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Background For patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making. Materials and Methods Patients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS). Results In total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS. Conclusion This single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.

The recently identified bilateral macroscopic tubarial salivary glands present a potential opportunity for further toxicity mitigation for patients receiving head and neck radiotherapy. Here, we show superior dosimetric sparing of the tubarial salivary glands with proton radiation therapy (PRT) compared to intensity-modulated radiotherapy (IMRT) for patients treated postoperatively for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved, equivalent IMRT plan to serve as a reference. The main end point was dose delivered to the tubarial salivary glands by modality, assessed via a 2-tailed, paired t-test. We also report disease outcomes for the entire cohort, via the Kaplan-Meier method. Sixty-four patients were identified. The mean RT dose to the tubarial salivary glands was 23.6 Gy (95% confidence interval (CI) 21.7 to 25.5) and 30.4 Gy (28.6 to 32.2) for PRT and IMRT plans (p0.0001), respectively. With a median follow-up of 25.2 months, the two-year locoregional control, progression-free survival and overall survival were 97.8% (95% CI 85.6% to 99.7%), 94.1% (82.8% to 98.1%) and 98.1% (87.4% to 99.7%), respectively. Our study suggests that meaningful normal tissue sparing of the recently identified tubarial salivary glands is achievable with PRT. The apparent gains with PRT did not impact disease outcomes, with only 1 observed locoregional recurrence (0 local, 1 regional). Further studies are warranted to explore the impact of the improved dosimetric sparing of the tubarial salivary glands conveyed by PRT on patient toxicity and quality of life.

BACKGROUND Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high-risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)-negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV-associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS-TMT. METHODS In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan-Meier methodology, and toxicities were ascertained via chart review. RESULTS In our cohort of 178 patients, 5-year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin-treated patients were 2.7%, 3.4%, and 11.0%, respectively. CONCLUSIONS Patients with HPV + OPSCC who underwent TORS-TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy.

Purpose To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calculation. Materials and Methods The DECT images were acquired at 80 kVp and 140 kVp and were processed with computed tomography scanner software to derive the electron density and effective atomic number images. Reference SPRs of tissue-equivalent plugs from Gammex (Middleton, Wisconsin) and CIRS (Computerized Imaging Reference Systems, Norfolk, Virginia) electron density phantoms were used for validation and comparison of SECT versus DECT calculated through the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California) application programming interface scripting tool. An in-house software was also used to create DECT SPR computed tomography images for comparison with the script output. In the workflow, using the Eclipse system application programming interface script, clinical plans were optimized with the SECT image set and then forward-calculated with the DECT SPR for the final dose distribution. In a second workflow, the plans were optimized using DECT SPR with reduced range-uncertainty margins. Results For the Gammex phantom, the root mean square error in SPR was 1.08% for DECT versus 2.29% for SECT for 10 tissue-surrogates, excluding the lung. For the CIRS Phantom, the corresponding results were 0.74% and 2.27%. When evaluating the head and neck plan, DECT optimization with 2% range-uncertainty margins achieved a small reduction in organ-at-risk doses compared with that of SECT plans with 3.5% range-uncertainty margins. For the liver case, DECT was used to identify and correct the lipiodol SPR in the SECT plan. Conclusion It is feasible to use DECT for proton-dose calculation in a commercial treatment planning system in a safe manner. The range margins can be reduced to 2% in some sites, including the head and neck.

We evaluated if proton therapy is associated with decreased acute toxicities compared to intensity-modulated radiation therapy (IMRT) in patients receiving concurrent chemoradiotherapy for head and neck cancers.We analyzed 580 patients with nonmetastatic head and neck cancers. Primary endpoint was any 90-day grade ≥3 toxicity, prospectively collected and graded per CTCAEv4. Modified Poisson regression models were used.Ninety-five patients received proton and 485 IMRT. The proton group had more HPV-positive tumors (65.6 vs. 58.0%, p = 0.049), postoperative treatment (76.8 vs. 62.1%, p = 0.008), unilateral neck treatment (18.9 vs. 6.6%, p 0.001) and significantly lower doses to organs-at-risk compared to IMRT group. Adjusted for patient and treatment characteristics, the proton group had decreased grade 2 dysgeusia (RR0.67, 95%CI 0.53-0.84, p = 0.004) and a trend toward lower grade ≥3 toxicities (RR0.60, 95%CI 0.41-0.88, p = 0.06).Proton therapy was associated with significantly reduced grade 2 dysgeusia and nonstatistically significant decrease in acute grade ≥3 toxicities compared to IMRT.

Background Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. Methods Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. Results There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P Conclusion Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.

