Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

Risk analysis of the Unity 1.5 T MR-Linac adapt-to-position workflow.

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps. METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was formed to identify and evaluate failure modes for all the steps taken during a daily treatment workflow. Failure modes of high severity and overall score were isolated and addressed. RESULTS: Mitigations were determined for high-ranking failure modes and implemented into the clinic. High-ranking failure modes existed in all steps of the workflow. Failure modes were then rescored to evaluate the effectiveness of the mitigations. CONCLUSION: Failure modes and effects analysis on the Unity MR-Linac highlighted areas in the ATP workflow that could be prone to failures and allowed our clinic to change the process to be more robust.

Automated tracking of morphologic changes in weekly magnetic resonance imaging during head and neck radiotherapy.

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy can impact dose delivery, necessitate adaptive replanning, and indicate patient-specific response to treatment. We have developed an automated system to track these changes through longitudinal MRI scans to aid identification and clinical intervention. The purpose of this article is to describe this tracking system and present results from an initial cohort of patients. MATERIALS AND METHODS: The Automated Watchdog in Adaptive Radiotherapy Environment (AWARE) was developed to process longitudinal MRI data for radiotherapy patients. AWARE automatically identifies and collects weekly scans, propagates radiotherapy planning structures, computes structure changes over time, and reports important trends to the clinical team. AWARE also incorporates manual structure review and revision from clinical experts and dynamically updates tracking statistics when necessary. AWARE was applied to patients receiving weekly T2-weighted MRI scans during head and neck radiotherapy. Changes in nodal gross tumor volume (GTV) and parotid gland delineations were tracked over time to assess changes during treatment and identify early indicators of treatment response. RESULTS: N = 91 patients were tracked and analyzed in this study. Nodal GTVs and parotids both shrunk considerably throughout treatment (-9.7 ± 7.7% and -3.7 ± 3.3% per week, respectively). Ipsilateral parotids shrunk significantly faster than contralateral (-4.3 ± 3.1% vs. -2.9 ± 3.3% per week, p = 0.005) and increased in distance from GTVs over time (+2.7 ± 7.2% per week, p < 1 × 10-5 ). Automatic structure propagations agreed well with manual revisions (Dice = 0.88 ± 0.09 for parotids and 0.80 ± 0.15 for GTVs), but for GTVs the agreement degraded 4-5 weeks after the start of treatment. Changes in GTV volume observed by AWARE as early as one week into treatment were predictive of large changes later in the course (AUC = 0.79). CONCLUSION: AWARE automatically identified longitudinal changes in GTV and parotid volumes during radiotherapy. Results suggest that this system may be useful for identifying rapidly responding patients as early as one week into treatment.

Any day, split halfway: Flexibility in scheduling high-dose cisplatin-A large retrospective review from a high-volume cancer center.

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

HPV-associated oropharyngeal cancer de-escalation strategies and trials: Past failures and future promise.

HPV-associated oropharynx squamous cell carcinomas are radiosensitive and chemosensitive, thus, portending a favorable prognosis. Treatment de-intensification strategies aim to reduce toxicity while maintaining efficacy. Although approaches that have substituted cisplatin with cetuximab or omitted chemotherapy have not been successful, Transoral Robotic Surgery with de-intensified adjuvant therapy has been promising. Additionally, personalized approaches are taking advantage of tumor biology and utilizing tumor reduction or hypoxia on imaging as a predictive marker to successfully de-escalate radiotherapy and chemotherapy.

Predictive classifier for intensive treatment of head and neck cancer.

BACKGROUND: This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer. METHODS: This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS). RESULTS: Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011). CONCLUSIONS: LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.

The 3 Bs of cancer care amid the COVID-19 pandemic crisis: "Be safe, be smart, be kind"-A multidisciplinary approach increasing the use of radiation and embracing telemedicine for head and neck cancer.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID-19) pandemic, government-mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in-person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard-of-care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high-volume cancer center at the domestic epicenter of the COVID-19 crisis.

'Optimism bias' in contemporary national clinical trial network phase III trials: are we improving?

