Reshma Jagsi

Development and Validation of a Heart Atlas to Study Cardiac Exposure to Radiation Following Treatment for Breast Cancer

PURPOSE Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. METHODS AND MATERIALS A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. RESULTS The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. CONCLUSIONS This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.

Surgeon recommendations and receipt of mastectomy for treatment of breast cancer

CONTEXT There is concern that mastectomy is overused in the United States. OBJECTIVES To evaluate the association of patient-reported initial recommendations by surgeons and those given when a second opinion was sought with receipt of initial mastectomy; and to assess the use of mastectomy after attempted breast-conserving surgery (BCS). DESIGN, SETTING, AND PATIENTS A survey of women aged 20 to 79 years with intraductal or stage I and II breast cancer diagnosed between June 2005 and February 2007 and reported to the National Cancer Institutes Surveillance, Epidemiology, and End Results registries for the metropolitan areas of Los Angeles, California, and Detroit, Michigan. Patients were identified using rapid case ascertainment, and Latinas and blacks were oversampled. Of 3133 patients sent surveys, 2290 responded (73.1%). A mailed survey was completed by 96.5% of respondents and 3.5% completed a telephone survey. The final sample included 1984 female patients (502 Latinas, 529 blacks, and 953 non-Hispanic white or other). MAIN OUTCOME MEASURES The rate of initial mastectomy and the perceived reason for its use (surgeon recommendation, patient driven, medical contraindication) and the rate of mastectomy after attempted BCS. RESULTS Of the 1984 patients, 1468 had BCS as an initial surgical therapy (75.4%) and 460 had initial mastectomy, including 13.4% following surgeon recommendation and 8.8% based on patient preference. Approximately 20% of patients (n = 378) sought a second opinion; this was more common for those patients advised by their initial surgeon to undergo mastectomy (33.4%) than for those advised to have BCS (15.6%) or for those not receiving a recommendation for one procedure over another (21.2%) (P < .001). Discordance in treatment recommendations between surgeons occurred in 12.1% (n = 43) of second opinions and did not differ on the basis of patient race/ethnicity, education, or geographic site. Among the 1459 women for whom BCS was attempted, additional surgery was required in 37.9% of patients, including 358 with reexcision (26.0%) and 167 with mastectomy (11.9%). Mastectomy was most common in patients with stage II cancer (P < .001). CONCLUSION Breast-conserving surgery was recommended by surgeons and attempted in the majority of patients evaluated, with surgeon recommendation, patient decision, and failure of BCS all contributing to the mastectomy rate.

Unacceptable Cosmesis in a Protocol Investigating Intensity-Modulated Radiotherapy With Active Breathing Control for Accelerated Partial-Breast Irradiation

PURPOSE To report interim cosmetic results and toxicity from a prospective study evaluating accelerated partial-breast irradiation (APBI) administered using a highly conformal external beam approach. METHODS AND MATERIALS We enrolled breast cancer patients in an institutional review board-approved prospective study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep-inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice daily. Dosimetric parameters in patients who maintained acceptable cosmesis were compared with those in patients developing unacceptable cosmesis in follow-up, using t-tests. RESULTS Thirty-four patients were enrolled; 2 were excluded from analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years, new unacceptable cosmesis developed in 7 patients, leading to early study closure. We compared patients with new unacceptable cosmesis with those with consistently acceptable cosmesis. Retrospective analysis demonstrated that all but one plan adhered to the dosimetric requirements of the national APBI trial. The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50) was lower in patients with acceptable cosmesis than in those with unacceptable cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference volume receiving 38.5 Gy (V100) was also lower in patients with acceptable cosmesis (15.5% vs. 23.0%; p = 0.02). CONCLUSIONS The hypofractionated schedule and parameters commonly used for external beam APBI and prescribed by the ongoing national trial may be suboptimal, at least when highly conformal techniques such as IMRT with management of breathing motion are used. The V50 and V100 of the breast reference volume seem correlated with cosmetic outcome, and stricter limits may be appropriate in this setting.

