The clinical benefit of hyperthermia in pancreatic cancer: a systematic review

Objective: In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. Methods and materials: We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (mp) and compared these between hyperthermia and control cohorts. Results: Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer mp in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%). Conclusions: Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.研究目的：胰腺癌因缺氧微环境而产生治疗抵抗，热疗（Hyperthermia）或可增强放化疗的疗效。本系统综述（Systematic Review）旨在验证下述假说的合理性：在放疗（Radiotherapy）和/或化疗（Chemotherapy）基础上联合热疗，可改善胰腺癌患者的治疗结局。 材料与方法：我们检索了MEDLINE与Embase数据库，并辅以手工检索，筛选纳入涉及胰腺癌患者热疗治疗的临床研究。采用牛津循证医学中心（Oxford Centre for Evidence-Based Medicine）证据等级量表对研究质量进行评估。本研究的主要结局为治疗有效性：我们计算了总体缓解率（Overall Response Rate）以及人群中位总生存期（mp，Median Overall Survival）的加权估计值，并对比热疗组与对照组队列的相关指标。 结果：最终共纳入14项研究，涉及395例局部晚期和/或转移性胰腺癌患者，其中248例接受热疗治疗。患者接受的热疗方式包括区域热疗（Regional Hyperthermia，n=189）、术中热疗（Intraoperative Hyperthermia，n=39）及全身热疗（Whole-body Hyperthermia，n=20），联合化疗、放疗或二者联合开展。纳入研究的质量普遍偏低，证据等级为3级（共5项研究）与4级。其中6项设置对照组的研究显示，热疗组的中位总生存期显著长于对照组（11.7个月 vs 5.6个月）。另有3项设置对照组的研究报告了总体缓解率，热疗组的缓解率同样优于对照组（43.9% vs 35.3%）。 结论：在化疗和/或放疗基础上联合热疗，或可对胰腺癌患者的治疗结局产生积极影响。但本次综述纳入的研究质量存在局限，未来需开展随机对照试验（Randomised Controlled Trials）以明确其治疗有效性。