ABSTRACT
CONTEXT: Postmenopausal women aged 55 years and older have 66% of incident breast tumors and experience 77% of breast cancer mortality, but other age-related health problems may affect tumor prognosis and treatment decisions. OBJECTIVE: To document the comorbidity burden of postmenopausal breast cancer patients and evaluate its relationship with age on disease stage, treatment, and early mortality. DESIGN AND SETTING: Data were collected on breast cancer patients' comorbidities by retrospective hospital medical records review and merged with information on patients' tumor characteristics collected from 6 regional National Cancer Institute Surveillance, Epidemiology, and End Results cancer registries. Patients were followed up until death or for 30 months from breast cancer diagnosis. PARTICIPANTS: Population-based random sample of 1800 postmenopausal breast cancer patients diagnosed in 1992 stratified by 3 age groups: 55 to 64 years, 65 to 74 years, and 75 years and older. MAIN OUTCOME MEASURES: Extent of disease, therapy received, comorbidity, cause of death, and survival. RESULTS: Seventy-three percent (1312 of 1800) of the sample was diagnosed with stage I and II breast cancer, 10% (n = 188) with stage III and IV breast cancer, and 17% (n = 300) did not have a stage assignment. Of the 1017 patients with stage I and stage II node-negative breast cancer, 95% received therapy in agreement with the National Institutes of Health consensus statement recommendation for early-stage breast cancer. Patients in older age groups were less likely to receive therapy consistent with the consensus statement (P<.001), and women aged 70 years and older were significantly less likely to receive axillary lymph node dissection as determined by logistic regression analysis (P<.01). Diabetes, renal failure, stroke, liver disease, a previous malignant tumor, and smoking were significant in predicting early mortality in a statistical model that included age and disease stage. Breast cancer was the underlying cause of death for 135 decedents (51.3%). Heart disease (n = 45, 17.1%) and previous cancers (n = 22, 8.4%) were the next major underlying causes. In the 30-month follow-up period, 263 patients (15%) died. CONCLUSION: Patient care decisions occur in the context of breast cancer and other age-related conditions. Comorbidity in older patients may limit the ability to obtain prognostic information (ie, axillary lymph node dissection), tends to minimize treatment options (eg, breast-conserving therapy), and increases the risk of death from causes other than breast cancer.
Subject(s)
Breast Neoplasms/epidemiology , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Cause of Death , Comorbidity , Female , Humans , Logistic Models , Middle Aged , Neoplasm Staging , Postmenopause , Prognosis , Proportional Hazards Models , SEER Program , Survival Analysis , United States/epidemiologyABSTRACT
BACKGROUND: Blacks are less likely than whites to develop bladder cancer; although once diagnosed, blacks experience poorer survival. This study sought to examine multiple biological and behavioral factors and their influence on extent of disease. METHODS: A population-based cohort of black bladder cancer patients and a random sample of frequency-matched white bladder cancer patients, stratified by age, gender, and race were identified through cancer registry systems in metropolitan Atlanta, New Orleans, and the San Francisco/Oakland area. Patients were ages 20-79 years at bladder cancer diagnosis from 1985-1987, and had no previous cancer history. Medical records were reviewed at initial diagnosis. Of the patients selected for study, a total of 77% of patients was interviewed. Grade, stage, and other variables (including age, socioeconomic status, symptom duration, and smoking history) were recorded. Extent of disease was modeled in 497 patients with urothelial carcinoma using logistic regression. RESULTS: Extent of disease at diagnosis was significantly greater in Blacks than in Whites. Older age group, higher tumor grade, larger tumors, and presence of carcinoma in situ were related to greater extent of disease in blacks and in whites. Large disparities between blacks and whites were found for socioeconomic status and source of care. Blacks had greater symptom duration and higher grade. Black women were more likely to have invasive disease than white women; this difference was not seen among men. Blacks in unskilled occupational categories, perhaps reflecting socioeconomic factors, were at much higher risk for muscle invasion than whites. CONCLUSIONS: While specific relationships between variables were noted, an overall pattern defining black and white differences in stage did not emerge. Future studies should examine the basis upon which occupation and life style factors operate by using biochemical and molecular methods to study the genetic factors involved.
