Outcome of uterine clear cell carcinomas compared to endometrioid carcinomas and poorly-differentiated endometrioid carcinomas.

OBJECTIVES: Our aim was to compare the survival between patients with clear cell carcinoma (CC) and patients with endometrioid carcinoma (EC). METHODS: Through the population-based Geneva Cancer Registry, we identified 1,380 resident women diagnosed with uterine cancer between 1970 and 2000. We excluded those with papillary serous endometrial carcinoma and uterine sarcomas. We categorized patients as CC (n = 32, 2.8%) or EC (n = 1,145, 97.2%). Uterine cancer-specific survival rates were calculated by Kaplan-Meier analysis. We used Cox proportional hazards analysis to compare uterine cancer mortality risks between groups, and adjusted these risks for other prognostic factors. RESULTS: CC patients presented with a more advanced stage at diagnosis than EC patients (p = 0.002). Compared to women with EC, women with CC had a significantly greater risk of dying from their disease (hazard ratio [HR] 2.9, 95% confidence interval (95% CI) 1.7-4.9). After adjustment for age, stage and adjuvant chemotherapy, the risk of dying from uterine cancer was still significantly higher for CC patients (HR 2.0, 95% CI 1.2-3.4). By univariate analysis, the risk of dying of endometrial cancer was not significantly higher in CC patients than in patients with poorly-differentiated EC (HR 1.3, 95% CI 0.7-2.3). CONCLUSION: This population-based investigation shows that patients with CC have a poorer outcome than those with EC. Studies to determine the role of adjuvant treatment in CC patients are needed.

Positive peritoneal cytology in early-stage endometrial cancer does not influence prognosis.

The aim of this study was to assess the prognostic importance of positive peritoneal cytology in early-stage endometrial cancer. All 278 stage I and 53 stage IIIA (without cervical involvement) endometrial cancer patients operated between 1980 and 1996, recorded at the Geneva Cancer registry, were included. Stage IIIA cancers were recategorised into 'cytological' stage IIIA (positive peritoneal cytology alone, n=33) and 'histological' stage IIIA (serosal or adnexal infiltration, n=20). Survival rates were analysed by Kaplan-Meier method and compared using log-rank test. The prognostic importance of cytology was analysed using a Cox model, accounting for other prognostic factors. The 5-year disease-specific survival of cytological stage IIIA cancer was similar to stage I (91 vs 92%) and better than histological stage IIIA cancer (50%, P<0.001). After adjustment for age, myometrial invasion, differentiation and radiotherapy, cytological stage IIIA patients were still at similar risk to die from endometrial cancer compared to stage I patients (hazard ratio (HR) 0.7, 95% confidence interval (CI): 0.18-2.3), while histological stage IIIA patients were at a four-fold increased risk to die from their disease (HR 4.2, 95% CI: 1.7-10.3). This population-based study shows that positive peritoneal cytology in itself has no impact on survival of patients with localised endometrial cancer. Based on the present and previous studies, FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) might consider reviewing its classification system.

Gamma-irradiation markedly inhibits the hydrated collagen gel contradiction by arterial smooth muscle cells.

BACKGROUND: Vessel wall responses to percutaneous transluminal coronary angioplasty include neointimal proliferation and arterial remodeling. The contraction of a collagen gel is a good in vitro model of wound repair and vascular remodeling. Because irradiation is an important new therapeutic modality capable of preventing restenosis, the purpose of this study was to evaluate the effect of irradiation on the contraction of a collagen gel by smooth muscle cells (SMCs), on SMCs viability, and on DNA synthesis. METHODS: We studied the effect of different doses of gamma-irradiation (0 [control], 6, 12, and 18 Gy) on the contraction of a collagen gel seeded with SMCs (calf carotid arteries) during a period of 15 days. RESULTS: Maximal gel diameter reduction (from 35 to 6.8 mm, +/-0.5 mm in control) was markedly inhibited in the 6-, 12-, and 18-Gy groups (35 to 13.7 mm, +/-0.8 mm; 35 to 15.5 mm, +/-0.9 mm; and 35 to 16.1 mm, +/-0.9 mm, respectively; P<0.0001). The irradiated gels showed a dose-dependent reduction in the SMC proliferation rate (P<0.0001) and an increase in the number of nonviable SMCs (P<0.002) 15 days after irradiation. CONCLUSIONS: Gamma-irradiation produces a significant dose-dependent inhibition of the contraction of collagen gels seeded with arterial SMCs. This effect is related to a significant decrease in SMC viability and a decrease in SMC proliferation rate. These findings shed light on mechanisms whereby irradiation may positively affect arterial remodeling after percutaneous transluminal coronary angioplasties.

