In this ppt we will learn about trials and 2d radiotherapy planning of carcinoma stomach.

1. STOMACH CANCER 2D
AND TRIALS
PRAGATHEESWARI G K

2. SURGERY – D1 /D2 ?
• The Dutch Gastric Cancer trial
• Sogun et al
• 1989 – 1993
• 711 patients
• Gastric adenoca
• D1 vs D2 resection
• Follow 15 .2 years

3. • 15 YR OS – 21% VS 29% D1 Vs D2
P VALUE- 0.34
• Death due to gastric cancer is low in D2 dissection
• P value ( 0.01)
• Death due to other cause is low in D2 dissection
• P value (0.12)
• Conclusion – local control, regional recurrence ,liver
metastasis ,death due to cancer , were significantly
low in D2 dissection and hence preferred.

4. PERIOP CHEMO VS SURGERY
ALONE
• MAGIC trial
• 1994- 2002
• 503 patients
• Surgery Vs periop chemo & surgery
• peri op chemo arm - 3 cycles of ECF before and 3 cycles after surgery given
• ECF – Epirubicin , cisplatin , 5FU

5. Results :
the median tumor diameter shrink from 5 to 3 cm pvalue <0.001
Less advanced pathological nodal disease p < 00.1
5 yr os – 13% increase
25 % reduction in death in perop chemo ar
Conclusion ;
• peri op chemotherapy is better than surgery alone in gastric cancer .

6. ECF FLOT
cT2 or
higher or N+
M0

7. ECF /ECX
• 360 Patient
• to receive either three pre-
operative and three
postoperative 3-week cycles of
• 50 mg/m2 epirubicin and
• 60 mg/m2 cisplatin on day 1 plus
• either 200 mg/m2 fluorouracil
as continuous intravenous
infusion ECF
• or 1250 mg/m2 capecitabine
orally on days 1 to 21 ECX
FLOT
• 356 patients
• four preoperative and four
postoperative 2-week cycles of
• 50 mg/m2 docetaxel,
• 85 mg/m2 oxaliplatin,
• 200 mg/m2 leucovorin and
• 2600 mg/m2 fluorouracil as 24-h
infusion on day 1

8. ECF
• Median survival –
• 50 month
• Toxicity – 27%
FLOT
• Median survival –
• 35 months
• Toxicity -27%
In locally advanced, resectable gastric or gastro-oesophageal
junction adenocarcinoma, perioperative FLOT improved overall
survival compared with perioperative ECF/ECX.

9. In locally advanced,
resectable gastric or
gastro-oesophageal
junction
adenocarcinoma,
perioperative FLOT
improved overall
survival compared with
perioperative ECF/ECX.

10. • Peri op chemo is better than surgery
• So now
• pre op chemo – surgery – post op chemo RT
along with chemo
• Is beneficial or not ?
• CRITICS TRIAL

11. CRITICS I – ChemoRadiotherapy After
Induction ChemoTherapy In Cancer Stomach I
• 2007 – 2015
• 788 patients
• Arm A- Chemo +surgery +chemo
Vs
• Arm B- chemo +surgery + chemoRT
• Surgery – curative , chemo – ECF , RT - EBRT 45Gy
• median OS 43 months vs 37 months p = 0.90
• 5yr SR 42% vs 40%
• CONCLUSION : no significant benefits between two
arms.

12. ADJUVANT CHEMOTHERAPY
• GASTRIC – (Global Advanced/Adjuvant Stomach Tumor
Research International Collaboration) group
• Meta analysis of 17 trials
• Adjuvant chemotherapy vs surgery alone
• Adj chemo – Fluoropyrimidine group
• Follow up 7 years
• 5 year OS 49.6% vs 55.3%
• P – 0.001 significant
• Conclusion – post operative chemotherapy with
fluorouracil based regimen shows survival benefits than
surgery alone.

13. CLASSIC -
• AIM: To evaluate effect of adjuvant chemotherapy with
capecitabine and oxaliplatin after D2 gastrectomy in gastric
cancer
• . Done in Korea China & Taiwan
• Stage Ib-IVA
• • Curative D2 gastrectomy was carried out within 6 weeks before
randomisation.
• At least 15 lymph nodes were examined to ensure adequate
disease classification

14. • Eight 3-week cycles of
Capecitabine (1000 mg/m2
BID on D1-14)
• IV Oxaliplatin 130 mg/m2 on
D1
• Only 67% of the pts in the
chemo arm received all 8
cycles of chemotherapy
• 90% patients dose
modifications vio adverse
events
1035patients
515 patients –
surgery alone
520 – sx f/b
adj chemo

15. • Conclusion – adjuvant treatment with capecitabine
plus oxaliplatin after D2 gastrectomy should be
considered for operable stage II or stage III gastric
cancer
3yr
DFS
3YR OS 5YR OS 5YR DFS
ADJ
CHEMO
74% 83% 78% 68%
SURGERY
ALONE
59% 78% 69% 53%
P VALUE <0.001 0.0493 0.0015 <0.001

16. Macdonald et al
• 556 patients randomly assigned
• to surgery plus postoperative chemoradiotherapy
• Vs
• surgery alone.
• The adjuvant treatment:
• 425 mg 5FU, plus 20 mg for five days,
• 45Gy/ 25# /1.8Gy with fluorouracil and leucovorin
• One month after the completion of radiotherapy, two
five-day cycles of fluorouracil 425 mg plus leucovorin

