Showing papers in "Cancer in 2000"

World Health Organization classification of tumors.

Abstract: World Health Organization Collaborating Centerfor International Histological Classification of Tu-mors, Armed Forces Institute of Pathology, Wash-ington, DC.Address for reprints: Leslie H. Sobin, M.D., ArmedForces Institute of Pathology, Alaska Avenue and14th Street, Building 54, Room 3009, Washington,DC 20306-6000.Received March 23, 2000; accepted March 23,2000.

An analysis of 8305 cases of carcinoid tumors.

Abstract: BACKGROUND Carcinoid tumors are unusual and most reports are anecdotal or limited in number. A series of 2837 cases was published in 1975. No recent large series is available. METHODS The authors evaluated 5468 cases identified by the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) from 1973 to 1991 together with 2837 carcinoid cases previously registered by 2 earlier NCI programs. To the authors' knowledge, the 8305 carcinoid tumors analyzed represent the largest current epidemiology series to date. RESULTS The most frequent sites for carcinoids were the gastrointestinal (GI) tract (73.7%) and the bronchopulmonary system (25.1%). Within the GI tract, most occurred in the small bowel (28.7%), appendix (18.9%), and rectum (12.6%). For all sites, age-adjusted incidence rates were highest in African American males (2.12 per 100,000 population per year). Associated noncarcinoid tumors were frequent in conjunction with small intestinal (16.6%), appendiceal (14.6%), and colonic carcinoids (13.1%). The highest percentage of nonlocalized lesions were noted for pancreatic (76.1%), colonic (71.2%), and small intestinal carcinoids (70.7%) and this corresponded to their poor 5-year survival rates (34.1%, 41.6%, and 55.4%, respectively). The best 5-year survival rates were recorded for appendiceal (85.9%), bronchopulmonary (76.6%), and rectal carcinoids (72.2%). These exhibited invasive growth or metastatic spread in only 35.4%, 27.2%, and 14.2% of cases, respectively. CONCLUSIONS Carcinoids appear to have increased in incidence in the past 20 years. In part, this may be due to different surgical rules of the various registries, improved diagnostic technology, and increased awareness. A cumulative analysis of all types of carcinoid tumors in the SEER group indicates that in 45.3% metastases are already evident at the time of diagnosis. The overall 5-year survival rate of all carcinoid tumors regardless of site was 50.4% ± 6.4%. Cancer 1997; 79:813-29. © 1997 American Cancer Society.

Assessing symptom distress in cancer patients: The M. D. Anderson Symptom Inventory

Abstract: BACKGROUND The purpose of this project was to develop the M. D. Anderson Symptom Inventory (MDASI), a brief measure of the severity and impact of cancer-related symptoms. METHODS A list of symptoms was generated from symptom inventories and by panels of clinicians. Twenty-six symptoms and 6 interference items were rated by a validation sample of 527 outpatients, a sample of 30 inpatients from the blood and bone marrow transplantation service, and a cross-validation sample of 113 outpatients. Clinical judgment and statistical techniques were used to reduce the number of symptoms. Reliability, validity, and sensitivity of the MDASI were examined. RESULTS Cluster analysis, best subset analysis, and clinical judgment reduced the number of symptoms to a “core” list of 13 that accounted for 64% of the variance in symptom distress. Factor analysis demonstrated a similar pattern in both outpatient samples, and two symptom factors and the interference scale were reliable. Expected differences in symptom pattern and severity were found between patients with “good” versus “poor” performance status and between patients in active therapy and patients who were seen for follow-up. Patients rated fatigue-related symptoms as the most severe. Groups of patients classified by disease or treatment had severe symptoms that were not on the “core” list. CONCLUSIONS The core items of the MDASI accounted for the majority of symptom distress reported by cancer patients in active treatment and those who were followed after treatment. The MDASI should prove useful for symptom surveys, clinical trials, and patient monitoring, and its format should allow Internet or telephone administration. Cancer 2000;89:1634–46. © 2000 American Cancer Society.

Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study.

Abstract: BACKGROUND Peritoneal carcinomatosis (PC) is a common evolution of digestive cancer, associated with a poor prognosis Yet it is poorly documented in the literature METHODS Three hundred seventy patients with PC from non-gynecologic malignancies were followed prospectively: the PC was of gastric origin in 125 cases, of colorectal origin in 118 cases, of pancreatic origin in 58 cases, of unknown origin in 43 cases, and of miscellaneous origins in 26 cases A previously reported PC staging system was used to classify these 370 patients RESULTS Mean and median overall survival periods were 60 and 31 months, respectively Survival rates were mainly affected by the initial PC stage (98 months for Stage I with malignant peritoneal granulations less than 5 mm in greatest dimension, versus 37 months for Stage IV with large, malignant peritoneal masses more than 2 cm in greatest dimension) The presence of ascites was associated with poor survival of patients with gastric or pancreatic carcinoma Differentiation of the primary tumor did not influence the prognoses of patients with PC CONCLUSIONS A better knowledge of the natural history of PC is needed, in view of the many Phase I, II, and III trials currently being conducted to evaluate aggressive multimodal therapeutic approaches to treating patients with PC from non-gynecologic malignancies Cancer 2000;88:358–63 © 2000 American Cancer Society

