Modified optimal fractionation for poor prognosis malignant gliomas: An elusive search

Abstract

The prognosis of malignant gliomas has not changed much over the last few decades despite refinements in neurosurgical techniques, high-precision radiotherapy, and newer chemotherapeutic agents. The median survival of poor prognosis malignant gliomas (older and/or poor performance status patients) still remains in the range of 6 Á/9 months following maximal safe resection and postoperative conventionally fractionated adjuvant radiotherapy with or without chemotherapy. However, six weeks of daily radiotherapy does seem inappropriate in relation to the short expected survival time in this subset and there is an increasing emphasis on reducing the overall treatment time and the number of hospital visits by such patients. This can be achieved either by accelerated radiotherapy or by hypofractionated radiation, both of which are equivalent to conventional fractionation in terms of palliative effect and survival, as in discussed in this review. Despite enough evidence, such alteration of fractionation has not gained widespread acceptance by the oncologic fraternity. This review has been conducted to collate the evidence that could help shift the paradigm from conventional to modified fractionation in poor prognosis malignant glioma patients.

Mathematical Modeling of PDGF-Driven Glioblastoma Reveals Optimized Radiation Dosing Schedules

“…Other recent work has successfully utilized mathematical modeling of cellular in vitro or rat-based in vivo systems to describe glioma behavior (Gao et al, 2013; Massey et al, 2012). Despite the multitude of work that has been done on optimal fractionation schedules, there has been very little success against aggressive gliomas in the clinic (Gupta and Dinshaw, 2005). …”

Assessment of compliance to treatment and efficacy of a resource-sparing hypofractionated radiotherapy regimen in patients with poor-prognosis high-grade gliomas

“…An ideal regimen should be short, welltolerated and convenient for the patients and their care-givers without compromising on efficacy. [8,11] Toward this end, hypoRT has emerged as an attractive option in terms of reducing the OTT as well as number of hospital visits by the patients and their care-givers. The outcomes with hypoRT regimens [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] have been comparable and not inferior to protracted conventionally fractionated schedules [ Table 3].…”

“…[7][8][9]11] A general consensus is that six weeks of daily fractionated radiotherapy may not be very appropriate for this subset of patients with limited life-expectancy. An ideal regimen should be short, welltolerated and convenient for the patients and their care-givers without compromising on efficacy.…”

“…[11] In this context, the use of few large dose fractions i.e. hypofractionated radiotherapy (hypoRT) has emerged as an attractive option in terms of reducing the overall treatment time (OTT) as well as the number of hospital visits.…”

A 3-dimensional DTI MRI-based model of GBM growth and response to radiation therapy

“…4, the standard radiation therapy protocol is compared to a hypofractionation protocol. Hypofractionation protocols similar to the one below have been tried in some studies with a thought to limiting the number of hospital visits which patients with a limited life expectancy need to make for treatment, and hopefully improving quality of remaining life (22).…”