The role of the spatially fractionated radiation therapy in the management of advanced bulky tumors

Abstract

Spatially fractionated radiation therapy (SFRT) refers to the delivery of a single large dose of radiation within the target volume in a heterogeneous pattern using either a custom GRID block, multileaf collimators, and virtual methods such as helical tomotherapy or synchrotron-based microbeams. The potential impact of this technique on the regression of bulky deep-seated tumors that do not respond well to conventional radiotherapy has been remarkable. To date, a large number of patients have been treated using the SFRT techniques. However, there are yet many technical and medical challenges that have limited their routine use to a handful of clinics, most commonly for palliative intent. There is also a poor understanding of the biological mechanisms underlying the clinical efficacy of this approach. In this article, the methods of SFRT delivery together with its potential biological mechanisms are presented. Furthermore, technical challenges and clinical achievements along with the radiobiological models used to evaluate the efficacy and safety of SFRT are highlighted.

Should Peak Dose Be Used to Prescribe Spatially Fractionated Radiation Therapy?—A Review of Preclinical Studies

“…Decades of preclinical studies have indicated that the microbeam and minibeam forms of SFRT have a significantly higher therapeutic index compared with conventional RT. Although strong clinical data supported by randomized trials is currently absent, clinical studies published so far using GRID and lattice therapy have indicated the potential of a higher therapeutic index for clinical cases challenging for conventional RT, especially when it is followed by conventional RT [ 11 , 30 ]. In recent years, SFRT has attracted renewed interest in the RT community, and a number of clinical trials are planned or underway [ 14 ].…”

Conebeam CT‐guided 3D MLC‐based spatially fractionated radiation therapy for bulky masses

“…Our ongoing research includes further optimizing the plan quality via spherical rather than cylindrical dose distribution by scripting and automating the template plan in the Eclipse TPS. Exploiting immunotherapy with our simple, yet clinically useful SFRT approach in the management of large and bulky tumors merits future investigation 11,12 . Additionally, further reducing dose to adjacent critical organs, while escalating tumor dose to the deep‐seated bulky masses by delivering even faster SFRT treatment with FFF‐beams, 23 and investigating its radiobiological response and tumor motion management 25 via DIBH for 3D‐conformal MLC‐based SFRT patients are currently underway.…”

“…Exploiting immunotherapy with our simple, yet clinically useful SFRT approach in the management of large and bulky tumors merits future investigation. 11,12 Additionally, further reducing dose to adjacent critical organs, while escalating tumor dose to the deep-seated bulky masses by delivering even faster SFRT treatment with FFF-beams, 23 and investigating its radiobiological response and tumor motion management 25 via DIBH for 3D-conformal MLC-based SFRT patients are currently underway. Moreover, a clinical follow-up of patients in a prospective clinical trial with higher tumor dose to deep-seated bulky tumors is ongoing to evaluate the pain-relief, tumor local control rates, and treatment-related toxicity profile for patients with MLC-based SFRT.…”

“…All these mechanisms can contribute to great treatment response that is clinically seen by a dramatic regression of large tumor masses. Unlike conformal radiation therapy, only a fraction of tumor volume is irradiated by primary beam, and other fraction receives only scattered radiation, therefore enhancing bystander effect to the tumor mass as described previously, and also enabling sparing adjacent critical organs and reducing skin oxicity 11,12 …”

“…Unlike conformal radiation therapy, only a fraction of tumor volume is irradiated by primary beam, and other fraction receives only scattered radiation, therefore enhancing bystander effect to the tumor mass as described previously, and also enabling sparing adjacent critical organs and reducing skin oxicity. 11,12 However, there are major limitations of the conventional physical single-field GRID-block therapy:(1) deepseated bulky tumors may only receive a third or less of the prescribed dose of 15 Gy. (2) It is difficult to manage skin toxicity, while escalating the tumor dose, and difficult to spare immediately adjacent critical organs.…”