Purpose This trial tested the safety and efficacy of a novel, deintensified radiation therapy (RT) approach after initial surgical resection for patients with human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods and Materials This single-arm phase 2 prospective clinical trial enrolled 60 patients with stage pT1-pT2 N1-3 HPV-associated OPSCC treated with transoral robotic surgery (TORS) and selective neck dissection at a single institution between May 2014 and September 2017. Patients had favorable features at the primary site (negative surgical margins ≥2 mm, no perineural invasion, and no lymphovascular invasion) but required adjuvant therapy based on lymph node involvement. Surgeries were all performed at a high-volume head and neck cancer center with expertise in TORS. Patients received postoperative RT to at-risk areas in the involved neck (60-66 Gy) and uninvolved neck (54 Gy). The resected primary site was treated as an active avoidance structure in the treatment planning of postoperative RT. Concurrent chemotherapy was administered for patients with extranodal extension. Results Median follow-up of the 60 patients enrolled was 2.4 years (range, 8.5-53.8 months). A single patient recurred at the primary site, for 2-year local control of 98.3%. One patient (1.7%) developed a regional neck recurrence, and 2 patients (3.3%) developed distant metastases. Measured 2-year local recurrence–free survival was 97.9% (95% confidence interval, 86.1%-99.7%). Overall survival was 100% at the time of analysis. The mean radiation dose to the primary site was 36.9 Gy (standard deviation, 10.3 Gy). Two patients (3.3%) experienced late soft tissue necrosis in the primary site surgical bed that resolved within 2 months. Feeding tube dependence rates were 0% during RT, 3.3% temporarily during follow-up, and 0% at last follow-up. Conclusions Deintensified postoperative RT that avoids the resected primary tumor site and targets only the at-risk neck after TORS for selected patients with HPV-associated OPSCC may be safe and is worthy of further study.

Although dose de-escalation is one proposed strategy to mitigate long-term toxicity in human papillomavirus associated oropharyngeal cancer, applying more stringent normal tissue constraints may be a complementary approach to further reduce toxicity. Our study demonstrates that in a postoperative setting, improving upon nationally accepted constraints is achievable and leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease control.We identified 92 patients at our institution between 2015 and 2019 with p16+ oropharyngeal cancer who were treated with adjuvant volumetric modulated arc therapy. We included patients treated to postoperative doses and standard volumes (including bilateral neck). Doses delivered to organs at risk were compared with recommended dose constraints from a recent cooperative group head and neck cancer trial of radiation therapy to 60 Gy. We applied validated and published NTCP models for dysphagia, dysgeusia, esophagitis, oral mucositis, and xerostomia relevant to oropharyngeal cancer.Achievable and delivered mean doses to most normal head and neck tissues were well below national recommended constraints. This translates to notable absolute NTCP reductions for salivary flow (10% improvement in contralateral parotid, 35% improvement in submandibular gland), grade ≥ 2 esophagitis (23% improvement), grade ≥ 3 mucositis (17% improvement), dysgeusia (10% improvement), and dysphagia (8% improvement). Locoregional control at a median follow-up of 26.3 months was 96.7%, with only 3 patients experiencing locoregional recurrence (1 local, 2 regional).Modern radiation therapy planning techniques allow for improved normal tissue sparing compared with currently established dose constraints without compromising disease control. These improvements may lead to reduced toxicity in a patient population expected to have favorable long-term outcomes. Stricter constraints can be easily achieved and should be used in conjunction with other evolving efforts to mitigate toxicity.

PURPOSE: Physical activity is associated with decreased hospitalization during cancer treatment. We hypothesize that activity data can help identify and triage high-risk patients with GI cancer undergoing concurrent chemoradiation. MATERIALS AND METHODS: This prospective study randomly assigned patients to activity monitoring versus observation. In the intervention arm, a 20% decrease in daily steps or 20% increase in heart rate triggered triage visits to provide supportive care, medication changes, and escalation of care. In the observation group, activity data were recorded but not monitored. The primary objective was to show a 20% increase in triage visits in the intervention group. Secondary objectives were estimating the rates of emergency department (ED) visits and hospitalizations. Crude and adjusted odds ratios were computed using logistic regression modeling. RESULTS: There were 22 patients in the intervention and 18 in the observation group. Baseline patient and treatment characteristics were similar. The primary objective was met, with 3.4 more triage visits in the intervention group than in the observation group (95% CI, 2.10 to 5.50; P < .0001). Twenty-six (65.0%) patients required at least one triage visit, with a higher rate in the intervention arm compared with that in the observation arm (86.4% v 38.9%; odds ratio, 9.95; 95% CI, 2.13 to 46.56; P = .004). There was no statistically significant difference in ED visit (9.1% v 22.2%; P = .38) or hospitalization (4.5% v 16.7%; P = .31). CONCLUSION: It is feasible to use activity data to trigger triage visits for symptom management. Further studies are investigating whether automated activity monitoring can assist with early outpatient management to decrease ED visits and hospitalizations.

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances.Trial registration: ClinicalTrials.gov, a service of the US National Institute of Health (NCT 03030859). Registered on 22 January 2017.

Purpose: Lymphedema is a common debilitating late effect among patients post-head and neck cancer (HNC) treatment. Head and neck lymphedema was associated with symptom burden, functional impairment, and decreased quality of life. The objective of this study was to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema, symptom burden, and neck range of motion among HNC survivors. Methods: This was a single-arm, pre- and post-design clinical trial. Eligible patients included those with lymphedema after completion of complete decongestive therapy (CDT) and 3 to 18 months after completion of cancer therapy. The intervention included PBM therapy 2 times a week for 6 weeks for a total of 12 treatments. Lymphedema, symptom burden, and neck range of motion were measured at baseline, end-of-intervention, and 4-week post-intervention. Results: Of the 12 patients enrolled in the study, 91.7% (n = 11) completed the study intervention and assessment visits, and no adverse events were reported. When comparing the baseline to 4-week post-intervention, we found statistically significant improvements in the severity of external lymphedema, symptom burden, and neck range of motion (all P Conclusion: PBM therapy was feasible and potentially effective for the treatment of head and neck lymphedema. Future randomized controlled trials are warranted to examine the efficacy of PBM therapy for HNC-related lymphedema. Trial Registration Number and Date of Registration: ClinicalTrials.gov Identifier: NCT03738332; date of registration: November 13, 2018.

