2Department of Surgery, Hofstra-NSLIJ School of Medicine, New Hyde Park, NY
3Department of Biostatistics, Feinstein Institute of Medical Research, North Shore University Hospital System, Manhasset, NY.
Methods: Data was collected from a tertiarycare hospital tumor registry and a total of 297 patients with gastric cancer were analyzed. Based on the date of surgery, these 297 patients were divided into Group 1(1990-2000)with 169 patients and Group 2 (2001-2010)with 128 patients.The Kaplan-Meier method was used for survival analysis and the curveswere compared using the log-rank test.
Results: Incomparing data between the two decades, average number of nodes dissected was 10 in group I while it was 15 in group II. The main difference between both groups,however,was an improved 5-year survival of 47% in Group II vs. 29% in Group I. Also significant was the fact that 49% of patients had stage 3+ disease at diagnosis in Group 1, compared to 30.4% in Group 2 (p<0.001/0.0089).No microscopic evidence of tumor at the margins of resection was found in 82% of patients in both groups. Although there was no statistical significance, there was a trend towards increased use of adjuvant chemo-radiation in Group II.
Conclusion: Our study demonstratesan improvement in survival over the last decade in patients with gastric cancer.This trend seems to be as a result of early diagnosis of gastric cancer, negative resection margins and more radicalnodal dissection.
2.Histological type: Patients with gastric adenocarcinoma, acinar cell carcinoma, carcinoid with adenocarcinoma, small cell carcinoma, large cell carcinoma, tumor cells of uncertain origin, and squamous cell carcinoma.
2.Gastroesophageal junction tumors.
A total of 297 patients were included in the final analysis of our study. Based on the date of surgery, these patients were then divided in to two groups: Group I (n=169), including patients who had surgery between January 1, 1990 to December 31, 2000, and Group 2 (n=128), including patients who had surgery between January 1, 2001 to December 31, 2010.
Standard methods of survival analysis were applied to the data, i.e., computing the Kaplan-Meier [6] product limit curves, where different stratification groups were used in each analysis. In cases where the subject was alive or lost to follow-up, the number of months until last follow-up was used and considered censored. Groups were compared using the log-rank test. Median survival rates for each group were obtained from the Kaplan- Meier/Product-Limit Estimates and their corresponding 95% confidence intervals were computed, using Greenwood's formula [7] to calculate the standard error.
A separate multivariate Cox proportional hazards model was developed for Group I (1990-2000) and Group II (2001- 2010) using backwards selection to evaluate the independent influences of prognostic factors on survival. Hazard ratios (HRs) and associated 95% confidence intervals were calculated. The variables included in the selection process were: age, sex, race, smoking history, alcohol history, pathological stage, number of nodes examined, margins, depth of invasion, and type of gastrectomy. It was determined that pathological stage was a linear combination of tumor invasion (T), node status (N), and distant metastasis (M), and therefore, these variables were not included in the selection process. The proportional hazards assumption was assessed and martingale residual plots analysis was applied to check the functional form of continuous variables. A result was considered statistically significant at the p<0.05 level of significance. All analyses were performed using SAS version 9.3 (SAS Institute Inc., Cary, NC).
Detailed information on patient demographicsis listed in Table 1. As shown in the table, there were no differences with respect to gender between the two groups. Race was a statistically significant factor between the two groups with patients in Group I predominantly whites and had higher prevalence of smoking while group II had more non-white patients (included African Americans, Hispanics, Asians and others), with more prevalent history of alcohol use.
The two groups were also analyzed based on the type of gastrectomy, TNM staging, depth of invasion, margin status and the number of nodes examined. Table 2 depicts the staging based on AJCC 6th edition. Based on the above data, the T status was statistically significant across both groups. T3 tumors were predominant in Group I(45.2% vs 24.2%) while group II predominantly had T2 disease (26.8% vs 38.3%; p= 0.0033). Similarly, group I had more patients with stage 3A cancer (28.6% vs 11.2%)while group II had more patients with stage 2 cancer (21.7% vs 25.6%) and this difference was statistically significant across the groups (p=0.0157).
