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 dis-ease, 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 associ-ated 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.(c) 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

PURPOSE:Randomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes. METHODS AND MATERIALS:Patients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50% < 60% and V100% < 35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with >6 months follow-up (FU). RESULTS:Of 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy. CONCLUSIONS:We report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.

In this population of pts with unresected nodal disease, boost RT to radiographically positive LN regions can be safely delivered with low rates of grade 3+ toxicity. The majority of failures were distant with no isolated LRFs. Failures were highest in the IMN/axSCV group (∼40%). Further treatment escalation is necessary for these pts.

Our ICVBT survey tool is designed to screen for "at-risk" patients, and provide a pathway for open dialogue between patients and physicians to potentially reduce undue harm during this important, yet sensitive treatment. To the best of our knowledge, this is the first such ICVBT survey tool to assess for a history of sexual trauma, and include SOGI and gender-inclusive questions. This adaptation has allowed our team to approach patients in a sensitive manner inclusive of their identity and prior experiences. Preliminary data is being collected and will be presented at the conference.

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.

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. (C) 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Extending the superior border of the breast tangent fields to include the low axilla is a technique employed to target the axillary lymph node (LN) without adding additional fields. This technique, commonly referred to as high tangents, is typically done in the supine position. The feasibility of delivering high tangents in the prone position has never been reported. Patients from 2012 to 2018 at a single institution who were prescribed treatment with high tangents using two tangentially opposed beams in the prone position were identified. The levels I–III axillary LNs were retrospectively contoured. The dose delivered to the LN, breast, and organs at risk was calculated using the original treatment plan. For LN, coverage was defined as > 90% of the prescribed dose. Forty-one patients treated with high tangents were identified. The median age was 62. Most patients underwent sentinel LN biopsy (88%), of which 59% had macroscopic disease and 30% had micrometastatic disease. Four patients had no axillary staging. Most patients (76%) were treated with hypofractionated radiation. The median distance from the superior border of the anterior oblique field to the humeral head was 0.6 cm (range: 0–1.5 cm). The mean coverage of the level I and level II axilla was 88.7% and 40.0% respectively. Axillary level I coverage for distance from the humeral head < 1 cm was 95.1%, whereas distance > 1 cm was 76.4% (p = 0.017). This series demonstrates the feasibility of high tangents in the prone position, offering good coverage of level I LN, particularly with < 1 cm distance from the humeral head.

Prone breast irradiation is a widely used technique to limit the dose to the heart and lungs. Yet, prone irradiation generally precludes inclusion of the axillary lymph nodes (LN). In this study we examine the feasibility of delivering high tangents with the patient in the prone position. Patients treated at a large academic center from 2012 to 2018 for whom the radiation oncologist prescribed high tangents and treated the patient in the prone position were identified. Any patient treated with a third field was excluded. The level I-III axillary LNs were retrospectively contoured using the RTOG breast contouring atlas. The dose delivered to the LN, breast, and organs at risk was calculated using the original treatment fields. For the LN, coverage was defined as >90% of the prescribed dose. Forty-one patients were identified who were treated with high tangents using two tangentially opposed beams in the prone position. The median patient age was 62; 46% of patients had left-sided breast cancer. Most patients had invasive ductal carcinoma (78%), T1 tumors (68%), intermediate grade (68%) and hormone receptor positive (90%), HER2 non-amplified disease (90%). Of the patients who underwent sentinel lymph node biopsy alone (n=37 with a median of 2.5 LN removed), 59% had macroscopic disease and 30% had micrometastatic disease. Four patients had no axillary staging. Thirty one patients (76%) were treated with a hypofractionated regimen. The median distance from the superior border of the tangent field to the humeral head was 0.6cm (range: 0-1.5cm). The mean coverage of the level I and level II axilla was 88.7% and 40.0% respectively. Axillary level I coverage for distance from the humeral head <1cm was 95.1%, whereas distance > 1cm was 76.4% (p=0.017). Axillary level II coverage for distance from the humeral head <1cm was 46.3%, whereas distance > 1cm was 27.6% (p=0.052). The average of the mean cardiac dose for all patients was 87cGy (123cGy for the left breast and 56cGy for right breast). The median ipsilateral lung V20 was 3.7%. The median maximum point dose was 109.4%. This series demonstrates the feasibility of high tangents in the prone position, offering good coverage of level I LN, particularly with <1cm distance from the humeral head, and partial coverage of level II LN. The mean cardiac dose and lung V20 is low for all patients.

Purpose: Hypofractionated whole-breast radiation therapy (RT) has proved to be equivalent to conventionally fractionated RT in multiple randomized trials. There is controversy regarding its use in younger women because of their underrepresentation in trials and the concern for late toxicity. We evaluated disease control and cosmetic outcomes in patients aged <50 years treated with hypofractionated RT in 4 prospective single-institutional trials. Methods and Materials: From 2003 to 2015, 1313 patients were enrolled in 4 prospective protocols investigating the use of adjuvant hypofractionated RT after breast-conserving surgery with a daily or weekly concomitant boost. We identified the records of 348 patients aged <50 years at consultation for this analysis. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method by study and across studies using meta-analytic methods. The late effects of RT, clinician-rated cosmesis, and patient-rated cosmesis were also evaluated. Results: With a median follow-up period of 66.9 months, the overall survival rate was 99.6%, the disease-free survival rate was 96.3%, and the local recurrence-free survival rate was 97.7% at 3 years. Clinician-rated cosmesis (n = 242) was excellent or good in 93.4% of cases and fair or poor in 6.6%. Patient-rated cosmesis (n = 259) was excellent or good in 86.1% and fair or poor in 13.9%. When patients rated themselves differently than their physicians, patients more often rated themselves poorly compared with their physicians (P = .0044, Cochran-Mantel-Haenszel test). Conclusions: At a median follow-up of 5 years, an analysis of patients aged <50 years demonstrated that hypofractionated RT was safe and effective, with good to excellent cosmesis as assessed by both clinicians and patients. (C) 2018 Elsevier Inc. All rights reserved.

Patients with early stage breast cancer or DCIS have excellent long-term prognosis after lumpectomy and adjuvant whole breast radiation. It is important to reduce radiation-related late cardiac morbidity and secondary lung cancer incidence from adjuvant breast irradiation. Two commonly used treatment techniques; deep inspiration breath hold (DIBH) and prone breast are compared with regard to dosimetry as well as estimated late cardiac morbidity and secondary lung cancer risks using published models. Thirty-four patients with left-sided DCIS or breast cancer who have undergone lumpectomy and required adjuvant whole breast irradiation were enrolled on a prospective trial comparing prone breast with supine DIBH planning (NCI-2017-00219). Patients underwent CT simulation in both positions, and two treatment plans were generated for each patient. Mean cardiac dose and ipsilateral lung doses were calculated. Absolute risk of death from ischemic heart disease (IHD) and risk of at least one acute coronary event (ACE) were estimated from published data by Darby, et al. [NEJM 2013] using individual patient's age and cardiac risk factors (as per tables S12 and S13). Risk of developing lung cancer based on ipsilateral lung dose was estimated from published data by Taylor, et al. [JCO 2017] (using excess rate ratio of 0.11/Gy and assuming baseline risk as per table S9) using individual patient's age and smoking history. The difference between radiation-related cardiac and lung cancer mortality between the supine DIBH and prone plans were compared using paired two-tailed T-test. Median age was 52 (range 38-75) for the entire cohort. Fourteen patients were smokers, and 22 patients possess at least one cardiac risk factor. Mean heart dose was 79.7 cGy and 76.5 cGy (p=0.37), and mean ipsilateral lung dose was 452.7 cGy and 45.2 cGy (p < 0.0001), for supine DIBH and prone plans, respectively. Estimated mean absolute risk of death from IHD by age 80 was 0.1% (range 0.0-0.2%) for both plans (p = 1.0). Estimated mean absolute risk of at least one radiation-related ACE by age 80 was 0.3% (range 0.1-0.6%) for both plans (p = 0.6). Estimated mean lung cancer risk by age 80 was 1.4% (range 0.5-15.4%) from supine DIBH plans and 1.0% (range 0.4-9.8%) from prone plans (p = 0.008). This result translates into an estimated excess lung cancer risk due to radiation by age 80 of 0.5% (range 0.1-6.0%) from supine DIBH plans and 0.0% (range 0.0-0.4%) from prone plans (p = 0.008). There was no observed difference in mean cardiac dose between supine DIBH and prone techniques, and a low absolute risk of both radiation-related ACE and risk of death from IHD. Whole breast radiation with prone technique results in lower ipsilateral lung dose compared to supine with DIBH. This lower lung dose translates into an absolute decrease of 0.5% in excess lung cancer risk for this cohort of patients receiving whole breast radiation based on published data.