Objectives Sex differences in surgically treated HPV-associated oropharyngeal squamous cell carcinoma are not defined due to the low number of affected women. We explored the oncologic outcomes of men and women with p16-positive oropharyngeal squamous cell carinoma treated with primary surgery. Materials and Methods Retrospective analysis of patients with HPV-related oropharyngeal cancer treated with surgery and pathology guided adjuvant therapy from 2007 to 2017. Primary end point was recurrence-free and overall survival. Results Of 468 men (86.7%) and 72 women (13.3%), women presented more often with clinical N0 nodal disease (25% vs 12.2%). There were no differences in adverse pathologic features or T stage, although women were more likely to present with N0 disease (16.7% vs 10%), less N2 disease (6.9% vs 17.7%, p = 0.03), and more stage I disease (88.9% vs 75%). As a result, women were more likely to undergo surgery alone (30.6% vs 14.1%) while men were more likely to require adjuvant radiation therapy (47.2% vs 36.1%). Four women (5.6%) and 30 men (6.4%, p = 0.8) died during follow-up. Multivariate analysis controlling for age, sex, treatment, and pathologic stage demonstrated no differences in overall survival between men and women. There were no differences in recurrence-free or overall survival between men and women at two and five years. Conclusions Although women undergoing transoral robotic surgery for HPV+ oropharyngeal squamous cell carcinoma may have less advanced disease, upfront surgery with pathology-guided adjuvant therapy produces similar oncologic results in men and women while accounting for disease burden.

Purpose: This study evaluates the toxicity and tumor response with concurrent nab-paclitaxel chemoradiotherapy (CRT) compared with standard (5-fluorouracil or gemcitabine) CRT. Materials and Methods: Fifty patients with borderline resectable or unresectable pancreatic adenocarcinoma from 2014 to 2017 were divided into 2 groups: concurrent nab-paclitaxel (100 to 125 mg/m2 weekly) CRT (median: 2.1 Gy fraction size and 52.5 Gy total) or standard CRT (median: 1.8 Gy fraction size, 54.5 Gy total). The primary endpoint was toxicity, and secondary endpoints were local failure and conversion to resectability. Comparisons were made using rank-sum or Fisher exact test and multivariable competing risk regression for the cumulative incidence of local failure. Results: There were 28 patients in the nab-paclitaxel CRT group and 22 in the standard CRT group; 88% had the unresectable disease. The median follow-up was 18 months. The median duration of chemotherapy before concurrent CRT was 1.9 and 2.3 months in the nab-paclitaxel and standard CRT groups (P=0.337), and radiotherapy dose was 52.5 Gy (range, 52.5 to 59.4 Gy) and 54.5 Gy (range, 45.0 to 59.4 Gy), respectively. There were no statistically significant grade ≥2 toxicities. The nab-paclitaxel CRT group experienced a nonstatistically significant lower incidence of local failure (hazard ratio=0.91, 95% confidence interval: 0.27-3.03, P=0.536). More patients in the nab-paclitaxel CRT group proceeded to surgery (9/28 compared with 3/22 in the standard CRT, P=0.186); of which 6 (25%) in the nab-paclitaxel CRT and 2 (10%) in the standard CRT groups were initially unresectable. Conclusions: Nab-paclitaxel CRT had similar toxicity compared with standard CRT in the treatment of borderline resectable or unresectable pancreatic cancer. Its use was associated with an arithmetically lower cumulative incidence of local failure and an arithmetically higher conversion to resectability, both of which were not statistically significant.

OBJECTIVE To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). STUDY DESIGN Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN-guideline-compliant adjuvant therapy at a single institution from 2007 to 2017. METHODS Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments. RESULTS Of 541 patients who completed guideline-indicated therapy, the estimated 5-year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09-0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5-year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P

Oral proliferative verrucous leukoplakia (PVL) is a rare, progressive form of leukoplakia with a high rate of malignant transformation. No therapies are known to lower the rate of malignant transformation and prevent a recurrence. An 84-year-old patient with a years-long history of symptomatic PVL of the hard palate refractory to CO2 laser ablation presented to the radiation oncology clinic for consideration of non-surgical management. High dose rate brachytherapy was used to deliver 36 Gy in 12 fractions to the hard palate using an Ir-192 source with a custom-molded applicator. By three months of follow-up, the patient had complete regression of the PVL and resolution of acute mucositis. With 18 months of follow-up, the patient remains disease- and symptom-free without toxicities of treatment. High dose rate surface applicator brachytherapy is a feasible and potentially effective treatment for oral PVL, yielding durable control with low long-term toxicity.

The effect of health insurance on management and outcomes in melanoma is unclear. Using the National Cancer Database (NCDB), we evaluated the effect of insurance on (1) stage at diagnosis, (2) receipt of immunotherapy, and (3) overall survival (OS) among patients with melanoma. We included patients with stage I-IV melanoma diagnosed from 2011 to 2015. Patients were stratified by age (below 65 vs. 65 y or above) and insurance (commercial, Medicare, Medicaid and uninsured). We evaluated the association between insurance and (1) stage at diagnosis (stage I-III vs. IV) and (2) receipt of immunotherapy (stage IV) using multivariable logistic regression. The association of insurance status with OS in metastatic patients who received immunotherapy was assessed using Kaplan-Meier and Cox proportional hazards analyses. The study included 167,130 patients; 52% had commercial insurance, 43% had Medicare, 3% had Medicaid and 2% were uninsured. In patients below 65 years, those with Medicaid and the uninsured had a higher likelihood of presenting with metastatic melanoma and were less likely to receive immunotherapy compared with those with commercial insurance. Further among those who received immunotherapy, patients with Medicaid (hazard ratio: 1.51, P=0.001) and no insurance (hazard ratio: 1.37, P=0.046) had an inferior OS. In patients 65 years or above, whereas Medicare was associated with an increased likelihood of presenting with metastatic disease, there was no significant difference in receipt of immunotherapy or OS as compared with commercial insurance. In this large modern cohort, insurance was associated with stage at diagnosis, receipt of immunotherapy, and OS for patients below 65 years old with melanoma.

