Top Line: Brain radiation is particularly toxic for older patients with less neurocognitive reserve.
The Study: Thus the ongoing efforts to strike the appropriate and particularly fine balance of efficacy and toxicity when treating older patients with glioblastoma multiforme (GBM). Two strategies include minimizing treatment volume and treatment days. On this single-arm phase 2 trial 40 patients age 65+ (median 70 years) received proton radiation over five to ten fractions as first-line treatment for GBM at the Mayo Clinics in Rochester and Phoenix. Pretreatment 18F-DOPA PET-imaging was performed on all patients. For those receiving five fractions (n=18), the PET+disease received 35 Gy, MRI contrast-enhanced disease 30 Gy and a 1.0 cm anatomically-constrained clinical margin + 0.2 cm planning margin received 25 Gy. When the target was >65cc (n=21), ten fractions were delivered with a prescription of 40/35/30 Gy to respective volumes. All patients received concurrent temozolomide, even thought two-thirds were MGMT-unmethylated. Median overall survival was 13 months, surpassing the 5-10 months reported in prior phase 3 trials on this age cohort. Grade 3+ radionecrosis occurred in 10% (n=4, 3 in the five-fraction arm). It’s worth noting, with all the novelty here, it’s hard to tease out how much the proton—as opposed to photon—therapy contributed to these outcomes: Even with dosimetric advantages in low doses to non-target brain, the realized clinical advantage in neurocognition remains unrealized. Perhaps most promising is 18F-DOPA PET-guided boost volumes, but….womp womp…it as of yet lacks FDA approval…pssst @RobertKenndedyJr. On the other hand, perhaps the much more accessible MRI spectroscopy could similarly guide small boost volumes, though little is know on the Venn diagram of these imaging modality sensitivities.
TBL: This prospective trial incorporating ultra-hypofractionated proton therapy with simultaneous boosts to PET+ disease can help guide future trials to think outside the box for making clinically meaningful progress in the treatment for GBM. | Vora, Lancet Oncol 2024
The Study: Thus the ongoing efforts to strike the appropriate and particularly fine balance of efficacy and toxicity when treating older patients with glioblastoma multiforme (GBM). Two strategies include minimizing treatment volume and treatment days. On this single-arm phase 2 trial 40 patients age 65+ (median 70 years) received proton radiation over five to ten fractions as first-line treatment for GBM at the Mayo Clinics in Rochester and Phoenix. Pretreatment 18F-DOPA PET-imaging was performed on all patients. For those receiving five fractions (n=18), the PET+disease received 35 Gy, MRI contrast-enhanced disease 30 Gy and a 1.0 cm anatomically-constrained clinical margin + 0.2 cm planning margin received 25 Gy. When the target was >65cc (n=21), ten fractions were delivered with a prescription of 40/35/30 Gy to respective volumes. All patients received concurrent temozolomide, even thought two-thirds were MGMT-unmethylated. Median overall survival was 13 months, surpassing the 5-10 months reported in prior phase 3 trials on this age cohort. Grade 3+ radionecrosis occurred in 10% (n=4, 3 in the five-fraction arm). It’s worth noting, with all the novelty here, it’s hard to tease out how much the proton—as opposed to photon—therapy contributed to these outcomes: Even with dosimetric advantages in low doses to non-target brain, the realized clinical advantage in neurocognition remains unrealized. Perhaps most promising is 18F-DOPA PET-guided boost volumes, but….womp womp…it as of yet lacks FDA approval…pssst @RobertKenndedyJr. On the other hand, perhaps the much more accessible MRI spectroscopy could similarly guide small boost volumes, though little is know on the Venn diagram of these imaging modality sensitivities.
TBL: This prospective trial incorporating ultra-hypofractionated proton therapy with simultaneous boosts to PET+ disease can help guide future trials to think outside the box for making clinically meaningful progress in the treatment for GBM. | Vora, Lancet Oncol 2024