Cellular and molecular mechanisms of action of bisphosphonates

Abstract: BACKGROUND Bisphosphonates currently are the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor-associated osteolysis and hypercalcemia, Paget's disease, and osteoporosis. These compounds have high affinity for calcium and therefore target to bone mineral, where they appear to be internalized selectively by bone-resorbing osteoclasts and inhibit osteoclast function. METHODS This article reviews the pharmacology of bisphosphonates and the relation between the chemical structure of bisphosphonates and antiresorptive potency, and describes recent new discoveries of their molecular mechanisms of action in osteoclasts. RESULTS Bisphosphonates can be grouped into two pharmacologic classes with distinct molecular mechanisms of action. Nitrogen-containing bisphosphonates (the most potent class) act by inhibiting the mevalonate pathway in osteoclasts, thereby preventing prenylation of small GTPase signaling proteins required for osteoclast function. Bisphosphonates that lack a nitrogen in the chemical structure do not inhibit protein prenylation and have a different mode of action that may involve the formation of cytotoxic metabolites in osteoclasts or inhibition of protein tyrosine phosphatases. CONCLUSIONS Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect osteoclasts. After more than 30 years of clinical use, their molecular mechanisms of action are only just becoming clear. Cancer 2000;88:2961–78. © 2000 American Cancer Society.

The unmet supportive care needs of patients with cancer

Abstract: BACKGROUND The aim of this study was to determine the prevalence and predictors of the perceived unmet needs of cancer patients undergoing treatment for their disease at public treatment centers. METHODS A total of 1492 consecutive patients attending the surgical, radiation, or medical oncology departments of 9 major public cancer treatment centers in New South Wales, Australia, were asked to participate. Of the 1370 eligible patients, 1354 (99%) consented to participate and 888 (65%) returned completed surveys. Eligible consenting patients were given a Supportive Care Needs Survey to complete at home and return by mail within 7 days. RESULTS Patients' perceived needs were assessed across the following five areas: psychologic, health system and information, physical and daily living, patient care and support, and sexuality. Patients' perceived needs were highest in the psychologic, health system and information, and physical and daily living domains. Logistic regression modeling revealed subgroups of patients with different types of needs. The significant predictors of reporting some unmet need for help varied according to the domain examined. CONCLUSIONS This statewide study shows that cancer patients experience high levels of unmet needs across the range of domains examined. The study provides information that may be valuable in identifying areas where interventions could be tested and evaluated in an attempt to address the unmet needs of people living with cancer. [See related article on pages 217–25, this issue.] Cancer 2000;88:225–36. © 2000 American Cancer Society.

COX-2 is expressed in human pulmonary, colonic, and mammary tumors.

Abstract: BACKGROUND The cyclooxygenase (COX) enzyme catalyzes the formation of prostaglandins, which can affect cell proliferation and alter the response of the immune system to malignant cells. The inducible form of COX, COX-2, has been shown to be important in carcinogenesis. METHODS The authors studied COX-1 and -2 expression in 20 tumors of the lung, colon, and breast (60 total) by using commercially available monoclonal and polyclonal antibodies on formalin fixed, paraffin embedded tissue. Our evaluation also included seven carcinoma-associated colonic adenomas and 10 mammary ductal carcinomas in situ (DCIS). Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system that approximates the use of image analysis-based systems. RESULTS Ninety percent of lung tumors (squamous cell carcinomas and adenocarcinomas), 71% of colon adenocarcinomas and 56% of breast tumors (DCIS and infiltrating ductal and lobular carcinomas) expressed COX-2 at a moderate to strong level, which was significantly different from the negligible expression in distant nonneoplastic epithelium (controls; P < 0.0001). Poorly differentiated histologic features were correlated with low COX-2 expression overall, especially in colon carcinomas. Among breast carcinomas, DCIS was more likely to express COX-2 than invasive carcinomas. Adenomatous colonic epithelium showed moderate COX-2 expression, as did adjacent nonneoplastic epithelium. COX-1 immunoreactivity was essentially weak to moderate in all tissues evaluated. CONCLUSIONS COX-2 expression is upregulated in well and moderately differentiated carcinomas of the lung, colon, and breast whereas COX-1 appears to be constitutively expressed at low levels. A possible COX-2 paracrine effect is suggested by moderate immunoreactivity in adjacent nonneoplastic epithelium. Cancer 2000;89:2637–45. © 2000 American Cancer Society.

Validation of the Edmonton Symptom Assessment Scale.

Abstract: BACKGROUND The Edmonton Symptom Assessment Scale (ESAS) is a nine-item patient-rated symptom visual analogue scale developed for use in assessing the symptoms of patients receiving palliative care. The purpose of this study was to validate the ESAS in a different population of patients. METHODS In this prospective study, 240 patients with a diagnosis of cancer completed the ESAS, the Memorial Symptom Assessment Scale (MSAS), and the Functional Assessment Cancer Therapy (FACT) survey, and also had their Karnofsky performance status (KPS) assessed. An additional 42 patients participated in a test-retest study. RESULTS The ESAS “distress” score correlated most closely with physical symptom subscales in the FACT and the MSAS and with KPS. The ESAS individual item and summary scores showed good internal consistency and correlated appropriately with corresponding measures from the FACT and MSAS instruments. Individual items between the instruments correlated well. Pain ratings in the ESAS, MSAS, and FACT correlated best with the “worst-pain” item of the Brief Pain Inventory (BPI). Test-retest evaluation showed very good correlation at 2 days and a somewhat smaller but significant correlation at 1 week. A 30-mm visual analogue scale cutoff point did not uniformly distinguish severity of symptoms for different symptoms. CONCLUSIONS For this population, the ESAS was a valid instrument; test-retest validity was better at 2 days than at 1 week. The ESAS “distress” score tends to reflect physical well-being. The use of a 30-mm cutoff point on visual analogue scales to identify severe symptoms may not always apply to symptoms other than pain. Cancer 2000;88:2164–71. © 2000 American Cancer Society.

