A Pilot Study of Interpersonal Psychotherapy for Depressed Women with Breast Cancer.

This study sought to examine the feasibility and preliminary efficacy of interpersonal psychotherapy (IPT) in the treatment of major depressive disorder (MDD) among women with breast cancer. Seven women with breast cancer and MDD received 12 sessions of IPT. Outcome measures included changes in depression severity, as measured by the Hamilton Rating Depression Scale (HAM-D), and global functioning, as measured by the Global Assessment Scale (GAF). Mixed linear models were used to examine whether change in depressive symptoms mediated change in global functioning. The HAM-D decreased from 21.3 (SD 8.1) to 11.1 (9.6) (p 0.02), whereas the GAF improved from 56.7 (5.5) to 70.3 (15.6) (p 0.049). A mixed regression model indicated that change in HAM-D scores predicted change in GAF scores (p 0.03). These results suggest that IPT is a promising treatment for depression in women with breast cancer. Randomized controlled trials are warranted to confirm the results of this study.

Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers.

UNLABELLED: Comparative effectiveness research has become an integral part of health care planning in most developed countries. In a simulated cohort of women, aged 30-65, who tested positive for BRCA1 or BRCA2 mutations, we compared outcomes of mammography with and without MRI, prophylactic oophorectomy with and without mastectomy, mastectomy alone, and chemoprevention. METHODS: Using Treeage 9.02 software, we developed Markov models with 25,000 Monte Carlo simulations and conducted probabilistic sensitivity analysis. We based mutation penetrance rates, breast and ovarian cancer incidence, and mortality rates, and costs in terms of 2009 dollars, on published studies and data from the Surveillance, Epidemiology, and End RESULTS (SEER) Program and the Centers for Medicare and Medicaid Services. We used preference ratings obtained from mutation carriers and controls to adjust survival for quality of life (QALYs). RESULTS: For BRCA1 mutation carriers, prophylactic oophorectomy at $1,741 per QALY, was more cost effective than both surgeries and dominated all other interventions. For BRCA2 carriers, prophylactic oophorectomy, at $4,587 per QALY, was more cost effective than both surgeries. Without quality adjustment, both mastectomy and BSO surgeries dominated all other interventions. In all simulations, preventive surgeries or chemoprevention dominated or were more cost effective than screening because screening modalities were costly. CONCLUSION: Our analysis suggested that among BRCA1/2 mutation carriers, prophylactic surgery would dominate or be cost effective compared to chemoprevention and screening. Annual screening with MRI and mammography was the most effective strategy because it was associated with the longest quality-adjusted survival, but it was also very expensive.

Breast cancer-related preferences among women with and without BRCA mutations.

Preference ratings are used to quantify quality of life in analyses used for health care policy making. Subjects indicated how many years of their life expectancy they would trade to avoid BRCA mutations, breast/ovarian cancer, and five preventive measures including prophylactic surgery, annual mammograms, and annual magnetic resonance imaging (MRI). Among 243 respondents, both the 83 women with mutations and the 160 controls rated mammography highest (most favorably), MRI next highest, having a child with a mutation lowest, and ovarian cancer next lowest. Controls rated prophylactic surgery higher than cancer (P < 0.01), but women with mutations did not. In logistic regression, controls were twice as willing as women with mutations to trade time except for screening modalities; younger, lower-income, and non-white women were more willing to trade time than older, higher-income, and white women. Our findings support the use of average-risk individuals' time trade-off preference ratings for health care policy development.

Comparing genetic ancestry and self-described race in african americans born in the United States and in Africa.

Genetic association studies can be used to identify factors that may contribute to disparities in disease evident across different racial and ethnic populations. However, such studies may not account for potential confounding if study populations are genetically heterogeneous. Racial and ethnic classifications have been used as proxies for genetic relatedness. We investigated genetic admixture and developed a questionnaire to explore variables used in constructing racial identity in two cohorts: 50 African Americans and 40 Nigerians. Genetic ancestry was determined by genotyping 107 ancestry informative markers. Ancestry estimates calculated with maximum likelihood estimation were compared with population stratification detected with principal components analysis. Ancestry was approximately 95% west African, 4% European, and 1% Native American in the Nigerian cohort and 83% west African, 15% European, and 2% Native American in the African American cohort. Therefore, self-identification as African American agreed well with inferred west African ancestry. However, the cohorts differed significantly in mean percentage west African and European ancestries (P < 0.0001) and in the variance for individual ancestry (P < or = 0.01). Among African Americans, no set of questionnaire items effectively estimated degree of west African ancestry, and self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry. Our findings suggest that self-reported race and ancestry can predict ancestral clusters but do not reveal the extent of admixture. Genetic classifications of ancestry may provide a more objective and accurate method of defining homogenous populations for the investigation of specific population-disease associations.

