Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis.

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

Transition to Value-based Healthcare: Development, Implementation, and Results of an Optimal Surgical Care Framework at a National Cancer Institute-designated Comprehensive Cancer Center.

BACKGROUND: The continued rise in healthcare expenditures has not produced commensurate improvements in patient outcomes, leading US healthcare stakeholders to emphasize value-based care. Transition to such a model requires all team members to adopt a new strategic and organizational framework. OBJECTIVE: To describe and report a strategy for the implementation of a novel patient-centered value-based "optimal surgical care" (OSC) framework, with validation and cost analysis in kidney surgery. DESIGN, SETTING, AND PARTICIPANTS: An observational study of care episodes at a single institution from 2014 to 2019 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multidisciplinary teams defined OSC by core and procedure-specific metrics using a combination of provider-based ("bottom-up") and "clinical leadership"-based ("top-down") strategies. Baseline OSC rates across were established, while identifying proportions of OSC achieved by coefficient of variation (CV) in total direct costs. Multivariable linear regression comparing cost between OSC and non-OSC encounters was performed, adjusting for patient characteristics. RESULTS AND LIMITATIONS: An analysis of 30 261 perioperative care episodes was performed. Following the implementation of an OSC framework, there was an increase in OSC rates across all procedure buckets using core (25%) and procedure-specific (26%) metrics. Among the tumors tested, kidney cancer surgical episodes held the highest OSC rate improvement (67%) with lowest variability in cost (CV 0.5). OSC was associated with significant total cost savings across all tumor types after adjusting for inflation (p < 0.05). Compared with non-OSC episodes, a significant reduction in the cost ratio of OSC was noted for renal surgery (p < 0.01), with estimated costs savings of $2445.87 per OSC encounter. CONCLUSIONS: Institutional change directing efforts toward optimizing surgical care and emphasizing value rather than focusing solely on expense reduction is associated with improved outcomes, while potentially reducing costs. The strategy for implementation requires serial performance analyses, engaging and educating providers, and continuous ongoing adjustments to achieve durable results. PATIENT SUMMARY: In this study, we report our strategy and outcomes for transitioning to a value-based healthcare model using a novel "optimal surgical care" framework at a National Cancer Institute-designated comprehensive cancer center. We observed an increase in optimal surgical care episodes across all specialties after 5 yr, with a potential associated reduction in cost expenditure. We conclude that the key to a successful and sustained transition is the implementation strategy, focusing on continual review and provider engagement.

Osteoradionecrosis rate in oropharynx cancer treated with dose volume histogram based constraints.

OBJECTIVES: Mandibular dose constraints are designed to limit high dose to small volumes to avoid osteoradionecrosis (ORN). Based upon a published experience, intermediate-dose constraints were introduced but have not been independently validated. We hypothesize that these constraints lower ORN rate without compromising other organs at risk (OAR). METHODS: Oropharyngeal cancer patients treated with standard fractionation adjuvant/definitive VMAT from 01/2014-08/2020 were included. In 09/2017, mandibular dose constraint was changed from historical constraint (HC) of D 0.1 cc < 70 Gy to modified constraints (MC) of V 44 Gy < 42%, V 58 Gy < 25%, D 0.5 cc < 70 Gy. OAR dosimetric changes and ORN development were evaluated. Regression modelling predicted long-term ORN cases in MC group. RESULTS: There were 174 patients, 71 in MC group. Seven cases of ORN in HC group at a median follow up (FU) of 39 months and 1 case of ORN in MC group at a median FU of 11 months were observed. More patients in the MC group met V 44 Gy (87% vs 62%, p < 0.01) and V 58 Gy constraints (92% vs 73%, p < 0.01). Mean doses to OARs did not rise. Mandible V 44 Gy and V 58 Gy were significantly associated with ORN (p < 0.01 and p = 0.03, respectively) across all patients. In the HC group, V 44 Gy was independently associated with ORN (p = 0.01). To account for shorter FU in MC group, logistic regression of ORN based on V 44 Gy in HC patients was performed. This predicts 3.2 ORN cases in the MC group (95% CI: 0.00-6.4). CONCLUSION: Achieving V 44 Gy and V 58 Gy was successful in 87% of cases without sacrificing target coverage or OARs and resulted in non-significant ORN decrease.

Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Retreatment of Recurrent or Second Primary Head and Neck Cancer After Prior Radiation: Executive Summary of the American Radium Society Appropriate Use Criteria.

Retreatment of recurrent or second primary head and neck cancers occurring in a previously irradiated field is complex. Few guidelines exist to support practice. We performed an updated literature search of peer-reviewed journals in a systematic fashion. Search terms, key questions, and associated clinical case variants were formed by panel consensus. The literature search informed the committee during a blinded vote on the appropriateness of treatment options via the modified Delphi method. The final number of citations retained for review was 274. These informed 5 key questions, which focused on patient selection, adjuvant reirradiation, definitive reirradiation, stereotactic body radiation, and reirradiation to treat nonsquamous cancer. Results of the consensus voting are presented along with discussion of the most current evidence. This provides updated evidence-based recommendations and guidelines for the retreatment of recurrent or second primary cancer of the head and neck.

Clinical and Histologic Features Associated With Malignant Transformation of Oral Cavity Dysplasia Managed at a Single North American Institution.

Importance: Reports characterizing clinical and histologic features associated with a higher risk for development of malignant lesions in the background of an oral potentially malignant disorder have largely reflected East Asian populations. Long-term studies among the North American population are rare. Objective: To evaluate risk of malignant transformation (MT) of oral dysplastic lesions by investigating the demographic, social, clinical, and histologic factors that may be associated with an increased rate as well as a decreased time to MT. Design, Setting, and Participants: This was a retrospective cohort study with medical record review at a single institution from January 1, 2000, to December 31, 2019, with follow-up for 20 years. Patients were excluded if they were younger than 18 years, the first biopsy diagnosis showed cancer, biopsies were never performed, biopsies were taken from sites outside of the oral cavity, there was no additional follow-up after the first visit, or the biopsy specimen was not characterized on the spectrum of dysplasia. Exposures: Diagnosis of leukoplakia of oral mucosa, unspecified lesions of oral mucosa, or other disturbances of oral epithelium. Main Outcomes and Measures: Main outcome measures included MT rate and time to MT as well as demographic, social, clinical, physical, and histologic features associated with MT. Results: Thirty-eight of 264 lesions (14%) in 241 patients (132 men and 109 women; mean [SD] age, 64 [13] years) underwent MT. Of the 38 lesions that underwent MT, 19 (50%) underwent transformation by 424 days, 28 (75%) by 870 days, and 34 (90%) by 1600 days. Nodularity, friability, and mass effect were more commonly observed in malignant lesions (nodularity: 42.9% vs 10.0%; difference, 32.9%; OR, 6.72; 95% CI, 3.03-14.89; friability: 42.9% vs 12.8%; difference, 30.1%; OR, 5.11; 95% CI, 1.66-15.69; mass effect: 54.2% vs 10.4%; difference, 43.8%; OR, 10.16; 95% CI, 4.12-25.09). Men were less likely than women to have multiple lesions in the oral cavity (OR, 0.40; 95% CI, 0.22-0.74). Having multiple abnormal sites was associated with higher percentage of MT (OR, 3.38; 95% CI, 1.63-7.01). Conclusions and Relevance: In this cohort study, nodularity and mass effect were associated with lesions that may push, displace, or invade surrounding tissue, and these were more likely to be present in oral dysplastic lesions that ultimately progressed to cancer. There may be less utility in continuing surveillance beyond 5 years.

Risk stratification after recurrence of human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancer: Secondary analysis of NRG Oncology RTOG 0129 and 0522.

BACKGROUND: No risk-stratification strategies exist for patients with recurrent oropharyngeal cancer (OPC). METHODS: Retrospective analysis using data from prospective NRG Oncology clinical trials RTOG 0129 and 0522. Eligibility criteria included known p16 status and smoking history, and locoregional/distant recurrence. Overall survival (OS) was measured from date of recurrence. Recursive partitioning analysis was performed to produce mutually exclusive risk groups. RESULTS: Hundred and fifty-four patients were included with median follow-up after recurrence of 3.9 years (range 0.04-9.0). The most important factors influencing survival were p16 status and type of recurrence, followed by surgical salvage and smoking history (≤20 vs. >20 pack-years). Three significantly different risk groups were identified. Patients in the low-, intermediate-, and high-risk groups had 2-year OS after recurrence of 81.1% (95%CI 68.5-93.7), 50.2% (95%CI 36.0-64.5), and 20.8% (95%CI 10.5-31.1), respectively. CONCLUSION: Patient and tumor characteristics may be used to stratify patients into risk groups at the time of OPC recurrence.