Early stage breast cancer is highly curable; thus minimizing late cardiac morbidity and secondary malignancy is a critical aim of treatment strategies. This study compares heart and lung doses between radiation plans generated supine with deep inspiratory breath hold (S-DIBH) and prone with free-breathing (P-FB) and examines the effect of breast volume (BV) on these dosimetric parameters. Patients with left breast DCIS or invasive cancer who require whole breast irradiation after lumpectomy were enrolled on a single-institutional prospective protocol. Patients were simulated P-FB and S-DIBH; plans were generated using both scans. BV was measured on the P-FB scan. Wilcoxon Signed Rank Test and Wilcoxon Rank Sum Test were used to compare the within-patient differences (WPD) between plans (S-DIBH minus P-FB) for the entire cohort and within BV groups defined by tertiles. The primary endpoint was difference in mean heart dose (MHD). All tests were 2-sided with alpha of 0.05 and no adjustment for multiplicity. Forty patients were enrolled on the protocol. Thirty-four patients are included in the analysis due to patient withdrawal (n=3) or inability to hold their breath (n=3). Sixteen patients were treated to a whole breast dose of 4005cGy, 10 to 4050cGY, and 8 to 4256cGy. Statistical analyses revealed WPD were similar across the 3 doses. Average MHD was 80cGy in S-DIBH; lower by 3cGy in P-FB (p=0.08). Average mean ipsilateral lung dose (MLD) was 453cGy in S-DIBH; lower by 408cGy in P-FB (p<.0001). Average mean and max LAD dose was 251cGy and 551cGy in S-DIBH respectively; higher by 73cGy (p=0.1) and 442cGy in P-FB (p=0.3) respectively. Average hot spot and separation was 109% and 22cm in S-DIBH respectively; lower by 2% and 6cm in P-FB respectively (p<0.0001). For patients with the smallest BV, S-DIBH improved MHD and max and mean LAD doses whereas for those with the largest BV, P-FB had improved cardiac dosimetry. With increasing BV, there was an increasing advantage of P-FB for MHD (p=0.05), and max (p=0.03) and mean (p=0.02) LAD dose. Similarly, as BV increased, the reduction in MLD, hot spot, and separation with P-FB (vs. S-DIBH) increased (p<0.05) (table). While mean heart dose did not differ between the P-FB and S-DIBH, mean lung dose was significantly lower with P-FB. Increasing breast size was significantly associated with improved cardiac dosimetry and hot spot reduction with P-FB. Small-breasted women are more likely to benefit from S-DIBH compared to P-FB for cardiac sparing with less disadvantage in lung dose and hot spot, than larger breasted women. WPD (S-DIBH – P-FB) based on BV.Abstract TU_5_3368; Table 1Small BV <592.1 cc (n=11)Intermediate BV 592.1cc- 920.3 cc (n=11)Large BV >920.3 cc (n=12)P ValueMHD, cGy-5.8*1.213.40.05Mean LAD dose, cGy-174.4*-83.3*30.00.02Max LAD dose, cGy-1004.9*-573.3*193.50.03MLD, cGy357.4373.8484.20.04Hot Spot %.9120.01Max separation, cm4.65.27.20.02*A negative value indicates that the values for S-DIBH were lower than for P-FB. Open table in a new tab

