Surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for gastric cancer: a systematic review and meta-analysis of randomised controlled trials.
Topic: Hyperthermia

Adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) is a therapy which combines thermotherapy and intraperitoneal chemotherapy. It is theoretically powerful for patients with advanced gastric cancer (AGC), but is there evident advantage in clinical practice? We need evidence to guide our decision-making.

PICO
Population: Patients with advanced gastric cancer (AGC)
Intervention: Surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy (IHIC)
Comparison: Standard care or surgery alone
Outcomes: Clinical outcomes and survival rates

Included studies:
title: Chemotherapy combined with or without hyperthermia for patients with oesophageal carcinoma: a prospective randomized trial.
abstract: From 1990 to 1991, 40 patients with squamous cell carcinoma of the thoracic oesophagus were admitted to our institutions and chemotherapy (oil Bleomycin p.o. and CDDP d.i.v.) either combined with or without hyperthermia was performed, in a prospective randomized trial carried out to investigate the effects of hyperthermia. The two groups (group A, consisting of 20 patients given chemotherapy alone; and group B, made up of 20 given chemotherapy with hyperthermia) were comparable with regard to various prognostic factors. Following the above treatment regimens, an oesophagectomy was done in 16 and 17 patients from groups A and B, respectively. A subjective improvement of dysphagia was seen in 8 (40.0%), and in 14 patients (70.0%), while a radiographic improvement was recognized in 5 (25.0%) and 10 cases (50.0%) in groups A and B, respectively. In the resected specimen of 16 (group A) and 17 patients (group B), histopathological evidence of the effectiveness of the treatments were recognized in 3 (18.8%) and 7 (41.2%) from groups A and B, respectively. Excluding the cases of superficial carcinoma (T1 tumour), histologic effectiveness of the treatments were recognized in 2 (14.3%) and 7 (58.3%) in groups A and B, respectively (p < 0.05). There was no difference in the occurrence of side effects between the groups. Therefore, the clinical and pathological effects were favourable in the hyperthermia combined with chemotherapy group, especially in the cases with advanced oesophageal cancer.
title: Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion.
abstract: To evaluate the effects of continuous hyperthermic peritoneal perfusion (CHPP) together with standard chemotherapy on the prognosis of patients with gastric cancer invading the serosa.
title: Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial.
abstract: Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients.
title: The regimen of gemcitabine and cisplatin combined with radio frequency hyperthermia for advanced non-small cell lung cancer: a phase II study.
abstract: This phase II randomised trial was designed to evaluate the therapeutic efficacy and feasibility of radio frequency regional hyperthermia in combination with chemotherapy for patients with advanced non-small lung cancer (NSCLC).
title: Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus--a prospective randomized trial.
abstract: From 1988 to 1990, 53 patients with squamous cell carcinoma of the thoracic oesophagus underwent subtotal oesophagectomy after either preoperative hyperthermo-chemoradiotherapy (HCR therapy) or chemoradiotherapy without hyperthermia (CR therapy), in a prospective randomized trial carried out to examine the effects of hyperthermia given preoperatively. The two groups (27 patients given HCR therapy and 26 given CR therapy) were found to be comparable with regard to prognostic factors of age, site of carcinoma, TNM stage, etc. Following preoperative evaluation by an upper GI series and endoscopy, a subtotal oesophagectomy was done for all 53 patients. All the resected specimens, including the lymph nodes, were histopathologically examined, and the effects of preoperative treatment were evaluated by findings in the upper GI series and endoscopy, as well as based on the histopathology of the excised tissues. There were no viable cancer cells in the resected specimens of seven patients in the HCR therapy group (26.9%) and of two patients in the CR therapy group (7.7%). In addition, no hyperthermia complications were observed. The study suggests that preoperative HCR therapy may be a more beneficial therapy than preoperative CR therapy in patients with squamous cell carcinoma of the oesophagus who undergo a subtotal oesophagectomy.
title: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.
abstract: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction.
title: Clinical outcomes of mild hyperthermia for locally advanced rectal cancer treated with preoperative radiochemotherapy.
abstract: The aim of this report was to determine the impact of hyperthermia (HT) on preoperative radiochemotherapy for locally advanced rectal cancer.
title: Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study.
abstract: Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence, there was no effective therapy for the prevention of peritoneal recurrence. This randomized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer.
title: Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study.
abstract: To compare the local tumour control, survival, and acute mucous toxicity of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy (RT) combined with intracavity hyperthermia versus conventional RT alone.
title: Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study.
abstract: Continuous hyperthermic peritoneal perfusion (CHPP) with a solution that contained 10 micrograms/ml mitomycin C was devised initially as a method for intraperitoneal thermochemotherapy. The authors conducted a randomized clinical trial to evaluate the efficacy of CHPP as a prophylactic treatment for prevention of peritoneal recurrence of gastric cancer with serosal invasion.
title: Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: randomized controlled study.
abstract: We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations.
title: Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma.
abstract: The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence, even when a curative gastrectomy is performed, because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal-invaded focus. In an attempt to prevent peritoneal recurrence, intraperitoneal hyperthermic chemoperfusion (IHCP) treatment was combined with aggressive surgery.
title: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.
abstract: A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.
title: [Application of hyperthermic intraoperative intraperitoneal chemotherapy in patients with gastric cancer].
abstract: To explore the effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) on the postoperative metastatic rate and survival rate of advanced gastric cancer (AGC).