Why we should give spatially fractionated radiation therapy (GRID) a second look—especially in nasopharyngeal carcinoma

GRID or spatially fractionated radiation therapy was historically used in the orthovoltage era to deliver large single 15–20 Gy doses of radiotherapy to tumours greater than 6 cm by creating a dosimetric distribution that is comprised of intervening “hot” and “cold” spots within the tumour. However, despite impressive response rates of 70% with GRID at such non-tumoricidal doses, the technique quickly fell out of favour with the advent of megavoltage linear accelerators. With the introduction of modern techniques like stereotactic body radiation therapy (SBRT) that have produced comparable response rates, it is possible that a commonality between both modalities pertains to the influence on the adaptive immune response within the tumour microenvironment. Here, we review the clinical evidence and potential mechanisms underpinning the clinical efficacy of GRID; we also propose potential scenarios where GRID represents a cost-effective and safe measure of delivering profound hypo-fractionated radiation therapy in the contemporary setting.