BACKGROUND:Positive surgical margins (PSMs) persist in many patients, even in early-stage oral cavity squamous cell carcinoma (ES-OCSCC), impacting recurrence rates and overall survival (OS). While high-volume facilities (HVFs) enhance surgical outcomes, their survival benefit in ES-OCSCC has not been assessed in an updated large cohort. The role of social determinants of health (SDOH) in predicting survival in this context is not well described. METHODS:This retrospective cohort study analyzed stage I and II OCSCC patients from the National Cancer Database between 2004 and 2020. Facilities were categorized by case volume into low-(<2 cases/year), medium-(2-10), and high-volume (>10). Hazards ratios estimated the impact of facility volume on OS, adjusting for clinical/surgical factors, and SDOH. Kaplan-Meier survival curves compared OS. RESULTS:Among 22,258 patients with ES-OSCC, 42.55% were treated at HVFs. PSMs rates were higher at LVFs (T1: 7.16%, T2: 13.63%) and MVFs (T1: 4.33%, T2: 7.56%) compared with HVFs (T1: 2.89%, T2: 4.74%). Treatment at LVFs was associated with higher odds of PSMs (OR = 2.8; 95% CI: 2.34-3.37, p < 0.001). Five-year OS was highest at HVFs (80.2%), followed by MVFs (77.1%) and LVFs (70.9%, p < 0.001). Survival remained worse at LVF/MVFs among those with negative surgical margins (NSMs) or PSMs receiving RT/CRT. SDOH, including government insurance (OR = 2.05; 95% CI: 1.27-3.17, p = 0.002) and proximity to treatment facility (OR = 1.28; 95% CI: 1.06-1.56, p = 0.01) increased PSM risk, while higher income (OR = 0.76; 95% CI: 0.6-0.97, p = 0.03) was protective. CONCLUSIONS:Facility volume and SDOH influence PSM rates and OS in ES-OCSCC. Patients treated at HVFs experienced better outcomes, emphasizing the need for improved surgical quality metrics and centralization of care, even for ES-OCSCC.

Purpose:Base of tongue (BOT) adenoid cystic carcinoma (ACC) is a rare, locally aggressive malignancy that is typically associated with a high rate of disease recurrence. Surgery alone is rarely curative and highly morbid. Outcomes of systemic therapies and low linear energy transfer radiation therapy (RT) are generally poor. Fast neutron therapy (NRT), a form of high linear energy transfer radiation, is advantageous in treating radioresistant salivary gland malignancies. Long-term cancer control and swallowing outcomes in patients with BOT ACC treated with NRT were retrospectively reviewed. Methods:Between 1994 and 2023, 63 patients ≥18 years (median age 61) with biopsy-confirmed BOT ACC, not treated previously with surgery or RT, underwent 3D-conformal NRT or intensity-modulated neutron therapy (IMNT) for localized M0 (77.8%) or M1 (22.2%) disease. Most patients had (T3-4) primary tumors. Kaplan-Meier method was used to estimate locoregional recurrence-free (LRFS), distant metastasis-free, and overall survival. Late toxicities (≥90 days after NRT) were reported per Common Terminology Criteria for Adverse Events v5.0. Treatment-related and post-treatment percutaneous endoscopic gastrotomy (PEG) tube utilization was evaluated. Results:For the entire cohort, 5-year LRFS was 53.4%, and 5-year overall survival was 75.1%. Among M0 patients, 3-year LRFS was 72.4%, 5-year LRFS was 59.4%, and 5-year distant metastasis-free was 44.1%. Prophylactic PEG tubes were placed in 58.1% of patients; 14.5% remained PEG-dependent ≥90 days post-treatment. Common toxicities included xerostomia and dysphagia. Among evaluable patients, 33.3% required PEG placement after 90 days due to disease or salvage therapy. Neither patient treated with IMNT required long-term PEG use. Conclusions:This is the first study to report clinical outcomes of NRT for BOT ACC. Swallowing outcomes were acceptable, with a low rate of persistent PEG dependence. NRT achieved significant locoregional control in many locally advanced primary tumors. Additional improvements in the therapeutic ratio and functional outcomes may be achievable with IMNT.

