Russell McBride

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.

Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma.

PURPOSE Anthracycline-based chemotherapy, which improves survival for patients with non-Hodgkins lymphoma, is often withheld from elderly patients because of its cardiotoxicity. We studied the cardiac effects of doxorubicin in a population-based sample of older patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS Among patients age > or = 65 years diagnosed with DLBCL from 1991 to 2002 in the Surveillance, Epidemiology, and End Results-Medicare database, we developed logistic regression models of the associations of doxorubicin with demographic, clinical, and cardiac variables. We then developed Cox proportional hazards models of the association between doxorubicin and subsequent congestive heart failure (CHF), taking predictors of CHF into account. RESULTS Of 9,438 patients with DLBCL, 3,164 (42%) received doxorubicin-based chemotherapy. Any doxorubicin use was associated with a 29% increase in risk of CHF (95% CI, 1.02 to 1.62); CHF risk increased with number of doxorubicin claims, increasing age, prior heart disease, comorbidities, diabetes, and hypertension; hypertension intensified the effect of doxorubicin on risk of CHF (hazard ratio = 1.8; P < .01). In the 8 years after diagnosis, the adjusted CHF-free survival rate was 74% in doxorubicin-treated patients versus 79% in patients not treated with doxorubicin. CONCLUSION Among patients receiving chemotherapy for DLBCL, those with prior heart disease were less likely than others to be treated with doxorubicin, and those who received doxorubicin were more likely than others to develop CHF. Various cardiac risk factors increased CHF risk, but only hypertension was synergistic with doxorubicin. Doxorubicin has dramatically improved survival of DLBCL patients; nonetheless, some subgroups may benefit from efforts to reduce doxorubicin-related CHF risk.

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.

Racial disparities in utilization of liver transplantation for hepatocellular carcinoma in the United States, 1998-2002.

BACKGROUND AND AIMS:The extent of use of liver transplantation on a population scale to treat hepatocellular carcinoma (HCC) in the United States is unknown. We assessed recent predictors of use of liver transplantation and its effect on survival for those with nonmetastatic HCC.METHODS:The Surveillance, Epidemiology, and End Results (SEER) program is a collection of population-based cancer registries. We identified adults registered in SEER with HCC between 1998 and 2002. We examined determinants for receipt of a liver transplant in univariate and multivariable analyses. Kaplan–Meier survival curves were constructed for those who received and did not receive a transplant for HCC.RESULTS:We identified 1,156 adults with small (5 cm or less) nonmetastatic HCC. Approximately 45% were white, 29% Asian, 17% Hispanic, and 9% African American. Only 21% received a transplant. More recent year of diagnosis, younger age, being married, white race, and smaller tumor size each predicted receipt of transplant. African Americans and Asians were about half as likely to receive a transplant as compared with white patients (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.21–0.90 for African Americans, and 0.57, 95% CI 0.36–0.89 for Asians). Hispanics trended in the same direction, but this was not statistically significant (OR 0.66, 95% CI 0.39–1.12). Those who underwent liver transplantation for localized HCC had 3- and 5-yr survivals of 81% and 75%, respectively.CONCLUSIONS:Only one-fifth of those with small, nonmetastatic HCC received liver transplantation. Transplanted patients have long-term survival similar to that of the best single-institution studies. However, marked racial variations were seen, with African Americans and Asians significantly less likely to receive a transplant after controlling for other variables.

Patterns of Use and Risks Associated With Erythropoiesis-Stimulating Agents Among Medicare Patients With Cancer

BACKGROUND Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist. METHODS We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database; who were diagnosed with colon, non-small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided. RESULTS Among 56,210 patients treated with chemotherapy from 1991 through 2002, 15,346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991-2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12,522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34,820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups. CONCLUSION Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.

Adverse Event Reporting in Cancer Clinical Trial Publications

PURPOSE Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. METHODS A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. RESULTS A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. CONCLUSION Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

Within-stage racial differences in tumor size and number of positive lymph nodes in women with breast cancer

Black women have higher breast cancer mortality rates, are more likely to be diagnosed at an advanced stage of disease, and have worse stage‐for‐stage survival than white women. It was hypothesized that differences in the tumor size and number of positive lymph nodes within each disease stage contribute to the survival disparity.

Esophagectomy compared with chemoradiation for early stage esophageal cancer in the elderly

Esophagectomy has been the traditional treatment of choice for early stage esophageal cancer. However, esophagectomy is associated with high mortality and morbidity in the elderly, and these patients often receive chemoradiation instead. The authors of this report compared outcomes of esophagectomy versus chemoradiation in a population‐based sample of elderly patients with early stage esophageal cancer.

Surgeon characteristics and use of breast conservation surgery in women with early stage breast cancer

Background:Most women with localized breast cancer have a choice between mastectomy and breast conserving surgery (BCS). Aside from clinical factors, this decision may be associated with surgeon and patient characteristics. We investigated the effect of surgeon characteristics on the BCS rate. Methods:We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women >65 years, diagnosed with stages I-II BC, between 1991 and 2002, and used the Physician Unique Identification Number linked to the American Medical Association Masterfile to obtain information on surgeons. We investigated the association of patient demographic, tumor, and surgeon-related factors with receipt of BCS, using Generalized Estimating Equations to control for clustering. Results:Of 56,768 women with breast cancer, 30,006 (53%) underwent BCS, whereas 26,762 (47%) underwent mastectomy. Between 1991 and 2002, the proportion of patients undergoing BCS increased from 35% to 60%. In a multivariate analysis, patients who received BCS were younger, of higher SES, and had more favorable tumor characteristics. They were also more likely to be black and live in metropolitan areas. Women who underwent BCS were more likely to have surgeons who were female (OR = 1.40; 95% CI: 1.25–1.55), US-trained (OR = 1.12; 95% CI: 1.02–1.22), with a larger patient panel (OR = 1.29; 95% CI: 1.21–1.39), and completed training after 1975 (OR = 1.16; 95% CI: 1.08–1.25), than surgeons of patients who underwent mastectomy. Conclusions:Surgeon characteristics, such as gender, training, year of graduation, and volume, are small but significant independent predictor of BCS. Efforts to differentiate whether these associations reflect patients’ preferences, quality of physician training, surgeon attitudes, physician-patient communication, or other effects on decision-making are warranted.

Influence of private practice setting and physician characteristics on the use of breast cancer adjuvant chemotherapy for elderly women.

Although >70% of younger women with nonmetastatic breast cancer (BC) received adjuvant chemotherapy, only approximately 15% to 20% of elderly women with BC received chemotherapy. The decision to treat may be associated with nonmedical factors, such as patient, physician, or practice characteristics. In the current study, the association between oncologist characteristics and the receipt of chemotherapy in elderly women with BC was evaluated.