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Biomedical subjects

Victor R Grann

Publications and source records attributed to Victor R Grann.

At least 19 recordsLinked to original sources

Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer.

BACKGROUND: An important advance in medical oncology has been the use of adjuvant chemotherapy for lymph node-positive colon cancer. However, to the authors' knowledge, the effect of the interval between surgery and the initiation of chemotherapy on survival has not been investigated. METHODS: The authors analyzed predictors and outcomes of time intervals to treatment after surgery among patients older than 65 years who were diagnosed with stage III colon cancer between 1992 and 1999 using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Linear and logistic regression analyses were used to model predictors of delay, and Cox proportional hazards models were used to analyze the impact of treatment timing on survival. RESULTS: Among 4382 patients with colon cancer, 1122 patients (26%) began adjuvant chemotherapy within 1 month, 2391 patients (55%) began adjuvant chemotherapy in 1 to 2 months, 454 patients (10%) began adjuvant chemotherapy in 2 to 3 months, and 415 patients (9%) began adjuvant chemotherapy >/=3 months after surgery. Intervals of >/=3 months (delay) were associated with older age, increased comorbid conditions, well/moderately differentiated grade, and being unmarried. Colon cancer-specific mortality was associated with a delay in the initiation of chemotherapy (hazards ratio [HR], 1.48; 95% confidence interval [95% CI], 1.15-1.92), advanced age, increased comorbidity, poorly differentiated tumor grade, the presence of >/=4 positive lymph nodes, and undergoing surgery in a nonteaching hospital. All-cause mortality was associated with intervals >2 months between surgery and chemotherapy (2 to 3 months: HR, 1.41; 95% CI, 1.15-1.74; >/=3 months: HR, 1.62; 95% CI, 1.31-1.99) compared with <1 month. CONCLUSIONS: In the older population that was studied, only 9% of patients initiated adjuvant chemotherapy >3 months after the date of curative surgery. However, delay in initiation was associated with both cancer-specific and all-cause mortality. Determining whether these results were because of chemotherapy timing or other associated factors will require further study.

Age Factors↗

Outcomes and diffusion of doxorubicin-based chemotherapy among elderly patients with aggressive non-Hodgkin lymphoma.

BACKGROUND: In the past 25 years, clinical trials have demonstrated the benefits of chemotherapy for patients with aggressive non-Hodgkin lymphoma. The authors analyzed the predictors and outcomes of chemotherapy among elderly patients with lymphoma. METHODS: Patients age >/=65 years who were diagnosed with Stage III and IV diffuse large B-cell lymphoma [according to the SEER Summary Staging Manual, 2000] between 1991 and 1999 in the Surveillance, Epidemiology, and End Results-Medicare data base were categorized by treatment: no chemotherapy, a doxorubicin-containing regimen, a regimen without doxorubicin, or chemotherapy not otherwise specified. Among the patients who survived for >6 weeks after diagnosis and who had a chemotherapy regimen specified, logistic regression analysis was used to identify predictors of doxorubicin-based treatment, and Cox proportional-hazards regression was used to analyze outcomes. RESULTS: Less than 66% of patients received any chemotherapy in the 6 months after diagnosis, and 42% of untreated patients died within 6 weeks. Older age, congestive heart failure, and other comorbidities were strong predictors of treatment without doxorubicin. From 1991 to 1999, the proportion of patients who received doxorubicin increased from <20% to >50%. Patients who received doxorubicin survived more than twice as long (24.4 months) as patients who did not receive doxorubicin (11.2 months). Survival was no better among patients who received chemotherapy without doxorubicin than among patients who received no chemotherapy. CONCLUSIONS: By 1999, doxorubicin-based chemotherapy had gained general acceptance for use among the elderly, although nearly 50% of elderly patients still were not receiving it. Given the clinical trial-based evidence of its benefits, in the absence of specific contraindications, most patients, including the elderly, should be treated with regimens that include doxorubicin.

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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.

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Breast biopsy and race/ethnicity among women without breast cancer.

BACKGROUND: Breast biopsy is essential for definitive breast cancer diagnosis, but may also play a role in determining eligibility for breast cancer preventive measures or clinical trials. In addition, the prevalence of a history of negative breast biopsy can be viewed as an indicator of the adequacy or intensity of health care in a given population. We therefore analyzed the association of a history of breast biopsy with race/ethnicity and other factors in a cohort of women without a cancer diagnosis who completed a risk assessment form for participation in the Study of Tamoxifen and Raloxifene (STAR) and a sociodemographic questionnaire. METHODS: Subjects were recruited at our large, urban teaching hospital. We developed a logistic regression model with biopsy (ever/never) as the outcome and age, race/ethnicity, educational attainment, and insurance coverage as the independent variables. RESULTS: Among 805 unaffected predominantly minority subjects, white women were more than three times as likely as black and Hispanic women (OR=3.3, 95% CI 1.9-5.9), and insured women were twice as likely as uninsured women (OR=2.0, 95% CI 1.4-2.9) to have had a biopsy. Biopsy results were also associated with race/ethnicity. DISCUSSION: We view these observations as hypothesis-generating rather than definitive. If confirmed, the associations we observed between negative biopsies and insurance status may reflect disparities in the timeliness and effectiveness of follow-up of suspicious lesions found via mammography. Our findings may also be relevant to the well-known association of breast cancer stage at diagnosis with low income and minority race/ethnicity.