Purpose: The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensitymodulated radiation therapy (IMRT) for oropharynx cancer and to use a model-based approach to investigate the added value of PBT in preventing treatment complications.Methods and Materials: For patients with advanced-stage oropharynx cancer treated with curative intent (PBT, n = 30; IMRT, n = 175), NTCP models were developed using multivariable logistic regression analysis with backward selection. For PBTtreated patients, an equivalent IMRT plan was generated to serve as a reference to determine the benefit of PBT in terms of NTCP. The models were then applied to the PBT-treated patients to compare predicted and observed clinical outcomes (calibration- in-the-large). Five binary endpoints were analyzed at 6 months after treatment: dysphagia >= grade 2, dysphagia >= grade 3, xerostomia >= grade 2, salivary duct inflammation >= grade 2, and feeding tube dependence. Corresponding toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Paired t tests and Wilcoxon rank tests were used to compare mean NTCP results for endpoints between PBT and IMRT.Results: NTCP models developed based on outcomes from all patients were applied to those receiving PBT. NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing significantly higher NTCP values with IMRT. PBT was associated with statistically significant reductions in the mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of >= grade 2 dysphagia and >= grade 2 xerostomia.Conclusions: NTCP models predict significant improvements in the probability of short-term, treatment-related toxicity with PBT compared with IMRT for oropharyngeal cancer. This study demonstrates an NTCP model-based approach to compare predicted patient outcomes when randomized data are not available. (C) 2019 Elsevier Inc. All rights reserved.

Purpose One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC. Materials and Methods This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.

PURPOSE/OBJECTIVE(S) To identify the patient characteristics, treatment indications, and toxicities among patients receiving proton beam therapy (PBT) in the final year of life at a tertiary academic medical center. MATERIALS/METHODS A retrospective review of patients who received PBT within the final 12 months of life was performed. Electronic medical records were reviewed for patient and treatment details from 2010-2019. Follow-up was calculated from start of PBT until death or last follow-up. Treatment intent was retrospectively defined as curative treatment for localized disease, for isolated local recurrence, oligometastatic disease, durable local control, or palliation of symptoms. Durable local control was defined as treatment for durable control of otherwise incurable disease whereas palliation was defined as treatment for symptom palliation only. Acute ( 3 months) toxicities were graded using the CTCAE v5.0. Chi-square test was performed to evaluate factors associated with palliative treatment. Simple logistic regression was used to evaluate factors associated with any acute toxicity. RESULTS During the study period, 299 patients were treated at the end of life (EOL) out of 5802 total patients treated with PBT (5.2%). Mean age was 66 years (19-94 years), with 58% male. The most common cancers were non-small cell lung cancer (27%), hepatocellular carcinoma (13%), and small cell lung cancer (6%). Eleven percent of patients were treated for symptom palliation; the remainder were treated for durable local control (57%), definitively (16%), for an isolated local recurrence (14%), or oligometastatic disease (2%). Forty-five percent received PBT for re-irradiation. Concurrent systemic therapy was delivered to 47%. Median prescribed dose was 50 Gy (15-80 Gy). Mean treatment time was 34 days (1-189 days). Seven patients received split-course proton therapy for hepatocellular carcinoma. Median time from final fraction to death was 139 days (1-363 days). On average, patients spent 24% of the remaining days of life receiving PBT. Acute toxicity of any grade was noted in 85% of patients (31% G1, 53% G2, 15% G3). Fifty-two patients (17%) experienced chronic toxicity, the most severe of which was a tracheo-esophageal fistula (G4). In the chi-square test, breast and hematologic malignancy were associated with palliative intent (χ2 (1, N = 14) = 15.9, P < 0.001; (χ2 (1, N = 14) = 15.9, P < 0.001). In the simple logistic regression model, concurrent systemic therapy was positively associated with any acute toxicity (OR: 2.0, P = 0.05). CONCLUSION The number of patients treated with PBT at the EOL was low compared to all-comers. Many of these patients received treatment with definitive doses and concurrent systemic therapy. Nearly half received re-irradiation. Grade 3 or higher acute toxicity was moderate, and some patients spent a large portion of their remaining days on treatment. Thus, the incorporation of a prognostic indicator in clinical practice may further optimize use of PBT.