The annual report to the nation on the status of cancer, 1973–1997, with a special section on colorectal cancer

Abstract: BACKGROUND This annual report to the nation addresses progress in cancer prevention and control in the U.S. with a special section on colorectal cancer. This report is the joint effort of the American Cancer Society, the National Cancer Institute (NCI), the North American Association of Central Cancer Registries (NAACCR), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS). METHODS Age-adjusted rates were based on cancer incidence data from the NCI and NAACCR and underlying cause of death as compiled by NCHS. Joinpoint analysis was based on NCI Surveillance, Epidemiology, and End Results (SEER) program incidence rates and NCHS death rates for 1973–1997. The prevalence of screening examinations for colorectal cancer was obtained from the CDC's Behavioral Risk Factor Surveillance System and the NCHS's National Health Interview Survey. RESULTS Between 1990–1997, overall cancer incidence and death rates declined. Joinpoint analyses of cancer incidence and death rates confirmed the declines described in earlier reports. The incidence trends for colorectal cancer have shown recent steep declines for whites in contrast to a leveling off of the rates for blacks. State-to-state variations occurred in colorectal cancer screening prevalence as well as incidence and death rates. CONCLUSIONS The continuing declines in overall cancer incidence and death rates are encouraging. However, a few of the top ten incidence or mortality cancer sites continued to increase or remained level. For many cancer sites, whites had lower incidence and mortality rates than blacks but higher rates than Hispanics, Asian and Pacific Islanders, and American Indians/Alaska Natives. The variations in colorectal cancer incidence and death rates by race/ethnicity, gender, age, and geographic area may be related to differences in risk factors, demographic characteristics, screening, and medical practice. New efforts currently are underway to increase awareness of screening benefits and treatment for colorectal cancer. Cancer 2000;88:2398–424. © 2000 American Cancer Society.

Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.

Abstract: BACKGROUND A retrospective review of treatment results comparing women with clear cell carcinoma of the ovary (CCC) with a group with serous adenocarcinoma of the ovary (SAC) was conducted. METHODS Between 1988–1998, 662 patients with epithelial ovarian carcinoma were identified through the medical records department and the tumor registry at 4 institutions. After the central pathologic review, 101 patients with pure or dominant (≥ 90%) CCC (15.3%) were entered into the current study. Two hundred thirty five patients with pure SAC were selected as a group for comparison. All patients underwent staging laparotomy followed by platinum-based chemotherapy. Distribution of the International Federation of Gynecology and Obstetrics (FIGO) disease stage, response to chemotherapy, and prognosis for patients with CCC were compared with the same values in patients with SAC. RESULTS Patients with CCC were significantly more likely to have FIGO Stage I disease than were patients with SAC (48.5% vs. 16.6%). A high recurrence rate was noted in those patients with Stage IC CCC (37%). In those patients with Stage IC disease, the survival rates for patients with CCC were lower than those for patients with SAC. The 3-year and 5-year survival rates for Stage III CCC patients were significantly lower compared with Stage III SAC patients. The response rate to platinum-based chemotherapy in patients with CCC was significantly lower than that in patients with SAC. CONCLUSIONS CCC is an intriguing histologic type of epithelial ovarian cancer that demonstrates a clinical behavior distinctly different from that of SAC. Cancer 2000;88:2584–9. © 2000 American Cancer Society.

Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.

Abstract: BACKGROUND Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. METHODS After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (≤ 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. RESULTS Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. CONCLUSIONS Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC. Cancer 2000;89:500–7. © 2000 American Cancer Society.

Early Lung Cancer Action Project

Abstract: BACKGROUND The Early Lung Cancer Action Project (ELCAP) was designed to evaluate the usefulness of annual computed tomography (CT) screening for lung carcinoma. With the baseline results having been reported previously, the focus of the current study was on the early results of the repeat screenings. METHODS A cohort of 1000 high-risk individuals was recruited for baseline and annual repeat CT screening. At last follow-up, a total of 1184 annual repeat screenings had been performed. A positive result from the screening test was defined as newly detected, one to six noncalcified pulmonary nodules with interim growth. The diagnostic workup of the individuals was guided by recommendations supplied by the ELCAP investigators to the collaborating clinicians. RESULTS Of the 1184 repeat CT screenings, the test result was positive in 30 (2.5%). In 2 of these 30 cases, the individual died (of an unrelated cause) before diagnostic workup and the nodule(s) resolved in another 12 individuals. In the remaining 16 individuals, the absence of further growth was documented by repeat CT in 8 individuals and further growth was documented in the remaining 8 individuals. All eight individuals with further nodular growth underwent biopsy and malignancy was diagnosed in seven. Six of these seven malignancies were nonsmall cell carcinomas (five of which were Stage IA and one of which was Stage IIIA) and the one small cell carcinoma was found to be of limited stage. The median size dimension of these malignancies was 8 mm. In another two subjects, symptoms prompted the interim diagnosis of lung carcinoma. Neither of these malignancies was nodule-associated but rather were endobronchial; one was a Stage IIB nonsmall cell carcinoma and the other was a small cell carcinoma of limited stage. CONCLUSIONS False-positive screening test results are uncommon and usually manageable without biopsy; compared with no screening, such screenings permit diagnosis at substantially earlier and thus more curable stages. Annual repetition of CT screening is sufficient to minimize symptom-prompted interim diagnoses of nodule-associated malignancies. Cancer 2001;92:153–9. © 2001 American Cancer Society.

Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials.

Abstract: BACKGROUND Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases. METHODS Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3–4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. RESULTS Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group. CONCLUSIONS In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases. Cancer 2000;88:1082–90. © 2000 American Cancer Society.