Adult↗

Duration of adjuvant chemotherapy for colon cancer and survival among the elderly.

PURPOSE: In randomized trials, patients with stage III colon cancer who received 6 months of fluorouracil (FU)-based adjuvant chemotherapy had better survival than patients who did not. However, little is known about the predictors of, or the survival associated with, duration of chemotherapy in the community. PATIENTS AND METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify individuals > or = 65 years of age diagnosed with stage III colon cancer between 1995 and 1999. We used logistic and Cox proportional hazards regression models to analyze factors associated with early discontinuation of FU-based chemotherapy among these elderly colon cancer patients. RESULTS: Among 1,722 patients who received 1 to 7 months of FU-based chemotherapy, older age, being unmarried, and having comorbid conditions were associated with receiving less than 5 months of treatment. Among the 1,579 patients who survived > or = 8 months, the 1,091 (69.1%) who received 5 to 7 months of treatment had lower overall (hazard ratio [HR], 0.59; 95%, CI 0.49 to 0.71) and colon cancer-specific (HR, 0.53; 95% CI, 0.43 to 0.66) mortality than the 488 (30.9%) who received 1 to 4 months of treatment. CONCLUSION: More than 30% of elderly patients who initiated FU-based chemotherapy for stage III colon cancer and survived for at least 8 months discontinued treatment early. Mortality rates among such patients were nearly twice as high as among patients who completed 5 to 7 months of treatment. If the association we observed between duration of treatment and survival is confirmed, additional investigation is warranted to determine whether dose-intensity, cumulative dose, or other factors related to receipt of full adjuvant treatment are responsible.

Age Factors↗

Delay of adjuvant chemotherapy initiation following breast cancer surgery among elderly women.

BACKGROUND: Delay in the diagnosis of breast cancer is associated with worse stage distribution at diagnosis and decreased survival. However, the occurrence of delay in the delivery of adjuvant therapy and its impact on prognosis is not well understood. METHODS: To investigate the timeliness of initiation of adjuvant chemotherapy following surgery for breast cancer, we used data from the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Among women > or = 65 years diagnosed between 1992 and 1999 with stages I-II breast cancer, we used linear regression and Cox proportional hazards models to investigate the time intervals between surgery and initiation of adjuvant chemotherapy, factors associated with delay, and the effect of delay on survival. RESULTS: Our sample consisted of 5003 women who received adjuvant chemotherapy. Of these, 47% initiated chemotherapy within 1 month, 37% between 1 and 2 months, 6% between 2 and 3 months and 10% >3 months (delay) following surgery. Delay was associated with increasing age, residing in a rural location, being unmarried, earlier tumor stage, hormone receptor positivity, mastectomy, and non-receipt of radiation therapy. Survival did not differ among patients who initiated chemotherapy within 1, 2, or 3 months after surgery. Delay beyond 3 months was, however, associated with increased disease-specific mortality (HR 1.69; 95% CI 1.31-2.19) and overall mortality (HR 1.46; 95% CI 1.21-1.75). CONCLUSIONS: Among older patients, moderate delays in the receipt of adjuvant chemotherapy occur frequently, but long delays (>3 months) are uncommon. While early initiation of therapy is no benefit, significant delays are associated with increased mortality. Whether this reflects the medical impact of the delay of chemotherapy or factors associated with delay is unclear, but until this is clarified, patients should be encouraged to initiate treatment without significant delay.

Age Factors↗

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.

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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.

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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.

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Barriers to minority participation in breast carcinoma prevention trials.

BACKGROUND: Breast carcinoma prevention trials must recruit large cohorts of women who have an above-average risk of developing breast carcinoma. Recruitment for the Study of Tamoxifen and Raloxifene (STAR) trial required volunteers to complete a risk assessment questionnaire form (RAF). Women whose estimated risk of developing breast carcinoma in the next 5 years was > or = 1.67% based on the Gail model were invited to participate in STAR. Less than 4% of participants in the previously conducted P1 (tamoxifen vs. placebo) trial were minority women. We, therefore, studied barriers to minority participation in STAR among black, white, and Hispanic women who completed an RAF. METHODS: The authors analyzed the association of Gail model risk factors, education, and insurance with race/ethnicity using chi-square tests and two-sided P values. They developed logistic regression models of trial eligibility, controlling for the Gail model risk factors, education, and insurance status. RESULTS: Among 823 women who completed an RAF, white women were 10 times as likely as Hispanic women and 45 times as likely as black women to be eligible for STAR. Age at first birth (P = 0.04), having an affected first-degree relative (P < 0.0001), having had a biopsy (P < 0.0001), education (P < 0.0001), and insurance status (P < 0.0001) varied by race/ethnicity. All variables except insurance status were associated with eligibility when race was excluded from the model. In a model that included race/ethnicity, the same factors remained statistically significant. CONCLUSIONS: These findings suggested that both the race/ethnicity adjustment and socioeconomic factors were barriers to eligibility for and contribute to low minority participation in breast cancer prevention trials.

