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Radiation for Gastric (Stomach) Cancer

Surgery is the best treatment for gastric cancers and In general the stomach does not tolerate radiation well, so radiation alone is rarely used unless the cancer is inoperable. It is more common to use radiation before surgery (called preoperative go here) or after surgery called postoperative as noted below.

The role of postoperative radiation (after resection) has been controversial but the recent INT-0116 Trial/ SWOG 9008 has established a role for postoperative chemo-radiation go here and table below .

also see anatomy and sections and radiation port, nodes #1, nodes#2, nodes#3, see the NCCN guidelines here and here

Some of the other studies using radiation to treat gastric cancer  are noted below

INT-0116 PostOp ChemoRad for resected AdenoCa of Stomach and GE junction (45Gy + 5FU/LV) ASCO 2000
  Radiation-Chemo No Adjuvant
DFS/3y 49% 32%
OS/3y 52% 41%
median survival 42 months 27 months
 
Role of post-operative chemoradiation in resected gastric cancer.

Macdonald JS.  J Surg Oncol. 2005 Jun 1;90(3):166-70.

Saint Vincent's Comprehensive Cancer Center, New York, New York.

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%-80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months). The improvements in disease-free and overall survival resulting from post-operative chemoradiation have defined a new standard of care. An update of the results of INT-0116 analysis performed in 2004 with 7 years median follow-up, not only confirms the benefits from post-operative chemoradiation but also shows that chemoradiation does not produce significant long-term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might downstage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre-operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and antiangiogenesis agents.

Results of radiation therapy in gastric cancer.

Willett CG.   Semin Radiat Oncol. 2002 Apr;12(2):170-5.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.

Radiation therapy has been used in the treatment of patients with gastric cancer in two clinical settings: definitive therapy for locally advanced, unresectable tumors and adjuvant therapy following surgery for high-risk disease. For patients with locally advanced, unresectable or subtotally resected gastric carcinoma, radiotherapeutic approaches with and without chemotherapy have been employed, because these tumors appear localized, without clinically detectable metastases. Combined treatment with radiation therapy and chemotherapy appears to prolong survival but rarely results in long-term cure. Although only a modest effect was seen on survival, importantly, these studies established the foundation of contemporary combined-modality therapy and have served to stimulate further clinical investigation in gastric cancer as well as other gastrointestinal disease sites. For patients undergoing resection and lymphadenectomy with curative intent, the development of local or regional failure is common, occurring in 40% to 65% of patients. Sites of local and regional failure following resection include the gastric/tumor bed in 20% to 55%, the anastomosis in 25% to 50%, and the regional nodes in 40% to 50% of patients. Intergroup Trial 0116 (INT 0116), a phase III trial, has recently demonstrated that adjuvant radiation therapy with concurrent and maintenance 5-fluorouracil (5-FU) and leucovorin (LV) reduces local failure and improves survival. Adjuvant therapy is now routinely administered to patients undergoing resection of gastric cancer for high-risk disease. Ongoing trials are now investigating new systemic agents with radiation therapy to establish efficacy compared to 5-FU and LV, as well as evaluating neoadjuvant approaches prior to resection.

The role of radiation therapy in gastric cancer.

Minsky BD  Semin Oncol 1996 Jun;23(3):390-6

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.

Radiation therapy has been used as an adjuvant, primary, and palliative treatment modality for gastric cancer. In the adjuvant setting, the role of postoperative radiation therapy plus chemotherapy is being examined in the phase III Intergroup trial 0116. Until the results of this trial are available, the standard treatment after a complete resection (with or without positive locoregional lymph nodes) is observation alone. In patients who are selected to receive adjuvant therapy, locoregional radiation to 45 Gy plus 5-fluorouracil (5-FU)-based chemotherapy is recommended. In patients with locally unresectable or residual disease, postoperative radiation therapy and 5-FU-based chemotherapy may decrease locoregional failure and improve survival. Intraoperative radiation therapy appears promising; however, it remains investigational. In the palliative setting, radiation therapy offers symptomatic relief in the majority of patients.

Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach.

Regine WF, Mohiuddin M     Int J Radiat Oncol Biol Phys 1992;24(5):921-7

Thomas Jefferson University Hospital, Philadelphia, PA 19107.

