Between September 1990 and March 1995, 189 patients were treated with high-dose-rate endobronchial brachytherapy. Most patients (70%) presented with either recurrent or persistent symptomatic endobronchial tumor after standard therapy. A minority of the patients (12%) had small endobronchial tumor and were unfit for surgical resection or radiotherapy. Treatment was delivered weekly and consisted of three to four 8- to 10-Gy radiotherapy fractions applied at 10 mm from the source. Major symptomatic improvement was obtained on hemoptysis (74%), dyspnea (54%), and cough (54%). Complete endoscopic response occurred in 54.5% of the cases. Median survival was 7 months for the entire group. For small strictly endobronchial tumors, complete response rate was 95.5%, median survival was 17 months, and 30-month survival was 46%, with a plateau starting at 18 months. The rate of late grade 3 to 4 toxicity was 17%, including hemoptysis (n = 13), stenosis (n = 12), local necrosis (n = 8), and bronchial fistula (n = 3). By univariate analysis, no factor was found to be predictive of late toxicity. Our study confirms the benefit of endobronchial brachytherapy in the palliative treatment of endobronchial recurrences and in the curative intent treatment of small endobronchial tumors in patients not suitable for other forms of therapy.
Proton therapy is widely acknowledged as one of the most effective methods in the selective destruction of cancer cells. Its development has, however, been hampered by the complexity, the size and the cost of the necessary equipment, which were up to now not adapted to the hospital environment. Things are changing in this regard. At the beginning of 1994, the Massachusetts General Hospital (MGH) of the Harvard Medical School in Boston, MA, USA, a pioneer in proton therapy since 1959, selected a team led by IBA to supply the proton therapy equipment of its new Northeast Proton Therapy Centre (NPTC). The present paper presents the integrated system being build for the NPTC. This equipment includes a compact 235 MeV isochronous cyclotron, a short energy selection system transforming the fixed energy beam extracted from the cyclotron into a variable energy beam, one or more isocentric gantries fitted with a nozzle, one or more horizontal beam lines, a global control system including an accelerator control unit and several independent but networked therapy control stations, a global safety management system, and a robotic patient positioning system.
Si le pronostic des formes precoces des cancers du col uterin est maintenant favorable grâce aux associations radiochirurgicales, le pronostic des formes localement evoluees reste sombre. Nous rapportons les resultats preliminaires d'une etude retrospective portant sur 29 patientes porteuses de tumeurs localement evoluees traitees entre decembre 1987 et janvier 1990 par une association de radiotherapie et de cisplatine. L'âge median est de 47 ans. Il s'agit de 1 stade ib, 5 stades ila, 6 stades ilb, 7 stades illa, 9 stades illb et 1 stade IVa
Les irradiations par capture de neutrons visent à détruire sélectivement et efficacement les cellules tumorales au moyen de réactions nucléaires produites sélectivement en leur sein. Pour ce faire, du 10B est apporté préférentiellement à l'intérieur des tumeurs au moyen d'une molécule vectrice, puis l'ensemble des tissus est irradié par des neutrons thermalisés (E = 0,025 eV). Lors des réactions de capture de neutrons sur 10B, le noyau final se scinde en une particule α et un ion 7Li qui emportent une énergie de 2,79 MeV et qui détruiront tout sur leurs parcours d'une dizaine de micromètres. Ces captures sont utilisées soit exclusivement lors d'une irradiation par neutrons ≪lents≫, c'est la thérapie par capture de neutrons, soit en potentialisation d'une irradiation par neutrons ≪rapides≫, c'est la potentialisation par capture de neutrons. Les premiers essais cliniques américains des années 1951 à 1961 pour le traitement des gliomes de haut grade ont été un échec en raison d'une localisation préférentielle de 10B à l'intérieur des vaisseaux et des capillaires sanguins intracérébraux. Actuellement, un certain nombre d'éléments nouveaux permettent de penser que la méthode peut être utilisée en clinique pour le contrôle local de tumeurs radiorésistantes: des molécules vectrices plus performantes; des faisceaux de neutrons mieux calibrés; une meilleure connaissance de la radiobiologie liée à ce type d'irradiation. Parmi les tumeurs pouvant bénéficier de ce type d'irradiation, il y a les gliomes de haut grade, les mélanomes cutanés et sans doute oculaires, et peut-être les sarcomes des tissus mous.
Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,α)7 Li nuclear reactions produced within themselves. Following the capture reaction, an α particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10μm. These captures, used exclusively with a ‘slow’ neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an ‘epithermal’ neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5cm depth in the tissues, delayed after the fast neutron peak at 1.8cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.
The French National Agency for Medical Evaluation (ANDEM) was requested to assess the effectiveness of proton and neutron beam therapy in cancer treatment compared to conventional radiotherapy. This task was accomplished by a critical appraisal of the clinical and economic literature. According to the published economic literature and the capital and staffing cost analysis, it appears that the costs of proton therapy are likely to be two or three times greater than those of photon conformal therapy. According to the published clinical literature, proton beam therapy should be proposed as a routine treatment only for uveal melanoma and skull base cancers. Neutron beam therapy should be proposed as a routine treatment for inoperable salivary gland tumors; its use may be also discussed in cases of stage C-Dl prostate cancers and soft tissue sarcomas. Based on the current scientific evidence and given the incidence rate of these tumors, the time and material requirements, the current French proton/neutron beam facilities are able to meet the current demand. For other cancers the medical and economic potential of proton therapy is still an open question.