PURPOSE/OBJECTIVE(S) Toxicity mitigation is a salient focus in the treatment of HPV-associated oropharyngeal cancer. As the standard of care evolves, toxicity mitigation can be facilitated by adopting more stringent normal tissue constraints. We hypothesize that further reduction in currently accepted constraints leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease outcomes. MATERIALS/METHODS This was a retrospective, single-institution study of patients with oropharynx cancer treated with adjuvant volumetric modulated arc therapy to standard doses (60-66 Gy) and volumes (i.e., bilateral neck) from 2015-2018. Doses delivered to organs at risk were compared to recommended dose acceptance criteria from a recent, cooperative trial of RT to 60 Gy (NRG HN002). We applied validated, published NTCP models for xerostomia, dysphagia, dysgeusia, oral mucositis and esophagitis relevant to oropharyngeal cancer. RESULTS 92 patients were identified. Median follow-up was 2.2 years. The doses achieved and corresponding estimates of NTCP are shown in Table 1, as compared to a nationally recognized standard (NRG HN002). Notable NTCP reductions were observed for salivary flow, dysphagia, dysgeusia, mucositis, and esophagitis. The use of more stringent constraints did not impact disease outcome, with only a total of 3 patients having experienced locoregional recurrence (1 local, 2 regional), for an overall locoregional control of 96.7%. CONCLUSION Improved normal tissue sparing compared to current dose constraint standards is achievable with contemporary RT planning techniques. These improved constraints may lead to decreased toxicity, while preserving excellent disease outcomes. Our constraints can easily be adopted as standard of care and used in conjunction with other efforts to mitigate toxicity.

PURPOSE/OBJECTIVE(S) Patients undergoing concurrent chemoradiotherapy (CRT) for head and neck cancer often experience significant toxicities. Proton therapy permits decreased dose delivery to non-target structures and the potential for superior organs-at-risk sparing. The aim of this study was to evaluate if proton therapy is associated with decreased acute grade ≥3 toxicities compared to photon therapy in the setting of concurrent CRT for head and neck cancers. MATERIALS/METHODS This study included 654 adult patients with nonmetastatic, locally advanced head and neck cancer treated with definitive concurrent CRT from January 1, 2011 to April 30, 2019 at one institution. 90-day toxicity data were prospectively collected as defined by Common Terminology Criteria for Adverse Events, version 4. Acute toxicities were grouped into five categories for analysis: mucosal (mucosal infection, mucositis), oral cavity (dry mouth, dysgeusia), swallow (aspiration, dysphagia), constitutional (fatigue, anorexia, dehydration), and skin (dermatitis, edema, superficial soft tissue necrosis, alopecia) toxicities. Modified Poisson regression models with covariate adjustment were used to model toxicity risk following multiple imputation for missing covariate values. Ten hypotheses were tested. Thus, the Bonferroni multiple testing correction was applied and statistical significance was assessed at the 0.005 level. RESULTS One hundred and six patients received proton therapy and 548 received photon therapy. Patients receiving proton therapy were older (mean age [SD] 61.2 [12.2] vs 58.9 [9.30], P = 0.029) and were more likely to be HPV-positive (67.0% vs 57.0%, P = 0.036). Proton therapy patients had lower dose to the parotid glands (right mean [SD], 21.8 Gy [12.9] vs 27.9 [11.3], P < 0.001; left 23.1 Gy [12.7] vs 27.2 [11.0], P = 0.001), oral cavity (13.7 Gy [9.88] vs 28.8 [10.8], P < 0.001) and constrictor muscle (35.6 Gy [10.37] vs 43.7 [9.24], P < 0.001) compared to photon therapy patients. Charlson-Deyo comorbidity scores were similar for both groups (mean [SD] 6.18 [1.74] vs 6.40 [2.57], P = 0.39), as were the distributions for sex (P = 0.118), race (P = 0.16), cancer stage (P = 0.163), and baseline ECOG (P = 0.57). In covariate-adjusted analyses, proton therapy was associated with a significantly lower relative risk of any 90-day grade ≥3 toxicity (0.57, 95% CI 0.40-0.83, P = 0.003). For acute grade 2 toxicity proton therapy was associated with significantly reduced relative risk of oral cavity toxicity (0.74, 95% CI 0.61-0.90, P = 0.002) but higher skin toxicity (1.35, 95% CI 1.14-1.59, P = 0.0004). CONCLUSION Concurrent chemoradiotherapy with proton therapy for head and neck cancers was associated with lower dose to nontarget structures and significantly reduced acute grade ≥3 toxicity and acute grade 2 oral cavity toxicity compared to photon therapy. Grade 2 skin toxicity favored photon therapy.

Background Patients with human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV-negative OPSCC. Methods Retrospective analysis HPV-negative OPSCC patients who underwent TORS, neck dissection and pathology-guided adjuvant therapy (2005-2017). Results Fifty-six patients (91.1% stage III/IV) were included. Three-year overall survival, locoregional control, and disease-free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow-up 30.6 months, interquartile range 18.4-66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long-term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively. Conclusion The TORS approach for resectable HPV-negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity.

We conducted a phase I dose-escalation trial of radiation with ipilimumab in patients with melanoma with ≥2 metastatic lesions. Here, we report the final full clinical analysis. Patients received RT (6 or 8 Gy x 2 or 3 doses) to a single lesion followed by 4 cycles of ipilimumab. The primary endpoint was maximum tolerated dose of RT, and secondary endpoint was response at non-radiated sites. Twenty-two patients with treatment-naïve (n = 11) or treatment-refractory (n = 11) Stage IV melanoma were enrolled. There were 31 treatment-related adverse events (AEs), of which 16 were deemed immune-related. Eleven patients had grade 3 AEs (no grade 4/5). There were no dose-limiting toxicities related to the radiation/ipilimumab combination. Five of 22 patients (22.7%, 95% CI 7.8–45.4%) had partial response as best response and three (13.6%) had stable disease. Median overall survival was 10.7 months (95% CI, 4.9 months to not-estimable) and median progression-free survival 3.6 months (95% CI, 2.9 months to 7.8 months). Seven patients were still alive at the time of last follow-up (median follow-up 89.2 months), most of whom received pembrolizumab after progression. Radiotherapy followed by ipilimumab was well tolerated and yielded a response rate that compares favorably to the objective response rate with ipilimumab alone. Furthermore, 32% of patients are long-term survivors, most of whom received pembrolizumab. Based on these results, the recommended dose that was used in subsequent Phase 2 trials was 8 Gy x 3 doses. Clinical Trial Registration: NCT01497808 (www.clinicaltrials.gov)

