Radiosurgical palliation of aggressive murine SCCVII squamous cell carcinomas using synchrotron-generated X-ray microbeams

Abstract

Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), was tested at the European Synchrotron Radiation Facility (ESRF). The left tibiofibular thigh of a mouse bearing a subcutaneously (sc) implanted mouse model (SCCVII) of aggressive human squamous-cell carcinoma was irradiated in two orthogonal exposures with or without a 16 mm aluminium filter through a multislit collimator (MSC) by arrays of nearly parallel microbeams spaced 200 microm on centre (oc). The peak skin-entrance dose from each exposure was 442 Gy, 625 Gy, or 884 Gy from 35 microm wide beams or 442 Gy from 70 microm wide beams. The 442/35, 625/35, 884/35 and 442/70 MBRSs yielded 25 day, 29 day, 37 day and 35 day median survival times (MST) (post-irradiation), respectively, exceeding the 20 day MST from 35 Gy-irradiation of SCCVIIs with a seamless 100 kVp X-ray beam.

A preclinical microbeam facility with a conventional x‐ray tube

“…These treatment fields selectively destroy tumor tissue 2 , 3 , 4 while leaving penetrated healthy tissue unimpaired 5 , 6 . The remarkable resistance of normal tissue to microbeams has been demonstrated in various preclinical studies, beginning with neutron beams in the 1960s (Refs.…”

Emerging neurosurgical applications of synchrotron-generated microbeams

“…This radioresistance phenomenon was not observed in 9L glioma microvessels, confirming the presence of a differential response to between normal and tumour brain tissues in rodents, an effect that can have significant clinical applications [19]. The neoplastic vasculature appears to be unable to replicate the fast repair of the segments hit by the peak dose, facilitating the development of radionecrosis over the irradiated tumor [12,20,28].…”

“…Unidirectional irradiation using microbeam arrays has been delivered to adult rat brain [11,13,15,16], suckling rats cerebellum [16], piglets cerebellum [1], duckling embryo brain [18], skin and muscle of the mouse leg [19,20], rat leg [21] and rat spinal cord [12]. The exceptional resistance of the normal-tissue to high dose microbeam irradiation with no evidence of late tissue effects [12,22,23,24] lead to the development of a new concept in radiobiology, the tissue sparing effect, described in the next paragraph.…”

“…Most of the experimental activity performed until now has been focused on the study of the effects of arrays of parallel microbeams [4,5,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][28][29][30]. MRT has been applied to several tumor models including intracerebral gliosarcoma (9LGS) in rats [11,13,30], murine mammary carcinoma (EMT-6) [19] and human squamous-cell carcinoma (SCCVII) in mouse and rat [9,20]. Rats bearing the intracranial 9L gliosarcoma irradiated anteroposteriorly with arrays composed of 27 gm thick microbeams spaced 100 gm on-center showed a clear survival advantage after MRT: 4 out of 14 rats irradiated at 625 Gy incident doses were longterm survivors with little brain damage revealed in histopathology [11].…”

Synchrotron Radiation Therapy from a Medical Physics point of view

“…At the ESRF the center-to-center distances between beams range from 100 to 400 µm in MRT and it is 1200 µm in MBRT. The preclinical studies in MRT indicate a remarkable healthy tissue sparing capability [10,11,12,13,14,15] and the ablation of highly aggressive tumours in several animal models [16,17,18,19,20,21,22]. In MBRT, the first preclinical studies indicate that minibeams still keep (part) of the healthy tissue sparing capability observed in MRT [9,23].…”