Preoperative Hyperthermochemoradiotherapy Research Articles

Outcomes of surgical treatment in patients with anorectal fistula cancer

BackgroundNo standard treatment for anorectal fistula cancer, such as multidisciplinary therapy, has been established due to the rarity of the disease. Herein, we investigated patients with cancer associated with anorectal fistula who underwent surgery to clarify the clinicopathological characteristics and to propose future perspectives for treatment strategies.Case presentationSeven patients with cancer associated with anorectal fistula who underwent rectal amputation in our institute were analyzed with regard to clinical characteristics, pathological findings, surgical results, and prognosis. Four cases had Crohn's disease as an underlying cause. All seven cases were diagnosed as advanced stage. Preoperative [18F]-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography/computed tomography (FDG-PET/CT) showed abnormal FDG accumulation in six cases including four mucinous adenocarcinomas. Three cases that received preoperative hyperthermo-chemoradiotherapy achieved pathological R0 resection. Postoperative recurrence was observed in four cases including three with Crohn's disease and one resulting in death.ConclusionsAnorectal fistula cancer is rare and difficult to be diagnosed at early stages. Mucinous adenocarcinoma associated with anorectal fistula tends to exhibit abnormal FDG accumulation by FDG-PET/CT unlike common colorectal mucinous adenocarcinoma. Preoperative hyperthermo-chemoradiotherapy may be effective in obtaining pathological complete resection.

SUVmax-based Parameters of FDG-PET/CT Reliably Predict Pathologic Complete Response After Preoperative Hyperthermo-chemoradiotherapy in Rectal Cancer.

To determine the most reliable predictor for pathologic complete response (pCR) in patients who underwent preoperative chemoradiotherapy and regional hyperthermia (HCRT) for rectal cancer. Thirty-six patients were enrolled. The local control status of the patients was assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), magnetic resonance imaging (MRI), and colonoscopy before and after HCRT. The relationships between various parameters of these clinical examinations and pCR were analyzed. Ten (28%) patients achieved pCR. The accuracies of predicting pCR using FDG-PET/CT, MRI, and colonoscopy were 78%, 61%, and 75%, respectively. FDG-PET/CT was the only independent predictive modality for pCR (p=0.021). The maximum standardized uptake value (SUVmax) and SUVmax normalized to liver uptake (SLR) after HCRT showed the highest sensitivity (90%) and the decreasing rate of SUVmax and SLR demonstrated the highest specificity (89%) for pCR. SUVmax-based parameters of FDG-PET/CT after HCRT were the most reliable predictors for pCR.

HLA class I expression and its alteration by preoperative hyperthermo-chemoradiotherapy in patients with rectal cancer.

ObjectiveEnhancing immunologic responses, including human leukocyte antigen (HLA) class I expression on tumor cells and recognition and elimination of tumor cells by tumor-specific cytotoxic T lymphocyte (CTL), is considered a novel concept of radiotherapy. The present study examined patients who underwent preoperative hyperthermo-chemoradiotherapy (HCRT) for locally advanced rectal cancer to assess the correlation between HLA class I expression and clinical outcome.Materials and MethodsSeventy-eight patients with locally advanced rectal adenocarcinoma who received preoperative HCRT were enrolled. The median age of the patients was 64 years (range, 33–85 years) and 4, 18, and 56 patients had clinical stage I, II and III disease, respectively. Formalin-fixed and paraffin-embedded tissues excised before and after HCRT were subjected to immunohistochemical analysis with an anti-HLA class I-A, B, C antibody. HLA class I expression was graded according to tumor cell positivity.ResultsIn pre-HCRT, the number of specimens categorized as Grade 0 and 1 were 19 (24%) and 58 (74%), respectively. Only 1 patient (1%) showed Grade 2 expression. However, 6 (8%), 27 (35%), 7 (9%), and 12 (15%) post-HCRT specimens were graded as Grade 0, 1, 2, and 3, respectively. There was a significant increase in HLA class I expression in post-HCRT specimens (p<0.01). However, neither pre- nor post-HCRT HLA class I expression affected overall survival and distant metastasis-free survival in clinical stage III patients. Univariate analysis revealed that Post-HCRT HLA class I expression showed a significant negative relationship with LC (p<0.05). Nevertheless, multivariate analysis showed that there was no correlation between HLA class I expression and clinical outcome.ConclusionHCRT increased HLA class I expression in rectal cancer patients. However, multivariate analysis failed to show any correlation between the level of HLA class I expression and prognosis.