Background: Previous studies have found that overestimating treatment effects (i.e. 'optimism bias') leads to underpowered clinical trials. The prevalence of 'optimism bias' in contemporary National Clinical Trials Network (NCTN) cancer clinical trials is unknown. Methods: We conducted a systematic review of NCTN phase III randomized trials published from January 2007 to January 2017. We compared the hypothesized versus observed treatment effects in each trial, and examined whether trial-related factors were correlated with the study results. We also reviewed the methods of each protocol to assess whether a rationale for the hypothesized effect size was provided. Results: We identified 161 clinical trials, of which 130 were eligible for analysis. Original protocols could not be located for 8 trials (5.0%). Twenty-eight trials (21.5%) observed a statistically significant difference in the primary end point favoring the experimental treatment. The median ratio of observed-to-expected hazard ratios among trials that observed a statistically significant effect on the primary end point was 1.07 (range: 0.33-1.28) versus 1.32 (range: 0.86-2.02) for trials that did not, compared with 1.34 and 1.86, respectively, for National Cancer Institute (NCI) trials published between 1955 and 2006. An effect size at least as large as the one projected in the protocol trials was observed in 9.8% of trials, compared with 17% of NCI trials published from 1955 to 2006. Most trials (64.6%) provided no rationale to support the magnitude of the proposed treatment effect in the protocol. Conclusions: Despite a reduction in 'optimism bias' compared with previous eras, most contemporary NCTN phase III trials failed to establish statistically significant benefits of new cancer therapies. Better rationalization of proposed effect sizes in research protocols is needed.

Higher Rates of Inadequate Adjuvant Radiation Dose Among Older Adults with Head and Neck Cancer.

OBJECTIVE: To determine the rate of inadequate radiotherapy and identify risk factors associated with inadequate adjuvant radiotherapy for head and neck cancer among older adults. METHODS: A retrospective review of the National Cancer Database (NCDB) was performed to identify patients diagnosed with squamous cell cancer of the head and neck between 2004 and 2017. Patients with a single malignancy, negative surgical margins, no extranodal extension, and receipt of adjuvant radiation without systemic therapy were included in the study cohort. The main outcome of interest was the adjuvant radiation dose received. Participant data were compared using univariable, multivariable, and correlation analyses to evaluate risk factors for inadequate radiation therapy (RT) dosing. RESULTS: Among 7608 patients, 1010 patients (13.3%) received an inadequate radiation dose and 6598 (86.7%) received an adequate dose. Patients living in a higher income zip-code, younger age, and those who received intensity-modulated RT (IMRT) were more likely to receive an adequate radiation dose (p < 0.05). Patients older than 70 and 80 years old had a greater likelihood of receiving an inadequate radiation dose (≥70 vs. <70: 16.9% vs. 12.5%; p < 0.05 and ≥80 vs. <80: 20.6% vs. 13.0%%; p < 0.05). Similarly, increasing age was negatively correlated with radiation dose (correlation coefficient: -0.05; p < 0.001). CONCLUSION: A substantial proportion of older patients receiving adjuvant radiation do not complete the full treatment. Older age, year of diagnosis, non-IMRT, and living in a lower-income zip code were associated with early termination of RT. Future studies should examine strategies to improve tolerance of adjuvant RT so that more patients complete the full treatment. LEVEL OF EVIDENCE: 3; Cohort Study Laryngoscope, 134:2206-2211, 2024.

Osteoradionecrosis Rates After Head and Neck Radiation Therapy: Beyond the Numbers.

PURPOSE: Osteoradionecrosis (ORN) is a severe late complication of head and neck radiation therapy shown to have profound negative effect on the quality of life of cancer survivors. Over the past few decades, improvements in radiation delivery techniques have resulted in a decrease in the incidence of ORN. However, even with modern radiation therapy techniques, ORN remains an important clinical concern. In recent literature, there is a wide range of reported ORN rates from 0% to as high as 20%. With such a high level of variability in the reported incidence of ORN, oncologists often encounter difficulties estimating the risk of this serious radiation therapy toxicity. METHODS AND MATERIALS: In this review, the authors present a summary of the factors that contribute to the high level of variability in the reported incidence of ORN. RESULTS: Variable definition, variable grading, and heterogeneity of both study inclusion criteria and treatment parameters can each significantly influence the reporting of ORN rates. CONCLUSIONS: Given numerous factors can affect the reported incidence of ORN, a thorough understanding of the clinical context behind the reported ORN rates is needed to comprehend the true risk of this important radiation therapy toxicity.