Subject(s)
Black People , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/pathology , White People , Adult , Black or African American , Aged , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/epidemiology , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Staging , Smoking , Socioeconomic Factors , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/epidemiologyABSTRACT
With parametric cure models, we can express survival parameters (e.g. cured fraction, location and scale parameters) as functions of covariates. These models can measure survival from a specific disease process, either by examining deaths due to the cause under study (cause-specific survival), or by comparing all deaths to those in a matched control population (relative survival). We present a binomial maximum likelihood algorithm to be used for actuarial data, where follow-up times are grouped into specific intervals. Our algorithm provides simultaneous maximum likelihood estimates for all the parameters of a cure model and can be used for cause-specific or relative survival analysis with a variety of survival distributions. Current software does not provide the flexibility of this unified approach.
Subject(s)
Actuarial Analysis/methods , Algorithms , Hodgkin Disease/mortality , Likelihood Functions , Melanoma/mortality , Skin Neoplasms/mortality , Survival Analysis , Humans , Models, BiologicalABSTRACT
OBJECTIVES: The purpose of this study was to determine factors correlating with the risk of postoperative mortality after transmyocardial laser revascularization (TMR). BACKGROUND: Clinical studies have indicated that TMR reduces angina by an average of two classes in patients with medically refractory symptoms not treatable by coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty. Factors which correlate with mortality after TMR, however, have not been extensively investigated. METHODS: One hundred thirty-two patients with severe angina underwent TMR as sole therapy with a CO2 laser. Age, gender, ejection fraction, prior CABG, unstable angina and the severity of coronary artery disease (graded on the basis of a newly proposed Anatomic Myocardial Perfusion index, AMP) were each determined. Each vascular territory (left anterior descending artery [LAD] left circumflex artery and posterior descending artery [PDA]) was graded as either having (AMP = 1) or not having (AMP = 0) blood flow through an unobstructed major vessel in the territory. Univariate and multivariate analysis determined which factors correlated with mortality. RESULTS: Patients with at least one AMP = 1 vascular territory (overall AMP = 1) had a 5% (4/82) postoperative mortality rate (POM), compared with 25% (12/49) with overall AMP 0 (p = 0.002). Left anterior descending artery AMP (p = 0.03) and previous CABG (p = 0.04) each correlated with the risk of POM. However, multivariate analysis indicated that no factor improved the correlation obtained with overall AMP by itself. With regard to overall mortality (Kaplan-Meier curves), univariate analysis also revealed correlations with overall AMP (p < 0.001), LAD AMP (p = 0.005), previous CABG (p = 0.003) and PDA AMP (p = 0.05) each individually correlated with mortality. Multivariate analysis indicated that overall AMP = 1, female gender and previous CABG together correlated best with lower postoperative mortality. CONCLUSIONS: Patients with good blood flow to at least one region of the heart through a native artery or a patent vascular graft have a markedly reduced risk of perioperative and longer term mortality.
Subject(s)
Angina Pectoris/mortality , Angina Pectoris/surgery , Laser Therapy , Myocardial Revascularization , Aged , Female , Humans , Male , Middle Aged , Myocardial Revascularization/methods , Odds Ratio , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
Black women are more likely to be diagnosed with later stage breast cancer and have higher mortality rates from breast cancer than white women. To determine whether cancer treatment varies for white and black women, we analyzed data from the National Cancer Institute (NCI) Black-White Cancer Survival Study (BWCSS). Data from hospital medical records, central review of histology slides, and patient interviews on 861 breast cancer cases (in situ and invasive) were examined. Minimum expected therapy was defined for each disease stage as a basic minimum course of treatment that incorporated current practice, state-of-the-art knowledge, and recommendations advanced by NIH Consensus Conferences up to and including the one held in 1985. Patients in this study were diagnosed during 1985-1986. Using logistic regression techniques, those who received at least the minimum expected therapy were compared to those who did not. Thirty-six percent of the patients with late stage disease did not receive minimum expected therapy compared to four percent of the patients with early stage disease. Older women and women with no usual source of care were significantly less likely to receive minimum expected therapy. Overall, 21% of black women did not receive minimum expected therapy compared to 15% of white women.
