesorectal excision with sharp dissection has been associated with excellent local control when compared to blunt dissections. However, this has not obviated the need for perioperative radiation therapy, as demonstrated by an increase in local failures if this is omitted.110–112
Oncologic Imaging
Endorectal US is the preferred nonsurgical staging tool for determining the T stage of rectal malignancy, with an overall accuracy of approximately 85% to 90%.113 US is probably not needed in cases where there is a large mass with clear extension into the deep portions of the wall (or surrounding tissues) based on CT or examination. There is some tendency to overstage T2 lesions as T3 (beyond the muscularis propria); however, the accuracy remains superior to other imaging modalities.114 The nodal staging accuracy is somewhat less at approximately 80%, which is comparable to results with either MRI or CT.113 Accurate staging is critical when determining treatment for rectal cancer. Although surgery alone is sufficient for patients with stage I disease, surgery and chemoradiotherapy are indicated for patients with stage II or III tumors. The German Rectal Cancer Study Group showed that preoperative chemoradiotherapy is associated with improved local control with less acute and late toxicity than postoperative chemoradiotherapy.115 In this study, 18% of patients in the immediate surgery group, believed to have stage II or III disease by EUS, were found to have stage I disease after surgical resection. Thus, further improvements in preoperative staging are needed to appropriately select patients for neoadjuvant therapy.
THE BLADDER AND URETHRA
Oncologic Anatomy
The bladder is a distensible muscular organ, which may be contained completely within the pelvis when empty or may extend far into the abdominal cavity with distention. The trigone is the posterior and inferior portion of the bladder, defined by the two ureteral orifices posteriorly and the urethral orifice inferiorly. The trigone remains fixed at the base with distension, while the superior most surface expands to accommodate urine. Due to this distensibility, this bladder is surrounded by loose connective tissue and fat. Anterior to the bladder this loose connective tissue is termed the space of Retzius, or retropubic space.
The urethra inferiorly has a short course to the introitus in the female, measuring approximately 4 to 5 cm in length. In the male, it is approximately 20 cm in length and traverses the prostate and penis to the meatus.
The lymphatic drainage of the base and posterior wall of the bladder may preferentially drain to the obturator and internal iliac basins via anterior pathways. In contrast, the external iliac chain may receive primary drainage from the lateral and superior bladder wall, and tumors arising from the bladder neck may also spread to the presacral nodal basins.105
Oncologic Imaging
Bladder tumors are often inadequately evaluated with conventional imaging techniques such as radiographic intravenous urograms and US. CT urography is useful for the diagnosis of superficial tumors but provides limited visualization of the depth of tumor invasion within the bladder wall. PET has limited utility in the primary diagnosis due to urinary excretion of FDG that can obscure bladder disease. Notwithstanding, PET is still performed as part of staging in order to identify distant metastases. Given the imaging limitations, cystoscopy with biopsy is the preferred method of confirming diagnosis and characterizing the primary tumor stage. Regional nodal involvement is best initially characterized by contrast-enhanced CT; however, the role of MRI is evolving, particularly for evaluation of lymph nodes utilizing novel contrast agents including USPIO.116
CERVIX, UTERUS, AND OVARIES
Oncologic Anatomy
The uterus lies between the bladder anteriorly and the rectum posteriorly, covered by a layer of peritoneum. Laterally lie the fallopian tubes and ovaries, which are anchored medially by the ovarian ligament (or utero-ovarian ligament) and laterally by the suspensory ligament of the ovary (or infundibulopelvic [IP] ligament). The ovarian arteries originate from the abdominal aorta, just inferior to the renal vessels, following a course anterior to the psoas on the left and crossing anterior to the inferior vena cava to the psoas on the right, both sides crossing anterior to the ureter and then crossing medially with the IP ligament to the ovaries. The fold of the peritoneum over the uterus continues laterally over these structures, forming the broad ligament. Similar to the testes, the right ovarian vein drains to the inferior vena cava, while the left ovary drains to the left renal vein.
