6th ICHNO Abstract Book

page 22 6 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 16 – 18 March 2017 Barcelona, Spain __________________________________________________________________________________________ 6th ICHNO

propensity for infiltrating adjacent tissues, mostly by perineural invasion. Combined with frequent origin in anatomical sites with difficult access, the surgeon is frequently disappointed following the attempted clear margin resection. A University of Michigan study reported 80% of skull base AdCC resection specimens with positive surgical margins, despite the preoperative impression that resection with clear margins would be possible (Naficy,1999). The latest trend is thus against super- radical surgery that still frequently fails to achieve negative margins. In this line, for parotid AdCC, there is consensus to preserve a normally functioning facial nerve, relying on RT to deal with residual microscopic disease (Vander Poorten,2012).Historically, a low prevalence of occult nodal metastasis in AdCC is assumed. Neck dissection is classically only performed for cN+ disease, which is infrequently encountered. For specific MiSG subsites (oral cavity-oropharynx), recent scrutinized literature appraisal of “elective neck dissection (END) specimens” suggests a higher rate of occult metastasis, ranging from 15 to 44%, (Suarez, 2016) and especially in AdCC with high-grade transformation, lymph node metastasis may occur in 43–57% of patients (Hellquist,2016), suggesting to reconsider the role of END in these patients. It remains unclear, however, whether regional control, let alone survival, is improved by performing END as compared to primary RT to the neck nodes. Salvage surgery Local salvage surgery is rarely feasible and indicated(Spiro 2013). When local recurrence occurs, frequently distant metastasis (DM) is imminent. In the MSKCC database of 191 patients with recurrent SGC only 2 of 22 patients with locally resectable disease were effectively salvaged. Generous radical surgery should be considered and almost invariably patients will need flap reconstruction (free flaps, but frequently pedicled flaps like the MPM are a sound option in extensively operated and radiated necks). There are retrospective data that re-resection followed by chemo-reirradiation gives better DFS in those selected for surgical salvage(Pederson,2010; Erovic,2010). Prognostic factors In general, prognosis of AdCC is poor and the experience of many authors is that ‘‘cure is never achieved’’ in this‘‘clinically high grade’’ neoplasm. Disease-related deaths occur for as long as patients are followed. One series reports an overall survival of 24.5% and a recurrence-free survival of 22.6% at 15 years. (Huang,1997). In the posttreatment setting, the appearance of DM determines long term prognosis. In one study, on average, death occurred at 32 months following the occurrence of lung metastases and at 21 months following metastases elsewhere (van der Wal,2002). The most important clinical factor is TNM stage at presentation, which is closely linked to the site of origin (Spiro and Huvos,1992;Vander Poorten,2000). Remarkably early stage disease can do well, with T1N0 tumors being reported with 10, 15 and 20 years DSS of 94%, 81% and 73% respectively, and T2N0 already doing significantly worse (DSS 50%, 40% and 33% at 10, 15 and 20 years, respectively). As stated above, nodal metastases can be histopathologically detected when the primary tumor is surgically removed together with a neck dissection. Metastases are often small, which may explain why clinical examination or imaging may fail to detect them. Histological prognostic factors are tumor grade and perineural/intraneural invasion. Tumors showing a predominantly “solid” growth pattern have been repeatedly associated with worse prognosis, advanced stage and development of DM. PerineuraI invasion has been inconsistently associated with DM and adverse final outcome. In this respect, recently, a prognostically

relevant distinction has been made between perineural (P2: no impact on survival) and intraneural invasion (P1: independent predictor of poor prognosis).(Teymoortasch,2014;Amit,2015) Among molecular biological factors with prognostic relevance are (1) cell cycle-based proliferation markers (high Ki-67, PCNA, MCM and AgNOR expression), and specific genetic and epigenetic changes in (2) growth factor receptor proteins and ligands(c-KIT, VEGF- C/VEGFR-3, Eph2a, EGFR, NGF), (3) cell cycle oncogenes (cyclin D1, SOX-4, SOX-10, NFκB, PI3K, STAT3 and mTOR), (4) DNA damage repair proteins (p53), (5) cell adhesion proteins (loss of E-cadherin expression, ICAM-A, increased expression of Ezrin and ILK), (6) estrogen receptors, (7) lymphangiogenesis markers (podoplanin) and (8) transcription factors. Most notably the reciprocal translocation t(6;9) (6q22–23; 9p23–24), fusing the MYB gene on chromosome 6q22–q23 and the transcription factor NFIB on chromosome 9p23–p24, has recently been associated with prognosis in AdCC. SP-040 Radiotherapy in adenoid cystic carcinoma (ACC) of the head and neck A. Jensen 1 1 University of Munich, Radiation Oncology, Munich, Germany Abstract text Adenoid cystic carcinoma (ACCs) is a rare disease with an incidence of 1.3/100,000 per year. Many patients are diagnosed with advanced tumours, especially when these are located in the paranasal sinus, hence both surgical and radiotherapy treatments remain a challenge. Standard treatment consists of complete resection followed by adjuvant radiotherapy in the presence of risk factors. Due to their aggressive local growth patterns, high radiation doses are needed to achieve long-term local control. In standard photon radiotherapy though, this can be difficult to achieve faced with close proximity of critical structures at the base of skull. Neutron radiotherapy for salivary gland malignancies was explored in the early 1980s due to its increased biological effectiveness and did indeed demonstrate superior local control rates. Long-term toxicities however, were substantial. Due to their physical properties, charged particle beams can achieve highly conformal dose distributions through sharp dose gradients thereby leading to improved normal tissue sparing especially at complex anatomical sites. In consequence, the use of particle therapy and especially carbon ion therapy (C12) for adenoid cystic carcinoma has been intensively investigated by both Japanese and European groups. Recent analyses showed significantly improved control and survival rates in patients treated with a combination regimen of C12 plus IMRT. Results were confirmed by the prospective COSMIC trial and validated in a larger patient cohort. Moreover, control rates did not differ according to resection status in patients with T4 tumours treated C12. Therefore, debulking surgery with sometimes substantial morbidity may have to be reconsidered. Management of local recurrence following full course radiotherapy also presents a problem in ACC. When surgery is not feasible, the most active chemotherapeutic regimen can achieve response rates of between 40-50%. Due to the physical beam properties, re- irradiation with charged particles and comparatively high re-irradiation doses can be feasible and achieves response rates of >50% with moderate toxicity. However, further dose escalation needs to be considered carefully as the risk of higher-grade late toxicity increases. Particle therapy is also a good option to treat patients with locally recurrent disease, when surgery may not be feasible. In summary, particle therapy is a good treatment option