Pathologic staging changes in oral cavity squamous cell carcinoma: Stage migration and implications for adjuvant treatment

abstracts

Annals of Oncology

Table: 1148P Disposition and Baseline characteristics of patients treated with the investigational new drug AL101 18 6 12 1.5 84 56.5 610122 642 10 2

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Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): IDDI; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genentech. All other authors have declared no conflicts of interest.

1150P the ACCURACY trial, 12 pts with Notch1-4act mut are inhibitor AL101. The trial will advance to stage 2 data on these first 12 pts will be presented at the meet03691207. Editorial acknowledgement: Francesca Balordi, PhD, of The Lockwood Group (Stamford, CT, USA), in accordance with Good Publication Practice (GPP3) guidelines, funded by Ayala Pharmaceuticals, Inc. Legal entity responsible for the study: Ayala Pharmaceuticals, Inc. Funding: Ayala Pharmaceuticals, Inc. Disclosure: R. Ferrarotto: Honoraria (self), Advisory / Consultancy: Ayala Pharmaceuticals; Honoraria (self): Regeneron. A. Ho: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Ayala Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Research grant / Funding (self): Celldex Therapeutics; Research grant / Funding (self): Bayer; Research grant / Funding (self): Eli Lilly and Company; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Allos Therapeutics; Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi Genzyme; Honoraria (self), Advisory / Consultancy: Sun Pharma; Honoraria (self), Advisory / Consultancy: Regeneron; Honoraria (self), Advisory / Consultancy: TRM Oncology; Research grant / Funding (self), Travel / Accommodation / Expenses: Kura Oncology; Travel / Accommodation / Expenses: Ignyta. L.J. Wirth: Honoraria (self), Advisory / Consultancy: Ayala Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Eisai. C. Rodriguez: Honoraria (self), Advisory / Consultancy: Cue Biopharma; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck. E. Dekel: Shareholder / Stockholder / Stock options, Full / Part-time employment: Ayala Pharmaceuticals. R.M. Walker: Shareholder / Stockholder / Stock options, Full / Part-time employment: Ayala Pharmaceuticals. C. Nadri-Shay: Shareholder / Stockholder / Stock options, Full / Parttime employment: Ayala Pharmaceuticals. A. Vergara-Silva: Shareholder / Stockholder / Stock options, Full / Part-time employment: Ayala Pharmaceuticals. All other authors have declared no conflicts of interest.

1149P

Pathologic staging changes in oral cavity squamous cell carcinoma: Stage migration and implications for adjuvant treatment

Z. Husain1, N.C-J. Lee2, A. Eskander3, H. Park2, S. mehra2, B. Burtness2 Radiation Oncology, Sunnybrook Health Sciences Centre - Odette Cancer Centre, Toronto, ON, Canada, 2Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA, 3Otolaryngology, Sunnybrook Health Sciences Centre - Odette Cancer Centre, Toronto, ON, Canada

1

Background: The American Joint Committee on Cancer 8th Edition (AJCC 8) for oral cavity squamous cell carcinoma (OCSCC) incorporates depth of invasion (DOI) into the pathologic tumor classification (pT) and pathologic extranodal extension (pENE) into the pathologic nodal classification (pN). We sought to evaluate the incidence and prognostic importance of stage migration as a result of these changes on the AJCC 8 staging system.

v466 | Head And Neck Cancer, Excluding Thyroid

Expression of immune response biomarkers in head and neck squamous cell carcinoma (HNSCC) in irradiated area

