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Supplement |
The Crump Institute for Molecular Imaging, The Ahmanson Biological Imaging Center, Department of Molecular and Medical Pharmacology, University of California Los Angeles School of Medicine, Los Angeles, California; Duke University School of Medicine, Durham, North Carolina
Key Words: FDG PET • Health Care Financing Administration • oncology • neurology • literature review • cardiology
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INTRODUCTION |
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 TOP INTRODUCTION INTERPRETING SPREADSHEETS IN...ONCOLOGIC APPLICATIONSCARDIAC APPLICATIONSNEUROLOGICAL APPLICATIONSSUMMARYAPPENDIX A. LITERATURE SEARCH...APPENDIX B. DATA ANALYSIS...APPENDIX C. ABBREVIATIONS LEGENDREFERENCES |
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The goal of this document is to provide a summary of all FDG PET literature for the specified periods, with tabulated values of sensitivity, specificity, percentage in management changes, etc. This document is not intended to be a formal meta-analysis or cost-effectiveness analysis of the available literature. Instead, it is meant to provide an overview of the available literature, so that future detailed studies can use this document as a starting point.
Because of the difficulty of searching all FDG PET literature, this document inevitably does not include some research articles and abstracts that may be useful. The authors have tried to make the search as comprehensive as possible, but some literature may have been overlooked. Details of the literature search strategy are provided in Appendix A. Although a formal meta-analysis is not performed, a simple weighted averaging of data using various strategies is presented (Appendix B). This weighted averaging is meant to give only a general indication of the overall accuracy values and, therefore, should be interpreted with care. A data pooling analysis is also included.
The document is organized to show, first, how the tabulated data should be interpreted. This is followed by oncologic, cardiac, and neurologic application sections that provide, for each disease process, a disease background section, a case example illustrating the clinical implementation of FDG PET, an explanation of why FDG PET helped, a key management issues section (see also Maisey et al. (285)), and a summary of evidence for FDG PET with management change data for the disease and references to the relevant full literature search (in tabulated form) for the accuracy of FDG PET in specific applications. The numbers of patient studies utilized in calculating summary management changes are displayed in Tables 20 and 24 along with management figures and are embedded (without display) within the individual spreadsheets as selected from the data lines that report management change information. In addition, a summary of results from the literature search on FDG PET in all cancers is provided, as well as a summary of FDG PET literature searched for the oncologic, cardiac, and neurologic applications. A full reference list is also provided at the end. Appendix A gives details on the way in which literature was searched and analyzed, and Appendix B reports some alternate approaches to summarizing the data.
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INTERPRETING SPREADSHEETS IN THIS DOCUMENT |
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TOPINTRODUCTIONINTERPRETING SPREADSHEETS IN...ONCOLOGIC APPLICATIONSCARDIAC APPLICATIONSNEUROLOGICAL APPLICATIONSSUMMARYAPPENDIX A. LITERATURE SEARCH...APPENDIX B. DATA ANALYSIS...APPENDIX C. ABBREVIATIONS LEGENDREFERENCES |
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A summary for each application is provided in bold. The bolded summary totals for number of patients, number of patient studies, and number of lesions reflect the totals retrieved from the literature for all studies listing data that is inclusive of that application. Each study entry is listed with complete reported data that may include data relevant to several applications. This accounts for data repeated across applications within a given spreadsheet and is discussed in Appendix A. From within each application are selected the respective study data applicable to that application (e.g., recurrence data in instances in which both staging and recurrence data may have been listed in a given entry) and used in the weighted average formulas generating that application’s summary values, which are listed in the statistical ratio columns. These selected N values for total patient studies and total lesions do not appear in the individual spreadsheets but are embedded in the formulas and appear with the application’s summary values in the overall summary sheets at the end of this report. Note that a weighted average is used, which weights studies by the number of patients, so that results obtained with more patients are given more credit. If lesion-by-lesion analysis was performed, a separate value for that analysis is also listed.
All tabular matter is presented here in the form in which it was submitted to HCFA, with the exception of various corrections to tabulation errors found in certain spreadsheets and their carryover to the overall summary sheets, and the placement of table numbers according to the style of this journal.
