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sTable 1 shows radiation characteristics of Group A, B, and C. sTable 2 shows characteristics of CART-BCMA cells during manufacturing and at peak expansion in vivo in Group A, B, and C. sTable 3 shows details of radiation received after CART-BCMA therapy. sFigure 1 shows soluble BCMA serum levels before cyclophosphamide lymphodepletion on Day -3. sFigure 2 shows that prior radiation exposure is not associated with the level of CART-BCMA cells in vivo at peak expansion. sFigure 3 shows radiation was not associated with the level of persistent CART-BCMA cells in peripheral blood at Day 28. sFigure 4 shows level of CART-BCMA cells at peak expansion and Day 28 correlated with clinical response, and within responders, receipt of prior radiation was not associated with differences in CART=BCMA levels.

Purpose:B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cells (CART-BCMA) are a promising treatment for relapsed/refractory multiple myeloma (r/rMM). We evaluated the safety and feasibility of bridging radiation (RT) in subjects treated on a phase I trial of CART-BCMA.Experimental Design:Twenty-five r/rMM subjects were treated in three cohorts with two doses of CART-BCMA cells ± cyclophosphamide. We retrospectively analyzed toxicity, response, and CART manufacturing data based on RT receipt.Results:Thirteen subjects received no RT 18–35). Group C had qualitatively lower rates of grade 4 (G4) hematologic toxicities (25%) versus A (61.5%) and B (62.5%). G3–4 neurotoxicity occurred in 7.7%, 25%, and 25% in Group A, B, and C, respectively. G3–4 cytokine release syndrome was observed in 38.5%, 25%, and 25% in Group A, B, and C, respectively. Partial response or better was observed in 54%, 38%, and 50% of Group A, B, and C, respectively. RT administered P = 0.002) and P = 0.069) before apheresis was associated with lower in vitro proliferation during manufacturing; however, in vivo CART-BCMA expansion appeared similar across groups.Conclusions:Bridging-RT appeared safe and feasible with CART-BCMA therapy in our r/rMM patients, though larger future studies are needed to draw definitive conclusions.

PURPOSE: Communication is crucial in any clinical environment for efficient delivery of care and ensuring patient safety. A 2016 National Database of Nursing Quality Indicators questionnaire indicated poor physician-nurse satisfaction with communication in our department. We addressed gaps in our communication procedures by implementing a communication policy with a secure mobile messaging platform, and we surveyed care team members to evaluate the effectiveness of the implementation. METHODS: We designed a policy around best communication practices and implemented a secure mobile messaging platform, Cureatr, which enables closed-loop, two-way communication that is compliant with the Health Insurance Portability and Accountability Act. Pre- and postimplementation surveys evaluated self-reported impression of efficiency, timeliness, effectiveness, and overall quality of communication, which were scored on a 5-point Likert scale. The number of messages sent was evaluated as a measure of uptake in use, and patient navigation data were queried to measure changes in clinic workflow. RESULTS: After implementation of Cureatr and a communication policy, survey responses demonstrated a clear improvement in staff satisfaction with the efficiency, timeliness, effectiveness, and overall quality of communication. The number of messages sent reflected a progressive increase in use of Cureatr; however, a consistent improvement in clinical workflow as measured by a decrease in patient in-room time was not appreciated. CONCLUSION: Implementing a secure messaging application with a communication policy improved cancer care team satisfaction with communication on all levels. Additional work is needed to evaluate the impact of secure messaging on clinical workflows, patient satisfaction, and staff well-being.

Background and Purpose: Photon Stereotactic Body Radiotherapy (SBRT) for primary and metastatic tumors of the liver is challenging for larger lesions. An in silico comparison of paired SBRT and Stereotactic Body Proton Therapy (SBPT) plans was performed to understand the potential advantages of SBPT as a function of tumor size and location. Methods and materials: Theoretical tumor volumes with maximum diameter of 1–10 cm were contoured in the dome, right inferior, left medial, and central locations. SBRT and SBPT plans were generated to deliver 50 Gy in 5 fractions, max dose

Purpose: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cells (CART-BCMA) are a promising treatment for relapsed/refractory multiple myeloma (r/rMM). We evaluated the safety and feasibility of bridging radiation (RT) in subjects treated on a phase I trial of CART-BCMA. Experimental Design: Twenty-five r/rMM subjects were treated in three cohorts with two doses of CART-BCMA cells ± cyclophosphamide. We retrospectively analyzed toxicity, response, and CART manufacturing data based on RT receipt. Results: Thirteen subjects received no RT Conclusions: Bridging-RT appeared safe and feasible with CART-BCMA therapy in our r/rMM patients, though larger future studies are needed to draw definitive conclusions.

