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C T Coughlin

Publications and source records attributed to C T Coughlin.

At least 19 recordsLinked to original sources
PubMed1994

Brain hyperthermia: I. Interstitial microwave antenna array techniques--the Dartmouth experience.

PURPOSE: Microwave antennas of various designs were inserted into arrays of nylon catheters implanted in brain tumors with the goal of raising temperatures throughout the target volume to 43.0 degrees C. METHODS AND MATERIALS: All antennas were flexible, and included dipole, choke dipole, modified dipole, and helical designs driven at 915 or 2450 MHz. Antennas were tested in brain-equivalent phantom in arrays. Phase shifting and phase rotation techniques were incorporated into the treatment system to steer power in the tumor, assisted by a treatment planning computer that predicted power deposition patterns and temperature distributions. Choke antennas were designed and tested to reduce a dependence of the central power location on depth of insertion into tissue. Temperature data analysis used only central and orthogonal axes mapping data measured at 2.0 mm intervals. RESULTS: A total of 23 patients were treated, using from one to six microwave antennas. Minimum tumor temperatures, averaged over the 60 min treatment, ranged from 37.2-44.3 degrees C (mean 40.0 degrees C) and maximum average tumor temperatures ranged from 46.5-60.1 degrees C (mean 49.1 degrees C). The percentage of all measured temperatures reaching therapeutic levels (> or = 43.0 degrees C) was 70.9. T90, the temperature at which 90% of all measured temperatures equaled or exceeded, was 40.8 degrees C, and T50 was 44.2 degrees C. CONCLUSION: Patient data analysis showed that the array of four dipole antennas spaced 2.0 cm apart were capable of heating a volume of 5.9 cm (along the central array axis) x 2.8 cm x 2.8 cm.

Brain Neoplasms↗
PubMed1994

Platinum drug delivery and radiation for locally advanced prostate cancer.

Combined therapies of cisplatin and radiation have resulted in clinical reports of apparent efficacious control of locoregional cancer and enhanced survival. Mechanisms of interaction between platinum and radiation that may explain these clinical observations all have in common the prediction that higher concentrations of platinum in all tumor cells close in time to irradiation should lead to greater potentiation of radiation-induced killing of those cells. Cisplatin is thus viewed as providing some radiation-equivalent, or a radiation dose-effect factor, for sterilization of tumors. One disease site that has not been well investigated for response to cisplatin plus radiation therapy, but that could benefit from it, is locally advanced prostate cancer. A body of literature now supports the view that local control of stage C (T3, N0, M0) prostate cancer is correlated with disease-free survival. This correlation makes prostate cancer a candidate for potentially achieving improved cure rates following local tumor sterilization by combining cisplatin with radiation therapy. The need and approaches to optimize delivery of cisplatin within tumor tissue is explored. Increasing cisplatin concentration to all the cells of a tumor, i.e., homogeneously delivering systemic high-dose cisplatin, should benefit the efficacious response otherwise expected for cisplatin combined with radiation. Strategies to increase the homogeneity of cisplatin delivery to a tumor are considered to be those that increase perfusion to that tumor. Vasoactive agents used in anticancer protocols are especially considered for their potential value in serving to increase tumor perfusion. These protocol-inclusive agents include certain cytokines and L-arginine antagonists, and should be better managed and accepted in practice compared to other vasoactive agents that need to be developed as specific additives to protocol designs.

Amino Acid Oxidoreductases↗
PubMed1993

A coaxial microwave applicator for transurethral hyperthermia of the prostate.

Benign prostatic hyperplasia (BPH) is a common disease of elderly men. The current definitive treatment for urinary obstruction caused by this disease is surgery (transurethral resection of the prostate, or TURP). Recent evidence suggests that hyperthermia may be a useful nonsurgical alternative for treatment of symptomatic BPH. A transurethral microwave applicator has been designed around a Foley catheter for delivery of local hyperthermia to the prostate. The Foley balloon is used to maintain the antenna position within the prostatic urethra. The Foley catheter also features an antenna choke to confine power deposition to the intended region. The antenna is a coaxial dipole designed to operate at 915 MHz. Qualitative and quantitative specific absorption rate (SAR) patterns are shown for this antenna. In vivo experiments in dog prostate demonstrate that temperatures > 42 degrees C can be obtained > 1 cm away from the catheter, while maintaining a maximum urethral temperature of 47 degrees C to 48 degrees C. Histology obtained acutely after the hyperthermia treatments showed minimal damage to the periurethral tissues. We conclude from these studies that this microwave applicator is capable of providing local hyperthermia to the prostatic tissues with a predictable and well-circumscribed thermal distribution.