BACKGROUND Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes. METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated. RESULTS We identified 2164 patients who met the eligibility criteria. The median follow-up for all patients was 3.73 [interquartile range (IQR) 2.27-6.07] years. Five-year OS was 97.7% (95%CI: 96.8%-98.6%) with 28 deaths; 5-year LRFS was 98.0% (97.2-98.8) with 31 IBTRs. We identified 37 patients with isolated IBTR, 19 (51.4%) as ductal carcinoma in situ and 18 (48.6%) as invasive disease, of whom 83.3% had an in situ component. Median time from initial diagnosis to IBTR was 1.97 (IQR: 1.03-3.5) years. Radiotherapy information was available for 30 of 37 patients. Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed. Twenty-five of thirty-two (78.1%) patients had concordant hormone receptor status, HER-2 receptor status, and estrogen receptor (ER) (P = 0.006) and progesterone receptor (PR) (P = 0.001) status from primary to IBTR were significantly associated. There were no observed changes in HER-2 status from primary to IBTR. The concordance between quadrant of primary to IBTR was 10/19 [(62.2%), P = 0.008]. Tumor size greater than 1.5 cm (HR = 0.44, 95%CI: 0.22-0.90, P = 0.02) and use of endocrine therapy upfront (HR = 0.36, 95%CI: 0.18-0.73, P = 0.004) decreased the risk of IBTR. CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Hypofractionated whole breast radiation (RT) has been shown to be equivalent to conventionally fractionated RT in multiple randomized trials. There is controversy regarding its use in younger women due to their underrepresentation in these trials and concern for late normal tissue toxicity. In this analysis, we evaluate the long term outcomes and clinician and patient reported cosmesis in women less than age 50 treated on 4 prospective single-institutional trials that utilized hypofractionated RT with a concomitant boost. From 2003-2015, 1303 patients were enrolled in 4 prospective protocols investigating the use of hypofractionated RT with either a daily (40.5 Gy/15 + 7.5 Gy/15 daily) or weekly (40.5 Gy/15 daily + 6 Gy/3) concomitant boost. All trials included breast cancer patients with stage I-II disease after segmental mastectomy. Three trials also included patients with DCIS. Patients < age 50 at consultation were included in this analysis. Overall survival (OS), Disease free survival (DFS), and Local recurrence free survival (LRFS) were estimated using the Kaplan Meier method. Patients with follow-up <6 months were excluded for cosmetic endpoints. Clinician rated cosmesis, recorded on a scale from 1-4 using a LENT SOMA instrument, was collected for each follow-up visit. Patient rated cosmesis using a uniform scale was recorded. There were 348 patients < 50 years old identified, with a median follow-up (FU) of 66 months. Median age was 45 (range 24-49) with a median of 2.5 months between surgery and RT. The majority of patients (76%) had invasive cancer of whom 87% were node negative, 31% had high grade disease, 87% were estrogen receptor positive, 82% were HER2 negative, 49% received adjuvant chemotherapy and 77% received hormonal therapy (HT). Of the DCIS patients, 38% were high grade and 36% received HT. The majority of patients were treated prone (96%); 70% with a daily concomitant boost and 30% with a weekly boost. OS was 98.8% at 5 years. Five year DFS was 94.5% and LRFS was 96.8%. Clinician rated global cosmesis (n = 236 patients, median FU 35 months) was 55% excellent, 37% good, 6% fair, and 1% poor. Rates of grade 2+ asymmetry were 8.5%, 3% for retraction, 6.4% telangiectasia, and 1.7% dimpling. Rates of grade 2+ edema, skin thickening, fibrosis and hyperpigmentation were all <1%. Patient rated cosmesis (n = 259, FU 39 months) was 29% excellent, 57% good, 11% fair, and 3% poor. There was no difference between patients < 40 (n = 46) compared to patients ≥40 in clinician rated cosmesis (mean 3.47 vs 3.5, P = 0.7) or patient reported cosmesis (3.05 vs 3.1, P = 0.5). In a large cohort of patients less than age 50 treated on prospective single-institutional trials, hypofractionated radiation is safe and effective, with good to excellent long-term cosmesis as assessed by both clinicians and patients.