Subject(s)
Black or African American/statistics & numerical data , Breast Neoplasms/ethnology , Breast Neoplasms/therapy , Health Services Accessibility/statistics & numerical data , Income/statistics & numerical data , White People/statistics & numerical data , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Educational Status , Female , Georgia , Health Care Surveys , Health Services Accessibility/economics , Humans , Louisiana , Middle Aged , National Institutes of Health (U.S.) , Neoplasm Staging , Odds Ratio , San Francisco , Social Class , Surveys and Questionnaires , Survival Analysis , United StatesABSTRACT
Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.
Subject(s)
Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Adenocarcinoma/pathology , Aged , Arteriosclerosis/pathology , Carcinoma, Squamous Cell/blood supply , Carcinoma, Squamous Cell/epidemiology , China/epidemiology , Esophageal Neoplasms/blood supply , Esophageal Neoplasms/epidemiology , Esophagectomy , Esophagus/blood supply , Esophagus/innervation , Female , Humans , Lymph Nodes/pathology , Male , Middle Aged , Risk Factors , United StatesABSTRACT
BACKGROUND: Colon carcinoma primarily affects persons 65 years and older. Seventy-five percent of the incident tumors affect persons in this age group. Because of their advanced age, older patients already may be coping with other concomitant major physical illnesses. This article documents preexisting diseases in older colon carcinoma patients at diagnosis and evaluates the effects of their comorbidity burden on early mortality. METHODS: Prevalence of comorbid conditions was assessed by a retrospective medical records review of an age-stratified random sample of male and female patients aged 55-64 years, 65-74 years, and 75+ years (males, n=799; females, n=811). Data were collected on comorbidity by the National Institute on Aging (NIA) and National Cancer Institute (NCI) and merged with NCI Surveillance, Epidemiology, and End Results (SEER) tumor registry data. RESULTS: Hypertension, high impact heart conditions, gastrointestinal problems, arthritis, and chronic obstructive pulmonary disease emerged as the most prominent comorbid conditions in the NIA/NCI SEER Study sample. The prevalence of comorbidity in the number and type of conditions was similar for both men and women (e.g., 40% of each gender had > or = 5 comorbidities). Within 2 years of diagnosis, 28% (n=454) of the patients had died. The number of comorbid conditions was significant in predicting early mortality in a model including age, gender, and disease stage (P=0.0007). Certain comorbidities, classified as "current problem," added significantly to a basic model (e.g., heart problems, alcohol abuse, liver disease, and deep vein thrombosis). CONCLUSIONS: Although disease stage at time of diagnosis of colon carcinoma is a crucial determinant of patient outcome, comorbidity increases the complexity of cancer management and affects survival duration. Cancer control and treatment research questions should address comorbidity issues pertinent to the age group primarily afflicted with colon carcinoma (i.e., the elderly).
