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Biomedical subjects

Benjamin D Smith

Publications and source records attributed to Benjamin D Smith.

18 recordsLinked to original sources

Postmastectomy radiation and survival in older women with breast cancer.

PURPOSE: Clinical trials indicate that postmastectomy radiation therapy (PMRT) improves survival for women age younger than 70 years with high-risk breast cancer. However, for women age 70 years or older, the benefits of PMRT are unknown. As recent evidence suggests that certain adjuvant treatments appropriate for younger women may only be marginally beneficial for older women, we sought to determine whether PMRT improves survival for older women with breast cancer. METHODS: Using the Surveillance, Epidemiology and End Results Medicare data spanning 1992 to 1999, we identified 11,594 women age 70 years or older treated with mastectomy for invasive breast cancer. A proportional hazards model adjusted for clinical-pathologic covariates tested whether PMRT was associated with improved overall survival for low-risk (T1/2 N0), intermediate-risk (T1/2 N1), and high-risk (T3/4 and/or N2/3) patients. RESULTS: A total of 502 (7%) of 7,416 low-risk, 242 (11%) of 2,145 intermediate-risk, and 785 (38%) of 2,053 high-risk patients received PMRT. Median follow-up was 6.2 years. For low- and intermediate-risk patients, PMRT was not associated with survival. For high-risk patients, PMRT was associated with a significant improvement in survival (hazard ratio, 0.85; 95% CI, 0.75 to 0.97; P = .02). Five-year adjusted survival was 50% for patients not treated with PMRT or chemotherapy, 56% for patients treated with PMRT only, 57% for patients treated with chemotherapy only, and 59% for patients treated with both PMRT and chemotherapy. CONCLUSION: PMRT is associated with improved survival for older women with high-risk breast cancer. Randomized clinical trials are urgently needed to confirm this finding and define optimal treatment strategies for this patient group.

Age Factors↗

Effectiveness of radiation therapy in older women with ductal carcinoma in situ.

BACKGROUND: For women with ductal carcinoma in situ (DCIS), radiation therapy after conservative surgery lowers the risk of recurrence. However, emerging evidence suggests that radiation therapy confers only a marginal absolute benefit for older women with DCIS. In a cohort of older women with DCIS, we sought to determine whether radiation therapy was associated with a clinically significant benefit. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 1992, through December 31, 1999, we identified 3409 women aged 66 years or older treated with conservative surgery for DCIS. A proportional hazards model tested whether radiation therapy was associated with a lower risk of a combined outcome, defined as a subsequent ipsilateral in situ or invasive breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. The 5-year event risk was determined for patients without and with high-risk features, which were defined as at least one of the following: age 66-69 years, tumor larger than 2.5 cm, comedo histology, and/or high grade. All statistical tests were two-sided. RESULTS: Radiation therapy was associated with a lower risk for each component of the combined outcome (hazard ratio = 0.32, 95% confidence interval [CI] = 0.24 to 0.44). For high-risk patients, the 5-year event risk was 13.6% without radiation therapy versus 3.8% with radiation therapy (difference = 9.8%, 95% CI = 6.5 to 13.2; P<.001). For low-risk patients, the 5-year event risk was 8.2% without radiation therapy versus 1.0% with radiation therapy (difference = 7.2%, 95% CI = 3.6 to 10.9; P<.001). Among healthy women aged 66-79 years, the number needed to treat with radiation therapy to prevent one event in 5 years was 11 for high-risk patients and 15-16 for low-risk patients. CONCLUSION: For older women with DCIS, radiation therapy appears to confer a substantial benefit that remains meaningful even among low-risk patients.

Age Factors↗

Rationalization and regionalization of treatment for ductal carcinoma in situ of the breast.