Animals↗
PubMed1992

Interstitial microwave hyperthermia and brachytherapy for malignancies of the vulva and vagina. I: Design and testing of a modified intracavitary obturator.

A vaginal obturator was fabricated to be used in combination with implanted catheters to provide microwave hyperthermia and brachytherapy to the vulva and vaginal wall. This site is difficult to heat or irradiate solely with interstitial techniques. The obturator was modified to provide grooves for the mounting of interstitial catheters into the outer wall and was matched with a template for circumferential implants. Power deposition tests were done using arrays of three microwave antenna designs: dipole (hA = hB = 3.9 cm), helical (3.9 cm coil, shorted), and modified dipole (1.0 cm helix on dipole tip) to test the performance of the obturator. The obturator and four non-obturator catheters were positioned in muscle-equivalent phantom. Two obturator catheters along with two free-standing catheters formed the obturator array. Four freestanding catheters formed the non-obturator array. Power deposition or specific absorption rate (SAR) measurements were made along the central axis, bisect, and diagonal transect of each array. SAR results showed that antennas in the obturator wall radiated as dipole theory predicts, although with less power density when compared to antennas in the same catheters spaced 1.8 cm from the obturator. This could be compensated for by increasing the power to the antennas in the obturator by 42%. Adjacent pairs of antennas were placed 90 degrees out of phase for 0.25 sec and rotated around the array. Phase rotation demonstrated that the central array SAR peaks could be lowered from 100% to 50% SAR, with dipole antennas thus resulting in lowered peak temperatures and the ability to heat larger volumes by improving the distribution of power. With helical antennas, there was 50% SAR at the array center when operated coherently without phase rotation. Three patients were treated with the obturator and a custom-made template using dipole antennas, and temperatures were measured in five obturator catheters. Therapeutic heating was measured in the catheters on the obturator between antennas in contact with the vaginal mucosa.

Brachytherapy↗
PubMed1991

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 7.5 mm from the microwave source at the longitudinal location of maximum heating along the antenna in the left cerebral cortex. Temperatures were measured with fiberoptic probes in a coronal plane at this location in an orthogonal catheter at 1.0 mm intervals. Six antennas were evaluated, including dipole, modified dipole, and four shorted helical antennas with coil lengths from 0.5 to 3.9 cm. Antenna performance evaluated in tissue equivalent phantom by adjusting frequency at a fixed insertion depth of 7.8 cm or adjusting insertion depth at 915 MHz showed dipoles to be much more sensitive to insertion depth and frequency change than helical antennas. Specific absorption rate (SAR) was measured in a brain/skull phantom and isoSAR contours were plotted. In vivo temperature studies were also used to evaluate antenna performance in large and small canine brain tissues. A helical antenna with a 2.0 cm coil length driven at 915 MHz was chosen for the beagle experiments because of tip heating characteristics, well-localized heating along the coil length, and heating pattern appropriate to the smaller beagle cranial vault. Verification of lesion dimensions in 3-D was obtained by orthogonal MRI scans and histology to document the desired heat effect, which was to obtain an imagable lesion with well-defined blood-brain-barrier breakdown and necrotic zones. The desired lesion size was between 1.5 to 2.5 cm diameter radially, in the coronal plane with the greatest diameter.

Animals↗
PubMed1991

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 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28 days, 5 days a week. One hundred thirty-seven patients were randomized and 126 patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200 x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification was performed on lesions less than 5 cm or greater than or equal to 5 cm. The study was closed on May 31, 1988 when interim statistical analysis suggested that further accrual would not reveal a difference between arms. Response rate overall was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x 2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of 34.4%. There was no difference between arms.

Adolescent↗
PubMed1990

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). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2-23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.

Adolescent↗
PubMed1990

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. There was a notable lack of significant acute morbidity, with the exception of a severe symptomatic peripheral neuropathy associated with cisplatin doses of 200 mg/m2. This was not evident with doses of cisplatin up to 150 mg/m2.

Adult↗
PubMed1989

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.