C. Pflumio1, J. Thomas2, J. Salleron3, J-C. Faivre4, C. Borel5, G. Dolivet6, X. Sastre-Garau2, L. Geoffrois7 1 Medical Oncology, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`s-Nancy, France, 2Pathology, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`s-Nancy, France, 3Biostatistics and Data Management, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`s-Nancy, France, 4Radiation Therapy, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`s-Nancy, France, 5Medical Oncology, Centre Paul Strauss Centre de Lutte contre le Cancer, Strasbourg, France, 6Department of Surgical Oncology/ CNRS-UMR 7039 CRAN, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`s-Nancy, France, 7Medical Oncology, Institut de Cance´rologie de Lorraine, Vandoeuvre-le`sNancy, France Background: HNSCC occurring in previously irradiated area have a poor prognosis. With immunotherapy, the inhibition of negative regulators of immune checkpoints programmed cell death ligand-1 (PD-L1) and CD8þ tumor-infiltrating lymphocytes (TILs) have been of greatest importance for antitumor immune response. Yet, the immune landscape of pretreated area remains poorly documented and should be investigated, especially since locoregional recurrences have recently been described as a predominant site of hyperprogression. We aimed to assess the tumoral microenvironment in terms of biomarkers for tumor immune response in irradiated area compared to de novo tumors. Methods: This retrospective monocentric study analyzed 100 HNSCC tumor tissues from patients who had undergone surgery between January 2010 and November 2017. We compared the immune microenvironment in 50 de novo tumors and 50 tumor recurrence occurring within irradiated area. Formalin-fixed and paraffin embedded tumor tissue samples were reviewed by an experimented pathologist for immunohistochemistry. We assessed p16 status, CD3þ and CD8þ TILs and PD-L1 expression on tumor and immune cells, in stromal and intratumoral components. Results: The density of CD3þ TILs was significantly lower, whether in intratumoral or stromal region within irradiated areas (p ¼ 0.003 and p ¼ 0.020 respectively). The expression of CD8þ TILs was not significantly different between the two cohorts. The percentage of tumor cells expressing PD-L1 TC (TPS¼1%) was significantly lower in tumours developed within irradiated area than in de novo tumors (56.0% vs 86.0%) (p < 0.001). Immune cells expressing PDL-1 were less frequent in tumors within irradiated areas. Predominant microenvironment type in irradiated area cohort was adaptative immune resistance. Conclusions: There were persistence of cytotoxic cells and lower expression of PD-L1 and CD3þ TILs in tumors within irradiated area. This study provides first hypothesis to explain the fact that these lesions are less responsive to immunotherapy although they may still have antitumor capacity. The assessment of predictive biomarkers in patients treated by immunotherapy in randomized trials is required. Legal entity responsible for the study: Dr Lionnel Geoffrois. Funding: Has not received any funding. Disclosure: C. Borel: Honoraria (self): Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck Serono. All other authors have declared no conflicts of interest.

Volume 30 | Supplement 5 | September 2019

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Screened/Enrolled (signed consent), n Screen failures, n Treated, n Median number of cycles, n Gender, n Male Female Median age, years Race, n White Black Asian Other Not Reported N/A ECOG performance status, n 0 1 N/A Disease status, n With nodal or visceral metastases With bone-exclusive metastases Type of mutations, n domain

Methods: From the National Cancer Database, cohorts were identified from patients with OCSCC undergoing definitive surgery between 2004-2013 for pT (n ¼ 7,184), pN (n ¼ 13,627), and pathologic Stage (pStage; n ¼ 5,580) analysis. Results: DOI and pENE were prognostic in all groups except AJCC 7 pN3. Upstaging was seen in 12.4% of patients for pT classification, 13.3% for pN classification, and 24.8% for overall pathologic stage grouping. Notably, upstaging led to similar or improved five-year overall survival (5-YR OS) for every AJCC 8 pT/N classification except pStage IVB. AJCC 7 pT1 tumors upstaged to AJCC 8 pT3 tumors had improved overall survival compared to the remainder of the pT3 group (71.7% vs 43.7%, respectively, P < 0.0001). A multivariable analysis of up-staged pT3N0 patients demonstrated a reduced risk of death with receipt of PORT (HR 0.56, 95% CI 0.33-0.95, P ¼ 0.03). Conclusions: Upstaging is common in AJCC 8, and upstaged tumors demonstrate improved survival; these factors that should be kept in mind when interpreting data using the new staging system. Postoperative radiotherapy may reduce death in newly upstaged pT3N0 patients, and further study is needed in this area. Legal entity responsible for the study: Yale School of Medicine. Funding: Research reported in this publication was supported by the National Institute on Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number T35DK104689 (NCJL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This publication was made possible by the Yale School of Medicine Medical Student Fellowship (NCJL). Disclosure: B. Burtness: Honoraria (self), Research grant / Funding (institution): Advaxis;