BACKGROUND:The optimal treatment de-escalation approach for HPV-related oropharyngeal squamous cell carcinomas (OPSCC) is unknown. The objective was to assess two de-escalation approaches: primary radiotherapy (RT) vs. transoral surgical (TOS). PATIENTS AND METHODS:Patients with T1-T2 N0-2 HPV-related OPSCC were randomly assigned to primary RT (60 Gy with concurrent weekly cisplatin in node-positive) vs. TOS + neck dissection (ND) (and adjuvant reduced-dose RT depending on pathology). The primary endpoint was 2-year OS (hypothesized to be 94 % in each arm, compared to 84 %). Secondary endpoints included comparisons of survival and quality of life between arms. The trial was stopped early due to two treatment related deaths in the surgical arm. RESULTS:Sixty-one patients were randomized (n = 30 in RT arm and n = 31 in TOS+ND arm), with a median age of 62 years (IQR: 57-68). The majority were male (n = 51) and never-smokers (n = 31). Median follow-up was 3.7 years (IQR: 3.1-4.5 years). In the RT arm, the primary endpoint for acceptability was met (p = 0.008), and two-year OS was 100 % (95 % confidence interval [CI]: 100-100 %). In the TOS+ND arm, the primary endpoint was not met (p = 0.296) and two-year OS was 90 % (95 % CI: 71-97 %), significantly worse than the RT arm (p = 0.041). Two-year progression-free survival (PFS) were 100 % (95 % CI: 100-100 %) vs. 86 % (95 % CI: 67-95 %) respectively (p = 0.012). Mean (± SD) 2-year MDADI total scores were 89 ± 13 vs. 83 ± 11, respectively (p = 0.11), and grade 2-5 toxicity rates were similar (n = 21 vs. n = 24 respectively, p = 0.51), with no additional grade 5 events. CONCLUSION:For treatment de-escalation, a primary RT approach achieved excellent oncologic and functional outcomes and should be tested in phase III de-escalation trials. TRIAL REGISTRATION:Clinicaltrials.gov NCT03210103.

BACKGROUND:Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT). With no well-established standard treatment, OPTIMAL-HN aimed to demonstrate the non-inferiority of multimodal analgesia (MMA; analgesic medications with different mechanisms of action) to opioid analgesia alone. METHODS:OPTIMAL-HN (ClinicalTrials.gov identifier: NCT04221165) was an open-label, non-inferiority, randomized clinical trial. We enrolled HNC patients receiving curative-intent RT/CRT and experiencing moderate ≥ 4/10 RIM pain. We randomized 1:1, stratified by RT vs. CRT, to opioids alone (standard arm) or MMA (pregabalin, acetaminophen, naproxen, and opioids if required). The primary endpoint was mean pain score (range: 0-10) during the last week of RT. Secondary endpoints included mean weekly opioid use, duration of opioid requirement, quality of life, weight loss, and toxicity. All analyses were pre-specified, including testing for superiority if non-inferiority was demonstrated. RESULTS:Forty-nine patients were enrolled, 25 in the opioid analgesia arm and 24 in the MMA arm. Median follow-up was 4.2 months. The primary endpoint, mean pain score during the last 7 days of RT, was 5.1 (95 % confidence interval [CI]: 4.1-6.1) in the opioid arm and 4.9 (95 % CI: 3.8-5.9) in the MMA arm (non-inferiority p = 0.039, superiority p = 0.72). Analyzing all pain scores from enrollment to 6-weeks post-RT, MMA demonstrated both non-inferiority and superiority compared to opioids alone (non-inferiority p = 0.0024, superiority p < 0.001). One patient in the MMA arm was admitted with acute kidney injury, possibly related to the analgesic regimen. Arms were similar for all other secondary endpoints. CONCLUSIONS:MMA demonstrates non-inferiority to opioid analgesia alone in managing RIM pain during the last week of RT and superiority when analyzing the post-RT time period. MMA should, therefore, be considered an effective mode of analgesia for HNC patients receiving RT.

Purpose The rate of long-term feeding tube usage for patients treated with definitive (chemo)radiation is unknown. This analysis aims to determine predictive factors of feeding tube use years after treatment completion on NRG Oncology head and neck cancer trials that accrued from 2002 to 2014. Methods and Materials This is an unplanned, post hoc secondary analysis in the long term of both oropharynx cancer (OPC) and all treated patient feeding tube rates 6 months to 9 years after chemoradiation completion for patients treated on the multicenter prospective trialsNRG/RTOG 0129, 0522, and 1016. Results Median (min-max) follow-up was 6.7 years (interquartile range, 3.4-8.2) for OPC patients. Five hundred ninety-eight of 1839 (33%) OPC patients had a feeding tube 6 months after treatment. This decreased to 4% at 1 year and 3% at 9 years. Predictors of a feeding tube posttreatment were treatment with 3D conformal (3DCRT) accelerated chemoradiation with concomitant boost (AFX3DCRT), older age, feeding tube at registration, T4 tumor stage, and >10 pack-years of smoking. AFX3DCRT was independently significantly more associated with feeding tube use when compared to all other regimens. Among all treated patients (n = 2387), the median follow-up was 6.3 years (interquartile range, 2.7-8.2). Intensity modulated radiation therapy (IMRT) regimens had significantly less feeding tubes than 3DCRT (AFXIMRT + Cetux + C: hazard ratios [HR], 0.75 [0.63-0.89]; AFXIMRT + Cetux: HR, 0.81 [0.67-0.98]) for all patients. Primary site did not significantly influence feeding tube utilization (nontonsil/tongue base HR, 0.97 [0.85-1.11]). Conclusions 3DCRT accelerated fractionation chemoradiation is associated with increased posttreatment feeding tube use for both OPC patients and all patients treated when compared to IMRT-based regimens. Other predictors of posttreatment feeding tube use are largely known prior to treatment initiation. Patients treated for nontonsil/tongue base primary tumors did not have higher rates of feeding tube utilization.

PURPOSE:The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking.METHODS:We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial.RESULTS:Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041).CONCLUSION:On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).

BACKGROUND:This ORATOR sub-study evaluated swallowing physiology in patients treated with transoral robotic surgery (TORS) versus radiotherapy (RT) for early-stage oropharynx cancer. METHODS:Swallowing physiology was evaluated using videofluoroscopy and outcomes were compared across treatment arms and correlated with MDADI scores. RESULTS:Of the 68 patients in the ORATOR trial, 21 participated in this sub-study (30.8%), including 15 RT Arm and six TORS Arm patients. Swallowing profiles were not significantly different between the arms. MBSImP pharyngeal scores for RT Arm versus TORS Arm patients were 4.8 (±2.1) versus 4.3 (±1.5) at baseline, 6.2 (±1.2) versus 9.6 (±4.8) at 6 months and 5.9 (±1.8) versus 8.0 (±4.7) at 12 months. MBSImP pharyngeal scores demonstrated weak associations with several MDADI subscales and PAS scores. CONCLUSIONS:To best describe swallowing outcomes in studies of RT and/or surgery, instrumental swallowing assessments should be strongly considered in addition to quality of life measures.

BackgroundEpstein-Barr virus (EBV)-related nasopharyngeal cancer (NPC) is a common type of cancer in certain areas of the world such as southeast Asia, but is uncommon in Canada. There is currently no reliably effective standard treatment for incurable metastatic EBV-related NPC that progresses after first-line therapy with gemcitabine/cisplatin.MethodsWith his consent, the health records of a patient with relapsed metastatic EBV-related NPC treated with pembrolizumab immunotherapy were retrospectively reviewed and reported.Case reportA male patient presented at age 15 with stage IVA EBV-related NPC. Despite response to initial chemoradiation and adjuvant chemotherapy, the patient experienced metastatic cancer relapse in lymph nodes and bone. There was initial response to gemcitabine/cisplatin chemotherapy, but the cancer progressed after 7 cycles. The patient was then switched to pembrolizumab and had a near complete clinical response after 14 cycles. Serum EBV titers have normalized and CT imaging shows only some healed bone metastasis. Retrospective assessment of tumor CPS PD-L1 was >20. Hypothyroidism developed, possibly due to radiation treatment, but otherwise he did not experience any other immune-mediated toxicities on or following treatment, which lasted in total 2 years with 41 cycles. To date, the patient has been observed off pembrolizumab for over one year and is highly functional without evidence of disease progression.ConclusionThis case illustrates the potential benefit of immunotherapy for improving survival and quality of life in selected patients with metastatic EBV-positive cisplatin-refractory NPC.

