Abstract
Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence.Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments.Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%].Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.
Highlights
Gastric cancer (GC) is the third leading cause of cancer death worldwide in 2012 (Job Action Sheets, 2014)
We only included the randomized controlled trials (RCTs) that compared at least two arms of following treatments: surgery alone, perioperative FLOT, surgery combined with neoadjuvant treatments involving chemotherapy or chemoradiotherapy listed in the National Comprehensive Cancer Network (NCCN) guidelines
A total of 2434 patient treated in seven different treatments were included: 701 treated with surgery alone; 113, perioperative cisplatin with fluorouracil (CF); 207, preoperative CF; 610, perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX); 356, perioperative FLOT; 234, preoperative radiotherapy combined with CF (RT/CF); 213, preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC)
Summary
Gastric cancer (GC) is the third leading cause of cancer death worldwide in 2012 (Job Action Sheets, 2014). Complete surgical resection currently is the only curative treatment for localized GC (Van de Velde and Peeters, 2003; van Cutsem et al, 2011). GC is often diagnosed at an advanced stage which is unsuitable for radical surgery (Van de Velde and Peeters, 2003). Even despite potentially curative surgical resections, the prognosis of patients with more advanced GC (T2–4) remains poor due to metastatic disease or local recurrence after radical gastrectomy (Briasoulis et al, 2006; Reim et al, 2013). Perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT) have demonstrated high efficacy against resectable gastroesophageal cancer (Al-Batran et al, 2017). Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence
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