TROD7-8 OCAK 2017

RADISSON BLUE, LISTANBUL

GIS Topics for Banu Atalar, MD

Rectal Cancer: The initial results for a phase III study of short-term versus long-term

chemoradiotherapy in locally advanced rectal cancer (STELLAR trial) Phase I trial of Trametinib and Neoadjuvant 5FU Chemoradiation in Locally

Advanced Rectal Cancer

HCC and liver metastases: Combined Analysis of Two Prospective Trials of Individualized Adaptive

Stereotactic Body Radiation Therapy for the Treatment of Hepatocellular Carcinoma or Liver Metastases

A Pilot Study of Transarterial Chemoembolization Followed by Stereotactic Radiation Therapy for Locally Advanced Hepatocellular Carcinoma

RECTAL CANCER

SHORT vs LONG

Polish Study, 2006

(Bujko,Br J surgery, 2006)

cT3 or cT4 rectal cancer

N=316

5 Gy x 5155 hasta

50.4 Gy+ bolus5-FU+ LV

weeks 1&5 157 hasta

Surgery

7 gn4-6 hafta

4yr LR: short 11% vs CRT 16% (NS)

4yr OS: short 66% vs CRT 67% (NS)

Early Gr 3-4 toxicity higher in CRT arm: 3 vs 18% with NS difference in severe

late toxicity.

KTRT ile downstaging daha fazla

TROG StudycT3N0-N2M0

rectal ACA

50.4 Gy+ CI 5-FU+ surgery

in 4-6 weeks

6 Cycles adjuvant Chemo

SCRT (5 Gy x 5) + surgery in 1

week

4 Cycles adjuvant Chemo

pCR 1% vs 15%

Downstaging28% vs 45%P=0.002

Ngan JCO 2012

Stockholm III (1998-2013)- Toxicity Group 1: SCRT + immediate surgery within 1 week

Group 2: SCRT + surgery at 4-8 wks

Group 3: Conventional RT + surgery at 4-8 weeks

Interim results: no significant differences in postoperative complications between groups (46.6, 40.0 and 32%; P = 0.164).

Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37)

Pettersson Br J Surg 2010

Stockholm trials-Downstaging

Uzun dnem sonularbekleniyor.

Polish Study II, Phase 3, 2016

(Bujko, Ann Oncol, 2016)

cT3 or cT4 rectal cancer

N=514

5 Gy x 5+ FOLFOX x 3

50.4 Gy+ bolus5-FU+ LV

weeks 1&5 (weekly oxali)

Surgery pCR 16% vs 12%

3Y OS 73% vs 65%, p=0.046

LF 22 vs 21% at 3Y p=0.8212 hafta RT-cerrahi

Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer the RAPIDO trial

Primary objective is 3YDFS Secondary objectives

to describe the toxicity profile the rate of completion of preoperative

treatment fraction of patients with a radical

resection (R0) to determine the rate of pathological

complete response (pCR) local recurrence rate after 3 years quality of life (QoL) functional outcome and overall survival

Sweden & The Netherlands

Optimal Timing of Surgery from the end of RT GRECCAR-6 trial cT3-T4, or N+ who recd std CRT Randomized to 7 weeks or 11 weeks until surgery Primary endpoint pCR

Results pCR at 7 wks: 15% and 11 wks: 17% Similar rates of anastomotic leakage More difficulty with perineal wound healing after APR in 11 wks (43%) vs 7 wk

(17%) Higher morbidity and greater surgical complications with waiting 11wks

Lefevre JCO 2016

RECTAL CANCERIst Oral Presentation

The initial results for a phase III study of short-term versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR trial)

AY. Tang1, J. Jin1, S. Li1, N. Li1, Y. Zhu2, S-X. Liu3, W-L. Wang4, J. Wang5, X. Wang6, G-F. Li7, M. Shi8, L. Fan9, K. Zhang10, H. Ren1, Y-X. Li1, H. Fang1, W-H. Wang1, Y-W. Song1, Y-P. Liu1, S-L. Wang1, Y. Tang1, B.

Chen1

Corresponding Author: Jing Jin11Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China2Radiation Oncology, Zhejiang Provincial Cancer Hospital, Hangzhou, China3Radiation Oncology, Jilin Provincial Cancer Hospital, Changchun, China4Radiation Oncology, Guizhou Provincial Cancer Hospital, Guiyang, China5Radiation Oncology, Hebei Provincial Cancer Hospital, Shijiazhuang, China6Radiation Oncology, West China Hospital, Sichuan University, Chengdu, China7Radiation Oncology, Beijing Hospital, Beijing, China8Radiation Oncology, Xijing Hospital, Xian, China9Radiation Oncology, Sichuan Provincial Cancer Hospital, Chengdu, China10Radiation Oncology, Qinghai Red Cross Hospital, Xining, China

Purpose and type of STELLAR trial Purpose

To compare effectiveness of short-course radiotherapy (SCRT) followed by chemotherapy with chemoradiotherapy (CRT) in locally advanced rectal cancer.

Interim analysis Planned when first 100 patients finished TME surgery.

