PubMed Health⌕ Search

Biomedical subjects

C T Coughlin

Publications and source records attributed to C T Coughlin.

34 records · Page 2Linked to original sources
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↗
PubMed1985

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. Both these effects are expected to result in an improved therapeutic ratio. The latter effect may include inhibition of recovery from radiation-induced potentially lethal damage (PLD) and sublethal damage (SLD). Evidence for RS by carboplatin with an enhancement ratio (ER) of 1.8 is presented in Chinese hamster lung cells (V79) irradiated in culture under hypoxic conditions. Potentiation of radiation therapy in mice bearing a transplanted mouse mammary tumor (MTG-B) is reported as a supra-additive tumor growth delay when 60 mg/kg carboplatin is administered either 30 minutes before or immediately after 20 Gy of X-irradiation. Improved efficacy resulting from ongoing clinical trials coordinating cisplatin with radiation should support the role for carboplatin as a potentiator of radiation therapy since this second generation complex of platinum also interacts with radiation and larger concentrations of platinum should be attainable in tumors using the new drug.

Animals↗
PubMed1985

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. A significant number of both false negative and false positive clinical assessments are revealed by this comparison. In addition, it appears that local control of bulky head and neck cancer is approached by 4800 cGy combined soon after cisplatin. Discussion of the likely bases for this apparently favorable clinical interaction between cisplatin and radiation is presented.

Cisplatin↗
PubMed1985

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. Additional thermometry was obtained using nonperturbed fiberoptic thermometry probes inserted into the catheters' housing antennas. No significant complications, such as bleeding or infection, were observed. This approach to cancer therapy is shown to be feasible and it produces controlled, localized hyperthermia, with temperatures of 50 degrees C or more in tumors. This technique may offer a therapeutic option for pelvic, intra-abdominal and head and neck tumors.

Adult↗
PubMed1984

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. At the completion of all therapy, 20 of 23 patients evaluable for response had achieved complete remission. Toxicity was tolerable and all patients are being followed closely to assess durability of remission and overall survival.

Adult↗
PubMed1983

Interstitial hyperthermia in combination with brachytherapy.

Flexible coaxial cables were modified to serve as microwave antennas operating at a frequency of 915 MHz. These antennas were inserted into nylon afterloading tubes that had been implanted in tumors using conventional interstitial implantation techniques for iridium-192 seed brachytherapy. The tumor volume was heated to 42-45 degrees C within 15 minutes and heating was continued for a total of 1 hour per treatment. Immediately following a conventional brachytherapy dose and removal of the iridium seeds the tumors were heated again in a second treatment. This interstitial technique for delivering local hyperthermia should be compatible with most brachytherapy methods. The technique has proved so far to be practical and without complications. Temperature distributions obtained in tissue phantoms and a patient are described.

Brachytherapy↗
PubMedDate not supplied

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. The transducer was resonant at 1.0 MHz and was tested in a water tank and in an acoustic absorbing medium where the steady-state temperatures were measured. A comparison between a single 10 cm element and the concentric ring modification with all rings at equal power density showed the performance to be nearly identical. In vivo experiments in canine thigh verified the phantom predictions as individual rings were energized. Theoretical intensity calculations were made and compared favourably to water tank test results. Clinical hyperthermia treatments for chest wall and head and neck tumours showed that the temperature distribution could be highly modified by adjusting the power to individual rings while holding the transducer stationary. Automated temperature mapping parallel to the transducer face was used to compare a single element applicator to the concentric ring applicator in clinical treatments on the same lesion. The concentric ring applicator was radially adjustable and was found to be advantageous in lowering the central peak temperatures and flattening the temperature distribution in tumours. A comparison between the single element clinical and operating room series showed that when pain is removed as a treatment limiting factor, higher central tumour temperatures are possible and more of the tumour volume achieves therapeutic temperatures. The concentric ring design improves the temperature distribution such that the higher central temperatures will not be necessary.

