Zdeněk Zoul

Liposomal doxorubicin combined with regional hyperthermia: Reducing systemic toxicity and improving locoregional efficacy in the treatment of solid tumors

Summary Incorporation of doxorubicin into polyethylene glycol-coated (pegylated) liposomes increases the therapeutic index, prolongs circulation time and enhances tumor localization. Pegylated liposomal doxorubicin (PLD) is an established therapeutic agent in epithelial ovarian carcinoma (EOC), breast carcinoma or Kaposi’s sarcoma, and PLD administration results in reduction of toxicity. Addition of regional hyperthermia increases liposome extravasation, induces the doxorubicin release from the liposomes, and the combination of hyperthermia and doxorubicin itself may be supra-additive, resulting in enhanced antitumor efficacy in the heated region. Encouraging results have been reported for the combination of PLD and hyperthermia in EOC, breast carcinoma and hepatocellular carcinoma.

Weekly Paclitaxel Combined with Local Hyperthermia in the Therapy of Breast Cancer Locally Recurrent after Mastectomy – a Pilot Experience

Background: The combination of chemotherapy and hyperthermia (HT) is a promising approach in the treatment of malignant tumors. In the present report we evaluate the efficacy and toxicity of a combination of weekly paclitaxel combined with local hyperthermia in breast cancer. Patients and Methods: 7 patients were treated for inoperable local recurrence of breast cancer after mastectomy, irradiation, and chemotherapy or hormonal therapy. They weekly received paclitaxel (60–80 mg/m²) in 3-h infusions followed by local HT 41–44 °C for 45 min for 6–18 cycles. Results: Objective local response was observed in all treated patients (complete response in 4 patients and partial response in 3 patients). There were no grade 3 or 4 toxicities, neurologic toxicity or hypersensitivity reactions. Local tolerance to this regimen was also good, with only 4 patients developing mild transient erythema. Conclusion: Our experience indicates that the combination of weekly paclitaxel and HT may be effective in the treatment of locally recurrent breast cancer after mastectomy.

Pegylated Liposomal Doxorubicin in Combination with Hyperthermia for Treatment of Skin Metastases of Breast Carcinoma: A Case Report

Background: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. Case Report: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx®) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41–43 °C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. Conclusion: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.

Endovascular brachytherapy of transjugular intrahepatic portosystemic shunt

Purpose: To evaluate the technical feasibility and efficacy of endovascular brachytherapy with Iridium-192 in the prevention of restenosis caused by neointimal hyperplasia of transjugular intrahepatic portosystemic shunt (TIPS).Materials and Methods: The endovascular brachytherapy with high dose rate automatic afterloading system was performed in six patients with recurrent of stenosis of TIPS. We used a single dose fraction of 12 Gy delivered at 3 millimeter (mm) from the source axis to the stenotic vessel segment in five patients with spiral Z-stent, and 15 Gy at 5 mm in one patient with Wallstent.Results: Follow-up time ranged from 148 to 639 days. In one patient, restenosis occurred in the treated vessel segment, diagnosed 71 days after endovascular brachytherapy by doppler ultrasound. All other patients were, during the follow-up time, without restenosis in the irradiated vessel segment. Radiation-associated side effects were not observed.Conclusions: Endovascular brachytherapy of TIPS is technically feasible and may be done as a part of the percutaneous revision of the shunt. This pilot study may be the largest experience of treating TIPS restenosis in humans to date. For definitive conclusions, a lot of studies are needed.

Cutaneous Recurrence of Malignant Mesothelioma of the Tunica Vaginalis Testis: a Rare Case Report

Background: Mesothelioma of the tunica vaginalis testis is a rare and aggressive cancer; fewer than 90 cases have been reported. It occurs in all age groups, but its highest incidence appears between 55 and 75 years of age. Less than 5% of all malignant mesotheliomas arise from the tunica vaginalis testis. Case Report: The authors present a rare case of localized malignant mesothelioma of the tunica vaginalis testis. Diagnosis and treatment are described. Conclusion: Mesothelioma of the tunica vaginalis testis can be asymptomatic for a long time. In more than half of the cases, the clinical manifestations imitate a hydrocele or a tumor mass in the scrotum. Despite treatment, this tumor has a very poor prognosis with a median survival of 23 months.

Endovascular brachytherapy in the prevention of vascular restenosis

PURPOSE To evaluate the technical feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS Ten patients with recurrence of stenosis in the femoropopliteal region underwent PTA followed by endovascular irradiation with Iridium-192 a high-dose rate after-loading technique. We used a single fraction of dose 12 Gy given in 3 mm from the source axis in the stenotic vessel segment. RESULTS During follow-up of 59-580 days restenosis occurred in four patients 111, 460, 472 and 580 days after irradiation. All other patients are without restenosis. No radiation-associated side effects were observed. CONCLUSIONS Endovascular brachytherapy of restenosis in the femoropopliteal region is technically feasible, and may be done as a part of the PTA. These encouraging results open the possibility of reduction of restenosis by the present method.

Endovascular brachytherapy potentiated by hyperthermia in the prevention of vascular restenosis. A case report.

BACKGROUND The combination of hyperthermia and radiotherapy has additive or synergistic effects. This combination has been studied extensively in radiation oncology, but not in the prevention of vascular restenosis. CASE REPORT A patient with restenosis of cephalic vein underwent percutaneous transluminal angioplasty (PTA) followed by endovascular irradiation with 192Iridium (12 Gy) using a high dose rate afterloading technique. After endovascular irradiation, one fraction of external ultrasound hyperthermia was administered to the irradiated segment. There was no restenosis in the treated vessel segment according to duplex sonography performed 192 days after treatment. No radiation or hyperthermia associated side effects were observed. CONCLUSIONS Present observations suggest that endovascular brachytherapy of restenosis potentiated by hyperthermia is a technically feasible and well-tolerated treatment. The additive and synergistic effects of hyperthermia, in conjunction with radiation, could be of benefit in the prevention of vascular restenosis.