Impact of Cancer Care Regionalization on Patient Volume.

BACKGROUND: Cancer centers are regionalizing care to expand patient access, but the effects on patient volume are unknown. This study aimed to compare patient volumes before and after the establishment of head and neck regional care centers (HNRCCs). METHODS: This study analyzed 35,394 unique new patient visits at MD Anderson Cancer Center (MDACC) before and after the creation of HNRCCs. Univariate regression estimated the rate of increase in new patient appointments. Geospatial analysis evaluated patient origin and distribution. RESULTS: The mean new patients per year in 2006-2011 versus 2012-2017 was 2735 ± 156 patients versus 3155 ± 207 patients, including 464 ± 78 patients at HNRCCs, reflecting a 38.4 % increase in overall patient volumes. The rate of increase in new patient appointments did not differ significantly before and after HNRCCs (121.9 vs 95.8 patients/year; P = 0.519). The patients from counties near HNRCCs, showed a 210.8 % increase in appointments overall, 33.8 % of which were at an HNRCC. At the main campus exclusively, the shift in regional patients to HNRCCs coincided with a lower rate of increase in patients from the MDACC service area (33.7 vs. 11.0 patients/year; P = 0.035), but the trend was toward a greater increase in out-of-state patients (25.7 vs. 40.3 patients/year; P = 0.299). CONCLUSIONS: The creation of HNRCCs coincided with stable increases in new patient volume, and a sizeable minority of patients sought care at regional centers. Regional patients shifted to the HNRCCs, and out-of-state patient volume increased at the main campus, optimizing access for both local and out-of-state patients.

Proton Therapy for HPV-Associated Oropharyngeal Cancers of the Head and Neck: a De-Intensification Strategy.

OPINION STATEMENT: The rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.

A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy.

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.

Optimizing Outpatient Radiation Oncology Consult Workflow by Using Time-Driven Activity-Based Costing: Efficiency and Financial Impacts.

PURPOSE: Clinical efficiency is a key component of value-based health care. Our objective here was to identify workflow inefficiencies by using time-driven activity-based costing (TDABC) and evaluate the implementation of a new clinical workflow in high-volume outpatient radiation oncology clinics. METHODS: Our quality improvement study was conducted with the Departments of GI, Genitourinary (GU), and Thoracic Radiation Oncology at a large academic cancer center and four community network sites. TDABC was used to create process maps and optimize workflow for outpatient consults. Patient encounter metrics were captured with a real-time status function in the electronic medical record. Time metrics were compared using Mann-Whitney U tests. RESULTS: Individual patient encounter data for 1,328 consults before the intervention and 1,234 afterward across all sections were included. The median overall cycle time was reduced by 21% in GI (19 minutes), 18% in GU (16 minutes), and 12% at the community sites (9 minutes). The median financial savings per consult were $52 in US dollars (USD) for the GI, $33 USD for GU, $30 USD for thoracic, and $42 USD for the community sites. Patient satisfaction surveys (from 127 of 228 patients) showed that 99% of patients reported that their providers spent adequate time with them and 91% reported being seen by a care provider in a timely manner. CONCLUSION: TDABC can effectively identify opportunities to improve clinical efficiency. Implementing workflow changes on the basis of our findings led to substantial reductions in overall encounter cycle times across several departments, as well as high patient satisfaction and significant financial savings.

Development and clinical implementation of a digital workflow utilizing 3D-printed oral stents for patients with head and neck cancer receiving radiotherapy.

OBJECTIVES: We describe the development of 3D-printed stents using our digital workflow and their effects on patients enrolled in the lead-in phase of a multi-center, randomized Phase-II trial. MATERIALS AND METHODS: Digital dental models were created for patients using intraoral scanning. Digital processes were implemented to develop the mouth-opening, tongue-depressing, and tongue-lateralizing stents using stereolithography. Time spent and material 3D-printing costs were measured. Physicians assessed mucositis using the Oral Mucositis Assessment Scale (OMAS) and collected MD Anderson Symptom Inventory (MDASI) reports and adverse events (AEs) from patients at various time points (TPs). OMAS and MDASI results were evaluated using paired t-test analysis. RESULTS: 18 patients enrolled into the lead-in phase across 6 independent clinical sites in the USA. 15 patients received stents (average design and fabrication time, 8 h; average material 3D-printing cost, 11 USD). 10 eligible patients with complete OMAS and MDASI reports across all TPs were assessed. OMAS increased significantly from baseline to week 3 of treatment (mean difference = 0.34; 95 % CI, 0.09-0.60; p = 0.01). MDASI increased significantly from baseline to week 3 of treatment (mean difference = 1.02; 95 % CI, 0.40-1.70; p = 0.005), and week 3 of treatment to end of treatment (mean difference = 1.90; 95 % CI, 0.90-2.92; p = 0.002). AEs (grades 1-3) were reported by patients across TPs. Mucositis and radiation dermatitis were primarily attributed to chemoradiation. CONCLUSIONS: 3D-printed stents were successfully fabricated and well tolerated by patients. As patients enroll in the randomized phase of this trial, data herein will establish a baseline for comparative analysis.

A phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiation therapy yields high rates of local control for brain metastases, but patients in rural or suburban areas face geographic and socioeconomic barriers to its access. We conducted a phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases in an integrated academic satellite network for patients 18 years of age or older with 4 or fewer brain metastases. Dose was based on gross tumor volume: less than 3.0 cm, 27 Gy in 3 fractions and 3.0 to 3.9 cm, 30 Gy in 5 fractions. Median follow-up was 10 months for 73 evaluable patients, with a median age of 68 years. Median intracranial progression-free survival was 7.1 months (95% confidence interval = 5.3 to not reached), and median survival was 7.2 months (95% confidence interval = 5.4 to not reached); there were no serious adverse events. Outcomes of this trial compare favorably with contemporary trials, and this treatment strategy provides opportunities to expand stereotactic radiation therapy access to underserved populations.

Changes in Apparent Diffusion Coefficient (ADC) in Serial Weekly MRI during Radiotherapy in Patients with Head and Neck Cancer: Results from the PREDICT-HN Study.

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman's correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th−95th percentiles in weeks 1−4 (p < 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies.

Stereotactic body ablative radiotherapy for reirradiation of small volume head and neck cancers is associated with prolonged survival: Large, single-institution, modern cohort study.

BACKGROUND: Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses. METHODS: We reviewed patients who received definitive-intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed. RESULTS: One hundred and thirty-seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1-year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02). CONCLUSIONS: In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy.

Five-Year Longitudinal Analysis of Patient-Reported Outcomes and Cosmesis in a Randomized Trial of Conventionally Fractionated Versus Hypofractionated Whole-Breast Irradiation.

PURPOSE: There are limited prospective data on predictors of patient-reported outcomes (PROs) after whole-breast irradiation (WBI) plus a boost. We sought to characterize longitudinal PROs and cosmesis in a randomized trial comparing conventionally fractionated (CF) versus hypofractionated (HF) WBI. METHODS AND MATERIALS: From 2011 to 2014, women aged ≥40 years with Tis-T2 N0-N1a M0 breast cancer who underwent a lumpectomy with negative margins were randomized to CF-WBI (50 Gray [Gy]/25 fractions plus boost) versus HF-WBI (42.56 Gy/16 fractions plus boost). At baseline (pre-radiation), at 6 months, and yearly thereafter through 5 years, PROs included the Breast Cancer Treatment Outcome Scale (BCTOS), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Body Image Scale; cosmesis was reported by the treating physician using Radiation Therapy Oncology Group cosmesis values. Multivariable mixed-effects growth curve models evaluated associations of the treatment arm and patient factors with outcomes and tested for relevant interactions with the treatment arm. RESULTS: A total of 287 patients were randomized, completing a total of 14,801 PRO assessments. The median age was 60 years, 37% of patients had a bra cup size ≥D, 44% were obese, and 30% received chemotherapy. Through 5 years, there were no significant differences in PROs or cosmesis by treatment arm. A bra cup size ≥D was associated with worse BCTOS cosmesis (P < .001), BCTOS pain (P = .001), FACT-B Trial Outcome Index (P = .03), FACT-B Emotional Well-being (P = .03), and Body Image Scale (P = .003) scores. Physician-rated cosmesis was worse in patients who were overweight (P = .02) or obese (P < .001). No patient subsets experienced better PROs or cosmesis with CF-WBI. CONCLUSIONS: Both CF-WBI and HF-WBI confer similar longitudinal PROs and physician-rated cosmesis through 5 years of follow-up, with no relevant subsets that fared better with CF-WBI. This evidence supports broad adoption of hypofractionation with boost, including in patients receiving chemotherapy and in a population with a high prevalence of obesity. The associations of large breast size and obesity with adverse outcomes across multiple domains highlight the opportunity to engage at-risk patients in lifestyle intervention strategies, as well as to consider alternative radiation treatment regimens.

Outcomes after salvage for HPV-positive recurrent oropharyngeal cancer treated with primary radiation.