Medullary thyroid carcinoma

Abstract: Unlike most other carcinomas arising from the follicular cell of the thyroid, medullary thyroid carcinoma (MTC) is a malignancy with neuroendocrine features, derived from the parafollicular C cell, which is of ectodermal neural crest origin. In most studies, MTC represents 3–12% of thyroid cancers, the majority of which are sporadic. However, in approximately 25–30% of cases, MTC is inherited, and is associated with one of three familial syndromes: multiple endocrine neoplasia (MEN) syndrome type 2A, MEN type 2B, and familial MTC (Table 10.1). In contrast to sporadic cases of MTC, germline RET proto-oncogene mutations are often detected in inherited cases, which may facilitate early diagnosis.

Paclitaxel-induced cell death: Where the cell cycle and apoptosis come together

Abstract: BACKGROUND Compelling evidence indicates that paclitaxel kills cancer cells through the induction of apoptosis. Paclitaxel binds microtubules and causes kinetic suppression (stabilization) of microtubule dynamics. The consequent arrest of the cell cycle at mitotic phase has been considered to be the cause of paclitaxel-induced cytotoxicity. However, the biochemical events, downstream from paclitaxel's binding to microtubules, that lead to apoptosis are not well understood. METHODS The authors examined recent scientific literature about the mechanisms by which paclitaxel exerts cytotoxicity. RESULTS In addition to an arrest of the cell cycle at the mitotic phase in paclitaxel-treated cells, recent discoveries of activation of signaling molecules by paclitaxel and paclitaxel-induced transcriptional activation of various genes indicate that paclitaxel initiates apoptosis through multiple mechanisms. The checkpoint of mitotic spindle assembly, aberrant activation of cyclin-dependent kinases, and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) are shown to be involved in paclitaxel-induced apoptosis. Consistent with observations that microtubules of different status (e.g., cytoskeletal microtubules vs. mitotic spindles) have different sensitivity to paclitaxel, the concentration of paclitaxel appears to be the major determinant of its apoptogenic mechanisms. CONCLUSIONS Advances in research of the cell cycle and apoptosis have extended our understanding of the mechanisms of paclitaxel-induced cell death. Further elucidation of resistance and enhancement of paclitaxel-induced apoptosis should expedite the development of better paclitaxel-based regimens for cancer therapy. Cancer 2000;88:2619–28. © 2000 American Cancer Society.

The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the "different disease" hypothesis.

Abstract: BACKGROUND A high proportion of US patients with gastric carcinoma do not receive surgical treatment To sharpen staging criteria and facilitate comparisons with surgical series, an analysis of patients whose treatment included gastrectomy was undertaken In addition, to evaluate the “different disease” hypothesis as an explanation for superior Japanese results, outcomes for Japanese Americans were examined METHODS Data were obtained from National Cancer Data Base (NCDB) reports of 50,169 gastric carcinoma cases diagnosed during the years 1985–1996 and treated with gastrectomy In addition to demographic and treatment information, 5-year and 10-year relative survival rates are presented, with stage defined according to fifth edition American Joint Committee on Cancer (AJCC) staging procedures RESULTS Stage-stratified 5-year and 10-year relative survival rates were as follows: Stage IA, 78%/65%; Stage IB, 58%/42%; Stage II, 34%/26%; Stage IIIA, 20%/14%; Stage IIIB, 8%/3%; and Stage IV, 7%/5% Stage-stratified survival for Japanese Americans was higher Males had a poorer prognosis than females, and the male-to-female ratio for Japanese Americans was lower Proximal tumors were associated with a worse prognosis than distal tumors; the proportion of Japanese Americans with proximal disease was less than in the overall patient group Japanese Americans underwent resection of adjacent organs less frequently In this series, adjuvant therapy did not substantially affect survival Overall, 20% were 10-year survivors; of these, 67% were lymph node negative and 98% had ≤ 8 involved lymph nodes Five-year stage-stratified survival increased for cases with ≥ 15 lymph nodes analyzed Stage migration was evident in cases with ≤ 15 nodes examined CONCLUSIONS The current AJCC/International Union Against Cancer TNM staging system fails to accommodate the effect of proximal location on prognosis Largely because Japanese Americans present with fewer proximal tumors, have a lower male-to-female ratio, and undergo adjacent organ resection less frequently, stage- stratified survival for Japanese Americans appears to be superior In the US, surgical undertreatment of patients with this disease appears to be a problem Cancer 2000;88:921–32 © 2000 American Cancer Society

Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.

Abstract: BACKGROUND. In the treatment of prostate carcinoma, radiotherapy and surgery are common choices of comparable efficacy; thus a realistic comparison of the potential long term sequelae, such as the risk of second malignancy, may be of relevance to treatment choice. METHODS. Data regarding the rate of incidence from the Surveillance, Epidemiology, and End Results Program cancer registry (1973‐1993) were used to compare directly second malignancy risks in 51,584 men with prostate carcinoma who received radiotherapy (3549 of whom developed second malignancies) with 70,539 men who underwent surgery without radiotherapy (5055 of whom developed second malignancies). Data were stratified by latency period, age at diagnosis, and site of the second malignancy. Directly comparing the risks in the radiotherapy group with those in the surgery group largely avoids problems associated with underreporting second malignancies. RESULTS. Radiotherapy for prostate carcinoma was associated with a small, statistically significant increase in the risk of solid tumors (6%; P 5 0.02) relative to treatment with surgery. Among patients who survived for $ 5 years, the increased relative risk reached 15%, and was 34% for patients surviving $ 10 years. The most significant contributors to the increased risk in the irradiated group were carcinomas of the bladder, rectum, and lung, and sarcomas within the treatment field. No significant increase in rates of leukemia was noted. CONCLUSIONS. Radiotherapy for prostate carcinoma was associated with a statistically significant, although fairly small, enhancement in the risk of second solid tumors, particularly for long term survivors. The pattern of excess second malignancies among men treated with radiotherapy was consistent with radiobiologic principles in terms of site, dose, and latency. In absolute terms, the estimated risk of developing a radiation-associated second malignancy was 1 in 290 for all prostate carcinoma patients treated with radiotherapy, increasing to 1 in 70 for long term survivors ($ 10 years). Improvements in radiotherapeutic techniques, along with diagnosis at younger ages and earlier stages, are resulting in longer survival times for patients with prostate carcinoma. Because of the long latency period for radiation-induced tumors, this may result in radiation-related second malignancy risk becoming a more significant issue. Cancer 2000;88:398 ‐ 406. © 2000 American Cancer Society.

