In advanced hepatocellular carcinoma, proton therapy failed to deliver a survival benefit in the Phase III NRG-GI003 trial, which was stopped early for futility. The results reinforce that modality switching alone may not translate into better outcomes when endpoints are not met against photon radiation. For small cell lung cancer brain metastases, a Phase III NRG Oncology trial found stereotactic radiosurgery improved median survival by nearly doubling it versus hippocampal-avoidant whole-brain radiotherapy, without improving neurocognitive outcomes. The trial design separates survival impact from cognitive endpoints, a distinction that may influence how clinicians weigh trade-offs. Finally, a Mayo Clinic-led randomized study reported that splitting postoperative stereotactic radiosurgery into three or five fractions reduced recurrence at the surgical site and was associated with a 31% lower risk of death. Across studies, fractionation and timing are emerging as actionable levers even as proton therapy’s impact remains limited.