Faculty Bibliography

PURPOSE/OBJECTIVE: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/METHODS: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.

BACKGROUND:Hypofractionation has historically been underutilized among breast cancer patients with connective tissue diseases given a theoretical risk for increased toxicity and their overall underrepresentation in clinical trials that established hypofractionation as standard of care. We aim to compare the rates of toxicity in patients with autoimmune connective tissue diseases treated with conventionally fractioned radiation therapy (CF-RT) and hypofractionated RT (HF-RT) including accelerated partial breast irradiation. MATERIALS AND METHODS/METHODS:1,983 patients treated with breast conservation between 2012 and 2016 were reviewed for diagnosis of autoimmune disease. Univariate analysis using binary logistic regression was performed to evaluate the effect of disease and treatment variables on acute and late toxicity. Multivariate analyses using Cox regression models were used to evaluate the independent associations between covariates and the primary endpoints. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for reach risk group. RESULTS:92 patients with autoimmune disease were identified. Median follow-up was 59 months. 35% of patients received CF-RT and 65% of patients received hypofractionated RT (HF-RT), of which 70% received whole breast radiation (WBI) without regional nodal irradiation (RNI), 12% received WBI with RNI, and 18% received accelerated partial breast radiation. Patients who received CF-RT were significantly more likely to have AD symptoms (78% vs 37%, p<0.001), to be managed on DMARDs (41% vs 15%, p=0.013) and to have active autoimmune disease (84% vs 43%, p<0.001). On multivariate analysis, HF-RT was associated with a significantly decreased odds of acute and late grade 2/3 toxicity compared to CF-RT fractionation (acute: OR 0.200 95% CI 0.064-0.622, p=0.005; late: OR 0.127 95% CI 0.031 - 0.546, p=0.005). CONCLUSION/CONCLUSIONS:Hypofractionation including APBI is associated with less acute or late grade 2/3 toxicity in this population.

PURPOSE/OBJECTIVE:The omission of radiation therapy (RT) in elderly women with stage 1 estrogen-receptor positive (ER+) breast cancer receiving endocrine therapy (ET) is an acceptable strategy based on randomized trial data. Less is known about the omission of ET +/- RT. PATIENT AND METHODS/METHODS:We analyzed SEER-Medicare data for 13,321 women ≥ 66 years with stage I ER+ breast cancer from 2007-2012 who underwent breast conserving surgery. Patients were classified into 4 groups: 1) ET+RT (reference) 2) ET alone (ET), 3) RT alone (RT) and 4) neither RT nor ET (NT). Second breast cancer events (SBCE) were captured using Chubak's high-specificity algorithm. We used Chi-square tests for descriptive statistics, multivariable multinomial logistic regression to estimate relative risks (RR) of undergoing a treatment, and multivariable, propensity-weighted competing-risks survival regression to estimate standardized hazard ratio (SHR) of SBCE. We set significance at p≤0.01. RESULTS:Most women underwent both treatments, with 44% undergoing ET+RT, 41% RT, 6.6% ET, and 8.6% NT but practice patterns varied over time: from 2007-2012, RT decreased from 49% to 30%, whereas ET and ET+RT increased (ET: 5.4% to 9.6%; ET+RT: 38% to 51%). Compared to patients 66-69 years, patients 80-85 years were more likely to receive NT (OR=8.9), RT (OR=1.9), or ET (OR=8.8) vs. ET+RT (p<0.01).3% of subjects had an SBCE (2.2% ET+RT, 3.0% RT, 3.2% ET, 7.0% NT). Relative to ET+RT, NT and ET were associated with higher SBCE (NT: SHR 3.7, p<0.001; ET: SHR 2.2, p=0.008)), whereas RT was not associated with a higher SBCE (SHR 1.21, p=0.137). Clinical factors associated with higher SBCE were HER2 positivity and pT1c (SHR 1.7, p=0.006). CONCLUSIONS:Treatment with RT alone in older women with stage I ER+ disease is decreasing. RT alone is not associated with an increased risk for SBCE. By contrast, NT and ET are both associated with higher SBCE in multivariable analysis with propensity weighting. Further study of the omission of endocrine therapy in this patient population is warranted.