Brachytherapy↗
PubMed1989

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. Results of clinical studies integrating cisplatin and radiation that can be judged for perceived survival benefit are evaluated in comparison with existing radiobiologic information. Both the clinical and radiobiologic results lead to similar conclusions at this time. Cells that are relatively sensitive to the cytotoxic action of cisplatin alone would best be considered for combined treatment with radiation. Large and infrequent, rather than small and frequent, individual administrations of cisplatin are better used with radiation for enhanced therapeutic effectiveness. Administration of cisplatin close in time to radiation is best for therapeutic response, although perceived efficacy follows from rather flexible integrations of these two modalities. It is not possible to know if clinical efficacy results from radiation potentiation as opposed to some degree of additivity of the two modalities. It is nonetheless useful to anticipate strategies that might lead to radiation potentiation by cisplatin in therapeutic designs. Two general mechanisms by which cisplatin potentiates radiation-induced cell killing are identified. One mechanism of potentiation is free radical-mediated, at least in part leads to an active radiolytic species following one-electron reduction of cisplatin, and is more readily expressed with bacterial cells than with mammalian cells in tissue culture. A second mechanism of potentiation is biochemical in nature, involves an effect of cisplatin on cellular components in ways that inhibit the recovery of radiation-induced damage, and likely applies more to the potentiation of oxic mammalian cells than bacterial cells. The latter mechanism is not universally supported in the literature. However, a unifying hypothesis, and one in need of confirmation at this time, is that the biochemical mechanism of radiation potentiation by cisplatin operates in oxic mammalian cells that are inherently sensitive to the cytotoxic action of cisplatin. This hypothesis ostensibly applies to tumor cells that are responsive to chemotherapy with cisplatin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

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. Tumor systems studied included head and neck, ovary, lung, cervix, and prostate. Median survival times are as follows: squamous cell carcinoma of the head and neck (trial 1), 36 months; ovarian carcinoma, 19; and squamous cell carcinoma of the lung, 14. Median survival has not yet been reached in trials of squamous cell carcinoma of the head and neck (trial 2), cervical carcinoma, or adenocarcinoma of the prostate.

Carcinoma↗
PubMed1987

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. Transient or permanent worsening of previous neurologic deficit, seen in 7 patients, has been the most common morbidity.

Adult↗
PubMed1986

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. Using quantitative bacteriologic techniques, would infection was found to be no more frequent after platinum-enhanced irradiation than after irradiation alone; however, there was the additive effect of weight loss associated with combined cisplatin treatment and irradiation.

Animals↗
PubMed1986

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. Furthermore, no toxicity has been seen in animals or human volunteers. We report here a clinical trial of oral nafazatrom at five dose levels in patients with advanced cancer. Thirty patients with a wide variety of advanced malignancies were treated for 26-638+ days (median 82 days). No tumor responses were seen. Toxicity included two cases with mild skin rashes, one case with nausea and vomiting, and one case with diarrhea. Nafazatrom is a safe and well-tolerated agent. Maximum activity would be predicted to occur in the adjuvant treatment of cancer and we feel that further efforts should proceed to identify the appropriate dose for such a trial.

Adult↗
PubMed1986

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. After-loading catheters suitable for both treatment modalities were implanted using a computerized tomography-assisted technique. Thermometry data confirmed the ability of a microwave antenna system to achieve reliable temperature distributions, and reasonable patient tolerance was documented.

Adult↗
PubMed1986

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. These MoAbs were chosen because they have broad reactivity with AML cells but not with pluripotent progenitor cells. At the time of transplant, 6 patients were in second complete remission, 1 each was in third complete or partial remission, and 2 were in early first relapse. The patients were treated with cyclophosphamide (60 mg/kg a day for 2 days) and total body irradiation (200 cGy twice a day for 3 days) and given infusions of MoAb-treated bone marrow. Full bone marrow reconstitution was observed in eight patients; two patients did not recover platelets. Seven of the ten patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0, 3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to myeloid differentiation antigens does not interfere with pluripotential stem cell engraftment. Longer follow-up and a controlled study are necessary to prove that the apparent efficacy of this therapeutic approach in some patients is attributable to MoAb-mediated killing of leukemia cells.

Antibodies, Monoclonal↗
PubMed1986

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. Of the 13 patients so treated, all but one showed objective evidence of tumor regression according to chest x-ray. Six patients are still alive from 12 to 37 months after the start of treatment, including four who are asymptomatic and without apparent tumor and two with persistent local disease. Of the seven patients who died, four had metastatic disease (including one with local recurrence as well), one (who had been resistant to therapy) had persistent local disease, and two died too early to allow comment on efficacy (although autopsy in one case showed no evidence of locoregional tumor). This program is both active and tolerable, and deserves further study.

Aged↗