6011 Background: No systemic therapy standard of care exists for recurrent/metastatic malignancies of the salivary glands (SGC) and immune checkpoint inhibitors (ICIs) have low response rates. Preclinical data in solid tumors suggest syngergistic antitumor effects of ICIs with hypofractionated radiation (XRT). This study explored the safety and activity of nivolumab (N) and ipilimumab (I)with palliative XRT. Methods: This phase I/II open label single arm trial enrolled patients (pts) with incurable SGCs (WHO 2017) with evidence of progression, ECOG 0-1, no prior antiPD1 or CTLA4 directed therapy, RECIST 1.1 measurable disease excluding the XRT site. Pts received N 3mg/kg IV Q 2 weeks x 12 doses followed by 480 mg IV Q4 weeks x 8 doses and I 1 mg/kg IV Q6 weeks x 4 doses. XRT was given to a total dose of 24Gy in 3 fractions every other day over 1 week (wk) and initiated 2 wks after the first dose of N and I. Research blood collection was obtained prior to wks 1, 8 and 16. The primary endpoint was safety and tolerability using CTCAE v. 4, secondary endpoints were objective response rates (ORR) by RECIST 1.1 criteria in non-radiated sites of measurable disease, overall survival (OS) and progression free survival (PFS). The study was approved by the FHCC IRB and registered on clinicaltrials.gov (NCT03749460). Results: Between 4/2019 and 5/2022, 20 pts were enrolled, the median age was 58 (range 27-77) years, 10 (50%) were male, 12 (60%) had ECOG 0, and 7 (35%) were Asian. Most common histologies were adenoid cystic 9 (45%) and salivary duct 4 (20%), 15 (75%) had no prior systemic therapy. Ten (50%) had both local and distant disease, 14 (70%) had commercial NGS testing, all had TMB < 10mut/Mb, MSI-stable tumors. All patients completed XRT with the most common XRT site being the lung 13(65%) and bone 7(35%). The median number of N doses received was 12 (range 3-20) and I doses 4 (range 1-4). Enrollment was halted until first 6 pts were assessed for dose limiting toxicities during initial 12 wks of treatment, none were observed. Among all pts enrolled, 5 (20%) Grade 3 AEs were observed: adrenal insufficiency, hypokalemia , lung infection, hypotension, and mania. No grade 4/5 toxicities were observed. One pt was not evaluable for RECIST 1.1 due to rapid disease progression: partial responses were observed in 4 (20%: 2 pts with salivary duct, 1 acinic cell and 1 adenoid cystic) with a median duration of 15.5 months (mos) (range 6-16 mos), stable disease in 6 (30%) all lasting 6 mos or greater, and progressive disease in 9 (45%). With a median follow-up of 16 mos, median OS was 25 mos (95% CI: [1.56, 2.59]) and median PFS was 7.2 mos (95% CI: [0.21, 1.56]). Exploratory correlative peripheral blood analysis is ongoing and will be reported. Conclusions: Nivolumab/ipilimumab and palliative XRT results in low rates of severe toxicities, modest ORR but durable ORR/SD. Further work is necessary to explore predictors for response. Clinical trial information: NCT03749460 .

