Faculty Publications

PURPOSE: To study the time spent with radiation-induced dermatitis during a course of radiation therapy for breast cancer in women treated with conventional or intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: The study population consisted of 804 consecutive women with early-stage breast cancer treated with breast-conserving surgery and radiation from 2001 to 2006. All patients were treated with whole-breast radiation followed by a boost to the tumor bed. Whole-breast radiation consisted of conventional wedged photon tangents (n = 405) earlier in the study period and mostly of photon IMRT (n = 399) in later years. All patients had acute dermatitis graded each week of treatment. RESULTS: The breakdown of the cases of maximum acute dermatitis by grade was as follows: 3%, Grade 0; 34%, Grade 1; 61%, Grade 2; and 2%, Grade 3. The breakdown of cases of maximum toxicity by technique was as follows: 48%, Grade 0/1, and 52%, Grade 2/3, for IMRT; and 25%, Grade 0/1, and 75%, Grade 2/3, for conventional radiation therapy (p < 0.0001). The IMRT patients spent 82% of weeks during treatment with Grade 0/1 dermatitis and 18% with Grade 2/3 dermatitis, compared with 29% and 71% of patients, respectively, treated with conventional radiation (p < 0.0001). Furthermore, the time spent with Grade 2/3 toxicity was decreased in IMRT patients with small (p = 0.0015), medium (p < 0.0001), and large (p < 0.0001) breasts. CONCLUSIONS: Breast IMRT is associated with a significant decrease both in the time spent during treatment with Grade 2/3 dermatitis and in the maximum severity of dermatitis compared with that associated with conventional radiation, regardless of breast size.

BACKGROUND: The results of radiation on the local control of triple receptor-negative breast cancer (negative estrogen [ER], progesterone [PR], and HER-2/neu receptors) was studied. METHODS: Conservative surgery and radiation were used in 753 patients with T1-T2 breast cancer. Three groups were defined by receptor status: Group 1: ER or PR (+); Group 2: ER and PR (-) but HER-2 (+); and Group 3: triple-negative (TN). Factors analyzed were age, menopausal status, race, stage, tumor size, lymph node status, presentation, grade, extensive in situ disease, margins, and systemic therapy. The primary endpoint was 5-year locoregional recurrence (LRR) isolated or total with distant metastases. RESULTS: ER- and PR-negative patients were statistically significantly more likely to be black, have T2 disease, have tumors detectable on both mammography and physical examination, have grade 3 tumors, and receive chemotherapy. There were no significant differences noted with regard to ER- and PR- patients by HER-2 status. There was a significant difference noted in rates of first distant metastases (3%, 12%, and 7% for Groups 1, 2, and 3, respectively; P = .009). However, the isolated 5-year LRR was not significantly different (2.3%, 4.6%, and 3.2%, respectively; P = .36) between the 3 groups. CONCLUSIONS: Patients with TN breast cancer do not appear to be at a significantly increased risk for isolated LRR at 5 years and therefore remain appropriate candidates for breast conservation. Cancer 2009;115:946-51. (c) 2009 American Cancer Society.

OBJECTIVES: Inflammatory breast cancer (IBC) is a clinical staging based on history and physical findings. Dermal lymphatic invasion (DLI) can occur with or without IBC. We examine how these independently affect outcome in women treated with postmastectomy radiation. METHODS: Four hundred thirty-two patients treated with postmastectomy radiation for invasive mammary cancer were assessed. Kaplan-Meier methodology was used to calculate rates of locoregional recurrence (LRR), distant metastases (DM) and overall survival (OS). Variables entered into univariate and multivariate analysis included T stage, IBC, DLI, estrogen receptor/progesterone receptor status, HER-2/neu status, N stage, extracapsular node extension (ECE), and use of chemotherapy (CT). Median follow-up is 58 months. RESULTS: For all 432 patients, the rate of LRR was 3% and DM 28%. Seven percent are alive with disease (AWD) and 26% are dead of disease (DOD). Thirty-one patients had IBC without DLI, 21 had DLI without IBC, and 18 had both IBC and DLI. For DLI 10% developed LRR, 45% DM, 7.5% are AWD and 50% are DOD. Of patients with IBC, 8% developed LRR, 44% DM, 8% are AWD and 48% DOD. DLI was the only significant independent predictor for LRR (HR 4.8, P < 0.05). Predictors of DM and OS were IBC, > or =4 positive nodes, and CT. CONCLUSIONS: DLI and IBC are independent predictors of poor outcome after postmastectomy radiation. DLI is associated with an increased risk for LRR, and IBC with worse rates of DM and OS. Patients with both features have worse outcome than those with either alone.

PURPOSE: To determine independent predictors of lymphedema (LE) after breast radiotherapy and to quantify added risks of LE from regional node irradiation (RNI). MATERIALS AND METHODS: A total of 2,579 women with T1-2, N 0-3, M0 breast cancer treated with breast conservation between 1970 and 2005 were studied. A total of 2,169 patients (84%) received radiation to the breast (B), 226 (8.8%) to the breast and supraclavicular LNs (B+SC), and 184 (7.1%) to the breast, supraclavicular LNs, and a posterior axillary boost (B+SC+PAB). Median follow-up was 81 months (range, 3-271). RESULTS: Eighteen percent of patients developed LE. LE risks were as follows: 16% (B), 23% (B+SC), and 31% (B+SC+PAB) (p < 0.0001). LE severity was greater in patients who had RNI (p = 0.0002). On multivariate analysis, RT field (p < 0.0001), obesity index (p = 0.0157), systemic therapy (p = 0.0013), and number of LNs dissected (p < 0.0001) independently predicted for LE. In N1 patients, the addition of a SC to tangents (p < 0.0001) and the addition of a PAB to tangents (p = 0.0017) conferred greater risks of LE, but adding a PAB to B+SC RT did not (p = 0.8002). In the N2 patients, adding a PAB increased the risk of LE 4.5-fold over B+SC RT (p = 0.0011). CONCLUSIONS: LE predictors included number of LNs dissected, RNI, obesity index, and systemic therapy. LE risk increased when a SC or PAB were added in the N1 subgroup. In the N2 patients, a PAB increased the risk over B+SC. The decision to boost the axilla must be weighed against the increased risk of LE that it imposes.

