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Biomedical subjects

Victor R Grann

Publications and source records attributed to Victor R Grann.

31 records · Page 2Linked to original sources

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.

Aged↗

Facilitating cancer research using natural language processing of pathology reports.

Many ongoing clinical research projects, such as projects involving studies associated with cancer, involve manual capture of information in surgical pathology reports so that the information can be used to determine the eligibility of recruited patients for the study and to provide other information, such as cancer prognosis. Natural language processing (NLP) systems offer an alternative to automated coding, but pathology reports have certain features that are difficult for NLP systems. This paper describes how a preprocessor was integrated with an existing NLP system (MedLEE) in order to reduce modification to the NLP system and to improve performance. The work was done in conjunction with an ongoing clinical research project that assesses disparities and risks of developing breast cancer for minority women. An evaluation of the system was performed using manually coded data from the research project's database as a gold standard. The evaluation outcome showed that the extended NLP system had a sensitivity of 90.6% and a precision of 91.6%. Results indicated that this system performed satisfactorily for capturing information for the cancer research project.

Biomedical Research↗

Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer.

Disparities in breast cancer survival have been observed between African American and white women. There are also known differences in mean baseline white blood cell (WBC) count among racial and ethnic groups. If the WBC count falls below conventionally defined treatment thresholds for patients undergoing adjuvant chemotherapy, reduced doses or treatment delays may occur, which could lead to race-based differences in treatment duration. We used the tumor registry at Columbia-Presbyterian Medical Center to identify 1178 women with newly diagnosed stage I and II breast cancer from whom we collected base-line information for 73 African American women and 126 age- and tumor stage-matched white women. Of these women, 43 African American and 93 white women underwent adjuvant chemotherapy. African American women had statistically significantly lower WBC counts than white women at diagnosis (6.2 x 10(9)/L for African American women versus 7.4 x 10(9)/L for white women, difference = 1.2, 95% confidence interval [CI] = 0.2 to 1.2; P =.02) and after treatment (5.3 x 10(9)/L for African American women versus 6.4 x 10(9)/L for white women, difference = 1.1, 95% CI = 0.2 to 2.5; P =.03). Overall, African American women required a statistically significantly longer duration of treatment than white women (19 weeks versus 15 weeks, respectively, difference = 4 weeks, 95% CI = 0.5 to 7.2 weeks; P =.03). The lower baseline WBC counts and longer duration of treatment for early-stage breast cancer in African American women compared with those in white women result in lower dose intensity of treatment for African American women, possibly contributing to observed racial differences in breast cancer survival.

Adult↗

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.

Aged↗

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.

Age Factors↗

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.

Adult↗

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.

Age Factors↗

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.

Age Factors↗

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.

Adult↗

Population screening for cancer-related germline gene mutations.

Over the past 5 years, tests for germline (heritable) gene mutations associated with high risk of chronic diseases, such as breast cancer, have become increasingly available. Appropriately used, tests for such mutations could lead to reductions in disease morbidity and mortality. Population screening has been proposed for some cancer-related mutations; however, not all populations are suitable for such screening. The benefits of screening and preventive treatments for individuals with cancer-related mutations in different populations depend on the prevalence and penetrance of the mutation, the mortality associated with the disease, the age of the person screened at testing, and the potential effects of preventive measures on risk of developing the disease, quality of life, and costs. The criteria normally used to assess cancer screening tests can be applied, with some modifications, to tests for cancer-related genetic mutations and can help physicians, insurance companies, and health-policy makers to decide whether or not specific genetic tests should be used to screen specific populations.

Breast Neoplasms↗