Purpose CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in 2 US Food and Drug Administration–approved therapies: tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging-RT may offer a supplemental approach. Methods and Materials Thirty-one patients receiving commercial tisa-cel (n = 13) or axi-cel (n = 18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were categorized into 2 groups: (1) bridging-RT within 30 days of CART infusion or (2) nonbridging-RT (NBRT), in which patients received either remote RT greater than 30 days before CART infusion or no prior RT. Results Five patients received bridging-RT within 30 days of CART infusion. Median bridging-RT dose was 37.5 Gy and was completed a median of 13 days before infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), and 23% (n = 6) and 15% (n = 4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (odds ratio [OR] = 26.67, P = .001) and CRS correlated with neurotoxicity (OR = 12.22, P = .028). There was a trend toward an association for CRS with metabolic tumor volume (OR = 1.06/mL, P = .141) and TLG (OR = 1.01/mL x standard uptake value, P = .099). Conclusions Bridging-RT before commercial CART does not appear to increase the risk for CART-related toxicities or negatively affect outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pretreatment metabolic tumor burden may be associated with CART-associated CRS; however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.

Use of immune therapy in metastatic cancers is rapidly expanding; however, its combination with commonly prescribed palliative radiation fields and doses is not well studied. To investigate this, we evaluated the toxicity of combined immune therapy and palliative cervical or thoracic spine radiotherapy. Patients receiving cervical or thoracic spine radiation were evaluated based on administration of immune therapy within 30 days of radiation, use of 3D conformal or simpler techniques, and minimum 1 follow-up from end of treatment. Thirty patients were evaluable. Median survival following radiotherapy was 87 days. Pembrolizumab was most commonly combined with radiation (11 patients), then nivolumab (10), ipilimumab (3), and atezoliumab (2). Four patients (13.3%) had grade 3 toxicity requiring hospitalization (vomiting, esophagitis) and 12 patients (40%) had grade 2 toxicity (esophagitis, dysphagia). Ten patients (33.3%) had no toxicity. Three of the 4 patients with grade 3 toxicity received concurrent ipilimumab and nivolumab. Median dose was 30 Gy (range, 20–39) and fractions were 10 (range, 5–15). There was a trend toward increased grade 2+ toxicity with greater number of vertebral levels irradiated, 5.7 ± 3.4, vs. 4.0 ± 1.6 for none/grade 1 (P = .086). Seven of 7 patients exposed to ipilimumab developed grade 2+ toxicity vs 39% in the remaining patients (P = .007 for interaction). Radiation dose, fractionation, and timing of immune therapy were not significant contributors. Combined immune therapy and radiotherapy for palliation of spine metastases suggests increased toxicity when a greater number of vertebral bodies are irradiated, or when combined immune therapy agents are utilized.

Background The interaction between immune checkpoint blockade (ICB) and radiation (RT) for brain metastases has not been well understood. Given that acute neurotoxicity from this combination is not well characterized, we reviewed patients receiving ICB and RT for brain metastases. Methods Patients treated with ICB and cranial RT from 2010 through 2017 were reviewed. ICB and RT must have been administered within 30 days of each other. Treatment parameters, performance status, symptoms prior to treatment, and toxicity were extracted from the electronic medical record. Survival was calculated from the end of RT to last follow-up or death. Results Seventy-eight patients were included. Median follow-up was 177 days (range, 12-1603). Median age was 64 years old (range, 29-98) and 47 (63%) were male. The main tumor types were melanoma (n = 47) and nonsmall-cell lung cancer (n = 19). Fifty-seven patients were treated with stereotactic radiosurgery (SRS) and 21 with whole-brain radiotherapy (WBRT). Most patients received single-agent ICB, though 4 patients received nivolumab and ipilimumab. Forty-one (53%) patients reported no neurologic toxicity. Grade 2 or greater neurologic toxicities were reported in 12 (21%) and 8 (38%) patients in the SRS and WBRT groups, respectively. WBRT was associated with a greater risk of any neurotoxicity, though there was no correlation between ICB agent and toxicity. Sequencing of ICB and RT (ie, Conclusions ICB during SRS or WBRT does not appear to worsen acute neurotoxicity compared to historical controls of RT alone.

