Therapeutic Individualization for Patients With Locally Advanced Gastric and Gastroesophageal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether the R0 rate, pathological response degree, patterns of recurrence and long-term outcomes may be initially predicted in patients with locally advanced gastroesophageal junction and gastric cancer treated with a neoadjuvant approach and salvage surgery.

Detailed Description
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Patients with locally advanced gastroesophageal junction and gastric cancer with T3-4 and/or N+ are included. Initially, patients are diagnosed by computerized tomography scan and endoscopic ultrasound. The neoadjuvant strategy consisted of 3-4 cycles of preoperative chemotherapy (group A) or 3-4 courses of induction chemotherapy followed by concurrent chemoradiotherapy (group B). Chemoradiotherapy comprised weekly chemotherapy concurrently with daily external beam radiotherapy up to 45 Gy). Surgery is scheduled 4 to 6 weeks after the end of CRT. Pathological response is graded according to the Becker criteria. Statistical analysis is performed IBM SPSS v20. Nonlinear mixed effects (NLME) modelling is applied to evaluate the impact of dynamic changes in tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) on the clinical outcome of these patients.

Official Title
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Approximation to the Therapeutic Individualization in Patients With Locally Advanced Gastric and Gastroesophageal Cancer Through Modelling and Generation of Predictive Gene Signatures

Conditions
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Gastric Cancer, Effects of Chemotherapy, Surgery

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the stomach or gastroesophageal cancer Age ≥18 years old Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 Body mass index ≥ 18 No prior chemotherapy or chemoradiotherapy TNM stage of T3-T4 and/or positive regional lymph nodes (N+) by endoscopic ultrasound or computed tomography (CT) No evidence of metastasis (M0) Adequate hematological, liver and renal functions (ALT and AST≤2.5 UNL, total bilirubin ≤1.5 UNL, and serum creatinine ≤1.5 UNL) Exclusion Criteria: Patients with previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated Patients with evidence of severe or uncontrolled systemic disease Medically unfit for chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>3-4 cycles of preoperative chemotherapy Surgery | |
| Group B<br>3-4 cycles of induction chemotherapy Radiotherapy with concurrent chemotherapy for 5 weeks Surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the period from diagnosis until death (from any cause). Nonlinear mixed effects population modelling to evaluate the impact in clinical outcome of dynamic markers as tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR). | From date of diagnosis until death, assessed up to 10 years | 
| Disease Free Survival | DFS was defined as the time from diagnosis to the first date of local or distant cancer. Nonlinear mixed effects population modelling to evaluate the impact in clinical outcome of dynamic markers as tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR). | From date of diagnosis until treatment failure, assessed up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Response at the Time of Surgery | Specimen analysis according to TNM classification. Pathological complete response is defined as no invasive cancer cells in the surgical specimen. | Weeks 10 to 28 | 
| R0 Resection rate at the Time of Surgery | The R0 resection rate after the neoadjuvant protocol. R0 is defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. | Weeks 10 to 28 | 
| Tumor Regression Grade at the Time of Surgery | Estimate of tumor regression grade at the time of surgery according to Becker Criteria: Grade 1a, No residual tumor; Grade 1b, <10% residual tumor; Grade 2, 10-50% residual tumor; Grade 3, >50% residual tumor. | Weeks 10 to 28 | 
| Lymph nodes response at the Time of Surgery | Participants were assessed for node-negative lymph nodes at the time of surgery according to TNM classification. Node-negative (pN0) participants had no regional lymph node metastasis. | Weeks 10 to 28 | 
| Estimate of TN Change From Baseline to Surgery | Estimate of TN change due to neoadjuvant treatment is defined as the estimate of the evidence of downstaging between baseline and surgery | Weeks 10 to 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Neoadjuvant therapy, Pharmacodynamics, Pharmacokinetics, Nonlinear Dynamics