Trimodality therapy for HPV-positive oropharyngeal cancer: A population-based study: Trimodality therapy for HPV+ OPC Publication date: November 2019 Source: Oral Oncology, Volume 98 Author(s): Nina N. Sanford, William L. Hwang, Luke R.G. Pike, Allen C. Lam, Trevor J. Royce, Brandon A. Mahal Abstract Background Although HPV status is a well-established prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), approximately 20% of HPV-positive patients die from their disease. We therefore sought to ascertain whether there is a benefit to trimodality therapy with surgery among patients with locally advanced (LA) disease receiving chemoradiation. Methods The SEER Head and Neck with HPV Status Database identified adult patients with non-metastatic OPSCC between 2013 and 2014 with known HPV status who received chemoradiation as part of definitive treatment. The primary outcome was cancer-specific mortality (CSM) for locally-advanced (LA) (T3-T4, or N2-N3, per AJCC 7) versus early-stage (ES) (T1-T2 and N0-N1) disease, stratified by HPV status. The secondary outcome was overall survival (OS). Results Among 2974 patients who met study criteria, 671 patients (22.6%) received upfront surgery (trimodality therapy). In the LA setting, there was a significant reduction in CSM with trimodality therapy compared to chemoradiation alone in HPV-positive (Adjusted Hazard Ratio [AHR] 0.19, 95% Confidence Interval [CI] 0.04–0.80; P = 0.024), but not HPV-negative disease [Pinteraction = 0.04]. There was no benefit to trimodality therapy for ES disease, regardless of HPV status. There was also an improvement in OS with trimodality therapy for HPV-positive LA patients (AHR = 0.28, p = 0.006, 95% CI = 0.11–0.70). In contrast, trimodality therapy was not associated with improved OS for HPV-negative patients regardless of stage. Conclusions HPV status may predict for improved outcomes with surgery/trimodality therapy in LA OPSCC. Our findings support prospective investigations to optimize care for the subset of HPV-positive patients who are at greatest risk of cancer death, where trimodality therapy may be appropriate.

Malignant peripheral nerve sheath tumors: Analysis of the national cancer database Publication date: November 2019 Source: Oral Oncology, Volume 98 Author(s): Alia Mowery, Daniel Clayburgh Abstract Objectives Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcoma (STS) that carries significant mortality. Given the rarity of MPNST, current knowledge on the disease is limited. We aim to characterize patient, tumor, and treatment factors, and determine variables associated with 5-year overall survival (OS) in individuals with MPNST. Materials and Methods We utilized the National Cancer Database (NCDB) to identify adult patients diagnosed with MPNST from 2004 to 2015, and analyze patient, tumor, treatment, and survival data. American Joint Committee on Cancer (AJCC 8) staging criteria for STS was utilized. Results In our cohort of 2,858 patients with MPNST, median age at diagnosis was 47. The 5-year OS rate was 52%. Age, race, tumor size, and treatment regimen significantly predicted 5-year OS on univariate analysis. AJCC 8 stage appeared to predict 5-year OS in head and neck tumors (though not significantly), but not trunk and extremity tumors. Conclusion While our cohort of patients with MPNST are typically relatively young and healthy, 5-year OS is only 52%. Notably, age extremes, large tumor size, and certain treatment regimens are associated with worse outcomes. While AJCC 8 staging guidelines may have some value in predicting OS in head and neck tumors, they do not reliably risk stratify patients with trunk and extremity MPNST. Ultimately, MPNST is associated with high mortality with few modifiable risk factors, and survival may not be adequately predicted by current staging systems.

Prognostic factors associated with achieving total oral diet following osteocutaneous microvascular free tissue transfer reconstruction of the oral cavity Publication date: November 2019 Source: Oral Oncology, Volume 98 Author(s): Sagar Kansara, Tao Wang, Sina Koochakzadeh, Nelson E. Liou, Evan M. Graboyes, Judith M. Skoner, Joshua D. Hornig, Vlad C. Sandulache, Terry A. Day, Andrew T. Huang Abstract Introduction Osteocutaneous microvascular free tissue transfer (OMFTT) is the current standard in reconstruction of large bony defects of the oral cavity. Although being able to swallow ranks as a top priority for patients undergoing OMFTT, factors associated with achieving an oral diet following surgery remain unclear. We sought to describe the rate of total oral diet achievement, and to identify possible pre-, intra-, and post-operative factors associated with achievement in patients undergoing OMFTT. Methods Retrospective review between January 1, 2010 and March 31, 2018 at two tertiary academic centers. Results 249 patients (67% male, mean age 58 years) met inclusion criteria, with a median follow up of 15 months. Overall, 142 (57%) of patients achieved a total PO diet post-operatively, with median time to achievement of 3.2 months. Multivariate analysis identified that lack of concurrent glossectomy (SHR 1.72 [1.09–2.70], p = 0.02), N0/1 disease (SHR 1.92 [1.16–3.13], p = 0.011), avoidance of post-operative fistula formation (SHR 1.96 [1.22–3.23], p = 0.005), pre-operative G-tube independence (SHR 3.33 [1.69–6.25], p < 0.001), and successful dental rehabilitation (SHR 2.08 [1.43–3.03], p < 0.001) are independently associated with total oral diet achievement. Conclusions Bony resections not requiring glossectomy, limited nodal disease burden, pre-operative gastrostomy-independence, avoidance of post-operative fistula, and dental rehabilitation are independently associated with achievement of total oral diet following OMFTT reconstruction of the oral cavity. Counseling patients on associated risk factors is important in guiding post-treatment expectations. Minimization of post-operative fistula, and maximization of dental rehabilitation may significantly improve total oral diet achievement in this patient population.

