Towards an Explainable AI Platform to Study Interruptions in Cancer Radiation Therapy.

Radiation therapy interruptions drive cancer treatment failures; they represent an untapped opportunity for improving outcomes and narrowing treatment disparities. This research reports on the early development of the X-CART platform, which uses explainable AI to model cancer treatment outcome metrics based on high-dimensional associations with our local social determinants of health dataset to identify and explain causal pathways linking social disadvantage with increased radiation therapy interruptions.

The Role of Dental Practitioners in the Management of Oncology Patients: The Head and Neck Radiation Oncology Patient and the Medical Oncology Patient.

This narrative review addresses the role of a dentist in the management of oncology patients, highlighting the oral complications that arise in head and neck radiation oncology patients and medical oncology patients. The prevention and management of these complications are discussed.

Defining Radiation Treatment Interruption Rates During the COVID-19 Pandemic: Findings From an Academic Center in an Underserved Urban Setting.

PURPOSE: Our purpose was to characterize radiation treatment interruption (RTI) rates and their potential association with sociodemographic variables in an urban population before and during the COVID-19 pandemic. METHODS AND MATERIALS: Electronic health records were retrospectively reviewed for patients treated between January 1, 2015, and February 28, 2021. Major and minor RTI were defined as ≥5 and 2 to 4 unplanned cancellations, respectively. RTI was compared across demographic and clinical factors and whether treatment started before or after COVID-19 onset (March 15, 2020) using multivariate logistic regression analysis. RESULTS: Of 2,240 study cohort patients, 1,938 started treatment before COVID-19 and 302 started after. Patient census fell 36% over the year after COVID-19 onset. RTI rates remained stable or trended downward, although subtle shifts in association with social and treatment factors were observed on univariate and multivariate analysis. Interaction of treatment timing with risk factors was modest and limited to treatment length and minor RTI. Despite the stability of cohort-level findings showing limited associations with race, geospatial mapping demonstrated a discrete geographic shift in elevated RTI toward Black, underinsured patients living in inner urban communities. Affected neighborhoods could not be predicted quantitatively by local COVID-19 transmission activity or social vulnerability indices. CONCLUSIONS: This is the first United States institutional report to describe radiation therapy referral volume and interruption patterns during the year after pandemic onset. Patient referral volumes did not fully recover from an initial steep decline, but local RTI rates and associated risk factors remained mostly stable. Geospatial mapping suggested migration of RTI risk toward marginalized, minority-majority urban ZIP codes, which could not otherwise be predicted by neighborhood-level social vulnerability or pandemic activity. These findings signal that detailed localization of highest-risk communities could help focus radiation therapy access improvement strategies during and after public health emergencies. However, this will require replication to validate and broaden relevance to other settings.

Independent Predictors for Hospitalization-Associated Radiation therapy Interruptions.

Purpose: Radiation treatment interruption associated with unplanned hospitalization remains understudied. The intent of this study was to benchmark the frequency of hospitalization-associated radiation therapy interruptions (HARTI), characterize disease processes causing hospitalization during radiation, identify factors predictive for HARTI, and localize neighborhood environments associated with HARTI at our academic referral center. Methods and Materials: This retrospective review of electronic health records provided descriptive statistics of HARTI event rates at our institutional practice. Uni- and multivariable logistic regression models were developed to identify significant factors predictive for HARTI. Causes of hospitalization were established from primary discharge diagnoses. HARTI rates were mapped according to patient residence addresses. Results: Between January 1, 2015, and December 31, 2017, 197 HARTI events (5.3%) were captured across 3729 patients with 727 total missed treatments. The 3 most common causes of hospitalization were malnutrition/dehydration (n = 28; 17.7%), respiratory distress/infection (n = 24; 13.7%), and fever/sepsis (n = 17; 9.7%). Factors predictive for HARTI included African-American race (odds ratio [OR]: 1.48; 95% confidence interval [CI], 1.07-2.06; P = .018), Medicaid/uninsured status (OR: 2.05; 95% CI, 1.32-3.15; P = .0013), Medicare coverage (OR: 1.7; 95% CI, 1.21-2.39; P = .0022), lung (OR: 5.97; 95% CI, 3.22-11.44; P < .0001), and head and neck (OR: 5.6; 95% CI, 2.96-10.93; P < .0001) malignancies, and prescriptions >20 fractions (OR: 2.23; 95% CI, 1.51-3.34; P < .0001). HARTI events clustered among Medicaid/uninsured patients living in urban, low-income, majority African-American neighborhoods, and patients from middle-income suburban communities, independent of race and insurance status. Only the wealthiest residential areas demonstrated low HARTI rates. Conclusions: HARTI disproportionately affected socioeconomically disadvantaged urban patients facing a high treatment burden in our catchment population. A complementary geospatial analysis also captured the risk experienced by middle-income suburban patients independent of race or insurance status. Confirmatory studies are warranted to provide scale and context to guide intervention strategies to equitably reduce HARTI events.