Study typeProspective, Multicenter, Phase III, Open Label, Randomized Study (NCT02533271)

Trial Design

Aged 18-70 Distal or middle third

rectal adenocarcinomas T3-T4 and/or N+ diagnosed by

MRI ECOG PS 0-1 No previous anti-cancer

treatments

Estimated Enrollment: 552Ra

ndom

ize

1:1

Long-term CRT

CAPOX 6#, q21

TME

SCRT CAPOX 4#, q21TM

E

Stratified by status of mesorectal fascia (MRF) : (MRF- vs. MRF+) Non inferiority comparison

Primary Endpoint3y-DFS

Secondary EndpointsOS, LC, DM, Surgical complications, Toxicities, QOL

Control group

Experimental group

Pelvic RT: 45-50.4 Gy /1.8-2.0 GyConcurrent Capecitabine: 825 mg/m2 bid, 5f/w

CAPOX:Capecitabine (1000 mg/m2, bid, d1-14)Oxaliplatin (130mg/m2, d1)

Pelvic RT: 25 Gy /5 Gy

CAPOX 2#, q21

Trial flow chartPotentially eligible n=184

Excluded, did not meetInclusion criteria n=12

Randomised n=172

Allocated to CRT n=84

Allocated to 55Gy + CTn=88

Underneoadjuvant treatment

Experimental n=28 Control n=26

Waiting for surgery

n=13

No surgery n=10

Had finishedneoadjuvant treatment

n=60

Had finishedneoadjuvant treatment

n=58

Received surgery

n=37

Waiting for surgery

n=10

No surgery n=10

Received surgery

n=38

Until September 1, 2016, 172 eligible patients from 10 Chinese hospitals were enrolled Baseline characteristics

Analysis

Toxicities Analysis

Surgery and Histopathology analysis

Results

Baseline characteristics SCRT + CT(N=88) CRT(N=84)No. % No. %

Age in years (range) 57y20-70y 52y34-70yDistance from tumor to anal verge (cm) 4cm0-10cm 4cm0-8cmGender Male

Female6523

73.8%26.2%

6123

72.6%27.4%

Clinic T staging (base on MRI) T1T2T3

T3aT3bT3cT3d

T4

05

659

3816

218

05.7%

73.8%10.2%41.2%18.2%

2.2%20.5%

03

698

3820

312

03.5%

82.1%9.5%

45.2%23.8%

3.6%14.3%

Clinic N staging (base on MRI) N0N1N2

164230

18.2%47.7%34.1%

213825

25%45.2%29.8%

Clinic staging (base on MRI) IIIII

1672

18.2%81.8%

2163

25%75%

MRF status PositiveNegative

3454

38.6%61.4%

3153

36.9%63.1%

MRI: Magnetic Resonance ImagingMRF: Mesorectal fascia

ResultsToxicities related to

neoadjuvant treatmentGrading SCRT + CT(N=60) CRT(N=58)

No. % No. %

Period during 5 5Gy or chemoradiotherapy

01-23-4

29310

48.3%51.7%

0

0553

094.8%5.2%

Period between 5 5Gy and chemotherapy

01-23-4

183012

30%50%20%

NANANA

NANANA

Period during chemotherapy 01-23-4

0537

088.3%11.7%

NANANA

NANANA

Period of all neoadjuvant treatment

01-23-4

04317

071.6%28.4%

0553

094.8%5.2%

NA: not applicable; Grading of toxicities was presented according to CTCAE version 3

ResultsTolerance to neoadjuvant treatment SCRT + CT(N=60) CRT(N=58)

No. % No. %

Dose reduction of radiotherapy 0 0 1 1.7%

Interrupt of radiotherapy 0 0 2 3.4%

Dose reduction of neo-/ concurrent chemotherapy

6 10% 3 5.1%

Delay of neo-/ concurrent chemotherapy 6 10% 0 0

Interrupt of neo-/ concurrent chemotherapy 2 3.3% 0 0

Full-dose completion rate of CRT NA 54 93.1%

Full-dose completion rate of SCRT + CT 52 86.6% NA

NA: not applicable

ResultsTreatment after neoadjuvant

radiotherapy or chemotherapySCRT + CT(N=60) CRT(N=58)

No. % No. %

Radical surgery 37 61.7% 38 65.5%

Wating for surgery 13 21.6% 10 17.2%

Wait and watch due to CCR of tumor 7 11.7% 0 0

Refuse to surgery 3 5% 6 10.3%

Additional chemotherapy due to unresectable tumor

0 0 2 3.5%

Recurrence (LR or DM) 0 0 3 5%

CCR: clinic complete responseLR: local recurrenceDM: distant metastasis

Surgery and Histopathology SCRT + CT(N=37) CRT(N=38)No. % No. %

Operative model Anterior resectionAbdominoperineal resectionHartmanns

15211

40.5%56.7%2.8%

16220

42.1%57.9%

0

R0 resection YesNo

343

91.9%8.1%

344

89.5%10.5%

pCR rate 9 25.7% 3 7.9%Duration of operation (min, range) 196min90-500min 184min90-345min

Amount of bleeding during operation (ml, range) 50ml20-200ml 30ml20-200ml

Time from operation to liquid diets (day, range) 5.5d3-9d 6d3-9d

Time from operation to leaving hospital (day, range) 8d7-11d 8d6-14d

Reoperation 00% 12.6%

pCR: pathologic complete responsepCR(9) + cCR(7) =16

Results

Lokal ileri rektum kanserinde Preoperatif 55Gy RT ve takiben KT: