K. Potts

HPV: A factor in organ preservation for locally advanced larynx and hypopharynx cancer?

PURPOSE/OBJECTIVE To assess the interaction of HPV/p16 status and therapy rendered in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx. MATERIALS AND METHODS Forty-seven consecutive patients receiving definitive treatment between 2009 and 2011 for locally advanced larynx or hypopharynx cancer with high-risk HPV and/or p16 testing performed were identified and retrospectively investigated. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) were assessed. RESULTS Of 47 evaluable patients, there were 38 (81%) with laryngeal and 9 (19%) with hypopharyngeal tumors, 13 (28%) of which were found to be either HPV or p16 positive. At a median follow-up of 24 months, comparing HPV/p16+ versus HPV/p16- patients, there was no difference in OS, DFS, or LRFS. There was an improvement in 2-year DFS (60% vs 100%, P=.03) and LRFS (80% vs 100%, P=.08), in HPV/p16+ patients treated with chemo/RT versus surgery. There was an improvement in 2-year DFS (100% vs 68%, P=.04) and LRFS (100% vs 72%, P=.05) in HPV/p16+ versus HPV/p16- patients who received chemo/RT. CONCLUSIONS Patients with HPV/p16+ tumors fared more favorably with chemo/RT than up-front surgery, with improvements in DFS and LRFS. In patients treated with the intent of organ preservation therapy, HPV/p16+ patients had no observed treatment failures. HPV/p16 status should be taken into account when considering organ preservation for locally advanced larynx and hypopharynx cancers.

Persistent tracheostomy after primary chemoradiation for advanced laryngeal or hypopharyngeal cancer

Despite the demonstrated survival equivalence between chemoradiation and ablative surgery as primary treatment for advanced laryngeal and hypopharyngeal cancers, a subset of patients who undergo organ‐preservation therapy have persistent tracheostomy requirement after completion of treatment.

Sentinel lymph node status is the most important prognostic factor in patients with melanoma of the scalp.

To compare clinicopathologic and prognostic factors associated with scalp melanomas and nonscalp melanomas of the head and neck (H&N).

Treatment outcome in the residually positive neck after definitive chemotherapy and irradiation

Determine prevalence of viable malignancy in patients undergoing neck dissection (ND) for residual neck disease following concomitant chemotherapy and irradiation (chemo/xrt) for upper aerodigestive squamous carcinoma. To determine survival in groups with a neck complete response to those who had residual disease requiring neck dissection.

Impact of transcutaneous neuromuscular electrical stimulation on dysphagia in patients with head and neck cancer treated with definitive chemoradiation.

The purpose of this study was to investigate the role of transcutaneous neuromuscular electrical stimulation (TNMES) therapy in maintaining swallowing function during chemoradiation for locally advanced head and neck cancer.

Human papillomavirus E7 serology and association with p16 immunohistochemistry in squamous cell carcinoma of the head and neck

BACKGROUND Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with improved survival and treatment response as compared to HPV-negative cancers. P16 overexpression is widely accepted as a surrogate marker for HPV positivity. METHODS A total of 92 serum samples from 75 head and neck squamous cell carcinoma (HNSCC) patients were examined for HPV16 and 18 E7 antibodies by ELISA. Available tissue was tested for HPV-DNA by PCR, and p16 immunohistochemistry was obtained from a deidentified database. RESULTS Of 75 HNSCC patients, 25 were HPV E7 seropositive. Seropositivity was strongly associated with cancers of the oropharynx, and correlated with positive p16 immunohistochemistry (IHC) and HPV-DNA. Post-treatment serum was available in a limited subset of patients, revealing a decrease in antibody titers following response to treatment. CONCLUSIONS HPV E7 seropositivity correlated with positive tumor HPV-DNA and p16 expression, and was strongly associated with cancers of the oropharynx. E7 serology warrants further study as a potential biomarker in HPV-positive HNSCC.

Risk factors for hemorrhage after chemoradiation for oropharyngeal squamous cell carcinoma.