From 1975 to 1988, 120 consecutive patients with locally advanced (T3/T4 or N1/N2) adenocarcinoma of the stomach underwent attempted curative resection. Seventy patients were treated with surgery alone while 50 patients also received adjuvant therapy consisting of either chemotherapy (5-FU/FAM) alone, radiation therapy alone, or chemotherapy+radiation therapy. Adjuvant therapy was tolerated relatively well with only one patient experiencing a grade 3 (RTOG/EORTC) toxicity, and none experiencing grade 4/5 toxicity. In patients with T3/T4 tumors, the median survival was 10 months for surgery alone as compared to 18 months for the adjuvant treatment group, and a 5-year survival of 10% versus 24% in the adjuvant therapy group (p = .01). In patients with lymph node positive disease, the median survival was 10 months in patients treated with surgery as compared to 15 months for those treated with adjuvant therapy, and a 5-year survival of 8% for surgery alone versus 16% for the adjuvant therapy group (p = .04). Patients having both T3/T4 tumor and positive lymph nodes had a median survival of 9 months with surgery versus 13 months for the adjuvant therapy group, and a 5-year survival of 4% versus 22% (p = .03) for the adjuvant group. Seventy-four patients were evaluable for pattern of relapse. Thirty developed locoregional recurrence; 17 of 38 (45%) in the surgery alone group and 13 of 36 (36%) in the adjuvant therapy group. The improvement in local control in the adjuvant group was totally accounted for by the group receiving both chemotherapy and radiation therapy, in which the recurrence rate was 19%. Statistically significant improvement in the 2-year local control rate was limited to patients with negative surgical margins who received radiation, 93%, versus those who did not, 55% (p = 0.03). The modest improvement in survival seen in patients receiving adjuvant therapy appears to be related to improved local control. No improvement in the rate of distant failure was seen. Chemotherapeutic regimens used seem to be critical in enhancing the effects of radiation in improving local control and survival. Results may be further improved by the extended use of intraoperative radiation.

A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma. Gastrointestinal Tumor Study Group.       Cancer 1982 May 1;49(9):1771-7

This controlled trial compared to survival of 90 patients with locally advanced gastric carcinoma treated with either chemotherapy alone (5-FU and methyl-CCNU) or external radiotherapy of 5000 rad combined with the same chemotherapy. The minimum period of followup is 4 years. During the initial 12 months, combined modality therapy was associated with an increased number of early deaths attributable to progression of tumor within the radiation field, or nutritional and hematologic complications. During the second to fourth years of followup, patients treated with combined radiation therapy have shown a significantly lower death rate compared to those treated with chemotherapy alone, with eight of 45 patients alive and disease-free. Patients who received only chemotherapy, in contrast, have demonstrated a continued probability for tumor relapse and death, with three of 45 patients alive at 4 years. Palliative resection of the primary tumor was associated with an improved survival, independent of the form of postoperative therapy employed. It is possible that the superior late survival achieved with combined modality therapy in this program can be further improved with measures to decrease the toxicity of upper abdominal irradiation, and with the use of more effective forms of chemotherapy.

Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil--an Eastern Cooperative Oncology Group study.

Klaassen DJ   J Clin Oncol 1985 Mar;3(3):373-8

One hundred ninety-one patients with pathologically confirmed, locally unresectable adenocarcinoma of the stomach (57 patients) and pancreas (91 patients), were randomly allocated to therapy with 5-fluorouracil (5-FU) alone, 600 mg/m2 intravenously (IV) once weekly, or radiation therapy, 4,000 rad, plus adjuvant 5-FU, 600 mg/m2 IV, the first three days of radiotherapy, then follow-up maintenance 5-FU, 600 mg/m2, weekly. Forty-three patients (22%) could not be analyzed because of ineligibility or cancellation, thus 148 patients were evaluable. The median survival time was similar for both treatment programs and for both types of primary carcinoma, and was as follows: gastric primary carcinoma, 5-FU, 9.3 months; 5-FU plus radiotherapy, 8.2 months; pancreatic primary carcinoma, 5-FU, 8.2 months; 5-FU plus radiotherapy, 8.3 months. Substantially more toxicity was experienced by patients treated with the combined modality arm than by those patients receiving 5-FU alone. Severe or worse toxicity experienced by patients with gastric primary carcinoma treated by 5-FU was 19%, and the combined modality arm was 31%. The toxicity experienced by patients with pancreatic primary carcinoma treated with 5-FU was 27%, and the combined modality arm was 51%. Significant prognostic variables included: weight loss in stomach-cancer patients; and performance status, degree of anaplasia, and reduced appetite in pancreas-cancer patients.

