Kevin Scher

Treatment at high‐volume facilities and academic centers is independently associated with improved survival in patients with locally advanced head and neck cancer

The treatment of head and neck cancers is complex and associated with significant morbidity, requiring multidisciplinary care and physician expertise. Thus, facility characteristics, such as clinical volume and academic status, may influence outcomes.

Association of Quantitative Metastatic Lymph Node Burden With Survival in Hypopharyngeal and Laryngeal Cancer

Importance Nodal staging for laryngohypopharyngeal cancers is based primarily on size and laterality, with less value placed on absolute number of metastatic lymph nodes (LNs). We are aware of no studies to date that have specifically addressed the prognostic effect of quantitative nodal burden in larynx or hypopharynx malignancies. Objective To assess the independent impact of quantitative metastatic LN burden on mortality risk. Design, Setting, and Participants Univariate and multivariable models were constructed to evaluate the association between patients’ number of metastatic LNs and their survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Participants were patients with squamous cell carcinoma of the larynx or hypopharynx undergoing upfront surgical resection for curative intent at a US hospital between 2004 and 2013, as identified in the National Cancer Database. A neck dissection of a minimum of 10 LNs was required. Main Outcomes and Measures Overall survival. Results Overall, 8351 cases were included (mean [SD] age, 61 [10.1] years; 6499 men [77.8%]; 4710 patients with metastatic LNs and 3641 with no metastatic LNs). Mortality risk escalated continuously without plateau as number of metastatic nodes increased, with the hazard per node (hazard ratio [HR], 1.19; 95% CI, 1.16-1.23; Pu2009<u2009.001) most pronounced up to 5 positive LNs. Extranodal extension was also associated with increased mortality (HR, 1.34; 95% CI, 1.13-1.59; Pu2009<u2009.001). Increasing number of nodes examined was associated with improved survival, albeit to a lesser degree (per 10 LNs: HR, 0.97; 95% CI, 0.96-0.98; Pu2009<u2009.001) and without a detectable change point. Other nodal factors, including nodal size, contralateral LN involvement (TNM stage N2c), and lower LN involvement (levels 4-5), were not associated with mortality in multivariable models when accounting for number of positive LNs. A novel, parsimonious nodal staging system derived by recursive partitioning analysis exhibited greater concordance with survival than the TNM staging system outlined in the American Joint Committee on Cancer’s AJCC Staging Manual, 8th edition. Conclusions and Relevance The number of metastatic nodes is a predominant independent factor associated with mortality in hypopharyngeal and laryngeal cancers. Moreover, standard nodal staging factors like LN size and contralaterality have no independent prognostic value when accounting for positive LN number. Deeper integration of quantitative metastatic nodal disease may simplify staging and better triage the need for adjuvant therapy.

Facility Volume and Survival in Nasopharyngeal Carcinoma

INTRODUCTIONnDefinitive treatment of nasopharyngeal carcinoma (NPC) is challenging owing to its rarity, complicated regional anatomy, and the intensity of therapy. In contrast to other head and neck cancers, the effect of facility volume has not been well described for NPC.nnnMETHODS AND MATERIALSnThe National Cancer Database was queried for patients with stage II-IVB NPC diagnosed from 2004 to 2014 and treated with definitive radiation. Patients with incomplete staging, unknown receipt or timing of treatment, unknown follow-up duration, incomplete socioeconomic information, or treatment outside the reporting facility were excluded. High-volume facilities (HVFs) were defined as the top 5% of facilities according to the annual facility volume.nnnRESULTSnThe present analysis included 3941 NPC patients treated at 804 facilities with a median follow-up duration of 59.4 months, including 1025 patients (26.0%) treated at HVFs. Treatment at HVFs was associated with significantly improved overall survival (OS) on multivariable analysis (hazard ratio 0.79, 95% confidence interval 0.69-0.90; P=.001). In propensity score-matched cohorts, 5-year OS was 69.1% versus 63.3% at HVFs versus lower volume facilities (LVFs), respectively (P=.003). Similar results were seen when facility volume was analyzed as a continuous variable. The effect of facility volume on survival varied by academic status (P=.002 for interaction). At academic centers, the propensity score-matched cohorts had 5-year OS of 71.4% compared with 62.4% (P<.001) at HVFs and LVFs, respectively. In contrast, the 5-year OS was 63.5% versus 67.9% (P=.68) in propensity score-matched patients at nonacademic HVFs and LVFs.nnnCONCLUSIONSnTreatment at HVFs was associated with improved OS for patients with NPC, with the effect exclusively seen at academic centers.