PURPOSE: HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) carries a favorable prognosis for patients, yet nearly 30% of patients will experience disease relapse. We sought to detail patterns of failure, associated salvage therapy, and outcomes for patients with recurrent HPV-positive OPSCC. METHODS AND MATERIALS: This is a single institution retrospective study of patients with recurrent HPV-positive OPSCC irradiated from 2002 to 2014. The primary study outcome was overall survival (OS, calculated using the Kaplan-Meier method). Secondary aims included patterns of first failure with descriptive details of salvage therapy. Solitary recurrences were defined as initial presentation of recurrence in a single site (primary, neck or oligometastatic), and multi-site was defined as local and regional and/or multiple sites of distant recurrence. Survival outcomes were compared using the log-rank test. RESULTS: The cohort consisted of 132 patients. The median follow-up was 59 months for surviving patients. Estimated 2-year and 5-year OS rates were 47% and 32%, respectively. Comparative 2-year and 5-year OS rates were 65% and 46% versus 19% and 9% for the solitary group and multi-site group, respectively (p < .001). CONCLUSIONS: Patients with recurrent HPV-positive OPSCC experience 5-year survival of approximately 32%. However, patients with a "solitary" recurrence including disease at the primary site, neck or oligometastatic site have more favorable long-term outcomes.

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial.

AIM: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer. METHODS: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response. RESULTS: Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P < 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT. CONCLUSIONS: HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.

Proton Therapy for Head and Neck Cancer: A 12-Year, Single-Institution Experience.

PURPOSE: To characterize our experience and the disease control and toxicity of proton therapy (PT) for patients with head and neck cancer (HNC). PATIENTS AND METHODS: Clinical outcomes for patients with HNC treated with PT at our institution were prospectively collected in 2 institutional review board-approved prospective studies. Descriptive statistics were used to summarize patient characteristics and outcomes. Overall survival, local-regional control, and disease-free survival were estimated by the Kaplan-Meier method. Treatment-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03) scale. RESULTS: The cohort consisted of 573 patients treated from February 2006 to June 2018. Median patient age was 61 years. Oropharynx (33.3%; n = 191), paranasal sinus (11%; n = 63), and periorbital tissues (11%; n = 62) were the most common primary sites. Patients with T3/T4 or recurrent disease comprised 46% (n = 262) of the cohort. The intent of PT was definitive in 53% (n = 303), postoperative in 37% (n = 211), and reirradiation in 10% (n = 59). Median dose was 66 Gy (radiobiological equivalent). Regarding systemic therapy, 43% had received concurrent (n = 244), 3% induction (n = 19), and 15% (n = 86) had both. At a median follow-up of 2.4 years, 88 patients (15%) had died and 127 (22%) developed disease recurrence. The overall survival, local-regional control, and disease-free survival at 2 and 5 years were, respectively, 87% and 75%, 87% and 78%, and 74% and 63%. Maximum toxicity (acute or late) was grade 3 in 293 patients (51%), grade 2 in 234 patients (41%), and grade 1 in 31 patients (5%). There were 381 acute grade 3 and 190 late grade 3 unique toxicities across 212 (37%) and 150 (26%) patients, respectively. There were 3 late-grade 4 events across 2 patients (0.3%), 2 (0.3%) acute-grade 5, and no (0%) late-grade 5 events. CONCLUSIONS: The overall results from this prospective study of our initial decade of experience with PT for HNC show favorable disease control and toxicity outcomes in a multidisease-site cohort and provide a reference benchmark for future comparison and study.

Work Outcomes after Intensity-Modulated Proton Therapy (IMPT) versus Intensity-Modulated Photon Therapy (IMRT) for Oropharyngeal Cancer.

PURPOSE: We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT). PATIENTS AND METHODS: In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores. RESULTS: Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT. CONCLUSION: In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

Highly conformal reirradiation in patients with prior oropharyngeal radiation: Clinical efficacy and toxicity outcomes.

BACKGROUND: Reirradiation of head and neck cancer is associated with high rates of locoregional failure and potentially severe treatment-related toxicity. We report our institutional experience of reirradiation using modern highly conformal radiotherapy approaches in patients with prior oropharyngeal radiation. METHODS: We reviewed patients receiving curative-intent reirradiation with intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton beam radiotherapy at our institution from 1999 to 2019. Disease control, survival, and toxicity rates following reirradiation were determined. RESULTS: Sixty-nine patients were evaluated. Local control (LC), progression-free survival, and overall survival at 2 years following reirradiation were 77%, 35%, and 51%, respectively. Grade 3 or greater (G3+) late toxicities occurred in 46% of patients and 41% required feeding tube placement during or after reirradiation. CONCLUSIONS: In select patients with prior oropharyngeal radiation, highly conformal reirradiation offers acceptable LC, but G3+ toxicity and out-of-field failure rates remain high. These findings warrant continued evaluation of new multimodality approaches to improve oncologic outcomes.

