OncoFlash – Research Updates in a Flash! (February 2023)

1. Is FLASH radiotherapy (RT) ready for the primetime? Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial. Mascia AE et al. JAMA Oncol. 2022 [[1]Mascia A.E. Daugherty E.C. Zhang Y. et al.Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial.JAMA Oncol. October 23, 2022; https://doi.org/10.1001/jamaoncol.2022.5843Crossref PubMed Scopus (33) Google Scholar].•Prospective, non-randomised study of 10 patients with extremity bone metastases evaluating the clinical workflow, toxicity and efficacy of proton FLASH RT delivered with the aim of pain control.•Single 8 Gy was delivered with a nominal dose rate of 60 Gy/sec using high-energy, pencil-beam scanning proton therapy FLASH fields.•Average on-couch treatment time was 18.9 (11–33) minutes per patient and 15.8 (11–22) minutes per treatment site.•Median follow-up time was 4.8 (2.3–13.0) months. Twelve adverse effects were reported, 11 of which were grade 1, and the other (pain) was grade 2. Eight of the adverse effects were related to skin toxicity.•In eight of 12 sites (67%) treated, patients reported pain relief, which was complete in six (50%). Transient pain flare occurred in four of 12 treated sites (33%).•FAST-01 is the first in human clinical trial of ultra-high-dose-rate proton FLASH RT, demostrating feasiblity, safety and potential efficacy in pain control relating to bony metastases. We must however question the use of an advanced and expensive radiotherapy technique in this setting. Perhaps these resources would be better used elsewhere. 2. Is pembrolizumab better than cetuximab with concurrent RT for locally advanced head and neck cancer when patients are unfit for cisplatin? Pembrolizumab versus cetuximab, concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase 2 trial. Tao, Y. et al. Annals of Oncology, 2022 [[2]Tao Y. Biau J. Sun X.S. Sire C. Martin L. Alfonsi M. et al.Pembrolizumab versus cetuximab, concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase 2 trial.Annal Oncol. 2022; https://doi.org/10.1016/j.annonc.2022.10.006Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar].•First randomised trial comparing 3-weekly pembrolizumab versus weekly cetuximab given concurrently with RT (dose up to 69.96Gy in 33 fractions) for locally advanced head and neck squamous cell carcinoma in 133 patients unsuitable for cisplatin-based chemo/RT.•The primary endpoint was locoregional control (LRC) at 15 months and there were multiple secondary endpoints including progression-free survival (PFS), overall survival (OS) and acute and late toxicities.•With a median follow-up of 25 months, 15-month LRC were 59% with cetuximab and 60% with pembrolizumab (OR 1.05 [95% CI: 0.43–2.59], p = 0.91).•No significant differences were reported for PFS (HR 0.85 [95% CI 0.55–1.32], p = 0.47) or OS (HR 0.83, [95% CI: 0.49–1.40], p = 0.49).•Adverse events of ≥ grade 3 were more frequent in the cetuximab arm: 92% versus 74% (p = 0.006).•The most common ≥ grade 3 events were mucositis, dysphagia (more frequent in pembrolizumab arm), dermatitis and rash.•Pembrolizumab given concurrently with RT did not improve LCR or survival, but resulted in less toxicity, compared to cetuximab in this population.•It is important however to highlight that pembrolizumab costs roughly twice the amount of money as cetuximab. 3. Is 3-week hypofractionated pre-operative RT a safe regime for patients with soft tissue sarcoma (STS)? Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial. Guadagnolo B A et al. Lancet Oncol 2022 [[3]Guadagnolo B Ashleigh Bassett Roland L. Mitra Devarati Farooqi Ahsan Hempel Caroline Courtney Dorber et al.Andrew J Bishop. Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.Lancet Oncol. 2022; https://doi.org/10.1016/S1470-2045(22)00638-6Date accessed: November 4, 2022Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar].•Single-centre, open-label, single-arm, phase II trial investigating the safety of moderately hypofractionated pre-operative RT in patients with soft tissue sarcoma (STS) delivering a total prescribed dose of 42.75Gy in 15 fractions (2.85Gy/day for 3 weeks and radiobiological equivalent to 48–50Gy in 25 fractions) to a standard target delineation volume.•The primary endpoint was major wound complications occurring within 120 days of surgery. Secondary endpoints were recurrence-free survival, time to relapse, patterns of local recurrence and acute and late toxicities.•Included 120 patients with STS of the trunk (18%) and upper (17%) and lower (65%) extremities recruited between December 2018 and January 2021.•After a median follow-up after surgery of 24 months, 37 (31%, 95% CI 24–40) patients developed major wound complications. Most (62%) of these patients had lower limb STS.•No ≥ grade 3 acute toxicities were reported, and four patients (3%) reported ≥ grade 3 late RT toxicities of which two were femur fractures, one lymphoedema and one skin ulceration.•Six (5%) patients developed local relapse at a median time of 16 months after surgery.•This study suggests that patients with STS may be safely treated with a 3-weekly moderately hypofractionated pre-operative RT regimen therefore reducing hospital attendances for patients. However, caution is advised given the results are from a single institution, with no randomised comparison with standard fractionation and absence of long-term toxicity data. 4. Is the use of hypofractionated high dose proton beam therapy (PBT) effective in the management of patients with unresectable liver metastases? A phase II trial of hypofractionated high-dose proton beam therapy for unresectable liver metastases. Kim K et al. Radiotherapy and Oncology. Nov 2022 [[4]Kim Kangpyo Jeong Il Yu Park Hee Chul Yoo Gyu Sang Lim Do Hoon Noh Jae Myoung et al.A phase II trial of hypofractionated high-dose proton beam therapy for unresectable liver metastases.Radiother Oncol. November 2022; 176: 9-16https://doi.org/10.1016/j.radonc.2022.09.003Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar].•Phase II prospective trial of hypofractionated high dose PBT in 46 patients with 49 unresectable liver metastases, enrolled between January 2019 and January 2021.•The primary endpoint was 6-month freedom from local progression (FFLP) rate.•Dose of 60Gy relative biological effectiveness (Gy RBE) in 5 fractions (biologically effective dose [BED] 132 GyE) or 70Gy RBE in 10 fractions (BED 119GyE). All patients had a liver function of Child-Pugh class A and their primary cancer was controlled.•Intensity modulated proton therapy (IMPT) was used in 71.4% of patients and passive scattered beam in the remainder. The PBT technique was decided based on tumour size and respiratory motion techniques.•Thirty patients (61.2%) had colorectal cancer as primary cancer site. Other sites included stomach, oesophagus, pancreas, lung and other. The median size of the liver lesions was 2.3cm.•The 6-month FFLP rate was 95.2%. Smaller metastasis size and the use of systemic agents were associated with improved 1-year FFLP rates (87.4% <3cm vs. 74.1% >3cm [p = 0.087] and 94.1% with systemic therapy vs. 75.8% without [p = 0.051], respectively.•One patient had a grade 2 gastric ulcer, but all other toxicities were grade 1.•This study suggests that, despite potential confounding factors (metastasis size and use of systemic therapy), hypofractionated PBT with a BED> 100GyE is feasible and safe for patients with liver metastasis. The reasonably selected patient population (mostly colorectal primaries) however, may have positively affected the FFLP rate which would likely still be high following photon-based RT.