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ONCOLOGIC APPLICATIONS |
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TOPINTRODUCTIONINTERPRETING SPREADSHEETS IN...ONCOLOGIC APPLICATIONSCARDIAC APPLICATIONSNEUROLOGICAL APPLICATIONSSUMMARYAPPENDIX A. LITERATURE SEARCH...APPENDIX B. DATA ANALYSIS...APPENDIX C. ABBREVIATIONS LEGENDREFERENCES |
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Disease Background.
Lung cancer is among the most frequent and most lethal of cancers striking both men and women. It is the most rapidly increasing tumor in industrialized countries. Most lung cancers are caused by smoking. However, smoking is a less important factor in adenocarcinoma, the lung cancer most rapidly increasing in the United States. Lung cancer accounts for 22% of all cancers in men and 8% of all cancers in women. Five-year survival is achieved by only 13% of all lung cancer patients. Basic treatment for non-small cell lung cancer (NSCLC) is surgical, with only 20% of patients presenting as operable. Patients who are not operable receive palliative chemotherapy or radiation. Small cell lung cancer patients respond well initially to chemotherapy and radiation and generally do not undergo surgery. Their long-term prognosis is poor.
Case Example.
A 62-y-old patient with known NSCLC was evaluated before planned lobectomy. The patient had no symptoms (e.g., headaches). FDG PET revealed extensive metastatic disease to the brain in addition to the primary cancer in the lung.
Why Did FDG PET Help? Because the FDG PET scan showed that the patient had much more extensive disease than previously thought (Fig. 1, arrows), lobectomy was not a management option for this patient. The patient had no symptoms related to the brain metastases, but the FDG PET whole-body survey scan caught tumor spread to the brain.
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Summary of Evidence for FDG PET in Lung Cancer.
For staging: An estimated 37% change (Table 1) was noted in management effect, based on 1,565 patient studies (Table 24).
Colorectal Cancer
Disease Background.
The colon and the rectum are parts of the large intestine and are responsible for absorption of various substances not absorbed by the small intestine. In western industrialized countries, colorectal cancer is the second most common cause of death from cancer. However, 20-fold variations in international incidence rates have been noted, with the highest rates found in Connecticut in the United States. Primary treatment is surgical, leading to a 50% 5-y survival rate. Adjuvant chemotherapy (chemotherapy before removal of the tumor) is now more commonly used. Radiation is sometimes used for rectal carcinoma and less often for colon cancer. Approximately 20% of patients with recurring cancers are eligible for further resection, with half relapsing early because of previously unidentified metastatic sites. Imaging helps to determine the spread (or lack thereof) of the primary tumor in the colon or rectum.
Case Example.
A patient with carcinoma of the rectum was treated with surgery and radiotherapy. One year later, results of a blood test indicated rising carcinoembryonic antigen (CEA) levels. A CT scan did not reveal the site of tumor recurrence. An FDG PET study showed a liver focus (Fig. 2, arrows), which was proven by biopsy to be recurrent rectal cancer.
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Key Management Issues.
Summary of Evidence for FDG PET in Colorectal Cancer.
For staging: An estimated 36% change was noted in management effect, based on 236 patient studies (Table 2).
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Melanoma
Disease Background.
With an increasing mortality rate second only to that of lung cancer, malignant melanoma is the most rapidly increasing cancer in white populations, with incidence increasing at >5%/y since 1973. The most common cancer striking young women between ages 25 and 29, melanoma accounts for 18% of all cancers in young adults 15–39 y old. Melanoma risk factors include preexisting skin lesions and lighter hair color, with red-haired and blond individuals having 3 and 2 times greater risk than average, respectively. An overall increase in risk appears related to strong solar ultraviolet radiation. Approximately 20% of patients who present with nodal metastases with no distant metastases are cured by surgery. For isolated metastases to the brain and lung, surgery can improve survival. Thus FDG PET’s role in identifying truly isolated metastases is central to the making of rational decisions about radical surgical removal of metastases.
Case Example.
A 63-y-old patient had a melanoma removed from the skin overlying the right scapula (shoulder region). A second metastasis was excised at the nape of the neck. An FDG PET scan was ordered to stage the patient’s cancer. Increased FDG metabolism was seen after surgery at the shoulder site (Fig. 3, far right, top arrow). In addition, multiple metastases were seen within the anterior mediastinum, left lung, left adrenal, left axilla, and para-aortic nodes.
