Perioperative Chemotherapy for Gastric Cancer
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- Fatourou, E., Macheras, A., Misiakos, E.P. et al. Ann Surg Oncol (2009) 16: 226. doi:10.1245/s10434-008-0117-6
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Persiani et al. report on perioperative chemotherapy for gastric cancer in a most recent issue of Annals of Surgical Oncology.1 Although this is a small, nonrandomized study, careful selection of patients with locally advanced gastric cancer (LAGC) for perioperative chemotherapy merits our comments considering the current debate on optimal adjuvant treatment.
Currently, there is no consensus on the adjuvant treatment of gastric cancer.2 Controversy exists on the selection of appropriate patients for perioperative chemotherapy in Europe.3 Despite the positive results of the MAGIC trial I,4 this study considered all patients with stage II/III in the absence of subgroup analysis.5 Thus, it is unknown whether stage II or III patients are most likely to benefit from this adjuvant treatment. In Japan, standardized D2 surgery plus postoperative S-1 chemotherapy is currently the standard treatment for stage II/III patients on the basis of an excellent, large-scale, phase III randomized multicenter trial.6 In the USA, gastrectomy followed by postoperative chemoradiotherapy has been the standard of care based on the results of the INT-0116 trial.7,8
In the study by Persiani et al., 24 patients with LAGC received three preoperative cycles of chemotherapy (epidoxorubicin, etoposide, cisplatinum) followed by D2 surgery. Response rate was approximately 40%. This finding is consistent with most other neoadjuvant studies. A reasonable question is: why should the 60% of patients who are nonresponders receive three additional postoperative cycles according to standardized protocol of perioperative chemotherapy given the unnecessary toxicity of this regimen in nonresponders?
There is obviously an urgent need to identify gastric cancer patients who are most likely to respond to adjuvant chemotherapy and discriminate them from those who are less likely to benefit from a certain chemotherapeutic regimen. The tumor–node–metastases (TNM) staging system apparently has less discriminatory accuracy for selecting responder patients to chemotherapy. Efforts and hope have been focused on understanding cancer biology, and developments in pharmacogenomics research provide fascinating future opportunities. But at present there is no robust predictive marker ready for the clinic.9
There has been an explosion in biomedical research for the identification of personalized susceptibility to cancer and other common complex disease. If successful, these basic science developments could lead to personalized medicine which would dramatically improve clinical outcomes. This is a major goal but at present remains a dream.10 Particularly for cancer patients, clinical use of robust personal genetic and genomic markers to guide preventive and therapeutic interventions would maximize the benefits for patients with various solid tumors.11 However, at present, personalized preventive and therapeutic approach is a reality only for a small proportion of the population with hereditary diffuse gastric cancer who are carriers of rare mutations in the CDH1 gene12 or hereditary breast–ovarian cancer in women with BRCA1 or BRCA2 mutations.13–17 However, despite advances in local and distant control,18–22 tailored management of sporadic cancer remains elusive. Cancer is a highly complex disease with involvement of a large numbers of low-penetrance genes. Complex biological processes including cancer heterogeneity, angiogenesis, and microenvironment should be better explored while many challenges and hurdles remain to be overcome in order to achieve a personalized practice in individuals with cancer.23,24 A comprehensive step-by-step treatment-guided algorithm is currently provided, aiming at tailoring the most effective therapeutic approach in individual patients with gastric cancer and breast cancer. 25–27
Clinical decision-making for patients with stage II and III gastric cancer is difficult. Appropriate locoregional treatment is crucial not only for reducing locoregional recurrence but also because evidence from randomized trials indicates also improved overall survival. Thus D2 surgery for R0 resection has been the standard of care for gastric cancer. Whether adjuvant chemotherapy should be administrated before or after D2 surgery is unclear. New, large-scale, phase III randomized trials with the potential for biospecimen collection—–biobanks—and molecular cancer research are needed for robust conclusions and efforts toward personalized management of gastric cancer. 2,25