IMPORTANCE Knowledge of the risk factors for oropharyngeal hemorrhage after chemoradiation therapy will guide clinicians in monitoring high-risk patients in order to prevent a life-threatening complication. OBJECTIVE To determine risk factors for the development of oropharyngeal hemorrhage following chemoradiation therapy without surgery for oropharyngeal squamous cell carcinoma. DESIGN Retrospective review of medical records of patients treated during the period January 2005 through December 2010. SETTING University of Louisville Hospital. PARTICIPANTS The study population comprised 139 patients with a diagnosis of oropharyngeal squamous cell carcinoma who were treated with chemoradiation therapy without surgery. All patients received primary treatment from our institution. Those with recurrent tumors or prior oropharyngeal resections, with the exception of tonsillectomy, were excluded from the study. Patients were divided into 2 groups: those who did not hemorrhage following treatment (n = 129) and those who developed oropharyngeal hemorrhage (n = 10), defined as hemorrhage necessitating procedural intervention. MAIN OUTCOMES AND MEASURES Four clinical variables were measured: T category, radiation therapy method, weight loss, and age. RESULTS Results from logistic regression analysis showed that significant risk factors for hemorrhage were advanced T category (odds ratio [OR], 8.40 [95% CI, 2.44-46.61]; P < .001), radiation therapy method (OR, 79.94 [95% CI, 2.64-<999.90]; P = .008), weight loss (OR, 0.89 [95% CI, 0.79-0.98]; P = .01), and increased age (OR, 0.93 [95% CI, 0.86-0.99]; P = .03). After multiple logistic regression analyses, only advanced T category remained statistically significant (adjusted OR, 6.6 [95% CI, 1.2-∞]; P = .02). Results from Kaplan-Meier survival analysis on all patients showed that those who hemorrhaged had significantly shorter survival time than those who did not (P = .04). However, after multivariate analysis with a Cox proportional hazards regression model, hemorrhage no longer remained a significant factor (P = .13). CONCLUSIONS For patients with oropharyngeal squamous cell carcinoma treated with chemoradiation without surgery, advanced T category is the most important determinant of developing oropharyngeal hemorrhage; furthermore, hemorrhage occurs in the presence of either recurrent and/or persistent disease or radiation necrosis. Survival analysis indicates that development of hemorrhage is a poor prognostic marker for overall survival.

Cyclical hypofractionated radiotherapy technique for palliative treatment of locally advanced head and neck cancer: institutional experience and review of palliative regimens.

BACKGROUND Effective palliation in patients with locally advanced head and neck cancer is important. Cyclical hypofractionated radiotherapy (Quad Shot) is a short-course palliative regimen with good patient compliance, low rates of acute toxicity, and delayed late fibrosis. OBJECTIVE To review use of the Quad Shot technique at our institution in order to quantify the palliative response in locally advanced head and neck cancer. METHODS The medical records of 70 patients with head and neck squamous cell carcinoma who had been treated with the Quad Shot technique were analyzed retrospectively (36 had been treated with intensity-modulated radiation therapy and 34 with 3-D conformal radiotherapy). They had received cyclical hypofractionated radiotherapy administrated as 14.8 Gy in 4 fractions over 2 days, twice daily, repeated every 3 weeks for a total of 3 cycles. The total prescribed dose was 44.4 Gy. Primary endpoints were improvement in pain using a verbal numeric pain rating scale (range 1-10, 10 being severe pain) and dysphagia using the Food Intake Level Scale, and the secondary endpoints included overall survival (OS), local regional recurrence-free survival (LRRFS), progression-free survival (PFS) and time to progression. RESULTS Pain response occurred in 61% of the patients. The mean pain scores decreased significantly from pre to post treatment (5.81 to 2.55, 𝑃 = .009). The mean initial dysphagia score improved from 2.20 to 4.77 55 (𝑃 = .045). 26% of patients developed mucositis (≤ grade 2), with 9% developing grade 3-level mucositis. 12 patients had tumor recurrence. The estimated 1-year PFS was 20.7%. The median survival was 3.85 months with an estimated 1-year OS of 22.6%. Pain response (hazard ratio [HR], 2.69; 95% confidence index [CI], I.552-1.77) and completion of all 3 cycles (HR, 1.71; 95% CI, 1.003-2.907) were predictive for improved OS. LIMITATIONS This study is a retrospective analysis. CONCLUSION Quad Shot is an appropriate palliative regimen for locally advanced head and neck cancer.

Prognostic significance of HPV status in postoperative squamous-cell carcinoma of the head and neck.

BACKGROUND There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting. OBJECTIVE To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting. METHODS We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators. RESULTS Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; 𝑃 = .010 and 𝑃 = .018, respectively). LIMITATIONS Retrospective, single-institution study; small patient cohort; short follow-up time. CONCLUSION The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.

Effect of time to simulation and treatment for patients with oropharyngeal cancer receiving definitive radiotherapy in the era of risk stratification using smoking and human papillomavirus status

The effect of increasing time to definitive radiotherapy (RT) for patients with oropharyngeal squamous cell carcinoma (SCC) is unknown.