|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2001 American Society for Clinical Oncology
Postoperative Adjuvant Chemoradiation Therapy for Patients With Resected Gastric Cancer: Intergroup 116City of Hope National Medical CenterDuarte, CA To the Editor:In the November 2000 Supplement of the Journal of Clinical Oncology, Dr Kelsen presents his discussion of the results of Intergroup trial 116 of postoperative chemoradiation in patients with resected gastric cancer.1 Although a final analysis of the original trial has not yet been published, presentation of its preliminary results at the Thirty-Sixth Annual Meeting of the American Society of Clinical Oncology, May 19-23, 2000, has already left a major impact on the way patients are treated after gastrectomy.2 Kelsen’s discussion, which I read with great interest, highlights several points that I would certainly agree with, especially the question of whether an adequate operation had been performed in many of the patients who were entered onto this trial. However, his statements on the recommended extent of lymphadenectomy deserve some specification. In Intergroup 116, 54% of patients underwent less than a D1 lymph node dissection (LND), 36%, a D1 lymphadenectomy, and only 10%, a D2 procedure. As a result, 64% of patients in the control group experienced a recurrence, which involved regional sites in 72%, local sites in 29%, and distant sites in 18%. Peritoneal spread was not listed separately. It seems that the benefit of postoperative chemoradiation in relapse pattern and survival was achieved primarily through the radiation component. Although the extent of LND has remained an issue of debate, several centers in the United States have adopted a policy of more radical (D2) dissections in association with potentially curative gastrectomies, despite a lack of survival benefit in two European randomized trials.3,4 D2 LND has been recommended as the preferred extent of regional resection in the National Comprehensive Cancer Network guidelines (as well as in Intergroup 116),5 primarily for four reasons: more precise pathologic staging, better regional disease control, a putative survival benefit to a small subset of patients (those with otherwise unrecognized, isolated N2 disease), and its safe performance in experienced hands when splenectomy and pancreatectomy are avoided.6,7 In an attempt to demystify the complex Japanese LND rules for easier use by surgeons in the United States, this would translate into recommending a retroperitoneal lymphadenectomy of left gastric, common hepatic celiac, and splenic arterial nodes aside from the perigastric (D1) nodes, removal of which is easily included in the process of gastrectomy. Using such an extended retroperitoneal LND approach in association with a potentially curative gastrectomy as surgical standard, our institutional experience with gastric cancer recurrence differs significantly from Intergroup 116 results. Over the past 10 years, 73 patients underwent gastrectomy, and 82% of them had a negative margin (R0) resection. At a median follow-up for survivors of 30 months, recurrent disease was identified in 35 patients (48%). Twenty-nine percent received adjuvant therapy, without a significant impact on survival or recurrence. Isolated local but not regional recurrence was seen in two patients (3%). Locoregional recurrence in the setting of diffuse peritoneal or hematogenous, systemic disease was identified in 16%, while another 11% of patients had peritoneal involvement and another 18% had distant disease without locoregional involvement. A significant predictor of systemic failure was N3 status; for peritoneal failure, it was a T3 or T4 classification. N2 disease had a distant failure risk similar to N1 and a peritoneal recurrence risk similar to N3 categories. These failure patterns resemble those obtained in Asian series8 and are different from outcomes in Intergroup 116. I would strongly advocate such extended retroperitoneal (D2) LND for every patient undergoing potentially curative gastrectomy. I would have doubts as to whether the Intergroup 116 regimen would present a useful or effective adjuvant treatment regimen for patients treated with such surgical standards, as this extended retroperitoneal dissection seems more likely to decrease the need for additional regional therapy in the form of radiation. Instead, patients primarily at high risk for peritoneal or systemic failure, given these pathologic predictors, should be treated with intraperitoneal or systemic adjuvant chemotherapy approaches as outlined by Kelsen and by others.1,9,10 Those patients who remain primarily at risk for locoregional but not for diffuse peritoneal or systemic recurrence (eg, with positive margin [R1], few involved lymph nodes, and no serosal invasion11) will likely benefit from the Intergroup 116 regimen. REFERENCES
1.
Kelsen DP: Postoperative adjuvant chemoradiation therapy for patients with resected gastric cancer: Intergroup 116. J Clin Oncol 18: 32s-34s, 2000 (suppl) 2. Macdonald JS, Smalley S, Beneditti J, et al: Postoperative combined radiation and chemotherapy improves disease-free survival and overall survival in resected adenocarcinoma of the stomach and GE junction: Results of Intergroup Study INT-0116 (SWOG 9008). Proc Am Soc Clin Oncol 19: 1a, 2000 (abstr 1)
3.
