FLOT vs. CROSS – What is the Role of Radiotherapy? - Chemotherapy Alone The Role of Radiation in Neoadjuvant Setting for Esophagogastric Cancer Weijing Sun, MD, FACP University of Kansas Medical Center
Roles of Chemotherapy vs. Radiotherapy in Peri-operative Setting Chemotherapy – broader benefits – Systemic and local benefits – Either early or locally advanced Radiation – limited benefits – Local only – SCC vs. Adeno CA – early early local disease – may be not needed – more locally advanced – not enough – Adding with chemo – increased toxicity Sensitization: which to which?
Is it a fare comparison: Chemotherapy vs. Chemoradiation? 1 + 1 =? • 1 (person) + 1 (person) = 2 (persons) • 1 (man) + 1 (woman) = ? • 1 (T3N0) + 1 (T2N1) = 2 of ? • 1 (T3N0, poorly diff. ) + 1 (T2N1, well diff.) = 2 of ? • 1 (3 agents combination) ≥ 1 (2 agent chemo) = (2 agent chemo + XRT) ?
What do we need to debate the role of XRT? (with or without Chemotherapy?) • Increasing the resectability, pCR (of…), Disease • Decreasing the recurrence (of …) • Increasing the tolerability (of…) • Improving the quality of life (of …), (for…) Patients (and …) • Improving the Survival (DFS, OS) (of…)
Gastroesophageal Junction 5cm Type 1 Adenocarcinoma of the distal esophagus 1cm Type 2 Cancer of the cardia GE Junction 2cm Type 3 Subcardial cancer 5cm Siewert JR and Stein HJ. Br J Surg . 1998;85(11):1457-1459.
• Disease Characteristics – TNM staging system (diagnostic tools: precision vs accuracy vs…) – Location – Histopathological features and + – Heterogeneity at different levels – Risk of recurrence: locally vs systemically… • Patients’ Characteristics • Age, gentle, race… • PS, Co-mobilities • Family… • Behavior… • Other significant factors • Country, City, metropolitan vs suburban vs countryside… • Social economic status • Financial status • Education level • Influences from… • Other uncontrollable (controllable) factors …
5- YR
Cross trial FLOT4 trial Cross trial FLOT4 trial (ChemoXRT Arm) (ChemoXRT Arm) (FLOT Arm) (FLOT Arm) N=178 N=178 N=356 N=356 cT Medan Age 60 (37-79) 62 (54-69) cT1 1 (1%) 3 (1%) Male (%) 134 (75%) 268 (75%) cT2 26 (15%) 49 (14%) PS WHO ECOG cT3 150 (84%) 267 (75%) 0 144 (81%) 246 (69%) cT4 0 28 (8%) 1 34 (19%) 109 (31%) N Adenocarcinoma 134 (75%) 356 (100%) N0 59 (33%) 77 (22%) (N-) (Signet cell 28%; diffuse 27 %, intestinal 45%;) N1 116 (65%) 279 (78%) (N+) Location Distal Esophageal 104 (58%) Siewert type 1: 80 (23%) Van Hagen P. et al NEJM 2012; 366:2074-84 Al-Batran S-E et al Lancet 2019 393:1948-57 GEJ 39 (22%) Siewert type 2&3: 118 (33%) Stomach - 158 (44%)
Overall Survival: Cross (All) Overall Survival: FLOT Overall Survival: Cross (AdenoCA) FLOT: DFS
Cross trial (ChemoXRT Arm) FLOT4 trial (FLOT Arm) N=178 N=356 Surgery 94% 94% R0 92% 85% Median LN # 15 24 Van Hagen P. et al NEJM 2012; 366:2074-84 Path Response ypCR 23% ≤ ypT1 25% Al-Batran S-E et al Lancet 2019 393:1948-57 Cunnningham D, et NEJM 2006 355:11-20 N0 31% 49%
Neoadjuvant chemo or chemoradiation for patients with advanced adenocarcinoma of the esophagus: propensity score-matched study Favi F, et al EJSO 43 (2017) 1572e1580
Supporting info
ARTIST 2 Primary Endpoint
ARTIST 2 Subgroup Analysis of DFS Presented By Se Hoon Park at 2019 ASCO Annual Meeting
Summary Roles of Chemotherapy vs. XRT in Perioperative Setting Chemotherapy – broader benefits – Systemic and local benefits – Either early or locally advanced Radiation – SCC! AdenoCA +/- – early early local disease – either not needed or could replace the surgery – more locally advanced – not enough – Adding with chemo – increased toxicity Sensitization: which to which? ‘Head to Head’ Randomized Study( ies) – needed, but unlikely Molecular Biology Based Evidence besides the clinic characteristics- Pt selection
Questions? Thank you!
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