Combined 5-fluorouracil (5-FU) and radiation therapy following resection of locally advanced gastric carcinoma.

Gez E, J Surg Oncol 1986 Feb;31(2):139-42

Twenty-five patients with locally advanced but resectable adenocarcinoma of the stomach were given concomitant postoperative radiotherapy to the tumor bed and chemotherapy with 5-Fluorouracil (5-FU). Twenty-two of the patients had regional lymph node involvement and seven had residual tumor in the surgical margins. Radiotherapy was delivered to a total dose of 5,000 rads in 7 weeks with a two-week split. 5-FU was given daily the first 3 days of each treatment period and was then continued weekly for a minimum of 1 year. At a median follow-up time of 19 months, 11 patients have relapsed, two locally and nine distally, and all have died. Thirteen patients remain alive, all but one disease-free, for a median of 21 months from diagnosis. One additional patient died of unrelated causes, free of tumor. The actuarial median survival for the whole group stands at 33 months with a projected 5-year survival of 40%. Treatment has been well tolerated.

Intraoperative radiotherapy and external beam radiation therapy in gastric adenocarcinoma with R0-R1 surgical resection.

Glehen O,    Eur J Surg Oncol 2000 Nov;26 Suppl A:S10-2

Universite Claude Bernard, Lyon 1, France.

The aims of this study were to evaluate the results of intraoperative radiotherapy (IORT) and external beam therapy (EBRT) in the treatment of gastric adenocarcinoma. METHODS: From 1986 to 1999, 87 patients who underwent surgical resection for gastric adenocarcinoma combined with IORT were reviewed. A R0 surgical resection was performed in 82 patients and five underwent R1 resection. The stage was: pT1 in 12, pT2 in 19, pT3 in 44 and pT4 in seven. Thirteen patients were pN1 and 43 were pN2, The IORT dose ranged from 12 to 23 Gy. Patients with pT3 and/or pN tumours underwent EBRT with a standard dose of 44-46 Gy. RESULTS: The post-operative mortality and morbidity rates were 2.3 and 6.8%, respectively. The 5-year survival rate for R0 patients was 60%, for R0-pN0 was 90% and for R0-pN+ patients was 55%. The local failure rate in the 19 pN+ patients was 21%. CONCLUSION: IORT and EBRT combined with surgical resection may provide overall survival, improving the local control after gastrectomy.

Treatment of adenocarcinoma of the stomach with resection, intraoperative radiotherapy, and adjuvant external beam radiation: a phase II study from Radiation Therapy Oncology Group 85-04.

Avizonis VN, Ann Surg Oncol 1995 Jul;2(4):295-302

LDS Hospital, Salt Lake City, UT 84143, USA.

Fewer than 10% of patients presenting with adenocarcinoma of the stomach in the United States can expect to be cured. These discouraging results have led to trials of various adjuvant therapies. Some studies suggest a role for radiation in improving regional control. Radiation doses, however, are limited by the tolerance of abdominal organs. METHODS: Between 1985 and 1989, the Radiation Therapy Oncology Group conducted a phase II study to determine the feasibility of using intraoperative radiotherapy (IORT) in the treatment of adenocarcinoma of the stomach. Forty-three patients were entered into the study. Patients underwent maximal surgical resection (subtotal or total gastrectomy and regional node dissection) and IORT doses of 12.5-16.5 Gy were delivered in 27 patients. Adjuvant external beam radiation was given to 23 of the 27 patients with total doses ranging from 24 to 50 Gy. RESULTS: Two-year actuarial survival in the 27 patients receiving IORT was 47% and median survival was 19.3 months. Disease-free survival was 27%. Fifteen percent failed locally only, 26% with distant metastases only and 22% with both. Acute postoperative complications occurred in 14% with one fatality. Severe late complications occurred in 7% with one fatality. CONCLUSIONS: Intraoperative radiotherapy combined with surgical resection and postoperative radiotherapy appears to be feasible without excessive morbidity in a multiinstitutional study. Its ultimate value requires further study.