Safety of IMRT Treatment With Inhomogeneous Dose in Patients With Relapsed High-grade Gliomas.

Relapsed GBMs have a life expectancy of a few months and re-radiation has proven to be safe in terms of toxicity and effective in increasing OS. One of our studies \[Ciammella P, 2013, 8:222\] reported a median survival of 9.5 months in patients with recurrent GBM and treated with stereotactic radiotherapy with a total dose of 25 Gy in 5 consecutive sessions, in which the dose was prescribed to 70% isodose with a homogeneous gradient towards the center of the target volume. The identification with functional imaging of specific areas with higher tumor cell density, and the possibility of delivering precisely, thanks to the most advanced therapy units, different doses to the different sub-volumes, can lead to an increase in the maximum dose that can be delivered at the expense of the most aggressive areas (with a greater effect on the tumor), compared to smaller doses in areas with lower signal alteration. This selectivity of the doses should allow an increase in the efficacy of the therapy and therefore a hypothetical increase in local control, compared to a radio-induced toxicity on the surrounding healthy tissues almost comparable to that achieved with the previous hypofractionated treatments \[Ciammella P, 2013\]. In fact, delivering many high doses to the entire volume would result in an excess of radio-induced necrosis within the irradiated regions with high dose, as well as the impossibility of minimizing the doses on healthy areas and / or on non-neoplastic critical areas keeping them at internal dose ranges related to minimal and acceptable toxicity levels. Since there are no studies providing clear indications on the acute and late toxicity of irradiated healthy tissues that have already been the subject of a first course of radiotherapy (STUPP), the choice of safety is the primary objective of the study.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

relapsed GBM after standard surgery-radio-chemotherapy treatment or other therapeutic lines or GBM secondary to anaplastic astrocytomas previously treated with RT and chemotherapy or recurrent anaplastic astrocytomas

* ECOG Performance Status 0-2, Performance Karnofsky Score\> 60.
* Written informed consent.
* Life expectancy\> 3 months.
* Availability of the patient to be followed for all the phases of the chemotherapy treatment and for the subsequent follow-up.-

Exclusion Criteria:

Patients with KPS \<70%.

* Participation in other studies that involve the administration of experimental drugs or explicitly exclude the possibility of participating in other studies in general or in studies whose features include aspects of this study.
* Any concurrent medical or psychological condition that may prevent participation in the study or compromise the ability to provide informed consent.
* Pregnant and lactating patients

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