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Key Management Issues.
Summary of Evidence for FDG PET in Melanoma.
For staging: An estimated 26% change was noted in management effect, based on 283 patients (Table 3).
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Disease Background.
Both Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL) are common malignancies that are increasing in frequency. The underlying problem in lymphoma arises from the individual’s white blood cells, cells involved in helping to fight infections. Significant differences exist between HD and NHL, and these differences factor into both diagnosis and treatment. HD begins as a unifocal disease located in a single group of malignant lymph nodes and spreads via adjacent associated lymph node groups. Limited disease is treated appropriately with radiation therapy, resulting in complete cures for a high percentage of patients. Even after recurrence, treatment still may result in permanent cure. Patients with advanced disease have a poorer prognosis and usually require chemotherapy in addition to other treatments. NHL is a multifocal disseminated disease, usually requiring combined chemotherapy, sometimes radiotherapy, and, in some instances, high-dose chemotherapy with bone marrow transplantation. In most patients the disease is ultimately fatal. However, long remission and cure can be induced effectively in high-grade tumors that would be rapidly fatal if untreated. Low-grade NHL, which has a better prognosis untreated, does not respond as well to chemotherapy and consequently can result in a worse prognosis after treatment.
Case Example.
A 27-y-old man with lymphoma underwent an FDG PET study before chemotherapy in July 1999 (Fig. 4, top row). At that time, evidence of cancer was found in the right shoulder and thoracic spine (arrows). The first follow-up FDG PET scan (Fig. 4, middle row) showed nonspecific bone marrow response to chemotherapy (a common finding). The second follow-up scan (Fig. 4, bottom row) demonstrated complete remission, with the right shoulder and thoracic spine regions no longer showing increased FDG metabolism.
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Key Management Issues.
Summary of Evidence for FDG PET in Lymphoma.
For staging: An estimated 21% change was noted in management effect, based on 407 patient studies (Table 4).
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For recurrence: An estimated 10% change was noted in management effect, based on 158 patient studies (Table 4).
Head and Neck Cancer
Disease Background.
Cancer of the head and neck is relatively uncommon in the western world, occurring in 2%–4% of all cancers. In contrast, it comprises up to 40% of all cancers in some Asian countries. In the western cases, the majority are squamous cell tumors with a variable aggressiveness that depends on site and histological appearance. Strong environmental links have been found with tobacco and alcohol usage and with other factors, such as chemicals, fumes, and viruses. Multidisciplinary teams of head and neck surgical oncologists, radiation oncologists, imaging specialists, and medical oncologists operating in specialized centers are required for good outcomes. Treatment is directed at maintaining the form and function of the head and neck structures as well as eradicating the disease. Because of the need to limit surgery and the fact that local nodal spread is the most important prognostic factor, imaging has an important role in the management of these tumors. After treatment, conventional anatomical imaging procedures prove less useful because of the distortion of anatomy caused by treatment. Therefore, FDG PET is of particular importance in follow-up imaging of suspected recurrence.
Case Example.
A patient with a right alveolar ridge carcinoma was referred for FDG PET scanning before surgery for staging purposes. Results of a CT scan (Fig. 5A, 5C) indicated that the tumor extended superiorly into the maxillary sinus. Registered PET and CT images showed uptake of FDG within the primary site arising from the alveolar ridge (Fig. 5B) but no evidence of tumor within the sinus itself (Fig. 5D). This illustrates how the FDG PET scan can identify the extent of disease when inflammatory tissue and tumor are co-located.
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Key Management Issues.
Summary of Evidence for FDG PET in Head and Neck Cancer.
For diagnosis/staging: An estimated 33% change was noted in management effect, based on 15 patient studies (Table 5).
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Breast Cancer
Disease Background.
In the United States, breast cancer is currently second only to lung cancer as the leading cancer causing death in women. It is the most common single cause of death for women ages 35–50 y. Cure can be achieved with early diagnosis and treatment, but a multidisciplinary approach is required. Treatment includes surgery, which is becoming progressively less radical, together with chemotherapy. Hormone and radiation therapy also are used ther-apeutically. Imaging is an important part of detection, staging, and management of most breast cancer patients. Although mammography has helped to detect breast cancer in many women, many cancers are missed in women who have dense breasts, implants, or have been treated previously for breast cancer. In addition, more methods are needed to better detect the spread of breast cancer and to monitor treatment and recurrence.
