[Update of clinical programs using hadrontherapy 2008-2012]. / Évolution des indications cliniques en hadronthérapie 2008-2012.

Hadrontherapy, a type of radiation therapy dealing with heavy charged particles, has become for the past decade one of the most sophisticated and attractive approach in the management of cancer. This is related with major technological innovations that have made available, at a relatively cheap cost, compact proton accelerators equipped with rotational gantries. The implementation of pencil beam scanning should also make treatment planning and delivery much easier and faster than conventional approaches. Until now, approximately 100,000 patients have been treated with protons worldwide. Due to more complex technological and biological challenges, light ion therapy - mainly carbon ions - has developed at a lower pace, except in Japan where most of the 15,000 treated patients have been enrolled. Current indications for protons include firstly, locally aggressive tumours non or incompletely resected, that are located close to critical normal structures: ocular melanomas, skull base and spinal canal low grade sarcomas, selected ENT carcinomas (like adenoid cystic); secondly, improvement of tolerance to radiations: delayed, mainly in paediatric malignancies, due to the exquisite sensitivity of organs under development (including to carcinogenesis); immediate, on bone marrow, mucosae… mainly in concomitant radiation-chemotherapy interactions (tested in esophagus, and lung). Most promising indications for carbon ions include inoperable highly radioresistant primaries, such as mucosal melanomas, high grade bone and soft part sarcomas, and pancreatic carcinomas. Altered fractionations are also of interests that could translate in clinical and economical benefits. Controversies have risen whether more common indications, like prostate, should also be explored.

[Protontherapy: basis, indications and new technologies]. / La protonthérapie : bases, indications et nouvelles technologies.

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

[Is proton beam therapy the future of radiotherapy? Part I: clinical aspects]. / La protonthérapie: avenir de la radiothérapie? Première partie: aspects cliniques.

Proton beam therapy uses positively charged particles, protons, whose physical properties improve dose-distribution (Bragg peak characterized by a sharp distal and lateral penumbra) compared with conventional photon-based radiation therapy (X-ray). These ballistic advantages apply to the treatment of deep-sited tumours located close to critical structures and requiring high-dose levels. [60-250 MeV] proton-beam therapy is now widely accepted as the "gold standard" in specific indications in adults--ocular melanoma, chordoma and chondrosarcoma of the base of skull --and is regarded as a highly promising treatment modality in the treatment of paediatric malignancies (brain tumours, sarcomas…). This includes the relative sparing of surrounding normal organs from low and mid-doses that can cause deleterious side-effects such as radiation-induced secondary malignancies. Other clinical studies are currently testing proton beam in dose-escalation evaluations, in prostate, lung, hepatocellular cancers, etc. Clinical validation of these new indications appears necessary. To date, over 60,000 patients worldwide have received part or all of their radiation therapy program by proton beams, in approximately 30 treatment facilities.

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer.

BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.

[Proton beam therapy in pediatric radiotherapy]. / La protonthérapie en radiothérapie pédiatrique.

Pediatric tumors still represent a formidable challenge despite the considerable therapeutical advances that have been reported for the past 30 years. This is largely related with the untowards side-effects of local therapy that are still acknowledged as the "price for cure". In this setting, Proton therapy a sophisticated radiotherapeutical modality seems to represent a real breakthrough due to its unique ability to spare close and distant normal organs compared with modern photons techniques. We summarize in this paper current clinical and dosimetrical evidences including an update of the Orsay series on 108 children.

[Early diagnosis of postinfarction ventricular aneurysm. Value of contrast scintigraphy]. / Le diagnostic précoce de l'anévrysme ventriculaire post-infarctus. Intérêt de la scintigraphie de contraste.

Early diagnosis of a ventricular aneurysm after myocardial infarction may provide a valuable means of preventing certain complications. We studied 55 patients with acute myocardial infarction on the 8th day by Technetium 99 angioscintigraphy with study of wall motion and ejection fraction at equilibrium. The results were compared with left ventriculography performed three months after infarction. Angioscintigraphy demonstrated 17 cases of dyskinesia, 16 cases of hypokinesia, and 22 cases of akinesia, divided into two subgroups depending on whether the ejection fraction was lower (n = 11) or higher than 40% (n = 11). Contrast angiography at 3 months confirmed the presence of 27 aneurysms, 17 akinetic plaques and 11 cases of hypokinesia. Comparison between the two series of investigations showed excellent correlations: in the group of dyskinesia (17 cases) an aneurysm was confirmed in 15 cases; in the group of hypokinesia (16 cases) only one aneurysm was demonstrated by the reference angiography. The results were less uniform in the group with akinesia. In the subgroup with a low ejection fraction, 9 out of 11 cases progressed to aneurysm and, in retrospect, should be considered as likely aneurysms. There were only 2 aneurysms (2/11) in the subgroup with localised akinesia and a high ejection fraction. The overall results suggest that angioscintigraphy at the 8th day of myocardial infarction is a reliable means of detecting left ventricular aneurysm; in cases of dyskinesia or widespread akinesia with an ejection fraction of less than 40% the presence of an aneurysm was confirmed in 24 out of 28 patients (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemodynamic effects of hydralazine in the cardiac insufficiency of non-obstructive myocardiopathy]. / Effets hémodynamiques de l'hydralazine dans l'insuffisance cardiaque de la myocardiopathie non obstructive.

The haemodynamic effects of a single dose of between 0.15 and 0.25 mg/kg hydralazine were studied during cardiac catheterisation of 9 patients with primary congestive cardiomyopathy and heart failure. The systemic arterial resistances decreased (--1 370 +/- 400 dynes/s.cm-5/m2, p less than 0.05); the reduction of pulmonary arterial resistances was less marked (--420 +/- 400 dynes/s.cm-5/m2, p less than 0.05). Intraaortic pressure was reduced (--16 +/- 12 mmHg, p less than 0.02) as was average pulmonary arterial (--4.2 +/- 4,2 mmHg, p less than 0.05) and left ventricular end diastolic pressures (--4.2 +/- 3.0 mmHg, p less than 0,02). Systolic index increased in all cases (+13 +/- 5 ml/syst/m2, p less than 0.001). Heart rate was unchanged. This was due to the improvement of left ventricular function by the reduced impedence. These results confirm the place of hydralazine in the treatment of certain forms of heart failure.