Treatment of intrahepatic malignancy with radiofrequency ablation:radiologic-pathologic correlation

Abstract: BACKGROUND Radiofrequency (RF)-induced tissue coagulation represents a new approach for the thermal destruction of tumors within the liver. The purpose of the current study was to 1) assess technique safety; 2) determine the extent and evolution of induced cellular damage; and 3) correlate the observed pathologic effects with radiologic studies. METHODS Twenty-three tumors measuring ≤ 8 cm (19 colorectal metastases and 4 hepatomas) in 22 patients were treated with RF (range, 500–1550 milliamperes) using internally cooled electrodes. All treated tumors were resected to allow pathologic analysis. Eleven tumors were treated intraoperatively under ultrasonographic guidance and excised immediately. Twelve tumors were treated percutaneously using ultrasound or computed tomography (CT) guidance and subsequently were excised 3–7 days after ablation. Contrast-enhanced CT (n = 12) and magnetic resonance imaging (MRI) (n = 2) were performed after ablation of all percutaneously treated patients. RESULTS Tumors treated intraoperatively did not demonstrate definitive coagulative necrosis. However, pathologic abnormalities suggestive of tissue injury were observed with hematoxylin and eosin staining, and absent cytosolic and mitochondrial enzyme activity suggested irreversible cellular damage. In contrast, specimens removed > 3 days after ablation showed definite, contiguous coagulative necrosis without intervening areas of viable tumor. CT and MRI scans demonstrated circumscribed hypodense, nonenhancing regions surrounding the electrode tract as early as 15 minutes after ablation. These corresponded within 2 mm to measurements of coagulation at pathology. CONCLUSIONS RF ablation is a minimally invasive and safe approach to the treatment of tumors in the liver. Tumors treated with RF energy do not immediately demonstrate coagulative necrosis, but do show evidence of irreversible cellular damage. The extent of tumor necrosis correlates closely with findings at contrast-enhanced imaging. Cancer 2000;88:2452–63. © 2000 American Cancer Society.

Expression of hypoxia‐inducible factor 1α in brain tumors

Abstract: BACKGROUND Hypoxia inducible factor-1 (HIF-1) plays a critical role in angiogenesis during vascular development. The authors tested the hypothesis that HIF-1 expression correlates with progression and angiogenesis in brain tumors. METHODS The authors investigated the expression of the HIF-1α and HIF-1β subunits in human glioma cell lines and brain tumor tissues using Western blot analysis and immunohistochemistry. RESULTS In glioblastomas multiforme (GBMs), HIF-1α primarily was localized in pseudopalisading cells around areas of necrosis and in tumor cells infiltrating the brain at the tumor margin. In contrast, HIF-1α was expressed in stromal cells throughout hemangioblastomas (HBs). Like HIF-1α, HIF-1β was most highly expressed in high grade tumors but was expressed more widely than HIF-1α, including cells away from necrotic zones. In the brains of mice injected with Glioma 261 cells, a pattern of HIF-1α expression identical to that observed in human GBMs was noted. CONCLUSIONS In GBMs, the heterogeneous pattern of HIF-1α expression appears to be determined at least in part by tissue oxygenation, whereas in HBs the homogeneous expression of HIF-1α may be driven by an oncogenic rather than a physiologic stimulus. Cancer 2000;88:2606–18. © 2000 American Cancer Society.

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

Abstract: BACKGROUND. The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. METHODS. The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. RESULTS. Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. CONCLUSIONS. Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value.

Current health behaviors and readiness to pursue life-style changes among men and women diagnosed with early stage prostate and breast carcinomas.

Abstract: BACKGROUND Cancer survivors are at increased risk for developing secondary tumors, diabetes, osteoporosis, and cardiovascular disease, thus making them an important target population for health-related interventions. However, little is known regarding cancer survivors' behaviors and their interest in pursuing healthier diets, exercise, and smoking cessation. METHODS A 65-item survey was mailed to 1667 patients diagnosed with early stage carcinoma of the breast or prostate that requested data regarding demographics, health behaviors, stage of readiness for smoking cessation, exercise, increased fruit and vegetable (F&V) consumption, and decreased fat intake, as well as interest in specific health programs and when, relative to diagnosis, these programs should be offered. RESULTS Responses from 978 cancer survivors suggested that the overwhelming majority (85%) reported their health as good to excellent. The majority of respondents (55%) ate fewer than 5 daily servings of F&Vs, with prostate carcinoma patients reporting eating significantly fewer servings than patients with breast carcinoma (P < 0.001). In contrast, 69% of respondents reported adherence to a low fat diet, again with lower practice rates among prostate carcinoma patients than patients with breast carcinoma (P = 0.006). The majority of respondents (58%) reported routine exercise and 8% were current smokers. Significantly more breast carcinoma patients than prostate carcinoma patients were current smokers (P = 0.03). There was strong interest in health promotion programs across behaviors, and a fair amount of concordance between low fat dietary behaviors and exercise, as well as consumption of five daily servings of F&Vs. The majority of patients expressed a preference for programs that could be delivered via mailed brochure, with 57% of respondents indicating that programs should be initiated at the time of diagnosis or soon after (within 6 months). CONCLUSIONS The results of the current study suggest that although many cancer survivors already practice healthy life-style behaviors, there is a substantial proportion who do not. Interventions especially are needed to increase daily FV however, given the fair degree of clustering between dietary and exercise behaviors, multiple risk factor interventions also may be warranted. Among cancer survivors, receptivity is high for health promotion programs, especially those that can be delivered by mail and soon after diagnosis. Cancer 2000;88:674–84. © 2000 American Cancer Society.

Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.

Abstract: BACKGROUND Axillary lymph node dissection for staging the axilla in breast carcinoma patients is associated with considerable morbidity, such as edema of the arm, pain, sensory disturbances, impairment of arm mobility, and shoulder stiffness. Sentinel lymph node biopsy electively removes the first lymph node, which gets the drainage from the tumor and should therefore be associated with nearly zero morbidity. METHODS Postoperative morbidity (increase in arm circumference, subjective lymphedema, pain, numbness, effect on arm strength and mobility, and stiffness) of the operated arm was prospectively compared in 35 breast carcinoma patients after axillary lymph node dissection (ALND) of Level I and II and 35 patients following sentinel lymph node (SN) biopsy. RESULTS Patient characteristics were comparable between the two groups. Postoperative follow-up was 15.4 months (range, 4–28 months) in the SN group and 17.0 months (range, 4–28 months) in the ALND group. Following axillary dissection, patients showed a significant increase in upper and forearm circumference of the operated arm compared with the SN patients, as well as a significantly higher rate of subjective lymphedema, pain, numbness, and motion restriction. No difference between the two groups was found regarding arm stiffness or arm strength, nor did the type of surgery affect daily living. CONCLUSIONS SN biopsy is associated with negligible morbidity compared with complete axillary lymph node dissection. Cancer 2000;88:608–14. © 2000 American Cancer Society.

American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group.

Abstract: Background The American Joint Committee on Cancer (AJCC), which regularly reviews TNM staging systems, established a working party to develop recommendations for colorectal carcinoma. Methods A multidisciplinary consensus conference using published literature developed an arbitrary classification system of prognostic marker value (Category I, IIA, IIB, III, and IV), which forms the framework for this report. Results The working party concluded that several T categories should be subdivided: pTis into intraepithelial carcinoma (pTie) and intramucosal carcinoma (pTim); pT1 into pT1a and pT1b corresponding to the absence or presence of blood or lymphatic vessel invasion, respectively; and pT4 into pT4a and pT4b according to the absence or presence of tumor involving the surface of the specimen, respectively. The working party also recommended that TNM groups be stratified based on the presence or absence of elevated serum levels of carcinoembryonic antigen (CEA) (>/= 5 ng/mL) on preoperative clinical examination. In addition, the working party also concluded that carcinoma of the appendix should be excluded from the colorectal carcinoma staging system because of fundamental differences in natural history. Conclusions The TNM categories and stage groupings for colorectal carcinoma published in the current AJCC manual have clinical and academic value. However, a few categories require subdivision to provide increasing discrimination for individual patients. The serum marker CEA should be added to the staging system, whereas multiple other factors should be recorded as part of good clinical practice. Although many molecular and oncogenic markers show promise to supplement or modify the current staging systems eventually, to the authors' knowledge none have yet been evaluated sufficiently to recommend their inclusion in the TNM system.

Classification of isolated tumor cells and micrometastasis.

Abstract: BACKGROUND Findings of isolated (disseminated or circulating) tumor cells (ITC) by immunocytochemistry and molecular pathology methods have led to varied interpretations and different applications of the TNM system. METHODS An analysis of the relevant literature was undertaken. In addition, optional proposals for the classification of ITC, micrometastasis, and cytologic results in pleural and peritoneal washings are presented. RESULTS Immunocytochemistry has a lower false-positive rate than nonmorphologic methods such as flow cytometry or the polymerase chain reaction; therefore the method(s) used always should be recorded. At the current time, the independent prognostic significance of ITC in regional lymph nodes and in the general circulation (blood, bone marrow, and other distant sites) is difficult to assess. To enable comparisons of treatment results and to avoid variation in staging, a finding of ITC should not be considered in the TNM and residual tumor (R) classifications, at least not at the current time. However, for future evaluation of their prognostic significance, the respective findings should be documented according to uniform criteria. CONCLUSIONS ITC should be distinguished from micrometastasis. To investigate the independent prognostic significance of ITC and of positive lavage cytology, uniform data collection according to the proposed coding schema is recommended. [See editorial on pages 2589–92, this issue.] Cancer 1999;86:2668–73. © 1999 American Cancer Society.

Prognostic value of intratumoral natural killer cells in gastric carcinoma.