Case Example.
A 61-y-old woman with breast cancer showed several foci of tumor involvement in the chest and spine (Fig. 6, top row) on her initial FDG PET scan. After chemotherapy, an FDG PET study was requested to look for tumor response to chemotherapy (Fig. 6, bottom row). The small foci of FDG accumulation seen throughout the chest and spine clearly had resolved. Post-therapy CT was positive (still showed tumor mass) because of necrosis and edema from therapy.
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Key Management Issues.
Summary of Evidence for FDG PET in Breast Cancer.
For diagnosis: An estimated 100% change was noted in management effect, based on six patient studies (Table 6). Because of the limited number of patient studies upon which this management change is based, this value should be interpreted with caution.
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For recurrence: An estimated 40% change in management effect, based on 23 patient studies (Table 6).
Brain Tumors
Disease Background.
The incidence of primary brain tumors in the population is 11 in 100,000, with overall metastatic brain disease being more common. Typically, space-occupying lesions are caused by primary tumors, with >50% of patients presenting with some form of epilepsy. New treatments are being introduced, including guided biopsy and surgery (which are frequently image guided), targeted radiation, chemotherapy, and radioactive seed implantation. Outlook remains poor, with survival <1 y for patients with high-grade tumors. Imaging is increasingly required to detect disease, particularly recurrent disease, and in planning and guiding therapy and biopsy. An especially difficult task is determining if cancer has come back after radiation therapy.
Case Example.
The preferred treatment for brain tumors is surgical removal. FDG PET scans are useful for evaluating the efficacy of surgical procedures. A 64-y-old woman with a diagnosis of glioblastoma multiforme (aggressive brain tumor) was operated on to remove the tumor and was treated with radiation. Subsequent contrast-enhanced MRI (Fig. 7, left) suggested possible tumor recurrence. Note the area of contrast accumulation near the surgical region (white arrow). The lack of a corresponding FDG accumulation in that region in the FDG PET image (Fig. 7, right) suggested that the contrast enhancement observed in the MR image was the result of radiation necrosis and that no residual tumor was present at that time.
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Key Management Issues.
Initial management.
Post-treatment management.
Summary of Evidence for FDG PET in Brain Tumors.
For recurrence: An estimated 31% change was noted in management effect, based on 89 patient studies (Table 7).
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Disease Background.
Ovarian cancer is the fifth leading cause of cancer death in women in the United States, with 14,500 deaths and 25,400 new cases diagnosed each year. Approximately one-third of all new cases will have metastatic disease at the time of diagnosis, with another third developing clinical metastases during the first year after surgical resection. The current recommendation for management of patients without evidence of metastatic disease at 1 y after diagnosis is to perform second-look laparotomy for clinical staging and possible tumor resection. For early-stage ovarian cancer, accurate diagnosis is very difficult.
Cervical cancer is one of the most common cancers, accounting for 6% of all malignancies in women, with an estimated 16,000 new cases of invasive cancer of the cervix and 5,000 deaths in the United States each year. The prognosis for this disease is markedly affected by the extent of disease at the time of diagnosis.
Cancer of the endometrium, a common type of cancer in women, is a disease in which cancer cells are found in the lining of the uterus (endometrium). Cancer of the endometrium is different from cancer of the muscle of the uterus (sarcoma of the uterus). Cancer of the endometrium is the most common pelvic gynecologic malignancy and accounts for 13% of all cancers in women. It is a highly curable tumor.
Case Example.
A 50-y-old woman with a history of ovarian cancer showed rising tumor markers in an annual blood test that looked for possible tumor recurrence. A follow-up CT scan was unable to find the source of the recurrence. An FDG PET study showed that the tumor had metastasized to the right lobe of the liver (Fig. 8, arrows on site of metastasis viewed on 4 different sections through the whole body). No other areas of metastasis were seen.
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Key Management Issues.
Summary of Evidence for FDG PET in Ovarian, Uterine, and Cervical Cancer.
For recurrence: An estimated 17% change was noted in management effect, based on 30 patient studies (Table 8).
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Disease Background.