Nomogram to predict risk of early mortality following definitive or adjuvant radiation and systemic therapy for head and neck cancer.

Purpose/Objectives: We sought to create nomograms to predict individual risk of early mortality, which can identify patients who require interventions to prevent early death. Methods: We included patients in the National Cancer Database with non-metastatic squamous cell carcinoma of the head and neck who received radiation and systemic therapy between 2004 and 2017 in the definitive or adjuvant setting. Early mortality was defined as any death less than 90 days after starting radiation. Multivariable logistic regression was used to assess the relationship between covariates and early mortality. Nomograms to predict the risk of early death were created for both the definitive and adjuvant settings. Results: Among 84,563 patients in the definitive group and 18,514 patients in the adjuvant group, rates of early mortality were 3.5 % (95 % CI 3.4-3.7 %) and 2.2 %, (95 % CI 1.9-2.4 %), respectively. Patients above the age of 70 had an early mortality rate of 7.8 % (95 % CI 7.3-8.2 %) in the definitive group and 4.4 % (95 % CI 3.6-5.4 %) in the adjuvant group. In the multivariable analysis, age, comorbidity, T and N category, and tumor site were associated with early mortality in both cohorts (p < 0.05 for all). Nomograms including age, comorbidity, T and N category and tumor site performed better than age alone at predicting early mortality (AUC for definitive group: 0.70 vs 0.66; AUC for adjuvant group: 0.71 vs 0.61). Conclusion: Nomograms including age, comorbidity, T and N category and tumor site were developed to predict the risk of early death following definitive or adjuvant chemoradiation.

Clinical Experience With an Offline Adaptive Radiation Therapy Head and Neck Program: Dosimetric Benefits and Opportunities for Patient Selection.

PURPOSE: The objective of this study was to develop a linear accelerator (LINAC)-based adaptive radiation therapy (ART) workflow for the head and neck that is informed by automated image tracking to identify major anatomic changes warranting adaptation. In this study, we report our initial clinical experience with the program and an investigation into potential trigger signals for ART. METHODS AND MATERIALS: Offline ART was systematically performed on patients receiving radiation therapy for head and neck cancer on C-arm LINACs. Adaptations were performed at a single time point during treatment with resimulation approximately 3 weeks into treatment. Throughout treatment, all patients were tracked using an automated image tracking system called the Automated Watchdog for Adaptive Radiotherapy Environment (AWARE). AWARE measures volumetric changes in gross tumor volumes (GTVs) and selected normal tissues via cone beam computed tomography scans and deformable registration. The benefit of ART was determined by comparing adaptive plan dosimetry and normal tissue complication probabilities against the initial plans recalculated on resimulation computed tomography scans. Dosimetric differences were then correlated with AWARE-measured volume changes to identify patient-specific triggers for ART. Candidate trigger variables were evaluated using receiver operator characteristic analysis. RESULTS: In total, 46 patients received ART in this study. Among these patients, we observed a significant decrease in dose to the submandibular glands (mean ± standard deviation: -219.2 ± 291.2 cGy, P < 10-5), parotids (-68.2 ± 197.7 cGy, P = .001), and oral cavity (-238.7 ± 206.7 cGy, P < 10-5) with the adaptive plan. Normal tissue complication probabilities for xerostomia computed from mean parotid doses also decreased significantly with the adaptive plans (P = .008). We also observed systematic intratreatment volume reductions (ΔV) for GTVs and normal tissues. Candidate triggers were identified that predicted significant improvement with ART, including parotid ΔV = 7%, neck ΔV = 2%, and nodal GTV ΔV = 29%. CONCLUSIONS: Systematic offline head and neck ART was successfully deployed on conventional LINACs and reduced doses to critical salivary structures and the oral cavity. Automated cone beam computed tomography tracking provided information regarding anatomic changes that may aid patient-specific triggering for ART.