IMPORTANCE The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. OBJECTIVE To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. DESIGN, SETTING, AND PARTICIPANTS This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. INTERVENTIONS Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). MAIN OUTCOMES AND MEASURES The primary end pointwas overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. RESULTS Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 ofmyocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes.

1.1 Introduction: Malignant triton tumours (MTTs) are a rare and aggressive subset of malignant peripheral nerve sheath tumours (MPNSTs). A systematic review was conducted to better understand the prognosis and prognostic factors of MTTs in adult patients, and provide treatment guidance for clinicians encountering this rare tumour. 1.2 Methods: A PubMed search was conducted using keywords: “rhabdomyoblastic,” “rhabdomyosarcomatous,” “triton,” “case series” and “case report”. Reference list search was also completed. Two independent investigators completed abstract and full-text reviews. Articles were restricted to peer-reviewed articles in English language only containing adult MTT cases (≥ 18 years), and excluding articles with insufficient treatment/outcome data. Univariable and multivariable Cox proportional hazards regression was performed to identify significant predictors of overall survival (OS) and progression-free survival (PFS). 1.3 Results: A total of 123 cases from the literature and 1 case from our institution were included in the final analysis. The 2-year and 5-year OS was 46.2% and 32.2%, and the 2-year and 5-year PFS was 27.1% and 21.3%, respectively. On multivariable analysis for OS, prior radiation exposure (hazard ratio [HR]: 3.99, p = 0.027), central nervous system or spine disease site (HR: 5.86, p < 0.001) and positive neurofibromatosis 1 (NF1) status (HR: 3.42, p < 0.001) were associated with worse survival. Adjuvant radiotherapy (HR: 0.58, p = 0.038) was associated with improved survival. Positive NF1 status (HR: 2.34, p < 0.001) and positive margins (HR: 3.28, p < 0.001) were associated with worse PFS. 1.4 Conclusions: MTTs are rare and have poor long-term survival. Negative surgical margins and adjuvant radiation were found to be associated with improved outcomes.

