Definitive Radiation With Nodal Boost for Patients With Locally Advanced Breast Cancer.

PURPOSE: The optimal local therapy of patients with nodal disease in supraclavicular (SCV), internal mammary nodes (IMN) and level III axilla is not well studied. We aimed to evaluate the outcomes of patients with breast cancer and advanced nodal disease that received a nodal boost. METHODS AND MATERIALS: This retrospective study included 79 patients with advanced nodal disease who underwent adjuvant radiation with a nodal boost to the SCV, IMNs, and/or axilla. All patients had radiographic changes after systemic therapy concerning for gross nodal disease. Overall survival, disease-free survival (DFS), and local recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS: All patients received an initial 50 Gy to the breast/chest wall and regional nodes, of whom 46.8% received an IMN boost, 38.0% axillary (ax)/SCV boost, and 15.2% both IMN and ax/SCV boost (IMN + ax/SCV). Most patients had hormone receptor positive (74.7%) and human epidermal growth factor receptor 2 negative disease (83.5%). In addition, 12.7% of patients had clinical (c) N2 disease, 21.5% cN3A disease, 51.9% cN3B disease, and 5.1% cN3C disease. Most patients received chemotherapy (97.5%). The median nodal boost dose was 10 Gy (range, 10-20 Gy), with 21.6% of IMN, 16.7% of ax/SCV, and 16.7% of IMN + ax/SCV receiving 14 to 20 Gy. With a median follow up of 30 months, the 3-year local recurrence-free survival, DFS, and overall survival rates were 94.5%, 86.3%, and 93.8%, respectively. Crude rates of failure were 13.9% (10.1% distant failure [DF] alone; 3.8% DF + locoregional failure [LRF]). Rates of failure by boost group were 13.3% for ax/SCV (10.0% DF alone; 3.3% DF + LRF), 5.4% for IMN (2.7% DF alone, 2.7% DF + LRF), and 41.7% for IMN + ax/SCV (33.3% DF, 8.3% DF + LRF). There were no LRFs without DFs. The median time to failure was 22.8 months (interquartile range, 18-34 months). Clinical tumor size and IMN + ax/SCV versus IMN or ax/SCV alone was associated with worse DFS (hazard ratio [HR]: 9.78; 95% confidence interval [CI], 2.07-46.2; P = .004 and HR: 9.49; 95% CI, 2.67-33.7; P = .001, respectively). On multivariate analysis, IMN + ax/SCV versus IMN or ax/SCV alone retained significance (HR: 4.80; 95% CI, 1.27-18.13; P = .02). CONCLUSIONS: In this population of patients with locally advanced breast cancer, the majority of failures were distant with no isolated LRFs. Failures were the highest in the IMN + ax/SCV group (∼40%). Further treatment escalation is necessary for these patients.

A Prospective Trial to Compare Deep Inspiratory Breath Hold With Prone Breast Irradiation.

PURPOSE: To compare heart and lung doses for adjuvant whole breast irradiation (WBI) between radiation plans generated supine with deep inspiratory breath hold (S-DIBH) and prone with free-breathing (P-FB) and examine the effect of breast volume (BV) on dosimetric parameters. METHODS AND MATERIALS: Patients with left breast ductal carcinoma in situ or invasive cancer receiving adjuvant WBI were enrolled on a single-institutional prospective protocol. Patients were simulated S-DIBH and P-FB; plans were generated using both scans. Wilcoxon signed-rank and rank-sum tests were used to compare intrapatient differences between plans for the entire cohort and within BV groups defined by tertiles. RESULTS: Forty patients were enrolled. Thirty-four patients are included in the analysis owing to patient withdrawal or inability to hold breath. With WBI dose of 4005 to 4256 cGy, mean heart dose (MHD) was 80 cGy in S-DIBH and 77 cGy in P-FB (P = .08). Mean ipsilateral lung dose (MLD) was 453 cGy in S-DIBH and 45 cGy in P-FB (P < .0001). Mean and max left anterior descending artery doses were 251 cGy and 551 cGy in S-DIBH, respectively (P = .1), and 324 cGy and 993 cGy in P-FB, respectively (P = .3). Hot spot and separation were 109% and 22 cm in S-DIBH, respectively, and 107% and 16 cm in P-FB, respectively (P < .0001). For patients with smallest BV, S-DIBH improved MHD and left anterior descending artery doses; for those with largest BV, P-FB improved cardiac dosimetry. With increasing BV, there was an increasing advantage of P-FB for MHD (P = .05), and max (P = .03) and mean (P = .02) left anterior descending artery doses, and the reduction in MLD, hot spot, and separation with P-FB increased (P < .05). CONCLUSIONS: MHD did not differ between P-FB and S-DIBH, whereas MLD was significantly lower with P-FB. Analysis according to breast volume revealed improved cardiac dosimetry with S-DIBH for women with smallest BV and improved cardiac dosimetry with P-FB for women with larger BV, thereby providing a dosimetric rationale for using breast size to help determine the optimal positioning for WBI.