Prescribing, recording, and reporting in endovascular brachytherapy. Quality assurance, equipment, personnel and education.

Endovascular brachytherapy is a new, rapidly growing field of interest in radiotherapy for the prevention of neointimal hyperplasia after angioplasty in both coronary and peripheral arteries. Many physics aspects of these treatments have already been addressed in the report of the American Association of Physicists in Medicine task group on 'Intravascular brachytherapy', but up to now there are no generally accepted recommendations for recording and reporting radiation doses and volumes. The terminology to be used by all individuals involved in such treatments (radiation oncologists, physicists, and interventionalists) is not clearly defined. The Endovascular Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology Working Group in this document presents recommendations for a common language for general use in endovascular brachytherapy. This proposal addresses general terms and concepts for target and dose specification as well as detailed recommendations for dose prescription, recording and reporting in endovascular brachytherapy for both peripheral and coronary arteries. Additionally, quality assurance and radiation safety aspects are briefly addressed, as are aspects related to equipment, personnel, and training and education related to endovascular brachytherapy.

Mechanisms of neointima formation and remodeling in the porcine coronary artery.

BACKGROUND: To characterize the cells responsible for neointima formation after porcine coronary artery wall injury, we studied the expression of smooth muscle cell (SMC) differentiation markers in 2 models: (1) self-expanding stent implantation resulting in no or little interruption of internal elastic lamina and (2) percutaneous transluminal coronary angioplasty (PTCA) resulting in complete medial rupture and exposure of adventitia to blood components. METHODS AND RESULTS: The expression of alpha-smooth muscle (SM) actin, SM myosin heavy chain isoforms 1 and 2, desmin, and smoothelin was investigated by means of immunohistochemistry and Western blots in tissues of the arterial wall collected at different time points and in cell populations cultured from these tissues. The expression of smoothelin, a marker of late SMC differentiation, was used to discriminate between SMCs and myofibroblasts. Both stent- and PTCA-induced neointimal tissues and their cultured cell populations expressed all 4 markers. The adventitial tissue underlying PTCA-induced lesions temporarily expressed alpha-SM actin, desmin, and SM myosin heavy chain isoforms, but not smoothelin. When placed in culture, adventitial cells expressed only alpha-SM actin. CONCLUSIONS: Our results suggest that SMCs are the main components of coronary artery neointima after both self-expanding stent implantation and PTCA. The adventitial reaction observed after PTCA evolves with a chronology independent of that of neointima formation and probably corresponds to a myofibroblastic reaction.

Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty. The Dose-Finding Study Group.

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement.

Open magnetic resonance imaging using titanium-zirconium needles: improved accuracy for interstitial brachytherapy implants?