Purpose/Objective(s) Clinical and treatment factors that engender long-term gastrostomy tube (g-tube) dependence are poorly defined. We attempted to identify potential predictors. Materials/Methods All eligible patients treated on RTOG 0129, RTOG 0522, and NRG/RTOG 1016 were grouped according to treatment received: standard fractionation RT (3DSFX) + cisplatin (C), accelerated fractionation RT (3DAFX) + C, accelerated IMRT (AFX) + C, AFX + C + cetuximab (cetux) and AFX + cetux. G-tube rates were compared at baseline (pre-treatment), 6-months after radiation completion, and annually from years 1 to 9 post treatment. Time to g- tube placement was analyzed using Cox proportional hazards models for variables of interest. Additionally, a separate review was performed for patients with no g-tube at 3 years' post-treatment (survivors with acceptable post-treatment swallowing) to evaluate late g-tube placement. Results 2389 patients were identified, 1839 of which had oropharynx cancer (OPC). AFX+C was the most common management (n=843, 35%). The G-tube rate at treatment initiation was 14%. At one-year post-treatment the rate was 19% and at 9 years the number was 8%. The RTOG 0129 g-tube rate was significantly higher than that of later studies (RTOG 0522 HR 0.7, 0.6-0.8; NRG/RTOG1016 HR 0.85 (0.72-0.99). Patients treated with 3D regimens had significantly higher feeding tube rate at baseline, 6 months, 1 year, and 2 years post-treatment (3DSFX + C: 25%/45%/29%/13% and 3DAFX + C: 22%/41%/26%/17%, respectively) when compared to accelerated IMRT regimens (all time points p < 0.001). There was no difference in feeding tube rate between treatment groups from years 3 – 9. Among OPC patients the predictors of feeding tube placement were older age (HR 1.01, 1.00-1.02), T4 primary (1.3, 1.1-1.6) and >10 pack year smoking history (HR 1.2, 1.0-1.4). Treatment regimen, tumor location, and p16-status did not affect g-tube placement. Among all patients, predictors of g-tube placement were older age (HR 1.01, 1.01-1.02); T4 primary (HR 1.3, 1.2-1.5), AJCC 7th ed N2c/N3 (1.3, 1.1-1.6); and >10 pack year smoking history (HR 1.2, 1.0-1.3). At 3 years there were 989 patients alive with follow-up who never required a gastrostomy tube. Of the 249 of these patients with 9 years' follow-up the g-tube rate was 6%. From univariable model predictors of feeding tubes placed more than 5 years after treatment completion were T3 category, T4 category, >10 pack years smoking, non-tonsil or tongue base primary, and p16-negative tumors. Conclusion G-tube rates were highest in patients managed with 3DCRT on RTOG 0129; utilization has significantly decreased over time. Radiation acceleration treatment intensification does not increase g-tube use during treatment or survivorship. Predictors of feeding tube use are increasing age, T4 primary tumors and >10 pack year smoking history.