More patients in group II underwent partial / subtotal gastrectomy compared to group I (60% vs 33.7%), while the number of total / radical gastrectomy remained the same. Although, this was statistically significant (p 0.0001), 47.9% patients in group I and 21% of group II patients underwent undefined extent of gastrectomy that could not be delineated from the data available. Considering overall stages, 49% of patients had Stage 3+ disease at diagnosis in Group 1, compared to 30.4% in Group 2 (p<0.001/0.0089). An R0 resection (no microscopic evidence of tumor) was achieved in 82% of patients across the groups.
|
1990-2000 |
2001-2010 |
|
||
|
N |
% |
N |
% |
p-value |
Sex |
|
|
|
|
|
Male |
111 |
65.68 |
84 |
65.63 |
0.9920 |
Female |
58 |
34.31 |
44 |
34.38 |
|
Race |
|
|
|
|
|
Whites |
141 |
83.43 |
84 |
65.63 |
0.0004 |
Non-whites |
28 |
16.57 |
44 |
34.38 |
|
Tobacco history |
|
|
|
|
|
Yes |
135 |
80.36 |
80 |
62.50 |
0.0006 |
No |
33 |
19.64 |
48 |
37.50 |
|
Alcohol history |
|
|
|
|
|
Yes |
54 |
32.14 |
60 |
46.88 |
0.0099 |
No |
114 |
67.86 |
68 |
53.13 |
|
1990-2000 |
2001-2010 |
|
||
|
N |
% |
N |
% |
p-value** |
T |
|
|
|
|
|
Tis |
5 |
2.98 |
9 |
7.03 |
0.0033 |
T1 |
28 |
16.67 |
29 |
22.66 |
|
T2 |
45 |
26.79 |
49 |
38.28 |
|
T3 |
76 |
45.24 |
31 |
24.22 |
|
T4 |
14 |
8.33 |
10 |
7.81 |
|
N |
|
|
|
|
|
N0 |
64 |
39.75 |
59 |
47.20 |
0.0964 |
N1 |
67 |
41.61 |
41 |
32.80 |
|
N2 |
26 |
16.15 |
16 |
12.80 |
|
N3 |
4 |
2.48 |
9 |
7.20 |
|
M |
|
|
|
|
|
M0 |
149 |
90.85 |
115 |
94.26 |
0.2847 |
M1 |
15 |
9.15 |
7 |
5.74 |
|
Stage |
|
|
|
|
|
0 |
5 |
3.11 |
9 |
7.20 |
0.0157 |
1A |
21 |
13.04 |
23 |
18.40 |
|
1B |
21 |
13.04 |
23 |
18.40 |
|
2 |
35 |
21.74 |
32 |
25.60 |
|
3A |
46 |
28.57 |
14 |
11.20 |
|
3B |
14 |
8.70 |
10 |
8.00 |
|
4 |
19 |
11.80 |
14 |
11.20 |
|
Depth of invasion |
|
|
|
|
|
Mucosa |
13 |
7.74 |
28 |
22.05 |
<0.0001 |
Submucosa |
3 |
1.79 |
12 |
9.45 |
|
Musc. Propria |
30 |
17.86 |
45 |
35.43 |
|
Serosa |
8 |
4.76 |
19 |
14.96 |
|
Adjacent organs |
11 |
6.55 |
19 |
14.96 |
|
Metastasis |
3 |
1.79 |
4 |
3.15 |
|
Unknown |
100 |
59.52 |
0 |
0.00 |
|
Margins |
|
|
|
|
|
No residual tumor |
140 |
82.84 |
105 |
82.68 |
0.0835 |
Microscopic tumor |
12 |
7.10 |
17 |
13.39 |
|
Macroscopic tumor |
6 |
3.55 |
1 |
0.79 |
|
Unknown |
11 |
6.51 |
4 |
3.15 |
|
Nodes examined |
10.58 ± 8.65 (median=9) |
14.97 ±10.60 (median=12) |
<0.0001 |
||
Nodes positive |
3.77 ± 6.33 (median=1) |
3.58 ± 5.62 (median=1) |
0.6096 |
||
Type of Gastrectomy |
|
|
|
|
|
Partial / Subtotal gastrectomy |
57 |
33.7 |
77 |
60.1 |
0.0001 |
Total / Radical Gastrectomy |
31 |
18.3 |
24 |
18.7 |
|
Gastrectomy, NOS |
81 |
47.9 |
27 |
21.0 |
This trend could have resulted from two factors as depicted from our results:
1.Diagnosis of gastric cancer at an earlier stage as evidenced by increasing number of patients diagnosed with earlier stage disease in group II.
2.More aggressive nodal dissection with an average of 15 nodes in group II as opposed to 10 nodes in group I.
