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6067Background: With results of chemo-radiotherapy de-escalation trials for Human Papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) pending, any reduction in toxicity may be offset by t...

e17551 Background: Chemoradiotherapy (CRT) with 3 cycles (#) of high-dose cisplatin (HDC) (100mg/m2 weeks 1,4 & 7) and 70Gy over 7 weeks is associated with improved overall survival (OS) compared with radiotherapy (RT) alone in locally advanced OPC. Human Papilloma Virus (HPV) related tumours have superior outcomes and de-escalating treatment is a contemporary issue. Our study objectives were to determine if 2# HDC were non-inferior to 3#, how this was influenced by prognostic factors including stage, smoking history and p16 status, and to explore toxicity attributed to HDC. Methods: A single centre, retrospective analysis was undertaken for OPC patients who received CRT with HDC between Oct 2009 -Dec 2012. Those with distant metastatic disease or receiving induction chemotherapy were excluded. Data extracted included HPV and smoking status, tumour stage by 7thEd AJCC TNM and ICON-S classification, # HDC completed, toxicity and OS. Log-rank test was used for OS analysis. Results: 63, 96 and 4 patients received 3, 2 and 1 # HDC respectively. Median RT dose was 70Gy (range 66-70). 110 (67.5%) were p16 +, 28 (17.2%) were p16 negative and 25 (15.3%) unknown. 52 had omission of #3 HDC predominantly due to neutropenia (33%), nephrotoxicity (23%) and ototoxicity (12%). 19 had delays in #2 HDC resulting in omission of #3 due to completion of RT. There was no difference in OS between 3 #(mean OS (yrs)+/- SEM: 6.05+/- 0.22) or 2# HDC (5.70+/- 0.21) in all comers (p = 0.255). For RTOG0129 low risk p16+ patients, there was no significant difference (p = 0.896) between 3# (6.33+/- 0.24; n = 24) and 2# (6.18+/- 0.25; n = 44) HDC. Similar results were evident for ICON-S stage I for 3# (6.36+/-0.19; n = 25) vs 2# (6.30+/- 0.19; n = 42) HDC (p = 0.932). For RTOG 0129 intermediate risk p16 + OPC there was a significant difference (p = 0.017) in OS favouring 3# (6.29+/-0.22; n = 20) versus 2# (4.81+/-0.67; n = 10) HDC. For p16 negative patients there was no difference (p = 0.265) in OS between 3# (4.06+/-0.94; n = 9) and 2# (5.17+/-0.48; n = 22) HDC. Conclusions: This data suggests that cisplatin de-escalation does not confer inferior OS in low risk HPV related OPC. Significant toxicities with HDC influenced the ability to complete prescribed treatment.

6008 Background: We report on the first multi-centre randomized phase III trial of post-operative radiotherapy (PORT) vs post-operative chemo-RT (CRT) in high-risk cutaneous squamous cell carcinoma of the head and neck (cSCCHN) (NCT00193895). Methods: The primary objective was to determine whether there was a freedom from loco-regional relapse (FLRR) difference between patients randomly assigned to 60-66Gy (6-6.5 weeks) with or without weekly carboplatin (AUC 2) following resection of gross disease. Patients were stratified to high-risk nodal (either extracapsular nodal extension, intra-parotid nodal disease of any size or number, cervical nodal disease with ≥2 nodes or largest node > 3cm) or high-risk primary (T3-T4 or in-transit metastases). Patients with both features were stratified to the high-risk nodal group. Secondary objectives included disease-free survival (DFS), overall survival (OS) and acute & late toxicity (CTCAE V3). Results: 321 patients were randomly assigned between 2005-2014, with 11 not commencing treatment protocol due to disease progression or withdrawal of consent. Of the 310 patients commencing treatment protocol (157 RT and 153 CRT), 230 (74%) had high-risk nodal, 70 (22%) high-risk primary and 10 (3%) both. Median follow up was 60 months, median RT dose was 60Gy and 85% randomised to CRT completed 6 cycles of carboplatin. The 2- & 5-year FLRR (95% CI) for the RT arm was 88% (83-93%)/83% (77-90%) and for CRT 89% (84-94%)/87% (81-93%) (HR 0.85; 95%CI [0.46-1.55]; p = 0.59). The 2- & 5 year DFS (95% CI) for the RT arm was 78% (72-85%)/67% (60-76%) and for CRT 83% (77-89%)/73% (66-81%) (HR 0.85; 95%CI [0.55-1.29]; p = 0.43). The 2- & 5 year OS (95% CI) for the RT arm was 88% (83-93%)/76% (69-84%) and for CRT 88% (83-94%)/79% (72-86%) (HR 0.95; 95%CI [0.58-1.57]; p = 0.84). 134 (43%) experienced Grade 3/4 skin toxicity; 49% RT, 37% CRT (p = 0.039). 12 (3.9%) experienced Grade 3/4 subcutaneous fibrosis; 2.5% RT, 5.2% CRT. Conclusions: While surgery and PORT provided excellent FLRR with acceptable toxicity, the addition of weekly carboplatin did not improve outcomes in high-risk cSCCHN. Clinical trial information: NCT00193895.

TPS2616 Background: EBC-46 is a novel protein kinase C (PKC) activator being developed for intratumoral treatment of cutaneous and subcutaneous tumors. Studies in syngeneic and xenograft mouse mode...