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

Arsenic exposure and anemia in Bangladesh: a population-based study.

OBJECTIVE: The purpose of this study was to examine the association between arsenic exposure and anemia, based on blood hemoglobin concentration. METHODS: Hemoglobin measures, skin lesions, arsenic exposure, and nutritional and demographic information were collected from 1954 Bangladeshi participants in the Health Effects of Arsenic Longitudinal Study. We used general linear modeling to assess the association between arsenic exposure and hemoglobin concentration, examining men and women separately. RESULTS: Arsenic exposure (urinary arsenic >200 microg/L) was negatively associated with hemoglobin among all men and among women with hemoglobin <10 d/L. Other predictors of anemia in men and women included older age, lower body mass index, and low intake of iron. Among women, the use of contraceptives predicted higher hemoglobin. CONCLUSIONS: The study suggests an association between high arsenic exposure and anemia in Bangladesh.

Radiation therapy, cardiac risk factors, and cardiac toxicity in early-stage breast cancer patients.

PURPOSE: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer. METHODS AND MATERIALS: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women > or = 65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. RESULTS: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. CONCLUSION: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years.

Cost-effectiveness of preventive strategies for women with a BRCA1 or a BRCA2 mutation.

BACKGROUND: For BRCA1 or BRCA2 mutation carriers, decision analysis indicates that prophylactic surgery or chemoprevention leads to better survival than surveillance alone. OBJECTIVE: To evaluate the cost-effectiveness of the preventive strategies that are available to unaffected women carrying a single BRCA1 or BRCA2 mutation with high cancer penetrance. DESIGN: Markov modeling with Monte Carlo simulations and probabilistic sensitivity analyses. DATA SOURCES: Breast and ovarian cancer incidence and mortality rates, preference ratings, and costs derived from the literature; the Surveillance, Epidemiology, and End Results (SEER) Program; and the Health Care Financing Administration (now the Centers for Medicare & Medicaid Services). TARGET POPULATION: Unaffected carriers of a single BRCA1 or BRCA2 mutation 35 to 50 years of age. TIME HORIZON: Lifetime. PERSPECTIVE: Health policy, societal. INTERVENTIONS: Tamoxifen, oral contraceptives, bilateral salpingo-oophorectomy, mastectomy, both surgeries, or surveillance. OUTCOME MEASURES: Cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: For mutation carriers 35 years of age, both surgeries (prophylactic bilateral mastectomy and oophorectomy) had an incremental cost-effectiveness ratio over oophorectomy alone of 2352 dollars per life-year for BRCA1 and 100 dollars per life-year for BRCA2. With quality adjustment, oophorectomy dominated all other strategies for BRCA1 and had an incremental cost-effectiveness ratio of 2281 dollars per life-year for BRCA2. RESULTS OF SENSITIVITY ANALYSIS: Older age at intervention increased the cost-effectiveness of prophylactic mastectomy for BRCA1 mutation carriers to 73,755 dollars per life-year. Varying the penetrance, mortality rates, costs, discount rates, and preferences had minimal effects on outcomes. LIMITATIONS: Results are dependent on the accuracy of model assumptions. CONCLUSION: On the basis of this model, the most cost-effective strategies for BRCA mutation carriers, with and without quality adjustment, were oophorectomy alone and oophorectomy and mastectomy, respectively.

Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.

PURPOSE: Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged > or = 65 years with long-term follow-up. PATIENTS AND METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. RESULTS: Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. CONCLUSION: When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

Racial disparities in treatment and survival among women with early-stage breast cancer.