A Dosimetric Comparison of Oral Cavity Sparing in the Unilateral Treatment of Early Stage Tonsil Cancer: IMRT, IMPT, and Tongue-Deviating Oral Stents.

INTRODUCTION: Tongue-deviating oral stents (TDOS) are commonly used during unilateral neck radiation therapy to reduce unnecessary dose to nontarget oral structures. Their benefit in the setting of highly conformal treatment techniques, however, is not defined. The goal of this study was to investigate the potential benefit of TDOS use on dosimetric parameters in unilateral intensity modulated radiation therapy (IMRT) and intensity modulated proton therapy (IMPT). METHODS: A total of 16 patients with T1-2 tonsil cancer treated at a single institution were selected, of which 8 were simulated/treated with a TDOS and 8 without a TDOS. All received definitive unilateral IMRT to a dose of 66 Gy in 30 fx. IMPT plans were generated for each patient for study purposes and optimized according to standard institutional practice. RESULTS: For IMRT plans, the presence of a TDOS (vs without) was associated with a significantly lower oral mucosa mean dose (31.4 vs 35.3 Gy; P = .020) and V30 (42.7% vs 57.1%; P = .025). For IMPT plans, the presence of TDOS (vs without) was not associated with any improvement in oral mucosa mean dose (18.3 vs 19.9 Gy; P = .274) or V30 (25.0% vs 26.2%; P = .655). IMPT plans without TDOS compared with IMRT plans with TDOS demonstrated reduced oral mucosa mean dose (P < .001) and V30 (P < .001). CONCLUSION: The use of a TDOS for the unilateral treatment of well-lateralized tonsil cancers was associated with oral mucosa sparing for IMRT, but not for IMPT. Moreover, mucosa sparing was improved for IMPT plans without a TDOS compared to IMRT plans with a TDOS.

Radiation Oncology Strategies to Flatten the Curve During the Coronavirus Disease 2019 (COVID-19) Pandemic: Experience From a Large Tertiary Cancer Center.

During the coronavirus disease 2019 pandemic, minimizing exposure risk for patients with cancer and health care personnel was of utmost importance. Here, we present steps taken to date to flatten the curve at the radiation oncology division of a tertiary cancer center with the goal of mitigating risk of exposure among patients and staff, and optimizing resource utilization. Response to the coronavirus disease 2019 pandemic in this large tertiary referral center included volume reduction, personal protective equipment recommendations, flexible clinic visit interaction types dictated by need and risk reduction, and numerous social distancing strategies. We hope these outlined considerations can assist the wider radiation oncology community as we collectively face this ongoing challenge.

Rescue of Immunotherapy-Refractory Metastatic Merkel Cell Carcinoma With Conventionally Fractionated Radiotherapy and Concurrent Pembrolizumab.

Merkel cell carcinoma has historically had dismal prognosis with limited cytotoxic chemotherapy options that provide durable control of metastatic disease. The advent of anti-programmed death protein (anti-PD1)/anti-programmed death-ligand 1 (anti-PD-L1) directed immunotherapy has shown initial promise in Merkel cell carcinoma and radiation might augment immune responses. We present a case report of a 70-year-old male who underwent resection of Merkel cell carcinoma of the right thigh with a close margin and positive right inguinal involvement. Due to high-risk features, the patient was treated with adjuvant radiation to the right groin and with systemic carboplatin/etoposide, but developed local failure requiring salvage surgical resection. The patient then developed metastatic disease with biopsy proven retroperitoneal involvement refractory to doxorubicin/cyclophosphamide chemotherapy. The patient was then transitioned to single-agent pembrolizumab with a partial response for 10 months until developing progressive disease involving the left inguinal and left external iliac nodal regions. The progressive left inguinal/pelvic disease was treated with conventionally fractionated intensity modulated radiation therapy to a dose of 45 Gy delivered in 25 fractions. Following radiation therapy, the patient had complete response of all sites of disease throughout the body on imaging by RECIST criteria including retroperitoneal and mediastinal disease outside the radiation field. At 20 months post-radiation, the patient remains on pembrolizumab without evidence of disease on imaging. Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy. Ongoing prospective trials evaluating the utility of radiation in conjunction with immunotherapy for Merkel cell carcinoma are anticipated to provide clarity on the frequency and durability of abscopal responses when radiation is combined with immune checkpoint inhibitors.