Purpose/Objective(s) In addition to chemotherapy toxicities, most HNC patients receiving CRT experience moderate to severe radiation-induced pharyngitis. Management includes escalating analgesics, dietary modification, supplemental hydration, and feeding tubes for nutritional support as needed. Uncontrolled symptoms can interrupt or truncate curative intent treatment, impacting both quality of life and cancer outcomes. In 2014, a fulltime NP role dedicated to symptom management during and immediately post-CRT was initiated at our center. We assessed the impact on patient Emergency Department (ER) visits, hospitalizations and deaths. Materials/Methods Patients receiving definitive primary CRT with curative intent were identified during 12 month periods prior to (April 2012-March 2013) and three years after (April 2017-March 2018) initiation of the NP from records of H&N MDT case conferences. We hypothesized that ER visits and hospitalizations would be reduced with NP care. Effects on treatment delivery were secondary outcomes. Patient demographic, tumor, treatment, ER visit, hospital admission, and mortality data were extracted retrospectively from the electronic medical record. Unadjusted comparisons were done using the chi-square test for categorical variables and t-test for continuous variables with p<0.05 considered of significance. This project was approved by the institutional REB. Results 105 and 120 patients were identified in the pre-NP and post-NP cohorts, respectively. Post-NP patients were younger (mean age 63.2 vs 67.3 years), more often had oropharyngeal cancer (81.5% vs 56.2%), did not receive weekly carboplatin (0.0% vs 8.6%), and received cisplatin scheduled q3weekly less often (45.0% vs 71.4%) and weekly more often (48.3% vs 16.2%). Patients received a mean of 3.6 visits and 4.3 phone calls with the NP. There was no difference in ER visits within 42 days of treatment between cohorts (55.2% vs 55.8%). However, hospital admissions were reduced (60.0% vs 45.8%, p=0.034). Length of stay was similar, and there was no difference in 90-day mortality (2.9% vs 2.5%). Conclusion This before-and-after study showed a 23.7% reduction in hospitalizations after introduction of the NP role, consistent with the findings of others (Terzo 2017). Over 50% of patients visited the ER at least once and 1 in 40 died in both cohorts. Time trends included a 14.3% increase in the number of patients receiving CRT; and shifts in patient age, cancer type and cisplatin schedule consistent with an increasing incidence of HPV-related oropharyngeal cancer. We cannot rule out effects of these trends or other interventions on our results. Additional limitations include inability to harmonize staging between cohorts and lack of quality of life and cost effectiveness data. Nevertheless, these data support the value of a NP role focused on HNC patients receiving CRT to optimize outcomes. In addition to chemotherapy toxicities, most HNC patients receiving CRT experience moderate to severe radiation-induced pharyngitis. Management includes escalating analgesics, dietary modification, supplemental hydration, and feeding tubes for nutritional support as needed. Uncontrolled symptoms can interrupt or truncate curative intent treatment, impacting both quality of life and cancer outcomes. In 2014, a fulltime NP role dedicated to symptom management during and immediately post-CRT was initiated at our center. We assessed the impact on patient Emergency Department (ER) visits, hospitalizations and deaths. Patients receiving definitive primary CRT with curative intent were identified during 12 month periods prior to (April 2012-March 2013) and three years after (April 2017-March 2018) initiation of the NP from records of H&N MDT case conferences. We hypothesized that ER visits and hospitalizations would be reduced with NP care. Effects on treatment delivery were secondary outcomes. Patient demographic, tumor, treatment, ER visit, hospital admission, and mortality data were extracted retrospectively from the electronic medical record. Unadjusted comparisons were done using the chi-square test for categorical variables and t-test for continuous variables with p<0.05 considered of significance. This project was approved by the institutional REB. 105 and 120 patients were identified in the pre-NP and post-NP cohorts, respectively. Post-NP patients were younger (mean age 63.2 vs 67.3 years), more often had oropharyngeal cancer (81.5% vs 56.2%), did not receive weekly carboplatin (0.0% vs 8.6%), and received cisplatin scheduled q3weekly less often (45.0% vs 71.4%) and weekly more often (48.3% vs 16.2%). Patients received a mean of 3.6 visits and 4.3 phone calls with the NP. There was no difference in ER visits within 42 days of treatment between cohorts (55.2% vs 55.8%). However, hospital admissions were reduced (60.0% vs 45.8%, p=0.034). Length of stay was similar, and there was no difference in 90-day mortality (2.9% vs 2.5%). This before-and-after study showed a 23.7% reduction in hospitalizations after introduction of the NP role, consistent with the findings of others (Terzo 2017). Over 50% of patients visited the ER at least once and 1 in 40 died in both cohorts. Time trends included a 14.3% increase in the number of patients receiving CRT; and shifts in patient age, cancer type and cisplatin schedule consistent with an increasing incidence of HPV-related oropharyngeal cancer. We cannot rule out effects of these trends or other interventions on our results. Additional limitations include inability to harmonize staging between cohorts and lack of quality of life and cost effectiveness data. Nevertheless, these data support the value of a NP role focused on HNC patients receiving CRT to optimize outcomes.

