Showing papers in "Cancer in 1995"

Small adenocarcinoma of the lung. Histologic characteristics and prognosis

Abstract: Background. Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma. Method. Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns. Results. Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types. Conclusion. Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis. Cancer 1995;75:2844–52.

The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma

Abstract: Background. From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy. Methods. Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone. Results. At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 curatively operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01). Conclusions. Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group. Cancer 1995 ;75 : 2269-75.

Efficacy of breast cancer screening by age. New results swedish two-county trial

Abstract: Background. Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women. Various possible reasons have been suggested for this, but none firmly is established. Methods. The Swedish Two-County Study is a randomized trial of breast cancer screening of women aged 40-74 years, comprising with 133,065 women with a 13-year follow-up of 2467 cancers. The Breast Cancer Detection Demonstration Project (BCDDP) is a nonrandomized screening program in the United States, with a 14-year follow-up of 3778 cancers in women aged 40-74 years. The Swedish results by age were updated. The lesser effect of screening at ages 40-49 years was investigated in terms of sojourn time (the duration of the preclinical but detectable phase) size, lymph node status, and histologic type of the tumors diagnosed in the Swedish Study and their subsequent effect on survival using survival data from both studies. Results. In the Swedish Trial, a 30% reduction in mortality associated with the invitation to screening of women aged 40-74 years was maintained after 13-years of follow-up. The reduction was 34% for women aged 50-74 years and 13% for women aged 40-49 years. Results indicated that the reduced effect on mortality for women aged 40-49 years was due to a differential effect of screening on the prognostic factors of tumor size, lymph node status, and histologic type. The mean sojourn times in the age groups 40-49 years, 50-59 years, 60-69 years, and 70-74 years were 1.7, 3.3, 3.8, and 2.6 years, respectively. Conclusions. These results suggest that much, although not all, of the smaller effect of screening on mortality in women aged 40-49 years is due to faster progression of a substantial proportion of tumors in this age group and the rapid increase in incidence during this decade of life. It is concluded that the interval between screenings should be shortened to achieve a greater benefit in this age group. It is estimated that a 19% reduction in mortality would result from an annual screening regime. Cancer 1995 ;75 :2507-17.

Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type

Abstract: Background. Rates of cancer in children usually are presented in 5-year age groups, despite large variations of incidence within these groups. The purpose of this report is to provide histology-specific incidence rates within single-year age groups, stratified by sex and race, among children. Methods. Data from the National Cancer Institute's SEER Program were used to calculate incidence rates among children younger than 15 years of age at diagnosis. The SEER population denominator file was modified to allow calculation of rates within single years of age. Results. Large differences in rates within 5-year age groups were found for many histologic types. Retinobiastoma and Wilms' tumor, for instance, had up to eight-fold differences. Substantial differences also were observed for non-Hodgkin's lymphoma, neuroblastoma, Hodgkin's disease, acute lymphoid leukemia, acute myeloid leukemia, and osteosarcoma. In general, rates were higher among males than females, although female rates were often higher among young children. Rates of white children were generally higher than those of black children, especially during the first 5 years of life. Embryonal tumors comprised the majority of neoplasms during the first 2 years of life. Conclusion. Important demographic patterns of cancer incidence in children are obscured when data are summarized into 5-year age groups. Cancer 1995;75:2186–95.

Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification‐an intergroup rhabdomyosarcoma study

Abstract: Background. There is a need to develop a single prognostically significant classification of rhabdomyosarcomas (RMS) and other related tumors of children, adolescents, and young adults which would be a current guide for their diagnosis, allow valid comparison of outcomes between protocols carried out anywhere in the world, and should enhance recognition of prognostic subsets. Method. Sixteen pathologists from eight pathology groups, representing six countries and several cooperative groups, classified by four histopathologic classification schemes 800 representative tumors of the 999 eligible cases treated on Intergroup Rhabdomyosarcoma Study II. Each tumor was classified according to each of the four systems by each of the pathologists. In addition, two independent subsamples of 200 of the 800 patients were reviewed according to the new system, so that 343 distinct patients were reviewed once, and 57 of these twice. Results. A study of the survival rates of all subtypes in the sample of 800 patients led to the formation of a new system. This was tested on two independent subsets of 200 of the original cases and found to be reproducible and predictive of outcome by univariate analysis. A multivariate analysis of the 343 patients classified according to the new system indicated that a survival model including pathologic classification and known prognostic factors of primary site, clinical group, and tumor size was significantly better at predicting survival than a model with only the known prognostic factors. Conclusion. This new classification, termed International Classification of Rhabdomyosarcoma (ICR) by the authors, was reproducible and predictive of outcome among patients with differing histologies treated uniformly on the Intergroup Rhabdomyosarcoma II protocols. We believe it should be utilized by all pathologists and cooperative groups to classify rhabdomyosarcomas in order to provide comparability among and within multi-institutional studies. Cancer 1995;76:1073-85.