PURPOSE: Black women with breast cancer are known to have poorer survival than white women. Suboptimal treatment may compromise the survival benefits of adjuvant chemotherapy. We analyzed the association of race and survival with duration of treatment and number of treatment cycles among women receiving chemotherapy for early-stage breast cancer. PATIENTS AND METHODS: Patients were women in the Henry Ford Health System tumor registry who were diagnosed with stage I/II breast cancer between January 1, 1996, and December 31, 2001, who received adjuvant chemotherapy. We calculated an observed/expected ratio of treatment duration and of completed chemotherapy cycles for each patient. Using Cox proportional hazards models, we analyzed the association of early treatment termination and treatment duration with all-cause mortality, controlling for age, race, stage, hormone receptor status, grade, comorbidity score, and doxorubicin use. RESULTS: Of 472 eligible patients, 28% (31% black, 23% white; P = .03) received fewer cycles of treatment than expected. Black race, receipt of < or = 75% of the expected number of cycles, increasing age, hormone receptor negativity, and a comorbidity score of more than 1 were associated with poorer survival. Among the 344 patients receiving the expected number of cycles, 60% experienced delays. These delays did not reduce survival. CONCLUSION: This study is the first to find that a substantial fraction of women with early-stage breast cancer terminated their chemotherapy prematurely and that early termination was associated with both black race and poorer survival. A better understanding of the determinants of suboptimal treatment may lead to interventions that can reduce racial disparities and improve breast cancer outcomes for all women.

Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival.

PURPOSE: Delays in the diagnosis of breast cancer are associated with advanced stage and poor survival, but the importance of the time interval between lumpectomy and initiation of radiation therapy (RT) has not been well studied. We investigated factors that influence the time interval between lumpectomy and RT, and the association between that interval and survival. PATIENTS AND METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on women aged 65 years and older, diagnosed with Stages I-II breast cancer, between 1991 and 1999. Among patients who did not receive chemotherapy, we studied factors associated with the time interval between lumpectomy and the initiation of RT, and the association of delay with survival, using linear regression and Cox proportional hazards modeling. RESULTS: Among 24,833 women with who underwent lumpectomy, 13,907 (56%) underwent RT. Among those receiving RT, 97% started treatment within 3 months; older age, black race, advanced stage, more comorbidities, and being unmarried were associated with longer time intervals between surgery and RT. There was no benefit to earlier initiation of RT; however, delays >3 months were associated with higher overall mortality (hazard ratio, 1.92; 95% confidence interval, 1.64-2.24) and cancer-specific mortality (hazard ratio, 3.84; 95% confidence interval 3.01-4.91). CONCLUSIONS: Reassuringly, early initiation of RT was not associated with survival. Although delays of >3 months are uncommon, they are associated with poor survival. Whether this association is causal or due to confounding factors, such as poor health behaviors, is unknown; until it is better understood, efforts should be made to initiate RT in a timely fashion.

Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study.

BACKGROUND: Although the risk of bowel perforation is often cited as a major factor in the choice between colonoscopy and sigmoidoscopy for colorectal screening, good estimates of the absolute and relative risks of perforation are lacking. METHODS: We used a large population-based cohort that consisted of a random sample of 5% of Medicare beneficiaries living in regions of the United States covered by the Surveillance, Epidemiology, and End Results (SEER) Program registries to determine rates of perforation in people aged 65 years and older. We identified individuals who were cancer-free and had undergone colonoscopy or sigmoidoscopy between 1991 and 1998, calculated both the incidence and risk of perforation within 7 days of the procedure, and explored the impact on incidence and risk of perforation of age, race/ethnicity, sex, comorbidities, and indication for the procedure. We also estimated the risk of death after perforation. Risks were calculated with odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: There were 77 perforations after 39 286 colonoscopies (incidence = 1.96/1000 procedures) and 31 perforations after 35 298 sigmoidoscopies (incidence = 0.88/1000 procedures). After adjustment, the OR for perforation from colonoscopy relative to perforation from sigmoidoscopy was 1.8 (95% CI = 1.2 to 2.8). Risk of perforation from either procedure increased in association with increasing age (P(trend)<.001 for both procedures) and the presence of two or more comorbidities (P(trend)<.001 for colonoscopy and P(trend) =.03 for sigmoidoscopy). Compared with those who were endoscopied and did not have a perforation, the risk of death was statistically significantly increased for those who had a perforation after either colonoscopy (OR = 9.0, 95% CI = 3.0 to 27.3) or sigmoidoscopy (OR = 8.8, 95% CI = 1.6 to 48.5). The risk of perforation after colonoscopy, especially for screening procedures, declined during the 8-year study period. CONCLUSIONS: The risk of perforation after colonoscopy is approximately double that after sigmoidoscopy, but this difference appears to be decreasing. These observations should be useful to clinicians making screening and diagnostic decisions for individual patients and to policy officials setting guidelines for colorectal cancer screening programs.