Black or African American↗

Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma.

BACKGROUND: The objective of this study was to assess hormone receptor status as an independent predictor of survival in a population-based cohort of women with breast carcinoma who were followed for up to 11 years. METHODS: Since 1990, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program has collected data on hormone receptor status among patients with breast carcinoma. In a cohort of 205,736 women with breast carcinoma age > or = 20 years at diagnosis who were entered into the SEER data base between 1990 and 2000, the authors analyzed the association of hormone receptor status with year of diagnosis, patient age, disease stage, tumor histology, tumor grade, race/ethnicity, and metropolitan/statewide residence areas. Kaplan-Meier survival curves were compared according to hormone receptor status, and Cox proportional-hazards regression models were used to assess the association of hormone receptor status with breast carcinoma-specific and all-cause mortality controlling for age, disease stage, tumor grade, tumor histology, race/ethnicity, and SEER region. RESULTS: Women who had tumors that were positive for both estrogen and progesterone hormone receptors had significantly better survival than other women with breast carcinoma in the overall cohort, within each stage, and in the younger and older age groups, although the survival advantage was greater among women age < or = 50 years than among older women. Hormone receptor status was associated with mortality even when patient age, disease stage, tumor grade, tumor histology, race/ethnicity, and metropolitan/statewide residence areas were taken into account. CONCLUSIONS: Hormone receptor status was identified as an independent predictor of outcome in women with breast carcinoma. Data from clinical trials with long follow-up may shed light on whether and how the benefit of hormonal and other treatment varies with hormone receptor status.

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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.

Adult↗

Patterns and outcomes of chemotherapy for elderly patients with stage II ovarian cancer: a population-based study.

BACKGROUND: The optimal treatment for patients with stage II ovarian cancer is controversial, although most experts recommend adjuvant chemotherapy. The purpose of this study was to assess the patterns of use of chemotherapy in women with stage II ovarian cancer, and to compare the survival of treated and untreated patients aged 65+ years in a population-based sample. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database of cancers diagnosed in approximately 14% of the U.S. population, we identified women who were diagnosed with stage II ovarian cancer between 1992 and 1996, survived >or=120 days beyond diagnosis, and were >or=65 years of age. Multivariate regression was used to compare those treated to those not treated with chemotherapy. Cox proportional hazards regression models were used to analyze patient survival. RESULTS: Of 236 women with stage II ovarian cancer, 160 (67.8%) received chemotherapy, and 118 (50%) received platinum-based regimens. Younger patients and those with higher-grade tumors were more likely to receive chemotherapy. The adjusted hazards ratio for mortality associated with any chemotherapy use was 0.67 (95% CI, 0.45-0.98), corresponding to an increase in median survival from 28 months to 35 months (P < 0.0001). CONCLUSIONS: This observational study found that most patients aged >or=65 years and diagnosed with stage II ovarian cancer between 1992 and 1996 were treated with chemotherapy. Grade and younger age were the most significant predictors of treatment, and treatment was associated with a 5-year mortality reduction of 33%. These findings are not definitive, but they may provide some guidance in the absence of randomized trials of adjuvant chemotherapy for older women with stage II ovarian cancer.

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Effectiveness of platinum-based chemotherapy among elderly patients with advanced ovarian cancer.

BACKGROUND: Platinum-based chemotherapy is the standard of care for women with advanced ovarian cancer based on the results of randomized trials. We previously showed that only about half of women over the age of 65 years with this disease received platinum-based chemotherapy, and that the likelihood of receiving it decreases with age. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify women diagnosed from 1/1/92 to 12/31/96 with stage III or IV ovarian cancer who survived > or =120 days beyond diagnosis, and were > or =65 years of age. Cox proportional hazards models and propensity scores were used to control for known predictors of receiving treatment and to estimate the relative effectiveness of different platinum-based regimens. RESULTS: Of the 1759 patients in the sample who met our eligibility criteria, 53% received platinum-based therapy. For this sample, the Cox proportional hazard ratio was 0.72 (95% CI, 0.62-0.91) for mortality associated with the use of any platinum-based therapy, and 0.59 (95% CI, 0.45-0.76) for combination platinum/paclitaxel therapy. Similar results were obtained using propensity score modeling. CONCLUSIONS: In this population-based study, we found that only about half of women with advanced ovarian cancer over age 65 were treated with platinum-based chemotherapy; however, survival improved by 38% in treated women, similar to the benefits described in randomized controlled trials among younger patients, and were greatest when platinum was combined with paclitaxel. An effort to increase the utilization of platinum combination therapy among older patients with advanced ovarian cancer is justified.

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