e18074 Background: For locally advanced salivary cancers, primary radiotherapy is an option for unresectable disease or when resection would cause significant morbidity. Surgery for locally advanced base of tongue (BOT) adenoid cystic carcinoma (ACC) is rarely curative and often results in permanent feeding tube dependence. Neutron radiotherapy (NRT) provides locoregional control in many patients, but data on long-term swallowing outcomes is limited. We examine patterns of feeding tube utilization after NRT for BOT ACC. Methods: Retrospective, single-institution study of BOT ACC patients ≥18 years treated with primary NRT or NRT for locoregional control (LRC) in M1 disease from 1992 to 2023. Baseline characteristics and complications were abstracted, including short and long-term (≥90 days) use of percutaneous endoscopic gastrotomy (PEG) tubes. LRC was calculated using Kaplan-Meier method. Results: 51 patients with cT3-T4 BOT ACC treated with NRT were identified. Prophylactic PEG was advised per institutional practice. 34 (67%) had PEG placed prophylactically prior to NRT, and 4 (8%) reactively due to treatment effects. Of evaluable patients (n=45), median LRC was 5.1 years (95%CI 3.0-NR). At last follow-up (median 2.4 yrs, living patients, range 1 mo-15 yrs), 27 had LRC and 18 had locoregional failure. At 90 days post-NRT, 35 patients were evaluable for utilization of PEG placed at time of treatment, and 7 had ongoing PEG use. At 6 mos, 3 had ongoing PEG use, and only one continued to have PEG use until last follow-up (39 mos). New late post-NRT PEG was placed in 12 patients, of whom 10 had history of prior PEG. 3 were placed due to post-NRT dysphagia, median 42 mos after NRT (range 4-48mos); all 3 retained the PEG until last follow-up (median 9 mos after placement). 9 required PEG due to disease progression/salvage therapy, median 71 mos after NRT (range 35-105mo); of whom 8 retained the PEG until last follow-up (median 13 mos after placement), while 1 had PEG removed after 2 mos. One patient required esophageal dilation for stricture 10 years after NRT. Conclusions: There is limited reported data on swallowing outcomes of patients with BOT ACC treated with primary RT. In this treatment refractory disease, NRT is a viable option for BOT ACC and provides organ preservation as an alternative to glossectomy in patients with locally advanced tumors and significant rates of LRC. Functional outcomes after NRT were favorable, and most patients regained oral independence. A minority of patients had subsequent PEG placed, mostly in those with disease progression or undergoing salvage local therapy. Cohort and PEG use (n=51). Characteristic n (%) or other Age, years, median (range) 61.0 (25-84) Female 32 (62.7) Out-of-state 46 (90.2) T stage 3 13 (25.5) 4 38 (74.5) M1 12 (23.5) Clinical stage III 11 (21.6) Iva-c 40 (78.4) New PEG ≥ 90 days after NRT (n=35) 12 (34.3)

e18063 Background: There is no standard of care systemic therapy in R/M SGC. Regimens containing ICIs are of interest, but overall response rates (ORRs) are low, and median duration of response (mDOR) and long term overall survival (OS) data are limited. We pooled mature data from two clinical trials evaluating the use of ICIs in SGC to evaluate long term outcomes. Methods: We combined the results of two phase I/II, open label, single arm trials utilizing ICIs in R/M SGC. NCT02538510 administered pembrolizumab 200 mg IV q3 weeks and vorinostat 400 mg PO 5 days on/2 days off. NCT03749460 administered nivolumab 3mg/kg IV q2 weeks x 12 doses, followed by 480 mg IV q4 weeks x 8 doses and ipilimumab 1 mg/kg IV q6 weeks x 4 doses with hypofractionated radiotherapy at 1-5 metastatic sites to a total dose of 24Gy/3 fractions over 1 week initiated 2 weeks after immunotherapy. All patients were ≥18 years with R/M disease, evidence of progression within 3 months of study entry, measurable disease per RECIST 1.1, EGOG PS 0-1, and adequate organ function at enrollment. PDL1 expression was not required for participation and prior ICI was not allowed. ORRs were evaluated by RECIST 1.1. OS and progression free survival (PFS) were estimated via the Kaplan-Meier method. Results: 45 patients were enrolled in the two studies from 11/2015-5/2022. The combined median age was 57 (IQR 46, 66). 26 (57.8%) were male; 33 (73.3%) were white and 10 (22.2%) were Asian. 27 (60.0%) had an ECOG PS of 0. Most common histology types were adenoid cystic carcinoma (21, 46.7%), acinic cell carcinoma (5, 11.1%), and salivary duct carcinoma (5, 11.1%). The ORR was 17.8% with all responders having a PR (n=8, histology types: 3 acinic cell, 2 adenoid cystic, 1 adenocarcinoma, 1 salivary duct, 1 lymphoepithelioma-like carcinoma). 20 (44.4%) had SD, with 16 (80.0%) of these responses lasting greater than 6 months. 16 (35.6%) had PD. One patient was not evaluable for RECIST due to rapid disease progression and death. At analysis, median follow up was 29.2 months (IQR 27.1-50.0) among survivors, mDOR was 26.7 months (range 7.1-69.5+), with three patients with ongoing response. Median OS and PFS were 25.4 (95% CI 14, 43.2) and 6.2 months (95% CI 3.9, 15.5) respectively. 23 (51.1%) patients received systemic therapy after trial ICI. Patients received: 4 additional ICI (3 PD-1 monotherapy, 1 ipi/nivo), 5 androgen deprivation therapy, 5 chemotherapy, 9 other treatments (dabrafenib/trametinib, everolimus, fam-trastuzumab deruxtecan, osimertinib, lenvatinib, investigational agents). Conclusions: Although SGC is heterogenous, responses to ICI were observed in multiple subtypes and were durable, similar to observations in other solid tumors. A significant proportion received subsequent lines of therapy post ICI, and exploration of ORR and PFS to next lines of therapy is of interest. Clinical trial information: NCT02538510 and NCT03749460 .