Bladder cancer is a disease in which cancer cells originate from the bladder wall. Approximately 70%–80% of patients with newly diagnosed bladder cancer will present with superficial bladder tumors. Those tumors that are noninvasive are often curable, and those that are deeply invasive are sometimes cured by surgery, irradiation, or a combination of modalities that includes chemotherapy. Some patients with distant metastases have achieved long-term complete response after treatment with combination chemotherapy regimens. The major prognostic factors in carcinoma of the bladder are the depth of invasion into the bladder wall and the degree of differentiation of the tumor. Transurethral surgery, intravesical medications, and cystectomy (bladder removal) have been used in the management of patients with superficial tumors and are all associated with 5-y survival rates for 55%–80% of patients treated. As with many cancers, the key to management is determining if the bladder cancer has spread beyond the bladder to the local lymph nodes or to distant parts of the body.
Case Example.
A patient with cancer of the bladder was scanned for staging purposes. Focal increased FDG uptake was seen within the posterior aspect (back) of the bladder, indicating primary disease only (Fig. 9, arrow). Mild accumulation of FDG also was seen around a right total hip replacement (Fig. 9A), possibly indicating active inflammation or infection, although the patient did not complain of any hip pain.
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Key Management Issues.
Summary of Evidence for FDG PET in Bladder Cancer.
For staging: An estimated 17% change was noted in management effect, based on 12 patient studies (Table 9).
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Gastroesophageal Cancer
Disease Background (Gastric Cancer).
Cancer of the stomach, also called gastric cancer, is a disease in which cancer cells originate from the tissues of the stomach. Cancer of the distal half of the stomach has been decreasing in the United States since the 1930s. However, in the last 2 decades, the incidence of cancer of the cardia and gastroesophageal junction (upper half of the stomach) has been rising rapidly. The incidence of this cancer, especially in patients younger than 40 y, has increased dramatically. In localized distal gastric cancer, >50% of patients can be cured. However, early stage disease accounts for only 10%–20% of all cases diagnosed in the United States. The remaining patients present with metastatic disease in either regional or distant sites. The overall survival rate in these patients at 5 y ranges from almost no survival for patients with disseminated disease to almost 50% survival for patients with localized distal gastric cancers confined to resectable regional disease. Even with apparent localized disease, the 5-y survival rate of patients with proximal gastric cancer is only 10%–15%. Although the treatment of patients with disseminated gastric cancer may result in palliation of symptoms and some prolongation of survival, long remissions are uncommon. Radical surgery represents the standard form of therapy with curative intent. Lesser surgical procedures also may play important roles in palliative therapy for patients with gastric cancer. Neoadjuvant or postoperative chemotherapy and/or radiation therapy are under clinical evaluation.
Disease Background (Esophageal Cancer).
Carcinoma of the esophagus is increasing rapidly in frequency in the west, with the rise most apparent in patients with adenocarcinoma of the esophagus. Much of the increase is thought to be related to reflux esophagitis and Barrett’s esophagus (conditions in which acid from the stomach damages the esophagus), but the exact cause is uncertain. Adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and western Europe, with most tumors located in the distal esophagus. Esophageal cancer is a treatable disease but is rarely curable. The overall 5-y survival rate in those cases amenable to surgery ranges from 5%–20%. The occasional patient with very early disease has a better chance of survival. Primary treatment modalities include surgery alone or chemotherapy with radiation therapy. Combined modality therapy (chemotherapy plus surgery or chemotherapy and radiation therapy plus surgery) is under clinical evaluation.
Case Example (Gastric Cancer).
A 35-y-old patient underwent surgery for gastric cancer. At the time of surgery, a portion of the stomach was removed around the tumor site. During surgery, it was noted that lymph nodes near the stomach also were involved. The patient therefore underwent chemotherapy to treat for spread of the gastric cancer. A CT scan was performed after 6 mo and showed questionable enlargement of lymph nodes in the abdomen. An FDG PET scan was ordered to determine whether the lymph nodes seen on the CT scan were in fact consistent with tumor involvement. The FDG PET scan (Fig. 10) shows several areas of focal increased FDG accumulation in the midabdomen (arrow), confirming tumor recurrence.
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Case Example (Esophageal Cancer).