Radiation effect on late cardiopulmonary toxicity: An analysis comparing supine DIBH versus prone techniques for breast treatment.

Two commonly used whole breast irradiation (WBI) techniques, deep inspiration breath hold (DIBH) and prone positioning, are compared with regard to dosimetry and estimated late cardiac morbidity and secondary lung cancer mortality using published models. Forty patients with left-sided DCIS or breast cancer who underwent lumpectomy and required adjuvant WBI were enrolled on a prospective trial comparing supine DIBH (S-DIBH) with prone free breathing (P-FB) planning. Patients underwent CT simulation in both positions; two plans were generated for each patient. Comparative dosimetry was available for 34 patients. Mean cardiac and lung doses were calculated. Risk of death from ischemic heart disease (IHD), risk of at least one acute coronary event (ACE), and lung cancer mortality were estimated from published data. Difference between S-DIBH and P-FB plans was compared using paired two-tailed t test. Estimated mean risk of death from IHD by age 80 was 0.1% (range 0.0%-0.2%) for both plans (P = 1.0). Mean risk of at least one ACE was 0.3% (range 0.1%-0.6%) for both plans (P = .6). Mean lung cancer mortality risk was 1.4% (range 0.5%-15.4%) for S-DIBH and 1.0% (range 0.4%-9.8%) for P-FB (P = .008). Excess lung cancer mortality due to radiation was 0.5% (range 0.1%-6.0%) with S-DIBH and 0.0% (range 0.0%-0.4%) with P-FB (P = .008). Both S-DIBH and P-FB provide excellent cardiac sparing. Prone positioning results in lower lung dose than S-DIBH and leads to an absolute decrease of 0.5% in excess lung cancer mortality for patients receiving WBI.

Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the era of highly active antiretroviral therapy.

INTRODUCTION: The incidence of invasive anal squamous-cell carcinoma in patients with HIV is increasing. We report the outcome after combined chemoradiotherapy for anal squamous-cell carcinoma in HIV-infected individuals. METHODS: Thirty-two HIV-positive patients treated at the St. Vincent's Cancer Care Center for anal squamous-cell carcinoma from 1997 through mid 2005 were reviewed retrospectively. All patients also received highly active antiretroviral therapy. Treatment consisted of radiotherapy concurrent with 5-fluorouracil and mitomycin C in most patients. Overall survival, anal cancer-specific survival, local recurrence, and toxicity were assessed. RESULTS: Median time from completion of radiotherapy to last follow-up of surviving patients was 35 months. Five-year locoregional relapse, anal cancer-specific survival, and overall survival were 16 , 75, and 65 percent, respectively. In multivariate analysis, locoregional recurrence, cancer-specific survival, and overall survival were all significantly associated with tumor size. Overall survival was independently associated with high viral load and low CD4 count. Acute toxicity included: Grade 3 skin in 25 percent of patients, Grade 3 diarrhea: 28 percent, and Grade 3 or 4 hematologic toxicity in 21 and 48 percent, respectively. More than two-thirds of patients required radiotherapy interruption. There was no negative impact of chemoradiotherapy on viral load. CONCLUSIONS: Outcome after chemoradiotherapy for HIV-related anal squamous-cell carcinoma in the era of highly active antiretroviral therapy is comparable to outcome in patients without HIV. However, significant toxicity is seen with standard treatment regimens. Earlier diagnosis and risk-adapted therapy could lead to improved survival and decreased treatment-related morbidity.