PROG 85-26: Three decades of effort, a lesson in patience

The long-awaited and remarkably mature results of PROG 85-26, a prospective, randomized dose-escalation trial of proton-based radiotherapy for skull base and cervical spine chondrosarcomas are reported in this issue of the journal. Studies of this duration are exceedingly rare in modern oncology. To follow patients for nearly three decades requires not only rigorous scientific discipline, but institutional commitment and a deep respect for the long natural history of this disease. For such a rare tumor, this effort is commendable. Skull base and upper cervical spine chondrosarcomas test the limits of sophistication in both neurosurgery and radiation oncology. Their proximity to the brainstem, spinal cord, cranial nerves, and major vessels provides no margin for error. Surgery is often necessarily conservative, and rarely R0. Conventional photon radiotherapy could not safely deliver the high doses required without risking unacceptable neurologic injury. Proton therapy, with its distinct dosimetric characteristics, offered the ability to escalate dose with less risk to critical structures, providing the rationale for this trial.