The uterine corpus or body is the cephalad two-thirds of the organ and is lined internally by the endometrium, which varies in thickness by the menstrual cycle and by menopausal status. The middle muscular layer, the myometrium, is primarily smooth muscle. The final outer layer is the serosa or perimetrium and is continuous with the peritoneum. The caudal one-third of the organ is the uterine cervix, which consists of firm connective tissue, approximately one-half of which extends into the vagina. The intravaginal portion is lined by nonkeratinized squamous epithelium (the ectocervix), whereas the cervical canal is lined by columnar epithelium (the endocervix).
Lateral to the uterine cervix and corpus is the parametrium that caudally consists of the paracervical tissue, including the cardinal ligament, uterine artery and vein, and the ureter as it courses anteriorly to the bladder. This caudal portion of the parametrium is of importance for evaluation of lateral spread of cervical cancer and can be staged on physical examination by the bimanual examination and, perhaps more importantly, with the rectovaginal examination, where the examining rectal finger can palpate these structures. Cephalad to this, the parametrium continues as the broad ligament, terminating at the suspensory ligament of the ovary. Posteriorly the cervix is anchored to the sacrum via the uterosacral ligament, which classically attaches at the third sacral foramen, although recent MRI studies would suggest a fair amount of individual variation.117
Oncologic Imaging
MRI of the pelvis is the most useful modality outside of the physical examination to determine the extent of disease within the uterus and cervix with an accuracy of approximately 85%.118–120 For endometrial carcinoma, T2- and postcontrast T1-weighted sequences are beneficial in staging, such as identifying the primary tumor, extent of invasion, and involvement of regional pelvic lymph nodes. In the setting of cervical cancer, T2-weighted sequences are often the most useful in determining the extent of disease and are preferred for MRI-guided brachytherapy.121 US can be useful during intracavitary brachytherapy to ensure the proper placement of a uterine tandem.
PET-CT has been proven to be sensitive and specific in the evaluation of lymph nodes within the pelvic and para-aortic chains with squamous cell carcinoma of the cervix (sensitivity approximately 85%, and specificity 95% for para-aortic nodes), although it is less well studied in endometrial and other primary gynecologic sites122 (Fig. 30.12). Investigators from Washington University have extensively studied FDG-PET in cervical cancer, showing that the initial maximum SUV of the primary tumor is predictive of response to treatment.123 Additionally, they found that a complete metabolic response to treatment was highly predictive of progression free survival (PFS); at 3 years, with complete response, PFS was 78% versus 33% in partial responders and 0% with PET progression.124 The prognostic significance of PET response to treatment has been confirmed by investigators in Melbourne.125
FIGURE 30.12. Positron emission tomography imaging of a patient with cervical cancer showing an 18-fluorodeoxyglucose-avid left external iliac lymph node.
PROSTATE
Oncologic Anatomy
The prostate lies in the center of the male pelvis, with its widest portion, the base, in close approximation to the bladder neck superiorly, narrowing to the apex inferiorly, supported by the urogenital diaphragm (UGD). Posteriorly, the gland is closely related to the ampulla of the rectum. The seminal vesicles are located superior to the prostate and extend somewhat laterally and posteriorly and are immediately posterior to the posterior wall of the bladder. Anteriorly lies the retropubic space filled with fat.
Within the prostate five distinct zones exist: the peripheral zone, the central zone, the transitional zone, the periurethral glandular tissue, and the anterior fibromuscular stroma.126 The peripheral zone accounts for the majority of the gland (70% of glandular tissue) as well as the majority of cancers (60% to 70%). The peripheral zone is located posteriorly and laterally within the gland. This zone is hyperintense on T2 MRI and care should be taken to include it when treatment planning with MRI. The central zone accounts for an additional 25% of glandular tissue and lies near the origin of the seminal vesicles, accounting for 10% of cancers. The transitional zone surrounds the urethra cephalad to the insertion of the ejaculatory duct, may hypertrophy with age, and is the origin of 10% to 20% of cancer within the prostate.