We previously reported in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs), pretreatment higher lactate dehydrogenase (LDH) and absolute (abx) neutrophils as well as lower percent (

Introduction: Unilateral radiation therapy is appropriate for select patients with oropharyngeal squamous cell carcinoma (OPSCC). The use of proton beam therapy (PBT) in the unilateral setting decreases the dose to the contralateral neck and organs at risk. This study aims to evaluate contralateral recurrences in patients who received ipsilateral PBT. Methods: We evaluated the Proton Collaborative Group database for patients treated with PBT for head and neck squamous cell carcinoma between the years 2015-2020 at 12 institutions. Dosimetric analysis was performed in five cases. Results: Our analysis included 41 patients that received ipsilateral PBT with a mean follow-up of 14.7 months. 37% patients (n = 15) were treated for recurrent disease, and 63% (n = 26) were treated for de novo disease. Oropharyngeal sites included tonsillar fossa (n = 30) and base of tongue (n = 11). The median dose and BED delivered were 69.96 CGE and 84 Gy, respectively. Eight (20%) patients experienced at least one grade 3 dysphagia (n = 4) or esophagitis (n = 4) toxicity. No grade >= 4 toxicities were reported. There was one (2.4%) failure in the contralateral neck. The 1-year locoregional control was 88.9% and the freedom from distant metastasis was 95.5% (n = 2). The dosimetric analysis demonstrated similar ipsilateral level II cervical nodal region doses, whereas contralateral doses were higher with photon plans, mean: 15.5 Gy and 0.7 CGE, D5%: 25.1 Gy and 6.6 CGE. Conclusions: Our series is the first to report outcomes for patients with OPSCC receiving unilateral PBT. The contralateral neck failure rate was excellent and comparable to failure rates with photon irradiation.

