Intensity-Modulated Radiation Therapy versus 3D Conformal Radiation Therapy in Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy for Breast Cancer: Looking Beyond Dosimetric Outcomes

Abstract

Prospective data and meta-analyses support the use of adjuvant regional nodal irradiation (RNI)/postmastectomy radiation therapy (PMRT) for the majority of women with axillary lymph node positive breast cancer. However, RNI increases dose to the heart and lung compared resulting in increased toxicity. Inverse-planned intensity modulated radiation therapy (IMRT) has the ability to reduce high dose to the heart/lung compared to traditional 3D conformal radiation therapy (3DCRT). Early concerns with IMRT were that it may be too conformal resulting in increased risk of local-regional failures (LRF). To date, clinical outcomes with IMRT have not been well studied in patients receiving RNI/PMRT. We have used planning target volume (PTV)-based, dose-volume analysis driven RNI/PMRT planning since 2013 using primarily 3DCRT but IMRT as needed to meet heart/lung planning objectives. We hypothesize that toxicity and LRF rates are similar between patients treated with IMRT and 3DCRT. We identified patients that received RNI/PMRT from 2013-2016. Patients received conventional fractionation (200 cGy/day) to the breast/chestwall, axillary, supraclavicular (SCV), and internal mammary chain (IMC) PTVs. We divided the cohort into 2 groups (IMRT vs. 3DCRT). We collected patient and disease characteristics, acute toxicity, LRF, and distant metastases (DM) events. Differences in characteristics were evaluated with the t-test or Chi-square test. The primary endpoint was the cumulative incidence of LRF as a first failure. We also evaluated the cumulative incidence of DM. We included 241 patients (69 IMRT, 172 3DCRT): 60% had stage III disease; 60% (ER+ or PR+)/HER2-; 20% triple-negative; 20% HER2+. IMRT group had higher rates of left-sided (65% vs. 47%, p=0.009) and grade 3 (58% vs. 43%, p=0.04) disease. The IMCs were irradiated in 97%. Treatment was well tolerated: grade 3 dermatitis 6% in each group with no other grade 3 toxicities. Grade 2 pneumonitis occurred in 2 (0.83%), both 3DCRT. Median follow-up is 3.5 years. There were 5 LRF events (2 IMRT, 3 3DCRT): 2 patients with isolated LRF (iLRF) and 3 patients with simultaneous LRF+DM resulting in 4-year LRF=2.1% (4.1% IMRT vs. 1.4% 3DCRT, p=0.55) and 4-yr iLRF=1.1% (1.5% vs. 0.8%, p=0.43). The iLRF (1 IMRT, 1 3DCRT) both occurred in the SCV region. The other LRF+DM event in the IMRT group was a chestwall/axillary/IMC recurrence post-mastectomy. The additional 2 LRF+DM events in the 3DCRT group included: ipsilateral SCV and level V nodes post-lumpectomy; and a lumpectomy bed recurrence. Most failures were DM: 4-year rate=15% (21.0% IMRT vs. 13.2% 3DCRT, p=0.58). In this modern cohort of patients receiving RNI/PMRT with a PTV-based approach, we saw rare high-grade toxicity, and we found no difference in LRF and DM rates between IMRT and 3DCRT patients. These data should provide reassurance that IMRT does not compromise disease outcomes and that IMRT can safely be used when needed to meet normal tissue constraints.