Accelerated partial breast irradiation (APBI) is increasingly used to treat select patients with early stage breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. This has led to controversy surrounding appropriate patients for APBI and an assessment of the toxicity and cosmetic outcomes of APBI as compared to whole breast irradiation (WBI). This paper reviews existing data for APBI, APBI delivery at our institution, and ongoing research to better define patient selection, treatment delivery, dosimetric considerations and toxicity outcomes.

PURPOSE/OBJECTIVE(S): The supraclavicular (SCV), medial axillary and internal mammary nodes (IMNs) are not typically resected in breast cancer patients (pts). The optimal local therapy of pts with nodal disease in these regions is not well-studied. We aim to evaluate outcomes of breast cancer patients with unresected nodal disease. MATERIALS/METHODS: We identified 79 pts at our institution from 2016- 2021 with unresected nodal disease in the axilla, SCV and/or IMNs defined as grossly enlarged nodes on CT, MRI or PET scan +/- biopsy confirmation. Pts were treated with breast/chest wall and regional nodal irradiation with an additional boost to the unresected nodal region. Distant failure (DF) and local-regional failure (LRF) were assessed. Kaplan-Meier was used to calculate disease-free survival (DFS), overall survival (OS) and local recurrence-free survival (LRFS). Logistic regression was used to identify variables associated with worse DFS. Acute and late toxicity of RT were evaluated.
RESULT(S): 33% of pts were treated with breast-conserving surgery, 65% with mastectomy and all had axillary surgery (81% ALND, 19% SLNB). 47% of pts received IMN boost (IMN), 40% axillary/SCV boost (axSCV) and 15% both IMN and axSCV boost (IMN/axSCV). Most had cT2-3 (72%), hormone receptor positive (75%), and HER-2 negative disease (84%). 57% of axSCV had cN3A disease; 84% of IMN and 83% of IMN/axSCV had cN3b disease. 7% of axSCV and 17% of IMN/axSCV had cN3c disease. Most pts received chemotherapy (97%). Median nodal boost dose was 10 Gy (range 10-20 Gy), with 17% axSCV, 22% IMN, and 17% IMN/axSCV receiving 14-20 Gy. Rates of acute and late grade 3 toxicity did not differ by boost location (acute: IMN: 20%, axSCV: 11% and IMN/axSCV 20%, P=0.559; late: IMN: 40%, axSCV: 25%, IMN/axSCV: 40%, P=0.630) nor by boost dose (10 Gy vs 14-20 Gy). There were no grade 4+ toxicities. With a median follow up of 30 months, the 3-year LRR, DFS, and OS was 94.5%, 86.3% and 93.8% respectively. Crude rates of failure for the entire group were 13.9% (10.1% DF; 3.8% DF+LRF). Rates of failure by boost group were axSCV: 13.3% (10% DF; 3.3% DF+LRF), IMN: 5.4% (2.7% DF, 2.7% DF+LRF), IMN/axSCV 41.7% (33.3% DF, 8.3% DF+LRF). There were no LRFs without DFs. Median time to failure was 23 months (IQR 18-34). On univariate analysis clinical tumor size (cT) and IMN/axSCV vs. IMN or axSCV alone was associated with worse DFS (HR: 9.78 95% CI 2.07-46.2, P=0.004 and HR: 9.49 95% CI 2.67-33.7, P=0.001). On multivariate analysis, cT approached significance (HR 6.15; 95% CI 0.95-39.8, P=0.05). IMN/axSCV vs. IMN or axSCV alone retained significance (HR 4.80; 95% CI 1.27-18.13, P=0.02). The difference between the axSCV vs. IMN group was not significant.
CONCLUSION(S): 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.
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PURPOSE/OBJECTIVE(S): Definitive radiation therapy (RT) is a curative treatment modality for gastric MALT. Reducing radiation dose to organs at risk (OAR) is imperative for patients with curative disease and excellent long-term prognosis. Advanced RT planning with DIBH and/or IMRT is available to improve the therapeutic ratio of RT by minimizing dose to normal tissues while maintaining adequate target coverage. We aimed to compare dosimetric parameters when using different radiation planning and delivery techniques in patients with gastric MALT. MATERIALS/METHODS: After institutional review board approval, we identified adult patients (age >= 18 years) with biopsy-proven gastric MALT who were treated at our institution from 2010 to 2020. Each patient underwent two simulation CT scans: free breathing (FB) and DIBH. Four plans were generated for each patient including DIBH-IMRT, DIBH-3DCRT, FB-IMRT, and FB-3DCRT with a prescribed dose of 30 Gy in 20 fractions. The CTV was defined as the entire stomach including the gastroesophageal junction to the pylorus. The PTV included a 1 to 1.5 cm expansion from the CTV. Paired t-tests were used to compare mean calculated dose values for each OAR based on treatment technique.
RESULT(S): Our cohort consisted of 8 patients (6 male, 2 female) with a median age 62.5 years (39 to 83 years). Compared to 3D-CRT, IMRT was associated with significantly decreased heart dose for both DIBH (Dmean 354.7 vs 440.5 cGY, P=0.029) and FB (Dmean 521.2 vs 699.6 cGY, P=0.006). IMRT was also associated with decreased dose to the left ventricle (LV), left anterior descending artery (LAD), liver, and lungs compared to 3D in both FB and DIBH. For IMRT plans, DIBH was associated with significantly lower heart V30 and V20 and a trend towards significance for lower heart Dmean (354.7 vs 521.2 cGY, P=0.059) in comparison to FB. For 3D plans, DIBH was associated with a lower heart V30 and V20, and a higher lung V20, V10, and V5 in comparison to FB.
CONCLUSION(S): Both IMRT and DIBH represent modalities for reducing heart dose in gastric MALT patients receiving definitive RT. IMRT also reduces LV, LAD, liver and lung dose regardless of technique used to account for respiratory motion whereas DIBH was not associated with reduced doses to the LAD, kidney, or liver.
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PURPOSE/OBJECTIVE(S): TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. MATERIALS/METHODS: Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% >= 90%, D98% >= 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant.
RESULT(S): Patients were treated to 12 Gy in 8 BID fractions (n=6) or 13.2 Gy in 8 BID fractions (n=3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2).
CONCLUSION(S): Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.
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PURPOSE/OBJECTIVE(S): The prognostic and treatment implications of isolated tumor cells (ypN0i+) and micrometastatic (ypN1mi) nodal disease after neoadjuvant chemotherapy (NACT) is not well-studied. These patients are excluded from the ongoing NSABP B-51 trial which only includes patients with macroscopic nodal disease after NACT. We evaluate the long-term outcomes and the role of post-mastectomy radiation therapy (PMRT) in breast cancer patients with ypN0i+ and ypN1mi disease after NACT and mastectomy (MX). MATERIALS/METHODS: Using the National Cancer Database (NC