Impact of the COVID-19 Pandemic on Canadian Radiation Oncology Practices.

PURPOSE: To survey Canadian radiation oncology (RO) practice leaders to determine the effect of the COVID-19 pandemic on radiation services and patient and staff issues in the early phase of the pandemic and 1 year later. METHODS AND MATERIALS: The RO leader (department or division head) from every Canadian cancer center with radiation services was identified. Two surveys were circulated to the identified leader via email from the Canadian Association of Radiation Oncology central office, using the SurveyMonkey survey tool: the first closed in June 2020 and the second (expanded) survey in June 2021, representing 2 points in time of the COVID-19 pandemic. Questions included patient volume, service interruptions and delays, and changes in scheduling and telemedicine use. Additional questions were included in the follow-up survey to determine further effects on disease presentation, volume, vaccination and access, and personnel issues. RESULTS: Telemedicine was widely adopted early in the pandemic and continued to be a common technique to communicate and connect with patients. Although many centers were deferring or delaying certain disease sites early in the pandemic, this was not as prevalent 1 year later. Reduced cancer screening and patients presenting with more advanced disease were concerns documented in the 2021 survey. A high level of concern regarding stress among health care professionals was identified. CONCLUSIONS: Canadian RO centers have faced numerous challenges during the COVID-19 pandemic but continued to provide timely and essential cancer care for patients with cancer. Future evaluation of RO center practices will be important to continue to document and address the effect of the COVID-19 pandemic on issues relevant to RO leaders, patients, and staff.

Variable Effect of the COVID-19 Pandemic on Radiation Oncology Practices in the United States.

PURPOSE: Early in the pandemic, the American Society for Radiation Oncology surveyed physician leaders at radiation oncology practices in the United States to understand how the field was responding to the outbreak of COVID-19. METHODS AND MATERIALS: Surveys were repeated at multiple points during the pandemic, with a response rate of 43% in April 2020 and 23% in January 2021. To our knowledge, this is the only longitudinal COVID-19 practice survey in oncology in the United States. RESULTS: The surveys indicate that patient access to essential radiation oncology services in the United States has been preserved throughout the COVID-19 pandemic. Safety protocols were universally adopted, telehealth was widely adopted and remains in use, and most clinics no longer deferred or postponed radiation treatments as of early 2021. Late-stage disease presentation, treatment interruptions, shortages of personal protective equipment, and vaccination barriers were reported significantly more at community-based practices than at academic practices, and rural practices appear to have faced increased obstacles. CONCLUSIONS: Our findings provide unique insights into the initial longitudinal effect of the COVID-19 pandemic on the delivery of radiation therapy in the United States. Downstream lessons in service adaptation and improvement can potentially be guided by formal concepts of resilience, which have been broadly embraced across the US economy.

Outcomes of primary radiotherapy with or without chemotherapy for advanced oral cavity squamous cell carcinoma: Systematic review.