Prone breast irradiation is a widely used technique to limit the dose to the heart and lungs. Yet, prone irradiation generally precludes inclusion of the axillary lymph nodes (LN). In this study we examine the feasibility of delivering high tangents with the patient in the prone position. Patients treated in a single institution from 2012 to 2016 for whom the radiation oncologist prescribed high tangents and treated the patient in the prone position were identified. Any patient treated with a third field was excluded. The levels I-III axillary LN were re-contoured using the RTOG breast contouring atlas. The dose delivered to the LN, breast, and organs at risk was calculated using the original treatment fields. For the LN, coverage was defined as >90% of the prescribed dose. Fifteen patients treated with high tangents using two tangentially opposed beams in the prone position were identified. The median patient age was 62; 53% of patients had left-sided breast cancer. Most patients had invasive ductal carcinoma (66%), T1 tumors (73%), intermediate grade (73%) and estrogen receptor (ER) positive (93%), HER2 negative disease (86%). Of the 15 patients, 11 underwent sentinel lymph node biopsy alone (with a median of 3 LN removed), 64% had macroscopic disease, 27% had microscopic disease. No patients had extranodal extension. Four patients had no axillary staging. Six patients (40%) received chemotherapy prior to radiation and 64% of patients with ER positive disease received endocrine therapy. Nine patients were treated with conventional fractionation and 6 with a hypofractionated regimen. The median distance from the superior border of the tangent field to the humeral head was 0.9cm (range: 0-1.5cm). The mean coverage of the level I and level II axilla was 80.6% and 31.4% respectively. Axillary level I coverage for distance from the humeral head <1cm was 94.7%, whereas distance > 1cm was 64.5% (p=0.006). Axillary level II coverage for distance from the humeral head <1cm was 42.1%, whereas distance > 1cm was 19.2% (p=0.11). Only 3 patients had any coverage of level III (mean 1.8%). The average mean cardiac dose was 92cGy (128.0cGy for the left breast and 50.8cGy for right breast). The median ipsilateral lung V20 was 2.9%. The median maximum point dose was 111.7%. This series represents the first report of delivering two tangential beams in the prone position intending to cover the breast and lower axillary nodes in the treatment field. This series demonstrates that this technique offers good coverage of level I LN, particularly with <1cm distance from the superior border of the tangents to the humeral head, and partial coverage of level II LN. The mean cardiac dose is low for all patients.

