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H Madoc-Jones

Publications and source records attributed to H Madoc-Jones.

11 recordsLinked to original sources
PubMed1992

Boron neutron capture therapy for murine malignant gliomas.

Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 microns. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3-(p-boronophenyl)alanine and irradiated with total tumor doses of 1000-5000 RBE-cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival. These mice were compared to mice that received D,L-3-(p-boronophenyl)alanine alone, neutron irradiation alone, photon irradiation alone, or no treatment. Additional normal mice received escalating doses of neutron irradiation to determine its toxicity to normal brain. BNCT caused a dose-dependent, statistically significant prolongation in survival at 1000-5000 RBE-cGy. At 3000 RBE-cGy, median survival rates of the BNCT and untreated control groups were 68 and 22 days, respectively, with a long-term survival rate of 33%. At 4000 RBE-cGy, median survival was 72 and 21 days, respectively, with a long-term survival rate of 43%. At lower radiation doses, the extended survival was comparable between the BNCT and photon-irradiated mice; however, at 3000 and 4000 RBE-cGy the median survival of BNCT-treated mice was significantly greater than photon-irradiated mice. The maximum tolerated single fraction dose to normal brain was approximately 2000 RBE-cGy.

Animals↗
PubMed1990

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors.

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam (with the B-10 distribution defined above) encompasses nearly the whole brain. Experimental calibration techniques for the conversion of normalized to absolute treatment plans are described.

Boron↗
PubMed1990

Clinical considerations for neutron capture therapy of brain tumors.

The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues.

Animals↗
PubMed1990

Uterine thickness determination using real-time ultrasonography: a guide for intracavitary brachytherapy in the treatment of endometrial carcinoma.

Two patients with medically inoperable stage I endometrial carcinoma were treated with intracavitary implants alone using Simon capsules, tandems, and ovoids. In both cases, uterine thickness was measured during the implant procedure by realtime ultrasonography. Tumor doses in both patients were then calculated to the midmyometrium and to the serosal surface of the uterus. These estimates, rather than the usual milligram-hours or points A and B, were used to make treatment decisions.

Brachytherapy↗
PubMed1990

Use of the omental J flap for better delivery of radiotherapy to the pelvis.

The surgically created omental J flap (or synthetic equivalents) can facilitate radiation therapy, particularly brachytherapy, in which adhesions of the pelvis would otherwise limit its value. The J flap used in this role has an occasional place in the management of patients with carcinoma and exemplifies how surgical procedures and irradiation can be combined for more effective treatment of carcinomas.

Brachytherapy↗
PubMed1990

Ultrasound for diagnosing and preventing malplacement of intrauterine tandems.

Postoperative B-mode ultrasound was used to evaluate final tandem position in 50 consecutive placements (28 patients). In 34% (17 of 50), the tandem was found to be suboptimally positioned; in 24% (12 of 50), it penetrated the myometrium; and in 10% (five of 50), it frankly perforated the uterus. The uterine fundus was the region most commonly perforated, and the anterior myometrium was the site most frequently penetrated. In all cases in which postoperative ultrasound showed malpositioning, the clinical and radiographic assessment indicated proper intracavitary placement. Ultrasound affected clinical management in 42% (21 of 50) of the placements involving 61% (17 of 28) of the patients. To improve tandem placement, we used intraoperative real-time ultrasound to guide 73 consecutive surgical insertions. Ultrasound clearly visualized the procedure, allowing tandems to be positioned with confidence even in the most difficult cases. The immediate feedback from intraoperative ultrasound eliminated malplacements and thus the need for a second anesthesia to reposition the tandem.

Brachytherapy↗
PubMed1986

Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea.

Seventeen patients with either chronic myelogenous leukemia (CML) or myelofibrosis with myeloid metaplasia (MMM) received 24 courses of splenic irradiation at this institution from 1973 to 1982. Eleven of the 17 patients had received prior chemotherapy. Patients were treated with 60Co gamma rays or 6 MV photons. The fraction size ranged from 15 to 100 rad and the total dose per treatment course from 15 to 650 rad, with the exception of one patient who received 1650 rad. Fourteen of 19 courses (71%) given for splenic pain yielded significant subjective relief while 17 of 26 courses given for splenomegaly obtained at least 50% regression of splenic size. Blood counts were carefully monitored before each treatment to limit hematologic toxicity. From this experience, the authors conclude that splenic irradiation effectively palliates splenic pain and reverses splenomegaly in the majority of patients with CML and MMM. Intermittent fractionation (twice or thrice weekly) is more convenient for the patient, appears to be as effective as daily treatment, and may be associated with less hematologic toxicity. Preliminary results of concurrent treatment with splenic irradiation and oral hydroxyurea show promise and warrant further study.

Adult↗
PubMed1977

New assessment of the prognostic significance of histopathology in Hodgkin's disease for laparotomy-negative stage I and stage II patients.

This paper describes preliminary radiotherapy results in 90 patients with Stage I and II Hodgkin's disease who were evaluated by laparotomy, including splenectomy, and liver and bone marrow biopsies. As a result of selection by laparotomy, the estimated five-year survival rate for these patients was 96%. No statistically significant differences were detected in the disease-free survival for patients with mixed cellularity, nodular sclerosis, and lymphocytic predominance disease. Since only one patient with lymphocytic depletion was in this series, no statement can be made regarding this rare histopathology. Patterns of new disease differed for Stage I and II patients. The major difference was that patients with nodular sclerosing Stage II presentations involving the mediastinum were at considerable risk of developing subsequent disease in the pulmonary parenchyma or the pleura. This finding, together with the demonstration that a histologic diagnosis of mixed cellularity did not carry an inferior prognosis, indicates the need for reassessment of the appropriateness of applying treatment programs based on results of lymphangiographically staged patients to Stage I and II patients evaluated by laparotomy.

Adolescent↗