Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial.

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period (P = .11). EORTC QLQ-C30 and H&N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm (P = .032) and worse pain in the TORS arm (P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P < .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.

Vertical Partial Laryngectomy With Temporoparietal Free-Flap Reconstruction for Recurrent Laryngeal Cancer: Long-Term Study.

Objective: Treatment options for recurrent early glottic carcinoma's include conservative and radical surgical options. These options offer similar survival benefits with different impacts of patient's quality of life. We previously present our experience with vertical partial laryngectomy (VPL) and showed high locoregional control rates with high-quality voice results and normal swallowing. Study Design: A long-term retrospective review. Setting: Tertiary Care Center. Methods: We analyzed all patients underwent VPL between the years 1995 to 2018. Long-term oncologic and functional outcomes were collected. Results: A total of 40 patients were included. The majority of whom were male (n = 38, 95%) with a mean age of 64.9 years (SD ± 9.5). With a median follow up time of 12 years (range 0-24), 9 patients (22.5%) had disease recurrence; the majority of whom (8 patients), had local recurrence and all were salvaged with total laryngectomy. Eight patients (20%) developed second primaries in the head and neck region with a median time to diagnosis of 77 months (range 8-227 months). Ten-years overall survival, disease specific survival, and local disease-free survival were 80%, 90%, and 80%, respectively. Five patients had postoperative laryngeal dysfunction with a total 10-years laryngectomy free survival of 70%. Conclusion: VPL has a sustainable oncologic outcome with a high long-term laryngectomy free survival rate. This entity is an acceptable conservative salvage option for selected postradiated recurrent laryngeal squamous cell carcinoma patients.

Sinonasal Malignancy Following Cranial Irradiation: A Scoping Review and Case Report of Sinonasal Teratocarcinosarcoma.

Background Radiation therapy is a mainstay of treatment for brain tumors, but delayed complications include secondary malignancy which may occur months to years after treatment completion. Methods We reviewed the medical records of a 41-year-old female treated with 60 Gy of radiation for a recurrent astrocytoma, who 6 years later developed a locally advanced sinonasal teratocarcinosarcoma. We searched MEDLINE, Embase, and Web of Science to conduct a scoping review of biopsy-proven sinonasal malignancy in patients who previously received cranial irradiation for a brain tumor. Results To our knowledge, this is the first report of a patient to present with a sinonasal teratocarcinosarcoma after receiving irradiation for a brain tumor. Our scoping review of 1,907 studies produced 14 similar cases of secondary sinonasal malignancy. Median age of primary cancer diagnosis was 39.5 years old (standard deviation [SD]: 21.9), and median radiation dose was 54 Gy (SD: 20.3). Median latency time between the primary cancer and secondary sinonasal cancer was 9.5 years (SD: 5.8). Olfactory neuroblastoma was the most common sinonasal cancer ( n = 4). Fifty percent of patients died from their sinonasal cancer within 1.5 years. Conclusion Patients who receive radiation exposure to the sinonasal region for treatment of a primary brain tumor, including low doses or scatter radiation, may be at risk of a secondary sinonasal malignancy later in life. Physicians who monitor at-risk patients must be vigilant of symptoms which may suggest sinonasal malignancy, and surveillance should include radiographic review with careful monitoring for a secondary malignancy throughout the entire irradiated field.

A multi-institutional feasibility lead-in trial of lymphatic mapping with SPECT-CT for evaluating contralateral disease in lateralized oropharynx cancer using 99m-technetium sulfur colloid.

BACKGROUND: Lymphatic mapping with SPECT-CT has been demonstrated to accurately define lymphatic drainage patterns in oropharyngeal cancer but there has yet to be a study demonstrating its feasibility across multiple institutions. METHODS: Twelve adult patients with lateralized oropharyngeal carcinoma (T1-T3) who were planned for definitive or adjuvant radiotherapy without contralateral nodal disease underwent injection of 99-m technetium sulfur colloid followed by static planar lymphoscintigraphy to verify tracer migration, and SPECT-CT acquired at 30 ± 15 min (optional) and 3 h (±1 h) (mandatory time-point). RESULTS: All 12 patients completed the study with 7/12 patients having the injections performed under local anesthetic and 5 patients requiring general anesthetic. There were no tracer migration failures and there were no serious adverse events or complications encountered. Four out of 12 patients (33%) showed contralateral drainage patterns. CONCLUSIONS: Lymphatic mapping with SPECT-CT of lateralized oropharyngeal squamous cell carcinoma can be performed safely across multiple institutions.

