Predictors of survival after hepatic resection among patients with colorectal liver metastasis.

Studies suggest improved survival following resection of colorectal cancer liver metastases (CLMs). We investigated predictors of survival among patients with CLM who underwent hepatic resection using the SEER-Medicare database to identify patients >/=65 years diagnosed with CLM, 1991-2003, who underwent hepatectomy. Cox proportional hazards models were used to identify factors associated with survival after hepatectomy. Of 923 patients with CLM who underwent hepatectomy, 514 were stages I-III and developed CLM>6 months after diagnosis (metachronous), and 409 were stage IV with CLM at diagnosis (synchronous). From the date of hepatectomy, 5 year survival was 22%; younger age, being married, female gender, surgery in an NCI-designated cancer centre, fewer comorbidities, fewer positive lymph nodes, and lower grade were associated with improved survival. Both 5-fluorouracil (5FU)-based chemotherapy and hepatic arterial infusion (HAI) of floxuridine-based chemotherapy following hepatectomy improved survival (HR=0.62, 95% CI: 0.50-0.78; HR=0.51, 95% CI: 0.28-0.97, respectively) in the synchronous, but not metachronous, group. The HR for overall mortality was higher in hospitals with a high vs low procedure volume (0.75, 95% CI: 0.58-0.94). A substantial subgroup of patients with CLM who undergo hepatectomy experiences long-term survival. High hospital procedure volume and use of 5FU-based or HAI-based chemotherapy after resection were associated with improved prognosis.

Variations in the use of adjuvant chemotherapy for node-positive colon cancer in the elderly: a population-based study.

BACKGROUND: Since 1990, the recommended adjuvant therapy for patients with surgically resected node-positive colon cancer has been 5-fluorouracil (5-FU), usually in combination with leucovorin or levamisole. The purpose of this study is to assess the distribution of adjuvant 5-FU treatment in the elderly. METHODS: The Surveillance, Epidemiology and End Results-Medicare database provides population-based information on cancer patients, representing approximately 14% of the United States population, along with health care utilization data from Medicare claims files. We studied patients with node-positive colon cancer diagnosed between 1992 and 1996 who survived at least 120 days beyond diagnosis (N = 4998). RESULTS: About 50% of elderly patients received 5-FU within 4 months of diagnosis. The proportion of patients treated with 5-FU increased by about 10% from 1992 to 1996. In a multiple logistic regression model, 5-FU treatment was less likely to be given to older patients (compared with those aged 65-69 years, the odds ratio (OR) [95% CI] was 0.82 [0.67-1.00] for ages 70 to 74 years, 0.47 [0.39-0.57] for ages 75 to 79, 0.17 [0.13-0.20] for ages 80 to 84, and 0.04 [0.03-0.05] for ages 85 to 88 years. Non-Hispanic black patients were less likely to be treated than non-Hispanic white patients (OR 0.46 [0.36-0.59]); patients with more than three positive lymph nodes were more likely to be treated than those with three or less, and those with comorbid conditions were less likely to be treated than those without such conditions. CONCLUSIONS: Despite its proven efficacy in reducing colon cancer mortality, 5-FU-based chemotherapy is not widely used among apparently eligible patients over age 65. Efforts are needed to ensure that elderly and non-Hispanic black patients receive appropriate treatment.

Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer.

PURPOSE: Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients. PATIENTS AND METHODS: Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits. RESULTS: Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups. CONCLUSION: Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.

Decision analysis of tamoxifen for the prevention of invasive breast cancer.

