As summer fades into fall, we have yet another ASTRO Annual Meeting in the books. With an overarching theme of provider wellness, we experienced moving keynote addresses discussing how to navigate the changing landscape of medicine while still maintaining high-quality, compassionate care (for both our patients and ourselves). There was also some interesting news on the science front, presented at the plenary session. In short, protons got the kibosh in the world of prostate cancer, we have yet another negative head and neck trial (HN005) and 70 Gy in 35 fractions with cisplatin remains standard of care for HPV-mediated oropharyngeal cancer, and LU005 was also a bust for small cell lung cancer. However, there was another player in the room that might just change the game for node-positive breast cancer…

The last decade has seen a dramatic shift in standard fractionation patterns for early stage, favorable breast cancer, with the most recent update from the FAST-Forward trial demonstrating noninferior 5-year local recurrence and overall survival for 5-fraction whole- breast radiation. 1 So now our discussions with these patients involve several options, including 3 weeks of radiation, 1 week of radiation, 5 days of partial breast radiation, and even omission at times. But those discussions have never carried over to higher-risk patients, namely, those with positive nodal involvement. Classically, all high-risk postmastectomy patients receive 5 weeks of adjuvant radiation. The most recent results from the RT CHARM trial may change that.

This multi-institutional, prospective randomized trial was designed to show noninferiority for pT0-2 pN1-2 or pT3N0 invasive breast cancer, postmastectomy, receiving standard-of-care 50 Gy in 25 fractions vs hypofractionation using 42.56 Gy in 16 fractions. All patients either had completed or partially completed reconstruction, with the primary endpoint being reconstruction complications. Patients with T4, N3, or internal mammary node involvement were excluded. With a median follow-up of 4.5 years, hypofractionation was found to be noninferior with only a 2.3% reconstruction complication rate increase over conventional fractionation and no difference in acute or late toxicity. 2 So while inflammatory and other very high-risk patients may still need 5 or more weeks of adjuvant radiation, perhaps it is a bit overkill for disease that is simply node-positive disease or > 5 cm.

Who wouldn’t want to shave 2 weeks off their radiation course? As with other hypofractionation regimens, this presents an opportunity to improve accessibility to and convenience of radiation therapy, without undermining oncologic outcomes.

Who wouldn’t want to shave 2 weeks off their radiation course? As with other hypofractionation regimens, this presents an opportunity to improve accessibility to and convenience of radiation therapy, without undermining oncologic outcomes. And we again find ourselves faced with increasingly nuanced discussions with patients. It will be curious to see how these results are implemented into the standard of care and whether hypofractionation for node-positive breast cancer patients will be integrated into NCCN guidelines. Meanwhile, we will continue to ask questions, remain skeptical, and be cautiously optimistic about exciting advances in cancer research.

References

1. Murray Brunt A, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. The Lancet. 2020;395(10237). doi:10.1016/S0140-6736(20)30932-6
2. Poppe MM, Le-Rademacher J, Haffty Jr BG, et al. A randomized trial of hypofractionated post-mastectomy radiation therapy (PMRT) in women with breast reconstruction (RT CHARM, Alliance A221505). Int J Radiat Oncol Biol Phys. 2024;120(2):S11. doi:10.1016/j.ijrobp.2024.07.002