Proposed Quality Indicators for Aspects of Pediatric Acute Otitis Media Management.

BACKGROUND: The high incidence of pediatric acute otitis media (AOM) makes the implications of overdiagnosis and overtreatment far-reaching. Quality indicators (QIs) for AOM are limited, drawing from generalized upper respiratory infection QIs, or locally developed benchmarks. Recognizing this, we sought to develop pediatric AOM QIs to build a foundation for future quality improvement efforts. METHODS: Candidate indicators (CIs) were extracted from existing guidelines and position statements. The modified RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness methodology was used to select the final QIs by an 11-member expert panel consisting of otolaryngology-head and neck surgeons, a pediatrician and family physician. RESULTS: Twenty-seven CIs were identified after literature review, with an additional CI developed by the expert panel. After the first round of evaluations, the panel agreed on 4 CIs as appropriate QIs. After an expert panel meeting and subsequent second round of evaluations, the panel agreed on 8 final QIs as appropriate measures of high-quality care. The 8 final QIs focus on topics of antimicrobial management, specialty referral, and tympanostomy tube counseling. CONCLUSIONS: Evidence of variable and substandard care persists in the diagnosis and management of pediatric AOM despite the existence of high-quality guidelines. This study proposes 8 QIs which compliment guideline recommendations and are meant to facilitate future quality improvement initiatives that can improve patient outcomes.

Nodal Metastases in Stage 3 Head and Neck Melanoma: Patterns of Metastases and Patterns of Failure.

OBJECTIVE: Stage 3 patients with clinically positive nodal metastasis are treated with therapeutic neck dissection and adjuvant systemic therapy. The aim of our study was to examined the predictability of pre-operative CT as a nodal drainage assessment tool. METHODS: Retrospective review of all patients with clinically positive head and neck cutaneous melanoma between 2010 and 2019. Clinical disease was diagnosed as radiological suspicious, biopsy-proven node. A pre-operative CT evaluation for nodal metastasis was compared to pathology report. RESULTS: A total of 53 patients were included. Forty patients (75.5%) were males with a mean age of 59 (SD 15.52). The majority of patients (26.4%) had an unknown primary site. The most common sites for primary were the cheek in eight patients (15.1%) followed by forehead (9.4%) and lateral neck (9.4%). Preoperative CT predicted nodal disease in 84.6% of cases. The primary region that mainly failed from the previously described clinical prediction was the upper anterior neck with 83.3% parotid involvement. A total of 10 patients (18.9%) were diagnosis with non-clinical nodes on pathology with a median non-clinical node of 1 (range 1-2). Of them, 9 (90%) were in the same clinical levels detected by CT. Pre-operative CT was associated with a neck level accuracy of 98.1%. CONCLUSION: Stage 3 head and neck melanoma with clinically positive nodal metastasis that are eligible for an adjuvant systemic treatment, may benefit from a highly selective neck dissection according to their pre-operative imaging studies. This should be further evaluated in a large-scale clinical trial. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Long-term outcomes in virtual surgical planning for mandibular reconstruction: A cost-effectiveness analysis.

OBJECTIVE: This study is an economic evaluation comparing virtual surgical planning (VSP) utilization to free hand mandibular reconstruction (FHR) for advanced oral cavity cancer, for which the cost effectiveness remains poorly understood. The proposed clinical benefits of VSP must be weighed against the additional upfront costs. METHODS: A Markov decision analysis model was created for VSP and FHR based on literature review and institutional data over a 35-year time horizon. Model parameters were derived and averaged from systematic review and institutional experience. VSP cost and surgical time saving was incorporated. We accounted for long-term risks including cancer recurrence and hardware failure/exposure. We calculated cost in US dollars and effectiveness in quality-adjusted-life-years (QALYs). A health care perspective was adopted, discounting costs and effectiveness at 3%/year. Deterministic and probabilistic sensitivity analyses tested model robustness. RESULTS: In the base case scenario, total VSP strategy cost was $49,498 with 8.37 QALYs gained while FHR cost was $42,478 with 8.27 QALY gained. An incremental cost-effectiveness ratio (ICER), or the difference in cost/difference in effectiveness, for VSP was calculated at $68,382/QALY gained. VSP strategy favorability was sensitive to variations of patient age at diagnosis and institutional VSP cost with one-way sensitivity analysis. VSP was less economically favorable for patients >75.5 years of age or for institutional VSP costs >$10,745. In a probabilistic sensitivity analysis, 55% of iterations demonstrated an ICER value below a $100,000/QALY threshold. CONCLUSIONS/RELEVANCE: VSP is economically favorable compared to FHR in patients requiring mandibular reconstruction for advanced oral cancer, but these results are sensitive to the patient's age at diagnosis and the institutional VSP cost. Our results do not suggest if one "should or should not" use VSP, rather, emphasizes the need for patient selection regarding which patients would most benefit from VSP when evaluating quality of life and long-term complications. Further studies are necessary to demonstrate improved long-term risk for hardware failure/exposure in VSP compared to FHR.

Development and Standardization of an Osteoradionecrosis Classification System in Head and Neck Cancer: Implementation of a Risk-Based Model.

PURPOSE: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN. METHODS: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared with 15 existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection). RESULTS: ORN was identified in 219 of 2,732 (8%) consecutive patients with HNC. Factors associated with high risk of ORN were oral cavity or oropharyngeal primaries, received IMRT dose ≥60 Gy, current/ex-smokers, and/or stage III to IV periodontal condition. The ORN rate for high-risk versus low-risk patients was 12.7% versus 3.1% (P < .001) with an AUC of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, ClinRad, was proposed on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems. CONCLUSION: We identified risk factors for ORN and proposed a novel ORN classification system on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN and may facilitate clinical care and clinical trials.

Length of Stay Prediction Models for Oral Cancer Surgery: Machine Learning, Statistical and ACS-NSQIP.

OBJECTIVE: Accurate prediction of hospital length of stay (LOS) following surgical management of oral cavity cancer (OCC) may be associated with improved patient counseling, hospital resource utilization and cost. The objective of this study was to compare the performance of statistical models, a machine learning (ML) model, and The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) calculator in predicting LOS following surgery for OCC. MATERIALS AND METHODS: A retrospective multicenter database study was performed at two major academic head and neck cancer centers. Patients with OCC who underwent major free flap reconstructive surgery between January 2008 and June 2019 surgery were selected. Data were pooled and split into training and validation datasets. Statistical and ML models were developed, and performance was evaluated by comparing predicted and actual LOS using correlation coefficient values and percent accuracy. RESULTS: Totally 837 patients were selected with mean patient age being 62.5 ± 11.7 [SD] years and 67% being male. The ML model demonstrated the best accuracy (validation correlation 0.48, 4-day accuracy 70%), compared with the statistical models: multivariate analysis (0.45, 67%) and least absolute shrinkage and selection operator (0.42, 70%). All were superior to the ACS-NSQIP calculator's performance (0.23, 59%). CONCLUSION: We developed statistical and ML models that predicted LOS following major free flap reconstructive surgery for OCC. Our models demonstrated superior predictive performance to the ACS-NSQIP calculator. The ML model identified several novel predictors of LOS. These models must be validated in other institutions before being used in clinical practice. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3664-3672, 2024.

Addressing Financial Toxicity in Head and Neck Cancer-A Crucial Imperative.

This Viewpoint calls for consideration of the financial costs of head and neck cancer care when choosing treatment strategies for patients who may face severe financial stress or insolvency due to cancer treatment.

Telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma.

BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck: The Phase 2 FIND Nonrandomized Controlled Trial.

Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects. Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control. Design, Setting, and Participants: This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022. Intervention: Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0. Main Outcomes and Measures: Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings. Results: The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%). Conclusions and Relevance: These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03281499.

Palliative Care as a Component of High-Value and Cost-Saving Care During Hospitalization for Metastatic Cancer.

