Adjuvant chemotherapy had been offered to patients who had been referred from elsewhere within 8 weeks’ post-surgery with adequate D2 lymphadenectomy. Patients who presented with tumour bleeding or perforation were also offered adjuvant chemotherapy after upfront gastric surgery. Similarly, to distal gastric cancer patients who presented with gastric outlet obstruction, upfront surgery was advised with adjuvant chemotherapy. All remaining patients were offered perioperative chemotherapy.
Regarding chemotherapy options, the patients in perioperative group A received Epirubicin, Cisplatin, Fluorouracil (ECF) or Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT), while those in adjuvant chemotherapy group B received Capecitabine and Oxaliplatin (CAPOX) regimen. ECF, FLOT,12 CAPOX11 regimens were in line with literature.
The primary outcomes were OS and DFS. The OS was defined as the length of time from the date of diagnosis till the last follow-up or death, and DFS as the length of time from the date of last treatment to tumour relapse or death. The median OS or DFS was defined as the point at which 50% of the population had not encountered the event, which was death in case of OS and progression in that of DFS.
Data was analysed using SPSS 23. Since the data was skewed, continuous data was expressed as median and interquartile range (IQR), while categorical data was expressed as frequencies and percentages. Survival data was calculated using Kaplan-Meier survival to determine differences between the two groups. The end points of interest were death and progression for OS and DFS, respectively. Survival plot and Log rank test were employed using the Kaplan-Meier analysis. P<0.05 was considered statistically significant.
Of the 520 cases of gastric cancer, 108(20.7%) formed the sample for the current study; 71(65.74%) being male subjects. The aga range was 27-80 years. The overall median age was 49.50 years (IQR: 28 years). There were 69(63.88%) patients in perioperative chemotherapy group A and 39(36.12%) in adjuvant chemotherapy group B (Table 1). At the time of analysis, in September 2021, the median follow-up for both groups was 28 months (IQR: 27.50 months).
There were 48(44.4%) patients who died; 17(35.41%) in group B, and 31(64.58%) in group A. Disease progression was found in 55(51%) cases; 23(41.81%) in group B and 32(58.18%) in group A. The probability of 2- and 3-year OS was 68.20% and 57.32% in group A, and 51.09% and 45.43%, respectively, in group B. The probability of 2- and 3-year DFS was 55.45% and 49.30% in group A, while 2-year DFS was 38.39% in group B which had no patient reaching the 3-year mark. The median OS for group A was 49.29 months (IQR: 44.50 months) and for group B it was 28.23 months (IQR: 25.00 months) (p=0.07). The median DFS was 35.46 months (IQR: 38.50 months) for group A and 10.19 months (IQR: 14.00 months) for group B (p=0.16) (Table 2).
Kaplan-Meier survival curve for OS (Figure 1) and DFS (Figure 2) expressed similar data.
Gastric surgery is the only curative treatment for locoregional gastric cancer.13 Patients with resectable gastric adenocarcinoma are treated with perioperative chemotherapy or adjuvant chemotherapy to achieve downstaging and elimination of micro-metastasis, respectively. To the best of our knowledge, the current study is the first presenting local retrospective comparative data of perioperative and adjuvant chemotherapy in operable gastric cancer.
The findings demonstrated a trend towards better OS and DFS with perioperative chemotherapy, though it was not statistically significant. This goes well with data from Europe and North America.14
In a study, ECF and FLOT were compared and the median OS was 50 months, while 2- and 3-year OS was 59% and 48%, respectively, and the median DFS was 30 months.12 The corresponding data in the current study was 49.29 months, 68.20%, 57.32% and 35.46 months. The difference could be due to younger age group in the current study and a smaller sample size compared to the earlier study.12 Gastric cancer is a disease of younger age in Asia.15
Another study10 showed superior results with perioperative ECF chemotherapy compared to the current study. Again, age of the subjects and the size of the sample could be the important variants.16
A meta-analysis reported statistically significant adjuvant chemotherapy benefits with respect to OS and DFS.17 Another meta-analysis favoured perioperative group compared to the adjuvant chemotherapy group even though there was no difference in 1- and 2-year survival between the groups.18
One study reported better response in DFS terms when patients were given adjuvant chemotherapy along with surgery compared to those who had surgery alone.11 The 3-year DFS for the adjuvant chemotherapy patients was 65%, while in the current study no patient in the adjuvant therapy group was able to reach the 3-year DFS point. The variance can be due to the difference between the sample sizes, as other study had 520 subjects11 compared to 39 in adjuvant arm of the current study.
Another study compared perioperative chemotherapy with adjuvant chemotherapy,19 with those in the perioperative group showing significant increase in OS and DFS compared to the adjuvant group, which is a finding similar to that of the current study.
There are limitations in the current study as the two groups were not equal in number and the sample size was limited. Also, the retrospective data has an inherent risk of bias. Ethnicity is a critical factor in this regard, but no comparable data could be found related to south Asian population. Moreover, treatment-related adverse events and dose reduction due to toxicity in both the arms of treatment were not documented in the current study.
A prospective, comparative study is recommended to further enhance understanding and improve the care of gastric cancer patients.
In operable gastric cancer cases, the difference between the groups was not significant, but there was a trend suggestive of the superiority of perioperative chemotherapy over adjuvant chemotherapy with respect to OS and DFS.
Conflict of Interest: None.
Source of Funding: None.
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