Prognostic significance of human papillomavirus status and treatment modality in hypopharyngeal cancer.

BACKGROUND: Management of hypopharynx cancer is often extrapolated from larynx cancer. This report analyses treatment patterns and survival limited to hypopharynx cancer using the National Cancer Database (NCDB). METHODS: There are 9314 patients diagnosed with hypopharynx cancer between 2004 and 2016. The association between treatment modality and survival was analyzed using Kaplan-Meier survival curves and multivariable Cox regression. RESULTS: Five-year overall survival ranged from 45% for stage I to 21% for stage IVB. Treatment modality did not influence survival in stage I/II. For stage III/IV, chemoradiation and surgery + adjuvant therapy were equivalent. Surgery yielded improved survival for T4 disease. Human papillomavirus (HPV)-positive tumors were present in 21% and were associated with improved hazard ratio of death (0.60, p = <0.0001). CONCLUSIONS: Survival is superior for T4 hypopharynx cancer managed with surgery, while treatment modality does not impact outcomes for other T-stages. HPV-positive tumors are associated with improved survival regardless of treatment.

A Pilot Study of a Collaborative Palliative and Oncology Care Intervention for Patients with Head and Neck Cancer.

Background: Palliative care improves symptoms and coping in patients with advanced cancers, but has not been evaluated for patients with curable solid malignancies. Because of the tremendous symptom burden and high rates of psychological distress in head and neck cancer (HNC), we evaluated feasibility and acceptability of a palliative care intervention in patients with HNC receiving curative-intent chemoradiation therapy (CRT). Methods: This was a prospective single-arm study in HNC patients receiving CRT at a single center in the United States. The intervention entailed weekly palliative care visits integrated with oncology care with a focus on symptoms and coping. The primary outcome was feasibility, defined as a >50% enrollment rate with >70% of patients attending at least half of the visits. To assess acceptability, we collected satisfaction ratings post-intervention. We also explored symptom burden, mood, and quality of life (QOL). Results: We enrolled 91% (20/22) of eligible patients. Patients attended 133 of 138 palliative care visits (96%); all 20 attended >85% of visits. Eighteen of 19 (95%) found the intervention "very helpful" and would "definitely recommend" it. QOL and symptom burden worsened from baseline to week 5, but subsequently improved at one-month post-CRT. Overall, patients valued the one-on-one format of the intervention and receipt of additional care. Conclusions: Our palliative care intervention during highly morbid CRT was feasible and acceptable with high enrollment, excellent intervention compliance, and high patient satisfaction. Future randomized studies will further explore the impact on patient-reported outcomes and health care utilization.

The impact of age on outcome in phase III NRG Oncology/RTOG trials of radiotherapy (XRT) +/- systemic therapy in locally advanced head and neck cancer.

PURPOSE: To examine the role age plays in the treatment and prognosis of locally advanced head and neck cancer (LAHNC) treated definitively with radiation alone or combined modality therapy. METHODS: A retrospective analysis was performed of three NRG/RTOG trials examining either radiation alone or combined radiation and systemic therapy for LAHNC. The effect of age (≥70 yrs.) on cause-specific survival (CSS), overall survival (OS), and toxicity was evaluated. RESULTS: A total of 2688 patients were analyzed, of whom 309 patients (11.5%) were ≥ 70. For all studies combined, the hazard ratio (HR) for CSS for patients age ≥ 70 vs. those <70 was 1.33 (95%CI: 1.14-1.55, p < 0.001). For OS, the HR for patients age ≥ 70 vs. those <70 for all studies combined was 1.55 (95% CI 1.35-1.77, p < 0.001). After adjustment for all covariates, age ≥ 70 was associated with worse OS regardless of adjustment for smoking and p16 status. The survival difference was more pronounced in those receiving combined radiation and systemic therapy. Hematologic and renal toxicities were increased in combined modality trials in patients ≥70 years old. CONCLUSIONS: Patients age ≥ 70 with LAHNC were underrepresented in these clinical trials. Their CSS and OS proved inferior to patients <70 years old.