A 59-y-old man with known esophageal cancer was referred for FDG PET scanning before surgery. CT demonstrated the presence of the primary tumor but no spread of disease. FDG PET showed uptake in the primary tumor (Fig. 11B, lower arrow) and a lymph node near the trachea (Fig. 11A, arrow, and 11B, upper arrow). The esophageal cancer had spread beyond the esophagus.
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Key Management Issues.
Summary of Evidence for FDG PET in Gastroesophageal Cancer.
For diagnosis: An estimated 14% change was noted in management effect, based on 99 patient studies with 276 lesion sites (Table 10).
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For diagnosis/staging: An estimated 14% change was noted in management effect, based on 109 patient studies (Table 10).
Hepatocellular Cancer
Disease Background.
Adult primary liver cancer is a disease in which cancer cells start to grow in the tissues of the liver. People who have hepatitis B or C or cirrhosis, a disease of the liver, are more likely than other people to get adult primary liver cancer. Primary liver cancer is different from cancer that has spread from another place in the body to the liver. Hepatocellular carcinoma is a relatively uncommon tumor in the United States, although its incidence is rising. It is the most common cancer in some other parts of the world. Hepatocellular carcinoma is potentially curable by surgical resection, but surgery is the treatment of choice for only the small fraction of patients with localized disease. Prognosis depends on the degree of local tumor replacement and the extent of liver function impairment. Therapy other than surgical resection is best administered as part of a clinical trial. Hepatocellular carcinoma is associated with cirrhosis in 50%–80% of patients. Five percent of patients with cirrhosis eventually develop hepatocellular cancer, which is often multifocal. Childhood liver cancer, also called hepatoma, is a rare disease in which cancer cells are found in the tissues of a child’s liver. Two types of cancer (hepatoblastoma and hepatocellular cancer) start in the liver and are identified by the way the cancer cells look under a microscope. Hepatoblastoma is more common in children younger than 3 y and may have a genetic cause. The overall survival rate for children with hepatoblastoma is 70% but is only 25% for hepatocellular carcinoma.
Case Example.
A patient presented to his doctor with vague abdominal symptoms. The work-up, which eventually included a CT scan, revealed that the patient had enlarged lymph nodes near the portal region of the liver. An FDG PET scan was ordered to further evaluate for tumor. The scan revealed uptake of FDG within a focus in the right lobe of the liver (Fig. 12, center). No other foci were present, indicating that the tumor was confined to the liver. The patient went on to have an appropriate surgery for localized hepatoma.
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Key Management Issues.
Summary of Evidence for FDG PET in Hepatocellular Cancer.
For staging: An estimated 60% change was noted in management effect, based on 20 patient studies (Table 11).
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Disease Background.
Adult soft tissue sarcoma is a disease in which cancer cells are found in the soft tissue of part of the body. The soft tissues of the body include the muscles, connective tissues (tendons), vessels that carry blood or lymph, joints, and fat. The prognosis for a patient with adult soft tissue sarcomas depends on several factors, including the patient’s age and the size, histologic grade, and stage of the tumor. Factors associated with a poorer prognosis are age older than 60 y, tumors >5 cm, and high-grade histology. Although low-grade tumors usually are curable by surgery alone, higher-grade sarcomas (as determined by the mitotic index and the presence of hemorrhage and necrosis) are associated with higher local treatment failure rates and increased metastatic potential. Soft tissue sarcomas are rare in children and adolescents. There are many different kinds of soft tissue sarcoma, depending on the soft tissue in which the cancer begins. Rhabdomyosarcoma is the most common type of childhood soft tissue sarcoma. It begins in muscles around the bone and can be found anywhere in the body.
Case Example.
A 41-y-old man had surgery and radiotherapy, first for a liposarcoma in the right thigh and 3 mo later for a solitary metastasis in the abdomen. He developed recurrent disease within the right thigh and was referred for FDG PET scanning. The FDG PET scan showed focal increased metabolism within the right thigh (Fig. 13A, B, and C), indicative of recurrent disease, surrounded by diffuse metabolism secondary to inflammation after surgery. High metabolism of FDG was also noted within lung metastases (Figs. 13C and D).
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Key Management Issues.
Summary of Evidence for FDG PET in Muscle and Connective Tissue Tumors.
Management change data for diagnosis and staging and other applications are not directly available from the literature (Table 12).
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Disease Background.