PURPOSE: To evaluate the benefit of using an open magnetic resonance (MR) machine and new MR-compatible needles to improve the accuracy of brachytherapy implants in pelvic tumors. METHODS AND MATERIALS: The open MR machine, foreseen for interventional procedures, allows direct visualization of the pelvic structures that are to be implanted. For that purpose, we have developed MR- and CT-compatible titanium-zirconium (Ti-Zr) brachytherapy needles that allow implantations to be carried out under the magnetic field. In order to test the technical feasibility of this new approach, stainless steel (SS) and Ti-Zr needles were first compared in a tissue-equivalent phantom. In a second step, two patients implanted with Ti-Zr needles in the brachytherapy operating room were scanned in the open MR machine. In a third phase, four patients were implanted directly under open MR control. RESULTS: The artifacts induced by both materials were significantly different, strongly favoring the Ti-Zr needles. The implantation in both first patients confirmed the excellent quality of the pictures obtained with the needles in vivo and showed suboptimal implant geometry in both patients. In the next 4 patients, the tumor could be punctured with excellent accuracy, and the adjacent structures could be easily avoided. CONCLUSION: We conclude that open MR using MR-compatible needles is a very promising tool in brachytherapy, especially for pelvic tumors.

Intraarterial beta irradiation induces smooth muscle cell apoptosis and reduces medial cellularity in a hypercholesterolemic rabbit restenosis model.

PURPOSE: Ionizing radiation has been shown to be a powerful inhibitor of neointimal hyperplasia following arterial injury in several animal models of post-percutaneous transluminal coronary angioplasty (post-PTCA) restenosis. This was previously shown to be associated with a reduction in smooth muscle cell (SMC) mitotic activity. This study evaluated the effect of intraarterial beta irradiation on the arterial wall SMC density and apoptosis. METHODS AND MATERIALS: Twenty-five carotid and 7 iliac arteries of hypercholesterolemic New Zealand white rabbits were injured using the Baumgartner technique. The impact of an 18 Gy beta radiation dose administered after balloon injury was studied and compared to a nonirradiated injured control group. The medial SMC density as well as the percentage of apoptotic cells were determined at 8 days, 21 days, and 6 weeks after injury using an automated computer-based software. Apoptotic cells were identified using in situ end-labeling of fragmented DNA. RESULTS: The values for medial apoptosis in control vs. irradiated arteries were: 0.014 +/- 0.023 vs. 0.23 +/- 0.28%, p = NS, at 8 days; 0.012 +/- 0.018 vs. 0.07 +/- 0.07%, p = 0.05, at 21 days; and 0 +/- 0 vs. 0.16 +/- 0.11%, p = 0.03, at 6 weeks. The overall incidence of medial apoptotic cells at all time points was 0.01 +/- 0.017 vs. 0.13 +/- 0.14% in controls and irradiated arteries respectively, p = 0.004. Medial SMC density was significantly decreased in irradiated arteries in comparison with controls (p < 0.01 at all time-points). CONCLUSIONS: Intraarterial beta irradiation stimulates medial SMC apoptosis in balloon-injured arteries. This, together with a decrease in SMC mitotic activity, contributes to a decrease in the arterial wall cellularity.

Feasibility and tolerance of pulsed dose rate interstitial brachytherapy.

PURPOSE: Pulsed dose rate (PDR) treatment is a new approach that associates the physical advantages of high-dose-rate (HDR) technology with the potential radiobiological advantages of low-dose-rate (LDR) brachytherapy. This retrospective study analyzes the feasibility, toxicity, and preliminary oncologic results in a series of 43 patients treated with PDR interstitial brachytherapy. METHODS AND MATERIALS: Twenty-four patients with pelvic, 17 patients with head and neck, and 2 patients with breast cancers were treated. Twenty-eight patients had primary and 15 recurrent tumors; 14 had received prior external irradiation to the same site. The doses per pulse at the prescription isodose were 0.4-1 Gy (median 0.5 Gy), delivered using a single cable-driven 0.3-1.0 Ci 192-iridium source (PDR Nucletron Micro-Selectron). RESULTS: The median treated volumes (at the prescribed isodose) were 28 cc for pelvic, 8.33 cc for head and neck, and 40 cc for breast malignancies. Of 14,499 source and 14,499 dummy source transfer procedures, 3 technical machine failure events were observed (0.02%). Grade 3 acute toxicities were seen in 5/43 patients (4 oral stomatitis, 1 vaginal mucositis) and grade 4 acute toxicity in one patient (rectovaginal fistula). Grade 3-4 late complications were observed in 4/41 (9.8%) patients: 1 pubic fracture, 1 rectovaginal fistula, 1 vesicovaginal fistula and 1 local necrosis. With a median follow-up of 18 months, 10/41 patients progressed locoregionally (6 pelvic, 4 head and neck), 3 developed local recurrence and distant metastasis (3 pelvic), 3 only distant metastasis (2 pelvic, 1 head and neck). Two patients are lost to follow-up. CONCLUSION: PDR interstitial brachytherapy for pelvic, head and neck, and breast malignancies is feasible and the acute and late toxicities seem acceptable. Although the physical advantages of PDR are clear, further follow-up is required to determine how results compare with those obtained with standard LDR brachytherapy.