Effect of prevention strategies on survival and quality-adjusted survival of women with BRCA1/2 mutations: an updated decision analysis.

PURPOSE: This study updates findings regarding the effects of prophylactic surgery, chemoprevention, and surveillance on the survival and quality-adjusted survival of women who test positive for BRCA1/2 mutations. MATERIALS AND METHODS: Markov modeling of outcomes was performed in a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations. The model incorporated breast and ovarian cancer incidence rates from the literature and mortality rates from the Surveillance, Epidemiology, and End Results Program. Quality adjustment of survival estimates were obtained from a survey of women aged 33 to 50 years. Sensitivity analyses were performed of varied assumptions regarding timing and effects of preventive measures on cancer incidence and adverse effects. RESULTS: A 30-year-old woman could prolong her survival beyond that associated with surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6 years with prophylactic oophorectomy, 4.6 years with both tamoxifen and prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years with both surgeries. She could prolong her quality-adjusted survival by 2.8 years with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both surgeries. The benefits of all of these strategies would decrease if they were initiated at later ages. CONCLUSION: Women who test positive for BRCA1/2 mutations may derive greater survival and quality adjusted survival benefits than previously reported from chemoprevention, prophylactic surgery, or a combination. Observational studies and clinical trials are needed to verify the results of this analysis of the long-term benefits of preventive strategies among BRCA1/2-positive women.

Outcomes of tamoxifen chemoprevention for breast cancer in very high-risk women: a cost-effectiveness analysis.

PURPOSE: To estimate the effects on survival, quality-adjusted survival, and health care costs of using tamoxifen for primary prevention in subgroups of women at very high risk for breast cancer. PATIENTS AND METHODS: A decision analysis was performed using a hypothetical cohort of women that included subgroups with atypical hyperplasia, Gail risk greater than 5, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. Data sources were the Breast Cancer Prevention Trial, the Surveillance, Epidemiology, and End-Results program, time trade-off preference ratings, the Group Health Cooperative of Puget Sound, and the United States Health Care Financing Administration. RESULTS: Our model predicted that tamoxifen would prolong the average survival of cohort members initiating use at ages 35, 50, and 60 years by 70, 42, and 27 days, respectively. It would prolong survival even more for those in the higher-risk groups, especially those with atypical hyperplasia (202, 89, and 45 days). Tamoxifen use was also projected to extend quality-adjusted survival by 158, 80, and 50 days in the atypical hyperplasia group. For younger women in the highest risk groups, chemoprevention with tamoxifen was estimated to have cost savings or be cost-effective, both with and without quality adjustments. CONCLUSION: Chemoprevention with tamoxifen may be particularly beneficial to women with atypical hyperplasia, 5-year Gail model risk greater than 5%, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. The benefits may be greater if tamoxifen is initiated before age 50 years rather than after and if the breast cancer risk reduction conferred by tamoxifen lasts longer than 5 years. For women with a very high risk of invasive breast cancer, chemoprevention with tamoxifen seems to be cost-effective.

Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study.