Pancreatic carcinoma is common in the United States, with approximately 30,000 patients each year diagnosed with pancreatic adenocarcinomas. Patients with inflammatory processes in the pancreas (pancreatitis) but no cancer can sometimes have high FDG uptake that is indistinguishable from cancers and, thus, must be differentiated from patients with cancer. FDG PET is being applied increasingly in pancreatic cancer diagnosis. Considering the very poor prognosis of pancreatic carcinomas, PET’s greatest role may prove to be in helping to characterize masses appearing in the pancreas, as opposed to more general tumor staging. This is an active area of current investigation.
Case Example.
A 52-y-old woman with a calcified pancreatic mass on CT (Fig. 14A, arrow) was referred for FDG PET scanning because of rising blood tumor markers. No uptake of FDG was seen within the mass (Fig. 14B). The patient was treated conservatively, under the assumption that she had inflammation of the pancreas (pancreatitis). Follow-up over 2 y with CT revealed no changes, indicating that FDG PET was correct and no tumor existed.
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Key Management Issues.
Summary of Evidence for FDG PET in Pancreatic Cancer.
For diagnosis: An estimated 50% change was noted in management effect, based on 26 patient studies (Table 13).
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For staging: An estimated 36% change was noted in management effect, based on 33 patient studies (Table 13).
For recurrence: An estimated 53% change was noted in management effect, based on 19 patient studies (Table 13).
For monitoring response: An estimated 16% change was noted in management effect, based on 19 patient studies (Table 13).
Prostate Cancer
Disease Background.
Prostate cancer rates increased 141.8% between 1973 and 1994. In 1998, new prostate cancer cases totaled 184,500, or, in other terms, one new case every 3 min. Prostate cancer continues to be the most frequently occurring malignancy (aside from skin cancers), representing 29% of all new cancer cases in American men. One out of every six men is at lifetime risk for prostate cancer. Approximately every 13 min, a life is lost to prostate cancer in the United States. African-Americans have the highest prostate cancer incidence rates in the world, exceeding those for white males in the United States by 34%. Prostate cancer mortality rates are two times higher for African-American men than for white American men.
Case Example.
A 75-y-old man, who was diagnosed with prostate cancer, was followed by blood levels for prostate specific antigen (PSA, a prostate tumor marker). A rising PSA was followed up with a CT scan (Fig. 15, left), which revealed lymph node involvement in the pelvis near the removed prostate. An FDG PET study confirmed what was seen on CT and, in addition, showed spread of cancer into the abdomen and chest (Fig. 15, middle and right).
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Key Management Issues.
Summary of Evidence for FDG PET in Prostate Cancer.
Management change data for staging patients are not directly available from the literature (Table 14).
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Disease Background.
Renal cell cancer, also called renal adenocarcinoma or hypernephroma, can often be cured if diagnosed and treated when still localized to the kidney and to immediately surrounding tissue. The probability of cure is directly related to the stage or degree of tumor dissemination. Even when regional lymphatics or blood vessels are involved with tumor, a significant number of patients can achieve prolonged survival and probable cure. When distant metastases are present, disease-free survival is poor, although occasionally, patients will survive after surgical resection of all known tumor. Because a majority of patients are diagnosed when the tumor is still relatively localized and amenable to surgical removal, approximately 40% of all patients with renal cancer survive 5 y. Occasionally, patients with locally advanced or metastatic disease may exhibit indolent courses lasting several years. Late tumor recurrence many years after initial treatment occurs occasionally. Renal cell cancer is one of the few tumors in which well-documented cases of spontaneous tumor regression in the absence of therapy exist, but this occurs very rarely and may not lead to long-term survival. Surgical resection is the mainstay of treatment of this disease. Even in patients with disseminated tumor, locoregional forms of therapy may play an important role in palliating symptoms of the primary tumor or of ectopic hormone production. Systemic therapy has demonstrated only limited effectiveness.
Case Example.
A 59-y-old man with a history of metastatic renal cell cancer and left kidney removal developed left-sided flank pain. Abdominal-pelvic CT was negative on initial review (Fig. 16, bottom row). FDG PET revealed a focus in the apex of the right lung and in the left flank (Fig. 16, top row, arrows). Because of the abnormality in the region of the left flank, the CT was reviewed again and a mass located in the posterior abdominal wall was found. Biopsy revealed metastasis from renal cell cancer.
