Faculty Bibliography

To our knowledge, this is the first case report describing radiation recall dermatitis (RRD) after donor lymphocyte infusion (DLI) after allogeneic stem cell transplant in a patient with Acute T cell Leukemia Lymphoma. Given its rare occurrence, unclear clinical characterization and etiology, RRD remains poorly understood. In the setting of novel immunotherapies and recent development of Covid 19 mRNA vaccines, we aimed to better characterize RRD and its most likely pathogenesis in our patient's case.

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.

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens' decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions.

Purpose/Objective(s): Radiation therapy-induced cell death produces cytosolic DNA that activates the cyclic GMP-AMP synthase (cGAS)-STimulator of INterferon Genes (STING) pathway, crucial for the induction of Type I interferons (IFN-I). Checkpoint inhibitor (CPI) resistance mechanisms have been linked to impaired IFN signaling. Preclinical data have shown STING agonists to reverse CPI resistance in tumors with prior exposure, particularly when used with anti-PD-1/PD-L1 therapies. TAK-676 (a synthetic STING agonist) potently modulates the innate immune system, leading to cytokine release, adaptive immune activation, and antitumor responses in preclinical studies (Appleman et al., AACR 2022). TAK-676 is being investigated as a single agent, and in combination with pembrolizumab, for advanced solid tumors, in a first-in-human phase 1 study (NCT04420884). TAK-676 is optimally designed for intravenous (IV) delivery, with a prolonged half-life in serum and enhanced tissue permeability, allowing access to tumor sites and lymphatic tissue. Following radiation therapy, TAK-676 has the potential to stimulate T-cell mediated antitumor immunity via STING-mediated IFN-I release, particularly when used with anti-PD-1/PD-L1 therapies. Here, we present a second phase 1 study to investigate the safety and preliminary antitumor activity of TAK-676 in combination with pembrolizumab following radiation therapy, in patients with advanced or metastatic NSCLC, TNBC, or SCCHN who have progressed on CPIs (NCT04879849). Materials/Methods: Patients aged >=18 years who progressed on CPIs and have >=2 lesions, of which one is targetable with radiation, are being enrolled. Patients receive 8 Gy x 3 followed by (after a minimum of 40 hours) escalating doses of IV TAK-676 on days 1, 8 and 15 of a 21-day cycle, and 200 mg of IV pembrolizumab on day 1 of each cycle until disease progression, intolerance, or withdrawal of consent. Dose escalation of TAK-676 will be guided by the Bayesian Optimal Interval design. At screening and between days 15-21 of cycle 1, patients with a safely accessible lesion outside of the radiation field will have paired biopsies collected once the pharmacologically active dose levels of TAK-676 have been observed. The primary objective is to determine the safety and tolerability of TAK-676 in combination with pembrolizumab following radiation therapy. Secondary objectives are to determine the recommended phase 2 dose of TAK-676 in combination with pembrolizumab following radiation therapy, and to assess the local (within the radiation field) and systemic (non-radiated lesions) preliminary antitumor activity. As of February 2022, ~10% of the planned patients have been enrolled.
Result(s): TBD
Conclusion(s): TBD
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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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Purpose/Objective(s): Breast re-irradiation (reRT) after repeat breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy in women presenting with low risk in-breast tumor recurrence (IBTR). However, there is limited data on optimal patient selection and safety of different fractionation regimens. This multi-institutional study reports safety and efficacy in a large cohort of women with IBTR treated with repeat BCS and reRT. Materials/Methods: Using electronic medical record search tools, we identified all patients who underwent repeat BCS followed by breast reRT from 2015-2021 at 2 institutions. Univariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS).
Result(s): We identified 66 patients with an IBTR treated with repeat BCS. In the initial RT course, 55% received whole breast RT (WBI) with conventional fractionation (<=2 Gy/fraction[fx]), 29% WBI with hypofractionation (2.6-2.7 Gy/fx), 6% partial breast irradiation (PBI) ultrahypofractionation (6-8 Gy/fx) and 11% had unavailable treatment details. There was a median of 11 years between initial breast cancer and IBTR. At time of recurrence, 36% of patients had tumors located in the same quadrant as the initial cancer, 41% had invasive carcinoma with ductal carcinoma in situ (DCIS), 41% had invasive carcinoma alone, 18% had DCIS alone, 92% had tumors < 2 cm, 68% had low-intermediate grade tumors and all were clinically node negative. For reRT, 95% received PBI (57.5% 45 Gy/1.5 Gy twice daily; 27% 45 Gy/1.8 Gy daily; 10.5% hypofractionation), and 5% received WBI (45-46.8 Gy in 1.8 Gy/fx), all of whom had received PBI for the initial course. Nine patients (13%) underwent adjuvant chemotherapy and 44 (67%) adjuvant hormone therapy. Median follow-up was 16 months (range 3-60). Twenty-one patients (32%) experienced any acute >= grade 2 events, and 17 (26%) experienced any late >= grade 2 toxicities. One patient experienced grade 3 fibrosis and one patient experienced grade 3 telangiectasia at 36 months. None had grade 4 or higher late adverse events. We found no association between fractionation of reRT or cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%.
Conclusion(s): In this large multi-institutional series of patients with recurrent breast cancer, second breast conservation surgery followed by reRT was effective with no local recurrences and excellent disease control outcomes, and toxicity appears to be acceptable. Longer follow-up and more prospective study are needed to further inform patient selection and establish the efficacy and tolerability of repeat breast conservation therapy in the setting of limited, low-risk recurrence.
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Purpose/Objective(s): The LGBTQ community is an understudied and medically underserved population who experience increased cancer risk and worse cancer outcomes. Negative provider interactions, including discrimination and lack of knowledge regarding LGBTQ-specific health issues are cited by patients as barriers to care, including in radiation oncology (RO). Notably, little is known regarding LGBTQ knowledge and attitudes among RO residents (ROR) or LGBTQ-specific training in RO residency training programs. Thus, we sought to assess the extent of current LGBTQ-specific training in U.S. RO residency programs. Materials/Methods: Two published surveys of LGBTQ-education in residency were adapted to RO. The first assessed LGBTQ education from the perspective of program directors (PD) and associate PDs (APD), while the second survey was to RORs. The surveys were sent to all ACGME-accredited U.S. RO residency PD, APD, and program coordinators (PC), with the ROR survey being disseminated by the respective PCs. Each survey consisted of subsections of attitudes and knowledge in the care of LGBTQ patients, RO program characteristics, program inclusion of LGBTQ-specific education, and individual demographics.
Result(s): There were 69 responses (29 PD, APD and 40 ROR). The majority of respondents (PD, APD/ROR) identified as white (79%/58%), non-Hispanic (76%/72%), male (55%/55%), and heterosexual (86%/78%). The majority of PD, APDs did not receive LGBTQ education in medical school (60%) or residency training (96%), while the majority of residents (68%) did receive LGBTQ training in medical school; yet, both groups felt this training was insufficient to care for LGBTQ patients during residency (76%/68%). Overall, respondents felt comfortable treating LGB (90%/85%) and T (79%/62.5%) patients. However, the majority did not feel confident in their knowledge for LGB (52%/62.5%) or T (79%/85%) health needs. The majority of respondents' programs have never had a didactic session on LGBTQ health (78%/80%) resulting in 61%/61% of respondents feeling their program inadequately prepares residents to work confidently with LGBTQ patients. However, the majority felt their program is receptive to incorporating LGBTQ health content into their curriculum (75%/75%) and expressed a personal interest in such education (97%/80%). Additional data will be available by time of conference.
Conclusion(s): We found an increase of LGTBQ education in medical schools between PD, APD and ROR, suggestive of a recent improvement in LGBTQ content; yet most residency programs still lacked any LGBTQ-specific education. While the majority felt comfortable treating LGBTQ patients, they simultaneously lacked confidence in knowledge regarding LGBTQ health needs; yet, possessed desire for additional education and belief that such trainings should require. Conclusion is that residencies need to do a better job incorporating LGBTQ health content into their curricula, which is supported by interest from ROR and program leadership.
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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.

