Faculty Bibliography

Improving diversity in residency programs has been increasingly emphasized as a means to address gender, racial, and ethnic disparities in medicine. However, limited attention has been given to the potential benefits of training physicians with differences other than gender or race and ethnicity. Americans with a disability represent about 27% of the U.S. population, whereas 1%-3% of physician trainees report having a disability. In 2013, a national survey identified only 86 physicians or trainees reporting deafness or hearing loss as a disability. To date, there are no published strategies on how to create an inclusive program for Deaf trainees. Herein, the authors report on the development of a Deaf and American Sign Language (ASL) inclusive residency program that can serve as an academic model for other programs, in any medical specialty, seeking to create an accessible training program for Deaf physicians and that can be adapted for trainees with other disabilities. In March 2017, the radiation oncology residency program at Johns Hopkins University matched an ASL-signing Deaf resident who would begin the program in July 2018. In preparation, department leadership engaged key stakeholders and leaders within the university's health system and among the department faculty, residents, and staff as well as the incoming resident to create an ASL inclusive program. A 5-step transition process for the training program was ultimately developed and implemented. The authors focused on engaging the Deaf trainee and interpreters, engaging health system and departmental leadership, contracting a training consultant and developing oral and written training materials for faculty and staff, and optimizing the workspace via accommodations. Through collaborative preparation, a Deaf and ASL-signing resident was successfully integrated into the residency program. The proposed 5-step transition process provides an effective, engaging model to encourage other institutions that are seeking to employ similar inclusivity initiatives.

Background/UNASSIGNED:The purpose of this study is to report on the prognostic role of pre- and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in a cohort of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) who was treated with multi-agent induction chemotherapy followed by five-fraction SBRT. Methods/UNASSIGNED:Patients treated with multi-agent induction chemotherapy followed by SBRT from August 2016 to January 2019 and who had laboratory values available for review were included in the study. Univariate (UVA) and multivariate analyses (MVA) were performed to determine associations between pre-/post-SBRT NLR and overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Results/UNASSIGNED:A total of 156 patients were treated with multi-agent induction chemotherapy followed by SBRT and had laboratory values available for review. On UVA, chemotherapy duration ≥4 months, poorly differentiated disease, inability to undergo resection, pre-SBRT ANC ≥3.7 No./µL, pre-SBRT NLR ≥2.3, and post-SBRT NLR ≥2.6 were associated with worse OS. Patients with post-SBRT NLR ≥2.6 had a median OS of 16.7 months versus median OS not yet reached in patients with post-SBRT <2.6 (P=0.009). On MVA, poorly differentiated disease [hazard ratio (HR) =1.82, 95% CI: 1.04-3.18, P=0.035], inability to undergo resection (HR =2.17, 95% CI: 1.25-3.70, P=0.006), and post-SBRT NLR ≥2.6 (HR =2.55, 95% CI: 1.20-5.45, P=0.015) were associated with inferior OS. On UVA, baseline CA 19-9 ≥219 U/mL, pre-SBRT platelet count ≥157×1,000/µL, and post-SBRT NLR ≥2.6 were associated with inferior LPFS. Patients with post-SBRT NLR ≥2.6 had a median LPFS of 18.3 months versus median LPFS not yet reached in patients with post-SBRT <2.6 (P=0.028). On MVA, only post-SBRT NLR ≥2.6 was associated with worse LPFS (HR =3.22, 95% CI: 1.04-9.98, P=0.043). Conclusions/UNASSIGNED:Post-SBRT NLR ≥2.6 predicted for inferior OS and LPFS in BRPC/LAPC patients treated with multi-agent chemotherapy and SBRT. These findings highlight the importance of further elucidating the immunologic effects of radiation therapy in this setting, which may have significant implications on both radiation design as well as combination strategies.

OBJECTIVE:To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. METHODS:Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. RESULTS:< 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. CONCLUSION:Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.

OBJECTIVES/OBJECTIVE:The purpose of this study was to determine if vertebral body and splenic dosimetry was associated with the development of lymphopenia in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation therapy (SBRT). METHODS:Patients with BRPC/LAPC who were treated with SBRT and who had lymphocyte counts and radiation treatment plans available for review were included in the study. Vertebral body levels T11-L3 and the spleen were retrospectively contoured for each patient. Univariate (UVA) and multivariable analyses (MVA) were performed to identify associations between vertebral body and splenic dosimetric parameters with absolute lymphocyte count (ALC) and grade ≥ 2 lymphopenia. Receiver operator characteristic curves were generated to identify dose-volume thresholds in predicting grade ≥ 2 lymphopenia. RESULTS:PTV (β: - 0.15, 95% CI - 0.30 to - 0.005, p = 0.042) were associated with post-SBRT ALC. On UVA and MVA, vertebral V15 (odds ratio [OR]: 3.98, 95% CI 1.09-14.51, p = 0.027), vertebral V2.5 (OR: 1.04, 95% CI 1.00-1.09, p = 0.032), and spleen V10 (OR: 1.05, 95% CI 1.09-1.95, p = 0.004) were associated with development of grade ≥ 2 lymphopenia. Development of grade ≥ 2 lymphopenia was more likely in patients with vertebral V15 ≥ 5.84% (65.5% vs 34.0%, p = 0.002), vertebral V2.5 ≥ 48.36% (48.9% vs 23.8%, p = 0.005), and spleen V10 ≥ 4.17% (56.2% vs 26.9%, p < 0.001). CONCLUSIONS:Increasing radiation dose to vertebral bodies and spleen were associated with the development of lymphopenia in BRPC/LAPC treated with SBRT. Optimization of vertebral body and splenic dosimetry may reduce the risk of developing lymphopenia and improve clinical outcomes in this population.