The Batson venous plexus is a series of valveless veins anterior to the vertebral bodies, which received drainage from the deep pelvic veins and prostate gland.127,128 It has been postulated that due to the lack of valves, this may represent a pathway of spread for metastases and provide an anatomic basis for the propensity of prostate cancer to involve the lumbosacral vertebral bodies.
The T staging of prostate cancer remains based primarily on the physical examination, where the examining rectal finger may palpate the size and extent of discrete ridges and nodules within the gland. It is important to palpate and document the presence of the lateral sulci of the gland, as evidence of effacement is highly suggestive of extracapsular extension (ECE) of disease. The examiner should also attempt to palpate the base of the seminal vesicles, although this is not always possible given body habitus and individual anatomy.
Oncologic Imaging
Transrectal US is invaluable for guiding biopsies for diagnosis of disease; however, it has limited specificity and sensitivity (approximately 40% to 50%) for determination of seminal vesicle involvement and ECE. CT has similar limitations, as the prostate gland has similar attenuation characteristics as the anterior and lateral venous plexus, the inferior UGD, and the bladder wall superiorly. CT can determine suspicious pelvic nodes and is currently the standard for defining pelvic radiation target volumes, if indicated. If CT alone is used for definition of the prostate for treatment planning, the penile bulb may provide a useful reference point for ascertaining the apex of the gland, which lies approximately 15 to 18 mm superior to the bulb, although there is significant interpatient variation.129 A retrograde urethrogram can be useful to identify the inferior aspect of the UGD and aid in the delineation of the apex approximately 12 to 15 mm superiorly.
MRI may be the optimal imaging modality for evaluation of the prostate itself and is an invaluable aid in treatment planning. As noted previously, the zonal anatomy of the prostate is only visible on T2-weighted imaging, and the apex can be clearly distinguished from the UGD and other neighboring structures (Fig. 30.13). The joint maximum sensitivity and specificity of determining extraprostatic disease on MRI is approximately 70%, although this may be improved with endorectal coils.130,131 Due to the increased tissue contrast, planning based on MRI results in a reduction of interobserver variability and a reduction in the volume of the prostate contours.132 In general, the prostate identified on CT is larger than that identified on MRI. Therefore, with MRI-based treatment planning, the accurate delineation of the GTV is more important (compared to CT where the GTV tends be slightly overestimated).
Many novel imaging modalities have been developed for prostate cancer but remain of uncertain utility in current practice. MRS has been explored to further define sites of disease within the prostate. However, the spatial resolution remains too low to accurately define regions for partial prostatic treatment.133 Similarly, radiolabeled antibodies to the prostate specific membrane antigen are commercially available and may aid in the detection of recurrent disease, but specificity and the impact on clinical outcomes again remain unclear.134 The use of lymphotrophic nanoparticle–enhanced MRI has also been explored for improved detection of involved lymph nodes with encouraging initial results.135
Radiolabeled antibodies to the prostate-specific membrane antigen may aid in initial staging of prostate cancer and the detection of recurrent disease. ProstaScint (Cytogen Corp, Princeton, NJ) imaging utilizes the radiolabeled monoclonal antibody indium-111 capromab pendetide, which is the most widely commercially available of the PSA-specific radiopharmaceuticals, to identify sites of local or metastatic disease. The use of 111In-ProstaScint scans is generally indicated for newly diagnosed patients with intermediate or high Gleason score at risk of advanced disease and patients with suspected residual or recurrent disease following definitive treatment, typically in the setting of a rising PSA. One of the earliest multicenter trials with ProstaScint validated the imaging study for diagnosing lymph node involvement with specificity, sensitivity, accuracy, and positive predictive values of 86%, 75%, 81%, and 79%, respectively.136 However, there is little consistency in available reported data, which has been attributed to high interobserver variability as the scans are difficult to interpret. ProstaScint single-photon emission computed tomography in conjunction with conventional CT or MRI has therefore been advocated to facilitate improved specificity by distinguishing sites of active disease from physiologic bone and vascular uptake.137 ProstaScint is most commonly utilized to help distinguish patients with a localized recurrence after surgery from those with systemic progression, the former being appropriate candidates for salvage radiotherapy.134 However, despite its potential utility, the precise role of ProstaScint and its impact on clinical outcomes remain unclear.
