Impact on outcome of delay in starting radiotherapy.
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Biomedical subjects
Publications and source records attributed to Abram Recht.
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PURPOSE: To compare outcomes for hypothetical cohorts of postmenopausal patients with estrogen receptor-positive tumors that are < or = 2 cm in size, with pathologically uninvolved axillary nodes, treated with radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery. METHODS: A Markov model was used to simulate patients' clinical course and estimate overall survival, recurrence-free survival, time with an intact breast, and death from breast cancer. Probabilities were derived from randomized trials and retrospective studies. Analyses were performed separately by age of diagnosis in 5-year increments from 50 to 80 years. Sensitivity analyses tested the stability of radiation benefit. RESULTS: The modeled recurrence-free survival benefit of giving radiation therapy was 3.35 years for women who were 50 years of age at diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year-old cohort, radiation therapy resulted in additional 0.60 years survival, compared with 0.04 years among 80-year-olds. A 50-year-old woman who received radiation therapy plus tamoxifen was less likely to die from breast cancer than if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An 80-year-old woman had a 1.17% chance of dying from breast cancer if she received radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative-risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit was strongly influenced by including unequal rates of developing distant disease after breast recurrence between the treatment arms and varying rates of local recurrence. CONCLUSION: The absolute and relative benefits of radiation therapy and individual patient preferences for different health states should be considered when selecting treatment.
BACKGROUND: At 5-year follow-up, patients with Paget disease of the breast who were treated with breast-conserving surgery (BCS) and radiotherapy (RT) had excellent results. The current report provides 10- and 15-year rates of tumor control in the breast, as well as disease-free and overall survival rates following BCS and RT in a cohort of patients with Paget disease presenting without a palpable mass or mammographic density. METHODS: Through a collaborative review of patients treated with BCS and RT from seven institutions, 38 cases of Paget disease of the breast presenting without a palpable mass or mammographic density were identified. All patients had pathologic confirmation of typical Paget cells at time of diagnosis. Thirty-six of 38 patients had a minimum follow-up greater than 12 months and constitute the study cohort. Ninety-four percent of patients underwent complete or partial excision of the nipple-areola complex and all patients received a median external beam irradiation dose of 50 Gy (range, 45-54 Gy) to the whole breast. Ninety-seven percent of patients also received a boost to the remaining nipple or tumor bed, a median total dose of 61.5 Gy (range, 50.4-70 Gy). RESULTS: With median follow-up of 113 months (range, 18-257 months), 4 of 36 patients (11%) developed a first recurrence of disease in the treated breast only. Two of the four recurrences in the breast were ductal carcinoma in situ (DCIS) only and two were invasive with DCIS. Two additional patients had a recurrence in the breast as a component of first failure. Actuarial local control rates for the breast as the only site of first recurrence were 91% at 5 years (95% confidence interval [CI], 80-100%) and 87% (95% CI, 75-99%) at both 10 and 15 years. Actuarial local control rates for breast recurrence, as a component of first failure, were 91% (95% CI, 80-100%), 83% (95% CI, 69-97%), and 76% (95% CI, 58-94%) at 5, 10, and 15 years, respectively. No clinical factors were identified as significant predictors for breast recurrence. Five-, 10- and 15-year actuarial rates for survival without disease of 97% (95% CI, 90-100%) and 5-, 10-, and 15-year actuarial rates of overall survival of 93% (95% CI, 84-100%) at 5 years and 90% (95% CI, 78-100%) at 10 and 15 years were reported. CONCLUSIONS: These data confirm excellent rates of local control, disease-free survival, and overall survival at 10 and 15 years following BCS and RT for Paget disease of the breast. This study continues to support the recommendation of local excision and definitive breast irradiation as an alternative to mastectomy in the treatment of patients with Paget disease presenting without a palpable mass or mammographic density.
PURPOSE: Many authors have studied the problems associated with the three-field breast treatment, yet the proposed solutions present their own difficulties. This study presents a technique that overcomes these difficulties, reduces scatter to the contralateral breast, and improves setup reproducibility. METHODS AND MATERIALS: Patients are set up with both arms raised superiorly on a breast board. A precise field-match is achieved by rotating the couch and collimator of the tangents, while the supraclavicular field is half-beam blocked using an independent jaw. The posterior borders of the tangents are conformally defined by multileaf collimation. Measurements were performed to verify the field matching and evaluate scatter doses. RESULT: A smooth dose transition was found at the match line at all depths. Corner blocks and lower wedges were not used, which reduced the scatter to the contralateral breast compared with our prior technique. CONCLUSION: The technique achieves a precise match while removing constraints on the tangents' length and decreasing scatter dose. Procedures for simulation, planning, and treatment have been devised, along with a new patient setup routine incorporating orthogonal setup films and tattoos. This technique has been successfully implemented in routine treatment since September 2001. A program calculating the setup parameters is available at our website.