BACKGROUND: Surgery with adjuvant radiotherapy is the accepted standard for treatment of advanced oral cavity squamous cell carcinoma (OCSCC); however, alternative evidence suggests that definitive (chemo)radiotherapy may have similar outcomes. METHODS: Systematic review was performed to assess the therapeutic value of radiotherapy or chemoradiotherapy as a primary modality for treating OCSCC. Meta-analysis of outcomes was performed between articles comparing radiotherapy and primary surgical treatment. RESULTS: Meta-analysis showed less favorable results of radiotherapy compared to surgery: overall survival at 3-years (odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.34-0.77) and 5-years (OR = 0.42; 95% CI = 0.29-0.60); disease-specific survival at 3-years (OR = 0.55; 95% CI = 0.32-0.96) and 5-years (OR = 0.55; 95% CI = 0.32-0.96). Odds of feeding tube dependency were higher in primary radiotherapy group (OR = 2.67; 95% CI = 1.27-5.64). CONCLUSIONS: Results of this study support the current perspective favoring primary surgical treatment for OCSCC in the absence of surgical contraindications.

Initial Impact and Operational Responses to the COVID-19 Pandemic by American Radiation Oncology Practices.

PURPOSE: In February 2020, the COVID-19 pandemic reached the United States. The impact of the pandemic on the US radiation oncology field remains unknown. The American Society for Radiation Oncology surveyed US radiation oncology practice leaders to gauge initial impact and immediate operational responses to the pandemic. METHODS AND MATERIALS: From April 16 to April 30, 2020, the American Society for Radiation Oncology surveyed US radiation oncology practice leaders by email to gauge initial impact and immediate operational responses to the COVID-19 pandemic. RESULTS: Two hundred twenty-two (43%) of 517 leaders responded from community and academic practices (62% and 34%, respectively), hospital-based and free-standing centers (69% and 29%), and metro and rural locations (88% and 12%). Practices reported treating an average of 1086 patients per year in 2019 (range, 0-7900) with an average daily treatment volume of 70 patients (range, 5-400). All practices reported uninterrupted operation. On average, practices were treating 68% of their typical volume (range, 10%-95%), with 92% implementing planned treatment postponement for lower risk patients. An estimated revenue decrease of 20% or more was experienced by 71% of practices. Confirmed COVID-19 patient cases were treated by 39% of practices. Seventy percent experienced staff shortages. Almost all (98%) practices implemented formal operational procedures to protect patients and staff, although personal protective equipment/infection control supply shortages were reported by 78% of practices. Seventy-four percent used telemedicine for virtual follow-up surveillance, and 15% leveraged telemedicine for on-treatment assessment. CONCLUSIONS: The clinical and financial impacts of the COVID-19 pandemic on US radiation oncology were deep and broad. Despite reported shortages in personal protective equipment, declines in revenue, and reduced patient volumes, practices adapted quickly by refining standard processes of care, implementing recommended safety measures, and employing telemedicine to facilitate treatment continuity. Patients with higher risk disease experienced uninterrupted access to care. We plan to continue regular surveying across the lifespan of the pandemic to document the geographic and temporal impact of COVID-19 on the field and its patients.

COVID's Impact on Radiation Oncology: A Latin American Survey Study.

PURPOSE: The impact of the COVID-19 pandemic on Latin American radiation therapy services has not yet been widely assessed. In comparison to centers in Europe or the United States, the scarcity of data on these terms might impair design of adequate measures to ameliorate the pandemic's potential damage. The first survey-based analysis revealing regional information is herein presented. METHODS AND MATERIALS: From May 6 to May 30, 2020, the American Society for Radiation Oncology's COVID-19 Survey was distributed across Latin America with support of the local national radiation therapy societies. Twenty-six items, including facility demographic and financial characteristics, personnel and patient features, current and expected impact of the pandemic, and research perspectives, were included in the questionnaire. RESULTS: Complete responses were obtained from 115 (50%) of 229 practices across 15 countries. Only 2.6% of centers closed during the pandemic. A median of 4 radiation oncologists (1-27) and 9 (1-100) radiation therapists were reported per center. The median number of new patients treated in 2019 was 600 (24-6200). A median 8% (1%-90%) decrease in patient volume was reported, with a median of 53 patients (1-490) remaining under treatment. Estimated revenue reduction was 20% or more in 53% of cases. Shortage of personal protective equipment was reported in 51.3% of centers, and 27% reported personnel shortage due to COVID-19. Reported delays in treatment for low-risk entities included early stage breast cancer (42.6%), low-risk status prostate cancer (67%), and nonmalignant conditions (42.6%). Treatment of COVID-19 patients at designated treatment times and differentiated bunkers were reported in 22.6% and 10.4% of centers, respectively. Telehealth initiatives have been started in 64.3% of facilities to date for on-treatment (29.6%) and posttreatment (34.8%) patients. CONCLUSIONS: Regional information regarding COVID-19 pandemic in Latin America may help elucidate suitable intervention strategies for personnel and patients. Follow-up surveys will be performed to provide dynamic monitoring the pandemic's impact on radiation therapy services and adoption of ameliorating measures.

