Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/ß = 1.4 (0.9-2.2) Gy.

PURPOSE: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. METHODS AND MATERIALS: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was used for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), α (dose-response slope using very low doses per fraction), and the ratio α/ß that characterizes dose-fractionation sensitivity. RESULTS: There was no significant difference between the α/ß value for the three risk groups, and the value of α/ß for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the α/ß value. CONCLUSIONS: The overall α/ß value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings.

Normal tissue complications after radiation therapy / Las complicaciones de la radioterapia en los tejidos sanos

This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of increasing the size of the irradiated volume, early and late tissue reactions, effects of changes in dose fractionation and dose rate, and combined chemotherapy and radiotherapy responses. Examples are given of increases in knowledge of clinical radiobiology from trials of new protocols. Potential modification to treatments include the use of biological response modifiers. The introduction of "response prediction" modifications to treatments might also be available in the near future. Finally, the paper points out that in some radiotherapy centers, the biologically-effective doses prescribed for combined brachytherapy and teletherapy treatment of cervix cancer are lower than those prescribed in other centers. This issue needs to be addressed further. The wealth of preclinical and clinical data has led to a much greater understanding of the biological basis to radiotherapy. This understanding has underpinned a variety of new approaches in radiotherapy, including both physical and biological strategies. There is also the important issue of treatment of a large number of cancers in developing countries, for which efficacious resource-sparing protocols are being continuously developed. A unified scoring system should be widely accepted as the new standard in reporting the adverse effects of radiation therapy. Likewise, late toxicity should be reported on an actuarial basis as a mandatory endpoint.

En este artículo se describen los mecanismos biológicos que intervienen en las reacciones provocadas por la radioterapia, tanto con tratamientos convencionales como con los más nuevos, y los aplicados en países en desarrollo. Asimismo, se describen las bases biológicas del período de latencia que precede a la aparición de las complicaciones tisulares; la relación entre la dosis de radiación y la incidencia de complicaciones; las consecuencias de aumentar el volumen irradiado; las reacciones tisulares tempranas y tardías; los efectos de cambios en el fraccionamiento de las dosis y en las tasas de dosis; y las reacciones observadas al aplicar una combinación de quimioterapia y radioterapia. Se ofrecen ejemplos de nuevos conocimientos en el campo de la radiobiología clínica que se han adquirido mediante ensayos con nuevos protocolos. Entre las posibles modificaciones de los tratamientos figura el uso de modificadores de la respuesta biológica; en el futuro próximo, podría contarse también con modificaciones de los tratamientos para poder "predecir la respuesta". Por último, las dosis cuya eficacia biológica está demostrada y que están prescritas para tratar el cáncer cervicouterino usando una combinación de braquiterapia y teleterapia son menores en algunos centros que en otros, como se explica en este trabajo. El asunto debe examinarse más a fondo. Una gran abundancia de datos de carácter preclínico y clínico ha permitido comprender mucho mejor las bases biológicas de la radioterapia, y ello a su vez ha llevado a una serie de innovaciones en este campo, tanto en forma de estrategias físicas como biológicas. También es importante prestar atención al tratamiento de una gran variedad de cánceres en países en desarrollo, para los cuales continuamente se elaboran protocolos terapéuticos eficaces orientados a ahorrar recursos. Debería adoptarse en todas partes un único sistema de puntuación para documentar los efectos nocivos de la radioterapia. Asimismo, la toxicidad tardía debería ser un parámetro clínico de valoración obligatoria y figurar en las estadísticas de los resultados del tratamiento