Subject(s)
Colonic Neoplasms/mortality , Age Factors , Aged , Colonic Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Survival RateABSTRACT
In 1992, the National Institute on Aging (NIA) and the National Cancer Institute (NCI) initiated a study to assess the prevalence of comorbid conditions in elderly patients with cancer. Seven cancer sites were selected for the study: breast, cervix, ovary, prostate, colon, stomach, and urinary bladder. This report on approximately 7600 patients in the study sample describes the NIA/NCI approach to developing information on comorbidity in elderly patients and addresses the chronic disease burden (i.e., comorbidity) and severity for six particular conditions: arthritis, chronic obstructive pulmonary disease (COPD), diabetes, gastrointestinal problems, heart-related conditions, and hypertension. Data on comorbidity were collected by abstracting information from hospital medical records. Patients were registered in six geographic areas of the NCI Surveillance, Epidemiology, and End Results (SEER) Program. A stratified random sample of patients aged 55 to 64, 65 to 74, and 75 years or older-with the index cancers were selected. Comorbidity data were matched with data from the conventional SEER monitoring system. Analyses showed that hypertension is the most prevalent condition and is also much more common as a current management problem rather than as history for the NIA/NCI SEER Study patients. Heart conditions varied slightly in the percentage of severity reported, but percentages for all tumors remained within a range of 13 to 26% for current and past categories. A similar range was observed for arthritis, with the higher percentage seen in the current problem category. For episodic complaints (e.g., gastrointestinal problems), a medical history was more common, except for cancers that involve complaints associated with the malignancy (e.g., colon and stomach cancers and, to a lesser extent, ovarian cancer). COPD and diabetes were less prevalent. Analyses currently under way will determine the impact of a patient's comorbidity burden on the cancer care continuum of diagnosis, treatment, and survival. The broad and independent effects of chronic conditions, singly and in combination, are being examined.
Subject(s)
Comorbidity , Geriatric Assessment , Neoplasms/epidemiology , Age Distribution , Aged , Female , Humans , Incidence , Male , Middle Aged , Neoplasm Staging , SEER Program , Severity of Illness Index , Sex Factors , United States/epidemiologyABSTRACT
BACKGROUND: A study of system delay, the time between the initial medical consultation and the establishment of a diagnosis, in breast cancer patients revealed that almost 40% of women reported delays of at least 4 weeks. The objective of this study was to explore the reasons for these prolonged intervals between initial medical consultation and establishment of a diagnosis. METHODS: A total of 367 female breast cancer patients from the National Cancer Institute's Black/White Cancer Survival Study were studied. Medical systems involved in the diagnosis and treatment of these women included hospital outpatient and emergency room, private clinic, public clinic, private doctor, and health maintenance organization. RESULTS: In about 25% of the cases, the delay was attributed by the woman to the patient herself, and the most common reason she gave was that she felt that the problem was not important. In about 45% of the cases, the provider and the health care system were said to be responsible for the delay through difficulties in scheduling or physician inaction, while in another 17% both the patient and the system were responsible. CONCLUSIONS: This study looked at the issue of how the behaviors of women and their providers contribute to the timing of breast cancer diagnosis. It is one of the only studies to examine the woman's role in delay. It is clear from this study that additional work is needed to look at this question. However, the results of this study suggest that efforts must be made to reduce the time needed to get an appointment with a physician or a diagnostic test, as well as to educate physicians and the women themselves regarding the importance of breast symptoms and the value of prompt evaluation, diagnosis, and treatment.
Subject(s)
Black or African American , Breast Neoplasms/diagnosis , Breast Neoplasms/ethnology , Health Services Accessibility/standards , White People , Adult , Aged , Case-Control Studies , Cohort Studies , Female , Georgia , Health Services Research , Humans , Louisiana , Middle Aged , San Francisco , Survival Analysis , Time Factors , Urban HealthABSTRACT
OBJECTIVE: This study examined the relationship of clinicopathologic, health status, medical system, and socioeconomic factors to differences in stage at diagnosis of endometrial cancer in black and white patients. STUDY DESIGN: A population-based study of 130 black and 329 white patients with invasive endometrial cancer was conducted as part of the National Cancer Institute's Black/White Cancer Survival Study. Logistic regression was used to determine the relative importance of factors thought to be related to stage at diagnosis after age and geographic location were adjusted for. RESULTS: High-grade (poorly differentiated) lesions increased the risk for stage III or IV disease (odds ratio 8.3, 95% confidence interval 3.4 to 20.3), as did serous histologic subtype (odds ratio 3.5, 95% confidence interval 1.4 to 8.8) and no usual source of care (odds ratio 5.5, 95% confidence interval 1.4 to 20.9). In the final statistical model these three factors also accounted for the majority of the excess risk of advanced stage for blacks. CONCLUSIONS: Black-white racial disparities in stage at diagnosis appear to be related to higher-grade lesions and more aggressive histologic subtypes occurring more frequently in black patients with endometrial cancer.