PURPOSE: Randomized controlled trials have demonstrated that palliative care (PC) can improve quality of life and survival for outpatients with advanced cancer, but there are limited population-based data on the value of inpatient PC. We assessed PC as a component of high-value care among a nationally representative sample of inpatients with metastatic cancer and identified hospitalization characteristics significantly associated with high costs. METHODS: Hospitalizations of patients 18 years and older with a primary diagnosis of metastatic cancer from the National Inpatient Sample from 2010 to 2019 were analyzed. We used multivariable mixed-effects logistic regression to assess medical services, patient demographics, and hospital characteristics associated with higher charges billed to insurance and hospital costs. Generalized linear mixed-effects models were used to determine cost savings associated with provision of PC. RESULTS: Among 397,691 hospitalizations from 2010 to 2019, the median charge per admission increased by 24.9%, from $44,904 in US dollars (USD) to $56,098 USD, whereas the median hospital cost remained stable at $14,300 USD. Receipt of inpatient PC was associated with significantly lower charges (odds ratio [OR], 0.62 [95% CI, 0.61 to 0.64]; P < .001) and costs (OR, 0.59 [95% CI, 0.58 to 0.61]; P < .001). Factors associated with high charges were receipt of invasive medical ventilation (P < .001) or systemic therapy (P < .001), Hispanic patients (P < .001), young age (18-49 years, P < .001), and for-profit hospitals (P < .001). PC provision was associated with a $1,310 USD (-13.6%, P < .001) reduction in costs per hospitalization compared with no PC, independent of the receipt of invasive care and age. CONCLUSION: Inpatient PC is associated with reduced hospital costs for patients with metastatic cancer, irrespective of age and receipt of aggressive interventions. Integration of inpatient PC may de-escalate costs incurred through low-value inpatient interventions.

Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

BACKGROUND: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). METHODS: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative.

PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

Development and Standardization of a Classification System for Osteoradionecrosis: Implementation of a Risk-Based Model.

Purpose: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN. Methods: Consecutive head-and-neck cancer (HNC) patients treated with curative-intent IMRT (≥ 45Gy) in 2011-2018 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared to fifteen existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection). Results: ORN was identified in 219 out of 2732 (8%) consecutive HNC patients. Factors associated with high-risk of ORN were: oral-cavity or oropharyngeal primaries, received IMRT dose ≥60Gy, current/ex-smokers, and/or stage III-IV periodontal disease. The ORN rate for high-risk vs low-risk patients was 12.7% vs 3.1% (p<0.001) with an area-under-the-receiver-operating-curve (AUC) of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, RadORN, was proposed based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems. Conclusion: We identified risk factors for ORN, and proposed a novel ORN classification system based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN, and may facilitate clinical care and clinical trials.

Individualized risk assessment of distant metastases in oral cavity carcinoma: a validated predictive-score model.

BACKGROUND: We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC). METHODS: Patients with OCC who were treated at 4 tertiary cancer institutions with curative surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort. RESULTS: Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001). CONCLUSIONS: Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

The impact of surgical resection margins on outcomes for adults with head and neck osteosarcomas: A Canadian sarcoma research and Clinical Collaboration (CanSaRCC) study.

OBJECTIVE: The aim of the study is to describe the factors that influence outcome in adults with head and neck osteosarcoma (HNO) with a specific focus on the margin status. METHODS: Patients with a diagnosis of HNO between the years 1996-2021 were reviewed from the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) Database. Baseline characteristics, pathology, treatment, and outcomes were analyzed. Univariable (UVA) and multivariable (MVA) Cox regression models were performed. 5-year locoregional control rate and overall survival (OS) were estimated using Kaplan-Meier method and Log-Rank test. RESULTS: Of 50 patients with a median age of 40 years (range 16-80), 27 (54%) were male. HNO commonly involved the mandible (n = 21, 42%) followed by maxilla (n = 15, 30%). Thirteen (33.3%) had low-intermediate grade and 26 (66.6%) had high grade tumors. Three patients (6%) had negative resection margins (>5 mm), 24 (48%) had close margins (1-5 mm), 15 (30%) had positive margins (<1mm) and 7 (16%) had unknown margin status. In total, 39 (78%) received chemotherapy - 22 (44%) received neoadjuvant chemotherapy while 17 (34%) received adjuvant chemotherapy. A total of 12 (24%) patients received radiotherapy, of whom 8 (16%) had adjuvant and 3 (6%) had neo-adjuvant. Median follow-up time was 6.3 years (range 0.26-24.9). Disease recurred in 21 patients (42%), of whom 15 (30%) had local recurrence only, 4 (8%) had distant metastasis, and 2 (4%) had both local and distant recurrence. 5-year locoregional control rate and OS was 62% and 79.2% respectively. Resection margins <3 mm was associated with lower 5 years OS and locoregional control rate (Log-Rank p = 0.02, p = 0.01 respectively). CONCLUSION: Osteosarcomas of the head and neck are rare and local recurrence remains a concern. Surgical resection with negative resection margins may improve survival, and a 3 mm resection margin threshold may optimize survival. Radiotherapy and/or chemotherapy should be considered in a multidisciplinary setting based on risk-features.