Jean-Jacques Mazeron

Cognitive impairment and morphological changes after radiation therapy in brain tumors: A review

Life expectancy of patients treated for brain tumors has lengthened due to the therapeutic improvements. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. Technical evolutions aim at enhancing the therapeutic ratio. Sparing of the healthy tissues has been improved using various approaches; however, few dose constraints have been established regarding brain structures associated with cognitive functions. The aims of this literature review are to report the main brain areas involved in cognitive adverse effects induced by radiotherapy as described in literature, to better understand brain radiosensitivity and to describe potential future improvements.

Can anticancer chemotherapy promote the progression of brain metastases

Brain metastases natural history from one primary tumor type might be accelerated or favored by using certain systemic chemotherapy. A great deal was described in mice and suggested in human with antiangiogenic drugs, but little is known about the metastatic progression generated by the perverse effect of anticancer drugs. A total of 413 patients who underwent treatment for brain metastasis (2013–2016) were included. The identification of all previous anticancer drugs received by patients from primary tumor diagnosis to brain metastases diagnosis was collated. The median value for the time of first appearance of brain metastasis in all patients was 13.1xa0months (SD 1.77). The values of brain metastasis-free survival (bMFS) for each primary cancer were: 50.9xa0months (SD 8.8) for breast, 28.5xa0months (SD 11.4) for digestive, 27.7xa0months (SD 18.3) for melanoma, 12.3xa0months (SD 8.3) for kidney, 1.5xa0months (SD 0.1) for lung and 26.9xa0months (SD 18.3) for others (pxa0<xa00.009). Through Cox multivariate proportional hazard model, we identified that the only independent factors associated with short bMFS were: lung primary tumor [odd ratio (OR) 0.234, CI 95% 0.16–0.42; pxa0<xa00.0001] and mitotic spindle inhibitor (taxanes) chemotherapy [OR 0.609, CI 95% 0.50–0.93; pxa0<xa00.001]. Contrariwise, breast primary tumor [odd ratio (OR) 2.372, CI 95% 1.29–4.3; pxa0<xa00.005] was an independent factor that proved a significantly longer bMFS. We suggest that anticancer drugs, especially taxane and its derivatives, could promote brain metastases, decreasing free survival. Mechanisms are discussed but still need to be determined.

Timeline metastatic progression: in the wake of the « seed and soil » theory

Little is known about the natural history of cancer and its evolution to metastasis. Paget was the first to postulate the important role played by microenvironment in metastasis progression. Since, the concept of his “seed and soil” theory has been supported and confirmed. Understanding the chronology and natural course that underlie metastasis is mandatory to deepen this concept and to progress in the development of novel therapeutic strategies. A total of 413 patients who underwent treatment for brain metastasis (2013–2016) were included. The identification of previous and newly diagnosed metastasis was made during the clinical and imaging follow-up. We identified 910 metastases in our series. The 2-, 5-, and 10-year survival estimates were 80% (SD 2), 59.1% (3), and 36% (4), respectively. The median time for first metastasis, referred as metastasis-free survival (MFS) was 15.2xa0months (SD 1.47). MFS were determined for each metastasis location and were as follows: 7.2xa0months (SD 8.0) for bone, adrenal 8.4xa0months (SD 9.4) for adrenal, 13.2xa0months (SD 1.7) for brain, 14.6xa0months (SD 5.4) for liver, 25.7xa0months (SD 11.7) for pleura, 27.7xa0months (SD 15.9) for peritoneum, 29.8xa0months (SD 7.2) for spine, 30.2xa0months (SD 5.2) for lungs, and 54.2xa0months (SD 12.4) for skin (pxa0<xa00.009 log rank). We identified a metastatic timeline process for breast cancer (pxa0<xa00.0001 log rank (Mantel–Cox)) and furthermore according to breast subtype cancer (pxa0<xa00.0001). We suggest that in addition to Paget’s theory, a timeline and a natural history of metastasis exist in patients with cancer. We suppose that some, but not all, primary cancers follow chronological and scheduled metastatic processes to invade organs.

Compte-rendu du troisième forum de l’European Society for Therapeutic Radiology and Oncology (ESTRO). Barcelone (Espagne), 24–28 avril 2015

Le troisième forum de lEuropean Society of Therapeutic Radiology and Oncology (ESTRO) sest tenu au centre des congrès de la ville de Barcelone, du 24 au 28 septembre 2015. Au total, plus de 4000 travaux scientifiques ont été présentés, dont plus de 1200 oralement. Seuls ceux dont les conclusions nous ont paru les plus marquantes font lobjet de ce compte-rendu. Le lecteur désirant plus dinformation pourra se reporter au supplément 1 du tome 115 de Radiotherapy & Oncology. Cancer de la prostate En se fondant sur lhypothèse dun rapport a/b bas dans les cancers de la prostate, il peut savérer intéressant de délivrer une irradiation hypofractionnée pour augmenter la dose par fraction. Lessai britannique CHHiP (Conventional or Hypofractionated High dose intensity modulated radiotherapy in Prostate cancer) a randomisé chez des patients atteints dun cancer de la prostate de risque faible ou intermédiaire une radiothérapie standard de 74 Gy en 37 fractions et une radiothérapie hypofractionnée de 60 Gy en 20 fractions ou 57 Gy en 19 fractions (abstract PO-720). Les patients ont été interrogés sur les symptômes dont ils souffraient avant la radiothérapie et à 24 mois (abstract PO-0720). Au total 1659 (82,5 %) ont répondu avant le traitement et 1444 (71,8 %) à 2 ans. Une augmentation temporaire des symptômes digestifs et urinaires a été observée à 10 semaines, liée à la toxicité aiguë du traitement (741/1308 [56,7 %] contre 408/1498 [27,2 %] avant la radiothérapie), mais il ny avait aucune différence entre les deux bras à 24 mois. Un essai randomisé multicentrique canadien a comparé dans une population de 398 patients atteints de cancer de la prostate de pronostic intermédiaire ou défavorable une curiethérapie de bas débit de dose et une radiothérapie externe de 78 Gy