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Key Management Issues.
Summary of Evidence for FDG PET in Renal Cell Cancer.
Management change data for diagnosis and staging and other applications are not directly available from the literature (Table 15).
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Disease Background.
Cancer of the testicle, a rare type of cancer, is a disease in which cancer cells are found in the tissues of one or both of a man’s testicles. Cancer of the testicle is the most common cancer in men 15–35 y old. Men who have an undescended testicle (a testicle that has never moved down into the scrotum) are at higher risk of developing cancer of the testicle. This is true even if surgery has been performed to place the testicle in the appropriate place in the scrotum. Prognosis and choice of treatment depend on the stage of the cancer and the patient’s general state of health.
Case Example.
A 27-y-old man with testicular cancer had his left testicle removed. An abdominal CT scan indicated an enlarged lymph node in the lower abdomen. A CT-guided biopsy was performed but did not reveal cancer. An FDG PET scan was ordered to make sure the biopsy was not wrong. The scan showed a focus of activity in the abdominal lymph node (Fig. 17, arrows), suggesting cancer spread. A repeat biopsy confirmed tumor in the abdominal lymph node site.
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Key Management Issues.
Summary of Evidence for FDG PET in Testicular Cancer.
For staging: An estimated 22% change was noted in management effect, based on 27 patient studies (Table 16).
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Thyroid Cancer
Disease Background.
Cancer of the thyroid is a disease in which cancer cells are found in the tissues of the thyroid gland. People who have been exposed to large amounts of radiation or who have had radiation treatment for medical problems in the head and neck have a higher chance of getting thyroid cancer. The cancer may not occur until 20 y or longer after radiation treatment. The four main types of cancer of the thyroid are: papillary, follicular, medullary, and anaplastic. The chance of recovery depends on the type of thyroid cancer, whether it is only in the thyroid or has spread to other parts of the body (stage), and the patient’s age and overall health. Some types of thyroid cancer grow much faster than others. Although thyroid cancer is relatively uncommon, it is nonetheless the most common malignancy of the endocrine system. Differentiated tumors (papillary or follicular) are highly treatable and usually curable. Poorly differentiated cancers (medullary or anaplastic) are much less common but aggressive, metastasize early, and have a much poorer prognosis. The incidence of this malignancy has been increasing over the last decade. The prognosis for differentiated carcinoma is better for patients younger than 40 y and who have no extracapsular extension or vascular invasion. Age appears to be the single most important prognostic factor. Thyroid cancer commonly presents as a cold nodule within the thyroid gland. The overall incidence of cancer in a cold nodule is 12%–15% but is higher in patients younger than 40 y.
Case Example.
A 62-y-old patient underwent surgery of the left thyroid for thyroid cancer. Routine yearly monitoring revealed elevated blood levels of calcitonin. A CT scan was ordered and was normal. An FDG PET scan revealed increased FDG accumulation in the neck (Fig. 18, arrows), which was confirmed by biopsy to be residual thyroid cancer.
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Key Management Issues.
Summary of Evidence for FDG PET in Thyroid Cancer.
For staging: An estimated 22% change was noted in management effect, based on 60 patient studies (Table 17).
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For recurrence: An estimated 53% change was noted in management effect, based on 21 patient studies (Table 17).
Unknown Primary Tumor
Disease Background.
Detection of the unknown primary lesion is very difficult. In many cases, patients present with obvious metastatic disease, often adenocarcinoma, in which the location of the primary lesion may never be found. In some cases, knowledge of the primary site is important, because the type of treatment may vary (e.g., breast cancers are more responsive to some treatments than are renal cancers). This knowledge also can be helpful in resection or treatment for cure of the primary lesion and metastases (e.g., head and neck cancers). FDG PET is useful in locating primary tumors after metastatic disease has appeared in regional lymph nodes. FDG PET is being applied increasingly in the search for unknown primary lesions. This application is still in evolution, but FDG PET should be considered strongly in the work-up of the unknown primary.
Case Example.
A 49-y-old woman presented with lymph node enlargement in the neck. Physical examination, CT, and mammography performed twice all failed to reveal the source of the primary cancer. An FDG PET study showed that the primary cancer was in the left breast (nonpalpable). The lymph node involvement was not seen in the sections shown in Figure 19.
