Abstract
Gastric cancer (GC) is common in the northeast and southern parts of India. Radical surgery is the cornerstone of treatment and offers the only chance for cure. This study was conducted to assess the outcomes of all resectable gastric cancers that presented to our tertiary cancer center in Northeast India. All patients undergoing upfront surgery for gastric cancer with curative intention between 2012 and 2017 were included in the study. A total of 116 patients who underwent upfront radical gastrectomy were included in the study. Males (58.6%) were more common than females (41.4%). Mean age at presentation was 56.12 years (range 26–89). The most common mode of presentation was pain abdomen (53.8%). The most common location of tumor was the distal part (81%) followed by the proximal part (10.3%). The most commonly done procedure was distal radical gastrectomy (56.9%) followed by subtotal gastrectomy (32.8%). Median number of lymph nodes isolated was 14. Fifty-four patients received adjuvant chemotherapy while 32 patients received adjuvant chemoradiation (CTRT). At a median follow-up of 14 months (range, 2–78 months), overall 5-year survival was 23.75% (mean survival 33.77 months, median survival 24 months). The 5-year survival for stages I–III was 100%, 26.25%, and 11.25%, respectively (P < 0.001). Though perioperative chemotherapy has a role in gastric cancer, it is not the substitute for radical D2 gastrectomy which is still the gold standard treatment especially in high-volume centers.
Keywords: MAGIC trial, D2 lymph node dissection, Perioperative chemotherapy, ACCORD 07 trial, Gastrectomy
Introduction
Adenocarcinoma of the stomach was the leading cause of cancer-related death worldwide through most of the twentieth century. It now ranks second only to lung cancer; an estimated 952,000 new cases are diagnosed annually, and an estimated 723,000 deaths (10% of all cancer deaths) worldwide [1]. Gastric cancer (GC) is common in the northeast and southern parts of India, although incidence in India is low compared with that in western countries and China [2–4]. Since the publication of the MAGIC [5] trial which showed a 13% improvement in 5-year survival with perioperative chemotherapy (36% vs 23%), many hospitals have adopted this approach for treatment gastric cancers. Still, radical surgery is the cornerstone of treatment and offers the only chance for cure. This study was conducted to assess the outcomes of all resectable gastric cancers that presented to our tertiary cancer center in Northeast India.
Materials and methods
It is a retrospective study. All patients undergoing upfront surgery for gastric cancer with curative intention between 2012 and 2017 were included in the study. Data were collected from the prospective database maintained by the Department of Surgical Oncology at Dr. B. Borooah Cancer Institute, Guwahati. The analysis was done using the Statistical Package for Social Sciences 21.0 (SPSS Version 21.0).
Results
A total of 224 patients were undergone surgery for gastric cancer. Out of which, gastrojejunostomy (GJ), feeding jejunostomy (FJ), and palliative gastrectomy were done in 66, 11, and 12 patients, respectively. The rest of the patients underwent radical gastrectomy, in which 116 patients were taken up for upfront surgery. Neoadjuvant chemotherapy (NACT) was given in 19 patients. A total of 116 patients who underwent upfront radical gastrectomy were included in the study.
Males (58.6%) were more common than females (41.4%). Mean age at presentation was 56.12 years (range 26–89). The most common mode of presentation was pain abdomen (53.8%). The most common location of tumor was the distal part (81%) followed by the proximal part (10.3%) (Table 1). The most commonly done procedure was distal radical gastrectomy (56.9%) followed by subtotal gastrectomy (32.8%). Median number of lymph nodes isolated was 14. Fifty-four patients received adjuvant chemotherapy while 32 patients received adjuvant chemoradiation (CTRT) (Table 2).
Table 1.
Clinicopathological factors
| Characteristics | Results |
|---|---|
| Age (mean years) | 56.12 (26–89) |
| Sex | |
| Male | 68 (58.6%) |
| Female | 48 (41.4%) |
| Location of tumor | |
| Proximal | 12 (10.3%) |
| Middle | 10 (8.6%) |
| Distal | 94 (81%) |
| Main presentation | |
| Pain abdomen | 62 (53.4%) |
| Vomiting | 26 (22.4%) |
| Gastric outlet obstruction (GOO) | 23 (19.8%) |
| Bleeding | 05 (4.3%) |
| T stage | |
| T1 | 2 (1.7%) |
| T2 | 22 (19%) |
| T3 | 38 (32.8%) |
| T4 | 54 (46.6%) |
| N stage | |
| N0 | 44 (37.9%) |
| N1 | 14 (12%) |
| N2 | 36 (31%) |
| N3 | 22 (19%) |
| TNM stage | |
| Stage 1 | 12 (10.3%) |
| Stage 2 | 52 (44.8%) |
| Stage 3 | 52 (44.8%) |
| Grade of tumor | |
| Well differentiated | 40 (34.5%) |
| Moderately differentiated | 44 (37.9%) |
| Poorly differentiated | 32 (27.6%) |
Table 2.