Subject(s)
Black People , Endometrial Neoplasms/ethnology , White People , Adult , Aged , Body Mass Index , Confidence Intervals , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Female , Health Status , Humans , Middle Aged , Multivariate Analysis , Odds Ratio , Risk Factors , Socioeconomic FactorsABSTRACT
OBJECTIVE: To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. DESIGN AND PARTICIPANTS: Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. MAIN OUTCOME MEASURE: Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. RESULTS: After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio = 1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer-specific mortality. CONCLUSIONS: Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women.
Subject(s)
Black People , Breast Neoplasms/mortality , Adult , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Comorbidity , Female , Humans , Middle Aged , Neoplasm Staging , Probability , Prognosis , Socioeconomic Factors , Survival Analysis , United States/epidemiology , White PeopleABSTRACT
BACKGROUND: Numerous studies have reported differences in cancer staging at diagnosis and in survival between Black and White patients with breast cancer. Utilizing data obtained from the National Cancer Institute's (NCI's) Black/White Cancer Survival Study for the period 1985-1986, a new study is presented here that systematically examines multiple explanatory factors (e.g., lack of mammograms) associated with these cancer-staging differences. PURPOSE: We evaluated within a single study the relationship of selected demographic, lifestyle, antecedent medical experiences, and health care access factors to cancer staging at diagnosis in Black and White breast cancer patients. METHODS: Data utilized in this population-based cohort study of 1222 eligible women (649 Black and 573 White) newly diagnosed for the period 1985-1986 with histologically confirmed primary breast cancer were obtained from the NCI's Black/White Cancer Survival Study. Sources of data included abstracts of hospital medical records, central review of histology slides by a study consultant pathologist, and patient interviews obtained from three metropolitan areas: Atlanta, New Orleans, and San Francisco-Oakland. Within each area, 70% of all Black incident cases were randomly selected, and a sample of White cases, frequency matched by age groups (20-49 years, 50-64 years, and 65-79 years), was selected for comparison. Stage of breast cancer at diagnosis was classified according to the international tumor-lymph node-metastases (TNM) system. Statistical models utilized in this study included the log-linear and polychotomous logistic regression with multiple predictor variables. RESULTS: Factors associated with cancer staging were differentially expressed in Blacks and Whites. Indicators of access to health care, a lack of mammograms, and an increased body mass index significantly (P < .02) contributed to stage differences in Blacks, whereas income was marginally associated (P = .06) with stage for Whites only. Nuclear grade, having a breast examination by a physician, and a history of patient delay explained approximately 50% of the excess risk for stage III-IV cancer versus stage I-IIN0 cancer among Blacks compared with Whites (odds ratio reduction from 2.19 to 1.68). CONCLUSION: These findings suggest that no single factor or group of factors can explain more than half of the race-stage differences noted in this study with respect to Black and White breast cancer patients.
Subject(s)
Black or African American , Breast Neoplasms/ethnology , White People , Adult , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Cohort Studies , Female , Health Behavior , Health Services Accessibility , Humans , Middle Aged , Neoplasm Staging , Odds Ratio , Regression Analysis , Risk Factors , Socioeconomic Factors , Survival Rate , United States/epidemiologyABSTRACT
The use of time dependent covariates has allowed for incorporation into analysis of survival data intervening events that are binary and non-reversible (for example, heart transplant, initial response to chemotherapy). We can represent this type of intervening event as a three-state stochastic process with a starting state (S), an intervening state (I), and an absorbing state (D), which usually represents death. In this paper we present three procedures for calculating survivorship functions which attempt to display the prognostic significance of the time dependent covariate. The first method compares survival from baseline for the two possible paths through the stochastic process; the second method compares overall survival to survival with state I removed from the process; and, the third method compares survival for those already in state I at a landmark time x to those in state S at time x who will never enter state I. We develop discrete hazard estimates for the survival curves associated with the three methods. Two examples illustrate how these methods can yield different results and in which situations one might employ each of the three methods. Extensions to applications with reversible binary time dependent covariates and models with both baseline and time dependent covariates are suggested.