OBJECTIVES: Increasing use of transoral robotic surgery (TORS) is likely to impact outcomes for HPV+ oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to describe oncologic outcomes for a large HPV+ OPSCC cohort after TORS and develop a risk prediction model for recurrence under this treatment paradigm. MATERIALS AND METHODS: 634 HPV+ OPSCC patients receiving TORS-based therapy at a single institution were reviewed retrospectively to describe survival across the entire cohort and for patients suffering recurrence. Risks for distant metastatic recurrence (DMR) and locoregional recurrence (LRR) were modeled using multivariate logistic regression analyses of case-control sub-cohorts. RESULTS: 5-year overall and recurrence-free survival were 91.2% and 86.1%, respectively. 5-year overall survival was 52.5% following DMR and 83.3% after isolated LRR (P=.01). In case-control analyses, positive surgical margins were associated with DMR (adjusted OR 5.8, CI 2.1–16.0, P=.001), but not isolated LRR, and increased DMR risk 4.2 fold in patients with early clinical stage disease. By contrast, LRR was associated with not receiving recommended adjuvant therapy (OR 13.4, CI 6.3–28.5, P

BACKGROUND Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS). METHODS Three-hundred and sixty-four patients with treatment-naive, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared. RESULTS The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P

Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear.Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates.Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20).In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.

Introduction The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits. Methods Creation of consensus document. Results The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system. Conclusions These guidelines support an ethical approach for the management of head and neck cancers during the COVID‐19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature.

Background and Methods There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID‐19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life‐threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. Results After careful consideration of the options, we took different approaches in the care of these two patients. Conclusions Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immunocompromised patients. We provide some general principles to help guide patient management during the current pandemic.

We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers. There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) and the other(s) followed for response. Of the 24 patients, 20 (83%) had treatment-related adverse events (AEs) (all grade 1 or 2). There were eight grade 3 AEs, none treatment related. There were no dose-limiting toxicities or grade 4/5 AEs. Stratum 1: two patients (of 12) with progression on prior PD-1 blockade experienced prolonged responses (9.2 and 28.1 months). Stratum 2: one patient experienced a complete response and two had prolonged stable disease (7.4 and 7.0 months). Immune profiling demonstrated that anti-PD-1 therapy and radiation induced a consistent increase in the proliferation marker Ki67 in PD-1-expressing CD8 T cells. HFRT was well tolerated with pembrolizumab, and in some patients with metastatic NSCLC or melanoma, it reinvigorated a systemic response despite previous progression on anti-PD-1 therapy. Clinical Trial Registration: NCT02303990 ( www.clinicaltrials.gov ).

Introduction The optimal management of locally advanced recto-sigmoid cancer is unclear. Although some experts advocate for upfront surgery, others recommend neoadjuvant chemoradiation followed by surgery. We used the National Cancer Database to characterize patterns-of-care and overall survival (OS) associated with these treatment strategies. Patients and Methods Patients with clinical stage II or III recto-sigmoid cancer who underwent surgery with or without adjunctive chemotherapy and/or radiotherapy from 2006 to 2014 were identified, and dichotomized into: (1) upfront surgery, and (2) neoadjuvant chemoradiation cohorts. Patterns-of-care were assessed using multivariable logistic regression. The association between neoadjuvant chemoradiation use and OS was assessed using Cox proportional hazards analysis with propensity score-matching. Results Of 9313 identified patients, 6756 (73%) underwent upfront surgery and 2557 (27%) received neoadjuvant chemoradiation. Treatment at academic facilities and higher clinical T stage were predictors of neoadjuvant chemoradiation use. Compared with upfront surgery, neoadjuvant chemoradiation resulted in fewer positive circumferential resection margins (384 [11%] patients vs. 108 [8%] patients; P = .001), and 478 [18.7%] patients achieved a pathologic complete response at surgery. In propensity score-matched analysis, neoadjuvant chemoradiation use was associated with improved OS (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90) compared with upfront surgery; 5-year estimated OS was 77.0% versus 72.0%, respectively. The improvement in OS persisted in landmark analysis of patients who survived at least 12 months. Conclusion Only a small percentage of patients with locally advanced recto-sigmoid cancer receive neoadjuvant chemoradiation even though its use might result in improved OS relative to upfront surgery. Prospective research is warranted to validate and standardize therapeutic strategies in patients with recto-sigmoid cancer.