TPS12144 Background: Patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) receive curative chemoradiation (CRT) with Cisplatin, as a standard of care. A meta-analysis of 52 randomized trials comparing Low Dose (LD) and High Dose (HD) schedules demonstrated differing toxicity profiles but hearing effects were not rigorously studied. Hearing loss associated with HD Cisplatin can result in survivorship challenges. A local study suggested a protective effect for LD Cisplatin in relation to ototoxicity and pharmacogenomic markers, MATE1 and COMT, to be associated with risk for ototoxicity. We hypothesize that LD cisplatin is associated with reduced frequency of hearing loss when compared to the standard HD cisplatin in LASCCHN patients on CRT and that differences in MATE1/COMT can predict for cisplatin-related ototoxicity and be identified prior to treatment. Our goal is to develop an innovative personalized treatment pathway incorporating predictive pharmacogenomics markers to improve the tolerability and survivorship outcomes of curative CRT for LASCCHN. Methods: This is a prospective, open-label, randomized clinical trial. Following informed consent, eligible LASCCHN patients planned for primary CRT will be stratified by tumor p16 status and then randomized in 1:1 fashion to either concurrent LD Cisplatin (40mg/m2 every week) or HD cisplatin (100mg/m2 every 3 weeks). The primary outcome is to measure the change in incidence of CTCAE grade ≥2 hearing loss and hearing-related quality of life (QOL) at 1 year. As part of secondary and exploratory outcomes, differences in survival, loco-regional control, global QOL and other toxicities (e.g. nephrotoxicity, neurotoxicity) will be assessed. The relationship between MATE1 and COMT, as predictors for cisplatin-related ototoxicity will be evaluated. Cost-effectiveness analyses comparing the two regimens will be assessed. Statistical plan: Based on rates of CTCAE grade ≥2 hearing loss in an earlier study (Winquist et al., 2016), assuming a conservative rate of hearing loss, amongst treated patients, of 60% with HD cisplatin and 30% with LD cisplatin, a total sample size of 92 patients would achieve > 80% statistical power, (two-sided, alpha = 0.05 test of two proportions) to detect these differences. 100 patients would be targeted to accrual for an assumed 5% noncompliance rate. For hearing related QOL, a two-sided, alpha = 0.05, two-sample t-test with 50 patients per group would achieve > 80% statistical power to detect an effect size of 0.60 and > 95% power to detect an effect size of 0.75. All analyses will be based primarily on the intent-to-treat population. An arms-length data and safety monitoring committee (DSMC) will review safety data bi-annually. Trial accrual status: 60 participants have been accrued. Clinical trial information: NCT03649048.

OBJECTIVE:We aimed to analyze risk factors associated with poor survival outcomes for metastatic cutaneous head-and-neck SCC to the parotid.METHODS:All patients undergoing surgery for metastatic cutaneous SCC to the parotid with curative intent between 2011 and 2018, were reviewed. Demographic and clinical characteristics were evaluated. Histopathological data including tumor size and histology, tumor grade, TNM stage, resection margins, lymphovascular invasion, and perineural invasion, were analyzed. Overall survival (OS), disease-specific survival (DSS), and freedom from locoregional recurrence (LRR) were assessed.RESULTS:Ninety patients were included (mean age, 77 years; 75 men [83.3%]). A total parotidectomy was performed in 48 patients (53.3%), and 42 (46.7%) underwent a superficial parotidectomy. Seventy patients (77.8%) underwent adjuvant RT. The median follow-up was 31 months (20-39 months). Tumor volume ≥ 50 cm3 and a shorter RT duration (<20 days) were associated with reduced OS (p = 0.002 and p = 0.01, p = 0.02 and p = 0.009, respectively), and DSS (p = 0.004 and p = 0.02, p = 0.04 and p = 0.02, respectively) on univariable and multivariable analysis, respectively. Only a shorter RT duration was associated with worse freedom from LRR on univariable and multivariable analysis, (p = 0.04 and p < 0.001, respectively). However, with death as a competing risk, a shorter duration of RT was not significantly associated with freedom from LRR.CONCLUSION:A shorter duration of adjuvant RT, and excised tumor volume ≥50 cm3 were predictive factors of reduced OS and DSS, and a shorter duration of RT was also associated with reduced freedom from LRR in patients with metastatic SCC to the parotid gland.LEVEL OF EVIDENCE:4 Laryngoscope, 133:1163-1168, 2023.

