Long-term outcomes of adjuvant proton radiotherapy (PRT) for residual pituitary adenoma (PA) in adults – a retrospective, single institute experience

PURPOSE: Pituitary adenomas (PA) are benign neoplasms treated by resection. Gross total resection is limited by extrasellar expansion in proximity to critical neurovascular structures. Residual tumor remains at risk of progression, with serious consequences such as optic compression or hormone hypersecretion. Adjuvant radiotherapy (RT) offers a rescue modality for both, impeding regrowth and hormonal relapse. Proton radiotherapy (PRT), owing to its favorable dose distribution and reduced exit dose through the Bragg peak, further expands the armamentarium of conventional RT modalities in cases of extrasellar macroadenomas in contact with vulnerable organs at risk. Hence, the present study provides initial evidence on the efficacy and toxicity of adjuvant PRT and offers insight into the decision-making criteria for selecting PRT over photon-based techniques. METHODS: Adjuvant PRT applied for 22 residual PA including 16 non-functioning- (NFPA) and 6 functioning PA (FPA) at a large particle-therapy center, who were reviewed for local tumor control, toxicity, hormone status and visual function. Assessment of PRT response accounted for neuro-oncology criteria. RESULTS: After a median follow up of 65 months 5-year local tumor control rate of PA (FPA and NFPA) and hormone control rate of FPA was 100%. Secondary hypopituitarism after PRT was rare (1/22). Despite treatment escalation with PRT, stable endocrine status during follow-up enabled significant reductions in required glucocorticoid supplementation. Visual improvement was reported in 64%. Toxicity was limited, with fatigue and headache being most frequent. CONCLUSION: Adjuvant PRT for complex residual PA is efficacious and safe for treating residual disease in extrasellar expansion. IMPORTANCE OF THE STUDY: Pituitary adenomas (PAs) with extrasellar extension in proximity to vulnerable neurovascular tissue or brain parenchyma carry risk of residual tumor after resection that is not amenable to further safe resection. Subsequent tumor regrowth may compress adjacent neurovascular structures resulting in frequent sequelae such as visual deterioration or central nerve palsies. Persistent hormone-secreting adenoma may further sustain endocrine dysregulation. Adjuvant radiation therapy represents an important treatment strategy to impede regrowth while minimizing toxicity to surrounding critical structures, thus achieving durable visual improvement and long-term hormonal control. Proton radiotherapy (PRT) may further improve the therapeutic ratio by exploiting its steep dose gradient and highly conformal dose distribution to enhance normal tissue sparing without compromising tumor control in selected complex PA. Therefore, the present study reports experience with adjuvant PRT for complex residual PA, demonstrating 5-year local tumor control of 100%, visual improvement in 64%, and stable hormone levels in 95%.