Faculty Bibliography

PURPOSE/OBJECTIVE(S)/OBJECTIVE:Radiation therapy (RT) positioning and planning are vital to minimizing toxicity in patients with synchronous bilateral breast cancer (SBBC). We studied clinical outcomes and setup reproducibility in SBBC patients treated in the prone position. MATERIALS/METHODS/METHODS:This retrospective study analyzed SBBC patients treated prone between 2012-2022. Demographics, clinical RT dose/field, dosimetry, on-treatment imaging, toxicity, and outcomes data were collected. RT delivery was standardized, with left breast treated first. After 2014, radiochromic (GaF) films were placed fractions 1-5 to evaluate field overlap, prompting re-simulation or re-planning if consistent overlap was detected. Positional shifts during setup were collected for bilateral whole breast irradiation (WBI) and partial breast irradiation (PBI). RESULTS:45 patients were included. Median age was 67 years old and median follow-up was 64 months. 35, 5, and 5 patients received bilateral WBI (1 with low axilla), bilateral PBI, a combination of WBI and PBI, respectively. The most common WBI dose was 40.5 Gy, with a simultaneous tumor bed boost to 48 Gy. PBI patients received 30 Gy in 5 fractions (n=4) or 40.05 Gy in 15 fractions (n=1). All patients who developed grade 2 (17.7%) and grade 3 (2%) dermatitis received bilateral WBI except for 1. 6 patients had acute dermatitis in the sternal area with overlap on GaF seen in 2 patients. Of 20 patients with late toxicity follow-up, 25% had late grade 1-2 dermatitis (20% received WBI). One patient recurred locally and distantly. Mean positional shifts were mostly sub-centimeter or sub-degree. Only 10% of patients had field overlap on GaF. CONCLUSION/CONCLUSIONS:To our knowledge, this is the first study examining patients treated for SBBC in the prone position. Prone bilateral RT is feasible with minimal shifts and overlap. However, higher rates of acute dermatitis occurred in bilateral WBI patients (vs. PBI), and overlap wasn't seen on GaF in all patients who developed midline dermatitis.

PURPOSE/OBJECTIVE:Intensity-modulated radiation therapy (IMRT) is increasingly used for total body irradiation (TBI) due to its ability to deliver myeloablative doses while sparing radiosensitive organs. To enable consistent evaluation in future National Clinical Trials Network (NCTN) studies, the xxx Hematologic Malignancies Working Group (HMWG) convened IMRT-TBI experts and NCTN leaders to develop consensus recommendations for standardized multi-institutional implementation. METHODS:A 47-question survey was distributed to NRG institutions utilizing IMRT-TBI to characterize current planning and delivery practices. Responses were analyzed for commonalities and variations. A multidisciplinary working group reviewed survey findings, developed consensus-based technical and clinical recommendations, and created a standardized template for IMRT-TBI integration into NCTN protocols. Topics included simulation, contouring, planning, organ-at-risk (OAR) constraints, quality assurance (QA), image-guided radiotherapy (IGRT), commissioning, credentialing, and safeguards for clinical trial conduct. RESULTS:Eight institutions with collective experience treating more than 750 patients with IMRT-TBI responded. Most centers used VMAT to the upper body with anteroposterior/posteroanterior (AP/PA) fields to the lower body, 3-9 isocenters, lower dose rates for lung fields (100-200 MU/min), and no physical bolus. Common OAR constraints included lungs mean dose <8 Gy, kidneys mean dose <6-8 Gy, and lenses maximum dose <90% of prescription. All respondents used auto-segmentation; 50% used auto-planning. QA practices varied, but patient-specific QA passing rates were high (>95% with 3%/2 mm gamma). Consensus recommendations for clinical trial use were established, including standardized PTV definitions, OAR sparing goals, dosimetric constraints, QA requirements, and credentialing processes. CONCLUSIONS:IMRT-TBI offers the potential for reduced toxicity and improved dose precision compared with 2D-TBI, but its complexity requires careful standardization in multi-institutional trials. The xxx HMWG and collaborating NCTN experts developed the consensus-based technical and clinical framework for incorporating IMRT-TBI into cooperative group protocols. Adoption of these recommendations will facilitate consistent implementation and enable rigorous evaluation of outcomes.

PURPOSE/OBJECTIVE:In patients with breast cancer, prone radiation therapy (RT) has been shown to reduce heart and lung dose. Though prone positioning is routinely used for whole breast RT, its use when treating the regional lymph nodes is not widespread. METHODS AND MATERIALS/METHODS:In this phase 1/2 trial for stage IB-IIA breast cancer treated with lumpectomy or mastectomy, patients received 40.5 Gy in 15 fractions to the breast or chest wall and regional lymph nodes with an integrated tumor bed boost for lumpectomy patients. Primary endpoints were grade >2 acute toxicity and dosimetric feasibility. Secondary endpoints were the incidence of resimulation to improve dosimetry and late toxicity. Exploratory endpoints were local recurrence, disease-free survival, distant recurrence-free survival, and overall survival. RESULTS:From 2009 to 2016, 97 patients were enrolled (68% lumpectomy and 32% mastectomy), among which 92 were treated in the prone position. Five patients were resimulated and treated supine. Among the prone-treated patients, there were no acute toxicities greater than grade 2. A total of 92%, 98%, and 89% met a planning target volume tumor V48 Gy ≥98%, breast V40.5 Gy ≥95%, and nodal V38.5 Gy ≥95%, respectively. All met the heart V5 Gy <5%, contralateral lung V5 Gy <15%, spinal cord dose maximum (Dmax) ≤37.5 Gy, esophagus V30 Gy <50%, and Dmax ≤40.5 Gy. Ninety-eight percent met the ipsilateral lung V10 Gy. Brachial plexus Dmax <42 Gy was met in 74% with a mean increase of 1.61 Gy (SD, 1.96 Gy) over the target. At a median follow-up of 8 years, grade 2 to 3 late toxicity was 23% for prone patients. There were 2 local recurrences (2%) and no chest wall or nodal recurrences. The 8-year distant recurrence-free survival, disease-free survival, and overall survival were 88% (95% CI, 81%-95%), 86% (95% CI, 78%-95%), and 91% (95% CI, 84%-98%), respectively. CONCLUSIONS:Toxicity was low, and outcomes were excellent in this prospective trial of prone hypofractionated nodal RT.