6055 Background: Head and neck sarcomas (HNS) are rare entities and confer substantial morbidity and mortality. Yet, the optimal management of HNS remains unclear. This study aimed to describe the epidemiology of HNS and to identify the most favorable treatment approach. Methods: We performed a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from 1990 until present. Articles in the English language reporting on survival outcomes of adult primary HNS patients treated with curative-intent were included. All estimates were weighted based on sample size. Analysis of variance (ANOVA) and two-sample t-tests were used as appropriate. Meta-analyses were performed using random effects models. This study was registered with PROSPERO, CRD42021220970. Results: A total of 3652 articles were identified, with 42 articles reporting on 21228 patients, meeting inclusion criteria. Mean ± SD age was 56.7 ± 14.6 years with 14170 (67.0%) men and 6991 (33.0%) women. The most common locations included skin and soft tissues (n = 12749, 63.3%), bones of skull and face (n = 2256, 11.2%), and oral cavity (n = 1775, 8.8%). The most common histologies included undifferentiated pleomorphic sarcoma (n = 5065, 24.8%), osteosarcoma (n = 2578, 12.6%), Kaposi sarcoma (n = 2316, 11.3%), chondrosarcoma (n = 2141, 10.5%), and hemangiosarcoma (n = 2072, 10.1%). 5459 patients had early stage I-II disease (76.9%) whereas 1643 had late stage III-IV disease (23.1%). Most received surgery alone (n = 10968, 61.0%), 3917 (21.8%) received surgery and radiotherapy (RT), 2173 (12.1%) received definitive RT/chemoradiotherapy (CRT), 811 (4.5%) received surgery and CRT, and 98 (0.5%) received surgery and chemotherapy. Negative margins were achieved in 6081 (76.5%). Mean ± SD follow-up was 55.3 ± 42.8 months. Weighted mean, 2-, 5-, and 10-year overall survival (OS) were 78.5 months, 75.9%, 63.2%, and 54.9% respectively. There was no significant difference in mean OS (P = 0.674) or 5-year OS (P = 0.965) between patients who received surgery alone, multimodality treatment with surgery and RT/CRT, or definitive RT/CRT. Mean ± SD 5-year OS was significantly higher with negative margins (62.7 ± 20.8%) compared with positive margins (22.7 ± 19.1%; P = 0.001). Mean ± SD local recurrence rate (LRR) was 32.0 ± 13.0%. LRRs were 41.8% for definitive RT/CRT, 39.3% for surgery and CRT, 33.6% for surgery alone, 24.7% for surgery and chemotherapy, and 20.1% for surgery and RT (P = 0.126). Conclusions: In the largest HNS study to date, negative margins were associated with an improvement in OS. Multimodality treatment did not confer an OS benefit. Definitive RT/CRT may be associated with a higher LRR. Randomized trials are needed to establish the optimal treatment approach for HNS.

e18039 Background: Angiosarcoma of the head and neck (ASHN) is a rare entity and confers substantial morbidity and mortality. Yet, the optimal management of ASHN remains unclear. This study aimed to describe the epidemiology of ASHN and to identify the most favorable treatment approach. Methods: We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from 1990 until present. Articles in the English language reporting on survival outcomes of adult primary ASHN treated with curative-intent, were included. All estimates were weighted based on sample size. Analysis of variance (ANOVA) and two-sample t-tests were used as appropriate. This study was registered with PROSPERO, CRD42021220970. Results: A total of 3652 studies were identified, with 14 articles reporting on 2265 ASHN patients, meeting inclusion criteria. Mean ± SD age was 70.6 ± 7.7 years with 1621 (66.6%) men and 812 (33.4%) women. ASHN involved the scalp (n = 176, 57.9%) and the face (n = 128, 42.1%). 249 patients had early stage I-II disease (39.6%) whereas 379 had late stage III-IV disease (60.4%). Most (n = 529, 45.6%) received surgery and radiotherapy (RT), 305 (26.3%) received surgery alone, 210 (18.1%) received definitive RT/chemoradiotherapy (CRT), 75 (6.5%) received surgery and CRT, and 33 (2.8%) received surgery and chemotherapy. Negative margins were achieved in 471 (55.9%) whereas 371 (44.1%) had positive margins. Mean ± SD follow-up was 41.7 ± 15.4 months. Weighted mean, 1-, 5-, and 10-year overall survival (OS) were 26.9 months, 67.3%, 30.6%, and 20.8% respectively. Mean and 5-year disease-specific survival (DSS) were 72.9 months and 50.3% respectively. Mean ± SD local recurrence rate (LRR) was 32.1 ± 11.7%. Median RT dose delivered was 60 Gy (interquartile range: 60-70). Patients who received surgery had a significantly higher mean OS (34.9 vs. 18.7 months, P = 0.04) and 5-year OS (30.1 vs. 14.2%, P = 0.01) compared with those who did not receive surgery. There was no significant difference in mean OS for receiving adjuvant chemotherapy (P = 0.99) or RT (P = 0.51). Conclusions: In the largest ASHN study to date, definitive surgical resection was associated with an improvement in OS. Multimodality treatment did not confer an OS benefit. Randomized trials are needed to establish the optimal treatment approach for ASHN.