PURPOSE: The recent Breast Cancer Prevention Trial has shown that tamoxifen may prevent invasive breast cancer. We used a Markov model to estimate the long-term effects of chemoprevention with tamoxifen on survival, quality-adjusted survival, and health care costs. METHODS: We used a hypothetical cohort of women with breast-cancer risk similar to that of participants in the Breast Cancer Prevention Trial, and a computer-based decision analysis (Markov model and 500 Monte Carlo simulations) to model the outcomes of interest. Survival calculations were from Surveillance, Epidemiology, and End-Results (SEER) data; preference ratings from a time trade-off questionnaire administered to a group of average-risk women; and cost estimates from the Group Health Cooperative of Puget Sound and the Health Care Financing Administration. We obtained utility measures for quality-adjustment by administering a time trade-off questionnaire to a group of community-based women. RESULTS: Use of tamoxifen prolonged the average survival of cohort members by 69 days (95% probability interval [PI] 27 to 117) for those who started use at age 35 years; 40 days (95% PI 16 to 67) for those who started use at age 50 years; and 27 days (95% PI 14 to 40) for those who started use at age 60 years. Tamoxifen extended quality-adjusted survival by 38 days (95% PI 0.1 to 82) at age 35, 25 days (95% PI 0 to 50) at age 50, and 22 days (95% PI 5 to 39) days at age 60. Chemoprevention with tamoxifen cost $46,619 (95% PI $27,928 to $98,796) per life year life saved for women who started at age 35; for women over age 50, it cost more than $50,000 per life year saved. DISCUSSION: Tamoxifen use may improve long-term survival and quality-adjusted survival among women who are at increased risk of breast cancer, but this benefit diminishes with age. Tamoxifen is cost-effective in comparison with other cancer treatment strategies for younger women only.

Prevention with tamoxifen or other hormones versus prophylactic surgery in BRCA1/2-positive women: a decision analysis.

PURPOSE: Recent randomized controlled trials have shown that tamoxifen and raloxifene may prevent invasive breast cancer. This decision analysis study compares the outcomes of chemoprevention with tamoxifen, raloxifene, or oral contraceptives with the outcomes of prophylactic surgery among women with high-risk BRCA1/2 mutations. PATIENTS AND METHODS: We used a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations and constructed a Markov model with Monte Carlo simulations, incorporating cumulative breast and ovarian cancer incidence rates from the literature and survival figures from SEER data. We assumed that prophylactic surgery reduces ovarian cancer risk by 45% and breast cancer risk by 90%, that tamoxifen reduces invasive breast cancer risk by 49%, and that raloxifene has similar efficacy and safety in premenopausal and postmenopausal women. We used data obtained from high-risk women by a time trade-off questionnaire to calculate quality-adjusted life-years. We based our cost estimates for hospital and ambulatory care on Health Care Financing Administration payments, the SEER-HCFA database, and the Pharmacy Fundamental Reference. RESULTS: In our model, a 30-year-old BRCA1/2+ woman could prolong survival by 0.9 years (95% probability interval, 0.4-1.2 years) by having bilateral oophorectomy, 3.4 years (2.7-3.7 years) by having bilateral mastectomy, and 4.3 years (3.6-4.6 years) by having both procedures instead of surveillance alone. Chemoprevention with tamoxifen and raloxifene increased survival by 1.6 years (1.0-2.1 years) and 2.2 years (1.3-2.8 years), respectively. Chemoprevention yielded more quality-adjusted life-years than did prophylactic surgery, even when treatment was delayed to age 40 or 50 years. All these procedures were cost-effective or cost-saving compared with surveillance alone. DISCUSSION: Our model suggests that although surgery may yield more substantial survival and cost benefits, quality of life issues may make chemoprevention a more attractive option for young women at high genetic risk.

The quality of life associated with prophylactic treatments for women with BRCA1/2 mutations.