Intraarterial beta irradiation to reduce restenosis after PTCA. Experimental and clinical experience.

The present data demonstrate clinical feasibility of intracoronary beta brachytherapy and fail to reveal any complications that could be attributed to it. Definitive conclusions regarding safety will have to await longer term evaluation. Proof of efficacy will require strict dose finding evaluation of higher doses than those used in the present pilot study followed by a controlled, randomized trial using both clinical and angiographic end-points.

[Role of intravascular brachytherapy in the prevention of vascular restenosis after angioplasty]. / Rôle de la curiethérapie endovasculaire dans la prévention de la resténose vasculaire après angioplastie.

About 30% of patients who underwent percutaneous transluminal coronary angioplasty show evidence of restenosis, which appears to be independent of the angioplasty method used. The restenosis is due of two factors, firstly migration of smooth vascular muscle cells of the vascular media to the intima and multiplication which lead to the formation of a neo-intima. Irradiation limits the proliferation by acting of the cells in the mitotic stage. The vascular target volume is not very thick and is difficult to define it, that why brachytherapy seems to be the best procedure to prevent restenosis. However, the development of this treatment present many difficulties. Different irradiation techniques have been studied. Such techniques include catheter containing radioactive sealed source, radioactive stent, or balloon containing radioactive liquid inside. Each of these methods have their own advantages, inconveniences, problems and risks. Radioisotope may be either beta or gamma emitters. Gamma emitter presents problems for radioprotection but the satisfactory dose distribution may be difficult to obtain using beta emitter. Choice of dose, dose rate and delay between the end of angioplasty and the beginning of brachytherapy is subject to some discuss. Animal experiments using radioisotope have shown reduction in cell proliferation. Human trials showed feasibility, safety of the method and real impact on restenosis prevention. However, long-term efficacy has not been proved because the follow-up of the patients is too short. A randomized trial of 192Ir brachytherapy for prevention of restenosis has recently shown the efficacy in short and median term. However, long term efficiency and secondary effects have not yet been established as the follow up time of this study is still too short. That is why, collaboration between cardiologists and radiotherapists and physicists is indispensable to enable the development of an optimal technique.

Feasibility and safety of beta irradiation in human coronary arteries.

We have developed a technique of endoluminally centred endovascular beta irradiation aimed at preventing restenosis after PTCA. The source consists of a pure metallic 90-Yttrium coil that can be positioned within the lumen at the target site by the use of a centering device and an afterloading console. Experimental evaluation of this approach showed that a dose of 18 Gy delivered at the inner arterial surface was highly effective in preventing fibrointimal hyperplasia in rabbit carotid and iliac arteries. A pilot clinical evaluation in the coronary arteries of 15 patients using the same dose demonstrated excellent feasibility and no unexpected side-effects. A dose-finding evaluation in the clinical setting is now planned.

Basic physics and biology of radiation therapy.

