Hyperthermia (HT) can be directly cytotoxic to cancer cells, and can also act as a radiation-sensitizer and chemo-sensitizer. Although the combination of HT with radiotherapy has been the primary focus for research, there is an equally strong rationale for combining HT with chemotherapy (CT). New chemotherapeutic agents, such as irinotecan, oxaliplatin, gemcitabine and taxane, have been demonstrated to show thermal enhancement in several in vitro and/or in vivo studies. With regional or local HT, drug- and heat-induced toxicity can be localized, and systemic toxicity can be avoided or minimized. Generally, regional HT is less invasive than interstitial or intracavitary local HT, and can enhance chemotherapeutic effects in specific sites in the body. In many instances, systemic CT represents the most useful option for patients with surgically incurable malignant neoplasms. An approach which combines systemic CT with regional HT should be of interest, since it can enhance the efficacy of systemic chemotherapeutic drugs in specific areas. Here, we review clinical results of systemic CT combined with regional HT for the treatment of malignant neoplasms.
An endoscopic local ablation therapy (ELAT) was developed using microwave coagulation therapy and radiofrequency ablation for the treatment of hepatocellular carcinoma (HCC) in 1994. Superficial HCCs, consisting of up to three nodules, if each is smaller than 4 cm, and without vascular invasion, are good candidates for ELAT. ELAT is chosen for patients with HCCs which are inaccessible percutaneously. In our department, percutaneous, endoscopic, and open body approaches were used in 52%, 33% and 15% of the 450 patients treated with thermal ablation, respectively. Thoracoscopic and laparoscopic approaches were selected for HCCs located at the hepatic dome and other sites. Among the 115 patients who were treated with ELAT, the mean tumor size was 25 mm (range : 5 to 50 mm), and the mean tumor number was 2.2 (range : 1 to 5). Patients with liver damage levels of B or C accounted for 68% of those treated. ELAT showed a 95% response rate calculated using the tumor necrosis ratio, and only a 4% local recurrence rate (median observation period : 2.8 years). The average intraoperative blood loss, operating time, blood transfusion, and postoperative hospital stay for patients treated with ELAT was 80 g, 3 hrs, 0%, and 8 days, respectively. These parameters were significantly better than those for patients who underwent partial hepatectomy (680 g, 4.4 hrs, 22% and 20 days). In spite of severe hepatic dysfunction, the 5-year cumulative survival rate in patients treated with ELAT was 60%, which is similar to results following partial hepatectomy. Complication rates in patients treated with ELAT were 6.9%. No tumor recurrence was seen at the portal site, and no implantation of malignant cells was observed. In conclusion, an approach using ELAT is recommended for superficial HCC due to its effectiveness and because it is a less invasive method of treatment.
For a number of reasons, Magnetic Resonance Imaging (MRI) is a unique tool for interventional use. It has a spatial resolution which is independent of the wavelength of the electromagnetic field used for imaging, has various imaging parameters which are related to the physical properties of the subject ; provides a superior soft-tissue contrast ; provides freedom in determining the slicing or viewing angle ; and it utilizes non-ionizing radiation. This technology offers assistance in therapeutic applications such as lesion identification, treatment planning, device tracking, temperature imaging and treatment evaluation. In this article, the role of MRI in assisting thermal therapy is briefly reviewed from a technical point of view.
We staged the Malignant gliomas in the thalamus and basal ganglia seen at one institution over a 20-year period were staged, and the clinical features of hyperthermic treatment in these site were examined. The subjects in this study were inpatients who received treatments at Niigata University. There were 43 patients with grade 3 or 4 glioma in the basal ganglia (24 patients in the thalamus and 19 patients in the putamen). For staging, tumors in the thalamus and putamen were classified by their sizes : less than 2 cm, 2-4 cm, and greater than 4 cm were classified as stages 1 to 3. Tumors which progressed outside of the basal ganglia were classified as stage 4, and those which progressed to the ventricle were classified as stage 5. The percentage of patients in stage 4 whose tumor invaded to the internal capsule or midbrain was 30%, and this percentage reached 40% when combined with patients in stage 5. Resection was performed in 14 patients. Tumors of the 29 remaining patients were biopsied. In 14 of the biopsied cases, needle electrodes were implanted in the tumors, and interstitial hyperthermia was performed. The electrodes (RF antennas) were stereotactically implanted in the tumor under local anesthesia simultaneously with biopsy. The heating strategy used was to control the RF output in order to heat the rim of the tumor up to a temperature of 43°C for a 40-60 minute heating period. The heating procedure was repeated twice a week for a total of 3 to 4 times, and combined with conventional radiation therapy with a dose of 50-60 Gy, and MCNU or ACNU chemotherapy. The Median Survival Time (MST) for overall survival was 11 months (thalamic cases : 17 months ; putamen cases : 11 months). The MST for cases receiving hyperthermia was 22 months, and for cases which did not receive hyperthermia, the MST was 9 months. Few malignant gliomas in the basal ganglia were removed with surgery because of their localization. In more than a few cases, local treatments were difficult and the prognosis was poor. However, there were responsive cases among the patients who underwent hyperthermia.
The aim of the work presented here was to evaluate the efficacy and safety of a new regimen which combines weekly cisplatin-based chemotherapy and regional hyperthermia for the treatment of advanced hormone-refractory prostate cancer. Cisplatin (10 mg/body weight) was administered intravenously at weekly intervals one hour before regional hyperthermia, and was applied for a maximum of 10 cycles. Therapy was discontinued after the first 10 cycles in patients who responded, or in cases of stable disease, and was resumed as soon as any signs of progression were noted. Of the 15 patients evaluated, 6 were confirmed to have achieved a greater than 50% decrease in prostate specific antigen (PSA) levels (40.0%). The median response duration was 19.5 months, and the median time to progression was 9.0 months. Reduction of pain along with improvement in the quality of life were seen. Pain was reduced in 7 patients who were symptomatic at the beginning of the study. Of the 15 patients, 9 resumed therapy after the planned 10 original cycles of therapy. Of these, 9 received 10 mg of docetaxel/mg body weight. 4 patients had prostatic specific antigen (PSA) levels under 4 ng/ml (26.7%), and 2 patients exhibited stable disease. The regimen was well tolerated, and minor general fatigue (NCI-CTC grade1) was recognized in 3 patients, but no anemia or thrombocytopenia was observed. The results of this study suggest the feasibility and tolerability of using the combination of weekly cisplatin administration along with regional hyperthermia. This combined therapy led to a rapid and long lasting decrease in PSA levels and palliative responses in patients with advanced hormone-refractory prostate cancer.
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