| Part1:The Recurrence Patterns, Efficacy and Prognostic Factors of Patients Receiving Adjuvant Chemoradiotherapy for Gastric CancerPurpose:To analysis the prognostic value of clinical-pathological factors on clinical outcomes and recurrence patterns of patients receiving adjuvant chemoradiotherapy (CRT) with locally advanced gastric cancer, as an evidence for the modulation of treatment modalities.Methods:From Mar.2002to Apr.2010,179patients with locally advanced gastric cancer undergoing adjuvant CRT were retrospectively investigated,69.2%of whom received D2dissection (examined nodes≥15). Patients were followed up for survival and recurrence status. The prognostic effect of clinical-pathological factors on clinical outcomes and recurrence patterns were investigated. Lymph node ratio was defined as positive to examined nodes.0and0.65were established as cut-off values for lymph node ratio stage (Nr stage).Results:The medium follow-up time was30months.3-year disease-free survival (DFS), overall survival (OS), locoregional recurrence-free survival, peritoneal metastasis-free survival and distal metastasis-free survival were59.6%,78.0%,95.5%,79.8%and84.2%. In patients with known first recurrence site, localregional recurrence, peritoneal metastasis and distal metastasis accounted for11%,59%and46%, respectively. Univariate analysis revealed N3,Nr2, stage IIIB-C, c-myc (+), and preoperative CA724(+) were correlated with worse DFS, with C-myc(+)identified as independent prognostic factors according to multivariate analysis. Similarly, factors associated with worse OS were N3,Nr2, stage ⅢB-C, c-myc(+),and radiation dose<45Gy, but only c-myc(+)had independent prognostic value. Peritoneal metastasis was related with c-myc(+).Conclusions:Lymph-node ratio stage is effective in the prognosis of patients with locally advanced gastric cancer undergoing adjuvant CRT. The expression of c-myc is associated with poor clinical outcomes, especially for increased peritoneal metastasis. Their relation with radiosensitivity is to be further studied. Part2:Predictive Factors of Chemoradiation after D2Ressection for Patients with Locally Advanced Gastric CancerPurpose:Adjuvant therapy with or without radiation for patients with locally advanced gastric cancer receiving D2dissection has been reported with similar outcome of DFS. However, whether patients with lymph node metastasis will benefit from adjuvant CRT hasn’t been well defined. The predictive value of biomarkers in CRT was not clear either. Our study focused on lymph node and c-myc status to see if they could be predictive factors for selection of adjuvant treatment for gastric cancer.Methods:From Jan.2005to Oct.2010,186patients with locally advanced gastric cancer undergoing D2dissection were retrospectively investigated. Of them93patients received CRT while the other93patients were well balanced with patient characteristics, operation type and pathological staging but treated with chemotherapy without radiation. Clinical outcomes including DFS, OS, local control, peritoneal metastasis, distal metastasis and recurrence patterns were compared. Lymph-node ratio (LNR) was defined as ratio of positive to examined nodes. Chemotherapies were5-Fu/oxaliplatin based combination regimen. Radiation was given as45-50.4Gy with3D conformal or IMRT techniques.Results:There were no difference between patients treated with adjuvant chemotherapy with or without radiation in3-y DFS (57.0%vs.62.0%, p=0.30),3-y OS (72.8%vs.77.4%, p=0.23), either as recurrence patterns. However, Benefits were observed in patients with more lymph node metastasis both of lymph node number (3-y DFS:35.8%vs.0%, p=0.052) and ratio (3-y DFS:84.7%vs.57.1%, p=0.046) if they received radiation or not. The median LNR was0.33for the whole group of patients. Patients with LNR>0.65or pN2resulted in significantly improved3-year distal metastasis-free survival (DMFS) in CRT group compared with patients with chemotherapy alone (75.2%vs.0%, p=0.026;100.0%vs.65.3%, p=0.036). Treatment completions were similar in the two groups.Conclusions:Lymph node status with LNR>0.65/N2and c-myc status could be predictors for adjuvant CRT. Further randomized studies are needed for validation and mechanism exploration. Part3:Impact of Nutrition on Treatment Compliance and Toxicities of Patients undergoing Chemoradiation after GastrectomyPurpose:Nutritional status is impaired by tumor-related gastroenteral symptoms, abnormal metabolism, decreased protein-energy intake and treatment toxicities. Our study prospectively investigated the impact of nutritional status on treatment toxicities and compliance of patients undergoing CRT after gastrectomy, and provided evidences for reasonable time of nutritional support.Methods:From Dec.2010to May.2012,40patients of gastric cancer received adjuvant CRT were investigated. Data collected were baseline patient characteristics as well as nutritional status including:weight loss in the peri-operative period, during CRT and adjuvant chemotherapy, nutritional risk screening (NRS)2002score, patient generated-subjective global assessment (PG-SGA) score and nutritional interventions. Treatment toxicities and compliance of CRT and adjuvant chemotherapy were recorded respectively. The correlation of nutritional status and its variety, toxicities and treatment compliance were analyzed. We segmented period according to the time of treatment: baseline, post-operation (Ti), pre-CRT (T2), CRT (T3), adjuvant chemotherapy (T4).Results:1. Weight loss appeared in each period but mostly observed before CRT: Compared to baseline pretreatment, medium weight loss of10.0%before CRT (T1-2) was found more than the loss during CRT (4.6%) significantly (p<0.05).2.Factors related to discontinuity of concurrent chemotherapy were:weight loss>7%in T1or>10%in T1-2; malnutrition before CRT; vomiting; greater than Grade Ⅱ toxicities of anorexia or leucopenia; the need of nutritional support during CRT.3. Factors related to incompliance of adjuvant chemotherapy were:weight loss>5%in T3, nausea or anorexia above Grade Ⅱ, hematological toxicities above Grade Ⅲ, NRS score>5at the end of CRT, and the requirement for nutritional support..Conclusions:Deterioration of nutritional status before one treatment approach would aggravate the toxicities and reduce compliance the following approach in gastric cancer patients with multi-modalities. Patients with more weight loss pre-CRT will reduce the tolerance of CRT while the nutritional decline during CRT would more negatively influence on the completion of adjuvant chemotherapy. Thus, early and persistent nutritional interventions are crucial considerations of strategies of multidisciplinary treatment for patients with gastric cancer.
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