An Analysis of Positron Emission Tomography Maximum Standard Uptake Value Among Patients With Head and Neck Cancer Receiving Photon and Proton Radiation.

PURPOSE: One main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical, given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors, including air-tissue interface, anatomic uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. In addition, the elevated relative biological effectiveness at the Bragg peak's distal end can also increase hot spots within and outside the target area. METHODS AND MATERIALS: The purpose of this study was to evaluate for a difference in positron emission tomography (PET) standard uptake value (SUV) after definitive treatment, between intensity modulated proton therapy (IMPT) and intensity modulated photon therapy (IMRT). In addition, we compared the biologic dose between PET areas of high and low uptake within the clinical target volume-primary of patients treated with IMPT. This work is assuming that the greater SUV may potentially result in greater toxicities. For the purposes of this short communication, we are strictly focusing on the SUV and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month posttreatment fluorodeoxyglucose PET scans for 100 matched patients with oropharyngeal cancer treated definitively without surgery using either IMPT (n = 50) or IMRT (n = 50). RESULTS: Our study found a significant difference in biologic dose between the high- and low-uptake regions on 3-month posttreatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the clinical target volume-primary at 3 and 6 months' follow-up between patients who received IMPT versus IMRT. CONCLUSIONS: Studies have proposed that proton's greater relative biological effectiveness at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes.

Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial.

BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. INTERVENTION: Short-term ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score. RESULTS AND LIMITATIONS: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards. CONCLUSIONS: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT. PATIENT SUMMARY: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Correlation of an Electronic Geriatric Assessment With Receipt of Adjuvant Radiation and Chemotherapy in Older Adults With Head and Neck Cancer.

Purpose: Treatment patterns for head and neck squamous cell carcinoma (HNSCC) vary among older adults because of concerns about their health status. Geriatric assessment may guide treatment for older adults with HNSCC by assessing their health status. Methods and Materials: We conducted a retrospective review of adjuvant treatment received by older patients with HNSCC who completed a novel geriatric assessment, the electronic Rapid Fitness Assessment, before treatment. The electronic Rapid Fitness Assessment yields an accumulated geriatric deficits (AGD) score. Higher AGD score indicates greater frailty. Comparators were age and performance status. The Wilcoxon rank sum test compared differences between those who did and did not receive adjuvant radiation therapy and chemotherapy. Results: The cohort included 73 patients, of whom 56 (77%) had oral cavity cancer. The most common geriatric deficits were major distress, social activity limitation, depression, and impaired activities of daily living. AGD score, age, and performance status were not associated with receipt of adjuvant radiation. Patients who received adjuvant chemotherapy had a significantly lower median AGD score than those who did not (3 vs 6; P = .044), but there was no association with age and performance status. Of the 17 patients with newly diagnosed disease and either positive margins or extranodal extension, only 9 received adjuvant radiation and only 3 received systemic therapy. Most often, systemic therapy was omitted because of patient preference or comorbidities and poor performance status. There was a nonstatistically significant lower AGD score between patients who did and did not receive standard fractionated radiation therapy (median, 4 vs 6.5; P = .13). Conclusions: Receipt of adjuvant chemotherapy was associated with frailty. Rates of chemotherapy utilization were very low, indicating the need for novel strategies to mitigate the toxicity burden in this patient population. Receipt of adjuvant radiation therapy was not associated with frailty; however, there was a trend toward lower frailty among those who did receive radiation therapy.

Differential use of postoperative psychosocial and physical services among older adults with head and neck cancer.