BACKGROUND:Young women with ductal carcinoma in situ (DCIS) represent a unique cohort given considerations for future risk reduction and treatment effects on fertility and quality of life. We evaluated national patterns of care in the treatment of young women and the impact of those treatments on overall survival (OS). METHODS:Women younger than 50 years of age diagnosed with pure DCIS from 2004 to 2016 in the National Cancer Database (NCDB) were identified. Clinical, demographic, and choice of local therapy are summarized and trended over time. OS was analyzed using Cox proportional hazard models. RESULTS:A total of 52,150 women were identified, and the most common surgical treatment was breast-conservation surgery (BCS; 59%). Bilateral mastectomy (BM) increased in frequency from 2004 to 2016 (11-27%; p < 0.001). In women < 40 years of age, BM (39%) surpassed BCS (35%) in 2010 with a continued upward trend. On multivariable analysis, no OS benefit of BM (hazard ratio [HR] 0.99, p = 0.90) or unilateral mastectomy (UM; HR 0.98, p = 0.80) was observed when compared with BCS + radiation therapy (RT). Inferior OS was seen with BCS, Black race, estrogen receptor (ER)-negative, and tumor ≥ 2.5 cm (p ≤ 0.006). In ER+ patients, there was a significant difference in endocrine therapy (ET) use between BM (11%), UM (33%), and BCS (28%) compared with BCS + RT (64%, p < 0.001). CONCLUSION/CONCLUSIONS:The use of BM for DCIS is increasing in younger patients and now exceeds breast-conservation approaches in women < 40 years of age with no evidence of improved OS. Among ER+ patients, the rates of ET are lower in the BM, UM, and BCS-alone groups compared with BCS + RT.

BACKGROUND:) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians' recommendations for adjuvant RT. METHODS:The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. RESULTS:Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors. CONCLUSIONS:DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.