Hypofractionated proton beam therapy with simultaneous integrated boost technique (SIB-PBT) can be used as a safe and effective local treatment for locally advanced pancreatic cancer (LAPC), particularly in patients with stable disease (SD) following induction chemotherapy, according to findings from the largest cohort to date presented at PTCOG-AO 2025.
SIB-PBT can be combined with chemotherapy and has the advantages of increasing the radiation dose to the tumour, reducing radiation to nearby normal organs, minimizing systemic therapy interruptions, and shortening the overall treatment time. [Sci Rep 2020;10:21712; Technol Cancer Res Treat 2018;17:1533033818783879]
“While a few studies have suggested the feasibility and potential benefits of PBT in LAPC, robust clinical evidence remains limited,” said Dr Tae Hyun Kim of Center for Proton Therapy at the National Cancer Center in Goyang, South Korea. “We aimed to assess the efficacy and safety of SIB-PBT in combination with systemic therapy in a real-world clinical setting and also explored the prognostic factors associated with survival, such as sequencing of systemic therapy and PBT, as well as the dose–response relationship.” [Radiother Oncol 2025;doi:10.1016/j.radonc.2025.111295]
Kim and colleagues reviewed data from 225 consecutive patients with LAPC treated with SIB-PBT between September 2014 and September 2024. The patients were grouped according to treatment sequence: Group I (n=110) received PBT after achieving SD post-induction chemotherapy, Group II (n=35) received PBT after disease progression post-chemotherapy, Group III (n=80) received PBT followed by maintenance chemotherapy.
The 1- and 2-year overall survival (OS) rates from PBT were 74.3 and 38.1 percent, respectively, with a median OS of 19.5 months, while median OS from initial treatment was 24.2 months. “This outcome suggests a potential benefit of PBT when compared with historical results from conventional fractionated radiotherapy [RT] or intensity-modulated RT. Moreover, the OS achieved in our study is comparable to or even better than some reported outcomes with stereotactic RT, and approaches the encouraging results seen in MRI-guided adaptive SBRT studies and carbon ion RT studies,” shared Kim.
The 1- and 2-year progression-free survival (PFS) rates from PBT were 47.9 and 22.1 percent, respectively, while median PFS was 11.4 months. The rates of freedom from local progression (FFLP) following PBT were 81.9 and 61.3 percent at 1 and 2 years, respectively, while median FFLP was not reached.
“OS from PBT was significantly longer for Group I vs Groups II and III [p<0.05 for all comparisons], while PFS after PBT was significantly longer in Groups I and III vs Group II [p<0.05 for each],” reported Kim. “In Group I, we observed a promising OS of 31.1 months. Furthermore, these patients consistently achieved the highest FFLP rates from both the first treatment and PBT, which indicates that consolidating a favourable response to initial chemotherapy with local PBT is an effective strategy for preventing local progression.”
The study also suggested a potential dose–response relationship for FFLP. Patients treated with 50 Gy had significantly better FFLP rates than those treated with 45 Gy. However, a higher incidence of late gastrointestinal adverse events (AEs) (eg, bleeding and ulcers) was reported in the 50 Gy vs 45 Gy group, highlighting the need to carefully balance the benefits of dose escalation with the potential for increased late toxicity to adjacent organs. Overall, SIB-PBT demonstrated a safe toxicity profile, with no acute ≥3 AEs and a low late AE rate of 2.2 percent.
“The present study, representing the largest reported cohort of PBT for LAPC to date, demonstrates that SIB-PBT could be a safe and effective local treatment modality. It is feasible in real-world clinical settings and allows individualized integration with systemic therapies. Notably, improved outcomes were observed when SIB-PBT was administered following a favourable response to induction chemotherapy,” concluded Kim.