Author: Ramesh Boggula, Yash Somnay, Hualin Zhang 👨🔬
Affiliation: Radiation Oncology, Keck School of Medicine of USC, Wayne State University 🌍
Purpose: Spatially fractionated radiation therapy (SFRT) allows delivery of therapeutic doses to bulky tumors otherwise limited by dose-volume effects that threaten organ-at-risk tolerances. For neglected breast/chest wall tumors causing mass effect and not surgically amenable, GRID boosts can supplant fractionated uniform boosts or palliative regimens. Here, we examine how SFRT influences normal tissue survival , comparing predicted normal tissue response and tumor control against open field equivalents.
Methods: Five women with inoperable breast/chest wall tumors (mean volume=115.7cc) received MLC-based GRID boosts (15Gy) followed by whole breast radiation therapy (40-50Gy EQD2). Differential dose-volume histograms were utilized to predict cancer cell and normal tissue survival using a modified linear quadratic model incorporating a high-dose repair coefficient (α/β=3.8-10). Volume-weighted mean cell survival enabled calculation of effective uniform doses (EUD) for GRID plans, which were compared to uniform boost plans prescribed to either the EUD or as a 10Gy fractionated boost. Normal tissue survival was then compared between GRID and open fields. Tumor control (TCP) and normal tissue complication probability (NTCP) were estimated using linear quadratic-based and phenomenological models.
Results: Mean EUD for GRID plans was ~3Gy. GRID therapy achieved approximately twice the normal tissue sparing of uniform EUD plans, and approximately 100-fold greater sparing than standard 10Gy boosts (p<0.001). TCP analysis showed no significant difference between GRID and conventional boost approaches. NTCP for cardiac mortality, radiation pneumonitis, and breast fibrosis were comparable across modalities. Clinical outcomes corroborated these findings, with complete response and minimal toxicity at mean follow-up of 13.2 months.
Conclusion: These results confirm the theoretical advantage of SFRT using GRID to achieve equivalent tumor cell kill while sparing normal tissues, aligning with our observed clinical outcomes. Further studies are warranted to refine TCP/NTCP modeling for GRID, particularly regarding long-term cardiac, pulmonary, and cosmetic endpoints in patients with bulky, inoperable breast tumors.