Comparative Effectiveness Analysis of 3D-Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy (IMRT) in a Prospective Multicenter Cohort of Patients With Breast Cancer.

ABSTRACT Purpose Simple intensity modulation of radiation therapy reduces acute toxicity compared to two-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiotherapy (IMRT) offers an advantage over forward-planned, three-dimensional conformal radiotherapy (3DCRT). Methods and Materials Using prospective data regarding patients receiving adjuvant whole breast RT without nodal irradiation at 23 institutions from 2011-2018, we compared incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle).  We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting (IPTW), adjusting for treatment facility as a random effect. Results Of 1,185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly-segmented forward-planned IMRT, 458 (59.2%) did; of 580 treated with inverse-planned IMRT, 245 (42.2%) did.  Of 1,296 patients treated with hypofractionation and 3DCRT 432 (33.3%) experienced acute toxicity; of 709 treated with highly-segmented forward-planned IMRT, 227 (32.0%) did; of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with IPTW, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% CI, 0.45-0.91) with conventional fractionation and 0.41 (95% CI, 0.26-0.65) with hypofractionation. Conclusions This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared to 3DCRT in reducing acute toxicity of breast radiotherapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness.