phosphorus-radioisotopes and Vascular-Diseases

Despite myelosuppression, polycythemic (PV) patients greater than 65 years of age have a high risk of vascular complications, and the leukemic risk exceeds 15% after 12 years. Is the addition of low-dose maintenance treatment with hydroxyurea (HU) after radiophosphorus (32P) myelosuppression able to decrease these complications? Since the end of 1979, 461 patients were randomized to receive (or not) low-dose HU (5 to 10 mg/kg/d), after the first 32P-induced remission, and were observed until death or June 1996. Maintenance treatment very significantly prolonged the duration of 32P-induced remissions and reduced the annual mean dose received to one-third. However, despite this maintenance, 25% of the patients had an excessive platelet count and the rate of serious vascular complications was not decreased, except in the most severe cases with short-term relapse of polycythemia. Furthermore, the leukemia rate was significantly increased beyond 8 years and a significant excess of carcinomas was also observed. The continuous use of HU did not decrease the risk of progression to myelofibrosis (incidence of 20% after 15 years). Life expectancy was shorter (a median of 9.3 years v 10.9 years with 32P alone), except in the most severe cases (initial 32P-induced remission lasting <2 years) in which maintenance treatment moderately prolonged the survival by reducing the vascular risk. In most cases of PV, in which the duration of the first 32P-induced remission exceeded 2 years, the introduction of HU maintenance did not reduce the vascular risk. Although it considerably decreased the mean dose of 32P received, HU maintenance therapy significantly increased the leukemia and cancer risks and reduced the mean life expectancy by 15%. However, in cases with more rapid recurrence, the introduction of maintenance treatment reduced the vascular risks and moderately prolonged survival. The use of HU as a maintenance therapy is therefore only justified in this situation.

Topics: Actuarial Analysis; Aged; Alkylating Agents; Combined Modality Therapy; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Risk; Survival Analysis; Vascular Diseases

The present report is based on an analysis of the evolution of 720 cases of Polycythaemia vera treated with pipobroman and 624 cases treated with hydroxyurea. General modes of treatment are identical for the two drugs, consisting of initial therapy at relatively high dose aimed at obtaining complete remission and maintenance therapy essential to conserve the improved clinical status. Both types of treatment must be adapted to suit the patient. Complete remission is achieved in 95 to 100% of cases with pipobroman and in 80 to 90% of cases with hydroxyurea. Incidents which may occur during initial therapy include cytopenia, more frequent and severe under treatment with hydroxyurea, rare transitory digestive troubles and cutaneous and mucous eruptions. Subject to control of the blood cell count every three to four months, maintenance therapy may be continued for many years and while the time lapse is as yet insufficient for hydroxyurea, resistance to pipobroman does not appear to develop even after more than 20 years of treatment. Although neither of these two drugs entirely avoids the occurrence of acute leukaemia which appears in 5 to 8% of subjects irrespective of the duration of therapy, on the contrary to observations in patients treated by bleeding alone, myeloid splenomegaly with myelofibrosis is rare and develops in no more than 2% of cases. The frequency of visceral cancers is not increased by either drug. Provided Polycythaemia vera is maintained in complete remission, thrombotic accidents occur no more often than in a normal population of the same age bracket.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Bloodletting; Combined Modality Therapy; Humans; Hydroxyurea; Leukemia; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Splenomegaly; Vascular Diseases

A new Monte Carlo code (IVBTMC) is developed for accurate dose calculations in intravascular brachytherapy (IVBT). IVBTMC calculates the dose distribution of a brachytherapy source with arbitrary size and curvature in a general three-dimensional heterogeneous medium. Both beta and gamma sources are considered. IVBTMC is based on a modified version of the EGSNRC code. A voxel-based geometry is used to describe the target medium incorporating heterogeneities with arbitrary composition and shape. The source term is modeled using appropriate phase-space data. The phase-space data are calculated for three widely used sources (32P, 90Sr/90Y, and 192Ir). To speed up dose calculations for gamma sources, a special version of IVBTMC based on the kerma approximation is developed. The accuracy of the phase-space data model is verified and IVBTMC is validated against other Monte Carlo codes and against reported measurements using radio-chromic films. To illustrate the IVBTMC capabilities, a variety of examples are treated. 32P, 90Sr/90Y, and 192Ir sources with different lengths and degrees of curvature are considered. Calcified plaques with regular and irregular shapes are modeled. The dose distributions are calculated with a spatial resolution ranging between 0.1 and 0.5 mm. They are presented in terms of isodose contour plots. The dosimetric effects of the source curvature and/or the presence of calcified plaques are discussed. In conclusion, IVBTMC has the capability to perform high-precision IVBT dose calculations taking into account the realistic configurations of both the source and the target medium.

