Largest Real-World Data of Regional Nodal Irradiation Using Ultra-Hypofractionated 5-Fraction Adjuvant Radiation Therapy for Breast Cancer from a Single Institute in India

Abstract

Safety data for ultra-hypofractionated (UHFRT) 5-daily fractions of the supraclavicular fossa (SCF) radiation therapy (RT) have been reported only on 384 patients treated in trial setting in UK-FAST-Forward (n = 286) and HYPORT study (n = 98). Internal Mammary nodal (IMN) RT has been reported only in 6 patients from HYPORT study. We report acute and late toxicities in largest real world regional nodal irradiation (RNI) cohort of not only with 5-daily but also with 5-weekly once RT regimen. Of 1435 patients (1463 breasts) who received 5-fraction RT in an IEC approved registry and prospectively followed, we report 999 consecutive cases receiving RNI with a median age of 49 years (IQR:42-56years). During pandemic all patients were treated with 5-fr regimens only to limit hospital visits whereas prior to and subsequently only in patients with advanced age or with issues precluding daily 15-20 treatments. Of these, 431 (43.1%) had locally advanced BC, and 280 (28%) patients presented with ≥cN2 disease. Median cT and pT sizes were 4cm (IQR:3-6cm) and 2.8cm (IQR:1.5-4cm) respectively. Tumor was Her2 positive in 290(29%) and TNBC in 220(22%). Of these 999 cases, 611 received NACT, 647 had mastectomy and 351 had breast conserving surgery (BCS). Simultaneous integrated tumor bed boost (SIB) was given in 341 (97.1%) of BCS cases. The fractionation used was 26 Gy/5-daily fractions (SIB = 32 Gy) in 762 and 28.5 Gy/ 5 once weekly fractionation (SIB = 33 Gy) in 232 cases. RNI included SCF in all 999 and IMN in 168 patients. Of the 831 cases not requiring IMN RT, 573 (70.4%) had 3D conformal RT (n = 573/831,70.4%) whereas Inverse-planned intensity modulated RT was used in 152/168 (90.4%) patients requiring IMN RT. All Mono-isocentric technique was used for all RNI cases treated with 3D CRT. Nearly half of the patients treated with SIB received additional boost dose with electrons (50.5%) and the remaining with IMRT. In these 999 patients treated with UHFRT the peak RTOG grade ≥II skin and pharyngeal toxicity was 7.2% and 8.1% respectively. Among the 341 BCS cases who received SIB with UHFRT, the RTOG acute grade II and III skin toxicity was seen in 6.6% and 0.3% cases respectively. The maximum skin toxicity at 2 weeks after completion of RT of grade ≥II was significantly higher with 5-weekly compared to daily regimen (16.1 vs 4.6, p<0.01). In contrast, the maximum pharyngeal toxicity of grade ≥II was significantly higher with 5-daily compared to weekly fractionation (8.8% vs 5.2%, p = 0.04). At median follow-up of 25 months (CI:23.6-26.3 months), none of our patients had developed symptomatic radiation pneumonitis, brachial plexopathy or any major cardiac event. Five-fraction adjuvant breast cancer RT is well tolerated with low acute toxicity burden even among patients requiring regional nodal irradiation. No brachial plexopathy was observed in cases treated with mono-isocentric RNI but longer follow-up is required to inform about the late toxicities and locoregional control rates.