Elsevier

The Lancet Oncology

Volume 4, Issue 8, August 2003, Pages 498-505
The Lancet Oncology

Review
Chemoradiation for resectable gastric cancer

https://doi.org/10.1016/S1470-2045(03)01170-7Get rights and content

Summary

The incidence of gastric cancer has been declining in recent years, however, the disease continues to be a worldwide public health problem. About two thirds of patients with gastric cancer undergo surgical resection with curative intent. R0 resection—complete local-regional tumour removal with negative resection margins—is the only curative modality. The optimum extent of lymph-node dissection (D1 vs D2) is controversial. Disease relapse, both local and distant, is common and the 5-year survival rate is disappointing. Adjuvant chemotherapy has been studied extensively in this setting but an effective regimen has not yet been identified. A recent intergroup study has shown that postoperative chemoradiation is effective in improving both disease-free survival (3-year, 48% vs 31%, p<0·001) and overall survival (3-year, 50% vs 41%, p=0·005) compared with surgery alone. Preoperative radiation as a single adjuvant therapy has also yielded improvements in local-regional control, disease-free survival, and overall survival compared with surgery alone. Preoperative chemotherapy or chemoradiation has been accepted to have a theoretical advantage over postoperative therapy and has now been shown to be a feasible option. Its efficacy, however, remains to be tested.

Section snippets

Disease progression

The primary treatment for gastric cancer is surgery. For example, in a study by Wanebo and colleagues, 77% of patients underwent surgery but only 35% of received adjuvant chemotherapy or radiation therapy.6 However, the National Cancer Database in the USA reported a lower proportion of patients who were treated with some type of surgery or surgery combined with adjuvant therapy;7 approximately 61–65% of patients with local–regional disease underwent surgery. Adjuvant chemotherapy, radiation, or

Patterns of relapse

Understanding patterns of disease relapse is crucial for designing appropriate adjuvant or preoperative therapy. Clinical and autopsy studies have revealed a high incidence of local–regional recurrence and distant relapse (primarily liver metastases and peritoneal seeding) after resection.12, 13, 14, 15, 16 Patients with primary cancer involving the gastroesophageal junction are more likely to have extra-abdominal spread, primarily lung metastases, than those whose cancer involved more distal

Adjuvant chemotherapy

The poor survival of patients who undergo curative resection alone for gastric cancer is indicative of the need for adjuvant therapy, especially in patients who have disease that has extended beyond the gastric wall and show lymph-node involvement at the time of surgery. Many phase II and III clinical trials have been done to find an effective adjuvant chemotherapy and several comprehensive reviews have been published on this topic. The combination of fluorouracil, doxorubicin, and mitomycin

Chemoradiation

The rationale for using chemoradiation as an adjuvant therapy for patients who have undergone R0 resection is that these patients are at risk for local–regional recurrence and distant metastases. Radiation in conjunction with surgery can improve local–regional control and systemic chemotherapy can suppress or eliminate microscopic distant metastasis and improve radiation cytotoxicity.

Chemotherapy may function as a radiosensitiser, improving the effect of radiation via various mechanisms. DNA is

Preoperative radiation

A randomised phase III trial from Beijing (China) has shown improved disease-free and overall survival rates and improved local–regional control when irradiation precedes resection for adenocarcinoma of the gastric cardia.46 Overall survival at 5 years were 30% in the 171 patients who received preoperative irradiation (40 Gy in 20 fractions over 4 weeks) and 20% in 199 patients who had only surgical resection (p=0·009). Local relapse was diagnosed in 39% of patients in the adjuvant irradiation

Conclusion

The large intergroup study clearly showed the value of postoperative chemoradiation. Further study is needed to develop more effective chemotherapy regimens. The advent of biological agents that target a specific cellular process provides a new avenue for further research. The use of chemotherapy as a radiosensitiser and systemic therapy need to be better defined. The concept of preoperative chemoradiation is attractive but remains investigational.

Search strategy and selection criteria

Published data were identified by searches of MEDLINE using the search terms, “gastric cancer”, “surgery”, and “radiation”. We also searched the Proceedings of ASCO up to 2001. We paid most attention to prospective trials of preoperative radiation and postoperative chemoradiation for resected gastric cancer. Less weight was given to single-arm trials, trials for locally advanced or unresectable gastric cancer, and adjuvant chemotherapy.

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