Low-kilovolt x-ray intraoperative radiotherapy for pT3 locally advanced colon cancer: a single-institution retrospective analysis.

BACKGROUND: Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT. METHODS: We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS. RESULTS: The median follow-up of patients was 20.5 months (range, 6.1-38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively. CONCLUSION: Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.

Location as Destiny: Identifying Geospatial Disparities in Radiation Treatment Interruption by Neighborhood, Race, and Insurance.

PURPOSE: Radiation therapy interruption (RTI) worsens cancer outcomes. Our purpose was to benchmark and map RTI across a region in the United States with known cancer outcome disparities. METHODS AND MATERIALS: All radiation therapy (RT) treatments at our academic center were cataloged. Major RTI was defined as ≥5 unplanned RT appointment cancellations. Univariate and multivariable logistic and linear regression analyses identified associated factors. Major RTI was mapped by patient residence. A 2-sided P value <.0001 was considered statistically significant. RESULTS: Between 2015 and 2017, a total of 3754 patients received RT, of whom 3744 were eligible for analysis: 962 patients (25.8%) had ≥2 RT interruptions and 337 patients (9%) had major RTI. Disparities in major RTI were seen across Medicaid versus commercial/Medicare insurance (22.5% vs 7.2%; P < .0001), low versus high predicted income (13.0% vs 5.9%; P < .0001), Black versus White race (12.0% vs 6.6%; P < .0001), and urban versus suburban treatment location (12.0% vs 6.3%; P < .0001). On multivariable analysis, increased odds of major RTI were seen for Medicaid patients (odds ratio [OR], 3.35; 95% confidence interval [CI], 2.25-5.00; P < .0001) versus those with commercial/Medicare insurance and for head and neck (OR, 3.74; 95% CI, 2.56-5.46; P < .0001), gynecologic (OR, 3.28; 95% CI, 2.09-5.15; P < .0001), and lung cancers (OR, 3.12; 95% CI, 1.96-4.97; P < .0001) compared with breast cancer. Major RTI was mapped to urban, majority Black, low-income neighborhoods and to rural, majority White, low-income regions. CONCLUSIONS: Radiation treatment interruption disproportionately affects financially and socially vulnerable patient populations and maps to high-poverty neighborhoods. Geospatial mapping affords an opportunity to correlate RT access on a neighborhood level to inform potential intervention strategies.

Association of Medicaid Insurance With Survival Among Patients With Small Cell Lung Cancer.

Importance: Small cell lung cancer (SCLC) is an aggressive neoplasm requiring rapid access to subspecialized multidisciplinary care. For this reason, insurance coverage such as Medicaid may be associated with oncologic outcomes in this disproportionately economically vulnerable population. With Medicaid expansion under the Affordable Care Act, it is important to understand outcomes associated with Medicaid coverage among patients with SCLC. Objective: To determine the association of Medicaid coverage with survival compared with other insurance statuses. Design, Setting, and Participants: This cohort study included adult patients with limited-stage (LS) and extensive-stage (ES) SCLC in the US National Cancer Database from 2004 to 2013. Data were analyzed in January 2019. Main Outcomes and Measures: Patients were analyzed with respect to insurance status. Associations of insurance status with survival were interrogated with univariate analyses, multivariable analyses, and propensity score matching. Results: A total of 181 784 patients with SCLC (93 131 [51.2%] female; median [interquartile range] age; 67 [60-75] years for patients with LS-SCLC and 68 [60-75] years for patients with ES-SCLC) were identified, of whom 70 247 (38.6%) had LS-SCLC and 109 479 (60.2%) had ES-SCLC. On univariate analyses of patients with LS-SCLC, Medicaid coverage was not associated with a survival advantage compared with being uninsured (hazard ratio, 1.02; 95% CI, 0.96-1.08; P = .49). Likewise, on multivariable analyses of patients with ES-SCLC, compared with being uninsured, Medicaid coverage was not associated with a survival advantage (hazard ratio, 1.00; 95% CI, 0.96-1.03; P = .78). After propensity score matching, median survival was similar between the uninsured and Medicaid groups both among patients with LS-SCLC (14.4 vs 14.1 months; hazard ratio, 1.05; 95% CI, 0.98-1.12; P = .17) and those with ES-SCLC (6.3 vs 6.4 months; hazard ratio, 1.00; 95% CI, 0.96-1.04; P = .92). Conclusions and Relevance: Despite of billions of dollars in annual federal and state spending, Medicaid was not associated with improved survival in patients with SCLC compared with being uninsured in the US National Cancer Database. These findings suggest that there are substantial outcome inequalities for SCLC relevant to the policy debate on the Medicaid expansion under the Affordable Care Act.