Determinants of delay and association with outcome in head and neck cancer: A systematic review.

INTRODUCTION: Head and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures. METHODS: A search strategy was conducted according to PRISMA guidelines to search electronic databases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible. RESULTS: Fifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined. CONCLUSION: Race, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined.

The hidden curve behind COVID-19 outbreak: the impact of delay in treatment initiation in cancer patients and how to mitigate the additional risk of dying-the head and neck cancer model.

PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.

Identification and management of late dysfunction in survivors of head and neck cancer: Implementation and outcomes of an interdisciplinary quality of life (IQOL) clinic.

BACKGROUND: Identifying and treating late dysfunction in survivors of head and neck cancer (HNC) is important; however, an effective way to do so is not established. METHODS: A quality improvement initiative altering our HNC survivorship clinic to include surveillance by rehabilitation providers was undertaken. The nature of dysfunction identified, along with the number and type of referrals to ancillary/support services were collected and compared to baseline. RESULTS: The baseline, single-provider, clinic evaluated 61 patients and referred 2 (3%) to ancillary/support services. Fifty-seven patients were evaluated in the interdisciplinary clinic, with 36 (63%) referred to at least one ancillary/support service for new/progressive dysfunction. Of 59 referrals made, 22 (37%) were for dysphagia, 17(29%) were for neck/shoulder dysfunction, and 28 (47%) were attended by the patient. CONCLUSION: Many HNC survivors exhibit late dysfunction appropriate for referral to ancillary/support services. A survivorship clinic including surveillance by rehabilitation specialists may optimize identification of dysfunction.

Ipsilateral radiation for squamous cell carcinoma of the tonsil: American Radium Society appropriate use criteria executive summary.

BACKGROUND: We conducted the current systemic review to provide up-to-date literature summary and optimal evidence-based recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil. METHODS: We performed literature search of peer-reviewed journals through PubMed. The search strategy and subject-specific keywords were developed based on the expert panel's consensus. Articles published from January 2000 to May 2020 with full text available on PubMed and restricted to the English language and human subjects were included. Several prespecified search terms were used to identify relevant publications and additional evidence published since the initial American College of Radiology Appropriateness Criteria Ipsilateral Tonsil Radiation recommendation was finalized in 2012. The full bibliographies of identified articles were reviewed and irrelevant studies were removed. RESULTS: The initial search and review returned 46 citations. The authors added three citations from bibliographies, websites, or books not found in the literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, or focused on unknown primary disease. Several commonly encountered clinical case variants were created and panelists anonymously rated each treatment recommendation. The results were reviewed and disagreements discussed. CONCLUSIONS: The panel provided updated evidence and recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil in the setting of primary radiation-based therapy and postoperative adjuvant radiotherapy. This committee did not reach agreements for some case variants due to a lack of strong evidence supporting specific treatment decisions, indicating a further need for research in these topics.

Rapid recurrence in head and neck cancer: Underappreciated problem with poor outcome.

BACKGROUND: Rapid recurrence, defined as gross tumor recurrence after primary operation but prior to initiating postoperative radiation therapy (PORT), is underappreciated in head and neck cancer (HNC). METHODS: CT simulation images in patients with HNC managed surgically with adjuvant therapy at a single center between 2010 and 2017 were retrospectively reviewed. RESULTS: A total of 194 patients with HNC were included. Rapid recurrence occurred in 39 patients (20%) with a median time from operation to CT simulation of 37 days. On multivariable analysis (MVA), extranodal extension (ENE) was the only predictor of rapid recurrence (P = .03). While rapid recurrence, ENE, and perineural invasion were all associated with poor overall survival (OS) on MVA, rapid recurrence was the strongest predictor (hazard ratio [HR] 5.47). CONCLUSION: Rapid recurrence occurs at an underappreciated rate and is associated with poor survival outcomes. Patients with ENE are at highest risk and may benefit from diagnostic imaging evaluations immediately prior to PORT.

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria.

BACKGROUND: The aims of this systematic review are to (a) evaluate the current literature on the impact of postoperative therapy for resected squamous cell carcinoma of the head and neck (SCCHN) on oncologic and non-oncologic outcomes and (b) identify the optimal evidence-based postoperative therapy recommendations for commonly encountered clinical scenarios. METHODS: An analysis of the medical literature from peer-reviewed journals was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Prospective studies and methodology-based systematic reviews and meta-analyses of postoperative therapy for SCCHN were identified by searching Medline (OVID) and EMBASE (Elsevier) using controlled vocabulary terms (ie, National Library of Medicine Medical Subject Headings [MeSH], EMTREE). Study screening and selection was performed with Covidence software and full-text review. The RAND/UCLA appropriateness method was used by the expert panel to rate the appropriate use of postoperative therapy, and the modified Delphi method was used to come to consensus. RESULTS: A total of 5660 studies were identified and screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 101 studies from 1977 to 2020 were identified, including 77 with oncologic endpoints and 24 with function and quality of life endpoints. All studies reported staging prior to the implementation of American Joint Committee on Cancer (AJCC-8). CONCLUSIONS: Prospective clinical studies and systematic reviews identified through the PRISMA systematic review provided good evidence for consensus statements regarding the appropriate use of postoperative therapy for resected SCCHN. Further research is needed in domains where consensus by the expert panel could not be achieved for the appropriateness of specific postoperative therapeutic interventions.

Survivin expression and impact on head and neck cancer outcomes.

INTRODUCTION: Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival. METHODS: We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes. RESULTS: Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p = 0.013), cytoplasmic (p = 0.018) and total compartments (p = 0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p = 0.0264) and total compartments (p = 0.0264), but not in the nucleus (p = 0.0729). CONCLUSIONS: Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.

Patterns of Multidisciplinary Care of Head and Neck Squamous Cell Carcinoma in Medicare Patients.

Importance: Multidisciplinary care (MDC) yields proven benefits for patients with cancer, although it may be underused in the complex management of head and neck squamous cell carcinoma (HNSCC). Objective: To characterize the patterns of MDC in the treatment of HNSCC among elderly patients in the US. Design, Setting, and Participants: This nationwide, population-based, retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from January 1, 1991, to December 31, 2011, to identify patients 66 years or older diagnosed with head and neck cancer and determine the dates of diagnosis, oncology consultations, treatment initiation, and speech therapy evaluation in addition to MDC completion. Multidisciplinary care was defined in a stage-dependent manner: localized disease necessitated consultations with radiation and surgical oncologists, and advanced-stage disease also included a medical oncology consultation, all before definitive treatment. Data were analyzed between December 2016 and September 2020. Main Outcomes and Measures: Rates of MDC across all subsites of head and neck cancer as measured by the presence of an evaluation for each oncologist on the MDC team and its effect on treatment initiation. Results: This cohort study assessed 28 293 patients with HNSCC (mean [SD] age, 75.1 [6.6] years; 67% male; 87% White) from the SEER-Medicare linked database. The HNSCC subsites included larynx (40%), oral cavity (30%), oropharynx (21%), hypopharynx (7%), and nasopharynx (2%). Overall, the practice of MDC significantly increased over time, from 24% in 1991 to 52% in 2011 (P < .001). For patients with localized (stage 0-II) tumors, 60% received care in the multidisciplinary setting, whereas 28% of those with advanced-stage disease did. A total of 18 181 patients (64%) were treated with initial definitive nonsurgical therapy across all stages. Regardless of stage and subsite, few patients (2%) underwent evaluation by a speech-language pathologist before definitive therapy. Multidisciplinary care prolonged the time to initiation of definitive treatment by 11 days for localized disease and 10 days for advanced disease. Conclusions and Relevance: This cohort study found that most elderly patients with localized HNSCC received MDC, whereas few patients with advanced-stage disease received such care, although a significant proportion received adjuvant therapy. Multidisciplinary care may prolong time to initiation of definitive treatment with an uncertain impact. Consultation with a speech-language pathologist before definitive therapy was rare.