1. Adjuvant Radiation is Required for Gastric Cancer
Christopher H. Crane, M.D.
Professor, Program Director GI Radiation Oncology

2. With no Adjuvant: Local Recurrence: Dominant POF Minnesota Second-look Laparotomy Series
Tumor Bed
Nodal
LRF only 24/82 (29%)
LRF + DM 72/86 (84%)
Gunderson, IJROBP (8), 1-11, 1981

3. Adjuvant Chemotherapy Ineffective Meta-analysis
20 studies (3658 pts, 2180 deaths)
Chemotherapy reduced the risk of death by 18% (HR=0.82; p<0.001)
Absolute advantage in survival: stage I: 80% 82% stage II: 50% 54% stage III: 20% 24%
Results similar to earlier meta-analysis by hermans (1993) in which HR was 0.88 ( )
Mari et al.Annals of Oncology,2000

4. MAGIC trial : Post-op Chemo Poor Compliance
In the chemo arm
86% completed pre-operative chemotherapy
91% of pts who started pre-operative chemo completed all 3 cycles
57% commenced post-operative chemotherapy and 43% completed all 6 cycles
The main reasons for failing to start post-operative chemo were death, progression, pt request and post-op complications

5. Randomized Data Adjuvant Gastric Ca / GEJ
CXRT vs CTX alone
Artist Trial
Stahl Trial

6. ARTIST
Phase III multi-institutional RCT comparing adjuvant chemoradiation vs. chemotherapy in patients with a D2 dissection
All Patients
Patients with stage Ib-IVa Gastric cancer resected with D2 dissection
Randomized to
Chemotherapy (XP)
N= 228
Xeloda 1000mg/m2 bid, CDDP 60mg/m2 on day 1
6 cycles
CRT
N = 230
XP x 2 45 Gy in 25 fractions + xeloda 825 mg/m2 bid  XP x 2
P =
N +
P =
Lee J et al. JCO 2012

7. ARTIST Trial Trend towards significant improvement in DFS (p = 0.086)
Larger numbers could have shown benefit
Significant improvement in DFS with CRT in N+ patients
Different patient population (primarily from Asia)

8. Overall survival (intent to treat).
Preoperative Chemotherapy vs Chemoradiation
GEJ ACa
Overall survival (intent to treat).
Overall survival (intent to treat). Arm A, n = 59 (chemotherapy and surgery): median survival time 21.1 months, 3-year survival rate 27.7%. Arm B, n = 60 (chemoradiotherapy and surgery): median survival time 33.1 months, 3-year survival rate 47.7%.
Stahl M et al. JCO 2009;27:
©2009 by American Society of Clinical Oncology

9. Intergroup Study INT-0116 Study designA N D O M I S E
5FU/LV
5FU/LV
Eligibility:
Resected
Stage IB- VI M0
5FU/LV
RADIATION
5FU/LV x 2
4,500 cGy
Gastric or
gastroesophageal
adenocarcinoma
OBSERVATION
Macdonald et al. NEJM, 345 (10): 725,2001

10. Patient Characteristics
Groups appear well matched
~ 70% were T3-T4
85% Node Positive
80% were distal stomach lesions

11. Results Initial Results (4 year f/u)
Median OS 39 vs. 27 m.o.
3-yr OS 50% vs 41%
3-yr RFS 48% vs 31%
Updated Results (> 10 year f/u)
HR for OS 1.32
HR for RFS 1.51
P =
P <
Macdonald et.al NEJM 2001
Smalley S R et al. JCO 2012

12. INT-0116 SURGICAL PROCEDURES < D1 = 54% D1 = 36% *D2 = 10%
(Based on 551 cases)
< D1 = 54%
D1 = 36%
*D2 = 10%
•No difference in overall survival by extent of dissection
*D2 lymph node dissection was recommended

13. Toxicity Grade 3 events 3 deaths from toxicity reported
33% GI
54% hematologic
3 deaths from toxicity reported
Only 65% of patients completed CRT
50% of these secondary to treatment toxicity

14. Conclusions: INT 0116 Less than a D1 most common
Adjuvant ChemoRT improves OS and DFS
Less than a D1 most common
Pt toxicity “acceptable”
Pivotal trial establishing chemoradiation as standard of care in United States

15. Conclusions Stahl Trial: Pre-op CXRT standard for GEJ Ca Artist Trial:
OS benefit with CXRT vs CTX
Artist Trial:
Post-op CXRT necessary for N+
XRT debatable for N0/D2 dissection
Minority of patients
Best results with pre-op CTX, post-op CXRT?
Critics Trial, stay tuned