The therapeutic use of ionizing radiation followed shortly after the discovery of X-rays by Roentgen in 1895. The radiobiological principles that underlie the clinical use of ionizing radiation have been ablated slowly over the past century. Ionizing radiation, which is used therapeutically for benign and malignant conditions, is characterized by the localized release of large amounts of energy. These radiations may be electromagnetic (X- or gamma rays) or particulate (electrons, protons, alpha particles, neutrons, etc.). In this paper we will review some basic radiation physics and radiation biology principles which might be unfamiliar to the interventional cardiologist interested in this evolving application of radiation to prevent restenosis.

Feasibility of intracoronary beta-irradiation to reduce restenosis after balloon angioplasty. A clinical pilot study.

BACKGROUND: With the aim of decreasing the incidence of restenosis after coronary balloon angioplasty, we developed a technique of intracoronary beta-irradiation using an endoluminally centered pure metallic 90Y source. The purpose of the present study was to evaluate the clinical feasibility and safety profile of this approach with a dose of 18 Gy delivered to the inner arterial surface. METHODS AND RESULTS: Between June 21 and November 15, 1995, fifteen patients (6 women and 9 men; mean age, 71 +/- 5 years) underwent intracoronary beta-irradiation immediately after a conventional percutaneous transluminal coronary angioplasty (PTCA) procedure. The PTCA/irradiation procedure was technically feasible in all attempted cases, and the delivery of the 18 Gy dose was accomplished without complications. In 4 patients, the intervention was completed through intra-arterial stent implantation because of dissection induced by the initial PTCA. During the follow-up period of 178 +/- 17 days (range, 150 to 225 days), no complication occurred that could be attributed to radiation therapy. No aneurysm or angiographically detectable thrombus was observed in any of the irradiated arterial segments. The clinical event rate (4 of 15 patients underwent further target lesion revascularization) and the angiographic follow-up (6 of 15 patients had a > 50%-diameter stenosis at the previously treated site) did not suggest a marked impact on the expected restenosis rate. CONCLUSIONS: This early experience demonstrates that our approach is feasible, and no side effects attributable to radiation were noted during a 6-month period of follow-up. Whether higher doses of beta-irradiation will favorably affect post-PTCA restenosis in patients must await further evaluation.

Endovascular beta-irradiation after percutaneous transluminal coronary balloon angioplasty.

PURPOSE: Intraluminal beta-irradiation has been shown to markedly decrease fibrointimal proliferation after arterial injury in experimental models. With the aim of reducing the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we undertook a pilot clinical evaluation to assess both the technical feasibility and the clinical safety of this treatment after balloon coronary angioplasty. METHODS AND MATERIALS: Between June 21 and November 15, 1995, 15 patients (6 women and 9 men, aged 72 +/- 5 years) underwent intracoronary beta-irradiation immediately after a conventional PTCA procedure. Both the PTCA and irradiation procedure were done in a conventional catheterization laboratory, using an endoluminally centered pure metallic 90Y source, a newly developed technique of intracoronary beta-irradiation. This was done after documenting the ability of the system to generate reproducible dose delivery to the arterial wall. RESULTS: Both the PTCA and the irradiation procedure were technically feasible in all attempted cases, and a dose of 18 Gy was delivered with a local exposure time of 391 +/- 206 s (range 153-768). In four patients, the intervention was completed by intraarterial stent implantation because of dissection induced by the initial PTCA. No in-hospital complications occurred, and serial creatine kinase measurements remained within the normal range in all cases. CONCLUSION: Our early experience thus suggests that reliable and reproducible dose delivery can be achieved, and that coronary endoluminally centered beta-brachytherapy is both feasible and safe on a short-term basis in the clinical setting. Whether this novel mode of therapy will favorably influence post-PTCA restenosis in patients, as it does in experimental models, must await long-term angiographic follow-up of the present series as well as further clinical study.

A novel system for intracoronary beta-irradiation: description and dosimetric results.