PURPOSE: Standard radiation for early breast cancer requires daily treatment for 6 to 7 weeks. This is an inconvenience to many women, and for some a barrier for breast conservation. We present the acute toxicity of a 4-week course of hypofractionated radiation. METHODS AND MATERIALS: A total of 75 patients completed radiation on a Phase II trial approved by the hospital institutional review board. Eligibility criteria were broad to include any patient normally eligible for standard radiation: age >/=18 years, invasive or in situ cancer, American Joint Committee on Cancer Stage 0 to II, breast-conserving surgery, and any systemic therapy not given concurrently. The median age was 52 years (range, 31-81 years). Of the patients, 15% had ductal carcinoma in situ, 67% T1, and 19% T2; 71% were N0, 17% N1, and 12% NX. Chemotherapy was given before radiation in 44%. Using photon intensity-modulated radiation therapy and incorporated electron beam boost, the whole breast received 45 Gy and the lumpectomy bed 56 Gy in 20 treatments over 4 weeks. RESULTS: The maximum acute skin toxicity by the end of treatment was Grade 0 in 9 patients (12%), Grade 1 in 49 (65%) and Grade 2 in 17 (23%). There was no Grade 3 or higher skin toxicity. After radiation, all Grade 2 toxicity had resolved by 6 weeks. Hematologic toxicity was Grade 0 in most patients except for Grade 1 neutropenia in 2 patients, and Grade 1 anemia in 11 patients. There were no significant differences in baseline vs. 6-week posttreatment patient-reported or physician-reported cosmetic scores. CONCLUSIONS: This 4-week course of postoperative radiation using intensity-modulated radiation therapy is feasible and is associated with acceptable acute skin toxicity and quality of life. Long-term follow-up data are needed. This radiation schedule may represent an alternative both to longer 6-week to 7-week standard whole-breast radiation and more radically shortened 1-week, partial-breast treatment schedules.

Locally advanced endometrial cancer comprises those patients considered at high risk for recurrence of disease and death from cancer, which include patients with pathologic stage III and IV endometrioid adenocarcinoma and patients with uterine papillary serous carcinoma regardless of stage. The management of locally advanced endometrial cancer patients remains an evolving issue. The primary treatment for these patients is surgical resection. Controversy exists over the optimal adjuvant treatment, particularly in patients whose disease is completely resected. This article addresses the role of adjuvant radiation therapy for these locally advanced high-risk endometrial cancer patients. In addition, this article reviews the current data and treatment approaches using radiation therapy in the management of these high-risk patients.

Objective: To determine the clinically observed incidence and severity of acute skin toxicity with breast intensity modulated radiation therapy (IMRT), and compare the results with a matched cohort of patients treated by conventional radiation therapy. Our hypothesis is that measures to decrease dose inhomogeneity within the breast and skin with IMRT will improve acute skin toxicity. Materials and Methods: The study population consists of 73 women with early stage breast cancer treated with breast-conserving surgery and IMRT. The IMRT technique involves an iteration method for optimization to generate the IMRT plan, Monte Carlo dose calculation, and a step-and-shoot technique using multileaf collimation for beam delivery. Other aspects of the technique including the clinical definition of the clinical target volume by the physician, patient positioning, tangential beam orientation, dose and field sizes were unchanged compared conventional tangential radiation. These patients were matched one-to-one to a control group of 60 women treated with conventional photon radiation by using their bra size and chest wall separation. The study end point was acute skin toxicity. Results: There were no observed differences in the acute toxicity based upon common terminology criteria for adverse events (CTC) for acute radiation dermatitis. There was no desquamation in 42% of IMRT patients, dry desquamation in 37% and moist desquamation in 21%. The degree of desquamation was greater for conventional patients compared with IMRT patients -52% grade 0, 10% grade 1, and 38% grade 2 (P = 0.001). Subgroup analysis showed desquamation was significantly lower with IMRT for small (P = 0.038) and large breast sizes (P = 0.037), but not medium sizes (P = 0.454). For large breast sizes, the incidence of moist desquamation grade 2 was 48% with IMRT compared with 79% in controls. Significant predictors of moist desquamation on stepwise logistic regression were use of IMRT (P = 0.0011) and breast size (P < 0.0001). Conclusions: IMRT is associated with a decrease in severity of acute desquamation compared with a matched control group treated with conventional radiation therapy. As with conventional radiation, breast size remains the most important prognostic factor for acute skin toxicity. The CTC grading system for acute radiation dermatitis is not sensitive when applied to modem breast cancer treatment because of its dependence of subjective rating of erythema and inability to gauge variations in desquamation. Further study of patient symptoms, quality of life, and cosmesis is needed to evaluate the benefit of IMRT for breast cancer.