Purpose/Objective(s) Patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) generally have a good prognosis, though those with locally advanced (LA) disease are at increased risk of locoregional failure (LRF) and distant metastases (DM). A recent SEER study suggested improvement in overall survival and cancer-specific mortality with trimodality therapy compared to definitive chemoradiation (dCRT) for LA HPV+ OPSCC, but is prone to confounding and lacks pattern of failure data. We therefore performed this retrospective analysis of oncologic outcomes for patients with T3/T4 HPV+ OPSCC treated at a high-volume TORS center with surgery +/- adjuvant therapy compared to dCRT alone. Materials/Methods Included were patients with cT3/T4 HPV+ OPSCC treated with dCRT or upfront TORS +/- adjuvant therapy from 2010-2019 with ≥1 year of follow-up. Patients with DM at diagnosis were excluded. Primary outcomes were freedom from LRF (FF-LRF) and LRF leading to death, defined as LRF directly resulting in death or occurring at the same time or before DM resulting in death. Secondary outcomes were freedom from DM (FF-DM) and cancer-specific survival (CSS). Patients were risk stratified based on criteria in the secondary analysis of RTOG 0129 by Ang et al (NEJM 2010): Low-risk: ≤10 pack-year (py) smoking, or > 10 py and N0–N2a disease (AJCC 7th ed.); Intermediate-risk: > 10 py and N2b-N3 disease. Fisher's exact test was used to compare demographics and Kaplan-Meier estimates to compare endpoints. Results 78 patients were treated with dCRT and 44 with upfront TORS. Significantly more dCRT patients were Intermediate-risk (per RTOG 0129 criteria) compared to TORS patients (35.9% vs 6.8%, P Conclusion This large, single-institution series of patients with T3/T4 HPV+ OPSCC treated with either dCRT or upfront TORS +/- adjuvant therapy shows high FF-LRF and low rates of LRF leading to death regardless of treatment. Even in patients with advanced T stage, dCRT was able to obtain excellent disease outcomes. Future prospective studies are warranted to determine which combinations of multimodality therapy are optimal for LA HPV+ OPSCC, incorporating both oncologic and functional outcome endpoints.

Purpose/Objective(s) This study sought to measure circulating plasma tumor-tissue modified human papilloma virus DNA (TTMV-HPV DNA) and kinetics following trans-oral robotic surgery (TORS), neck dissection, and adjuvant (chemo)radiation for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Materials/Methods Patients with p16+ OPSCC currently enrolled on an ongoing phase II clinical trial investigating radiation dose de-intensification following TORS and neck dissection (TORS version 2.0, NCT03729518) with available post-operative plasma samples were included. Plasma was collected following TORS procedure (∼6 weeks post-operatively), during adjuvant (chemo)radiation, and at treatment completion. Plasma samples were analyzed for TTMV-HPV DNA using a liquid biopsy assay. Multivariate robust linear regression analysis was used to identify clinicopathologic features associated with detectable post-operative TTMV-HPV DNA levels. Results Thirty-four patients were included (median age 59 years, IQR 55-62 years; 94% male). The majority of patients had pT1-2 (n = 32, 94%; 1 pT0,1 pT3) and pN1 (n = 32, 94%; 2 pN0) disease. Other pathologic features included LVI (n = 5, 15%), PNI (n = 2, 6%), close or positive margin (n = 9, 26%), number of positive nodes (median 1.5, IQR 1-2), largest node size (median 3.7 cm, IQR 3.0-4.4 cm), and ENE (n = 8, 24%; 4 macroscopic). The majority of patients had undetectable TTMV-HPV DNA following TORS (n = 31, 91%). Three patients (9%) had detectable TTMV-HPV DNA post-operatively with 2 having very low detectable levels (≤ 10 copies/mL) and 1 having a high detectable level (4421 copies/mL). Largest node size (P = 0.0083) and ENE (P = 0.041) were significantly associated with detectable post-operative TTMV-HPV DNA levels. Of those with initially undetectable TTMV-HPV DNA, levels remained undetectable during and after adjuvant (chemo)radiation with 1 patient developing a very low detectable level (7 copies/mL) following treatment. The 2 patients with low detectable TTMV-HPV DNA levels post-operatively (≤ 10 copies/mL) had complete clearance following adjuvant therapy. There were no locoregional recurrences (median follow-up 15 months, IQR 12-21 months) including the patient who developed a low detectable level (7 copies/mL) following treatment (currently 24 months post-TORS). The patient with the high detectable level post-operatively (4421 copies/mL) developed osseous metastatic disease 5 months post-TORS. Conclusion Tumor-tissue modified HPV DNA can be detected with high sensitivity following definitive surgery for p16+ OPSCC. Further prospective studies are warranted to determine if the observed range of post-operative values allows for stratification of patients into those with distant metastatic disease, persistent locoregional disease that warrants adjuvant therapy, versus active surveillance.