PURPOSE: A dosimetric evaluation of a new device dedicated to intravascular irradiation, associating a beta source and a centering device, was carried out before initiation of a clinical pilot study. METHODS AND MATERIALS: A 29-mm-long 90Y coil, coated with titanium and fixed to the end of a thrust wire, was introduced into the inner lumen of purpose-built centering balloons of different diameters (2.5, 3, 3.5, and 4 mm). Dose homogeneity was evaluated by studying both axial and circumferential dose variations, based on readings from thermoluminescent dosimeters (TLDs) placed on the balloon surface. Axial homogeneity was determined by comparing the readout values of dosimeters located on peripheral balloon segments with those located on segments adjacent to the midpoint of the source. The centering ability of the device was studied by comparing measurements on opposing surfaces of the balloon. The dose attenuation by water and contrast medium was evaluated and compared with that in air. The balloon contamination was studied using a contamination counter. The total 90Y coil activity was measured by liquid scintillation to relate activity to surface dose. RESULTS: Activity-surface dose correlation showed that for a linear coil activity of 1 mCi/mm, the mean dose rate at the surface of a 2.5-mm balloon filled with contrast medium was 8.29 Gy/min. The doses at the surface of larger balloons (3, 3.5, and 4 mm) filled with contrast were 78%, 59%, and 47%, respectively, of the dose measured at the surface of the 2.5-mm balloon. The coefficient of variation (CV) in surface dose for 2.5-, 3-, 3.5-, and 4-mm centering devices filled with contrast medium were 9%, 8%, 9%, and 12%, respectively. There was no statistically significant difference between readouts from central and peripheral balloon segments or among rows of dosimeters facing each other. For a 2.5-mm balloon, compared with air the dose attenuation by water and contrast medium was similar (0.70 and 0.69, respectively), but a significant difference was seen between the readouts of water- and contrast-filled balloons when the diameter was larger than 3 mm (p < 0.001). No contamination was found in the balloon shaft after source retrieval. CONCLUSION: The dosimetric tests showed very good surface dose homogeneity, demonstrating satisfactory centering of the source within the centering balloons. The achievable dose rates will permit intravascular irradiation within a short time interval. The absence of residual balloon contamination after source retrieval meets the requirements for a sealed source used in a clinical setting.

Intra-arterial 90Y brachytherapy: preliminary dosimetric study using a specially modified angioplasty balloon.

PURPOSE: Irradiation has been shown to be effective in preventing restenosis after dilatation in human peripheral arteries. We have developed a dedicated system for coronary intraarterial irradiation using a 90Y pure beta-emitting source inside a specially modified angioplasty balloon. This paper presents a preliminary dosimetric evaluation of this system. METHODS AND MATERIALS: Specially fabricated titanium-covered and activated yttrium wires (outer diameter 0.32 mm) were used for these studies. Dosimetry was performed using small thermoluminescent dosimeters (TLDs) placed on the surface of the 2-cm long angioplasty balloons, inflated with contrast medium to a diameter of 2.5, 3, 3.5, and 4 mm. Radioactive 90Y wires were left in the inner balloon catheter and the surface dose rate was measured and extrapolated to 72 h after activation to allow a comparison between the values obtained. After observing the poor centering of the source within the standard angioplasty balloon, a new centering balloon was developed. A conventional balloon was subdivided into four evenly spaced interconnecting chambers, thus assuring adequate centering of the inner catheter. Thermoluminescent dosimetric measurements were performed with a 3.5 mm centering balloon to evaluate the homogeneity of the surface doses compared to those measured with the conventional balloon. RESULTS: Thermoluminescent dosimetric measurements using the standard balloons filled with contrast medium were plotted semilogarithmically as a function of distance from the balloon surface. The logarithms of the measured doses fit a straight line as a function of depth. The doses at 1 mm and 3 mm are approximately 50 and 10% of the surface dose, respectively. Due to the poor centering of the source in the conventional balloons, the dispersion and standard deviations (SDs) of the measured surface doses increased proportionally to the balloon diameter (SDs are 1.89, 5.52, 5.79, and 6.46 Gy for 2.5, 3, 3.5, and 4 mm balloon diameters, respectively). For the 3.5 mm centering and conventional balloons the respective mean, minimum, and maximum surface doses were 8.41 Gy (min. 7.26; max. 9.46) and 7.89 Gy (min. 2.18; max. 16.06) and their standard deviations were 0.66 and 5.79 Gy, respectively. CONCLUSIONS: Conventional angioplasty balloons cannot ensure a homogeneous dose delivery to an arterial wall with an intralumenal 90Y beta source. Preliminary dosimetric results using a modified centering balloon show that it permits improved surface dose distribution (axial and circumferential homogeneity), making it suitable for clinical applications.