Abstract: BACKGROUND Natural killer (NK) cells are a group of effector cells that act nonspecifically against tumor cells. The correlation between intratumoral NK cell infiltration and clinicopathologic features remains unclear. METHODS The authors selected 146 patients with gastric carcinoma who underwent gastrectomy at Kagoshima University Hospital between 1985–1995. Immunohistochemical staining with the CD57 antibody was performed for the evaluation of NK cell infiltration. A total of 25 areas containing CD57 positive cells were selected and the number of NK cells were counted (magnification, ×200). The patients were divided into 2 groups: patients with a high level of NK infiltration (n = 39) (>25 NK cells/25 high-power fields [HPF]) and patients with a low level of NK infiltration (n = 107) ( 150 cells/HPF) and a low IL group (n = 77) (<150 cells/HPF). The Kaplan–Meier curve was used to analyze surgical outcome. Multivariate analyses were performed to evaluate prognostic factors. RESULTS Patients with a high level of NK infiltration had a higher rate of early gastric carcinoma, fewer metastases to the lymph nodes (P < 0.01), and less lymphatic invasion (P < 0.05) than patients with a low level of NK infiltration. NK cell infiltration also was found to correlate with depth of invasion, clinical stage, and venous invasion. There was no correlation between NK cells and lymphocytic infiltration (P = 0.07; correlation coefficient = 0.15). The 5-year survival rate of patients with a high rate of NK infiltration was 78%, which was significantly better than that of patients with a low level of NK infiltration (P < 0.01). Multivariate analysis did not show NK cell infiltration to be a significant prognostic factor. Combination analysis of the number of NK cells and lymphocytic infiltration was shown to be an independent prognostic factor (P = 0.02; hazard ratio = 1.32). CONCLUSIONS Patients with a high level of NK infiltration were found to have a better prognosis than those with a low level of NK infiltration. Combination analysis with lymphocytic infiltration may provide useful information regarding the immunologic condition of patients with gastric carcinoma. Cancer 2000;88:577–83. © 2000 American Cancer Society.

Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients.

Abstract: BACKGROUND The prognosis of patients with chordoma of the sacrum and mobile spine has been reported to be dismal and attributable in the majority of cases to intralesional surgery. The purpose of this study was to evaluate the clinical outcome of these patients using modern surgical principles aimed at complete resection and to identify prognostic factors. METHODS The clinical and morphologic features, type of surgery, and follow-up of 39 consecutive patients with chordoma were reviewed and analyzed statistically. RESULTS Thirty sacral and 9 mobile spine chordomas (size range, 3–20 cm; mean, 8 cm) occurring in 22 women and 17 men (median age, 55 years) were analyzed. The preoperative morphologic diagnosis was based on fine-needle aspiration (FNA) biopsy, core needle biopsy, or incisional biopsy. The final surgical margins were wide in 23 patients and marginal or intralesional in 16. The mean follow-up was 8.1 years (range, 0.1–23 years). Seventeen patients (44%) developed local recurrences and 11 patients (28%) developed metastases. The estimated 5-, 10-, 15-, and 20-year survival rates were 84%, 64%, 52%, and 52%, respectively. Local recurrence was associated significantly with an increased risk of metastasis and tumor-related death (P < 0.001). CONCLUSIONS New surgical techniques have improved local control and survival of patients with sacral or spinal chordoma significantly and have decreased progressive neurologic deterioration. Larger tumor size, performance of an invasive morphologic diagnostic procedure outside of the tumor center, inadequate surgical margins, microscopic tumor necrosis, Ki-67 > 5%, and local recurrence were found to be adverse prognostic factors. FNA is the preferred method for establishing the preoperative morphologic diagnosis of chordoma. Cancer 2000;88:2122–34. © 2000 American Cancer Society.

Ovarian carcinoma diagnosis

Abstract: BACKGROUND Ovarian carcinoma often is called the “silent killer” because the disease usually is not detected until an advanced stage. The authors' goal was to evaluate preoperative symptoms and factors that may contribute to delayed diagnosis for women with ovarian carcinoma. METHODS A two-page survey was distributed to 1500 women who subscribe to CONVERSATIONS!, a newsletter about ovarian carcinoma. Because the survey could be copied and given to other patients, 1725 surveys were returned from women in 46 states and 4 Canadian provinces. RESULTS The median age of the surveyed women was 52 years, and 70% had Stage III or IV disease (International Federation of Gynecology and Obstetrics). When asked about symptoms before the diagnosis of ovarian carcinoma, 95% reported symptoms, which were categorized as abdominal (77%), gastrointestinal (70%), pain (58%), constitutional (50%), urinary (34%), and pelvic (26%). Only 11% of women with Stage I/II and 3% with Stage III/IV reported no symptoms before their diagnosis. Women who ignored their symptoms were significantly more likely to be diagnosed with advanced disease compared with those who did not (P = 0.002). The time required for a health care provider to make the diagnosis was reported as less than 3 months by 55%, but greater than 6 months by 26% and greater than 1 year by 11%. Factors significantly associated with delay in diagnosis were omission of a pelvic exam at first visit; having a multitude of symptoms; being diagnosed initially with no problem, depression, stress, irritable bowel, or gastritis; not initially receiving an ultrasound, computed tomography, or CA 125 test; and younger age. The type of health care provider seen initially, insurance, and specific symptoms did not correlate with delayed diagnosis. CONCLUSIONS This large national survey confirms that the majority of women with ovarian carcinoma are symptomatic and frequently have delays in diagnosis. Cancer 2000;89:2068–75. © 2000 American Cancer Society.

Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors.