Though our study demonstrated improved survival
The concept of a more thorough nodal dissection became more accepted in the latter part of the 1990s to early 2000s, thus we divided our study population into 2 groups. Despite the conflicting evidence regarding the extent of nodal dissection, a recent SEER database review demonstrated a linear improvement in 5-year survival in patients with increasing number of lymph nodes resected [13]. On the other hand, several prospective randomized controlled trials and met-analyses failed to demonstrate a clear survival benefit with D2 vs D1 lymphadenectomy [14-16]. Although the benefit between a D1 or D2 lymphadenectomy are unclear, some studies suggest less than one third of patients undergo an adequate lymphadenectomy (>15 nodes) stressing the importance of the extent of lymphadenectomy for gastric cancer [17-19]. We therefore, postulate that the trend towards an increased 5-year survival results from aggressive nodal dissection and an earlier diagnosis.
- Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725-730.
- Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectablegastroesophageal cancer. N Engl J Med. 2006;355(1):11-20.
- Noguchi Y, Yoshikawa T, Tsuburaya A, Motohashi H, Karpeh MS, Brennan MF, et al. Is gastric carcinoma different between Japan and the United States? Cancer. 2000;89(11):2237-2246.
- Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ, et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11(5):439-449.
- Siegel R, Naishadham D, Jemal A. Cancer statistics. 2012. CA Cancer J Clin. 2012;62(1):10-29. doi: 10.3322/caac.20138.
- Lee E. T. Statistical Methods for Survival Data Analysis. 2nd ed. New York: John Wiley & Sons; 1992.
- Greenwood M. The Errors of Sampling of the Survivorship Table. Vol. 33 of Reports on Public Health and Medical Subjects. London: Her Majesty's Stationery Office. 1926.
- Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJ, Welvaart K, Songun I, et al. Dutch Gastric Cancer Group; Extended lymph-node dissection for gastric cancer. N Engl J Med. 1999;340(12):908-914.
- Cuschieri A, Fayers P, Fielding J, Craven J, Bancewicz J, Joypaul V, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet . 1996;347:995.
- Dai Q1, Jiang L, Lin RJ, Wei KK, Gan LL, Deng CH, et al. Adjuvant chemoradiotherapy versus chemotherapy for gastric cancer: A meta-analysis of randomized controlled trials. J Surg Oncol. 2015;111(3):277-284. doi: 10.1002/jso.23795.
- Seyedin S, Wang PC, Zhang Q, Lee P. Benefit of Adjuvant Chemoradiotherapy for Gastric Adenocarcinoma: A SEER Population Analysis. Gastrointest Cancer Res. 2014;7(3-4):82-90.
- Stiekema J, Trip AK, Jansen EP, Aarts MJ, Boot H, Cats A, et al. Does Adjuvant Chemoradiotherapy Improve the Prognosis of Gastric Cancer After an R1 Resection? Results from a Dutch Cohort Study. Ann Surg Oncol. 2014;22(2):581-588. doi: 10.1245/s10434-014-4032-8.
- Smith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol. 2005;23:7114-7124.
- Jiang L, Yang KH, Guan QL, Zhao P, Chen Y, Tian JH, et al. Survival and recurrence free benefits with different lymphadenectomy for resectable gastric cancer: a meta-analysis. J Surg Oncol. 2013;107(8):807-814. doi: 10.1002/jso.23325.
- Dent DM, Madden MV, Price SK. Randomized comparison of R1 and R2 gastrectomy for gastric carcinoma. Br J Surg. 1988;75(2):110-112.
- Degiuli M, Sasako M, Ponti A, Vendrame A, Tomatis M, Mazza C, et al. Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer.Br J Surg. 2014;101(2):23-31. doi: 10.1002/bjs.9345.
- Coburn NG, Swallow C, Quan ML, Law C. Significant regional variation in treatment and survival of gastric cancer . J Clin Oncol. 2005;23:309s.
- Baxter NN, Tuttle TM. Inadequacy of lymph node staging in gastric cancer patients: a population-based study. Ann Surg Oncol. 2005;12:981-917.
- Bilimoria KY, Talamonti MS, Wayne JD, Tomlinson JS, Stewart AK, Winchester DP, et al. Effect of hospital type and volume on lymph node evaluation for gastric and pancreatic cancer. Arch Surg. 2008;143(7):671-688 . doi: 10.1001/archsurg.143.7.671.