Development and validation of a clinical prediction-score model for distant metastases in major salivary gland carcinoma.

BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.

Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

Prediction of Wound Failure in Patients with Head and Neck Cancer Treated with Free Flap Reconstruction: Utility of CT Perfusion and MR Perfusion in the Early Postoperative Period.

BACKGROUND AND PURPOSE: Free flap reconstruction in patients with head and neck cancer carries a risk of postoperative complications, and radiologic predictive factors have been limited. The aim of this study was to assess the factors that predict free flap reconstruction failure using CT and MR perfusion. MATERIALS AND METHODS: This single-center prospective study included 24 patients (mean age, 62.7 [SD, 9.0] years; 16 men) who had free flap reconstruction from January 2016 to May 2018. CT perfusion and dynamic contrast-enhanced MR imaging with conventional CT and MR imaging were performed between 2 and 4 days after the free flap surgery, and the wound assessments within 14 days after the surgery were conducted by the surgical team. The parameters of CT perfusion and dynamic contrast-enhanced MR imaging with conventional imaging findings and patient demographics were compared between the patients with successful free flap reconstruction and those with wound failure as appropriate. P < .05 was considered significant. RESULTS: There were 19 patients with successful free flap reconstruction and no wound complications (mean age, 63.9 [SD, 9.5] years; 14 men), while 5 patients had wound failure (mean age, 58.0 [SD, 5.7] years; 2 men). Blood flow, blood volume, MTT, and time maximum intensity projection (P = .007, .007, .015, and .004, respectively) in CT perfusion, and fractional plasma volume, volume transfer constant, peak enhancement, and time to maximum enhancement (P = .006, .039, .004, and .04, respectively) in dynamic contrast-enhanced MR imaging were significantly different between the 2 groups. CONCLUSIONS: CT perfusion and dynamic contrast-enhanced MR imaging are both promising imaging techniques to predict wound complications after head and neck free flap reconstruction.

Novel Immunotherapeutic Approaches in Head and Neck Cancer.

Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in immune evasion and may serve as targets for future therapies. Pembrolizumab is now approved as a first line therapy. Despite the promise of currently approved immunotherapies there continues to be low response rates and additional strategies are needed. Here, alterations in the immune microenvironment and current therapeutic strategies are reviewed with a focus on novel immunologic approaches.

Genomic sequencing and precision medicine in head and neck cancers.

Head and neck squamous cell carcinoma (HNSCC) remains a common and deadly disease. Historically, surgical and chemoradiation treatments have been met with modest success, and understanding of genetic drivers of HNSCC has been limited. With recent next generation sequencing studies focused on HNSCC, we are beginning to understand the genetic landscape of HNSCCs and are starting to identify and advance targeted options for patients. In this review, we describe current knowledge and recent advances in sequencing studies of HNSCC, discuss current limitations and future directions for further genomic analysis, and highlight the translational advances being undertaken to treat this important disease.

Surveilling the Potential for Precision Medicine-driven PD-1/PD-L1-targeted Therapy in HNSCC.

Immunotherapy is becoming an accepted treatment modality for many patients with cancer and is now approved for use in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Despite these successes, a minority of patients with HNSCC receiving immunotherapy respond to treatment, and few undergo a complete response. Thus, there is a critical need to identify mechanisms regulating immune checkpoints in HNSCC such that one can predict who will benefit, and so novel combination strategies can be developed for non-responders. Here, we review the immunotherapy and molecular genetics literature to describe what is known about immune checkpoints in common genetic subsets of HNSCC. We highlight several highly recurrent genetic lesions that may serve as biomarkers or targets for combination immunotherapy in HNSCC.

Correlation of radiographic and pathologic findings of dermal lymphatic invasion in head and neck squamous cell carcinoma.

HNSCC that involves the skin is able to invade the dermal lymphatic system. Currently there is no way to identify patients with dermal lymphatic invasion preoperatively. The purpose of this study is to determine whether CT can predict dermal lymphatic invasion. Medical records, CT scans, and corresponding histopathologic slides were reviewed of HNSCC patients with skin resected as part of their treatment. Dermal lymphatic invasion was defined radiographically as linear reticulations of the dermis and subcutaneous fat adjacent to the tumor. Twelve patients were identified with imaging suggestive of dermal lymphatic invasion. The corresponding pathology slides showed only 1 of the 12 patients had dermal lymphatic invasion, whereas the other 11 specimens showed peritumoral inflammation without evidence of tumor invasion. This study demonstrates that the linear areas of reticulation are most commonly caused by peritumoral inflammation and are not due to dermal lymphatic invasion.