Expression of hypoxia-inducible factor 1α predicts clinical outcome after preoperative hyperthermo-chemoradiotherapy for locally advanced rectal cancer.

Hypoxia-inducible factor 1α (HIF-1α) is an intrinsic marker of tumor hypoxia. It has been considered that hypoxic conditions reduce radiosensitivity, but the role of HIF-1α in patients treated with preoperative therapy for rectal cancer is still unclear. The aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (HCRT) and the prognostic significance of HIF-1α expression in patients with locally advanced rectal cancer. Between 2003 and 2006, 50 patients with histologically proven rectal adenocarcinoma who underwent HCRT followed by surgery were investigated. HIF-1α expression was immunohistochemically evaluated using pre-treatment biopsies. The total radiation dose was 40-50 Gy and chemotherapy consisted of 5-FU and LV administered by continuous infusion on Day 1-5, Day 15-19, and Day 29-33 during radiotherapy. Hyperthermia treatment was performed for once a week for 2-5 sessions. The surgical operation was performed 8 weeks after HCRT and each resected specimen was graded by histological criteria of the Japanese Classification of Colorectal Carcinoma. The effects of HIF-1α on clinical outcomes were analyzed by univariate and multivariate analysis. Positive HIF-1α expression was recognized in 42.0% of samples (21/50). Resected specimens that showed pathological grades 1, 2, and 3 numbered 17, 24, and 9 cases, respectively. There were no significant differences between the HIF-1α-positive group and HIF-1α-negative group for pathological grading and pCR. Overall survival (OS) rate at 3 years in the HIF-1α-negative group was 85.2%, which was significantly better than the 60.6% in the HIF-1α-positive group. Recurrence-free survival (RFS) rate at 3 years in the HIF-1α-negative group was 82.8%, being significantly better than 47.6% in the HIF-1α-positive group. In addition, elevated HIF-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. HIF-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with HCRT.

L-type amino-acid transporter 1 expression predicts the response to preoperative hyperthermo-chemoradiotherapy for advanced rectal cancer.

AIM: To evaluate whether expression of L-type amino acid transporter 1 (LAT1) in pretreatment rectal cancer biopsies is predictive of tumour response to neoadjuvant hyperthermo-chemoradiotherapy (HCRT). PATIENTS AND METHODS: Forty-four patients with rectal adenocarcinoma who received neoadjuvant HCRT were investigated. LAT1 expression was immunohistochemically evaluated using pretreatment biopsies. The operation was performed after 2-3 months following HCRT and each resected specimen was graded by the histological criteria of the Japanese Classification of Colorectal Carcinoma. RESULTS: A positive LAT1 expression was recognized in 50.0% (22/44) of patients. Resected specimens were divided into 2 groups according to the histological grading criteria: good response (n=29) and poor response (n=15). LAT1-negative tumours had an 81.8% probability of good response and 18.2% probability of poor response. LAT1 expression showed marginally significant association with response to HCRT (p=0.05). CONCLUSION: LAT1 may be a useful predictive marker of response to HCRT in rectal cancer.

Inoperable Pancoast tumors treated with hyperthermia-inclusive multimodality therapies.

PURPOSE: This study aimed to assess the feasibility, efficacy and complication of hyperthermia-inclusive multimodality therapies for patient with inoperable Pancoast tumor. MATERIAL AND METHODS: Five patients with inoperable Pancoast tumor were treated with hyperthermia-inclusive multimodality therapies. They received thermoradiotherapy with/without chemotherapy. Radiation therapy was delivered using 10 MV X-rays with total dose of 68-70 Gy. In the latter half of the radiation therapy hyperthermia was performed for 2-4 sessions once a week with 8 MHz radiofrequency device. RESULTS: For primary response, 4 tumors showed partial response to the treatment with the exception of 1 tumor who showed stable disease. Only one patient was with a short follow-up period (9 months), all other patients survived 3 years or more without recurrence. Of them, 2 patients were recognized with local recurrence at 38.7 and 42.7 months after treatment and died at 66.9 and 78.5 months after treatment. The other 2 patients are disease-free survivor for 4 and 5 years after treatment. No severe non-hematological toxicity was observed in each patient. CONCLUSION: These data suggested that hyperthermia-inclusive multimodality therapies might be a promising approach for inoperable Pancoast tumor.