130 Background: Palliative radiation is an effective treatment modality for spinal metastases. Expanding use of immune therapy in metastatic cancer raises concern that side effects from treatment may be exaggerated, particularly to sensitive organs such as the esophagus. This retrospective review evaluates the toxicity of combined radiation and immune therapy in patients with cervical or thoracic spine metastases. Methods: Patients receiving radiation for cervical or thoracic spine metastases from 2012-2017 were selected based on (1) concurrent use of immune therapy and radiation (within 7 days) OR radiation within 30 days following immune therapy, (2) 3D conformal or simpler treatment technique, and (3) minimum 30 days follow up from end of treatment. Patient demographics, radiation treatment parameters, immune therapy agent(s), and maximum toxicity were extracted from the medical record. Isoeffective dose was calculated using the EQD2 model, assuming α/β of 3. Statistical analyses included t tests. Results: Twenty-two patients were identified. Pembrolizumab was most commonly combined with radiation (8 patients), followed by nivolumab (7), ipilimumab (3), and atezoliumab (2). Two patients received both nivolumab and ipilimumab. Three patients (14%) had grade 3 toxicity requiring hospitalization (vomiting, esophagitis), 8 patients (36%) had grade 2 toxicity (esophagitis, dysphagia), 3 patients (14%) had grade 1 toxicity (hoarseness, dysphagia), 8 patients (36%) had no toxicity. Two patients (67%) with grade 3 toxicity received concurrent nivolumab and ipilimumab. Median dose was 3600 cGy (EQD2) in 10 fractions. There was a trend to greater toxicity with increased number of vertebral levels treated (mean 3.4, 4.6, 5.625 and 6.3 for toxicity grade 0, 1, 2 and 3, respectively; p= 0.053). Dose, fractionation, and immune therapy agent were not found to be significant contributors. Conclusions: In this small cohort, combined immune therapy and radiation for palliation of cervical or thoracic spine metastases suggests increased toxicity when greater number of vertebral bodies are irradiated or when combined immune therapy agents are utilized. Further investigation with a larger cohort is warranted.

Background Obstructive voiding symptoms (OVS) are common following prostate cancer treatment with radiation therapy. The risk of urinary retention (UR) following hypofractionated radiotherapy has yet to be fully elucidated. This study sought to evaluate OVS and UR requiring catheterization following SBRT for prostate cancer. Methods Patients treated with SBRT for localized prostate cancer from February 2008 to July 2011 at Georgetown University were included in this study. Treatment was delivered using the CyberKnife® with doses of 35 Gy-36.25 Gy in 5 fractions. UR was prospectively scored using the CTCAE v.3. Patient-reported OVS were assessed using the IPSS-obstructive subdomain at baseline and at 1, 3, 6, 9, 12, 18 and 24 months. Associated bother was evaluated via the EPIC-26. Results 269 patients at a median age of 69 years received SBRT with a median follow-up of 3 years. The mean prostate volume was 39 cc. Prior to treatment, 50.6% of patients reported moderate to severe lower urinary track symptoms per the IPSS and 6.7% felt that weak urine stream and/or incomplete emptying were a moderate to big problem. The 2-year actuarial incidence rates of acute and late UR ≥ grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one month (58%) and 18 months (48%) post-treatment. However, Grade 3 UR was low with only 4 men (1.5%) requiring catheterization and/or TURP. A mean baseline IPSS-obstructive score of 3.6 significantly increased to 5.0 at 1 month (p < 0.0001); however, it returned to baseline in 92.6% within a median time of 3 months. Late increases in OVS were common, but transient. Only 7.1% of patients felt that weak urine stream and/or incomplete emptying was a moderate to big problem at two years post-SBRT (p = 0.6854). Conclusions SBRT treatment caused an acute increase in OVS which peaked within the first month post-treatment, though acute UR requiring catheterization was rare. OVS returned to baseline in > 90% of patients within a median time of three months. Transient Late increases in OVS were common. However, less than 10% of patients felt that OVS were a moderate to big problem at two years post-SBRT.