To compare acute toxicity of 3 weeks of prone whole breast accelerated intensity modulated radiation therapy (A-IMRT) with a daily boost versus once/week boost. Between 2009 and 2012, 398 patients with Stage 0-II breast cancer were prospectively enrolled into IRB-approved protocol 09-0030. All patients had undergone segmental mastectomy with negative margins of resection and invasive cancers had nodal assessment. Based on radiobiological estimates of equivalent tumor control, patients were randomly assigned to either Arm 1, 40.5 Gy to the index breast in 15 fractions at 2.7 Gy per fraction, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose at boost site = 48 Gy) or to Arm 2, 40.5 Gy to the index breast in 15 fractions at 2.7 Gy per fraction, with a weekly boost to the tumor bed of 2 Gy on the Friday of each week (total dose at boost site = 46.5 Gy). Patients were set up prone: only if lung or heart volume were in the field a supine set-up was attempted, and chosen if found to better spare these organs. Acute radiation toxicity observed during treatment or up to 60 days after treatment is reported by RTOG criteria. A total of 398 patients were enrolled, 200 in Arm 1, 198 in Arm 2. One patient was treated in the supine position in Arm 1, and 3 in arm 2. In Arm 1, 65% had stage I-II invasive breast cancer (9% with N1 disease) and 35% DCIS. In Arm 2, 77% had stage I-II invasive breast cancer (12% with N1 disease) and 23% DCIS. Baseline self-evaluation of cosmesis was the same in the 2 arms: 94% of patients report a good-excellent result, 6% report a fair result. Acute radiation toxicity is detailed in the Table. The percentage of patients with grade 2 or 3 wet desquamation was not significantly different in the daily arm compared to the weekly arm (6.5% vs. 3.5%, Fisher's exact test, p = 0.25, 2-sided). A tumor bed boost delivered either daily or weekly during prone A-IMRT to the breast results in comparable acute toxicity. Longer follow-up is needed to establish efficacy, late toxicity, and cosmetic results of each boost approach.Oral Scientific Abstract 208; TablePatients with One or More Radiation Related Acute Toxicities (Maximum Grade)Type of Acute Toxicity and Maximum GradeA-IMRT with Daily Boost (n = 200)A-IMRT with Weekly Boost (n = 198)Dry DesquamationGrade 13.0%5.6%Grade 2Grade 3EdemaGrade122.0%24.7%Grade 21.5%2.5%Grade 31.0%ErythemaGrade 179.5%79.2%Grade 25.5%6.1%Grade 3Wet DesquamationGrade 1Grade 26.5%2.5%Grade 31.0%Grade 2 or 36.5%3.5% Open table in a new tab

e11064 Background: We demonstrated in three prospective trials that taxane-based concurrent chemo-radiation achieves high pathological response rates that correlate with decreased recurrence rates and improved survival in locally advanced breast cancers (LABC, Adams et al, BCRT 2010). We now report the results among HER-2 positive LABC patients treated with trastuzumab and concurrent paclitaxel and radiotherapy, preoperatively. Methods: Patients with HER-2 positive LABC (stages IIB-IIIC) were prospectively treated as part of an IRB-approved neoadjuvant trastuzumab-paclitaxel-radiotherapy protocol. Paclitaxel was administered at a dose of 30 mg/m2 twice a week and trastuzumab was given weekly at a dose of 2 mg/kg (after initial loading with 4 mg/kg) for a total of 10 weeks. Radiotherapy was delivered to the breast and regional lymph nodes during weeks 2-7, daily, at 1.8 Gy per fraction to a total dose of 45 Gy. A 14 Gy boost (2 Gy per fraction) was added to the area of the originally palpable tumor site. Tumor response was assessed at definitive cancer surgery; defined as pathological complete response (pCR) in the absence of invasive cancer in breast and lymph nodes; pathological partial response (pPR) as the persistence of < 10 microscopic foci of invasive carcinoma in breast or lymph nodes. All other patients were classified as having achieved no pathologic response. Results: Twenty-one patients with HER-2 positive LABC were treated. The median age of the patients was 50 years (range 28-76). The most common toxicity was acute dermatitis; no grade IV toxicity was detected. Pathological response (pCR and pPR) after neoadjuvant trastuzumab/paclitaxel/radiation was achieved in 12 patients (57%, 95% CI: 37% - 76%). Responses were observed in 8/12 patients with hormone receptor (HR)-negative (7 pCR, 1 pPR) and in 4/9 patients with HR-positive cancers (3 pCR, 1 pPR). Conclusions: In HER-2 positive LABC, neoadjuvant trastuzumab during paclitaxel and concurrent radiotherapy resulted in a 57% pathological response rate, independently of HR status.