Topics: Brachytherapy; Calcinosis; Computer Simulation; Humans; Iridium Radioisotopes; Monte Carlo Method; Phosphorus Radioisotopes; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Sensitivity and Specificity; Software; Strontium Radioisotopes; Vascular Diseases; Yttrium Radioisotopes

The objective of this paper was to provide an update on the clinical and experimental evaluation of radioactive stents for the prevention of restenosis.. Direct ion implantation of 32P onto the surface of a 15-mm length balloon expandable stainless-steel Palmaz-Schatz stent was employed to render this commercially available vascular stent radioactive. 32Phosphorous, a pure beta-particle-emitting radioisotope, was selected because of its short half-life (14.3 days) and limited range of tissue penetration (3-4 mm). The vascular response to radioactive 7-mm length Palmaz-Schatz stents with activities 0.14 to 23 microCi of 32P were evaluated in animal models of arterial injury and restenosis. The Phase-1 isostent for restenosis intervention study (IRIS trial) was a nonrandomized safety trial designed to evaluate the use of a low activity 32P (0.5 to 1.5 microCi) 15-mm length Palmaz-Schatz stent for the treatment of de novo or restenosis native coronary arterial lesions.. In the porcine coronary restenosis model, at < or =0.5 microCi and > or =3.0 microCi stent activities, there was a 30% reduction in the neointimal and percent area stenosis as compared to nonradioactive stents. The 1.0 microCi stents, however, had nearly 2-fold greater neointimal formation and more luminal narrowing than the control stents. In the Phase 1 IRIS trial, 57 patients with symptomatic de novo or restenosis native coronary lesions have been treated with low activity (0.5 to 1.5 microCi) 32P Palmaz-Schatz coronary stents. Fifty-seven stents were successfully implanted without a major procedural complication (death, urgent coronary bypass, Q-wave myocardial infarction). There were no cases of stent thrombosis, target vessel revascularization, or other adverse events in the first 30 days after implant.. The early clinical results with a low-activity 32P Palmaz-Schatz radioactive stent demonstrate sufficient procedural and 30-day event-free survival to warrant consideration of additional clinical studies to determine the safety and efficacy of this therapy for the prevention of restenosis. Future studies will focus on optimal stent design for delivery of radiation, and will further evaluate safe and effective dosing strategies.

Topics: Animals; Constriction, Pathologic; Phosphorus Radioisotopes; Recurrence; Stents; Swine; Swine, Miniature; Vascular Diseases; Vascular Patency

Percutaneous transluminal coronary angioplasty (PTCA) is one of the most common therapies for obstructive coronary artery disease. Unfortunately, subsequent restenosis after percutaneous balloon angioplasty occurs in 30-50% of patients and remains one of the major unsolved problems of contemporary cardiology. The study of endovascular irradiation has been greatly stimulated by the discovery that the process of restenosis may be impaired by irradiation. The objective of this study was to examine a custom-made commercial 32P wire and to determine whether the present source presentation is suitable for this application.. Measurements of the dose distribution around a 3 mm long 32P source with an activity of 0.414 GBq (11.2 mCi) were made by using LiF thermoluminescent dosimeters and a scintillation detector. The source had the dimensions of 0.3 mm in diameter and 3 mm in length, and was first encapsulated by a plastic tube and then encapsulated in a specially manufactured Ni-Ti wire with a diameter of 0.4 mm and a length of 2.6 m. The detector size effect is removed from the measurements calculation. Loevinger's equation for the dose distribution around a 32P source was used for the calculations.. The dose rate at a radial distance of 1.5 mm was 53 cGy/s per GBq (1.96 cGy/s per mCi) and fell off rapidly perpendicularly to the axis of the source in an approximately exponential manner, from 53-5.3 cGy/s per GBq (approximately 2 to 0.2 cGy/s per mCi) as radial distances increased from 0.2 to 0.4 g/cm2 (1.5 to 3.5 mm away from the center of the source). The treatment length parallel along the wire could be as long as 24 mm for eight source dwell positions with the average dose rate of 59 cGy/s per GBq (2.2 cGy/s per mCi) and a variation of +/- 2.3% at a radial distance of 1.5 mm.. Our experiments show that the dose distribution is ideal for endovascular irradiation. The source was incorporated in the end of a flexible cable and with a half-life of 14.3 days is suitable for endovascular irradiation.

Topics: Brachytherapy; Dose-Response Relationship, Radiation; Phosphorus Radioisotopes; Radiotherapy Dosage; Vascular Diseases

Topics: Biophysical Phenomena; Biophysics; Combined Modality Therapy; Constriction, Pathologic; Humans; Models, Biological; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Radiotherapy, High-Energy; Stents; Vascular Diseases

The very-long-term follow-up of patients initially included in the PVSG protocols provides useful information. The excess risk of cancer after chlorambucil appears to persist for 5 years after stopping this treatment. The risk of leukaemia induced by marrow suppression (32P or chemotherapy) was marked before the 10th year, but low thereafter. Phlebotomy is unacceptable as permanent treatment because of the poor clinical tolerance and the frequency of vascular complications. This treatment is also associated with a risk of early progression towards myelofibrosis with myeloid splenomegaly. In the very long term, 15 years or more after the diagnosis, this complication is the major clinical risk, affecting almost 50% of our patients surviving at this time. The prevention of this type of complication could constitute one of the objectives of future protocols dealing with this disease.

Topics: Aged; Bloodletting; Chlorambucil; Follow-Up Studies; Humans; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radiotherapy; Treatment Outcome; Vascular Diseases

Topics: Humans; Peripheral Vascular Diseases; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Vascular Diseases