Purpose/Objective(s) Fast Neutron Radiotherapy (NRT) is a high linear energy transfer modality that can overcome tumor radioresistance to conventional radiotherapy (RT). This may be particularly beneficial in the palliative recurrent/metastatic setting. An ideal dose-fractionation in this setting is unknown. This study evaluates clinical and early toxicity outcomes of short course (2-4 fraction) palliative hypofractionated NRT (hNRT). Materials/Methods Clinical characteristics, oncologic treatment history, clinical (tumor shrinkage and/or symptom response) and radiographic responses were reviewed in a single-institution, IRB-approved retrospective review of patients who received at least one palliative treatment course with 3D conformal hNRT from 11/2016 to 12/2022. Results Twenty-seven patients with Stage IV cancer received hNRT at median age of 79yr (range = 47–100) with median follow-up of 5.4mo (range = 0.1-75.6). Histology included squamous (n = 7), urothelial (n = 6), Merkel (n = 5), adenocarcinoma (n = 3), renal cell (n = 2), and other (n = 4). Median hNRT dose was 6 Gy in 3 fractions (range = 3.45-10 Gy, 2-4 fractions), equivalent to around 18-30 Gy of x-rays. There were 48 hNRT treatment courses across 32 unique anatomic sites, which included head-and-neck (HN) (n = 14), bone (n = 5), genitourinary (n = 4), non-HN lymph nodes (n = 7), and non-HN skin (n = 2). Twenty-three unique treatment sites (across 19 patients) received a single hNRT course, whereas nine sites (across 9 patients) received 2-4 successive courses (median 37d between courses). 16 patients (60%) were on concurrent systemic therapy and 8 sites (25%) were previously irradiated with photon RT. Median overall survival time from the end of the first hNRT course was 400d (95% CI = 221-not reached). Of treatment sites receiving one hNRT course, 18 (78%) of 23 had clinical response, and 11 of 13 (85%) sites with radiographic follow-up had radiographic response. Of sites receiving 2 or more successive courses, 9 (100%) of 9 had clinical response and 6 of 8 (75%) sites with radiographic follow-up had radiographic response. Of 8 sites previously irradiated with photon RT, 6 (75%) had a clinical response of which 4 (50%) had a concurrent radiographic response. Of 20 sites receiving hNRT for pain relief/bleeding, 3 (15%) had symptom stability and 17 (85%) had partial-to-full clinical response, 11 of which had symptom progression at a median of 145d post-response. Of 12 sites receiving hNRT to slow disease progression and/or stimulate an immune response (n = 11 on concurrent immunotherapy or ADT), 10 (83%) had partial-to-full clinical response with radiographically stable-to-improved disease and 1 had radiographic progression. Overall, RTOG Grade 2 (n = 1) or 3 (n = 2) side effects were uncommon. No patients experienced pain flares. Conclusion Most patients treated with hNRT had symptom relief and radiographic response. None had pain flares and high-grade side effects were rare. Single or repeat-course hNRT may be a safe and effective method of palliation.

Fast neutron therapy is a high linear energy transfer (LET) radiation treatment modality offering advantages over low LET radiations. Multileaf collimator technology reduces normal-tissue dose (toxicity) and makes neutron therapy more comparable to MV x-ray treatments. Published clinical-trial and other experiences with fast neutron therapy are reported. Early comparative studies failed to consider differences in target-dose spatial conformality between x-ray and neutron treatments, which is especially important for organs-at-risk close to tumor targets. Treatments planning systems (TPS) for high-energy neutrons lag behind TPS tools for MV x-rays, creating challenges for comparative studies of clinical outcomes. A previously published Monte Carlo model of the University of Washington (UW) Clinical Neutron Therapy System (CNTS) is refined and integrated with the RayStation TPS as an external dose planning/verification tool. The collapsed cone (CC) dose calculations in the TPS are based on measured dose profiles and output factors in water, with the absolute dose determined using a tissue-equivalent ionization chamber. For comparison, independent (external) Monte Carlo simulation computes dose on a voxel-by-voxel basis using an atlas that maps Hounsfield Unit (HU) numbers to elemental composition and density. Although the CC algorithm in the TPS accurately computes neutron dose to water compared to Monte Carlo calculations, calculated dose to water differs from bone or tissue depending largely on hydrogen content. Therefore, the elemental composition of tissue and bone, rather than the material or electron density, affects fast neutron dose. While the CC algorithm suffices for reproducible patient dosimetry in fast neutron therapy, adopting methods that consider tissue heterogeneity would enhance patient-specific neutron dose accuracy relative to national standards for other types of ionizing radiation. Corrections for tissue composition have a significant impact on absolute dose and the relative biological effectiveness (RBE) of neutron treatments compared to other radiation types (MV x-rays, protons, and carbon ions).