Moisture Meter D (Delfin Technologies, Kuopio, Finland) measures the dielectric constant of the underlying tissue. It has been shown to increase in association with the development of radiation-induced skin fibrosis in the breast. The purpose of this study is to objectively define the phenotype of post-radiation therapy breast fibrosis as measured by Moisture Meter D. Skin changes in the treated breast were compared to the untreated one for 73 breast radiation therapy patients on clinical trials at NYU between 2000 and 2009. Patients were assessed by clinical exam (classified by RTOG criteria) and Moisture Meter D assessment. Specifically, the dielectric constant measured by the Moisture Meter D quantifies skin water content. It increases with the increase of protein-bound water and decreases with increasing free water content in the measured tissue. Patients were categorized into one of two groups by two distinct observers based on clinical assessment of fibrosis: RTOG grade 0-1 fibrosis, or grade 2-3 fibrosis. Comparison of the dielectric constants of the treated breast and the untreated breast by 2-tailed paired t-test was conducted for each patient, with each patient being her own control. Additionally, comparison of the dielectric constant in the treated breast was compared between patients with Grade 0-1 fibrosis versus patients with Grade 2-3 fibrosis by 2-tailed non-paired t-test. The p values < 0.05 were considered significant. Median time from treatment to measurement was 3 years, (range, 0-7). Median radiation dose was 48 Gy, range, 30-48 Gy. A total of 58/73 (79.5%) patients were found to have RTOG grade 0-1 fibrosis, while 15/73 (20.5%) patients had RTOG grade 2-3 fibrosis. The average dielectric constant in the treated breast of patients with Grade 0-1 fibrosis was 37.4 (STD 13.5) versus 60.5 (STD 9.6) among patients with grade 2-3 fibrosis (p < 0.0005). Regardless of the fibrosis grade, the average dielectric constant in the untreated breast was the same (31.9, STD 9.2 and 32.1, STD 9.6 for Grade 0-1 and 2-3, respectively) (p = 0.95). There was a statistically significant difference in the dielectric constant in the treated versus untreated breast in both patients with Grade 0-1 fibrosis (p < 0.05) and patients with Grade 2-3 fibrosis (p < 0.00005). We confirm that the clinical phenotype of radiation-induced breast fibrosis is associated with a significant increase in dielectric constant measurement when compared to the untreated breast. Also, RTOG grade 2-3 fibrosis is associated with a significant increase in dielectric constant measurement when compared to Grade 0-1 fibrosis. Moisture Meter D permits a non-invasive, reliable and quantifiable assessment of the radiation-induced fibrosis phenotype.

Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials.

e13136 Background: Lipoic acid analogs are a novel class of anticancer agents that target the altered form of pyruvate dehydrogenase (PD) and possibly α-ketoglutarate dehydrogenase (KDH) causing a significant inhibition of mitochondrial energy metabolism selectively in tumor cells, leading to apoptosis. CPI-613 (C), a member of this novel class, has shown excellent toxicity and efficacy profiles in preclinical models. We initiated a phase I dose-escalation study utilizing the combination of (C) and gemcitabine (G) in patients with metastatic solid tumors. Methods: Patients were treated with (G) 1000 mg/m2 on days 1, 8, and 15 and (C) at escalating doses on days 1, 4, 8, 11, 15 and 18 of a 21-day cycle. Three cohorts of patients each with 3 patients received (C) at a dose of 21, 42, and 70 mg/m2 respectively. Intrapatient dose escalation was allowed and patients received from 1 to 5 cycles of treatment. Tumor types included breast, colon, and pancreas. Plasma concentrations of (C) were assayed using a validated Liquid Chromatography-Mass Spectroscopy method. Results: 9 patients have been treated to date and accrual is ongoing. No DLT has been seen through the first 3 cohorts. The only AE grade 3 or higher were hematologic and attributable to (G). MTD has not yet been reached. PK studies show that plasma (C) levels are appropriately dose-related and plasma half-life was approx 2-6 hours. Response assessments for 8 patients in the first 3 cohorts show 4 pts (tumor types breast and colon) with stable disease that ranged from 4 to 16 weeks in duration. PET imaging showed a reduction from 4-42% as well in FDG avidity. Conclusions: CPI-613 in combination with (G) appears to be well-tolerated with promising efficacy in patients with solid tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cornerstone Pharmaceuticals Cornerstone Pharmaceuticals Cornerstone Pharmaceuticals Cornerstone Pharmaceuticals