Insurance status and head and neck radiotherapy interruption disparities in the Mid-Southern United States.

BACKGROUND: Relationships between health insurance coverage and radiotherapy (RT) interruption rates in patients with head and neck (H&N) cancer remain unclear. METHODS: We performed a retrospective cohort study at our academic center. Days of RT interruption for individual patients were tabulated, analyzed for explanatory variables, and geographically mapped. RESULTS: 894 of 7526 (11.9%) scheduled treatment days were interrupted, impacting 149 of 216 (69%) patients. Medicaid/uninsured patients experienced a 7.3 day mean interruption (SD = 9.9) vs 3.4 days (SD = 5.2) for Medicare/private patients (P < .001). RT interruption was predicted by insurance status in multivariate analysis (P = .008). Higher RT interruption rates overlapped geospatially with low predicted median household income and racial minority neighborhoods. CONCLUSION: Unplanned treatment interruptions are a key source for H&N RT quality shortfalls in Medicaid/uninsured patients. This is the first geographic benchmarking of H&N RT delivery disparities across a complete metropolitan region, and will guide interventions studies to reduce interruption risk.

"Eat to Live"-Piloting a Culinary Medicine Program for Head & Neck Radiotherapy Patients.

BACKGROUND: Head and neck radiotherapy (H&N RT) patients are at risk for malnutrition following treatment due to dysphagia and alterations in taste quality. This project studied feasibility of a food skills intervention strategy support food preparation, cooking confidence, and individualized dietary choices to support nutritional status in this patient population. METHODS: We piloted a monthly cooking class (called "Eat to Live") from November 2018 to January 2019. Every class included cooking and nutrition domains, organized around a specific meal of the day (i.e., breakfast, lunch, or dinner). Seven participants (4 patients, 3 caregivers) attended at least one class, with four participants (3 patients, 1 caregiver) completing all three classes. Pre- and post-study measures (self-administered questionnaires) assessed changes in cooking behavior, dietary choices, and taste sensation before and after the intervention. RESULTS: Healthful eating scores increased modestly from start to finish of the class (1.5 to 1.7 on a 3-point scale), with averaged patient preference scores for healthy foods increasing incrementally. This took place despite physical taste scores declining across the 3-month study. After completing the class, participants were more likely to select fresh fruits and vegetables, grains, lean cuts of meat, and dairy products. Patients also adopted positive behavioral modifications to their diets, such as eating out at restaurants less often and baking/grilling foods instead of frying. CONCLUSIONS: To our knowledge, this is the first published report on feasibility and patient acceptance of an evidence-based culinary medicine intervention in H&N RT patients. We observed objective improvements in dietary choices and cooking confidence in a small cohort of patient/caregiver dyads. This pilot work justifies follow-on development of a more comprehensive intervention optimized for patient convenience and longitudinal support.

The Evolving Role of Radiotherapy for Head and Neck Cancer.