Predictors of survival in head and neck mucosal melanoma

OBJECTIVESnTo evaluate hospital-based data of head and neck mucosal melanoma patients in order to identify predictors of survival.nnnMATERIALS AND METHODSnThe National Cancer Data Base was used to identify 1368 patients with head and neck mucosal melanoma diagnosed between the years of 2004 and 2012. The Kaplan-Meier method was utilized to estimate overall survival, and multivariate Cox regression analyses were performed to assess the impact of covariates on survival after adjusting for confounding variables.nnnRESULTSnMedian follow-up was 55.2months. Median survival of all patients was 29.3months, and the 5-year survival was 27.4%. After adjusting for other prognostic factors in multivariate analysis, paranasal sinus location [hazard ratio (HR)=1.54, 95% Confidence Interval (CI)=1.30-1.82, P<0.001)] and the use of radiotherapy alone for definitive local treatment (HR=2.27, 95% CI=1.72-2.98, P<0.001) were associated with worse survival. Similar results were seen in the subgroup of patients with complete clinical staging information. In terms of patterns of care, the use of combined surgery and radiotherapy as the primary local treatment modality has significant increased from 2004 and 2012 (P=0.03).nnnCONCLUSIONnOutcomes in mucosal melanoma of the head and neck remain suboptimal, despite increased use of multimodality local therapy, likely due to the high risk of distant metastases. Mucosal melanomas arising from the paranasal sinuses have particularly poor prognosis. Novel therapeutic paradigms for head and neck mucosal melanoma, incorporating systemic therapies to decrease the risk of distant relapse, should be pursued in clinical trials.

Impact of concomitant chemoradiation on survival for patients with T1-2N1 head and neck cancer

Single‐modality radiotherapy is considered a standard‐of‐care option for certain stage III, T1‐2N1 head and neck squamous cell carcinomas (HNSCCs). The role of concomitant chemoradiation is not well established because there have been no studies comparing chemoradiation with radiation alone in this population.

Perspectives in Head and Neck Medical Oncology

The modern treatment of locoregionally advanced disease often requires a multimodality combination approach. A number of chemotherapeutic agents can be combined with radiation, but the platinum agent cisplatin, a potent radiation sensitizer, is best studied in head and neck cancer. Newer agents such as cetuximab can be used in combination with radiation therapy for those patients who cannot tolerate cisplatin. For chemotherapy-naïve patients with metastatic head and neck cancer who demonstrate a good performance status, platinum doublet regimens are commonly used. Doublet regimens generally improve response rates compared to single-agent chemotherapies, although they have not demonstrated a survival benefit over single agents and they have added toxicity. Immunotherapies, alternative cytotoxic chemotherapies, and targeted therapies are second-line options for patients with disease that has progressed on platinum-based therapy. Immunotherapy, in particular, has gained focus by enhancing the ability of the immune system to recognize and destroy malignant cells. When multimodal approaches are used, as in combined chemotherapy and radiation therapy, toxicities are increased. It is imperative that patients are followed closely in order to maximize treatment benefit while minimizing complications.

Postoperative chemoradiotherapy in patients with head and neck cancer aged 70 or older with positive margins or extranodal extension and the influence of nodal classification

Postoperative concomitant chemoradiotherapy (CRT) improves outcomes for younger adults with head and neck squamous cell carcinoma (HNSCC) and positive margins or extranodal extension (ENE), but its benefit for older adults is not well established.

Quantitative survival impact of composite treatment delays in head and neck cancer: Treatment Delay and HN Cancer Survival

Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis‐to‐treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC.

Combined high‐intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base

There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression.