J. Balosso

Early breast cancer: influence of type of boost (electrons vs iridium-192 implant) on local control and cosmesis after conservative surgery and radiation therapy

Between December 1981 and December 1988, 329 consecutive patients with stage I and II breast cancers who underwent wide excision (n = 261) or quadrantectomy (n = 68) with (n = 303) or without (n = 26) axillary dissection were referred to radiotherapy. Final margins of resection were microscopically free from tumor involvement in all cases. Radiotherapy consisted in 40-45 Gy over 4-4.5 weeks to the breast, with (n = 168) or without (n = 161) regional nodal irradiation of 45-50 Gy over 4.5-5 weeks. A mean booster dose of 15 Gy was delivered to the primary site by iridium-192 implant in 169 patients (group 1) or by electrons in 160 patients (group 2). Twenty-seven percent (n = 88) of patients received tamoxifen for > or = 2 years. Adjuvant chemotherapy was administered in 22% (n = 71) of patients. Groups 1 and 2 were not strictly comparable. Group 1 patients were significantly younger, had smaller tumors, were treated with cobalt at 5 x 2 Gy per week and axillary dissection was more frequently performed. Group 2 patients were more frequently bifocal and more frequently treated by quadrantectomy and tamoxifen, and irradiation used accelerator photons at 4 x 2.50 Gy per week. No difference in terms of follow-up and survival rates was observed between the two groups. For all patients the 5- and 10-year local breast relapse rates were 6.7% and 11%, respectively. No difference was observed regarding local control either by the electron or the iridium-192 implant boosts. Axillary dissection and age had an impact on the breast cosmetic outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

A “One-day survey”: As a reliable estimation of the potential recruitment for proton- and carbon- ion therapy in France

To estimate the real figure of the potential patient recruitment for hadrontherapy we carried out a survey directly in 5 radiation therapy departments of the East of France as a one-day survey. The results presented account for 77 cases of potential indications among 532 evaluated medical records.

Quantification of dose uncertainties in cumulated dose estimation compared to planned dose in prostate IMRT.

BACKGROUND AND PURPOSEnIn prostate IMRT, the objectives were to quantify, for the bladder and the rectum: (i) the dose difference (DD) between the planned dose (PD) and the estimated cumulated dose (ECD) by deformable image registration (DIR); (ii) the dose accumulation uncertainties (DAU).nnnMATERIALS AND METHODSnA series of 24 patients receiving 80Gy in the prostate was used to calculate the ECDpts and the DDpts. To evaluate the DAU, a numerical phantom (ph) simulating deformations of main pelvic organs was used to calculate the ECDph using the same DIR method. A reference cumulated dose (RCDph) was calculated, based on the simulated deformations. The DAUph was defined by the differences between RCDph and ECDph.nnnRESULTSnFor the mean dose to the bladder, the standard deviation of DDpts was 6.9Gy (18.1Gy maximum) with a DAUph of 2.7Gy. For the rectum wall, it was 2.0Gy (4.2Gy maximum) with a DAUph of 1.2Gy. Volume differences between PDpts and ECDpts, along the dose-volume histogram, ranged from -30% to +37% and -14% to +14% for the bladder and rectum, respectively. The corresponding uncertainties ranged from -23% to +7% and -4% to +7% for the bladder and rectum, respectively.nnnCONCLUSIONSnLarge differences between planned and delivered doses to the bladder have been quantified and are higher than the uncertainties of the DIR method. For the rectum, the differences are smaller and close to the DIR uncertainties.

Activité physique et survie après cancer

Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011xa0to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

Rationale for carbon ion therapy in high-grade glioma based on a review and a meta-analysis of neutron beam trials

PURPOSEnThe standard treatment of high-grade glioma is still unsatisfactory: the 2-year survival after radiotherapy being only 10-25%. A high linear energy transfer (LET) ionising radiotherapy has been used to overcome tumour radioresistance. An overview of the field is needed to justify future prospective controlled studies on carbon ion therapy.nnnMATERIALS AND METHODSnA meta-analysis of clinical trials on neutron beam therapy and a literature review of clinical investigations on light ion use in high-grade glioma were carried out.nnnRESULTSnFour randomised controlled trials on neutron beam therapy were retained. The meta-analysis showed a non-significant 6% increase of two-year mortality (Relative risk [RR]=1.06 [0.97-1.15]) in comparison with photon therapy. Two phase I/II trials on carbon and neon ion therapy reported for glioblastoma 10% and 31% two-year overall survivals and 13.9 and 19.0 months median survivals, respectively.nnnCONCLUSIONnThis meta-analysis suggests that neutron beam therapy does not improve the survival of high-grade glioma patients while there is no definitive conclusion yet regarding carbon therapy. The ballistic accuracy and the improved biological efficacy of carbon ions renew the interest in prospective clinical trials on particle beam radiotherapy of glioma and let us expect favourable effects of dose escalation on patients survival.

Radiation tolerance of healthy tissues, high-LET beam particularities

The sensitivity of healthy tissue is the limit of radiation therapy. Most of the technological progress of radiotherapy along its history have been devoted to improve the sparing of healthy tissues while increasing the tumor dose. The use of hadrons has been justified first for neutrons by radiobiological considerations (high RBE and no oxygen effect), then for protons by ballistic considerations (Bragg peak). Neutron ballistic is so unfavourable and side effects are so important when large and deep tumors are irradiated that their indications have been dramatically reduced and no recent studies on late effect after high RBE irradiation have been carried out. Therefore, the renewal use, hopefully on a large scale, of high RBE beam such as carbon ions, demands a new appraisal of the radiation tolerance of healthy tissues. From the photon and the neutron experience should be drawn: (i) the typology of late effect; (ii) the time schedule of the observation, (iii) the equivalent dose associated with observable late effects; (iv) dose limitations according to the type of tissues, the acceptable adverse effects, the security required and the RBE of the part of the beam irradiating the healthy tissues. Commune scale and description of the late effects will have to be decided. The biological mechanisms of late effects associating slow cellular lost, micro vascular failure and active fibrosis will need further investigation in the frame of high RBE irradiation.

Le projet français ÉTOILE : données médicales actuelles de l’hadronthérapie par ions légers ☆

Resume Le Lawrence Berkeley Laboratory a ete le pionnier de l’hadrontherapie par ions legers avec pres de 2500 patients traites entre 1957 et 1993 par helium et neon. Le NIRS ( National Institute For Radiological Science , Chiba, Japon) a ete le premier centre medical dedie au traitement des cancers, avec plus de 1200 patients irradies depuis 1994 exclusivement par ions carbone. Des taux de controle local de 70 a 100xa0% a 3 ans pour des cancers radioresistants ont ete rapportes, justifiant l’utilisation de particules de haut TEL (tranfert d’energie lineique). Les possibilites d’hypofractionnement ont ete particulierement explorees pour les cancers du poumon et du foie (4 fractions actuellement), sans majoration de la toxicite. Les etudes d’escalade de dose ont mis en evidence un effet de la dose totale sur le controle tumoral et ont permis de preciser les contraintes de dose pour les tissus sains, en particulier pour le rectum. Plus de 140 patients ont ete irradies depuis 1997 dans le cadre du laboratoire de recherche GSI ( Gesellschaft Fur Schwerionenforschung , Darmstadt, Allemagne) pour des cancers radioresistants de la base du crâne par ions carbone seuls ou en association avec des photons, avec egalement un taux de controle local tres eleve. Les donnees medicales preliminaires semblent donc confirmer le gain therapeutique escompte de l’hadrontherapie par ions legers du fait de leurs proprietes balistiques et radiobiologiques et justifient les cinq projets europeens actuels de creation de centres medicaux dedies au traitement des cancers. Le projet francais «xa0Etoilexa0» s’integre dans le reseau europeen Enlight, dont l’objectif est de coordonner ces projets sur le plan technologique, medical et economique.

L'hadronthérapie : les ions carbone

Carbon ion therapy is an innovative radiation therapy. It has been first proposed in the forties by Robert Wilson, however the first dedicated centres for human care have been build up only recently in Japan and Germany. The interest of carbon ion is twofold: 1) the very sharp targeting of the tumour with the so called spread out Bragg peak that delivers most of the beam energy in the tumour and nothing beyond it, sparing very efficiently the healthy tissues; 2) the higher relative biological efficiency compared to X rays or protons, able to kill radioresistant tumour cells. Both properties make carbon ions the elective therapy for non resectable radioresistant tumours loco-regionally threatening. The technical and clinical experience accumulated during the recent decades is summarized in this paper along with a detailed presentation of the elective indications. A short comparison between conventional radiotherapy and hadrontherapy is proposed for the indications which are considered as priority for carbon ions.

De la trace des ions carbone à l’efficacité thérapeutique de l’hadronthérapie

Carbon ions, thanks to their relative biological effectiveness much higher than that of photons and protons and their ballistic characteristics similar to those of protons, can effectively treat radioresistant tumours. The reasons for this increased efficiency are found in the microdosimetric and radiobiological features of ions. The energy deposit or linear energy transfer increases along the range and reaches a very high level at the end producing the Bragg peak, where the linear energy transfer is about hundred times higher than that of photons. These massive energy deposits create multiple DNA lesions that are difficult to repair. DNA repair is associated with longer blockage of the cell cycle and more frequent chromosomal aberrations that are lethal to cells. The types of cell death are identical to those triggered in response to photon irradiation, but the response is earlier and more important at equivalent physical dose. Radiobiological differences between carbon ions and photons have been studied for some years and many aspects remain to be explored. In general, these phenomena tend to reduce the differences of radiosensitivity among different tissues. It is therefore in situation where tumours are relatively radioresistant compared to healthy tissue, that carbon ions must be used and not in the opposite situations where the fractionation of low linear energy transfer radiation is sufficient to provide the necessary differential effect to cure the tumour.

Radiothérapie des sarcomes : hadronthérapie, pour qui, pour quoi ?

The radiobiological properties of the hadrons (neutrons, protons, carbon ions) led to their therapeutic use in sarcomas, as a referent therapy or as an alternative to photon therapy. An extensive review of the literature has been conducted to assess the present indications and the perspectives for hadrontherapy. Compared to photons, neutrons are characterized by a higher biological efficiency that is on particular importance for these tumours usually considered as radio-resistant. Neutrons have been considered as a standard therapy for sarcoma patients, contra-indicated for surgery or with a definitive R2 resection, but their indications and use have been restricted due to the occurrence of late severe toxicities related to their poor ballistic properties. Thanks to their physical properties (Bragg Peak), protons are characterized by a higher conformity index compared to photons (and neutrons) with optimal organs at risk preservation that permits a dose escalation. Protontherapy is to date the standard of care for base of skull, spinal and paraspinal sarcomas. Carbon ions combined both advantages from protons and neutrons. Literature data permits to consider this radiation modality as a referent therapy for unresectable sarcomas. The ongoing diffusions of protons and carbon ions radiotherapy facilities will permit to offer these therapies to more patients and to conduct studies that are warranted to determine their indications and their results.