7th ICHNO Abstract book

page 86 7 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 14 – 16 March 2019 Barcelona, Spain __________________________________________________________________________________________ 7th ICHNO

Purpose or Objective To retrospectively evaluate the efficacy and safety of proton (PT) of adenoid cystic carcinomas (ACCs) of the head and neck region using pencil beam-scanning (PBS) technique in a single institution. Material and Methods A total of 35 patients who underwent treatment with PBS PT for histologically confirmed, non-metastatic or refractory ACC between 2001 and 2017 were included in this study. Outcome was evaluated by assessment of local control (LC), distant metastasis-free survival (DMFS), (any) progression-free survival (PFS) and overall survival (OS). Clinical and treatment-related factors were evaluated for prognostic significance. Adverse effects were evaluated according to CTCAE v.4. Results Median patient age was 45.4 years (range: 27.8 – 81.3). Twenty four patients (68.6%) had a T4 tumor clinical stage. Nine patients (25.7%) presented with inoperable disease and the remaining 26 (74.3%) underwent surgery (R0 for 5 patients, 19.2%; R1 for 13, 50% and R2 for the remaining 8, 30.8%). The median prescribed dose was 70.8 Gy (RBE) [range: 66.0–77.4 Gy(RBE)]. After a median follow-up of 22.6 months (range: 2.1 – 169.6), 13 patients presented with disease progression (local failure, 4; distant progression, 6; both local and distant, 3). Five tumor-related deaths were observed. The estimated 2- year LC was 92.2% (95% CI: 76.7–98.1%), DMFS was 77.8% (95%CI: 60.1–89.4%), PFS was 74.3% (95%CI: 56.4–86.9%), and the OS was 88.8% (95%CI: 72.5–96.4%).Five patients (14.3%) experienced grade 3 acute adverse events (AEs) and grade 3 late AEs were reported in 2 patients (5.8%). No grade 4&5 AEs were observed, both acute and late. In univariate analysis, the risk of local failure was influenced by patient age with a cutoff of 63.1 years (risk above vs below: 55.6% vs 7.7%; HR= 13.5, 95%CI: 1.6 – 116.7;p= 0.002). The risk of distant metastasis (DM) was influenced by the low-dose CTV1 volume (above vs below the cutoff point of 223.8 cm 3 : 50% vs 9.5%; HR= 10.5, 95%CI: 1.3 – 85.3,p= 0.03). The only factor predicting the combined risk of any failure, local or distant was the tumor T clinical stage (risk stage T4a-c vs stages T1-3 combined: 50% vs 9.1%; HR= 2.1, 95%CI: 1.01 – 4.4, p= 0.045). The tumor clinical stage IVB-C was a significant predictor of the risk of death (stage IVB-C: 50%, stage IV-IVA: 7.7%, other stages: 0%; HR= 9.3, 95%CI: 1.0 – 85.3; p= 0.049)

Universitaria Maggiore della Carità, Medical Oncology, Novara, Italy; 6 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy, Milan, Italy ; 7 Centro Nazionale Adroterapia Oncologica, Radiotherapy, Pavia, Italy; 8 Fondazione IRCCS Istituto Nazionale dei Tumori, Otolaryngology- Head and Neck Surgery, Milan, Italy; 9 Fondazione IRCCS Istituto Nazionale dei Tumori, Head and Neck Medical Oncology, Milan, Italy Purpose or Objective Information about mutational status of epithelial non- glandular sinonasal cancers (SNCs) are scanty and mainly derived from retrospective analysis of case series. Deepening the knowledge about molecular pathways involved in this disease may help identifying prognostic and therapeutic opportunities. Material and Methods We analyzed the mutational profile of diagnostic biopsies of the patients enrolled into 2 prospective clinical trials on multimodality treatment (induction chemotherapy, surgery if operable, photon and/or heavy ion radiotherapy) of patients with operable (SINTART-1) or inoperable (SINTART-2) SNCs. Formalin-fixed paraffin-embedded blocks were selected for genomics analysis by an experienced pathologist. The tumour area was manually macrodissected to enrich for tumour cells before nucleic acids extraction. DNA was isolated using GeneRead DNA FFPE Kit, while RNA using miRNAeasy FFPE kit (Qiagen). Screening of mutations was performed by sequencing using the IONS5xl and Ion AmpliSeqCancer_Hotspot_Panel_v2 (Life Technologies) covering 207 frequently mutated region in 50 cancer genes. Template preparation was performed using the Ion Chef System (Life Technologies) and sequencing was performed on IONS5xl according to manufacturer instructions. Results Overall, SINTART trials enrolled 67 patients and sufficient tumor material was available from 48 cases. All the patients had stage III-IV disease, not having received any previous treatment. The analyzed series was composed by squamous cell cancers (25%), sinonasal undifferentiated cancers (44%), sinonasal neuroendocrine cancers (22%), and intestinal- type adenocarcinomas (9%). Of the 48 cases analyzed, at least 1 mutation was detected in 46 out of 48 cases. A total of 26 genes were reported mutated at least in one sample and the most frequently mutated genes (>20%) included HRAS, TP53, KIT, PDGFRA, SMARCB1. Potentially druggable alterations were also reported in CDKN2A and PI3KCA (17% of the cases). Conclusion We reported a high rate of mutations in locally advanced, non pretreated, epithelial non-glandular SNCs. These findings may pave the way to clinical trials for targeted treatment of these rare diseases. The evaluation of tumor mutational burden by exome sequencing and its prognostic impact in SNCs is ongoing. PO-162 Patient outcome of pencil beam-scanning proton therapy in Head and Neck adenoid cystic carcinoma M. Pelak 1 , M. Walser 1 , B. Bachtiary 1 , A. Bolsi 1 , J. Hrbacek 1 , A. Lomax 1 , U. Kliebsch 1 , A. Pica 1 , D.C. Weber 1 1 Paul Scherrer Institute, Center for Proton Therapy, Villigen, Switzerland; 2 EBG MedAustron GmbH, Wiener Neustadt, Austria

Conclusion Proton beam therapy using PBS is an effective and safe way of delivering definitive and adjuvant irradiation in patients with ACC of the head and neck region. Most ACC patients that progressed after treatment failed distantly.