The length and quality of head and neck cancer survivorship continues to meaningfully improve. Radiotherapy has been central to this process through advances in treatment delivery, fractionation schemas, radiosensitizing systemic therapy, and thoughtful interplay with technical surgical improvements. The future looks brighter still, with ongoing progress in targeted biologic therapy, immuno-oncology, and molecular-genetic tumor characterization for personalized treatment. Head and neck cancer, a disease once fraught with nihilism and failure, is evolving into a major success story of modern multidisciplinary cancer care.

Veterans Affairs Insurance Disparities for Metastatic Lung Cancer in the Hawaiian Islands.

INTRODUCTION: The highest concentration of military personnel in the United States is located in Hawaii where occupational exposures, such as to asbestos in the Pacific Fleet shipyards, predispose them to thoracic malignancies. For this reason, Veterans Affairs (VA) insurance outcomes for lung cancer in Hawaii are of interest. METHODS: All cases of lung cancer in the Hawaii Tumor Registry from 2000 to 2015 were evaluated. The selection criterion included evidence of extensive-stage SCLC (ES-SCLC) or metastatic NSCLC. Overall survival was compared using the Kaplan-Meier log-rank method. Univariate analysis and multivariable analysis (MVA) were carried out to understand the variables associated with overall survival. RESULTS: There were 434 cases of ES-SCLC and 2139 cases of metastatic NSCLC identified. VA insurance (median survival [MS], 2 mo), Medicaid (MS, 4 mo), and Medicare (MS, 4 mo) had worse survival (log-rank p < 0.001) than private insurance (MS, 8 mo). In ES-SCLC, VA insurance (hazard ratio [HR], 2.74; 95% confidence interval [CI]: 1.50-5.01; p = 0.001) and Medicaid (HR, 1.46; 95% CI: 1.04-2.03; p = 0.027) had significantly worse survival compared with private insurance on MVA. VA insurance (HR, 1.84; 95% CI: 1.34-2.53; p < 0.001) and Medicaid (HR, 1.40; 95% CI: 1.20-1.63; p < 0.001) also had worse survival compared with private insurance in metastatic NSCLC on MVA. CONCLUSIONS: VA insurance coverage was associated with dismal survival for metastatic lung cancer that was effectively similar to hospice or supportive care, compelling further investigation to identify reasons for this disparity.

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.

Definitive Pelvic Radiotherapy and Survival of Patients With Newly Diagnosed Metastatic Anal Cancer.

Background: Chemotherapy with or without pelvic radiotherapy (RT) is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for metastatic anal cancer (MAC), despite limited clinical evidence for RT in this setting. In addition, increasing evidence shows that local therapies, including RT, may increase patient survival for some types of metastatic cancers. The purpose of this study was to evaluate the patterns of care and association between definitive pelvic RT and overall survival (OS) for patients with MAC. Methods: The National Cancer Database was analyzed to evaluate OS of patients with newly diagnosed MAC treated with chemotherapy with or without pelvic RT. Those who did not undergo treatment, treated with surgery, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results: From 2004 through 2015, 437 patients received chemotherapy alone and 1,020 received pelvic chemoradiotherapy (CRT). At a median follow-up of 17.3 months, CRT was associated with improved OS on univariate (P<.001) and multivariate analysis (hazard ratio [HR], 0.70; 95% CI, 0.61-0.81; P<.001). Propensity score-matched analysis demonstrated superior median survival (21.3 vs 15.9 months) and 2-year OS rates (46% vs 34%) with CRT compared with chemotherapy alone (P<.001). Landmark analyses limited to long-term survivors of ≥1, ≥2, and ≥4 years showed improved OS with CRT in all subsets (all P<.05). CRT with therapeutic doses (≥45 Gy) was associated with longer median survival than palliative doses (<45 Gy) and chemotherapy alone (24.9 vs 10.9 vs 15.6 months, respectively; P<.001). The benefit of CRT was present among not only those with distant lymph node metastasis (HR, 0.63; P=.04) but also those with distant organ disease (HR, 0.74; P<.001). Conclusions: In this large hypothesis-generating analysis, patients with newly diagnosed MAC who received definitive pelvic RT with chemotherapy lived significantly longer than those who received chemotherapy alone. Prospective trials evaluating definitive local RT for MAC are warranted.