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The ASCO guidelines panel found that PMRT reduces the risks of both local-regional recurrence and distant recurrence, and improves survival rates for patients with invasive breast cancer with involved axillary lymph nodes receiving systemic therapy. The benefits of PMRT, however, vary with regards to particular patient subsets (such as those defined by the number of involved axillary nodes). The panel agreed that PMRT is indicated routinely for patients with four or more positive axillary nodes, tumors larger than 5 cm in size, or locally advanced cancers. There was insufficient evidence for the panel to make recommendations or suggestions for the use of PMRT for patients with T1-2 tumors with one to three positive axillary nodes or for all patients receiving neoadjuvant systemic therapy. Physicians and patients are encouraged to participate in randomized trials exploring such issues, such as the ongoing intergroup study for patients with one to three positive axillary nodes.
Since its inception, the AJCC staging system for breast cancer has been in an almost constant state of evolution, striving with each revision to reflect the most up-to-date clinical research as well as the widespread consensus among physicians about appropriate diagnostic and treatment standards. To date, these revisions have essentially represented a "fine-tuning" of the initial judgment that tumor size, lymph node status, and presence of distant metastases are the most significant prognostic factors for breast cancer. With the problems of standardization and reproducibility being resolved, it is likely that histologic grade will join this group of independent markers and be incorporated into the AJCC staging system in the near future. Over the last 15 years. considerable attention has been focused on the discovery of new markers visualized with immunohistochemistry and RT-PCR that may be validated as independent prognostic indicators (reviewed by Mirza et al). To date, the usefulness of many of these markers has been limited by lack of standardization in measurement techniques, but several show great promise for the future. By increasing the number of prognostic markers that can give independent information about patient outcome, physicians will be better able to determine optimal treatment approaches for individual patients.
There is no consensus on the optimal combination of systemic therapy and radiation therapy for patients with early-stage breast cancer treated with conservative surgery. This article reviews prospective and retrospective studies that shed light on this topic. Patients with positive, close, or unknown microscopic margins appear to benefit from relatively early initiation of radiation therapy, whereas those with wider tumor-free margin widths do not. For patients at high risk of distant failure (such as those with = 4 positive axillary nodes), chemotherapy may be more effective when it begins before radiation therapy rather than after. Regimens of concurrent radiation therapy and chemotherapy tend to have higher acute and subacute complication rates than sequential regimens, but the actual rates vary substantially with the exact details of the overall treatment program. There are no data on the impact of the timing of tamoxifen administration on the effectiveness of radiation therapy. Tamoxifen does not appear to increase complication rates relative to the use of radiation therapy alone. Thus, the best way of giving combined-modality therapy is uncertain. Further retrospective and prospective studies to investigate the issues discussed herein should be performed.
BACKGROUND: Whether African-American women have biologically more aggressive breast carcinoma compared with white women and whether race acts as a significant independent prognostic factor for survival have not been determined. Alternatively, race merely may be a surrogate for socioeconomic status (SES). METHODS: A literature review was performed of clinical trials and retrospective studies in the U.S. that compared survival between white women and black women with breast carcinoma after adjustment for known prognostic factors (patient age, disease stage, lymph node status, and estrogen receptor status) to assess the impact of race and SES. RESULTS: Single institutional and clinical studies suggest that, when black patients are treated appropriately and other prognostic variables are controlled, their survival is similar to the survival of white patients. Twelve retrospective studies and 1 analysis of a clinical trial included SES and race as variables for survival. Only three of those studies revealed race as a significant prognostic factor for survival after adjusting for SES. CONCLUSIONS: SES replaces race as a predictor of worse outcome after women are diagnosed with breast carcinoma in many studies. However, black women present with more advanced disease that appear more aggressive biologically, and they present at a younger age compared with white women. Further research should be conducted concerning the precise elements of SES that account for the incidence of breast carcinoma, age at diagnosis, hormone receptor status, and survival to devise better strategies to improve outcome.
PURPOSE: To revise the American Joint Committee on Cancer staging system for breast carcinoma. MATERIALS AND METHODS: A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases. RESULTS: Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes; and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes. CONCLUSION: This revised staging system will be officially adopted for use in tumor registries in January 2003.