IMNT improves the therapeutic ratio compared to 3D conformal NT and expands indications for NT in patients with radiorefractory tumors. Acute toxicity compares favorably with photons. Longer clinical and toxicity follow-up is anticipated. A prospective trial is planned to evaluate quality of life measures.

BACKGROUND:Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear.METHODS:Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021.RESULTS:Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups.CONCLUSIONS:High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

Background: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). Methods: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade >= 3 adverse events (G = 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression-free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. Results: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. Conclusions: In the largest study to date examining PBBMs in ICI-treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.

Our pre-treatment clinical PSQA program and workflow provides useful information to guide IMNT treatment planning and delivery, and helps ensure the safe and accurate delivery of IMNT. Our early experiences suggest IMNT plans with smaller MF values are more likely to pass PSQA than plans with larger values of the MF.

Purpose/Objective(s) Acinic cell carcinoma is a rare subtype of salivary gland cancer, with little published data on management or survival outcomes. We aimed to describe a cohort of patients from a single institution, and to identify factors that impacted oncologic outcomes. Materials/Methods We retrospectively identified patients with acinic cell carcinoma who received treatment at our tertiary referral center. Demographic, tumor, and treatment data were collected. Locoregional control (LRC), relapse free survival (RFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and receipt of postoperative radiation therapy (PORT) in non-metastatic patients with oncologic outcomes using a stepwise Cox proportional hazards model. Results Between 1/1/1984 and 12/31/2019 65 eligible patients were identified. Patient characteristics are described in Table 1. All patients had disease originating within the parotid gland, and two patients were metastatic at presentation. The majority of patients received upfront surgical resection, with 79% receiving PORT. With a median follow up of 11.7 years, the 5-year OS, LRC, and RFS estimates were 85%, 71%, and 63%, respectively. 15 patients ultimately received palliative systemic therapy. In a multivariate analysis excluding those metastatic at presentation, age at diagnosis and nodal status were associated with OS, LRC, and RFS. PORT was not associated with survival outcomes on multivariate analysis. Conclusion Acinic cell patients receiving treatment at a single tertiary referral center demonstrate excellent five-year survival outcomes. With long term follow up, only age at diagnosis and nodal status were associated with survival outcomes. Further work is necessary to assess generalizability of these results. Acinic cell carcinoma is a rare subtype of salivary gland cancer, with little published data on management or survival outcomes. We aimed to describe a cohort of patients from a single institution, and to identify factors that impacted oncologic outcomes. We retrospectively identified patients with acinic cell carcinoma who received treatment at our tertiary referral center. Demographic, tumor, and treatment data were collected. Locoregional control (LRC), relapse free survival (RFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and receipt of postoperative radiation therapy (PORT) in non-metastatic patients with oncologic outcomes using a stepwise Cox proportional hazards model. Between 1/1/1984 and 12/31/2019 65 eligible patients were identified. Patient characteristics are described in Table 1. All patients had disease originating within the parotid gland, and two patients were metastatic at presentation. The majority of patients received upfront surgical resection, with 79% receiving PORT. With a median follow up of 11.7 years, the 5-year OS, LRC, and RFS estimates were 85%, 71%, and 63%, respectively. 15 patients ultimately received palliative systemic therapy. In a multivariate analysis excluding those metastatic at presentation, age at diagnosis and nodal status were associated with OS, LRC, and RFS. PORT was not associated with survival outcomes on multivariate analysis. Acinic cell patients receiving treatment at a single tertiary referral center demonstrate excellent five-year survival outcomes. With long term follow up, only age at diagnosis and nodal status were associated with survival outcomes. Further work is necessary to assess generalizability of these results.

AbstractBackgroundAnti‐PD1 checkpoint inhibitors (ICI) represent an established standard‐of‐care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown.MethodsWe retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni‐ and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression.ResultsOf the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty‐six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01–5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41–3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06–0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between toxicity and any patient characteristic.ConclusionsWe observed inferior OS, ORR, and rates of UH among ICI‐treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor‐risk population.