PURPOSE: Since 1986, the recommended therapy for patients with ovarian cancer has included surgery and chemotherapy with a platinum compound (cisplatin or carboplatin). The purpose of this study is to assess the use of chemotherapy in elderly patients with advanced ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database represents approximately 14% of the United States population and provides clinical and demographic information on cancer patients covered by Medicare, along with health care-utilization data from Medicare claims files. We analyzed the association of demographic and clinical factors with treatment among patients diagnosed from 1992 to 1996 with stage III or IV ovarian cancer, who survived > or = 120 days beyond diagnosis, and were > or = 65 years of age (N = 1,775). RESULTS: Approximately 83% of elderly patients received some form of chemotherapy within 4 months of diagnosis. In a multiple logistic regression model with patients aged 65 to 69 years as the reference, the odds ratios of receiving chemotherapy were 0.96 (95% confidence interval [CI], 0.63 to 1.46) for ages 70 to 74, 0.65 (95% CI, 0.43 to 1.00) for 75 to 79, 0.24 (95% CI, 0.15 to 0.37) for 80 to 84, and 0.12 (95% CI, 0.07 to 0.19) for 85+. Hispanic patients were less likely to receive chemotherapy than non-Hispanic white patients. Since 1992, paclitaxel has gradually replaced cyclophosphamide as the drug most commonly used with platinum. CONCLUSION: Despite its proven efficacy in treating ovarian cancer, chemotherapy seems to be used less among patients over age 65, especially those who are nonwhite and/or in the oldest age groups. Further research is needed to elucidate to what degree this represents appropriate clinical judgment and to what degree other factors, such as patient choice, play a role.

Use of adjuvant chemotherapy and radiation therapy for rectal cancer among the elderly: a population-based study.

PURPOSE: Combined adjuvant fluorouracil (5-FU)-based chemotherapy with radiation is now the standard of care for locally advanced rectal cancer in the United States. We investigated the use of these treatments for stages II and III rectal cancer among the elderly and the effectiveness of these treatments on a population-based scale. PATIENTS AND METHODS: The linked Surveillance, Epidemiology, and End-Results-Medicare database was used to identify 1,807 Medicare beneficiaries > or = 65 years of age with stage II or III rectal cancer who underwent surgical resection between 1992 and 1996. We excluded members of a health maintenance organization in the 12 months before or 4 months after their diagnosis and those who died within 4 months of diagnosis. We used multivariate analysis to identify factors associated with combined 5-FU and radiation therapy, and propensity score methodology to determine survival benefit for those treated. RESULTS: We found that 37% of patients received both adjuvant 5-FU and radiation therapy, 11% 5-FU alone, and 14% radiation alone. Decreasing age, increasing lymph node positivity, comorbid conditions, and nonblack race were associated with increased probability of treatment with 5-FU and radiation. Combined chemotherapy/radiation therapy was associated with improved survival for stage III (relative risk, 0.71; 95% confidence interval, 0.56 to 0.90), but not for stage II rectal cancer (relative risk, 0.89; 95% confidence interval, 0.70 to 1.14). CONCLUSION: The association of combined treatment with improved survival in node-positive disease was similar to that observed in other studies. In the absence of data from well-designed randomized controlled trials, our observational data support efforts on the part of clinicians to make appropriate referrals and provide combined treatment for elderly patients with stage III rectal cancer.

Cancer outcomes at the Hufeland (complementary/alternative medicine) klinik: a best-case series review.

PURPOSE: A best-case series review is an efficient tool with which to screen complex complementary and alternative treatments for cancer as candidates for further study. STUDY DESIGN: The National Cancer Institute and other agencies have adopted the best-case series method to evaluate cancer treatments involving complementary and alternative medicine (CAM) for further study. The authors conducted a best-case series review of the Hufeland Klinik. Established in 1985 in Bad Mergentheim, Germany, this facility treats more than 500 cancer patients per year. Hufeland treatment includes dietary modification, injections, ozone therapy, active fever therapy, psychotherapy, and sometimes hormone therapy and/or low-dose chemotherapy. The goal of the treatment is to prolong survival and to maintain good quality of life. METHODS: The clinic provided summaries of 27 cases in which patients with longer than expected survival had agreed to make their medical records available for review. The review involved pathologic confirmation of disease and radiologic confirmation of complete response (CR) or partial response (PR) not attributable to conventional treatment. RESULTS: Based on the summaries and an exhaustive 2-year search for medical records, slides, and imaging data, 12 of 27 cases were selected for full review, and 5 (3 CRs and 2 PRs) were judged best cases. CONCLUSION: Most patients with common cancers receive conventional treatment before coming to Hufeland, and many are treated with chemotherapy and/or hormonal therapy while there. Hence, only a few could be considered for review. With 5 of 12 patients showing a treatment response, the authors conclude that the Hufeland treatment merits further study. They also recommend the development of criteria with which to evaluate best-case series reviews of complex CAM treatments for patients with advanced cancer.

Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer.

BACKGROUND: Randomized clinical trials have demonstrated the efficacy of adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgical resection of node-positive colon cancer. Although this treatment became the standard in 1990 following a National Institutes of Health Consensus Conference, among those at least 65 years of age it is less likely to be offered to older or nonwhite patients. OBJECTIVE: To determine the association between 5-fu-based chemotherapy and survival in older patients. DESIGN: Retrospective cohort study. SETTING: Combined database of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and Medicare. PATIENTS: 4768 patients 65 years of age or older who received a diagnosis of node-positive colon cancer from 1992 to 1996, were covered by Medicare Parts A and B, and resided in the population covered by the SEER program. MEASUREMENTS: Propensity scores to control for known predictors of receiving treatment, Cox proportional hazards models to assess the association of 5-FU therapy with survival, and sensitivity analyses to estimate the possible effects of unknown confounders. RESULTS: Fifty-two percent of patients received 5-FU therapy. For this sample, the hazard ratio for death associated with 5-FU therapy was 0.66 (95% CI, 0.60 to 0.73). Confounding could have accounted for this association only if an unmeasured confounder were extremely unequally distributed between the treated and untreated groups or increased mortality by at least 50%. CONCLUSIONS: 5-Fluorouracil adjuvant therapy is significantly associated with reduced mortality in older patients, similar to the association found in randomized, controlled trials among younger patients. More frequent use of 5-FU therapy in older patients would probably reduce death from colon cancer.

Management of colorectal cancer in elderly patients: focus on the cost of chemotherapy.

The treatment of colorectal cancer has evolved dramatically over the last 15 years. Advances in surgery, radiotherapy and chemotherapy have enabled oncologists to cure more patients and offer improved quality of life to patients not amenable to cure. Specific knowledge of colorectal cancer care of the elderly, while lagging behind the treatment of younger patients, is beginning to emerge. Informed by recent trials, the approach towards elderly patients is shifting towards more aggressive treatment and multimodal therapy. Surgeons are operating on the elderly with greater frequency, less operative mortality and greater success; 5-year survival following potentially curative surgery has risen from 50% to 67%.Research of adjunctive therapy for colorectal cancer is enrolling more elderly patients, and with this has come an understanding of the role of chemotherapeutic agents in the treatment of the elderly, used individually and within multi-drug regimens. This research offers insight into how the elderly respond to chemotherapy, informing clinicians on anticipated benefits and toxicities of treatment. Fluorouracil-based regimens, which have long been the standard adjuvant chemotherapy, have been shown to offer benefits to the elderly compared with those not receiving adjuvant chemotherapy (71% versus 64% 5-year survival), and to cause similar toxicities as seen in younger patients. The role of novel chemotherapeutic agents in the treatment of elderly patients with colorectal cancer is also emerging, with studies finding that irinotecan, in combination with a fluorouracil-based regimen, can offer a further survival benefit of over 2 months compared with fluorouracil alone. While newer agents such as capecitabine, oxaliplatin, raltitrexed and tegafur/uracil (UFT) have been focused upon by clinical researchers, data on their use in the elderly remain unconvincing. Not only are we approaching a clearer understanding of the effectiveness of cancer care among the elderly, but research is also beginning to identify the cost effectiveness of both standard and emerging chemotherapeutic agents. Cost effectiveness of fluorouracil-based regimens, depending on delivery strategy, use of modulating agents and stage of cancer vary from US dollars 2000 per quality-adjusted life-year (QALY) to US dollars 20200 per QALY (1992 values). Irinotecan therapy has not been fully investigated from the perspective of cost effectiveness; the figure of US dollars 10000 per QALY (1998 values) for irinotecan monotherapy over fluorouracil regimens is likely an underestimate, while cost analysis of irinotecan and fluorouracil combination therapy has not yet been reported. Our understanding of cost effectiveness of other novel agents has lagged behind; further research on these agents is needed. Nonetheless, as the effects of these novel agents upon both outcomes and costs continue to be defined, both curative and palliative treatment of colorectal cancer in the elderly patient will become more sophisticated and effective.