Evaluation Studies as Topic↗
PubMedDate not supplied

Platinum levels and clinical responses of tumours treated by cisplatin with and without concurrent hyperthermia: a case study.

The heterogeneity of platinum distributed within tissue after clinical administration of cisplatin was evaluated for the first time. Platinum levels were correlated with the observed clinical responses of separate superficial histiocytic sarcomas located in the forearm of a 74-year-old male patient. One of four lesions received four weekly treatments with hyperthermia administered concurrently with 30 mg/m2 cisplatin, while three lesions were treated with cisplatin alone. The lesion receiving hyperthermia concurrently with cisplatin had a solid partial response during a 6-week period following this therapy, whereas two other tumours receiving cisplatin alone progressed. One lesion could not be clinically evaluated. Platinum levels were determined in multiple samplings from three of the four lesions and normal tissue in order to evaluate the validity of taking a single tumour sample of 100 mg or less for the analysis of platinum content. Such a small single sample might provide a value significantly different from the true average because of sampling error. The range in platinum distribution encompassed an average of three-fold difference within eight separate sample groups, with a factor of six being the greatest difference in a single sample group. This degree of heterogeneity is great enough to suggest that conclusions made from the analysis of small and single random tissue samples could be sufficiently in error to misdirect investigative or medical decisions.

Aged↗
PubMedDate not supplied

Interstitial microwave-induced hyperthermia and iridium brachytherapy for the treatment of obstructing biliary carcinomas.

In a phase I clinical study, 10 patients with obstructive biliary carcinomas were treated with single-antenna interstitial microwave hyperthermia and iridium-192 brachytherapy. For each patient a standard biliary drainage catheter was implanted percutaneously through the obstructed common bile duct. This catheter accommodated a single microwave antenna which operated at 915 MHz, and one or two fibreoptic thermometry probes for temperature measurement. Under fluoroscopic guidance the microwave antenna and temperature probes were positioned in the CT-determined tumour mass. The 60-min heat treatment achieved a central tumour temperature of 45-55 degrees C while keeping temperatures at the proximal and distal margins at 43 degrees C. Immediately following the hyperthermia treatment the microwave antenna and temperature probes were removed, and a single strand of iridium-192 double-strength seeds was inserted to irradiate the tumour length. A dose of 5500-7900 cGy calculated at 0.5 cm radially from the catheter was administered over 5-7 days. Upon removal of the iridium a second hyperthermia treatment was performed. A total of 18 hyperthermia treatments were administered to the 10 patients. In two cases the second hyperthermia treatment after brachytherapy was not possible due to a kink in the catheter, or bile precipitation in the catheter. All patients tolerated the procedure well, and there were no acute complications. To evaluate the volumetric heating potential of this hyperthermia method, specific absorption rate (SAR) values were measured at 182 planar points in muscle phantom. Insulated and non-insulated antenna performance was tested at 915 MHz in a biliary catheter filled with air, saline, or bile to mimic clinical treatments. The insulated antenna exhibited the best performance. Differences between antenna performance in saline and bile were also noted. In summary, this technique may have potential for tumours which obstruct biliary drainage and are accessible to percutaneous decompression using standard diagnostic radiological procedures.

Biliary Tract Neoplasms↗
PubMedDate not supplied

Techniques for intraoperative hyperthermia with ultrasound: the Dartmouth experience with 19 patients.