We compiled a sampling of the treatment techniques of intensity-modulated total body irradiation, total marrow irradiation and total marrow and lymphoid irradiation utilized by several centers across North America and Europe. This manuscript does not serve as a consensus guideline, but rather is meant to serve as a convenient reference for centers that are considering starting an intensity-modulated program.

PURPOSE/OBJECTIVE:Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS/METHODS:We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS:A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS:Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

PURPOSE/OBJECTIVE: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/METHODS: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.

Purpose/Objective(s): Radiation dermatitis (RD) is common after RT for breast cancer with data indicating potentially worse RD in African American (AA) patients (pts). Current measures of RD, such as the CTCAE, do not include hyperpigmentation, which may disproportionately affect how RD is classified and treated in pts with skin of color (SOC). We aim to characterize RD in SOC and identify factors, including baseline skin pigmentation (BSP) that predict RD. Materials/Methods: Pts treated with whole breast (WB) or chest wall (CW) with regional nodal RT or high tangents with 50 Gy in 25 fractions from 2015-2018 were identified. Three dermatologists independently classified BSP using photographs from CT simulation based on the Fitzpatrick scale ([FS], range=I-VI; I=light/pale white to VI=black/ very dark brown). SOC was defined as FS IV-VI. Pt characteristics were investigated for association with interventions to treat RD, clinician-graded acute RD, and late skin toxicity (NCI CTCAE scale) with Chi-squared and logistic regression analyses.
Result(s): 325 pts met eligibility criteria (58 African American [AA], 42 Asian, 151 Caucasian, 77 other). 40% (n=129) had SOC, 60% underwent CW RT, 40% WB RT and 82% had systemic therapy. Pts with SOC were more likely to be Hispanic (14% vs 8% p=0.007), AA (43% vs 1%, p<0.001) and have greater mean BMI (28.0 vs 26.5, p=0.02). Acute grade 2/3 RD was lower in SOC (FS I 60%, FS II 63%, FS III 52%, FS IV 64%, FS V 40%, FS VI 41%; p=0.049). Increased BSP (OR 0.83; p=0.01) and AA pts (OR: 0.22; p<0.001) had lower odds of acute grade 2/3 RD, whereas bolus and dosimetric parameters such as increased PTV volume had increased odds. On multivariable analysis (MVA), AA pts and bolus remained significant (OR: 0.14, p=0.01; OR: 6.63 p<0.001, respectively). Topical steroid use to treat RD was less frequent and oral analgesic use was more frequent in SOC (43% vs 63%, p<0.001; 50% vs 38%, p=0.05, respectively). Pts with increased BSP (OR 0.73, p<0.001), AA race (OR 0.19, p<0.001) and greater BMI had lower use of topical interventions whereas any boost phase, bolus, IMN RT and increased PTV volume had greater use. On MVA, AA pts (OR 0.27, p=0.04), boost (OR 2.04, p=0.033), IMN RT (OR 2.73, p=0.003) and PTV V105% (OR=1.002, p=0.03) retained significance. Late grade 2/3 hyperpigmentation was greater in SOC (16% vs 3%, p=0.01). Increased BSP (OR 2.14, p=0.001), AA pts (OR 8.18, p=0.02), bolus and CW boost had greater odds of grade 2/3 hyperpigmentation. On MVA, increased BSP (OR: 3.76, p=0.03) and bolus (OR: 14.1, p=0.01) retained significance.
Conclusion(s): We found less clinician-graded acute RD in SOC and AA pts, less frequent use of topical interventions but more oral analgesic use. We also found higher rates of late pigmentation change with increased BSP independent of race. These findings suggest that RD may be under-diagnosed in SOC. This study confirms the necessity for objective measures of RD that account for variability in BSP to accurately classify the severity of radiation skin toxicity in SOC and treat accordingly.
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We present the case of a 56-year-old female with a diagnosis of acute T-cell lymphoblastic leukemia who received myeloablative conditioning for bone marrow transplant with total body irradiation (TBI) using volumetric modulated arc therapy (VMAT) to the upper body and anterior-posterior/posterior-anterior (AP/PA) open fields to the lower body followed by hematopoietic stem cell transplant. Her clinical course was complicated by high-grade pulmonary toxic effects 55 days after treatment that resulted in death. We discuss the case, planning considerations by radiation oncologists and radiation physicists, and the multidisciplinary medical management of this patient.