Monitoring versus blunting styles of coping with cancer influence the information patients want and need about their disease. Implications for cancer screening and management

Abstract: Background. Two main psychologic coping styles for dealing with cancer and other health threats have been identified: monitoring (attending to) or blunting (avoiding) potentially threatening information. This article reviews results and implications from this research relevant to cancer screening and management. Methods. The Monitor-Blunter Style Scale has been used extensively to assess and categorize patients with regard to these coping styles to predict their differential responses to various cancer-related screening and management regimens. Results. Patients characterized by a monitoring coping style generally are more concerned and distressed about their cancer risk, experience greater treatment side effects, are more knowledgeable about their medical situation, and are less satisfied with and more demanding about the psychosocial aspects of their care. They also prefer a more passive role in clinical decision making, are more adherent to medical recommendations, and manifest greater psychologic morbidity in response to cancer-related threats. Conclusions. Patients fare better (psychologically, behaviorally, and physiologically) when the information they receive about their medical condition is tailored to their own coping styles: generally those with a monitoring style tend to do better when given more information, and those with a blunting style do better with less information. However, patients with a monitoring style who are pessimistic about their future or who face long term, intensely threatening, and uncontrollable medical situations may require not just more information, but also, more emotional support to help them deal with their disease. Cancer 1995; 76:167–77.

Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy.

Abstract: Background. The stratification of ductal carcinoma in situ (DCIS) of the human breast into prognostically relevant categories by size and histologic pattern is a current concern. Few studies have been able to follow women after the identification of any type of DCIS when they have had biopsy only. Methods. This is an extension of a follow-up study of a group of 28 women with small, noncomedo ductal carcinomas in situ that were excised by biopsy only, published in 1982. All these women have now been successfully followed for an average of almost 30 years. Results. The overall risk of development of invasive carcinoma for these women over almost 30 years is nine times that of the general population (95% confidence interval, 4.7–17). This is similar to the 11-fold elevation in relative risk that was determined after about 15 years of follow-up. All invasive carcinomas have developed in the same area in the same breast. There were two women in whom invasive carcinoma developed between 20 and 30 years after initial biopsy. One other woman had an extensive noncomedo DCIS that was identified 25 years after her initial biopsy, but had no evidence of invasive disease. Conclusion. The natural history of small, noncomedo DCIS can last over at least 2 decades, with invasive carcinoma developing at the same site in which DCIS was previously discovered in a significant percentage of women (broadly, between 25%–50%). This is quite different from the natural history of comedo DCIS or any type of DCIS treated purposefully by surgery alone.

The Functional Assessment of Cancer Therapy (FACT) Scale : development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors

Abstract: Background. This report describes the development and validation of a brain subscale for the Functional Assessment of Cancer Therapy (FACT) scale, and the revalidation of the subscales of the general version (FACT-G), which measure physical, social, family, emotional, and functional well-being and the quality of the relationship with the physician. Methods. 101 patients with primary brain tumors, after giving informed consent, participated in the last two phases of a four-phase validation process: item generation, item reduction, validation, and reliability testing. In the validation phase, FACT-G subscale and total scores as well as the brain subscale scores were correlated with other tests of mood, response, bias, and quality of life (QOL). Test-retest reliability testing was performed with 46 patients who had primary brain tumors. Results. Validity and reliability coefficients were high for the FACT-G and brain subscale, except for the comparison with a second QOL measure (FP-QLI) and the Karnofsky Performance Status (KPS). The lower scores were the result of inherent differences in the two QOL instruments and the relatively high performance status of the brain tumor patients, which restricted the KPS score range. Conclusion. The FACT-G has good psychometric properties supporting its broad generalizability and the brain subscale tests substantially different QOL issues than the core instrument. Use of this scale with the addition of the brain subscale provides a well rounded view of the various aspects of QOL from the patient's perspective. With modifications and further psychometric testing, the brain subscale may have broader applicability to subpopulations of patients with other brain disorders. Cancer 1995;75:1151–61.

Liver, gallbladder, extrahepatic bile ducts, and pancreas.

