Radiation-induced effects in multiprogrammable pacemakers and implantable defibrillators.

Twenty-three multiprogrammable pacemakers and four implantable cardioverter defibrillators (ICDs) containing either complementary metal-oxide semiconductor (CMOS) or CMOS/Bipolar integrated circuit (IC) technology were exposed to 6-MV photon and 18-MeV electron radiation at various dose levels. Of the 17 pacemakers exposed to photon radiation eight failed before 50 Gy, whereas four of the six pacemakers exposed to electron radiation failed before 70 Gy. Photon scatter doses were well tolerated.

Analysis and testing of a concentric ring applicator for ultrasound hyperthermia with clinical results.

A planar ultrasound transducer was modified by etching concentric circles on one surface of a piezoelectric ceramic to create four rings. The 10 cm diameter transducer had four active rings and an unenergized centre. The transducer housing was designed to be completely immersed in fluid, suitable for intraoperative hyperthermia.

Experimental brain hyperthermia: techniques for heat delivery and thermometry.

An experimental canine brain model was developed to assess the effects of hyperthermia for a range of time and temperature endpoints, delivered within a specified distance of an interstitial microwave antenna in normal brain. The target temperature location was defined radially at 5.0 or 7.

Fraction size in external beam radiation therapy in the treatment of melanoma.

RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of high dose per fraction irradiation in the treatment of melanoma. Retrospective analysis suggested a dose response curve of melanoma to external beam irradiation as the dose per fraction is increased. RTOG 83-05 randomized patients with measureable lesions to 4 x 8.

Lack of acute toxicity associated with a multimodality treatment of stage III ovarian epithelial carcinoma.

Eleven patients with advanced stage III ovarian epithelial carcinoma were treated primarily according to an aggressive multimodality plan utilizing cytoreductive surgery, chemotherapy (high-dose cisplatin and Cytoxan), and consolidative radiation therapy (abdominopelvic "bath" plus pelvic boost). The treatment was tolerated remarkably well. There was no evidence of progressive disease during treatment, and all patients showed a positive response.

Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow.

We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years).

Intraoperative radiation therapy and hyperthermia. Morbidity and mortality from this combined treatment modality for unresectable intra-abdominal carcinomas.

This is a report of a phase I trial of intraoperative radiation therapy in combination with intraoperative hyperthermia for the treatment of locally advanced, unresectable intra-abdominal carcinomas. Using an ultrasound transducer system specifically designed for intraoperative applications, 19 patients have been successfully treated, demonstrating the feasibility of this combination modality. The morbidity (58%) and mortality (11%) rates reported in this series are comparable to rates reported in series of similar patients receiving intraoperative radiation therapy alone.

Biologic and clinical developments of cisplatin combined with radiation: concepts, utility, projections for new trials, and the emergence of carboplatin.

Controlled experiments have shown that more than one mechanism leads to the potentiation of radiation-induced cell killing by cisplatin, and that this potentiation is not uniformly expressed among different cell types. A firm investigative base for the design of clinical trials using cisplatin and radiation has not been established. Coincident with this deficiency of experimental guidance, the independent clinical investigator has developed an array of therapeutic strategies applying different doses and sequences of cisplatin and radiation to a variety of tumor types.

Enhanced axonal transport of glycosaminoglycans in regenerating goldfish optic nerve.

Glycosaminoglycans (GAGs) derived from axonally transported proteoglycans were evaluated in regenerating goldfish optic tracts. Fish were administered unilateral optic nerve crushes and stored for 21 days at 21 degrees C. Retinas were labeled by bilateral injection of 35SO4 and sulfated macromolecules axonally transported to the optic tracts were analyzed 8 h postinjection.

Interstitial thermoradiotherapy.

The more recent engineering and clinical aspects of interstitial hyperthermia are reviewed. The advantages and difficulties of microwave, radiofrequency, and ferromagnetic seeds are evaluated and some future directions for improvements are outlined.

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies.

Over the past 5 years, 129 patients have been treated with a combination of high-dose cisplatin (CDDP) and radiation for locally advanced epithelial malignancies. The CDDP was administered at a dose of 100 mg/m2 by iv infusion over one-half hour, no more than 1 hour before irradiation, every 3 weeks during a full course of external beam irradiation. An attempt was made to take advantage of the interaction of high-dose CDDP and radiation.

Iridium-192 brachytherapy in combination with interstitial microwave-induced hyperthermia for malignant glioma.

A phase I clinical trial assessing the feasibility and safety of hyperthermia in combination with 192Ir brachytherapy (60 Gy) for the treatment of malignant glioma now includes 14 patients. Hyperthermia (42-43 degrees C at tumor margin for 60 min) has been induced using stereotactically implanted afterloading catheters and a microwave (915 or 2,450 MHz) antenna array. Thermometry recorded along each catheter confirms the general ability of the technique to heat such volumes, but thermal heterogeneities are documented.

Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid cell-specific monoclonal antibodies.

Second or third chemotherapy-induced remissions in acute myelogenous leukemia (AML) are limited by early relapse of the leukemia. We developed monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells to treat bone marrow from these patients ex vivo for autologous transplantation. In this pilot study, bone marrow was harvested from ten patients with AML in remission, treated with one or two complement-fixing MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation antigens, incubated with rabbit complement, and cryopreserved.