Treatment and outcome-related factors
| Variables | Results |
|---|---|
| Type of surgery | |
| Distal gastrectomy | 66 (56.9%) |
| Subtotal gastrectomy | 38 (32.8%) |
| Total gastrectomy | 12 (10.3%) |
| Lymph nodes harvested |
13.2 (mean) 14 (median) |
| Follow-up (in months) |
20.53 (mean) 14 (median) |
| Complications (Clavien–Dindo grade) | |
| Grade I | 12 (10.3%) |
| Grade II | 8 (6.9%) |
| Grade III | 6 (5.2%) |
| Grade IV | 4 (3.45%) |
| Grade V | 4 (3.45%) |
| Median hospital stay (in days) | 9 (5–42) |
| Overall survival (in years) |
33.77 (mean) 24.0 (median) |
| Resection | |
| R0 | 111 (95.68%) |
| R1 | 5 (4.3%) |
| Adjuvant therapy | |
| Chemotherapy | 54 (46.55%) |
| Chemoradiation | 32 (27.58%) |
| 5-year survival | |
| Overall | 23.75% |
| Stage 1 | 100% |
| Stage 2 | 26.25% |
| Stage 3 | 11.25% |
At a median follow-up of 14 months (range, 2–78 months), overall 5-year survival was 23.75% (mean survival 33.77 months, median survival 24 months). The 5-year survival for stages I–III was 100%, 26.25%, and 11.25%, respectively (P < 0.001) (Table 2; Fig. 1).
Fig. 1.
1 Kaplan Meier Curve(a) For overall survival. (b) According to TNM stage.Time (in months)
Discussion
Surgical resection of the primary tumor and regional lymph nodes is the cornerstone of treatment for patients with localized gastric cancer. In our study, only 19 patients (14%) received NACT. Major reasons for not giving NACT were the poor performance status, presenting as partial or total GOO, bleeding, etc. The tolerability to chemotherapy in our patients is not the same as that for western patients. In our institute, NACT is given when there is loss of fat plane with adjacent organs mainly pancreas and if there is large nodal disease. Shrikhande et al. [6] reported that up to 40% patients did not receive NACT due to emergency presentation or early-stage disease. We believe that real clinical practice is different in different countries and decisions are based on what is best in that scenario.
The observation that gastric cancer commonly remained localized to stomach and adjacent lymph node corroborates the Japanese view that radical systemic D2 lymphadenectomy has an increased survival benefit [7]. Excision of the primary lesion with omentum, and N1 and N2 lymph nodes can cure patients even in presence of lymph node metastasis [8, 9]. The extent of lymphadenectomy in the treatment of gastric cancer is still controversial. Radical gastrectomy with D2 lymphadenectomy, introduced by Japanese surgeons, offers survival advantage and is the current standard of care for nonmetastatic, resectable gastric cancer [10–12].
The Medical Research Council (MRC) D1 versus D2 lymphadenectomy trial concluded in 1999 that the classical Japanese D2 had no survival benefit over D1. However, D2 resection without pancreaticosplenectomy may be better than standard D1 [9, 13]. The Dutch D1D2 trial 15-year results of 2010 demonstrated an overall survival in 15 years of 21% in D1 and 29% in the D2 group.
Local recurrence was 22% in the D1 group versus 12% in the D2 group. Operative mortality of D2 was significantly higher, 10% versus 4%, and complication rate was 43% and 25% in D2 and D1 groups, respectively. In total, 20% of the D2 group with N2 nodes were still alive at 11 years, unlikely if D1 alone was performed [8]. Overall D2 has lower locoregional recurrence and gastric cancer–related death rates. It has significantly higher postoperative mortality, morbidity, and reoperation rates. Spleen preserving D2 resection is thus recommended for resectable gastric cancer [8, 9, 14].
The extent of resection is determined by the location of the tumor. Prospective, randomized trials failed to demonstrate a survival advantage for total gastrectomy over distal, subtotal gastrectomy for patients with tumors of the distal stomach [15]. Nonetheless, a total gastrectomy should be performed if necessary to achieve an R0 resection, as positive resection margins (R1 resections) lead to a very poor survival. In the Dutch gastric cancer trial, 10% of patients had a positive resection margin and a correspondingly inferior 3-year survival (18% vs 63%) compared with those who had a negative resection margin [16]. For proximal gastric cancers, at our institute, we perform total gastrectomy over a proximal gastrectomy.
Two well-conducted randomized trials, i.e., MAGIC [5] and ACCORD 07 [17], have established the role of preoperative systemic chemotherapy in gastric cancer. Only approximately one-third of patients in these trials underwent D2 lymph node dissection; it is unclear the extent of impact of lymph node dissection on the results. We routinely perform D2 lymph node dissection at our center which is the largest and high-volume center of northeast India.
Most of our patients present with symptoms of absolute or partial gastric outlet obstruction, melena, or hematemesis. Therefore, upfront surgery is beneficial in these patients. Though extranodal extension gives inferior results, it is identified mostly in postoperative histopathology. Poorly differentiated tumor also does badly in upfront surgery group, and we have started doing diagnostic laparoscopy in these patients before initiation of treatment. We are doing one study at our center to see the benefit of doing diagnostic laparoscopy in gastric cancer
Overexpression or amplification of Her2 neu occurs in approximately 20% of patients with gastric cancer; it varies with the subtype, being more common in intestinal type tumors. In ToGA trial, the median OS was 13.8 months for patients receiving trastuzumab plus chemotherapy versus 11.1 months for those receiving chemotherapy alone (HR, 0.74; P = 0.0046). At our center, the Her2 neu study is done in few selected patients of gastric cancer only because of financial constraint.
We have not compared with any other population and tried to show our own data from largest cancer center from northeast India. Our disease is sporadic and high grade and distal lesions are more common.
Conclusion
Though perioperative chemotherapy has a role in gastric cancer, it is not the substitute for radical D2 gastrectomy which is still the gold standard treatment especially in high-volume centers.
Footnotes
Publisher’s Note
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