Abstract: Background. The liver, gallbladder, bile ducts, and pancreas have a common embryologic origin; cancers that arise from these sites therefore are expected to share a similar spectrum of histologic types. These cancers are known for their extremely poor prognoses. Methods. Data from the Surveillance, Epidemiology, and End Results Program regarding the incidence, distribution of histologic types, stage of disease, and survival for cancers of the gallbladder (n = 4412), extrahepatic bile ducts (n = 3486), pancreas (n = 23, 116), and liver (n = 6,391) were reviewed. The most common histologic types are discussed, and the frequency of rare types is reported. Results. The incidence of biliary cancer decreased, while the incidence of hepatic and pancreatic cancer rose slightly over the 15-year period from 1973 to 1987. Age and sex distributions varied by histologic type. Greater than 98% of pancreatic and biliary cancers were carcinomas, and adenocarcinoma (not otherwise specified) was the most common histologic type recorded. In the liver, hepatocellular carcinoma was the most common type, followed by intrahepatic cholangiocarcinoma. The overall 5-year relative survival rates for these cancers were very low: gallbladder, 12.3%; extrahepatic bile duct, 12.7%; liver 3.1%; and pancreas 2.5% (all stages combined, 1978-1986). Conclusions. This review confirmed that these carcinomas are associated with a very poor outcome; however, survival was influenced by stage of disease and histologic type. In the gallbladder and extrahepatic bile ducts, papillary adenocarcinoma was associated with the best outcome of all histologic types, and in the exocrine pancreas, mucinous cystadenocarcinoma was associated with the best prognosis.

The National Cancer Data Base report on pancreatic cancer.

Abstract: Background. The National Cancer Data Base (NCDB) of the Commission on Cancer gathers data on time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1991) data for pancreatic cancer are described here. The NCDB data contain important reference information regarding patient and hospital demographics associated with the diagnosis and treatment of pancreatic cancer. Methods. Three Calls for Data have yielded a total of 17,490 cases for 1985, 1986, and 1991, from 937 hospital cancer registries across the United States. The data for 1991 represent 32% of all pancreas cancer cases for U.S. Results. A higher incidence of more advanced disease was reported for the youngest group of patients, Hispanics, African Americans, Asians, males and patients seen at smaller hospitals. For all patients combined, only 14.2% were reported to have had a pancreatectomy. Older patients, patients from lower income zip codes, and African Americans were somewhat less likely to have received a pancreatectomy. Cancer of the body of the pancreas was the anatomic subsite for which patients with pancreatic cancer were least likely to receive a pancreatectomy. Patients seen at hospitals with larger caseloads and at teaching hospitals were more frequently reported as having had a pancreatectomy. Between 1985-1986 and 1991, there was a trend from treatment with surgery only or radiation only toward more frequent use of combined chemoradiation without surgery. There was less radiation treatment reported as received by patients at hospitals with fewer than 150 annual cancer caseloads compared with hospitals with larger caseload. For patients with resectable tumors, a moderate survival advantage was reported compared with nonresectable tumors: 1-year, 48% versus 23%; 2-year, 24% versus 9%; 3-year, 17% versus 6% respectively. Conclusions. The NCDB provides a powerful tool for examining practice patterns and outcome of cancer care in the U.S. The present report, covering one-third of all patients treated in the U.S. in 1991, confirms the advanced disease status of patients with pancreatic cancer. Minority groups present with more advanced disease and are less likely to undergo resection, currently the only potentially curative therapy. Resectability rates appear to be higher in large caseload hospitals. Cancer 1995; 76:1671–7.

The importance of the lumpectomy surgical margin status in long term results of breast conservation

Abstract: Background. The impact of the surgical margin status on long term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. Methods. The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years. Results. The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. Conclusions. The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy. Cancer 1995; 76:259–67.

Non‐Hodgkin's lymphoma

Abstract: Background. Significant advances in the understanding of non-Hodgkin's lymphoma (NHL) have occurred in the past two decades, resulting in changes in terminology and classification practices, which may affect the analysis of the Surveillance, Epidemiology, and End Results (SEER) data. Methods. The incidence rates for each subgroup of NHL in the Working Formulation were reviewed from the National Cancer Institute's SEER data during three time periods: 1973-1977, 1978-1982, and 1983-1987. Results. NHL has significantly increased by 50% from 1973 to 1988. The most frequently occurring NHL is diffuse large cell lymphoma, constituting nearly 30% of all lymphomas. Increased incidence rates for large cell immunoblastic and small noncleaved cell NHL observed during the 1980s are attributable largely to the acquired immunodeficiency syndrome epidemic. Exposure to environmental agents such as herbicides and hair coloring dyes have recently been identified as factors that increase the risk of NHL, but the overall contribution of these factors remains to be identified. The increase in extranodal lymphomas is in part a consequence of the application of modern immunophenotypic and genotypic methods, which lead to the reclassification of pseudolymphomas as monoclonal B-cell neoplasms. The apparent dramatic decline in the incidence of diffuse small cleaved NHL appears to be artifactual, as well, secondary to changes in classification of NHL. Conclusions. With the enhanced ability of pathologists to delineate new clinicopathologic entities by immunophenotypic and molecular biologic studies, future modifications to the collection of SEER data may be appropriate. Such an approach will address the limitations of the Working Formulation and lead to a more accurate data base for the evaluation of epidemiologic trends.

The epidemiology of cervical carcinogenesis.

Abstract: Epidemiologic and laboratory data suggest that cervical cancer typically arises from a series of causal steps. Each step can be studied separately in the hope of better etiologic understanding and improved cancer prevention. The earliest identified etiologic step is infection of young women with specific types of venereally transmissible human papillomaviruses (HPVs). Cervical HPV infections often lead to low grade squamous intraepithelial lesions (mildly abnormal Pap smears). Human papillomavirus infections and their associated lesions are extremely common among young, sexually active women. The infections typically resolve spontaneously even at the molecular level within months to a few years. Uncommonly, HPV infections and/or low grade lesions persist and progress to high grade lesions. The risk factors for progression are mainly unknown but include HPV type and intensity, cell-mediated immunity, and reproductive factors. Nutritional factors or co-infection with other pathogens may also be involved at this apparently critical etiologic step between common low grade and uncommon high grade intraepithelial lesions. Except for advancing age, no epidemiologic risk factors have been found for the next step between high grade intraepithelial lesions and invasive cancer. At the molecular level, invasion is associated with integration of viral DNA. Based on worldwide research, the steps in cervical carcinogenesis appear to be fundamentally the same everywhere, with a central role for HPV infection. The importance of etiologic cofactors like smoking, however, may vary by region.

An overview of skin cancers

Abstract: The incidence and mortality rates of skin cancer are rising in the United States and in many other countries. Concerns about stratospheric ozone depletion adding to the problem have made many organizations look at public and professional health programs as a possible solution. Early detection can reduce the problem in the short term, because mortality due to melanoma is clearly related to the depth of invasion of the tumor when it is removed. This is the factor which is amenable to change in an education program on early detection. Exposure to sunlight is clearly related to risk of development of skin cancer, including both melanoma and nonmelanoma skin cancers. This is the component of the equation of constitutional predisposition plus exposure to environmental risk factors leading to skin cancer that is amenable to change as a result of educational programs. On the basis of available data, there is a case for further development, provision, and evaluation of public and professional education programs designed to control what is becoming a major public health problem in the community

Second primary tumors in patients with head and neck squamous cell carcinoma

Abstract: Background. The concept that a patient could develop cancer twice was first put forward by Billroth. Second primary neoplasms are a particular feature of head and neck cancer. Methods. This study examines the records of 3436 patients with squamous cell carcinoma of the head and neck, of whom 274 subsequently developed a second neoplasm. Results. The actuarial second primary rate was 9.1% at 372 months, and median time to presentation for the second tumor was 36 months. Second tumors were more likely to occur in male patients younger than 60 years at the time of their index tumor, and who had laryngeal and oral cavity index tumors. Patients whose index tumor was small at diagnosis had a greater chance of developing a second tumor as did those with no cervical lymph node metastases to the neck. Radiotherapy to the index tumor was not associated with an increased risk of developing a second tumor. The commonest sites for second tumors were the head and neck (50%) and the lung (34%), and 86% were squamous cell carcinomas. The tumor-specific mortality for those who developed a second primary tumor was 20% after 15 years compared with 44% for patients who did not develop a second primary tumor. The 5-year survival for patients who developed a secondary tumor from the time of its diagnosis was 26%. Conclusions. Second primary tumors in the head and neck of patients with cancer are not uncommon. If the second tumor occurs in the head and neck region, the prognosis is reasonably good. Cancer 1995;75:1343-53.

Increasing patient involvement in choosing treatment for early breast cancer.

Abstract: Background. This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions. Methods. Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation. Results. College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure. Conclusions. Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians. Cancer 1995;76:2275–85.

Acute-phase protein response and survival duration of patients with pancreatic cancer.

Abstract: Background. Current methods to predict survival duration of patients with pancreatic cancer are limited. The aim of this study was to determine whether certain nutritional indices and the acute-phase protein response are prognostic factors independent of disease stage for patients with unresectable pancreatic cancer. Methods. Variables at the time of diagnosis of 102 patients with unresectable pancreatic cancer were entered into a Cox's proportional hazards model. Included in the analysis were the serum concentration of C-reactive protein (CRP) and albumin, the extent of weight loss, age, sex, and disease stage (International Union Against Cancer criteria). Results. A multivariate analysis in which each factor was adjusted for the influence of the other factors revealed the patient age, disease stage, serum albumin, and serum CRP to be independent predictors of survival. The presence of an acute-phase protein response was the most significant independent predictor of survival duration. The median survival of those with an acute-phase protein response (CRP > 10 mg/L, n = 45) was 66 days compared with 222 days for those with no acute-phase protein response (n = 57, P = 0.001, Mann-Whitney Utest). Conclusion. The acute-phase protein response is a useful prognostic indicator for patients with unresectable pancreatic cancer. Moreover, the metabolic disturbances associated with an acute-phase protein response of patients with pancreatic cancer may be a worthwhile therapeutic target. Cancer 1995 ;75 :2077-82.

Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence

Abstract: Background. Nonsmall cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in women and men in the United States, with more than 157,000 estimated deaths in 1995. Surgical resection remains the mainstay of therapy in Stage I and II disease. However, local and distant recurrence account for the disappointing survival rates after resection. Appropriate selection of surgical procedures and effective use of adjuvant therapies will depend upon the elucidation of prognostic factors that predict for recurrence. Methods. A detailed analysis was undertaken to evaluate surgical therapy and to define risk factors associated with recurrence and cancer death in 289 consecutive patients with NSCLC who were diagnosed, resected and followed at the Duke University Medical Center from January 1, 1980, until December 31, 1988. These patients had no evidence of metastases on head and chest/abdominal computed tomograms and radionuclide bone scans before resection. Resected specimens from these patients pathologic verification of Stage I disease. Follow-up was complete in all cases through 8/1/94 (median, 61 months). Variables analyzed included age, sex, smoking history, presenting signs and symptoms, operative procedure, histopathology, hospital course including complications, and the time and location of any recurrence or cancer death. Results. The 30-day mortality rate was 5 of 289 (1.7%), with minor and major morbidity rates of 17% and 9%, respectively. Statistical comparison of lobectomy (193) wedge resection (75) and pneumonectomy (21) revealed significantly (P < 0.04) smaller tumors (T1), more comorbidity, and fewer complications for wedge resection patients. A trend (P < 0.09) toward an increased rate of local/regional recurrence and no difference in survival was also observed for wedge resection. One hundred five patients died of cancer (13-month median time to recurrence) for an actual 5-year survival of 63%. Significant univariate predictors of early recurrence and decreased survival (P < 0.01) were: male sex, the presence of symptoms, hemoptysis, chest pain, type of cough, tumor size in cm and by T-classification, visceral pleural invasion, high mitotic index, and vascular invasion. Significant (P < 0.05) multivariate independent variables for early recurrence and cancer death were the presence of symptoms, vascular invasion, pleural invasion, high mitotic index, and tumor size greater than 3 cm. Conclusion. Current surgical therapy for stage I NSCLC has an acceptable morbidity and mortality rate. The current data also stratify patients with Stage I NSCLC into high and low risk populations that can be used in future randomized trials of adjuvant therapy.

Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials

Abstract: Background. Eight randomized controlled trials (RCTs) of screening mammography were conducted involving women ages 40 to 49 years at entry. Current data gathered for periods ranging from 7 to 18 years of follow-up are available from these trials. Methods. Meta-analyses were performed using a Mantel-Haenszel estimator method to combine current follow-up data from the eight RCTs of mammography that included women ages 40 to 49 years. Results. Combining all current data on women ages 40 to 49 years at entry into the trials yielded a 14% benefit from screening mammography, without statistical significance at the 95% confidence level. Combining all data on women ages 40 to 49 years at entry, excluding results from the Canadian National Breast Screening Study, yielded a 23% benefit to women invited for screening, with statistical significance at the 95% confidence level. Conclusions. These results suggest that screening mammography in women ages 40 to 49 years at entry can reduce mortality from breast cancer when combined with adequate follow-up. Cancer 1995;75:1619-26.

Axillary lymph nodes and breast cancer: a review.

Abstract: Background. The value of surgical staging and treatment of the axillary lymph nodes with either surgery or radiotherapy in the initial management of patients with Stage I or II invasive breast cancer is controversial. Methods. A review of retrospective and prospective clinical studies was performed to assess the risks of axillary lymph node involvement and the effectiveness and morbidity of various treatment options. Results. The risk of axillary lymph node involvement is substantial for most patients, even those with small tumors. The morbidity resulting from a careful Level I/II axillary dissection or moderate-dose axillary radiotherapy is limited. Such treatment is highly effective in preventing axillary recurrence. The symptoms resulting from axillary failure can be controlled in many, but not all, patients. The available data suggest, but do not prove, that the initial use of effective axillary treatment may result in a small improvement in long term outcome in some patient subgroups. Conclusions. Most patients should be treated with either axillary surgery or irradiation. Highly selected subgroups of patients may have such low risks of involvement that specific axillary treatment is of little value. However, such subgroups have not yet been well defined. Treatment approaches that do not involve specific axillary treatment should be considered investigational at present, and the patients should be informed as to their potential risks. Prospective clinical studies of these issues should be pursued. Cancer 1995; 76:1491–512.