Treatment of the intact breast using tangent split beam fields and half 15 degree wedges as tissue compensators.

A 15 degree wedge inserted half way into the radiation field can be used effectively as a tissue compensator, in some cases reducing dose inhomogeneity by as much as 25%. The 15 degrees half wedge dosimetry and its application to a specific therapy technique is discussed in this article.

Preoperative irradiation potentiation with cisplatin: effect on rate of wound infection.

Platinum coordination complexes, such as cisplatin, potentiate the cytotoxicity of irradiation on squamous cell carcinoma and certain other solid tumors. Using a rat oro-cutaneous fistula model, an investigation was carried out to determine whether or not there was a concomitant potentiation with cisplatin of the deleterious effect of preoperative irradiation on the ability of a subsequent wound to handle a bacterial challenge. Auto-contaminated wounds were found to have increased rates of infection at single-dose orthovoltage pretreatments of 1,500 rads or more.

Actin isoform synthesis and mRNA levels in quiescent and proliferating rat aortic smooth muscle cells in vivo and in vitro.

The relative levels of actin isoform synthesis in rat aortic smooth muscle cells (SMC) have been studied in vivo and in culture by means of [35S]methionine incorporation. They have been compared to the functional levels of actin isoform mRNAs, assayed by translation of total cell RNA in a reticulocyte lysate or, in some cases, to the actin isoform RNA content, assayed by Northern-blot hybridization to a total actin cRNA probe. In normal media and in freshly isolated SMC, the relative levels of actin isoform synthesis and the actin mRNA translation products show a remarkable similarity, but differ from the proportions of actin isoforms present in a total cell extract (Gabbiani G, Kocher O, Bloom WS, Vandekerckhove J, Weber K: Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortic media.

Cisplatin and radiation therapy for locally advanced squamous cell carcinoma of the lung.

A pilot study was initiated to test the safety and efficacy of the simultaneous administration of high-dose cisplatin and irradiation in patients with locally advanced squamous cell carcinoma of the lung. Cisplatin was administered at 100 mg/m2 on Days 1 and 21 and was continued at 20 mg/m2 once a week to the completion of radiation therapy. Irradiation was begun on Day 22 and was administered 5 days a week for 6 weeks at a rate of 200 cGy per day to a total of 6000 cGy to the primary site, using a shrinking field technique.

A clinical trial of nafazatrom (Bay g 6575) in advanced cancer.

Nafazatrom (Bay g 6575) has been shown to be a potent inhibitor of tumor metastasis in preclinical models. It is believed to work by stimulating endogenous prostacyclin production. The drug has also been shown to inhibit the growth of certain experimental tumors, to be cytostatic for certain cell lines in tissue culture, and to induce differentiation in HL-60, neuroblastoma, and Friend erythroleukemia cell lines.

Interstitial hyperthermia and iridium brachytherapy in treatment of malignant glioma. A phase I clinical trial.

An oncolytic effect of hyperthermia in the 42 degrees to 43 degrees C range has been previously demonstrated in cell culture and animal models. To apply this modality clinically, an interstitial microwave antenna array system has been developed for the delivery of controlled hyperthermia to an intracranial tumor volume, and a Phase I clinical trial involving six patients with malignant gliomas was undertaken. The protocol to study technical feasibility and patient tolerance combined interstitial iridium-192 irradiation and interstitial hyperthermia with 60-minute hyperthermia sessions immediately before and after brachytherapy.

Intraoperative interstitial microwave-induced hyperthermia and brachytherapy.

Intra-operative placement of 11-gauge nylon catheters into deep-seated unresectable tumors for interstitial brachytherapy permits localized heating of tumors (hyperthermia) using microwave (915 MHz) antennas which are inserted into these catheters. Four preliminary cases are described where epithelial tumors at various sites were implanted with an antenna array and heated for 1 hour, both before and after the iridium-192 brachytherapy. Temperatures were monitored in catheters required for the appropriate radiation dosimetry but not required for the interstitial microwave antenna array hyperthermia (IMAAH) system.

Carboplatin as a potentiator of radiation therapy.

A rationale for coordinating the administration of carboplatin with radiation to achieve enhancement of cancer therapy is developed. This approach is based upon a review of the reports of effects in a variety of systems, effects attributed to interactions between cisplatin or other platinum analogs and radiation. Two major effects include radiosensitization (RS) of hypoxic cells with platinum present during irradiation and potentiation of cell kill with platinum complexes administered after irradiation.

Platinum based combined modality approach for locally advanced head and neck carcinoma.

Radiation therapy delivered soon after cisplatin administration is used for the treatment of advanced head and neck cancer. A radiation dose of 4800 cGy is given in standard fractions, followed by clinical evaluation and either surgical resection or an additional radiation dose of 2000 cGy. The histopathology of the surgical specimens from 21 patients undergoing resection in this protocol is compared with the corresponding clinical evaluation of tumor response.

Combined modality approach in the management of locally advanced head and neck cancer.

Twenty-five patients with stage III or IV locally advanced head and neck cancer were treated from February 1981 to November 1982 with a combined modality approach utilizing chemotherapy followed by irradiation and surgery. Induction therapy with cisplatin and bleomycin was followed by a sequence integrating weekly cisplatin into a program of locoregional irradiation. After the administration of 4800 cGy, patients received either "boost" irradiation or surgery.