Abstract Background Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients. Methods In this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain. Discussion This study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT. Trial registration ClinicalTrials.gov Identifier: NCT04221165 . Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

BackgroundHead-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting.MethodsPatients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time between appointments. Clinical and demographic data were collected for all patients.ResultsThe average time for patients to have their first appointment at the mdt clinic was 15.1 months, consisting of 3.9 months for patients to see a health care provider (hcp) for the first time since symptom onset and 10.7 months from first hcp appointment to the mdt clinic. Patients saw an average of 3 hcps before the mdt clinic visit (range: 1-7). No significant differences in time to presentation were found based on stage at presentation or anatomic site.ConclusionsAt our tertiary care cancer centre, a patient's clinical pathway to being seen at the mdt clinic shows significant delays, particularly in the time from the first hcp visit to mdt referral. Possible methods to mitigate delay include education about hnc for patients and providers alike, and a more streamlined referral system.

Malignant Triton Tumors (MTT) are rare and have a poor prognosis. Optimal treatment of this disease is not well understood. A systematic review was conducted to understand prognosis and provide guidance for treatment. A PUBMED search was completed using keywords "case series", "case report", "rhabdomyoblastic", "rhabdomyosarcomatous", and "triton". Inclusion criteria: English language, ≥ 1 adult patient with biopsy-proven MTT. Exclusion criteria: no treatment or outcome data available. Two investigators independently completed abstract and full-text reviews. Referenced articles meeting inclusion/exclusion criteria were also included. Univariable and multivariable Cox proportional hazards regression were performed to identify significant predictors of overall survival (OS) and progression-free survival (PFS). Two-hundred-eighty-five articles were identified using the search criteria and 13 were added following reference list search. One-hundred-seventy-one were excluded during abstract review and 30 during full-text review, leaving 97 articles and 123 cases. One additional case treated at our center was included for a total of 124 cases. The mean age was 43 years and 62.8% of the cases were male. The most common disease site was head and neck (28.2%). Treatments included surgery (95.9%), radiotherapy (60.7%) and chemotherapy (35.5%). Two-year OS was 46.2% and 2-year PFS was 27.1%. Significant predictors of OS included neurofibromatosis (NF) status, radiation exposure, central nervous system (CNS) or spine disease site, margin status, adjuvant radiotherapy, grade, mitoses, and divergent differentiation. Multivariable analysis (MVA) identified NF status (hazard ratio [HR]: 3.42, p<0.001), prior radiation exposure (HR: 3.99, p = 0.027), CNS/spine site (HR: 5.86, p<0.001) and adjuvant radiotherapy (HR: 0.58, p = 0.038) as significant predictors of OS. Similarly, significant predictors of PFS included NF status, CNS or spine site, margin status, radiotherapy, chemotherapy, and number of mitoses. On MVA, NF status (HR: 3.42, p<0.001), prior radiation exposure (HR: 3.99, p = 0.027), CNS/spine site (HR: 5.86, p<0.001) and adjuvant radiotherapy (HR: 0.58, p = 0.038) remained significant predictors for OS and NF status (HR: 2.34, p<0.001) and positive margin status (HR: 3.28, p<0.001) remained significant predictors of PFS. Prior radiation exposure, NF status and CNS/spine disease site have been identified as poor prognostic factors for patients with MTT. Our findings suggest adjuvant radiotherapy was associated with improved OS in patients with MTT.