Roles of Chemotherapy vs. Radiotherapy in Peri-operative Setting - - PowerPoint PPT Presentation

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…),
• Decreasing the recurrence (of …)
• Increasing the tolerability (of…)
• Improving the quality of life (of …), (for…)
• Improving the Survival (DFS, OS) (of…)

Disease Patients (and …)

Gastroesophageal Junction

5cm 1cm GE Junction 2cm 5cm

Siewert JR and Stein HJ. Br J Surg. 1998;85(11):1457-1459.

Type 1 Adenocarcinoma

• f the distal esophagus

Type 2 Cancer of the cardia Type 3 Subcardial cancer

• 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

(ChemoXRT Arm)

N=178 FLOT4 trial (FLOT Arm) N=356 Medan Age 60 (37-79) 62 (54-69) Male (%) 134 (75%) 268 (75%) PS WHO ECOG 144 (81%) 246 (69%) 1 34 (19%) 109 (31%) Adenocarcinoma 134 (75%) 356 (100%)

(Signet cell 28%; diffuse 27 %, intestinal 45%;)

Location Distal Esophageal 104 (58%)

Siewert type 1: 80 (23%)

GEJ 39 (22%)

Siewert type 2&3: 118 (33%)

Stomach

• 158 (44%)

Cross trial

(ChemoXRT Arm)

N=178 FLOT4 trial (FLOT Arm) N=356

cT

cT1 1 (1%) 3 (1%) cT2 26 (15%) 49 (14%) cT3 150 (84%) 267 (75%) cT4 28 (8%)

N

N0 59 (33%) 77 (22%) (N-) N1 116 (65%) 279 (78%) (N+)

Van Hagen P. et al NEJM 2012; 366:2074-84 Al-Batran S-E et al Lancet 2019 393:1948-57

Overall Survival: FLOT FLOT: DFS Overall Survival: Cross (All) Overall Survival: Cross (AdenoCA)

Cross trial (ChemoXRT Arm) N=178 FLOT4 trial (FLOT Arm) N=356 Surgery 94% 94% R0 92% 85% Median LN # 15 24 Path Response ypCR 23% ≤ ypT1 25% N0 31% 49%

Van Hagen P. et al NEJM 2012; 366:2074-84 Al-Batran S-E et al Lancet 2019 393:1948-57 Cunnningham D, et NEJM 2006 355:11-20

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

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? Summary Molecular Biology Based Evidence besides the clinic characteristics- Pt selection ‘Head to Head’ Randomized Study(ies) – needed, but unlikely

Questions?

Thank you!