Subject(s)
Data Interpretation, Statistical , Models, Statistical , Survival Analysis , Humans , Risk Factors , Stochastic Processes , Time FactorsABSTRACT
Two recent reports of the same combination chemotherapy program, cyclophosphamide, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, bleomycin, and prednisone (ProMACE-CytaBOM), in similar subsets of patients with advanced-stage aggressive-histology lymphoma used two different methods to report the actual dose-intensity (DI) data. One method treats DI as a property of a particular cycle of treatment within the entire population that received that cycle. The other treats DI as a characteristic of a particular patient's entire treatment course. We have applied both methods to the same set of data and provide evidence that the latter method is preferable for at least two reasons: (1) it more accurately reflects actual DI by clearly incorporating the duration of the actual treatment course and, thus, can be used to compare the administration of same or related regimens to distinct patient populations; and (2) it allows assignment of a numerical value to an individual patient's treatment course or a group of patients' treatment courses such that DI can be examined for its impact on treatment outcome just like any other prognostic factor. The observed differences in treatment outcome between the Southwest Oncology Group (SWOG) and National Cancer Institute (NCI) studies are not clearly related to differences in distribution of clinical prognostic factors in the two study populations. The differences in methods of reporting DI prohibit evaluation of the influence of dose-related variables on outcome in the two studies. Adoption of a standard method of calculating and reporting DI data would facilitate evaluation of the prognostic significance of DI.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Aged , Cohort Studies , Humans , Mathematics , Middle Aged , PublishingABSTRACT
The study population included 136 patients with stage IA, IB, IIA, IIB, or IIIA1 Hodgkin's disease. The median follow-up is 7.5 years. Among the 30 patients with peripheral IA disease, all patients achieved a complete response (CR) with radiation therapy, and no patient has relapsed. Patients of other stages were randomized to receive radiation therapy or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Among the 51 patients randomized to receive radiation therapy, 49 (96%) achieved complete remission, 17 (35%) have relapsed, and 10 (20%) have died. Fifty-two of the 54 (96%) assessable patients randomized to receive MOPP obtained CRs, seven (13%) have relapsed, and four (7%) have died. The projected 10-year disease-free survival of patients randomized to receive radiation therapy is 60%; for those randomized to receive MOPP, it is 86% (P2 = .009 in favor of MOPP). The projected 10-year overall survival for patients randomized to radiation therapy is 76%, and for MOPP-treated patients it is 92% (P2 = .051 in favor of MOPP). When the randomized patients with massive mediastinal disease or stage IIIA1 disease were excluded from the analysis, the disease-free (67% for radiation v 82% for MOPP) and overall survival (85% for radiation v 90% for MOPP) were not significantly different between the two arms. Subset analysis showed significant superiority of MOPP in the treatment of the following patient groups: stage IIIA1 or massive mediastinal disease, no B symptoms, initial erythrocyte sedimentation rate greater than 20 mm, four or more sites of disease, and younger than age 40 years. Preliminary analysis of this ongoing study shows that MOPP chemotherapy is at least as effective as radiation therapy in the treatment of the specific groups of early-stage Hodgkin's disease patients randomized. The final assessment of these two diverse treatment options will depend largely on the long-term survival and the incidence of early- and late-treatment complications for which patients are continuing to be observed.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Follow-Up Studies , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Humans , Infertility/chemically induced , Male , Mechlorethamine/administration & dosage , Middle Aged , Neoplasm Staging , Prednisone/administration & dosage , Procarbazine/administration & dosage , Prospective Studies , Survival Rate , Vincristine/administration & dosageABSTRACT