Organs at risk's tolerance and dose limits for head and neck cancer re-irradiation: A literature review Publication date: November 2019 Source: Oral Oncology, Volume 98 Author(s): F. Dionisi, F. Fiorica, E. D'Angelo, M. Maddalo, I. Giacomelli, E. Tornari, A. Rosca, F. Vigo, D. Romanello, M. Cianchetti, F. Tommasino, M. Massaccesi, E. Orlandi Abstract Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28  months (range, 6–90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3–4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.

The potential use of big data in oncology Publication date: November 2019 Source: Oral Oncology, Volume 98 Author(s): Stefan M. Willems, Sanne Abeln, K. Anton Feenstra, Remco de Bree, Egge F. van der Poel, Robert J. Baatenburg de Jong, Jaap Heringa, Michiel W.M. van den Brekel Abstract In this era of information technology, big data analysis is entering biomedical sciences. But what is big data, where do they come from and what can we do with it? In this commentary, the main sources of big data are explained, especially in (head and neck) oncology. It also touches upon the need to integrate various sources of clinical, pathological and quality-of-life data. It discusses some initiatives in linking of such datasets on a nation-wide scale in the Netherlands. Finally, it touches upon important issues regarding governance, FAIRness of data and the need to bring into place the necessary infrastructures needed to fully exploit the full potential of big data sets in head and neck cancer.

Human papillomavirus-associated squamous cell carcinoma of the larynx or hypopharynx: Clinical outcomes and implications for laryngeal preservation Publication date: November 2019 Source: Oral Oncology, Volume 98 Author(s): Ryan T. Hughes, William J. Beuerlein, Stacey S. O'Neill, Mercedes Porosnicu, Thomas W. Lycan, Joshua D. Waltonen, Bart A. Frizzell, Kathryn M. Greven Abstract Objectives Human papillomavirus (HPV) can be detected in approximately 25% of squamous cell carcinomas (SCC) of the larynx and hypopharynx. Though HPV is associated with improved survival and disease control in patients with oropharyngeal SCC, the role of HPV as a marker of favorable treatment outcomes in laryngeal and hypopharyngeal cancer is unclear. Materials and Methods Patients treated for laryngeal or hypopharyngeal SCC were reviewed. HPV status detected by p16 and/or HPV DNA PCR were abstracted from the medical record. A subset of samples (stage III-IV treated with primary radiotherapy) was retrospectively tested for p16 and HPV DNA. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were determined and compared between HPV-positive (p16+, PCR+ or both) and HPV-negative (p16- or PCR-) patients. Results In total, 279 patients were identified, 94 of which were tested for HPV. Eighty-two (87%) were negative and 12 (13%) were positive for HPV. At 3 years, there were no significant differences in OS (72% v. 83%), DFS (60% v. 71%) and LRC (80% v. 89%). Performance status, smoking history and stage predicted for OS, while performance status and stage predicted for DFS. Analysis of patients treated with primary radiotherapy revealed non-significantly higher rates of laryngeal preservation at 3 years (75% v. 100%). Conclusion HPV was detected in 13% of tested laryngeal/hypopharyngeal cancers. HPV does not appear to significantly impact survival or disease control in patients with SCC of the larynx or hypopharynx. Non-significant improvements in laryngeal preservation were observed in HPV-positive patients.

Successful tri-modality treatment of atypical carcinoma ex-pleomorphic adenoma with more than 50 nodal metastases Publication date: October 2019 Source: Oral Oncology, Volume 97 Author(s): Federico L. Ampil, Nestor de la Cruz Abstract Carcinoma ex-pleomorphic adenoma (CEPA), an extremely aggressive malignant tumor, bears a significant potential for locoregional recurrence and distant metastases. Management of the disease usually involves definitive surgery with postoperative radiotherapy administered for identified nodal metastases. Two cases of CEPA with many (>50) cervical lymph node metastases and other histopathological features were managed by tri-modality treatment scheme. No evidence of disease occurred during follow-up of at least 2 years. These cases may eventually establish the value of surgery with adjuvant radiochemotherapy in patients with CEPA and supernumerary nodal metastases.

Clinical validation of the Salivary HPV DNA assessment and its link to the locoregional disease burden in advanced HPV associated oropharyngeal cancer Publication date: October 2019 Source: Oral Oncology, Volume 97 Author(s): Rama Jayaraj, Chellan Kumarasamy, Madurantakam Royam Madhav, Sameep Shetty

Successful control of T4 and N3 human papillomavirus-related oropharyngeal squamous cell carcinoma after de-intensified chemoradiotherapy: Report of two cases Publication date: October 2019 Source: Oral Oncology, Volume 97 Author(s): Hidenori Tanaka, Yoichiro Tomiyama, Takahiro Michiba, Takahito Fukusumi, Norihiko Takemoto, Motoyuki Suzuki, Hidenori Inohara

Immune-checkpoint inhibitors in head and neck squamous cell carcinoma: cost-efficacy in second-line treatment based on programmed death-ligand 1 (PD-L1) level Publication date: October 2019 Source: Oral Oncology, Volume 97 Author(s): Jacopo Giuliani, Andrea Bonetti