Prostate imaging and pathologic analyses can be somewhat discordant. The lesions seen on imaging can often appear focal. However, prostatectomy specimens usually demonstrate the microscopic presence of cancer in multiple regions of the gland. Thus, attempts to severely restrict the therapeutic radiation dose distribution to focal areas of the prostate need to be done with care.
The normal rectum and bladder are commonly avoided structures during pelvic RT, and their location relative to surrounding tissues can be readily determined on planning CT. The interface between the bladder and prostate can be challenging and may be improved with placement of contrast agents within the bladder.
FIGURE 30.13. A coronal T2-weighted magnetic resonance image demonstrating the anatomy of the prostate. The regional anatomy is labeled as follows: the asterisk (*) is the central gland—a combination of the central zone and transitional zone; red arrows indicate the peripheral zone (PZ); blue arrowsindicate the seminal vesicles (SV) and their insertion in the base; green arrows indicate the urogenital diaphragm (UGD); yellow arrows indicate the penile bulb (PB).
THE LYMPHATIC SYSTEM
Oncologic Anatomy
The lymphatic system is a component of the circulatory system, and wherever arteries and veins pass, lymphatic vessels are also present (with the notable exceptions of the placenta and central nervous system). In the central nervous system, lymph is carried within perivascular lymph sheaths, as opposed to actual lymphatic vessels. The lymphatic system includes lymphatic vessels, lymph nodes, lymphatic organs such as the spleen, and the lymphocytes themselves. The lymphatic system is a loosely organized system but generally follows somewhat predictable paths. Small lymphatic vessels form within the tissues of the body, drain into one or more lymph nodes, and eventually drain into larger lymph trunks. These unite to form either the thoracic duct or right lymphatic duct, which empties into the venous system at the subclavian vein–internal jugular vein junction. The lymphatics are primarily involved in returning plasma from the interstitial space to the venous system, although they are also involved in absorption and transport of fat and in defense mechanisms. Radiation oncologists must become versed in an understanding of site-specific lymphatic spread, which is discussed at length within this chapter and elsewhere.
The primary tumors arising from the lymphatic system are leukemias and lymphomas. Leukemias are primarily managed with chemotherapy, although radiation therapy is often utilized in the setting of stem cell transplant (total body irradiation), central nervous system involvement (cranial or craniospinal irradiation), or in palliative settings. Lymphomas consist of multiple distinct entities that are often managed with radiation therapy.
Oncologic Imaging
Nodal Metastases
The accurate identification and characterization of lymph nodes have important diagnostic and prognostic implications in patients with both primary and secondary nodal disease. Prior to the advent of cross-sectional imaging, bipedal lymphangiography was the standard test for evaluating and staging nodal disease in the abdomen and pelvis. CT and MRI have supplanted lymphangiography in the morphologic assessment of nodal disease, which is further supplemented by the physiologic assessment offered by PET imaging. The utility of CT, MRI, and PET in the diagnosis of secondary nodal disease for various malignancies has been detailed earlier in this chapter.