One hundred ninety-three patients with stage II, III, or IV follicular large-cell, diffuse large-cell, diffuse mixed, immunoblastic, or diffuse small noncleaved-cell (non-Burkitt's) lymphoma were randomized to receive either cyclophosphamide 650 mg/m2 intravenously (IV), doxorubicin 25 mg/m2 IV, etoposide 120 mg/m2 IV on day 1, mechlorethamine 6 mg/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV on day 8, prednisone 60 mg/m2 orally daily days 1 through 14, procarbazine 100 mg/m2 orally daily days 8 through 14, and methotrexate 500 mg/m2 IV on day 15 with leucovorin 50 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate with cycles repeated every 28 days (ProMACE-MOPP) or same day-1 treatment as ProMACE-MOPP plus cytarabine 300 mg/m2 IV, bleomycin 5 U/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV, and methotrexate 120 mg/m2 IV on day 8, leucovorin 25 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate, and prednisone 60 mg/m2 orally daily days 1 through 14 with cycles repeated every 21 days (ProMACE-CytaBOM). Co-trimoxazole two double-strength tablets orally twice daily throughout the period of treatment was added to the ProMACE-CytaBOM regimen when an increased risk of Pneumocystis carinii pneumonia was found in the first 35 patients receiving this combination. Median follow-up is 5 years. Among the 99 patients treated with ProMACE-MOPP, 73 achieved a complete remission (CR) (74%), 30 complete responders have relapsed (41%), and 45 patients have died (45%), including two (2%) of treatment-related causes. Among the 94 patients treated with ProMACE-CytaBOM, 81 achieved a CR (86%), 22 complete responders have relapsed (27%), and 31 patients have died (33%). The complete response rate (P2 = .048) and survival (P2 = .046) were significantly higher for patients treated with ProMACE-CytaBOM. The mortality of ProMACE-CytaBOM treatment overall was six of 94 patients (6.4%). There was no treatment-related mortality among patients treated with prophylactic co-trimoxazole (n = 59). ProMACE-CytaBOM combination chemotherapy with co-trimoxazole prophylaxis is a safe and effective treatment for patients with aggressive histology malignant lymphoma and is superior to ProMACE-MOPP.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Male , Mechlorethamine/administration & dosage , Methotrexate/administration & dosage , Middle Aged , Neoplasm Staging , Prednisone/administration & dosage , Procarbazine/administration & dosage , Prospective Studies , Remission Induction , Survival Rate , Vincristine/administration & dosageABSTRACT
We have treated 76 patients with locally advanced breast cancer, 31 with stage IIIA, 41 with stage IIIB, and 4 with stage IV disease, with primary induction chemotherapy including an attempted hormonal synchronization in 70 patients. All were treated to maximum objective clinical response before proceeding to any local therapy. Patients achieving a complete response with a negative repeat biopsy generally received radiation therapy while patients with residual disease, partial response (PR) or no change (NC) status received debulking surgery prior to radiation therapy. Regardless of response to induction chemotherapy, patients received at least 6 additional months of chemotherapy following local therapy. Initial doses of combination chemotherapy were escalated to targeted myelosuppression. The objective response rate to induction chemotherapy was 93% with 49% complete response (CR), 44% PR, and 7% NC. The median numbers of cycles of chemotherapy to achieve a CR, PR, or NC were 5, 3, and 5, respectively. Three patients who currently have PRs are still on chemotherapy with continued tumor regression. Of 37 patients achieving a CR to chemotherapy, 35 were assessed by biopsies to determine pathological evidence of response. Twenty-three of the 37 patients (62%) were proven to be complete responders with negative biopsies. Twenty-four patients have relapsed, 6 with stage IIIA, 16 with stage IIIB, and 2 with stage IV. Five patients have had locoregional relapses alone, 4 locoregional and distant, and 15 distant alone. Median time to progression is 35.9 months for stage IIIA and 34.2 months for stage IIIB. Median survival is 35.3 months for stage IIIB and is indeterminate for stage IIIA. This aggressive primary chemotherapy regimen with hormonal synchronization followed by local therapy appears to provide excellent local control and encouraging early results on systemic disease control.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/radiotherapy , Combined Modality Therapy , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Estrogens, Conjugated (USP)/adverse effects , Estrogens, Conjugated (USP)/therapeutic use , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Heart Failure/chemically induced , Humans , Leucovorin/adverse effects , Leucovorin/therapeutic use , Leukopenia/chemically induced , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Tamoxifen/adverse effects , Tamoxifen/therapeutic useABSTRACT