PURPOSE/OBJECTIVE:The purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS/METHODS:Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes. RESULTS:Thirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009-0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57-10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41-9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25-9.16; p = 0.017). CONCLUSION/CONCLUSIONS:In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.

BACKGROUND:We investigate the time to and clinical factors associated with patient-reported difficulty swallowing in lung cancer patients treated with radiation therapy (RT). METHODS:Between October 2016 and October 2019, lung cancer patients treated with conventionally fractionated RT at a tertiary cancer center were identified. Weekly, patients reported difficulty swallowing (patient-reported outcome version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE] v.1: 0-none, 1-mild, 2-moderate, 3-severe, 4-very severe). Physicians graded dysphagia (CTCAE v.4: 0-none, 1-symptoms without altered intake, 2-symptomatic; altered eating/swallowing, 3-severely altered eating/swallowing, 4-life-threatening consequences, 5-death). Tumor-related difficulty swallowing was not recorded at baseline; thus, patients reporting ≥moderate symptoms ≤7 days of RT start were excluded. We evaluated the time to new patient reports of ≥moderate difficulty swallowing and CTCAE grade 2+ dysphagia and development over time using the cumulative incidence method. Multivariable logistic regression evaluated associations between clinical factors, esophageal V60, and development of esophageal symptoms. RESULTS:Of the 200 patients identified: median age was 69 years, 52% were male, and 89% had stage III+ disease. Patients received a median of 63 Gy with chemotherapy (91.5%). At least moderate difficulty swallowing during RT was reported by 76 of 200 patients (38%); clinicians rated dysphagia as altering oral intake or worse for 26 of 200 (13%). Median time to first report of symptoms was 21 days (interquartile ratio [IQR], 18-34.5) for the 76 patients who reported ≥moderate symptoms and 33 days (IQR, 24-42) in the 26 patients whose provider reported grade 2+ dysphagia. The 30-day incidence of patient-reported ≥moderate swallowing difficulty and provider grade 2+ dysphagia was 26% (95% CI: 20%-32%) and 6% (95% CI: 3%-9%), respectively. Esophageal V60 >7 % was the clinical factor most associated with patient-reported ≥moderate esophageal symptoms (odds ratio 6.1, 95% CI: 3.0-12.3). CONCLUSIONS:Patients report at least moderate difficulty swallowing more often and earlier than providers report grade 2+ dysphagia. Esophageal V60 ≥7% was most associated with development of moderate severity or worse patient-reported swallowing difficulty.

PURPOSE/OBJECTIVE:Variation in target positioning represents a challenge to set-up reproducibility and reliability of dose delivery with stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma (PDAC). While on-board imaging for fiducial matching allows for daily shifts to optimize target positioning, the magnitude of the shift as a result of inter- and intra-fraction variation may directly impact target coverage and dose to organs-at-risk. Herein, we characterize the variation patterns for PDAC patients treated at a high-volume institution with SBRT. METHODS:We reviewed 30 consecutive patients who received SBRT using active breathing coordination (ABC). Patients were aligned to bone and then subsequently shifted to fiducials. Inter-fraction and intra-fraction scans were reviewed to quantify the mean and maximum shift along each axis, and the shift magnitude. A linear regression model was conducted to investigate the relationship between the inter- and intra-fraction shifts. RESULTS:The mean inter-fraction shift in the LR, AP, and SI axes was 3.1 ± 1.8 mm, 2.9 ± 1.7 mm, and 3.5 ± 2.2 mm, respectively, and the mean vector shift was 6.4 ± 2.3 mm. The mean intra-fraction shift in the LR, AP, and SI directions were 2.0 ± 0.9 mm, 2.0 ± 1.3 mm, and 2.3 ± 1.4 mm, respectively, and the mean vector shift was 4.3 ± 1.8 mm. A linear regression model showed a significant relationship between the inter- and intra-fraction shift in the AP and SI axis and the shift magnitude. CONCLUSIONS:Clinically significant inter- and intra-fraction variation occurs during treatment of PDAC with SBRT even with a comprehensive motion management strategy that utilizes ABC. Future studies to investigate how these variations could lead to variation in the dose to the target and OAR should be investigated. Strategies to mitigate the dosimetric impact, including real time imaging and adaptive therapy, in select cases should be considered.

PURPOSE/OBJECTIVE:In patients undergoing stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma, the reproducibility of tumor positioning between deep-inspiration breath holds is unclear. We characterized this variation with fiducials at simulation and treatment and investigated whether a patient-specific breath-hold (PSBH) margin would help account for intrafraction variation at treatment. METHODS AND MATERIALS/METHODS: RESULTS: CONCLUSIONS:The interbreath-hold variation is not insignificant, especially in the SI direction. Acquiring multiple breath-hold CT scans at simulation can help quantify the reproducibility of the interbreath hold and design a PSBH margin for treatment.