Over the course of 3 years, tumours of 19 patients were heated with ultrasound in the operating room during surgical resection. Immediately following intraoperative radiation therapy, thermocouples were inserted into tumour and adjacent normal structures. Patients were then given a 60-min heat treatment with ultrasound after a 10-15-min heatup period. Temperatures were measured at a total of 133 fixed locations for the 19 patient series. Temperature mapping was done in the tumour volume when logistically feasible. Treatment sites included colorectal (n = 3), portahepatus (n = 1), pancreas (n = 7), liver (n = 1), pelvis (n = 3), sacrum (n = 2), and abdomen (n = 2). A sterile, constant-volume water circulating system was utilized to control surface temperatures. Three generations of completely immersible transducers were designed over the course of this study with a 4-cm height specification. Since the ultrasound transducer was assembled on the sterile field during surgery, a 1, 2 or 3 MHz ceramic element was placed in either a 6, 8 or 10 cm diameter aluminium housing to conform the acoustic field to the tumour size. Average of the maximum temperatures attained was 46.6 degrees C. Temperature with which 90% of all measured points equalled or exceeded (T90) was 39.2 degrees C. The T50 was 42.9 degrees C. This compared favourably with T90 and T50 of 38.8 and 41.9 degrees C, respectively, in our outpatient clinic series, in which superficial tumours were treated with a similar external applicator, and patient tolerance was often a treatment limitation.

Combined Modality Therapy↗
PubMedDate not supplied

Pattern of response to interstitial hyperthermia and brachytherapy for malignant intracranial tumour: a CT analysis.

Interstitial microwave hyperthermia in combination with iridium-192 brachytherapy has been administered to 23 cases of malignant brain tumours in a phase one clinical trial to assess the feasibility and safety of this treatment. In order to quantify the acute and long-term response of tumour and surrounding brain to this treatment, a morphometric computed tomography scan analysis was performed in 18 evaluable patients. Volumes defined by the outer margin of the contrast-enhancing rim, by the hypodense necrotic region within the enhancing rim and by the surrounding hypodensity region were calculated from computer measurements. Hyperthermia equipment performance (HEP) was calculated for the evaluation of heating. After the treatments, the volume of the inner hypodensity region decreased in seven patients and the volume increased in 11 patients. In five patients, the outer margin of the contrast-enhancing lesion showed an initial increase in volume followed by a decrease and in these patients higher HEP and longer survival were observed significantly. The volume of the surrounding hypodensity region varied following treatments, but in most instances, the region subsequently increased in the interval immediately prior to death. Contribution of heat effect to these changes are discussed and the significance of aggressive heating, which provides transient opening of blood brain barrier, is shown.

Adult↗
PubMedDate not supplied

Large stationary microstrip arrays for superficial microwave hyperthermia at 433 MHz: SAR analysis and clinical data.

Superficial hyperthermia with present day applicators provides a challenge when tumours exceed several cm in diameter. Unless microstrip applicators are scanned, the usable heat region often falls short of treating the entire region with 50% power or specific absorption rate (SAR). New microstrip applicator designs were evaluated through SAR analysis and compared to the traditional microstrip applicators used in the clinic at Dartmouth over the past six years. The new designs included fabricating thin archimedean spirals (1.0 mm strip width) incorporating dielectric substrate (epsilon = 5.3-10.8). The designs were optimized at 433 MHz for an arm length of 59 cm. Measurements in a plane 1.0 cm from the surface showed that thin spirals outperformed traditional designs by increasing the 50% SAR area by a factor of 2.5, while maintaining the same physical size. Arrays of four elements were fabricated from thin spirals, although SAR evaluation showed only 10-20% SAR between elements. Since this was deemed unacceptable and the design goal was to fabricate a stationary applicator that had at least 50% SAR between elements, dual element designs were created with gradually overlapped elements. It was found that overlapping three coils of the spiral created a large region that equalled or exceeded 50% SAR that could not be matched by single applicators. Coherent operation of the dual spiral array resulted in more central power deposition and incoherent operation resulted in more peripheral power deposition. SAR measurements at the fat/muscle interface showed an elongated heating pattern in hydroxyethylcellulose muscle equivalent phantom. Power deposition 1.0 cm deep in muscle retained the same basic size and shape with or without the fat layer. Patient treatments for chestwall tumours confirmed that the dual overlapping applicator heated a larger region without the sharp temperature peak associated with single applicators.

Adipose Tissue↗