Interferon beta (IFN-β) is a mainline treatment for multiple sclerosis (MS); however its exact mechanism of action is not completely understood. IFN-β is known as an immunomodulator; although recent evidence suggests that IFN-β may also act directly on neural stem/progenitor cells (NPCs) in the central nervous system (CNS). NPCs can differentiate into all neural lineage cells, which could contribute to the remyelination and repair of MS lesions. Understanding how IFN-β influences NPC physiology is critical to develop more specific therapies that can better assist this repair process. In this study, we investigated the effects of IFN β-1b (Betaseron®) on human NPCs in vitro (hNPCs). Our data demonstrate a dose-dependent response of hNPCs to IFN β-1b treatment via sustained proliferation and differentiation. Furthermore, we offer insight into the signaling pathways involved in these mechanisms. Overall, this study shows a direct effect of IFN β-1b on hNPCs and highlights the need to further understand how current MS treatments can modulate endogenous NPC populations within the CNS.

Streptococcus mutans, the primary causative agent of human dental caries, grows as a biofilm on the tooth surface, where it metabolizes dietary carbohydrates and generates acid byproducts that demineralize tooth enamel. A drop in plaque pH stimulates an adaptive acid-tolerance response (ATR) in this oral pathogen that allows it to survive acid challenge at pHs as low as 3.0. In the present study, we describe the growth of an S. mutans mutant, GMS901, that harbours an insertion–deletion mutation in gcrR, a gene that encodes a transcriptional regulatory protein. The mutant is acid-sensitive and significantly compromised in its ATR relative to the UA159 wild-type progenitor strain. Consistent with these findings are the results of real-time quantitative RT-PCR (qRT-PCR) experiments that support the GcrR-regulated expression of known ATR genes, including atpA/E and ffh. Although we observed gcrR transcription that was not responsive to acidic pH, we did note a significant increase in gcrR expression when S. mutans cells were grown in a manganese-restricted medium. Interestingly, the results of gel mobility shift assays indicate that the S. mutans SloR metalloregulatory protein is a potential regulator of gcrR by virtue of its manganese-dependent binding to the gcrR promoter region, and expression studies support the hypothesis that sloR transcription is responsive to manganese deprivation and acidic pH. Taking these results together, we propose that SloR–Mn modulates S. mutans gcrR expression as part of a general stress response, and that GcrR acts downstream of SloR to control the ATR.

196 Background: Obstructive urinary symptoms are common following prostate cancer treatment with radiation therapy. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT obstructive urinary symptoms would be more severe. This study sought to evaluate obstructive urinary symptoms and urinary retention requiring catheterization following SBRT for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital with a minimum of two years of follow-up were included in this study. Treatment was delivered using the CyberKnife with doses of 35 Gy to 36.25 Gy in five fractions. Urinary retention was recorded and scored using the CTCAE v.4. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at months 1, 3, 6, 9, and 12 and every six months thereafter. Results: Two hundred sixty nine patients at a median age of 69 received SBRT with a median follow-up of three years. Prior to treatment, 32.1% of patients utilized alpha-antagonists and 17.8% were dissatisfied with their urinary function. The two-year actuarial incidence rates of acute and late urinary retention greater than or equal to grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one month (57.9%) and 18 months (48.0%) post-treatment. However, grade 3 urinary retention was low with four men (1.5%) requiring catheterization and/or transurethral resection of the prostate. A mean baseline IPSS obstructive symptom score of 3.6 significantly increased to 5.0 at one month (p < 0.0001), however returned to baseline at three months (p = 0.74). Late IPSS increases were common, but transient. The IPSS obstructive symptom score returned to baseline in 79.6% of patients by six months and 92.6% by two years. Dissatisfaction with urinary function declined to 14% by two years post treatment (p < 0.05). Conclusions: Treatment of prostate cancer with SBRT resulted in an acute increase in obstructive urinary symptoms, which peaked at one month post-treatment. However, the risk of acute urinary retention requiring catheterization was low. Obstructive urinary symptoms returned to baseline in the majority of patients by six months and in more than 90% by two years.