Aspirin and reduced risk of esophageal carcinoma

Abstract: Background. Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) have been shown experimentally to inhibit chemically induced esophageal cancers. An epidemiologic study of more than 600,000 adults in the United States followed for 6 years found that aspirin use was associated with a reduced risk of death from esophageal cancer. Methods. The relation of aspirin use and esophageal cancer was examined using data from the National Health and Nutrition Examination Survey (NHANES I) and the National Epidemiologic Follow-up Studies (NEFS). Of the 14,407 United States residents followed for 12–16 years, esophageal cancer developed in 15. Persons were classified as nonusers, occasional users, or regular users of aspirin based on their response to two questions at the baseline examination: whether they had taken aspirin in the past 30 days and whether they had used pain medications regularly during the prior 6 months. Results. Occasional use was associated with a 90% decreased risk (95% confidence interval, 0.01–0.76) of developing esophageal cancer, and no person classified as a regular user developed the disease. Adjusting for cigarette smoking (ever vs. never) and alcohol intake (at least monthly vs. not) did not explain the finding. Conclusion. Aspirin use was associated with a 90% decreased risk of developing esophageal carcinoma. Further studies to determine whether aspirin is protective against both squamous cell esophageal carcinoma and adenocarcinoma of the esophagus are indicated.

Treatment of uveal melanoma metastatic to the liver. A review of the M. D. Anderson cancer center experience and prognostic factors

Abstract: Background. Liver metastasis develops in approximately two-thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. Methods. In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors retrospectively reviewed the cases and compared the results of systemic therapies, hepatic infra-arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. Results. The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life-table method of Kaplan and Meier. Patient-and tumor-related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. Conclusions. Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin-based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma. Cancer 1995; 76:1665–70.

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17. Intraductal carcinoma (ductal carcinoma in situ). The National Surgical Adjuvant Breast and Bowel Project Collaborating Investigators

Abstract: BACKGROUND Controversy exists concerning the natural history of ductal carcinoma in situ (DCIS) of the breast, including its pathologic expression and treatment. This controversy has been fostered largely by the retrospective nature and limited sample sizes of extant studies. METHOD Resolution of some of these issues was attempted by analyzing the pathologic features of 573 examples of DCIS obtained from a larger cohort of 790 women with DCIS enrolled in Protocol B-17 of the National Surgical Adjuvant Breast Project. This prospective randomized clinical trial was performed to assess the efficacy of local breast irradiation to reduce the incidence of second ipsilateral breast tumors (IBT) after lumpectomy. RESULTS Tumor and patient characteristics, including significantly less IBT for those treated by lumpectomy and irradiation than lumpectomy alone, were almost identical for the subset comprising this analysis and the total B-17 cohort reported previously. The presence of moderate/marked comedo necrosis, which was evaluated as an independent parameter rather than as a specific histologic type of DCIS and uncertain/involved lumpectomy margins were the only statistically significant independent predictors of IBT for patients treated by lumpectomy as well as irradiation. The latter markedly reduced the annual hazard rates for the IBT associated with these indicators. CONCLUSIONS Although not an endpoint of this study, the authors' findings suggest that the beneficial effect of irradiation in reducing IBT after lumpectomy for DCIS occurs with small (< 1.0 cm.) and larger lesions. Moderate/marked comedo necrosis and uncertain/involved lumpectomy margins represent independent predictors of IBT.

Completeness of hospital cancer case reporting from the SEER program of the national cancer institute

Abstract: Background. To ascertain the quality of data entering a population-based reporting system, an essential requirement is to study levels of completeness of case-ascertainment and reporting. This study represents an effort to quantify completeness of case reporting in the SEER (Surveillance, Epidemiology, and End Results) Program of the National Cancer Institute. Methods. Hospitals in each of the participating SEER areas were stratified according to their annual hospital cancer caseload for the year 1987. Within each caseload stratum, a random sample of hospitals was selected for inclusion in this study. Files in the medical record, pathology, and radiation oncology departments in each hospital were reviewed for SEER reportable cases. These cases were then matched against SEER case listings to identify unreported cases. Results. The crude estimated completeness of reporting for 1987 in the six participating SEER areas was 97.7% and the registry-caseload standardized rate was 96.8%. Variation was noted by SEER registry, hospital cancer caseload, and casefinding source (hospital department). Three-quarters of unreported cases were of invasive disease and one-fourth were in situ, primarily of the cervix uteri. Conclusions. There is variation in completeness of casefinding among SEER registries, hospital size, and hospital department source. Additional factors that appear to be related to case ascertainment are cancer site or type and who performs the casefinding function (hospital registry or central registry staff). Cancer 1995; 76:2343–50.