PURPOSE: This study was conducted to obtain and compare the preferences assigned to cancer states and prevention measures by women who had breast cancer, were at high risk for breast cancer, or had neither condition. PATIENTS AND METHODS: We administered a time trade-off questionnaire to 21 breast cancer patients, 28 women with a personal history of multiple breast biopsies or a family history of breast cancer, and 135 women without these conditions (the reference group). We stratified the reference group into two groups aged 20 to 32 years and 33 to 50 years, respectively. RESULTS: All four groups assigned higher preference to breast cancer than to ovarian cancer. Both reference groups preferred using a tamoxifen-like drug to having mastectomy or oophorectomy for cancer prevention; the high-risk and breast cancer groups did not. None of the four groups had a preference between prophylactic mastectomy and breast cancer. All the groups were willing to subtract more years from their life expectancy to protect offspring from genetic risk than to protect themselves. Reference group members in the 33- to 50-year age range had lower mean ratings than the breast cancer group for almost all the health states, and breast cancer patients were less willing than other respondents to trade time for health. Most of these differences were not statistically significant. The high-risk group was similar to the older reference group in time trade-off ratings. DISCUSSION: The time trade-off-based preferences of healthy women may be used to predict the treatment preferences of women with BRCA1/2 mutations. Obtaining healthy women's ratings of treatment outcomes may help health care policy makers envision the consequences of the difficult choices that high-risk women face.

Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2.

PURPOSE: To determine the survival benefit and cost-effectiveness of screening Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. METHODS: We used a Markov model and Monte Carlo analysis to estimate the survival benefit and cost-effectiveness of screening for three specific mutations in a population in which their prevalence is 2.5% and the associated cancer risks are 56% for breast cancer and 16% for ovarian cancer. We assumed that the sensitivity and specificity of the test were 98% and 99%, respectively, that bilateral prophylactic oophorectomy would reduce ovarian cancer risk by 45%, and that bilateral prophylactic mastectomy would reduce breast cancer risk by 90%. We used Medicare payment data for treatment costs and Surveillance, Epidemiology, and End Results data for cancer survival. RESULTS: Our model suggests that genetic screening of this population could prolong average nondiscounted survival by 38 days (95% probability interval, 22 to 57 days) for combined surgery, 33 days (95% probability interval, 18 to 43 days) for mastectomy, 11 days (95% probability interval, 4 to 25 days) for oophorectomy, and 6 days (95% probability interval, 3 to 8 days) for surveillance. The respective cost-effectiveness ratios per life-year saved, with a discount rate of 3%, are $20,717, $29,970, $72,780, and $134,273. CONCLUSION: In this Ashkenazi Jewish population, with a high prevalence of BRCA1/2 mutations, genetic screening may significantly increase average survival and, depending on costs and screening/treatment strategies, may be cost-effective by the standards of accepted cancer screening tests. According to our model, screening is cost-effective only if all women who test positive undergo prophylactic surgery. These estimates require confirmation through prospective observational studies and clinical trials.

Safety and costs of treating neutropenic fever in an outpatient setting.

PURPOSE: The purpose of this study is to analyze the safety of outpatient treatment for cancer patients with chemotherapy-induced neutropenic fever in a community hospital setting and to compare the costs of outpatient treatment with those of inpatient treatment for such patients. PATIENTS AND METHODS: We reviewed charts and charges for 32 consecutive patients initially treated for neutropenic fever with broad-spectrum antibiotics in the offices of Hematology/Oncology Associates (HOA) at the Bennett Cancer Center in the Stamford Hospital January 1997-June 1998. We also reviewed charts and charges for eight consecutive HOA patients with neutropenic fever who met the criteria for outpatient treatment but were initially hospitalized for other reasons during this period. We compared these two groups with respect to mean nadir absolute neutrophil count (ANC), mean number of days when ANC < 1,000 cells cu mm, and mean number of days of intravenous antibiotic treatment. We compared costs for ambulatory and hospital care of the two groups using Health Care Financing Administration (HCFA) payments in 1998 as a proxy for costs. RESULTS: Of 32 patients with neutropenic fever initially treated in the outpatient setting, only four required hospitalization. No patients in either group died in connection with neutropenic fever. Although outpatients received an average of 3.6 days and inpatients only 2.5 days of antibiotic treatment, outpatient treatment was significantly less costly than inpatient treatment. CONCLUSION: In a community hospital setting most cancer patients with neutropenic fever who meet certain criteria can be safely, effectively, and inexpensively treated as outpatients.

Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients.

PURPOSE: Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS: A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS: For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION: Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.