This network meta-analysis evaluated multidisciplinary treatments for locally advanced gastric cancer using data from 45 randomized controlled trials including over 10,000 patients. The analysis found that HIPEC plus adjuvant chemotherapy was the most effective at reducing recurrence and metastasis. Adjuvant chemotherapy combined with surgery improved overall survival and disease-free survival compared to surgery alone. While chemoradiotherapy reduced recurrence and mortality more than chemotherapy or radiotherapy alone, it also increased severe adverse events.

1. JOURNAL CLUB PRESENTATION
TOPIC: Multidisciplinary treatment for
locally advanced gastric
cancer: A systematic review and
network meta-analysis
Moderator : Dr SAYAID JAMEER SIR
Presenter : Dr RAKSHITH M S
GIMS GADAG

2. • AUTHORS
Zhiyuan Yu, Huaiyu Tu, Shuzhong Qiu, Xiaoyu Dong, Yonghui Zhang,
Chao Ma, Peiyu Li.
PUBLISHED
Journal of Minimal Access Surgery, 10-May-2023
TIME OF STUDY
until October 2021
STUDY DESIGN
Network meta-analysis

3. INTRODUCTION
• Gastric cancer is the third leading cause of cancer deaths and the fifth
most frequently diagnosed cancer
• Radical resection is the primary therapy for gastric cancer patients
• Locally advanced gastric cancer (LAGC) has a poor prognosis even
with experienced radical gastrectomy. Therefore, multidisciplinary
therapy including chemotherapy (CT) and radiotherapy (RT) has been
adopted to improve the treatment outcomes of patients with LAGC.
• Multidisciplinary therapy can be divided into neoadjuvant
(pre-operative) therapy, adjuvant (post-operative) therapy and
perioperative (pre-operative and post-operative)

4. At present
• Adjuvant CT
• Adjuvant RT
• Adjuvant CRT
• Neoadjuvant CT
• Neoadjuvant RT
• Neoadjuvant CRT
• Perioperative CT and
• HIPEC have emerged as multidisciplinary therapeutic methods for LAGC.
Overall survival (OS), disease-free survival (DFS), recurrence and metastasis,
long-term mortality, adverse events, operative complications and R0
resection rate were used as outcome indicators for meta-analysis.

5. PATIENTS AND METHODS
• This study includes 45 RCTs with 10077 participants were finally
analyzed.
Inclusion criteria Exclusion criteria
1. RCTs 1. Case–control studies, cohort studies, review
articles, case reports or meta-analysis
2. Gastric cancer with TNM I–IV (M0) stage 2. Repeated studies
3. LAGC patients received radical gastrectomy 3. Inoperable, recurrent or metastatic gastric cancer
4. Intervention and control groups treated with
different therapies, respectively, which included
surgery alone, adjuvant CT, adjuvant RT, adjuvant
CRT, neoadjuvant CT, neoadjuvant RT, neoadjuvant
CRT, perioperative CT and HIPEC
4. Required outcome indicators were not reported,
such as 5-year OS and DFS, recurrence and
metastasis, long-term mortality, adverse
events (grade ≥3), operative complication or R0
resection rate.

8. RESULTS
• Study selection and study characteristics
- A total of 8376 studies were identified based on retrieval strategy,
and 893 repetitive articles were excluded.
- After reading the titles and abstracts, 524 studies were left.
- Finally 10,077 patients from 45 RCTs were included.
- 12 studies from China and 8 studies from Japan, and the above 20
studies account for almost half of the included studies

10. NETWORK META ANALYSIS
• Possible order of recurrence and metastasis
HIPEC + adjuvant CT< adjuvant CRT< HIPEC< neoadjuvant RT<
neoadjuvant CT< adjuvant CT< adjuvant RT< perioperative CT< surgery
alone.
• Possible order of mortality
HIPEC + adjuvant CT < neoadjuvant CT < adjuvant CRT < adjuvant CT
< perioperative CT < surgery alone < adjuvant RT < neoadjuvant < HIPEC
< neoadjuvant RT

11. • Possible order of adverse events
Surgery alone < HIPEC + adjuvant CT < neoadjuvant CT < adjuvant CT
< perioperative CT < adjuvant CRT
• Possible order of operative complications
Neoadjuvant RT < surgery alone < HIPEC < neoadjuvant <
perioperative CT < adjuvant CT
• Possible order of R0 resection rate
Neoadjuvant RT < perioperative CT < neoadjuvant CT < adjuvant CT <
surgery alone

13. DISCUSSION
• Neoadjuvant therapy is used to degrade or decrease tumor stage and
improve the R0 resection rate of surgery.
• HIPEC and adjuvant therapy mainly aim to reduce tumor recurrence
and metastasis, and prolong the survival time of patients.
• Compared with RT or CT alone, CRT not only enhance the therapeutic
effect but also increase the risk of complications and side effects.

14. • Analysis results of recurrence and metastasis showed that HIPEC + adjuvant
CT seemed to be the best therapy, while surgery alone to be the worst.
• The peritoneum is the main site of distant metastasis of advanced gastric
cancer.
• The synergistic effect of hyperthermia CT, in HIPEC, associated with the
flushing effect of perfusion, could effectively kill and remove cancer cells
and small metastasis tumors in the abdominal cavity, to prevent and treat
intraperitoneal metastasis of gastric cancer.
• Existence of the blood-peritoneal barrier, a high concentration of drugs in
the abdominal cavity will not lead to increased drug concentration in blood
circulation.

15. • CT drugs can not only suppress tumors systematically but also
enhance tumor sensitivity to RT. Therefore, the combination of
adjuvant CT and RT can further improve the local control rate of
advanced gastric cancer while reducing the RT dose.

16. LIMITATIONS
• No direct comparison between many multidisciplinary therapies.
• CT regimens in each study were not identical, leading to
heterogeneity amongst different studies.
• Patients were in locally advanced stages
• Follow-up time for each included study was inconsistent.

17. CONCLUSION
• Adjuvant CT combined with surgery improved OS and DFS than surgery
alone.
• A combination of HIPEC with adjuvant CT seems to be the most effective
adjuvant therapy.
• Compared with CT or RT alone, CRT can reduce recurrence and metastasis,
and mortality, but increase severe adverse events.
• Neoadjuvant RT and CT both can improve R0 resection rate, but
neoadjuvant CT tends to increase surgical complications.