No abstract

Background Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for distant metastatic disease are limited. Methods A retrospective analysis of patients with recurrent OPSCC from two institutions between 2000-2012 was performed. P16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site and treatment modalities were compared by HPV tumor status. Overall survival was examined by Kaplan-Meier and Cox proportional hazards methods. Results The study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority were HPV-positive (n=80). HPV-positive tumor status was associated with longer time to recurrence (p<0.01). Anatomic site distribution of recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR] 0.23 (95%CI 0.09-0.58), p=0.002), longer time to recurrence (≥1 year; aHR 0.36 (0.18-0.74), p=0.006), and surgical salvage (aHR 0.26 (0.12-0.61), p=0.002) were independently associated with overall survival after recurrence. Surgical salvage was independently associated with improved overall survival compared to non-surgical treatment in both locoregional (aHR 0.15 (0.04-0.56), p=0.005) and distant metastatic recurrence (aHR 0.19 (0.05-0.75), p=0.018). Conclusions Surgical salvage is associated with improved overall survival for recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data is needed to confirm the role of surgical salvage for distant metastases.

Purpose To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in head and neck cancer patients through inhibition of myeloid derived suppressor cells (MDSCs). Experimental Design We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in head and neck squamous cell carcinoma (HNSCC) patients. Results Tadalafil augmented immune response, increasing ex vivo T cell expansion to a mean 2.4 fold increase compared to 1.1 fold in control patients (P= 0.01), reducing peripheral MDSC numbers to mean 0.81 fold change compared to a 1.26 fold change in control patients (P=0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P=0.002). Tumor specific immunity in response to HNSCC tumor lysate was augmented in tadalafil treated patients (P=0.04). Conclusions These findings demonstrate that tadalafil augments general and tumor-specific immunity in HNSCC patients and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor specific immune suppression in head and neck cancer patients, with potential for therapeutic application.

Evidence supporting prophylactic swallow exercises for patients with head and neck cancer (HNC) has not been universally demonstrated. This RCT examined diet level, feeding tube use, swallow function, and quality of life (QOL) of patients undergoing chemoradiotherapy who performed prophylactic swallowing exercises. Sixty HNC patients were randomized into exercise versus control groups. Swallowing, oromotor, toxicity, and QOL data were recorded (baseline, 3, 6, 12, 24 months). Physiological swallow function was examined at baseline and 3 months. Swallow exercises were completed twice daily. Oral intake at 3 months was 10% better in the exercise group, which was not statistically significant (p = 0.49). Significant (p < 0.05) differences in secondary outcomes including oromotor function, pharyngeal impairment, oral pharyngeal swallow efficiency, and incisal opening were noted at early time points (3–6 months) in the exercise group. Possible positive early improvements in swallow function are associated with swallowing exercises, although these improvements are not significant longer term.

Objective To develop a robotic surgery training regimen integrating objective skill assessment for otolaryngology and head and neck surgery trainees consisting of training modules of increasing complexity and leading up to procedure specific training. In particular, we investigate applications of such a training approach for surgical extirpation of oropharyngeal tumors via a transoral approach using the da Vinci Robotic system. Study Design Prospective blinded data collection and objective evaluation (OSATS) of three distinct phases using the da Vinci Robotic surgical system. Setting Academic University Medical Engineering/Computer Science laboratory Methods Between September 2010 and July 2011, 8 Otolaryngology Head and Neck Surgery residents and 4 staff “experts” from an academic hospital participated in three distinct phases of robotic surgery training involving 1) robotic platform operational skills, 2) set-up of the patient side system, and 3) a complete ex-vivo surgical extirpation of an oropharyngeal “tumor” located in the base of tongue. Trainees performed multiple (4) approximately equally spaced training sessions in each stage of the training. In addition to trainees, baseline performance data was obtained for the experts. Each surgical stage was documented with motion and event data captured from the application programming interfaces (API) of the da Vinci system, as well as separate video cameras as appropriate. All data was assessed using automated skill measures of task efficiency, and correlated with structured assessment (OSATS, and similar Likert scale) from three experts to assess expert and trainee differences, and compute automated and expert assessed learning curves. Results Our data shows that such training results in an improved didactic robotic knowledge base and improved clinical efficiency with respect to the set-up and console manipulation. Experts (e.g. average OSATS 25, Stdev. 3.1, module 1 – suturing) and trainees (average OSATS 15.9, Stdev. 3.9, week 1) are well separated at the beginning of the training, and the separation reduces significantly (expert average OSATS 27.6, Std. 2.7, trainee average OSATS 24.2, Std. 6.8, module 3) at the conclusion of the training. Learning curves in each of the three stages show diminishing differences between the experts and trainees, also consistent with expert assessment. Subjective assessment by experts verified the clinical utility of the module 3 surgical environment and a survey of trainees consistently rated the curriculum as very useful in progression to human operating room assistance. Conclusions Structured curricular robotic surgery training with objective assessment promises to reduce the overhead for mentors, allow detailed assessment of human-machine interface skills and create customized training models for individualized training. This preliminary study verifies the utility of such training in improving human-machine operations skills (module 1), and operating room and surgical skills (module 2 and 3). In contrast to cur...