PURPOSE: In ductal carcinoma in situ (DCIS) of the breast, conservative surgery plus radiotherapy (CS+RT) decreases risk of recurrence compared with CS alone. Although nearly one third of patients are reported as treated with CS alone, it is unclear whether this potentially "undertreated" group represents high- or low-risk patients. We evaluated national patterns of DCIS treatment from 1996 to 2001 by patient risk profile. METHODS AND MATERIALS: In a retrospective cohort of DCIS patients from the Surveillance, Epidemiology, and End Results data, patients were risk stratified on the basis of age at diagnosis, tumor grade, tumor size, and comedo histology. Treatment included CS alone, CS+RT, or mastectomy. Patients were followed for the development of ipsilateral invasive or in situ event. RESULTS: Of 14,202 patients, 19% were low-risk, 46% moderate-risk, and 35% high-risk. A total of 28% received CS alone, 40% CS+RT, and 31% mastectomy. Overall, only 17% of high-risk patients but 44% of low-risk patients received CS alone (p < 0.001). In multivariable analysis, older age, smaller tumor size, and treatment in San Francisco/Los Angeles predicted treatment with CS alone (p < 0.01). Yet despite the tendency to receive CS alone, patients in San Francisco/Los Angeles did not experience an increased risk of ipsilateral event (hazard ratio = 0.79; 95% confidence interval, 0.55-1.12). CONCLUSION: Patient risk profiles rationally affect treatment choice in DCIS patients, and the vast majority of high-risk patients do not receive CS alone. Additional follow up is needed to determine whether geographic variation in care influences long-term outcomes.

Breast Neoplasms↗

Effectiveness of radiation therapy for older women with early breast cancer.

BACKGROUND: Recent clinical trials have questioned the necessity of breast radiation therapy for older women with early breast cancer. However, the effectiveness of radiation therapy for older women in the community setting has not been addressed. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 1992, through December 31, 1999, to identify 8724 women aged 70 years or older treated with conservative surgery for small, lymph node-negative, estrogen receptor-positive (or unknown receptor status) breast cancer. We used a proportional hazards model to test whether radiation therapy was associated with a lower risk of a combined outcome, defined as a second ipsilateral breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. All statistical tests were two-sided. RESULTS: Radiation therapy, compared with no radiation therapy, was associated with a lower risk of the combined outcome (hazard ratio = 0.19, 95% confidence interval = 0.14 to 0.28). Radiation therapy was associated with an absolute risk reduction of 4.0 events per 100 women at 5 years (i.e., from 5.1 events without radiation therapy to 1.1 with radiation therapy) and 5.7 events per 100 persons at 8 years (i.e., from 8.0 events without radiation therapy to 2.3 with radiation therapy) (P < .001, log-rank test). Radiation therapy was most likely to benefit those aged 70-79 years without comorbidity (number needed to treat [NNT] to prevent one event = 21 to 22 patients) and was least likely to benefit those aged 80 years or older with moderate to severe comorbidity (NNT = 61 to 125 patients). CONCLUSION: For older women with early breast cancer, radiation therapy was associated with a lower risk of a second ipsilateral breast cancer and subsequent mastectomy. Patients aged 70-79 years with minimal comorbidity were the most likely to benefit, and older patients with substantial comorbidity were least likely to benefit.

Age Factors↗

The cutaneous B-cell lymphoma prognostic index: a novel prognostic index derived from a population-based registry.

PURPOSE: Three classification and prognostic systems exist for primary cutaneous B-cell lymphoma (PCBCL). Whereas the WHO classification defines its categories based on histology, both the European Organisation for Research and Treatment of Cancer classification and the conventional staging system consider skin site. We sought to incorporate both histology and skin site into a single prognostic index designed to predict survival in patients with PCBCL. METHODS: The associations between histology, skin site, and survival were determined using adjusted proportional hazards analysis conducted on 926 patients with PCBCL identified in the Surveillance, Epidemiology, and End Results data, spanning 1973 to 2001. RESULTS: Four primary CBCL prognostic index (CBCL-PI) groups were identified. Group IA included indolent histologies involving any skin site. Group IB included diffuse large B-cell histology involving favorable skin sites (head/neck, arm). Group II included diffuse large B-cell histology involving unfavorable skin sites (trunk, legs, disseminated) or immunoblastic large B-cell histology involving favorable skin sites. Group III included immunoblastic large B-cell histology involving unfavorable skin sites. The adjusted mortality hazards ratios were 1.0, 1.3 (95% CI, 0.99 to 1.7), 2.1 (95% CI, 1.6 to 2.7), and 4.5 (95% CI, 2.8 to 7.2) for groups IA/B to III, respectively. The corresponding 5-year relative survivals were 94%, 86%, 60%, and 34%. CONCLUSION: The CBCL-PI identifies adverse combinations of histology and skin site, helping to reconcile differences in current classification and prognostic systems for PCBCL.

Adult↗

Postmastectomy radiation and mortality in women with T1-2 node-positive breast cancer.

PURPOSE: To determine the relationship between postmastectomy radiotherapy (PMRT) and mortality in a population-based cohort of women with T1-2 node-positive breast cancer. PATIENTS AND METHODS: Using data from the Surveillance, Epidemiology, and End Results program, we identified 18,038 women with T1-2 node-positive invasive breast cancer who were treated with mastectomy between 1988 and 1995. The relationship between PMRT and mortality was determined using proportional hazards multivariate modeling and propensity score matched case-control analysis. RESULTS: Median follow-up was 8.1 years. Only 2,648 women (15%) received PMRT. After adjusting for covariates, PMRT use was not associated with mortality (hazard ratio [HR] = 0.96; 95% CI, 0.90 to 1.03). However, the interaction term for PMRT use and number of involved regional lymph nodes was significant (P = .002), suggesting that, above a certain threshold of involved nodes, a mortality benefit from PMRT may exist. Adjusted analysis stratified by number of involved nodes revealed that patients with seven or more involved nodes treated with PMRT experienced a significant reduction in all-cause (HR = 0.84; 95% CI, 0.76 to 0.93) and cause-specific mortality (HR = 0.86; 95% CI, 0.77 to 0.96). Propensity score matched case-control analysis confirmed that PMRT was associated with reduced mortality only in the subset of patients with seven or more involved nodes (HR = 0.81; 95% CI, 0.73 to 0.91 for all-cause mortality; and HR = 0.82; 95% CI, 0.72 to 0.93 for cause-specific mortality). CONCLUSION: For women with T1-2 breast cancer, PMRT is associated with a 15% to 20% relative reduction in mortality for patients with seven or more involved regional lymph nodes.

Aged↗

Primary cutaneous B-cell lymphoma treated with radiotherapy: a comparison of the European Organization for Research and Treatment of Cancer and the WHO classification systems.

PURPOSE: To determine the relationship between the WHO and European Organization for Research and Treatment of Cancer (EORTC) pathologic classifications for primary cutaneous B-cell lymphoma (CBCL) and the implication of this relationship on initial treatment. PATIENTS AND METHODS: Patients with primary CBCL treated with radiotherapy were identified retrospectively. Initial biopsy specimens were reviewed by two dermatopathologists and classified according to the EORTC and WHO systems. Primary outcomes were recurrence-free and overall survival. RESULTS: Thirty-four patients were identified; initial biopsy specimens were adequate for classification in 32 patients. Four different composite histopathologic subtypes of lymphoma were identified: 53% (17 of 32) follicle center cell by EORTC and diffuse large B-cell by WHO (FCC/DLB), 25% (eight of 32) follicle center cell by EORTC and follicular by WHO (FCC/Fol), 13% (four of 32) marginal zone by EORTC and WHO (MZ/MZ), and 9% (three of 32) large B-cell of the leg by EORTC and diffuse large B-cell by WHO (Leg/DLB). Five-year relapse-free survival ranged from 62% to 73% for FCC/DLB, FCC/Fol, and MZ/MZ but was 33% for Leg/DLB (P =.6). Five-year overall survival was 100% for FCC/DLB, FCC/Fol, and MZ/MZ but was 67% for Leg/DLB (P =.07). At 5 years, 21% of all patients had developed extracutaneous disease. CONCLUSION: Two-thirds of primary cutaneous FCC lymphomas by EORTC criteria satisfy WHO criteria for DLB lymphoma. Unlike DLB lymphoma presenting in nodal or noncutaneous sites, these lesions are associated with an indolent course and may be treated with local radiotherapy alone.

Aged↗

Management of mycosis fungoides. Part 1. Diagnosis, staging, and prognosis.

Mycosis fungoides is a low-grade lymphoproliferative disorder caused by CD4+ lymphocytes. It is the most common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize to the skin and produce patches, plaques, tumors, or erythroderma. Diagnosis of early mycosis fungoides can be difficult due to the nonspecific nature of cutaneous and histologic findings. However, recent advances in the application of histologic criteria, coupled with molecular biology tools such as immunophenotyping and polymerase chain reaction, have improved diagnostic accuracy. Independent prognostic factors include the extent and nature of skin involvement, the presence of extracutaneous disease, blood involvement, age > or = 60 years, and lactate dehydrogenase elevation. Accordingly, patients with limited patches and/or plaques (stage IA or IIA) experience long-term survival comparable to that of matched controls. The median survival is 11 years for patients with extensive patch/plaque (stage IB or IIA), 3.2 years for those with cutaneous tumors (stage IIB), 4.6 years for those with erythroderma (stage III), 1.2 years for those with pathologic nodal involvement (stage IVA), and 0.9 years for those with visceral disease (stage IVB). Over time, mycosis fungoides may progress to Sézary syndrome or transform to large-cell histology.

CD4-Positive T-Lymphocytes↗

Management of mycosis fungoides: Part 2. Treatment.

Mycosis fungoides is a low-grade lymphoproliferative disorder of skin-homing CD4+ lymphocytes that may produce patches, plaques, tumors, erythroderma, and, ultimately, systemic dissemination. Treatment selection is generally guided by institutional experience, patient preference, and toxicity profile, as data from phase III clinical trials are limited. Effective topical treatments currently include mechlorethamine (Mustargen), carmustine (BCNU, BiCNU), corticosteroids, bexarotene (Targretin, a novel rexinoid), psoralen plus ultraviolet A, ultraviolet B, and total-skin electron-beam radiotherapy. Effective systemic treatments include interferon, retinoids, bexarotene, denileukin diftitox (Ontak), extracorporeal photopheresis, chemotherapy, and high-dose chemotherapy with allogeneic bone marrow transplant. Each of these treatments is discussed in detail, followed by specific recommendations for each stage of mycosis fungoides.

Administration, Topical↗

Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma.

PURPOSE: The role of HER-2/neu in squamous cell carcinoma (SCC) of the head and neck is not well defined. The purpose of the current study is to measure the frequency of HER-2/neu expression, to demonstrate HER-2/neu gene amplification in the cases found to be positive for protein overexpression, and to investigate the prognostic significance of overexpression and/or amplification in SCC of the head and neck. EXPERIMENTAL DESIGN: A cohort of 77 patients with SCC of the oral cavity or oropharynx, with stage III or IV disease and uniformly treated with surgical resection and postoperative radiation, served as the primary patient population for the study. Of these, 56 patients had adequate follow-up and paraffin-embedded specimens available for analysis. Median follow-up was 6.1 years. Each of the paraffin-embedded specimens were immunohistochemically stained for HER-2/neu expression and graded for intensity of staining by a pathologist. All cases that demonstrated positive staining by immunohistochemistry were analyzed by fluorescence in situ hybridization (FISH) to assess HER-2/neu amplification status. RESULTS: Five-year survival for the 56 evaluable patients was 40%, with 25% experiencing local relapse, 18% regional relapse, and 25% distant relapse. The percentage of tumors staining positive for HER-2/neu by immunohistochemistry was 17%. There was no statistically significant correlation between HER-2/neu and T stage, N stage, tumor grade, survival, or disease-free survival. HER-2/neu expression did correlate with vascular endothelial growth factor expression. FISH analysis revealed four cases that were amplified for HER-2/neu. Of note, of the 4 amplified cases, 2 suffered regional relapse, 1 suffered distant metastasis, and all 4 expired by 5 years of follow-up. CONCLUSIONS: This is the first demonstration of HER-2/neu gene amplification by FISH in SCC of the head and neck. FISH validates a previously contested controversial role for HER-2/neu gene overexpression in SCC of the head and neck. The prognostic significance and clinical implications of HER-2/neu expression and amplification in head and neck cancer will require additional studies.

Adult↗