Selecting the best treatment for an individual patient.

Several factors concur in determining outcome for locally advanced gastric cancer patients. Shockingly, geographic origin of the patient seems to play a major role. In Eastern countries, the high level of surgery that can be expected grants a high percentage of success in a strategy that employs surgery as immediate treatment followed by adjuvant chemotherapy, mainly based on oral fluoropyrimidines (S-1 or Capecitabine), with satisfactory results. In Western countries, the expertise of the surgeon maintains its role as predictor of high likelihood of cure. Indeed, patients treated with standard D2 lymph node dissection have a significantly better survival than those who do not obtain the same kind of treatment. For patients who underwent a suboptimal resection (less than a D1) the classical indication is for a combined adjuvant chemoradiotherapy. In patients who obtain a good surgical outcome, the benefit of the addition of adjuvant chemotherapy is still debatable: the gain in survival seems to be small (around 8 \% at 5 years) and with noticeable toxicities (usually with dismal compliance for patients treated). On this basis, neoadjuvant treatment is a promising option even if there is a general lack of conclusive data regarding which is the best regimen to use. Even with the limitation of a small number of studies (with difficulties in enrollment), neoadjuvant chemotherapy is usually feasible, allows for a greater chance of receiving chemotherapy at all, and opens the possibility of a downstaging and downsizing of the tumor, allowing an easier surgery. Regarding this strategy preliminary results have also been presented about the addition of monoclonal antibodies. For example, in the TOGA trial, a significant benefit in terms of overall survival, response rate, and progression free survival was observed also for patients with locally advanced gastric cancer and not just for the metastatic ones. In the AVAGAST trial also, the addition of Bevacizumab failed to determine a significant improvement in the primary outcome, overall survival, for patients treated with the combination, but in the subgroup analysis, patients with locally advanced gastric cancer had a significantly better overall survival and response rate. This data was the basis for the newest neoadjuvant trial, of Cunningham et al., the MAGIC2 trial, with the peri-operative use of ECX+Bevacizumab. Finally, an increasing interest in the use of hyperthermic intraperitoneal chemotherapy in other types of solid tumors (including those of the gastrointestinal tract such as colon cancer) has led to evaluate this treatment modality in gastric cancer patients with peritoneal involvement. It should be noted that it is still to be considered an experimental approach, even though it would be intriguing to evaluate if a particular subset of patients, those who are more likely to develop peritoneal metastasis, may benefit from this technique in the adjuvant setting. It should be considered that other than histologic subtype (diffuse vs intestinal) there seems to be a series of polymorphisms of genes usually involved in cell interaction and migration that can explain a different metastatic pattern in resected patients. Further research on these determinants of metastatic spread could be used to select those patients who may benefit from HIPEC and those who may benefit from standard adjuvant or that gain no benefit at all.