Transoral Robotic Surgery as a Potential Immunotherapy Platform for the Treatment of HPV-related Oropharyngeal Squamous Cell Carcinoma

Ashish A. Patel DDS, MD, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Allen Cheng DDS, MD, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Rom Leidner MD, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Marka Crittenden MD, PhD, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Steven Seung MD, PhD, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Carlo B Bifulco MD, PhD, Department of Pathology, Providence Cancer Center, Portland, OR
Tuan G. Bui DMD, MD, FACS, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Ryan Montler PhD, Earle A. Chiles Research Institute, Portland, OR
Christopher Paustian PhD, Earle A. Chiles Research Institute, Portland, OR
Zipei Feng BS, Earle A. Chiles Research Institute, Portland, OR
Eric J. Dierks MD, DMD, FACS, FACD, Head and Neck Surgical Institute, Portland, OR
Hong-Ming Hu PhD, Earle A. Chiles Research Institute, Portland, OR
Andrew Weinberg PhD, Earle A. Chiles Research Institute, Portland, OR
Bernard A Fox PhD, Earle A. Chiles Research Institute, Portland, OR
R. Bryan Bell DDS, MD, FACS, Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Portland, OR
Background: Transoral robotic surgery (TORS) has been advocated as a means of de-escalating or “personalizing” adjuvant treatment of oropharyngeal squamous cell carcinoma (OSCC) based upon known histopathological risk factors. Despite its favorable prognosis, approximately 9-14% of patients with HPV-related OSCC will still fail conventional therapy.  Accumulating evidence points to the importance of an ongoing antitumor T cell response and tumor infiltration by active effector T cells prior to conventional therapy like surgery, chemotherapy or radiotherapy that corresponds with clinical outcome. Our group is interested in developing a clinical strategy directed at promoting T-cell effector function and memory prior to and after surgery with the potential to induce anti-OSCC immunity.  The purpose of this clinical investigation is to: I) evaluate our early experience with TORS in the definitive treatment setting for OSCC; II) establish an HPV-related OSCC tumor bank from resection specimens; and III) determine the feasibility of perioperative immune profiling and modulation in HPV-related disease.

Methods: I) The study group consisted of a cohort of 57 consecutive patients with previously untreated, HPV-related T1-T2 OSCC (tonsil or base of tongue) who underwent TORS (with simultaneous neck dissection) followed by risk-adapted adjuvant therapy from February 2011 to March 2014.  Demographic and staging information was analyzed and treatment outcomes described using the Kaplan Meier method.  II) A tumor bank was created from 31 of these patients that consists of cryopreserved, enzymatically isolated viable cells from the primary tumor and metastatic lymph nodes of resection specimens as well as autologous blood samples. We are attempting to develop primary cell lines and isolate tumor-infiltrating lymphocytes (TIL) from these specimens. III) Immunohistochemical, flowcytometric and functional analyses of these specimens are being carried and expression of OX40 and other immune modulators, including PD1, CTLA-4, CD103, and B7H3 in OSCC TIL and blood was characterized.  In addition, we plan to investigate which antigens are recognized and whether antigens present in a novel autophagasome vaccine that expresses antigens common to OSCC are recognized by TIL.

Methods of data analysis:Descriptive statistics with Kaplan Meier method of survival analysis

Results: (I) Most patients were treated for pN2 disease (N0=9%; N1=12%; N2a=9%; N2b=53%; N2c=14%; N3=2%) and all but four patients underwent adjuvant radiation therapy with IMRT technique following TORS. Negative resection margins were achieved in 92% of the patients. Extracapsular extension was common, having occurred in about 40% of the cases and, with only 3 exceptions, these patients underwent concomitant chemoradiation.  Disease free survival during the study period was 92%.  (II) Preliminary results have documented consistent staining and potential of the IHC and FACS-based systems to identify infiltrating cells. There are two confirmed HPV+ tumor cell lines are established thus far, with TIL cultures successfully isolated from 29 patients. III) There was a significant increase in expression of OX40 (p<.0001), PD1( p=.0003), CTLA-4 (intracellular, p=.0371), and B7H3 (p=.0004) by intratumoral Tregs compared to circulating Tregs.  

Conclusion: TORS combined with risk adapted adjuvant therapy for oropharyngeal cancer provides excellent loco-regional control and may provide a feasible platform in which to monitor anti tumor immunity following immunotherapy.

1. Weinstein GS, Quon H, O'Malley BW, et al.  Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: A subset analysis of the University of Pennsylvania Transoral Robotic Surgery Trial. Laryngoscope. 120:2010.

2. Weinstein GS, O'Malley BW, Cohen MA, et al. Transoral robotic surgery for advanced oropharyngeal carcnioma. Arch Otolaryngol Head Neck Surg 136(11):1079, 2010

 

See more of: Pre-Conference on Maxillofacial Oncology and Reconstructive Surgery
See more of: Maxillofacial Oncology and Reconstructive Surgery
See more of: Pre-Conference Program
<< Previous Abstract | Next Abstract >>