Purpose/Objective(s) This single arm open label phase II study sought to explore the safety and antitumor activity of combined antiPDL1 and CTLA4 blockade with hypofractionated radiation (XRT) in patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC) who have previously been treated with an immune checkpoint inhibitor (ICI). Materials/Methods Patients with RMHNSCC who progressed on prior ICI, ECOG 0/1, a bone or lung metastatic site amenable to XRT and RECIST 1.1 measurable disease apart from the radiated site were eligible. Durvalumab 1500mg IV x 13 doses and tremelimumab 75mg IV x 4 doses were both administered every 4 weeks. Hypofractionated image-guided (HIGRT) or stereotactic (SBRT) XRT was given in 3 fractions every other day to a total dose of 24 Gy starting week 2. The primary endpoint was safety; secondary endpoints were RECIST 1.1 responses in non-radiated measurable lesions and overall survival (OS). Blood was obtained at baseline and at week 4 for flow cytometric peripheral T cell analysis. The accrual goal was 20 patients with the first 6 patients representing a safety run in cohort. This project was approved by our institutional IRB and registered at clinicaltrials.gov (NCT035225). Results Between August 2018 and November 2020, 6 patients were enrolled, followed by study closure by the sponsor due to funding. All patients were male, 4 white and 2 Asian, with a median age of 64 years (range 47-67), 4 had oropharynx, 1 oral cavity and 1 hypopharynx as primary sites, 5 were never smokers. All patients had progressed on ICI in the R/M setting (2 nivolumab, 2 pembrolizumab, 1 avelumab and 1 durvalumab). Five patients completed XRT: 4 to lung lesions and 1 to a superior mediastinal LN, no toxicities attributed to the radiation were observed. One patient was unable to receive XRT due to progression. Only 2 patients completed more than 4 treatment cycles (median 2.5, range 1-13 cycles). One dose limiting toxicity (recurrent Grade 2 diarrhea) was observed. Four grade 3 toxicities (neck pain due to tumor, shingles, dyspnea due to disease progression and fatigue) were observed in 3 patients, one of which was deemed treatment related (fatigue). Among 5 evaluable pts, we observed 1 complete response (CR), 3 stable disease (SD), 1 disease progression (PD). The patient with a CR showed an increase in PDL1+ and PD1+ T cells at 4 weeks, which was not observed in the 3 other evaluable patients with PD and SD. With one surviving patient in follow up for 14 months, median OS was 8 months (range 4-14). Conclusion In this small study population of previously ICI treated RMHNSCC, durvalumab, tremelimumab and XRT resulted in expected toxicities and limited efficacy. Increase in peripheral PDL1+ and PD1+ T cells may correlate with response and may merit further study.

Purpose: For most disease sites, level 1 evidence is lacking for proton beam therapy (PBT). By identifying target populations that would benefit most from PBT, prospective registries could overcome many of the challenges in clinical trial enrollment. Herein, we report clinical outcomes of patients treated with PBT for locally advanced non-small cell lung cancer (LA-NSCLC).Methods and Materials: Data were obtained from the multi-institutional prospective database of the Proton Collaborative Group (PCG). Inclusion criteria of our study were stage III de novo or recurrent LA-NSCLC, use of PBT, and availability of follow-up data. Overall survival (OS) time was calculated from the start of treatment until death or last follow-up. Kaplan-Meier curves were generated for groups of interest and compared with log-rank tests. Cox regression modeling was used to evaluate the multivariate association between selected covariates and OS.Results: A total of 195 patients were included in the analysis. PBT was given with a median equivalent dose in 2 Gy fractions (EQD2) of 63.8 Gy (relative biological effectiveness). Pencil beam scanning was used in 20% of treatments. Treatment-related grade 3 adverse events were rare: 1 pneumonitis, 2 dermatitis, and 3 esophagitis. No grade 4 events were reported. Two cardiac-related grade 5 events occurred in patients with multiple risk factors. The median follow-up time for living patients was 37.1 months and the median OS was 19.0 months. On multivariate analysis, good performance status (hazard ratio, 0.27; [95% confidence interval, 0.15-0.46]; P < .0001), pencil beam scanning use (0.55; [0.31-0.97]; P = .04), and increased EQD2 (0.80; [0.71-0.90] per 10 Gy increase; P = .0002) were associated with decreased mortality.Conclusions: PBT appears to yield low rates of adverse events with an OS similar to other retrospective studies on PBT for LANSCLC. PBS use and increased EQD2 can potentially improve OS.(c) 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Little is known regarding peripheral blood bio-markers (PBBMs) for oncologic outcomes in recurrent/meta-static head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). We explored associations of PBBMs with outcomes and toxicities in R/M HNSCC treated with ICIs. in CPS 31 – analyses for ECOG, p16, and higher LDH (p=0.025), neutrophils (%: p=0.002, abs: p=0.001), monocytes (abs: p=0.043), NLR (p<0.001), lymphocytes (%: p<0.001, abs: p=0.005), eosino-phils OS and PFS, and lower% lymphocytes and higher LDH correlated with worse ORR. PBBMs are promising prognostic tools for immunotherapy in HNSCC and warrant further investigation in a large, prospec-tive study along with validation with CPS biomarker.

Purpose/Objective(s) Esthesioneuroblastoma (ENB) is a rare locally aggressive neuroendocrine sinonasal malignancy commonly presenting with skull base and intracranial invasion, which is often managed using multimodality therapy with surgery and radiotherapy (RT). Advances in surgical techniques as well as RT have improved outcomes for these complex tumors. Proton therapy has dosimetric advantages over conventional X-ray based approaches and may further improve the therapeutic ratio. We report our early experience with intensity modulated proton therapy (IMPT) in the management of ENB. Materials/Methods We retrospectively reviewed treatment records of patients with ENB treated at our center with IMPT from 2015-2021. IMPT was delivered with a 2 to 5 field pencil-beam scanning plan, initially with single-field optimization, then multi-field optimization after 2018. All pathology was internally reviewed. Event outcomes were calculated from date of biopsy to time of locoregional recurrence or death. Survival statistics were calculated using the Kaplan-Meier (KM) method using a scientific 2-D graphing and statistics software. Results 15 patients were identified, median age 52 (range 32-78), gender (male 12, female 3), Kadish stage (B – 2; C – 12; D – 1), AJCC T classification (T3 – 3, T4b – 12), 2 had nodal metastasis at diagnosis, Hyams (grade 2 – 10; grade 3-4 – 5). Local disease extent included: anterior cranial fossa – 11, middle cranial fossa – 2, dura – 12, brain parenchyma 1, nasopharynx – 2, orbit – 6. The majority (n=14) were managed with surgical resection followed by postoperative RT, and one underwent primary chemoradiation. Surgery included bifrontal craniotomy + extended endoscopic resection (n=7) and extended endoscopic resection alone (n=7). IMPT was delivered in conventional fractionation (n=12) or hyperfractionated accelerated course (n=3), median dose 68 CGE (range 60-72), neck coverage (n=11). Four received concurrent platinum-based chemotherapy. At median follow up of 20 months (IQR 16-51), 2 patients have died, unrelated to disease progression. Three patients have recurred including 1 local, 1 regional, and 1 distant metastasis (out of field dural metastases). Both patients with locoregional recurrence have undergone surgical salvage and have no evidence of disease. IMPT was well tolerated with expected acute toxicities. One patient developed frontal lobe brain necrosis at 3 years post-treatment managed conservatively, and one underwent functional sinus surgery for sinus obstruction. No de novo high grade visual toxicity was observed. KM 2-year locoregional recurrence-free survival was 83% and OS 88%. Conclusion IMPT is feasible in ENB with early outcomes demonstrating excellent local control and favorable toxicity profile in this cohort of patients with very locally advanced disease. IMPT may allow for improved coverage of tumor volumes in close proximity to numerous critical structures. Additional follow up is needed to track long term disease control outcomes and late toxicities.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study.Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States.Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric.Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.