7th ICHNO Abstract book

7th ICHNO 7 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 14 – 16 March 2019 Barcelona, Spain __________________________________________________________________________________________ page 91

ATC cell lines were assessed for CD47 expression by flow cytometry. CD47 was blocked in in vitro phagocytosis assays of co-cultured macrophages and ATC cell lines. Anti-CD47 antibody treatment was administered to immunocompromised mice subcutaneously xenotransplanted with ATC cell lines as well as to double- transgenic mice that develop orthotopic ATCs after tamoxifen induction. Results Human ATCs had a mean macrophage infiltration of 25%, a weak CD47 expression and a moderate expression of calreticulin, the dominant pro-phagocytic molecule. Surface CD47 and calreticulin were highly expressed in 8/8 ATC cell lines as analyzed by flow cytometry. Blocking CD47 increased phagocytosis of ATC cell lines in vitro compared to isotype control. Anti-CD47 antibody treatment significantly delayed tumor growth and increased the frequency of intratumoral macrophages in ATC xenotransplanted mice. In double-transgenic mice, anti-CD47 treatment resulted in increased intratumoral macrophage frequencies without affecting tumor growth kinetics. Conclusion ATCs express CD47 and are heavily infiltrated by macrophages. Anti-CD47 treatment increases phagocytosis of ATCs by macrophages in vitro and in vivo and might be a promising therapeutic option for ATC patients. PO-172 Carbon ion radiotherapy in active raster- scanned technique for malignant lacrimal gland tumors S. Akbaba 1 , T. Held 1 , K. Lang 1 , K. Herfarth 1 , J. Hoerner- Rieber 1 , P. Plinkert 2 , G. Auffarth 3 , S. Rieken 1 , J. Debus 1 , S. Adeberg 1 1 University Hospital Heidelberg, Radiation Oncology, Heidelberg, Germany; 2 University Hospital Heidelberg, Otorhinolaryngology- Head and Neck Surgery, Heidelberg, Germany; 3 University Hospital Heidelberg, Ophthalmology, Heidelberg, Germany Purpose or Objective We aimed to evaluate treatment outcome of carbon ion radiotherapy (CIRT) in active raster-scanned technique alone or in combination with intensity-modulated radiotherapy (IMRT) for lacrimal gland tumors regarding Twenty-four patients who received CIRT for malignant lacrimal gland tumors at the Heidelberg Ion Beam Therapy Center (HIT) between 2009 and 2018 were analyzed retrospectively for local control (LC), overall survival (OS) and distant progression-free survival (DPFS) using the Kaplan-Meier method. CIRT was applied either alone (n=3, 13%) or in combination with IMRT (n=21, 88%). The majority of patients had tumors in advanced stages (T4 stage, n=14, 58%), of adenoid cystic histology (ACC, n=18, 75%) or were irradiated for a macroscopic tumor disease (n=19, 79%). Additionally, toxicity was assessed according to the Common Toxicity Terminology Criteria for Adverse Events (CTCAE) version 5. Results Median follow up was 30 months (range 6-102 months) and overall median LC, OS and DPFS were 24 months (6-59 months), 36 months (range 9-102) and 31 months (6-102 months), respectively. We could achieve a 2-year LC, OS and DPFS of 93%, 96% and 87% with CIRT for all patients. Local failure occurred in patients with ACC solely and after a median time of 30 months (range 22-51 months) after completion of RT (p= 0.09 , n=5, 21%). Corresponding 2- year LC, OS and DPFS for ACC patients were 90%, 94%, 93% feasibility and safety. Material and Methods

of patients. Therefore, primary intensity modulated radiotherapy (IMRT) is the standard treatment for these tumors. A combination with carbon ions (CIRT) for local dose escalation may lead to an improved outcome. Thus, we aimed to present the first long-term clinical results of this therapy modality with a focus on local control (LC) and patterns of recurrence. Material and Methods We retrospectively analyzed fifty-nine patients with ACC of the nasopharynx who were treated with bimodal radiotherapy (RT) including intensity modulated radiotherapy (IMRT) and carbon ion boost (CIRT) at the Heidelberg Ion Therapy Center (HIT) between 2009 and 2018. Median age was 50 years (range 19-77 years) and patients had predominantly inoperable (n=42, 72%) or incompletely resected (n=17, 29%) tumors. Local control (LC), distant progression-free survival (DPFS) and overall survival (OS) were calculated using the Kaplan-Meier method and patterns of local recurrence were additionally assessed. Prognostic factors for survival outcome were identified with the log-rank test for univariate and the cox-regression model for multivariate analysis. Toxicity was assessed according to the Common Toxicity Terminology for Adverse Events (CTCAE) version 5. Results Median follow up was 32 months (range 7-106 months). At last follow up, 67% were still alive (n=39/58) of whom 74% were free of progression (n=29/39). Overall, progressive disease was seen in 45% of the patients (n=25/56) with local relapse in 34% (n=19/56) after a median time of 28 months (range 7-74 months) and distant relapse in 23% (n=13/56) after a median time of 34 months (range 8-152 months).The 2-year LC, DPFS and OS were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69% respectively. Local control was significantly inferior in patients with large tumor volumes (GTV >100c, p=0.020 ) and T4 stage tumors ( p=0.021 ). The majority of the recurrences occurred at the margin where critical structures were spared (n=11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% chronic side effects. Conclusion Bimodal radiotherapy for nasopharyngeal ACC resulted in adequate LC and OS with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC. PO-171 The “don’t eat me” signal CD47 – a therapeutic option in human anaplastic thyroid carcinoma? C. Schürch 1 , M. Roelli 2 , M. Wasmer 1 , F. Brühl 1 , S. Forster 1 , R. Maire 1 , S. Di Pancrazio 3 , M. Ruepp 3 , A. Perren 1 , A. Schmitt 1 , P. Krebs 1 , R. Charles 2 , M. Dettmer 1 1 University of Bern, Dep of Pathology, Bern, Switzerland ; 2 University of Bern, Institute of Biochemistry andMolecular Medicine, Bern, Switzerland; 3 University of Bern, Department of Chemistry and Biochemistry, Bern, Switzerland Purpose or Objective Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers and has a dismal prognosis. CD47 is a “don’t eat me” signal which prevents cancer cells from phagocytosis by binding to SIRPa on macrophages. So far, the role of macrophages and the CD47-SIRPa signaling axis in ATC is not well understood. Material and Methods We analyzed 20 primary human ATCs for macrophage markers and CD47 expression by immunohistochemistry.