Intra-arterial beta irradiation prevents neointimal hyperplasia in a hypercholesterolemic rabbit restenosis model.

BACKGROUND: Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems. METHODS AND RESULTS: Flexible 90-yttrium (90Y) coils inside a centering balloon were used to allow homogeneous intraarterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245 +/- 93 cells/cm in control, 42 +/- 27 in 6 Gy, 72 +/- 107 in 12 Gy, and 2 +/- 2 in 18 Gy groups; P < .001) and in total neointimal cells (891 +/- 415 cells/cm in control, 79 +/- 43 in 6 Gy, 192 +/- 264 in 12 Gy and 22 +/- 13 in 18 Gy groups; P < .0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26 +/- 10% in the control group to 1 +/- 1.3% in the 18 Gy group (P < .0001), but lower doses had no significant effect. CONCLUSIONS: Administration of intra-arterial beta irradiation with a 90Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.

High dose rate brachytherapy for prevention of restenosis after percutaneous transluminal coronary angioplasty: preliminary dosimetric tests of a new source presentation.

PURPOSE: Balloon dilatation of coronary artery stenosis has become a standard treatment of atherosclerotic heart disease. Restenosis due to excessive intimal cell proliferation, which subsequently occurs in 20-50% of patients, represents one of the major clinical problems in contemporary cardiology, and no satisfactory method for its prevention has thus far been found. Because modest doses of radiation have proved effective in preventing certain types of abnormal cellular proliferation resulting from surgical trauma, and brachytherapy has already been used successfully after dilation of peripheral arteries, development of a radioactive source suitable for coronary artery applications would be of great interest. METHODS AND MATERIALS: Nonradioactive flexible yttrium-89 wires (diameter of 0.15 and 0.26 mm) were activated within the thermal neutron flux of an experimental reactor. Standard angioplasty balloons (2 cm long, 2.5 mm in diameter when inflated) were inserted for dosimetry into a specially manufactured tissue equivalent phantom. Four wells, drilled perpendicular to the axis of the balloon, allowed for the insertion of thermal luminescent dosimeters (TLDs; 2 mm of diameter) and spacers. The angioplasty balloon was inflated with air or with contrast media. Radioactive yttrium-90 wires were left in the central lumen of the balloon for 2 min. Doses at the surface of the balloon, and at 1, 2, and 3 mm were determined from TLD readings. RESULTS: Doses obtained at the surface of the balloon, for a 2-min exposure for the 0.26 mm wire (balloon inflated with air) and the 0.15 mm wire (air or contrast), were 56.5 Gy, 17.8 Gy, 5.4 Gy, respectively. As expected for a beta emitter, the fall-off in dose as a function of depth was rapid. External irradiation from the beta source was negligible. CONCLUSIONS: Our experiments indicate that the dose rates attainable at the surface of the angioplasty balloon using this technique allow the doses necessary for the inhibition of intimal cell proliferation to be reached within a relatively short period of time. The thin yttrium-90 wires are very easy to handle, and their mechanical and radioactive properties are well suited to the requirements of the catheterization procedure.

Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus.

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.