The concept of rapid rescue radiosurgery in the acute management of critically located brain metastases: A retrospective short-term outcome analysis

Abstract

Background:Adaptive hypofractionated gamma knife radiosurgery has been used to treat brain metastases in the eloquent regions while limiting the risk of adverse radiation effect (ARE). Ablative responses might be achieved within days to weeks with the goal to preserve the neurological function. The application of this treatment modality in selected acute/subacute settings has been termed Rapid Rescue Radiosurgery (RRR) in our department. We report the expeditious effects of RRR during treatment and 4 weeks after treatment completion.Methods:In all, 34 patients with 40 brain metastases, each treated over a period of 7 days in three separate gamma knife radiosurgery sessions (GKRS 1-3) between November 2013 and August 2017, were retrospectively analyzed in terms of tumor volume reduction, salvage of organs at risk (OAR), and radiation induced toxicity under the period of treatment (GKRS 1-3 = one week) and at first follow-up magnetic resonance imaging (MRI) (4 weeks after GKRS 3).Results:Mean tumor volume at GKRS 1 was 12.8 cm3. Mean peripheral doses at GKRS 1, GKRS 2, and GKRS 3 were 7.7 Gy, 8.1 Gy, and 8.4 Gy (range: 6.0-9.5 Gy) at the 35% to 50% isodose lines. In the surviving group at first follow-up (n = 28), mean tumor volume reduction was − 10% at GKRS 3 (1 week) and − 48% four weeks after GKRS 3. There was no further clinical deterioration between GKRS 3 and first follow-up in 21 patients. Six patients died prior to first follow-up due to extracranial disease. No ARE was noticed/reported.Conclusions:In this study, RRR proved effective in terms of rapid tumor volume reduction, debulking, and preservation/rescue of neurological function.

Adaptive radiosurgery based on two simultaneous dose prescriptions in the management of large renal cell carcinoma brain metastases in critical areas: Towards customization

“…In this particular case, the positive clinical and radiographic evolution of Met 1 and Met 2 post-RRR were similar to previous reports from other authors and Sinclair et al [24,[26][27][28][29][30] Unfortunately, a deeper analysis of the kinetic effectiveness of RRR compared to single fraction treatments or other oligostaged approaches remains complex and will continue to be a source of bias; indeed, although a few groups have studied the specific effects of stereotactic hypofractionated radiotherapy on tumor kinetics in renal histology, [33,37] to the best of our knowledge, there are no or few studies comparing the ablative dynamics of brain lesions post single fraction versus post hypofractionation. Nonetheless, based on (i) the volumetric data post treatment of this case [Tables 1-3] (ii) our institutional experience, [26][27][28][29][30] and (iii) the available medical literature, [1,24,32,36] we suggest that, in the context of this case, the expeditious and lasting ablative effects triggered by this double prescription technique extended survival. [24,[26][27][28][29][30] Moreover, the fact that our patient developed an ARE at the site of Met 1 and Met 2 despite a hypofractionated approach, suggests that SF-GKRS would have led to greater perilesional edema and possibly substantial radionecrosis resulting in further neurologic damage.…”

“…Nonetheless, based on (i) the volumetric data post treatment of this case [Tables 1-3] (ii) our institutional experience, [26][27][28][29][30] and (iii) the available medical literature, [1,24,32,36] we suggest that, in the context of this case, the expeditious and lasting ablative effects triggered by this double prescription technique extended survival. [24,[26][27][28][29][30] Moreover, the fact that our patient developed an ARE at the site of Met 1 and Met 2 despite a hypofractionated approach, suggests that SF-GKRS would have led to greater perilesional edema and possibly substantial radionecrosis resulting in further neurologic damage. Several studies seem to support the latter proposal.…”

“…e rationale behind RRR can be found elsewhere in the literature. [26][27][28]31] Follow-up MRI at 1, 3, and 6 months confirmed subsequent tumor volume reduction of Met 1 with ensuing significant improvement of the patient's motor function […”

“…Aiming to decrease the risk of SF-GKRS associated ARE, different groups have explored alternative schedules with the aim of reducing toxicity whilst optimising local control; in this framework, volume-staged hypofractionation has become a vivid subject of discussion. [1,[26][27][28][29][30]36] Yamamoto et al conducted a three-stage gamma knife treatment study on 78 patients with e inclusion of underlying radiobiological parameters and inherent physio-mathematical variables are quintessential for triggering key microenvironmental events involving vascular damage and antitumor immunity. e rationale of the procedure can be found elsewhere.…”

“…to 90% of the tumor bed (previously coined baseline ablative isodose line or BAIL). [27] in the field of medical uro-oncology are reshaping the management of mRCC; however, the long-term effects of most agents, such as checkpoint, multitargeted tyrosine kinase, and mammalian target of rapamycin inhibitors require much improvement, particularly in the context of concurrent metastatic disease in the central nervous system. e latter might require a better understanding of key concurrent antitumoral mechanisms aiming to optimize the use of radiation such as the modulation of T-cell expansion, the regulation of postradiation blood-brain barrier permeability and the use of "scavenging" agents targeting angiogenesis and endothelial cell proliferation to further "downturn" tumor radioresistance.…”