Ninety-three stage III and IV patients with non-Hodgkin's lymphoma were randomized to either high dose CVP (cyclophosphamide 1500 mg/m2 i.v. day 1, vincristine 1.4 mg/m2 day 1, and prednisone 40 mg/m2 orally days 1-10) or high dose CAVP (cyclophosphamide 1000 mg/m2 i.v. day 1, doxorubicin 45 mg/m2 i.v. day 1, vincristine and prednisone as above). Overall, the complete response (CR) rates were similar (CVP 51%, CAVP 51%). Patients with the International Working Formulation diffuse large cell lymphoma had significantly higher CR with CAVP. No difference in CR duration was detected between the two regimens. CRs were durable with 68% of diffuse and 86% of diffuse large cell complete responders alive and disease free at 7 years. Survival was similar with both regimens except for patients with diffuse large cell lymphoma who survived longer with CAVP. Both regimens were equitoxic with neutropenia less than 1.0 x 10(9)/liter in 36% of courses, infections in 15% of courses, and fatal infections in three patients. These intermittent high dose cyclophosphamide equitoxic regimens produced durable responses. However, the doxorubicin-containing regimen is superior in diffuse large cell lymphoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Follow-Up Studies , Hematopoiesis/drug effects , Humans , Prednisone/administration & dosage , Prednisone/adverse effects , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
Analysis of recurrence rates in male breast cancer (MBC) has suggested that tumor size and degree of axillary lymph node involvement carry the same prognostic implications as for breast cancer in women. A similar spectrum of antineoplastic agents appears active in both females and males. Based on reports of active adjuvant chemotherapy of women with breast cancer, we initiated a trial of adjuvant chemotherapy of MBC in July 1974. Twenty-four patients have been treated with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). All patients had nodal involvement (median three nodes positive; seven patients had a single positive lymph node). All patients began adjuvant therapy within 4 weeks of either a radical or modified radical mastectomy. No postoperative radiotherapy was given. Median potential follow-up is 46 months. Four patients have recurred, one each at 15, 45, 61, and 65 months following mastectomy; two are dead of metastatic disease. The five-year survival rate projected by actuarial means is in excess of 80% (95% confidence interval: 74-100%). Based on these data, this treatment is highly encouraging when compared to other forms of treatment reported in the literature in which 5-year disease-free survival rates are less than 30%. We conclude that adjuvant therapy of MBC with a CMF regimen is feasible and may be associated with substantial improvement in disease-free survival and overall survival.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Combined Modality Therapy , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Neoplasm StagingABSTRACT
Survival benefit and prognostic factors useful for patient selection have not been previously analyzed for patients with recurrent pulmonary metastases from soft-tissue sarcomas. Twenty-nine patients in our study had two or more resections of pulmonary metastases from 1976 to 1983. There were no operative deaths and three complications for 40 operations (7.5%). Factors predictive of increased survival following the second resection of pulmonary metastases were resectability and a disease-free interval of greater than six months from the first thoracotomy to the second recurrence in the lung. The tumor doubling time of the first recurrence and the presence of three or fewer nodules on full-lung tomography before the first thoracotomy, which were predictors of survival following initial resection, also predicted survival following subsequent resections. Overall median survival following the second resection was 14.5 months (22% overall three-year survival). The postresection actuarial survival curves for patients undergoing 1, 2, or 3 or more resections were not significantly different. Our findings demonstrate that patients undergoing repeated resections of pulmonary metastases from soft-tissue sarcomas can achieve prolonged survival.