AUTHOR=Pelak Maciej J. , Flechl Birgit , Hug Eugen , Galalae Razvan , Konrath Lisa , Góra Joanna , Fossati Piero , Lütgendorf-Caucig Carola , Tubin Slavisa , Konstantinovic Rastko , Mock Ulrike , Fussl Christoph , Georg Petra 

TITLE=Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.962697

DOI=10.3389/fonc.2022.962697

ISSN=2234-943X

ABSTRACT=Aim
Data on the safety of moderately hypofractionated proton beam therapy (PBT) is limited. The aim of this study is to compare the acute toxicity and early quality of life (QoL) outcomes of normofractionated (nPBT) and hypofractionated PBT (hPBT).

Material and methods
We prospectively compared acute toxicity and QoL between patients treated with nPBT (dose per fraction 1.8 – 2.3 Gy, n = 90) and hPBT (dose per fraction 2.5 – 3.1 Gy, n = 49) in following locations: head & neck (H&N, n = 85), abdomen & pelvis (A&P, n = 43) and other soft tissue (ST, n = 11). The toxicities were grouped in categories: mucosal, skin and other site-specific and evaluated according to CTCAE v 4.03 at baseline, treatment completion and 3 months after PBT completion. QoL was evaluated with EORTC QLQ-C30 scale for all locations and additionally with EORTC QLQ-HN35 for H&N patients.

Results
Overall, the highest toxicity grades of G0/G1/G2/G3 were observed in 7 (5%), 40 (28.8%), 78 (56.1%) and 15 (10.8%) patients, respectively. According to organ and site no statistically significant differences were detected in the majority of toxicity comparisons (66.7%). For A&P, hPBT showed a more favorable toxicity profile compared to nPBT with a higher frequency of G0 & G1 and lower of G2 & G3 events, (p = 0.04), more patients with improvement (95.7% vs 70%, p = 0.023) and full resolution of toxicities (87% versus 50%, p = 0.008). Skin toxicity was unanimously milder for hPBT compared to nPBT in A&P and ST locations (p = 0.018 and p = 0.025, respectively). No significant differences in QoL were observed in 97% of comparisons for QLQ-C30 scale except loss of appetite in H&N patients (+33.3 for nPBT and 0 for hPBT, p = 0.02) and role functioning for A&P patients (0 for nPBT vs +16.7 hPBT, p = 0.003). For QLQ-HN35, 97.9% of comparisons did not reveal significant differences, with pain as the only scale varying between the groups (-8.33 vs -25, p=0.016).

Conclusion
Hypofractionated proton therapy offers non-inferior early safety and QoL compared to normofractionated irradiation and warrants further clinical investigation.