PURPOSE: Patients younger than 35 to 45 years old at the time of diagnosis of invasive breast cancer have been found to have a worse prognosis than older patients in many studies. However, the impact of patient age at diagnosis on the outcome of treatment with either lumpectomy and radiation therapy (RT) or mastectomy for patients with ductal carcinoma-in-situ (DCIS) of the breast has not been extensively analyzed. MATERIALS AND METHODS: Articles addressing the effect of patient age at diagnosis on the outcome of treatment of DCIS with lumpectomy and RT or mastectomy were identified through the MEDLINE and CancerLit databases and reference lists of relevant articles. Studies were reviewed to determine the impact of patient age at diagnosis on clinical and pathologic features of DCIS, the influence of age on outcome after lumpectomy and RT, and the impact of age on outcome after mastectomy. RESULTS: DCIS in younger patients more frequently contains adverse prognostic pathologic factors and extends over a greater distance in the breast than in older patients. In series with adequate follow-up, younger patients treated with lumpectomy and RT had a significantly higher rate of local recurrence than older patients, especially for invasive local recurrences. Some studies have suggested that careful attention to margin status and excising larger volumes of tissue can reduce this difference substantially. No available data show that younger patients have better long-term cancer-free survival rates if treated by mastectomy rather than lumpectomy and RT. CONCLUSION: Successful treatment of younger patients with DCIS with lumpectomy and RT requires careful attention to patient evaluation, selection, and surgical technique. When this is done, age at diagnosis should not be a contraindication to breast-conserving therapy.
PURPOSE: Breast cancer patients treated with conservative surgery and radiation therapy are at risk of developing second nonbreast malignancies (SNBMs). The purpose of this study was to determine the incidence of all SNBMs and SNBMs by specific location among long-term survivors and to compare the risk of these events to the age-specific incidence of malignancies as first cancers in the Surveillance Epidemiology and End-Results Program (SEER) population. METHODS AND MATERIALS: We analyzed the likelihood of SNBM development for 1884 patients with clinical Stage I or II breast cancer treated with gross excision and > or = 60 Gy (median 63) to the breast between 1970 and 1987. Fifty-seven percent received supraclavicular/axillary radiation (median dose 45 Gy, range 20-60) and 28% received systemic therapy. The median age at diagnosis was 52 years. The median clinical tumor size was 2 cm. Patients were considered at risk of an SNBM until the development of the first of distant metastases or contralateral breast cancer or death or, if alive and disease-free, until the last follow-up visit. The expected numbers of cancers were obtained from the SEER database, using the age-specific incidence for white women within 5-year age groups and 5-year calendar intervals. The median time at risk for an SNBM was 10.9 years (range 0.2-27.9). RESULTS: By 8 years of follow-up, 432 patients (23%) had developed distant metastases, 295 patients (16%) a local/regional recurrence, and 159 (8%) a contralateral primary. Of the 1884 patients in our cohort, 147 (8%) developed an SNBM compared with the 127.7 expected from SEER. This corresponds to an absolute excess of 1% of the study population and a relative increase of 15% greater than that expected from SEER (p = 0.05). Within the first 5 years, the observed and expected rates of SNBMs were identical (47 vs. 46.9). After 5 years, 24% more SNBMs were observed than expected (100 vs. 80.8, p = 0.02). Among patients <50 years old at breast cancer diagnosis, 43% more observed SNBMs occurred than expected (40 vs. 28, p = 0.02). For patients > or = 50 years, 7% more SNBMs were observed than expected (107 vs. 99.7, p = 0.25). Lung SNBMs were observed in 33 women, 52% more than the 21.67 predicted by SEER (p = 0.01). Most of the lung SNBMs occurred >5 years after treatment (n = 23) and in women who were >50 years at the time of their breast cancer diagnosis (n = 27). The observed incidence of ovarian cancer was significantly greater than expected among patients <50 years (7 vs. 1.96, p = 0.004) but was not different than expected for patients > or = 50 years (5 vs. 5.3, p = 0.61). Among the 7 sarcomas, 3 developed in the radiation field. CONCLUSIONS: SNBMs occur in a substantial minority (8%) of patients treated with conservative surgery and radiotherapy. However, the absolute excess risk compared with the general population is very small (1%). This excess risk is only evident after 5 years. In particular, a slightly increased incidence of lung SNBMs and a somewhat larger increase in ovarian cancer among younger patients was found. Our data suggest that preventive strategies to reduce the incidence of certain cancers (e.g., smoking cessation and prophylactic oophorectomy) and/or continued monitoring for SNBMs to increase the likelihood of early detection and treatment may be prudent in this population.