Current perceptions regarding surgical margin status after breast-conserving therapy: results of a survey.

Objective:The surgical margin status after breast-conserving surgery is considered the strongest predictor for local failure. The purpose of this study is to survey how radiation oncologists in North America (NA) and Europe define negative or close surgical margins after lumpectomy and to determine the factors that govern the decision to recommend reexcision based on the margins status. Methods:A questionnaire was sent to active members of the European Society of Therapeutic Radiation Oncology and the American Society for Therapeutic Radiology and Oncology who had completed training in radiation oncology. Respondents were asked whether they would characterize margins to be negative or close for a variety of scenarios. A second survey was sent to 500 randomly selected radiation oncologists in the United States to assess when a reexcision would be recommended based on surgical margins. Results:A total of 702 responses were obtained from NA and 431 from Europe to the initial survey. An additional 130 responses were obtained from the United States to the second survey regarding reexcision recommendations. Nearly 46% of the North American respondents required only that there be “no tumor cells on the ink” to deem a margin negative (National Surgical Adjuvant Breast and Bowel Project definition). A total of 7.4% and 21.8% required no tumor cells seen at <1 mm and <2 mm, respectively. The corresponding numbers from European respondents were 27.6%, 11.2%, and 8.8%, respectively (P <0.001). Europeans more frequently required a larger distance (>5 mm) between tumor cells and the inked edges before considering a margin to be negative. Conclusion:This study revealed significant variation in the perception of negative and close margins among radiation oncologists in NA and Europe. Given these findings, a universal definition of negative margins and consistent recommendations for reexcision are needed.

Radiation Field Design in the ACOSOG Z0011 (Alliance) Trial

PURPOSE ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. METHODS We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. RESULTS Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. CONCLUSION Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

Underascertainment of radiotherapy receipt in Surveillance, Epidemiology, and End Results registry data.

Surveillance, Epidemiology, and End Results (SEER) registry data have been used to suggest underuse and disparities in receipt of radiotherapy. Prior studies have cautioned that SEER may underascertain radiotherapy but lacked adequate representation to assess whether underascertainment varies by geography or patient sociodemographic characteristics. The authors sought to determine rates and correlates of underascertainment of radiotherapy in recent SEER data.

Adoption of intensity-modulated radiation therapy for breast cancer in the United States

BACKGROUND Although intensity modulation of the radiation beam has been shown to lower toxic effects for patients receiving whole-breast irradiation, relatively simple techniques may suffice. It is thus controversial whether such treatment justifies billing for intensity-modulated radiation therapy (IMRT). METHODS We used the claims data to determine billing for IMRT from Surveillance, Epidemiology, and End Results-Medicare records from 2001 to 2005 for 26,163 women aged 66 years or older with nonmetastatic breast cancer treated with surgery and radiotherapy. The impact of individual covariates (demographic, health services, tumor, and treatment factors) on cost of treatment was assessed using the Wilcoxon two-sample test. Two-sided multivariable logistic regression was used to identify predictors for IMRT use. Cost of radiation was calculated in 2005 dollars. All statistical tests were two-sided. RESULTS The number of patients with IMRT billing claims increased from 0.9% (49 of 5196) of patients diagnosed in 2001 to 11.2% (564 of 5020) in 2005. In multivariable analysis, IMRT billing was more likely for patients with left-sided tumors (odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.16 to 1.45), for those residing in a health service area with high radiation oncologist density (OR = 2.32, 95% CI = 1.47 to 3.68), for those treated at freestanding radiation centers (OR = 1.36, 95% CI = 1.20 to 1.53), or for those residing in regions where the Medicare intermediary allowed breast IMRT (OR = 10.87, 95% CI = 9.26 to 12.76, all P < .001). The mean cost of radiation was

Gender differences in the salaries of physician researchers

7179 without IMRT and

Gender differences in time spent on parenting and domestic responsibilities by high-achieving young physician-researchers

15 230 with IMRT. IMRT adoption contributed to an increase in the mean cost of breast radiation from

Asia's Ascent — Global Trends in Biomedical R&D Expenditures

6334 in 2001 to