ESTRO 2023 - Abstract Book

S65

Saturday 13 May

ESTRO 2023

1 Oxford University Hospital NHS Foundation Trust, Oncology, Oxford, United Kingdom; 2 Cardiff University, Centre For Trials Research, Cardiff, United Kingdom; 3 Swansea Bay University Health Board, Oncology, Swansea, United Kingdom; 4 The Christie NHS Foundation Trust, Oncology, Manchester, United Kingdom; 5 University of Oxford, Oncology, Oxford, United Kingdom; 6 Hull University Teaching Hospitals NHS Trust, Oncology, Hull, United Kingdom; 7 University of Cambridge, Oncology, Cambridge, United Kingdom; 8 Cardiff University, Wales Research and Diagnostic PET Imaging Centre, Cardiff, United Kingdom; 9 Betsi Cadwaladr University Health Board, Oncology, Rhyl, United Kingdom; 10 University Hospital Southampton NHS Foundation Trust, Oncology, Southampton, United Kingdom; 11 University Hospitals Bristol NHS Foundation Trust, Oncology, Bristol, United Kingdom; 12 Velindre University NHS Trust, Pharmacy, Cardiff, United Kingdom; 13 Velindre University NHS Trust, Medical Physics, Cardiff, United Kingdom; 14 Cardiff University, School of Engineering, Cardiff, United Kingdom; 15 University College London, Oncology, London, United Kingdom; 16 Velindre University NHS Trust, Oncology, Cardiff, United Kingdom Purpose or Objective The randomised phase II/III SCOPE2 is investigating two questions in patients with oesophageal squamous carcinoma (SCC) and adenocarcinoma (ACA) receiving definitive chemoradiation (dCRT): 1) does high dose RT (60Gy/25#) improve OS compared to standard dose (50Gy/25#) and 2) In PET non-responders (based on FDG-PET-CT on day 14 of cycle 1 induction chemotherapy) does switching chemotherapy from Cisplatin-Capecitabine (CisCap) to Carboplatin-Paclitaxel (CarPac) after 1 cycle improve treatment failure-free survival (TFFS) at 24 weeks. The dose escalation component (randomised phase III) is still ongoing; here, we report results of the PET substudy Materials and Methods Design: The PET substudy is a randomised Phase II component of a multicentre, open label, parallel, 2x2 (four arm) factorial study. Key Eligibility: Histologically confirmed cancer oesophagus/GOJ with <2cm extension into the stomach; selected for dCRT by a designated Multidisciplinary Team Meeting; age>=18; WHO PS 0-1; T1-4 and N+/-; total disease length ≤ 13cm. Baseline FDG-PET SUVmax ≥ 5 (performed within 5 weeks prior to start of treatment). Procedures: Repeat PET performed on Day 14 of 1st cycle of induction CisCap. Non-responders (drop in SUVmax<35%) were randomized to continue CisCap or switch to CarPac for cycle 2 followed by concurrent CRT with same chemotherapy. All patients were also randomized between 50Gy and 60Gy arms. Statistical Consideration: PET substudy was powered separately in SCC and ACA. For SCC 86 non-responders were required to detect a 20% improvement in 24wk TFFS (55% to 75% with CarPac; chi square, 87% power, 0.2 one sided alpha). For ACA, 27 patients would detect an improvement in 24 week TFFS from 55% with to 85% with CarPac (chi square, 80% power, 0.20 one sided alpha). RT Quality Assurance: An associated RTQA program ensured high quality RT was delivered. IDMC stopped PET substudy in Aug 2021 on the grounds of futility and possible harm. 63/103 (61%) participants were non responders (SCC=52/83; ACA=11/20) of whom 32 were randomised to continue CisCap and 31 switched to CarPac. The 24 week TFFS in the SCC cohort was no better in responders (who continued CisCap) than non-responders who stayed on CisCap or switched to CarPac (78.6% v 92.6% v 68%). In non-responders (SCC cohort) both 24-week TFFS [25/27(92.6%) vs 17/25(68%) p=0.028] and OS (42.5 mo v 20.4mo, adjusted HR 0.36, p=0.018) favoured CisCap over CarPac. PFS favoured CisCap but was non-significant (34.6 mo v 19.4mo, HR 0.58, p=0.15). Similar trend was seen in ACA (p=NS). Grade 3 /4 toxicity rate was comparable between arms [CarPac 22/31 (71.0%) vs CisCap 21/31 (67.7%)]. Conclusion Early PET response based on proposed SUVmax cut-off was not prognostic and did not predict treatment failure. Chemo switch based on early PET response using proposed cut-off cannot be recommended in this setting. A better discriminator for early treatment failure is required. OC-0104 A novel approach to assess preoperative toxicity in gastric cancer patients in the CRITICS trial R. van Amelsfoort 1 , P. González 2 , R. Simões 1 , E. Jansen 3 , A. Cats 4 , N. van Grieken 5 , K. Sikorska 6 , E. Meershoek – Klein Kranenbarg 7 , H. Putter 7 , C. vd Velde 7 , J. van Sandick 8 , M. Verheij 9 , I. Walraven 10 1 Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands; 2 Amsterdam Medical Centre, Radiation Oncology, Amsterdam, The Netherlands; 3 Netherlands Cancer Institute, Radiation Oncology, Amsterdam , The Netherlands; 4 Netherlands Cancer Institute, Gastrointestinal Oncology, Amsterdam, The Netherlands; 5 Amsterdam Medical Centre, Pathology, Amsterdam , The Netherlands; 6 Netherlands Cancer Institute, Biostatistics, Amsterdam, The Netherlands; 7 Leiden University Medical Center, Surgical Oncology, Leiden, The Netherlands; 8 Netherlands Cancer Institute, Surgical Oncology, Amsterdam, The Netherlands; 9 Radboud University Medical Center, Radiation Oncology, Nijmegen, The Netherlands; 10 Radboud University Medical Center, Health Evidence, Nijmegen, The Netherlands Purpose or Objective A substantial proportion of gastric cancer patients develop treatment-related toxicity. Since these side effects have a significant impact on health-related quality of life, the avoidance or mitigation of toxicity development is critical, hence optimal strategies that address this need, are warranted. The primary aim of this study was to identify clusters of locally advanced non-metastatic gastric cancer patients with distinct toxicity profiles and assess the prognostic potential of these clusters early during the first course of preoperative chemotherapy within the CRITICS study. Subsequently, we assessed whether membership of the identified clusters was associated with (1) treatment compliance and (2) with overall (OS) and For this study, we included all patients who participated in the CRITICS trial (NCT00407186) and who started the first course of preoperative chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE; version 3). Agglomerative hierarchical cluster modelling was used to identify clusters of patients with distinct toxicity profiles during the first chemotherapy course. For this, we randomly split the data into a training (80%) and a test (20%) set. Cox proportional hazards analysis was performed to assess the association between class membership and EFS and OS. Funding: Cancer Research UK (A17606) and Trial Sponsor: Velindre University NHS Trust. Results event-free (EFS) survival. Materials and Methods