Bonenkamp JJ, Hermans J, Sasko M, et al: Extended lymph-node dissection for gastric cancer: Dutch Gastric Cancer Group. N Engl J Med 340: 908-914, 1999 4. Cuschieri A, Weeden S, Fielding J, et al: Patient survival after D1 and D2 resections for gastric cancer: Long-term results of the MRC randomized surgical trial—Surgical Co-operative Group. Br J Cancer 79: 1522-1530, 1999[Medline] 5. NCCN: Practice guidelines for upper gastrointestinal carcinomas: National Comprehensive Cancer Network. Oncology (Huntingt) 12:179-223, 1998 (published errata appear in Oncology (Huntingt) 13:272, 1999, and 13:259, 1999)
6.
Brennan MF: Lymph-node dissection for gastric cancer. N Engl J Med 340: 956-958, 1999 (editorial) 7. Smith JW, Shiu MH, Kelsey L, et al: Morbidity of radical lymphadenectomy in the curative resection of gastric carcinoma. Arch Surg 126: 1469-1473, 1991[Abstract] 8. Yoo CH, Noh SH, Shin DW, et al: Recurrence following curative resection for gastric carcinoma. Br J Surg 87: 236-242, 2000[Medline] 9. Averbach AM, Jacquet P: Strategies to decrease the incidence of intra-abdominal recurrence in resectable gastric cancer. Br J Surg 83: 726-733, 1996[Medline] 10. Neri B, de Leonardis V, Romano S, et al: Adjuvant chemotherapy after gastric resection in node-positive cancer patients: A multicentre randomized study. Br J Cancer 73: 549-552, 1996[Medline] 11. Kim SH, Karpeh MS, Klimstra DS, et al: Effect of microscopic resection line disease on gastric cancer survival. J Gastrointest Surg 3: 24-33, 1999[Medline]
ResponseMemorial Sloan-Kettering Cancer CenterNew York, NY In Reply:Dr Schwarz raises the issue of whether the improved outcome seen with chemoradiation therapy as delivered in the investigational arm of Intergroup 116 would be replicated if patients had undergone an adequate lymph node dissection and did not require postoperative radiation therapy. He presents institutional experience suggesting that patients who underwent an extensive retroperitoneal lymph node dissection (D2) had a lower risk of local regional failure than seen in the surgery only control arm of Intergroup 116. On the basis of these data, he recommends a D2 dissection as a standard procedure for patients undergoing potentially curative gastrectomy, limiting the use of postoperative chemoradiation to patients with an R1 dissection, limited numbers of involved lymph nodes, and lesions less than stage T3. As I noted in my discussion, slightly more than half of the patients treated in Intergroup 116 had less than a recommended (D1) lymph node dissection.1 It is possible that the local regional failure rate would have been substantially lower if a D1 or D2 dissection had been performed. However, this is a hypothesis that remains to be proven. The only conclusion we can make from the preliminary data of Intergroup 116 presented to date is that for patients undergoing gastrectomy, postoperative chemoradiation therapy improves 3-year disease-free and overall survival compared with surgery alone. I believe that a strong effort should be made to educate and encourage surgeons who perform gastric cancer operations to at a minimum perform a D1 lymphadenectomy. Although, as Schwarz notes, a D2 dissection has been adopted as a standard approach at several American institutions, two recent large European trials failed to show benefit for the more extensive lymphadenectomy.2,3 We therefore do not have definitive data indicating that, in a multi-institutional study, D2 operations are superior. Second, it may well be that, as has been demonstrated for other malignancies (such as pancreatic cancer), high-volume centers can safely perform an appropriate lymphadenectomy with no increase in operative morbidity and mortality. Referral of newly diagnosed gastric cancer patients who have potentially curative lesions to high-volume centers should also be strongly encouraged. In summary, the role of radiation therapy in preventing local regional recurrence for patients undergoing at least a D1 dissection would be an appropriate question for a future clinical trial. Such a study could be designed in which all patients undergo an R0 resection with at least a D1 lymphadenectomy and are then randomly assigned to receive either chemotherapy as designed in Intergroup 116 or chemoradiation therapy, as in the experimental arm of 116. This would isolate the contribution of external-beam radiation therapy using the dose and schedule utilized in 116 for patients who underwent adequate lymph node dissections. REFERENCES 1. Kelsen DP: Postoperative adjuvant chemoradiation therapy for patients with resected gastric cancer: Intergroup 116. J Clin Oncol 18: 32s-34s, 2000 (suppl) 2. Bonekamp JJ, Hermans J, Sasako M, et al: Extended lymph-node dissection for gastric cancer: Dutch Gastric Cancer Group. N Engl J Med 340: 908-914, 1999 3. Cuschieri A, Weeden S, Fiedling J, et al: Patient survival after D1 and D2 resections for gastric cancer: Long-term results of the MRC randomized surgical trial—Surgical Cooperative Group. Br J Cancer 79: 1522-1530, 1999 This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