PURPOSE/OBJECTIVE(S) Recent landmark trials have suggested a survival benefit to definitive tumor directed therapies (DTDT) for selected patients with metastatic disease for various malignancies. We sought 1) to confirm the prognostic significance of metachronous oligometastatic burden for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and 2) to evaluate disease outcomes for oligometastatic HPV-associated OPSCC after upfront DTDT versus upfront systemic therapy. MATERIALS/METHODS This was a single institution retrospective observational cohort study of patients with HPV-associated OPSCC who developed metachronous metastases ≥3 months after primary treatment with trans-oral robotic surgery (TORS) from 2008-2017. At metastatic presentation, patients were classified as oligometastatic (≤5 metastases) or polymetastatic (> 5 metastases). Treatment was classified as DTDT (all metastases initially treated with surgery/radiotherapy) or as upfront systemic therapy. Overall survival (OS) was compared using log-rank tests at a significance of P < 0.05. Univariable and multivariable (MV) Cox proportional hazard models were used to assess the association of patient, disease, and treatment characteristics with survival. Variables with P < 0.15 on univariable analysis (initial metastatic treatment, metastatic site, and number of metastases) were included in the multivariable model. RESULTS Of 676 patients undergoing primary surgical management for HPV-associated OPSCC, 36 patients subsequently developed metachronous metastases. For those 36 patients, the median follow-up time after surgery was 27.5 months (range 4.5-127.0), and the median OS was 42.8 months. The median age at distant metastasis was 62 (range 32-86), and most patients were male (86.1%) and Caucasian (97.2%). Overall, 27 patients presented with oligometastasis and 9 with polymetastasis. Oligometastatic patients had improved median OS compared to polymetastatic patients (47.9 vs. 22.7 months, P = 0.020). For the 27 oligometastatic patients, 12 were initially treated with DTDT while 15 received systemic therapy. DTDT was associated with an improved median OS when compared to systemic therapy (median OS not reached for DTDT vs 40.7 months, P = 0.021), with 3 year OS of 90.0% and 55.0% respectively. DTDT was also associated with improved OS on MV Cox regression (hazard ratio = 0.06, 95% CI 0.004-0.73, P = 0.027) compared to systemic therapy when controlling for number of metastases and metastatic site. CONCLUSION Our study findings suggest that the extent of metastatic disease at metastatic presentation is related to prognosis, with oligometastasis associated with improved overall survival compared to polymetastasis. Among patients with oligometastatic disease, initial DTDT is associated with superior overall survival when compared to upfront systemic therapy.

Purpose To evaluate whether historic risk categories and indications for adjuvant therapy in the pre–human papillomavirus (HPV) and pre–transoral surgery (TOS) era were associated with clinically significant relapse rates in HPV+ oropharyngeal squamous cell cancer patients undergoing TOS. Methods and Materials A multi-institutional retrospective review of intermediate- and high-risk HPV+ oropharyngeal squamous cell cancer patients not receiving adjuvant therapy after TOS was performed. Perineural invasion, lymphovascular invasion, T3-T4, or ≥N2 disease were considered to be intermediate-risk factors, and extracapsular extension or positive margins were considered to be high-risk features, according to established risk categories. Results Median follow-up was 42.9 months. Among all 53 patients, the 3-year cumulative incidence of relapse was 26.0%. The 3-year cumulative incidence was 11.8% in the 37 intermediate-risk patients and 52.4% in the 16 high-risk patients. On univariate analysis only high-risk status was significantly associated with an increased risk of relapse (hazard ratio 3.9; P=.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. Conclusions Risk category was associated with clinically significant relapse rates after TOS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer.

Background: Local recurrence following definitive treatment for pancreatic adenocarcinoma is common and can be associated with significant morbidity and mortality. Retreatment options for these patients are limited. Proton beam reirradiation (PRT) may limit dose and toxicity to previously irradiated normal tissues in patients without evidence of metastatic disease. Methods: Between 8/2010–2/2015, 15 patients with isolated, locally-recurrent pancreatic cancer were treated with PRT. Acute toxicity was graded using CTC v 4.0 and defined as occurring within 90 days. Kaplan-Meier survival analysis was performed from the start of PRT. A log-rank test was used to compare survival with or without concurrent chemotherapy. Results: Median follow-up was 15.7 months [2–48] from the start of PRT. The median clinical target volume (CTV) was 71 cc [15–200]. Ten (67%) patients received concurrent chemotherapy. Median PRT dose was 59.4 Gy (37.5–59.4 Gy). The median time interval from the prior treatment course was 26.7 months (7–461.3). There was a rate of 13% acute ≥ grade 3 toxicities attributed to PRT. The median overall survival (OS) was 16.7 months (95% CI, 4.7–36) and OS at 1 year was 67%. The “in-field” failure free survival at one year was 87%. The locoregional progression free survival (LPFS) and distant metastasis free survival (DMFS) at 1 year was 72% and 64% respectively. Concurrent chemotherapy was associated with a higher median survival. Conclusions: PRT was well tolerated, resulted in prolonged clinical outcomes compared to historical controls, and should be considered as a treatment option with concurrent chemotherapy in selected patients with locally-recurrent pancreatic cancer.

Purpose To examine recent utilization and survival outcomes associated with use of adjuvant chemoradiotherapy (CRT) for patients with resected locally advanced head and neck cancer (LAHNC) with negative surgical margins (SM negative) and no extracapsular extension (ECE). Materials and Methods We conducted a retrospective observational cohort study using the National Cancer Database evaluating patients diagnosed in 2004 to 2012 with AJCC stage III to IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx treated with definitive surgery and adjuvant radiotherapy (RT) or CRT. We identified a subset of patients with SM negative and no ECE (n = 10,870). We determined factors associated with CRT use and examined overall survival of patients receiving CRT versus RT. We further evaluated survival outcomes by number of lymph nodes involved to assess whether this was associated with benefit from CRT. Results Among patients with resected LAHNC with SM negative and no ECE, 47% received adjuvant CRT. The use of CRT varied substantially according to several factors, including patient age, contralateral/bulky neck disease, increasing number of positive lymph nodes, and lower neck disease. CRT was associated with a statistically significant improvement in overall survival compared with RT alone (hazard ratio, 0.90; 95% CI, 0.86 to 0.94; P < .001). Survival benefits of CRT versus RT alone increased in patients with multiple positive lymph nodes. Conclusion The use of adjuvant CRT in patients with resected LAHNC with SM negative and no ECE is common. Substantial practice variation as well as the survival differences observed in this study support the conduct of additional research to guide personalized treatment approaches in this setting. The number of positive lymph nodes seems to be an appropriate selection factor for further investigation of CRT in such patients.