De 1981 à 1985, 428 patients présentant un carcinome épidermoïde de l'hypopharynx et/ou du larynx ont été traités avec intention curative par exérèse chirurgicale et irradiation postopératoire. Les deux-tiers des tumeurs étaient classés T3 et 60 % avaient un envahissement ganglionnaire clinique. Le taux d'échec local est respectivement de 8 %, 18 % et 13 % respectivement pour les cancers du larynx, du sinus piriforme et de la paroi postérieure, les échecs régionaux étant respectivement de 8 %, 23 % et 13 %. Il n'y a pas de site cervical à haut ou faible risque de rechute après curage mais la rupture capsulaire reste un facteur de mauvais pronostic. Le taux de survie à 5 ans de l'ensemble de la série est de 38 %, pour la localisation laryngée il atteint 62 %. Le risque de métastases est lié à l'envahissement ganglionnaire et à l'intervalle de temps entre la chirurgie et l'irradiation.
Le bul de cette étude prospective était de réduire le taux de récidives locales (RL), le taux de métastases à distance et ainsi d'améliorer la survie des patients. Les patients atteints d'un carcinome épidermoïde du sinus piriforme, de la margelle laryngée ou de la région rétro-crico-aryténoïdienne relevant d'une pharyngolaryngectomie totale étaient incluables dans cette étude. Le protocole prévoyait trois cures de chimiothérapie préopératoire (CDDP cisplatine 100 mg/m2 j1,5-FU 1 g/m2 j1 à j5) puis deux cures de la même chimiothérapie en postopératoire à j10 et j31. La radiothérapie postopératoire a été effectuée àj50. Parmi les 198 cancers de l'hypopharynx vus entre 1986 et 1989 à l'institut Gustave-Roussy, 60 ont été inclus dans ce protocole. La réponse tumorale aux trois cures initiales de chimiothérapie était: non réponse (NR): 22; réponse partielle (PR): 25; réponse complète (CR): 11: réponse non évaluable: 2. Parmi les 47 patients opérés, seulement deux pièces opératoires ont été considérées stérilisées à l'examen histologique et deux pièces avec uniquement des débris de kératine. Parmi les 39 patients ayant eu le protocole; 4 RL, 4 RL + M, 8 M, trois deuxièmes localisations au niveau des voies aérodigestives supérieures (VADS) et une leucémie aiguë myéloblastique ont été observées. Les résultats de cette étude, comparée à ceux d'une étude historique (199 patients) ayant le même délai d'observation, montrent un taux de survie identique à 2 ans, 78% contre 77% et de 42% contre 33% à 5 ans (NS).
In Asian countries, fast neutron therapy was first introduced at the National Institute of Radiological Sciences (NIRS), and followed by the Institute of Medical Science (IMS), Tokyo University, and Korea Cancer Center Hospital (KCCH). At NIRS, 2,129 patients were treated with d(30 MeV)+Be neutrons between 1975 and 1994. There were 274 patients referred for the treatment with P(50.5 MeV)+Be neutrons at KCCH during the period of 1986 through 1992. Unfortunately, fast neutron therapy performed at IMS was discontinued in 1991, where 458 patients had been treated with d(14 MeV)+Be neutrons since 1976. At NIRS, a vertical beam with multileaf collimator system was used for treatment of patients referred. The results showed that local control rates were 79% (19/24), 53% (14/26), and 89.3% (50/56) for carcinoma of the salivary gland, osteogenic sarcoma and carcinoma of the prostate, while complications for those were found to be 8.8, 8.3 and 17.8%, respectively. In the treatment of carcinoma of the lung, results were better for patients with adenocarcinoma than those with squamous cell carcinoma. Of 32 patients suffering from Pancoast tumor, 14 achieved local control, whereas 2 of 32 patients developed complications. On the other hand, salvage surgery was required in the treatment of malignant melanoma. In the treatment of malignant glioma, dose localization has to be improved in the target area to confirm local control. Experiences performed at KCCH have shown that, of 53 patients suffering from unresectable primary or recurrent rectal carcinomas, 28 achieved local control. It was concluded from the experiences with fast neutrons in Asian countries that adenocarcinomas as well as slowly growing tumors are indications for fast neutrons and that dose localization has to be improved in order to advance high LET radiation therapy. Clinical trials with 70 MeV protons started at NIRS in 1979, where the aim of study has been focused on treatment of choroidal melanoma, whereas, at Tsukuba University, 250 MeV protons have been used in the treatment of tumors deeply seated. Based on experiences of fast neutrons and protons, clinical trials with heavy ions initiated at NIRS in October 1994. Clinical studies with high LET radiations will be performed by using heavy ions in order to pursue indications of particle radiation therapy.