INTRODUCTION: Older adults undergoing head and neck cancer (HNC) surgery often have significant functional and mental health impairments. We examined use of postoperative physical, nutritional, and psychosocial services among a cohort of older adults with HNC comanaged by geriatricians and surgeons. MATERIALS AND METHODS: Our sample consisted of older adults who were referred to the Geriatrics Service at Memorial Sloan Kettering Cancer Center between 2015 and 2019 and took a geriatric assessment (GA) prior to undergoing HNC surgery. Physical, nutritional, and psychosocial service utilization was assessed. Physical services included a physical, occupational, or rehabilitation consult during the patient's stay. Nutritional services consisted of speech and swallow or nutritional consult. Psychosocial services consisted of psychiatry, psychology, or a social work consult. Relationships between each service use, geriatric deficits, demographic, and surgical characteristics were assessed using Wilcoxon rank-sum test or Chi-square test. RESULTS: In total, 157 patients were included, with median age of 80 and length of stay of six days. The most common GA impairments were major distress (61%), depression (59%), social activity limitation (SAL) (54%), and deficits in activities of daily living (ADL) (44%). Nutritional and physical services were used much more frequently than psychosocial services (80% and 85% vs 31%, respectively). Receipt of services was associated with longer median length of hospital stay, operation time, and greater deficits in ADLs. SAL was associated with physical and psychosocial consult and lower Timed Up and Go (TUG) score; instrumental ADL (iADL) deficits were associated with physical services; and depression and distress were associated with psychosocial services. DISCUSSION: The burden of psychosocial deficits is high among older adults with HNC. Future work is needed to understand the limited utilization of psychosocial services in this population as well as whether referral to psychosocial services can reduce the burden of these deficits.

Outcomes for Organ Preservation with Chemoradiation Therapy for T4 Larynx and Hypopharynx Cancer.

OBJECTIVE: Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long-term therapeutic and functional outcomes. METHODS: We reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA). RESULTS: The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-intensity-modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease-free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow-up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither. CONCLUSION: We report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1138-1145, 2023.

Osteoradionecrosis of the Jaw Following Proton Radiation Therapy for Patients With Head and Neck Cancer.

Importance: Proton radiation therapy (PRT) has reduced radiation-induced toxic effects, such as mucositis and xerostomia, over conventional photon radiation therapy, leading to significantly improved quality of life in patients with head and neck cancers. However, the prevalence of osteoradionecrosis (ORN) of the jaw following PRT in these patients is less clear. Objective: To report the prevalence and clinical characteristics of ORN in patients with oral and oropharyngeal cancer (OOPC) treated with PRT. Design, Setting, and Participants: This case series reports a single-institution experience (Memorial Sloan Kettering Cancer Center, New York, New York) between November 2013 and September 2019 and included 122 radiation therapy-naive patients with OOPC treated with PRT. Data were analyzed from 2013 to 2019. Main Outcomes and Measures: Clinical parameters, including sex, age, comorbidities, tumor histology, concurrent chemotherapy, smoking, comorbidities, and preradiation dental evaluation, were obtained from the medical record. Patients with clinical or radiographic signs of ORN were identified and graded using the adopted modified Glanzmann and Grätz grading system. Characteristics of ORN, such as location, clinical presentation, initial stage at diagnosis, etiology, time to diagnosis, management, and clinical outcome at the last follow-up, were also collected. Results: Of the 122 patients (mean [SD] age, 63 [13] years; 45 [36.9%] women and 77 [63.1%] men) included in this study, 13 (10.6%) developed ORN following PRT during a median (range) follow-up time of 40.6 (<1-101) months. All patients had spontaneous development of ORN. At the time of initial diagnosis, grade 0, grade 1, grade 2, and grade 3 ORN were seen in 2, 1, 9, and 1 patient, respectively. The posterior ipsilateral mandible within the radiation field that received the full planned PRT dose was the most involved ORN site. At a median (range) follow-up of 13.5 (0.2-58.0) months from the time of ORN diagnosis, complete resolution, stable condition, and progression of ORN were seen in 3, 6, and 4 patients, respectively. The 3-year rates of ORN and death in the total cohort were 5.2% and 21.5%, while the 5-year rates of ORN and death were 11.5% and 34.4%, respectively. Conclusions and Relevance: In this case series, the prevalence of ORN following PRT was found to be 10.6%, indicating that ORN remains a clinical challenge even in the era of highly conformal PRT. Clinicians treating patients with OOPC with PRT should be mindful of this complication.