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 Locally Advanced Rectal Cancer

L-type Amino-acid Transporter 1 Expression Predicts the Response to Preoperative Hyperthermo-chemoradiotherapy for Locally Advanced Rectal Cancer

Recent advances in preoperative hyperthermochemoradiotherapy for patients with esophageal cancer

Background and Objectives Hyperthermochemoradiotherapy (HCR) has been performed on numerous patients with esophageal cancer. The purpose of this study is to demonstrate the recent advances in HCR. Methods From 1965 to 1997, 294 patients given preoperative chemoradiotherapy (CR) or HCR were classified according to the anticancer agent that was administered (CR; group A given bleomycin (BLM); group B given cis-diamminedichloroplatinum (II) (CDDP), HCR; group C given BLM; and Group D given CDDP). The local response and the long-term results were investigated. Results The cases in which CR or HCR was evaluated to be effective numbered 44 (48.4%) in Ygroup A, 22 (73.3%) in group B, 79 (63.7%) in group C, and 36 (73.5%) in group D. A significant difference was observed between groups A and B (P< 0.05). The highest incidence of markedly effective cases was observed in group D. The 5-year survival rates for the group A and B patients were 17.2% and 43.9%, respectively (P< 0.01), while the same rates for those of groups C and D were 25.6% and 57.8%, respectively (P< 0.05). Our results thus showed CDDP to have a greater effect than BLM, while HCR had a greater effect than CR. Conclusions Preoperative HCR has improved thanks to recent advances in anticancer agents. J. Surg. Oncol. 1998;69:224–229. © 1998 Wiley-Liss, Inc.

Clinicopathologic Features of Patients with Oesophageal Cancer Obtaining a Histological Complete Response for Preoperative Hyperthermo-Chemo-Radiotherapy

From 1979 to 1993, 151 patients with resectable oesophageal cancer underwent preoperative hyperthermo-chemo-radiotherapy (HCR) followed by a subtotal esophagectomy. All resected specimens were histopathologically evaluated, and then were classified into two groups according to the efficacy of the preoperative HCR. Group A included 33 patients whose resected oesophagus was free of any cancer cells (grade 3). Group B included 118 patients, in which viable cancer cells remained in the resected specimens to various degrees (grade 1,2). The incidence of patients with well differentiated squamous cell carcinoma, node negative cases, or TNM stage I/II was significantly higher in group A than in group B (27.3% versus 9.3%, 72.7% versus 50.8%, 72.7% versus 50.8%, respectively). The recurrence rate was 33.3% (11/33) in group A, while it was 65.3% (77/118) in group B (p < 0.005). There was no case with any local recurrence in the former, while it was 8.5% (10/118) in the latter. The 1-, 3- and 5-year survival rates were 87.2%, 65.9% and 46.1% in group A, while they were 54.8%, 26.7% and 18.8% in group B (p < 0.005), respectively. Preoperative HCR may be expected of decreasing in the recurrence rate, including regional relapse when a grade 3 is obtained. Complete local control would further positively influence the prognosis.

Preoperative hyperthermochemoradiotherapy for soft tissue sarcoma

We investigated the efficacy of preoperative hyperthermia combined with radiation therapy and systemic chemotherapy (hyperthermochemoradiotherapy; HCRT) as a multimodality limb-sparing approach for soft tissue sarcomas. From January 1991 to December 1994, HCRT was performed in 13 patients with soft tissue sarcomas at our institute. Hyperthermia, with an intratumoral temperature of ≥42.0°C, was given for 1h for a total of eight to ten times. Radiation therapy (30–40Gy) was given at 200cGy per fraction. Two cycles of chemotherapy were given before surgery. It took 4–5weeks to accomplish the HCRT, and surgery was performed 3weeks later. Partial response (PR) was achieved in 3 patients and no change (NC) was shown in 10. The mean reduction of tumor volume was 20.2%. Pathological examination of the resected specimen revealed 10%–100% tumor necrosis (mean 76.4 %). There was no correlation between histologic response and reduction of tumor volume. Limb-sparing surgery was feasible in 12 patients (92.3%) and the final limb salvage rate was 84.6%. No local recurrence was observed during a mean follow-up time of 25months. Four patients developed distant metastases and 2 patients died of the disease. The results of this study indicate that HCRT is an effective treatment for limb-threatening soft tissue sarcomas.

Preoperative hyperthermochemoradiotherapy for patients with esophageal carcinoma or rectal carcinoma

Hyperthermia is effective for the treatment of carcinoma when applied concomitantly with chemotherapy and irradiation. However, it is difficult to heat deep portions of the body, such as the esophagus and the rectum. We therefore devised an electrode for radio frequency, and we have been successfully using this electrode in the treatment of both esophageal and rectal carcinoma. The 5 yr survival rates of patients with esophageal carcinoma, given either preoperative hyperthermochemoradiotherapy or chemoradiotherapy, were 43.2 and 14.7%, respectively. On the other hand, 11 patients with rectal carcinoma underwent radical surgery after preoperative hyperthermochemoradiotherapy. In the histologic studies of in the resected specimens, patients classified as marked, moderate, mild, and no effectiveness were seen in six, three, two, and zero cases, respectively. Since there were no severe side effects in patients given hyperthermia, this treatment deserves serious consideration when treating patients with malignant lesions in the esophagus or rectum.