Lymphoma
FDG PET-CT imaging plays an integral role in the management of both Hodgkin lymphoma (HL) and many non-Hodgkin lymphomas (NHL). Prior to PET, two nuclear medicine radionuclides—gallium-67 (Ga-67) and thallium-201 (Tl-201)—were routinely used in the staging of lymphoma. Activity on Ga-67 correlates with histopathologic grade, with high-grade lesions having more uptake. Tl-201, conversely, has avidity for low-grade but not high-grade lymphomas; therefore Tl-201 and Ga-67 scans were deemed complementary. However, the detection of abdominal disease is limited as both gallium and thallium are excreted into the bowel. Compared to Ga-67 scintigraphy, PET appears to have higher patient and site sensitivity.138 However Ga-67 may be better at detecting certain indolent NHLs, specifically splenic marginal zone and small lymphocytic lymphomas, which are routinely not FDG avid.139
Numerous studies have demonstrated the value of PET for initial staging of lymphoma and assessment of response to treatment. A recent meta-analysis showed a median sensitivity of 90.3% and a median specificity of 91.1% for lymphoma staging with dedicated PET with a maximum accuracy of 87.8%.140 In a review assessing combined PET-CT systems, the overall sensitivity and specificity for initial staging of NHL and HL was even higher.141 Compared with CT alone, PET-CT staging often leads to up-staging or down-staging, with the former occurring in 15% to 30% of patients and the latter in 1% to 15% of patients.142,143
In addition to diagnosis and staging, PET is useful in monitoring initial treatment response. Several studies have shown that residual PET abnormalities after chemotherapy strongly predict for subsequent relapse, either with chemotherapy alone144–146 or with combined modality therapy147,148 (Fig. 30.14). Mikhaeel et al.145 showed that posttreatment PET scans predicted outcome far better than posttreatment CT scans. Of 45 patients with aggressive NHL treated with chemotherapy, the relapse rate was 100% (9/9) for patients with residual FDG-avid disease versus 17% (4/36) for patients with negative posttreatment PET scans. Of these 45 patients, 33 also had posttreatment CT imaging. Only 41% of patients with abnormal CT imaging failed, while 25% of patients with negative CT scans eventually relapsed.
However, a negative PET after chemotherapy does not necessarily mean that all disease has been eradicated, simply that an excellent response to chemotherapy was achieved. This point was confirmed in a randomized trial in which patients with HL were randomized to observation or consolidation RT after achieving a PET compete response after chemotherapy. Even in the setting of a negative PET, consolidation RT still decreased the risk of recurrence.149
FIGURE 30.14. Postchemotherapy coronal positron emission tomography (PET) scan images of a patient with stage IVa Hodgkin’s disease demonstrating a hypermetabolic left supraclavicular lymph node. The lymph node was <1 cm on computed tomography (CT) and would not be considered suspicious. Biopsy confirmed persistent disease. Left: PET image. Right: PET-CT fusion image. (Image courtesy of Dr. Edward Coleman.)
SUMMARY
The term oncoanatomy describes the fusion of clinical oncology and anatomy, for the betterment of both. The successful practice of radiation oncology requires a thorough understanding of anatomy. Likewise, the study of malignancy and observations regarding spread of malignant tumors aids in the understanding and instruction of anatomy. Radiation oncologists have a unique opportunity to assist in the instruction of anatomy. For most medical students, gross anatomy is an early first-year course before significant clinical experience is obtained. Over the ensuing years of medical school and residency, much of this knowledge is lost as it is not routinely applied during clinical practice. It is incumbent on those who seek advanced training in fields such as surgery, radiology, and radiation oncology to again become students of anatomy, as the successful practice of such disciplines requires an in-depth understanding of anatomical principles.
An oncoanatomy course has been described.150,151 It consists of a monthly conference where the anatomy of a particular disease site is reviewed along with pertinent clinical implications. Following this didactic session, the presentation continues in the gross anatomy suite where anatomy faculty demonstrate on prosections. This course is attended by medical students, residents, and faculty members from multiple disciplines. The expertise of all involved contributes to a valuable educational environment.
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