PURPOSE/OBJECTIVES/OBJECTIVE:Since the COVID-19 pandemic, telemedicine has emerged as an alternative to office visits in routine radiation oncology practice. The purpose of this study was to identify factors associated with patient preference for an initial consult via telemedicine and correlation with clinical trial enrollment. MATERIALS/METHODS/METHODS:We evaluated breast cancer patients seen during the open enrollment of a prospective randomized trial from 06/01/2020 to 05/13/2021. Univariate and multivariate logistic regression models were used to identify factors associated with virtual vs in-person initial consultation. All statistical tests were two-sided and the null hypothesis was rejected for p<0.05. RESULTS:We identified 476 patient consultations with 259 office visits and 217 telemedicine visits. On multivariate analysis, increased age, unemployment, chemotherapy receipt and radiation at our institution were associated with decreased usage of telemedicine for consultation visit. Out of 217 patients who underwent a telemedicine initial consultation, 10% were eligible to enroll on the trial and of those eligible, 76% enrolled. Out of 259 patients who underwent office visit initial consultation, 14% were eligible to enroll on the trial and of those eligible, 53% enrolled. Among eligible patients, there was no statistically significant difference in clinical trial enrollment between telemedicine and office visits. CONCLUSION/CONCLUSIONS:Older patients, unemployed patients, those receiving chemotherapy and those who subsequently received radiation at our institution were less likely to use telemedicine for their initial consult. Despite these disparities in telemedicine usage, there was no difference in clinical trial enrollment. Telemedicine may be an effective platform for clinical trial enrollment though further strategies to improve its access are essential.

Superior vena cava (SVC) syndrome is commonly caused by malignancy but is rarely associated with breast cancer. The following case series describes three female breast cancer patients who were found to have disease recurrence years after initial diagnosis, presenting as facial swelling, collateral vessel formation, and shortness of breath consistent with SVC syndrome. All patients were treated with radiation therapy, and one patient required stenting due to tumor thrombus in the SVC. These cases highlight a rare complication of breast cancer that clinicians should recognize in patients who have undergone treatment particularly for right sided breast cancer with lymph node involvement.