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.

目标：鉴于胰腺癌对治疗的抵抗性源于其缺氧的微环境，高温可能增强放疗（化疗）的效果。本系统综述旨在探讨附加放疗和/或化疗的高温治疗能否改善胰腺癌患者治疗结果的假设的有效性。研究方法与材料：我们通过MEDLINE和Embase数据库检索，辅以人工检索，寻找涉及胰腺癌患者高温治疗的临床研究。采用牛津循证医学中心证据水平对研究质量进行评估。主要结局指标为治疗有效性；我们计算了总体反应率和加权估计的群体中位总生存期（mp），并比较了高温治疗组和对照组之间的差异。结果：共纳入14项研究，涉及395名患有局部晚期和/或转移性胰腺癌的患者，其中248名接受了高温治疗。患者接受了区域（n=189）、术中（n=39）或全身高温治疗（n=20），并联合化疗、放疗或两者兼而有之。研究质量较低，证据水平为3级（五项研究）和4级。包括对照组的六项研究表明，高温治疗组的中位总生存期（11.7个月）长于对照组（5.6个月）。在包括对照组的三项研究中，高温治疗组的总体反应率（43.9%）也优于对照组（35.3%）。结论：高温治疗与化疗和/或放疗联合使用，可能对胰腺癌患者的治疗结果产生积极影响。然而，所审查的研究质量有限，未来需要更多随机对照试验以确立其疗效。