17. Post operative chemo radiotherapy is given for
patients with high risk features, gastric
carcinoma
Surgery alone
• Median survival – 27
months
Surgery + adj chemo RT
• Median survival 36
months
• P<0.001

18. ARTIST

19. • Treatment was completed as planned by 75.4% of patients in the
XP arm and 81.7% in the XP/XRT/XP arm.
• Overall, the addition of XRT to XP chemotherapy did not
significantly prolong disease-free survival (DFS; P = .0862).
• in the subgroup of patients with pathologic lymph node
metastasis at the time of surgery (n = 396), patients randomly
assigned to the XP/XRT/XP arm experienced superior DFS when
compared with those who received XP alone (P = .0365), and the
statistical significance P = .0471).
• CONCLUSION :
• The addition of XRT to XP chemotherapy did not significantly
reduce recurrence after curative resection and D2 lymph node
dissection in gastric cancer.
• A subsequent trial (ARTIST-II) in patients with lymph node-positive
gastric cancer is planned.

20. After surgery adjuvant RT /
observation ?
SWOG - Intergroup trial 0116
• Between 1991 – 1998
• 559 patients
• T3 or higher, N+ disease
• Surgery alone Vs Surgery f/b adj chemo RT
• Adj arm – bolus FU , Leucovorin before , during and
after radiation therapy

21. Relapse status Surgery Surgery plus chemoRT
No relapse 24% 48%
Local 8% 2%
regional 39% 22%
Distant mets 18% 16%
Relapse free survival p – 0.001
Overall survival p- 0.004
Conclusion – in locally advanced cancer ADJUVANT CHEMO RT IS
BENEFICIAL THAN SURGERY ALONE.

22. TOGA - trastuzumab in gastro
oesopgaheal cancer
• In Her 2 neu positive inoperablelocally advanced
tumors, recurrence, metastatic adeno carcinoma
• Stomach and GE junction
• 594 patients
• 2005 – 2008
• Chemo vs chemo plus trastuzumab
• Median survival = 11 months vs 13.8months p = 0.0046
• Death rate decrease by 26% while adding trastuzumab.
• trastuzumab in Her 2 neu positive tumors – CAT 1

23. Key note 012
• 2013- 2014
• Advanced gastric and GE junction tumors
• Unresectable
• PDL1 positive tumors
• No discontinuation of therapy
• Overall response was noted in 22% patients.
• Pembrolizumab can be safely administered in these
patients.
• Now NIVOLUMAB is used in PDl_1 positive tumors (CAT
1)

24. FU in GIT tumors
• Moertal et al
• 1969
• 48 patients
• Unresectable gastric tumors
• 35 – 40Gy RT + 5 FU vs RT alone
• Median survival – 13 months vs 5.9 months p
<0.01
• FIRST TRAIL to demonstrate the benefit of FU in
GIT tract cancers

25. 2D

26. PATTERN OF RECURRENCE
• It is important the we know the pattern of
recureence , so that we ensure the proper
coverage in fields.

28. TARGET VOLUME
Post op :
pre treatment diagnostic studies ( EUS, OGD, PET , CT
SCANS ) to identify the the tumor and nodal groups
and CLIP PLACEMENT TO IDENTIFY THE TUMOR,
GASTRIC BED, ANASTOMOSES, STUMPS
● The treatment of remaining stomach should
depend on balance of normal tissue morbidity at the
risk of local failure in the relapsed stomach

29. • Position –supine
• Portals –
• AP –PA
• Dose 50.4Gy
/28#/1.8Gy /#
• Shielding – 2/3 of right
kidney, left kidney ,
liver

30. BORDERS
• SUPERIOR - Bottom of T8 or T9 to cover celiac
axis, GE junction, fundus, and the dome of left
hemidiaphragm
• INFERIOR - Bottom of L3 to coveR
gastroduodenal nodes and antrum
• LEFT -Include two third to three Fourth of left
hemidiaphragm to cover fundus,
suprapancreatic nodes and splenic nodes
• RT LATERAL-3 to 4 cm lateral to vertebral
bodies to cover the antrum, porta hepatis, and
gastroduodenal nodes
• Dose of RT-45-50Gy/25#/5weeks, 1.8-2Gy/#

31. MODIFICATIONS
• To reduce spinal cord dose
• AP / PA with more weightage to anterior portal
• Four field technique
• Posterior oblique portals

32. SEQUELAE OF THERAPY
• Anorexia, nausea, and fatigue - very common.
• Nutritional complications and myelo-suppression-especially in CRT
• Need careful nutritional support councelling and antiemetic therapy.
• Blood counts monitoring twice weekly during CRT to avoid sepsis or
bleeding.
• Achlorohydria -
• 16 to 36 Gy reduce secretion of pepsin and HCL (25% to 40%)
persisting 1 to 6 m, with 25% upto 1 to 5 yrs or more.
• Gastric late effects categorized by the Walter Reed Group
 dyspepsia,
 radiation gastritis,
 uncomplicated gastric ulcer,
 gastric ulcer with perforation
 obstruction

33. REFERENCE
• PEREZ ONCOLGY 7TH EDITION
• NCCN GUIDELINES
• DOBBS 3RD EDITION RADIOTHERAPY PLANNING

34. ACKNOWLEDGEMENT
Senior Assistant professor –
Dr.B.Grace mercy priscilla DMRT,MDRT
Professor –
Dr.B.Antoinette Mary Nithiya Dch,MDRT

35. THANK YOU