Survival benefit of adjuvant chemoradiotherapy for positive or close resection margin after curative resection of pancreatic adenocarcinoma

BackgroundThis study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma.MethodsFrom 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn’t receive any adjuvant therapy (noTx group).ResultsLocoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS.ConclusionsAdjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen–based randomized evidence is needed for these high-risk patients.     

Impact of single-nucleotide polymorphisms in DNA repair pathway genes on response to chemoradiotherapy in rectal cancer patients: Results from ACCORD-12/PRODIGE-2 phase III trial

We examined whether 66 germline single-nucleotide polymorphisms (SNPs) in 10 candidate genes would predict clinical outcome in 316 patients with resectable locally advanced rectal cancer (LARC) enrolled in the ACCORD-12 phase III trial who were randomly treated with preoperative radiotherapy plus capecitabine (CAP45; n = 155) or dose-intensified radiotherapy plus capecitabine and oxaliplatin (CAPOX50; n = 161). The primary endpoint was tumor response according to the Dworak score. Multivariate logistic regression models adjusted on treatment arm and T stage determined the SNPs prognostic and predictive values for tumor response. In univariate analysis, five SNPs in ERCC2, XPA, MTHFR and ERCC1 were associated with the Dworak score in the CAPOX50 arm. In the overall population, interaction with treatment arm was significant for ERCC2 rs1799787 (p_interaction = 0.05) and XPA rs3176683 (p_interaction = 0.008), suggesting a predictive effect for response to oxaliplatin-based chemoradiotherapy (CRT). All but XPA rs3176683 had a prognostic effect on tumor response. In a multivariate model, interaction remained significant for XPA rs3176683 ([OR 7.33, 95% CI 1.40–38.23], p_interaction = 0.018) and the prognostic effect significant for ERCC2 rs1799787 ([OR 0.55, 95%CI 0.32–0.93], p = 0.027) and ERCC1 rs10412761 ([OR 0.57, 95%CI 0.34–0.98], p = 0.042). Patients with the T/G haplotype of rs1799787 and rs10412761 had a 60% decrease in odds of response (p < 0.001). None of the five SNPs were associated with toxicity, overall and disease-free survival. These data suggest that genetic variation in DNA repair genes influences response to preoperative CRT in LARC and identify patients who benefit from the addition of oxaliplatin to CRT.     

不可手术切除的食管癌同步放化疗进展

食管癌起病隐袭，早期诊断率低，发现时绝大部分已失去手术机会，放疗或化疗生存率也不乐观。近年研究表明，对于不可手术切除的食管癌，同步放化疗成为标准治疗方式。我国食管癌以鳞癌为主区别于欧美国家，研究适合于我国食管癌特点的同步放化疗方案尤为重要。本文就近年来不可手术切除的食管癌同步放化疗的新进展做一综述。     

局部复发性食管癌放疗的研究进展

食管癌在我国已经是最常见的消化道恶性肿瘤之一，食管癌治疗失败的原因主要是局部复发和未控，并且发现大部分患者在食管癌根治术后1～2年内复发。目前手术治疗、再程放疗、放化疗、靶向治疗等是食管癌治疗的主要手段，本文将对食管癌复发的因素及不同的放疗方式进行综述，进一步为局部复发性食管癌的治疗提供参考。     

The impact of epidermal growth factor receptor mutations on the efficacy of definitive chemoradiotherapy in patients with locally advanced unresectable stage III non-small cell lung cancer: a systematic review and meta-analysis

Objectives: To investigate the impact of EGFR mutations on the efficacy of definitive chemoradiotherapy (CRT) in patients with locally advanced unresectable stage III NSCLC.

Methods: PubMed and EMBASE were searched for eligible studies. Efficacy outcomes included objective response rate (ORR), overall disease progression, local-regional recurrence (LRR), distant progression (DP), brain metastasis, progression-free survival (PFS) and overall survival (OS). Meta-analysis was performed when relevant data were available.

Results: The authors identified seven eligible studies including 695 patients. No significant difference was detected in ORR (Risk Ratio [RR] 1.13, 95% confidence interval [CI] 0.91–1.39, P = 0.28) and overall disease progression (RR 1.06, 95% CI 0.95–1.19, P = 0.29) between EGFR-mutant and EGFR-wild-type groups. EGFR-mutant group had significantly lower LRR (RR 0.49, 95% CI 0.33–0.72, P < 0.01), higher DP (RR 1.36, 95% CI 1.18–1.55, P < 0.01) and higher brain metastasis (RR 2.48, 95% CI 1.46–4.20, P < 0.01) than the EGFR-wild-type group. No sufficient data were available to perform pooled analysis regarding PFS and OS.

Conclusion: For patients with locally advanced unresectable stage III NSCLC treated with definitive CRT, the presence of EGFR mutations may be indicative of lower locoregional recurrence and higher distant progression, especially brain metastasis.     

Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta-analysis

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.