Abstract: BACKGROUND A new, internationally accepted histologic classification of renal cell carcinoma (RCC) and a new edition of the TNM staging system were introduced in 1997. In the latter, there was a dramatic change in the pT classification of organ-confined renal cancer in which the break point between category pT1 and pT2 was increased from 2.5 cm to 7 cm. METHODS To study the significance of the new pT classification and the new recommendations for histologic classification, 588 nephrectomy specimens were reevaluated to define morphologic prognostic parameters in RCC. pT classification (TNM 1997), histologic subtype, histologic tumor grade, presence of necrosis, and sarcomatoid differentiation were assessed. RESULTS The histopathologic review according to the new classification revealed 487 conventional (clear cell) (83%), 64 papillary (11%), 31 chromophobe (5%), and 6 collecting duct (1%) RCCs. Clinical follow-up was available for 470 RCCs. The new pT classification (1997) was strongly correlated with patient survival (P < 0.0001). Histologic grade, presence of necrosis, and sarcomatoid differentiation provided independent prognostic information on the clear cell subtype of renal cancer. Sarcomatoid differentiation, but not tumor necrosis, portended a dismal prognosis for patients with papillary RCC. Chromophobe RCC was associated with a significantly better prognosis than clear cell RCC (P = 0.05). Papillary RCC with scanty cytoplasm and small cells (type 1) behaved less aggressively than papillary tumors with eosinophilic cytoplasm and large cells (type 2; P < 0.001). CONCLUSIONS Accurate histologic classification according to the new recommendations has implications because the prognostic importance of other histologic features that are of independent significance varies with tumor subtype. The data suggest that the new pT classification allows good separation of prognostic groups of patients with renal cancer. Cancer 2000;89:604–14. © 2000 American Cancer Society.

The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways.

Abstract: BACKGROUND The two most common types of uterine endometrial carcinoma, endometrioid (UEC) and serous (USC), differ in their histopathologic appearance and biologic behavior. Recent studies suggest that these differences may be associated with distinct molecular genetic alterations. METHODS In the current study, the authors compared the frequencies of K-ras and p53 mutations and microsatellite instability (MI) between UEC and USC by analyzing all 3 molecular genetic changes in one set of tumors. Furthermore, the distribution of these molecular genetic alterations was determined among UECs of different histopathologic grade. The authors analyzed 58 UECs with known MI status for K-ras and p53 mutations. The K-ras and p53 genes were analyzed in 45 and 6 cases of USC, respectively. These results were combined with previous data on p53 mutations (21 cases) and MI (34 cases) in USC. RESULTS MI was present in 16 of 57 UECs (28%) but in none of 34 USCs. p53 mutations were found in 7 of 42 UECs (17%) and 25 of 27 USCs (93%) by direct sequencing of exons 5–8. UECs and USCs with p53 mutations showed strong immunoreactivity for p53 in about 85% of the cases, whereas about 15% of the cases were immunonegative. K-ras mutations at codon 12 were found in 15 of 58 UECs (26%) and in only 1 of 45 USC (2%) by dot blot oligohybridization after polymerase chain reaction amplification of exon 1. Notably, the frequency of both K-ras and p53 mutations and MI was significantly different between UEC and USC (P < 0.001). In UECs, MI and K-ras mutations occurred in low grade as well as in high grade tumors, whereas p53 mutations were present almost exclusively in high grade tumors. CONCLUSIONS The results of this study suggest that different molecular genetic pathways are involved in the pathogenesis of UEC and USC and that low grade UEC may progress to high grade UEC. These findings support the hypothesis that UEC and USC are separate entities and suggest that different molecular genetic alterations may be responsible for their distinct morphology and biologic behavior. Cancer 2000;88:814–24. © 2000 American Cancer Society.

Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996: An American college of surgeons commission on cancer patient care evaluation study

Abstract: BACKGROUND The American College of Surgeons Commission on Cancer (CoC) has conducted national Patient Care Evaluation (PCE) studies since 1976. METHODS Over 1500 hospitals with CoC-approved cancer programs were invited to participate in this prospective cohort study of U.S. thyroid carcinoma cases treated in 1996. Follow-up will be conducted through the National Cancer Data Base. RESULTS Of the 5584 cases of thyroid carcinoma, 81% were papillary, 10% follicular, 3.6% Hurthle cell, 0.5% familial medullary, 2.7% sporadic medullary, and 1.7% undifferentiated/anaplastic. Demographics and suspected risk factors were analyzed. Fine-needle aspiration of the thyroid gland (53%) or a neck lymph node (7%), thyroid nuclear scan (39%), and ultrasound (38%) constituted the most frequently utilized diagnostic modalities. The vast majority of patients with differentiated thyroid carcinoma presented with American Joint Committee on Cancer Stage I and II disease and relatively small tumors. For all histologies, near-total or total thyroidectomy constituted the dominant surgical treatment. No lymph nodes were examined in a substantial proportion of cases. Residual tumor after the surgical event could be documented in 11% of cases, hypocalcemia in 10% of cases, and recurrent laryngeal nerve injury in 1.3% of cases. Complications were most frequently associated with total thyroidectomy combined with lymph node dissection. Thirty-day mortality was 0.3%; when undifferentiated/anaplastic cancer cases were eliminated, it decreased to 0.2%. Adjuvant treatment, probably underreported in this study, consisted of hormonal suppression (50% overall) and radioiodine (50% overall). CONCLUSIONS In addition to offering information concerning risk factors and symptoms, the current PCE study compliments the survival information from previous NCDB reports and offers a surveillance snapshot of current management of thyroid carcinoma in the U.S. Identified opportunities for improvement of care include 1) more frequent use of fine-needle aspiration cytology in making a diagnosis; 2) more frequent use of laryngoscopy in evaluating patients preoperatively, especially those with voice change; and 3) improved lymph node resection and analysis to improve staging and, in some situations, outcomes. [See commentary on pages 1–4, this issue and communication on pages 192–201, this issue.] Cancer 2000;89:202–17. © 2000 American Cancer Society.