Partial mastectomy and breast reconstruction. A comparison of their effects on psychosocial adjustment, body image, and sexuality.

Abstract: Background. This retrospective study compared psychosocial adjustment, body image, and sexual function in women who had either breast conservation or reconstruction for early stage disease. Methods. Questionnaires were completed at a mean of 4 years after surgery by 72 women who had partial mastectomy and 146 women who had immediate breast reconstruction after mastectomy. Results. In general, fewer than 20% of women reported poor adjustment on the domains measured. The two groups did not differ in overall psychosocial adjustment to illness, body image, or satisfaction with relationships or sexual life. There was a specific advantage of partial mastectomy over breast reconstruction in terms of maintaining pleasure and frequency of breast caressing during sexual activity. Women who had undergone chemotherapy had more sexual dysfunction, poorer body image, and more psychological distress. Hormonal therapy and radiation therapy, however, did not measurably affect quality of life. Factors predictive of greater psychosocial distress included a troubled marriage, a poor body image, sexual dissatisfaction, less education, and treatment with chemotherapy. Conclusions. The choice of local treatment had little psychosexual impact, whereas chemotherapy was associated with long term impairments.

Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells

Abstract: Background Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by conventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MDR1, which is the product of the multidrug resistance (MDR) 1 gene, and MDR3 mRNA in NL cells, were examined. Methods Ten Japanese patients with NL were studied. Nine of these patients were examined before therapy. P-glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti-P-gp monoclonal antibody. In one case, the Rhodamine-123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. Results Nine of the 10 patients were P-gp positive. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. Conclusion The poor prognosis for patients with NL treated with chemotherapy may be explained by P-gp expression of the NL cells.

Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases.

Abstract: Background. Langerhans' cell histiocytosis (LCH) of bone is a disorder of histiocytic proliferation with variable and often unpredictable behavior. Method. The authors evaluated the clinical and pathologic features of 263 patients (172 children, 91 adults) with biopsy-proven LCH examined during an 80-year period at the Mayo Clinic. Only patients with bone involvement pathologically and/or radiographically were included in the study. Clinical follow-up was available for 245 patients and ranged from 3 months to 50 years (mean, 12 years: median, 10 years). Chi-square tests were used to determine associations between age, gender, extent of osseous involvement, visceral disease, and pathologic features. Survival analyses were performed by univariate and multivariate Cox regression methods. Results. Age at presentation ranged from 2 months to 71 years with a clear predominance in children. The most common presenting complaint was pain, often worse at night. The skull was the most frequent osseous site in children and adults. Diabetes insipidus was documented in 40 patients. Forty-four children developed skeletal recurrence and/or new bone lesions, 19 of whom had diabetes insipidus. Fourteen children and 3 adults died either directly or indirectly from LCH. One adult patient developed systemic amyloidosis. All but two of these pediatric patients were 3 years of age or younger at presentation. All children with hepatosplenomegaly (7 patients) and/or thrombocytopenia (9 patients) died. Nine of the 14 children who died presented initially with three or more bone lesions. Conclusions. The clinical behavior of LCH of bone is often unpredictable; however, young age at diagnosis, hepatosplenomegaly, thrombocytopenia, and polyostotic (≥3 bones involved) disease are associated with a poor prognosis (P < 0.005). Recrudescence in children, but not in adults, strongly correlates with the presence of diabetes insipidus (P < 0.0005).

Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases

Abstract: Background. Desmoplastic neurotropic melanoma (DNM) is a rare variant of malignant melanoma, the natural history and histogenesis of which still are being defined. Methods. The clinical and histologic features of 28 cases of DNM were studied. All published cases of DNM to date were reviewed. Paraffin sections from 26 cases were investigated with a panel of 10 tissue markers. The ultra-structural features of seven cases were evaluated. Results. A comparison of this study's findings with that of other published cases revealed many similarities regarding clinical and pathologic findings and outcome. The patients were white (15 men:13 women; mean and median age, 59 years; range, 22-83 years). Most tumors were located on the head and neck (75%) and were non-pigmented (57%). An associated intraepidermal melanocytic proliferation was identified in 85% of the patients (lentigo maligna in 56%). Histologically, the dermal tumors were composed of tapered, nonpigmented spindle cells in peripheral nerve sheath patterns resembling neuromas, schwannomas, neurofibromas, and perineurial proliferations accompanied by variable neurotropism and desmoplasia; desmoplasia was the most notable feature in most tumors. The mean depth of tumor invasion was 4.1 mm (range, 0.32-9.0 mm). Tumors with continuity between the epidermal and dermal components had a significantly thinner depth of invasion and a more extensive intraepidermal melanocytic proliferation than those tumors with a grenz zone between the two components (2.3 mm vs. 4.6 mm, P = 0.015). Mitotic activity ranged from 0/HPF in 10 cases, 1-6/high power field (HPF) in 12 cases, and to greater than 6/HPF in 4 cases. An ulcer was present in 5/27 tumors, regression in 4/27, a microsatellite in 1, and brisk and had nonbrisk tumor infiltrating lymphocytic responses in 2 and 14, respectively. Vimentin was uniformly positive and keratins AE1.3 and Cam 5.2 and Leu-7 were uniformly negative. S100 protein, also uniformly positive, had patchy reactivity in most tumors that expressed EMA (43%). Smooth muscle actin (52%), neuron-specific enolase (42%), and FXIIIa (30%) had patchy positivity. HMB-45 was reactive only in the epidermal and superficial papillary dermal component in 21% of cases. Ultrastructurally, the common features were long, often intertwining cellular processes, intercellular junctions, and discontinuous basal lamina. Melanosomes were not identified. Follow-up data available on 26/28 patients (mean, 36 months; median, 24 months; range, 5-132 months) showed 20 (70%) alive without disease, 2 alive with disease and 3 dead from disease. Seven patients had recurrent local tumor (multiple in four); four had lymph node metastases, and three had visceral metastases. Patients with recurrent disease of any type had significantly thicker tumors (5.4 mm vs. 3.4 mm, P = 0.046) and were more likely to have an ulcerated tumor (P = 0.03). Actuarial 5-year survival for tumors with greater than a 4-mm thickness was 72%, which was greater than that for other types of melanoma with greater than a 4-mm thickness. Conclusions. Desmoplastic neurotropic melanomas are neuroectodermal tumors that usually arise from an intraepidermal melanocytic proliferation but rarely develop de novo in the dermis. Schwannian and perineurial differentiation may account for the desmoplasia and neurotropism encountered in these neoplasms. Desmoplastic neurotropic melanomas present at a more advanced stage locally and may be associated with a better survival than associated with conventional melanomas of similar depth of invasion. Cancer 1995;75:478-94.

Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma

Abstract: Background. It is important to diagnose distant metastases disease in patients with newly diagnosed esophageal carcinoma, so that unwarranted surgery and its attendant risks are avoided. The purpose of this study was to determine (1) the percentage of esophageal cancer patients with distant metastases (M1) at presentation, (2) the locations of these distant metastases, and (3) how the metastases were diagnosed. Methods. All patients at the University of Michigan Medical Center with newly diagnosed esophageal cancer between 1982 and July, 1993, were identified. Records for these 838 patients were reviewed, and patients were classified as having M0 or M1 disease at presentation. For patients with M1 disease, the locations of distant metastases and the methods of diagnosis were recorded. Results. One hundred forty-seven of 838 (18%) patients had M1 disease. In 110 of 147 (75%) patients, M1 disease was detected before surgery via imaging or physical examination, including 102 of 147 (69%) via chest or abdominal computed tomography (CT). In no case staged as M0 by abdominal and chest CT was M1 disease detected on bone scan or head CT. Distant metastases were most commonly diagnosed in abdominal lymph nodes (45%), followed by liver (35%), lung (20%), cervical/supraclavicular lymph nodes (18%), bone (9%), adrenal (5%), peritoneum (2%), brain (2%), and stomach, pancreas, pleura, skin/body wall, pericardium, and spleen (each 1%). Conclusion. A significant percentage of patients with esophageal cancer have M1 disease at presentation. Imaging of the chest and abdomen is an effective method of screening such patients for M1 disease before treatment.

Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma.

Abstract: Background. Treatment with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL-2 was unknown. Methods. A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK. Interleukin-2 was administered at 3 × 106 U/m2/day on days 1–5, 13–17, 21–24, and 28–31. Patients on the LAK treatment arm underwent leukapheresis on days 8–10 and LAK cell reinfusion on days 13–15. The results are reported with long-term follow-up. The published experience with IL-2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administration of LAK. Results. Seventy-one patients were treated, 36 on the IL-2 arm and 35 on the IL-2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all patients was 13 months (95% confidence interval [CI], 9–18 months). There were no differences between treatment arms with regard to response (P=0.61) and survival (P=0.67). More patients on the LAK arm experienced pulmonary toxicity (P=0.008). The overall weighted response proportion was 16% (95% CI, 8%-24%) for the 39 published series of 1291 patients treated with IL-2. The 95% confidence intervals for response proportion overlapped when compared by schedule and by administration of LAK. Conclusions. The dose and schedule of IL-2 used in this study resulted in a low level of antitumor activity and the addition of LAK did not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL-2 and interferon-based regimens, continued investigation of these agents is warranted as is the study of new cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized tria.