The Promise of Proton Therapy for Central Nervous System Malignancies

Neurosurgery, Volume 84, Issue 5, May 2019, Pages 1000–1010

Radiation therapy plays a significant role in management of benign and malignant diseases of the central nervous system. Patients may be at risk of acute and late toxicity from radiation therapy due to dose deposition in critical normal structures.

In contrast to conventional photon delivery techniques, proton therapy is characterized by Bragg peak dose deposition which results in decreased exit dose beyond the target and greater sparing of normal structure which may reduce the rate of late toxicities from treatment. Dosimetric studies have demonstrated reduced dose to normal structures using proton therapy as compared to photon therapy. In addition, clinical studies are being reported demonstrating safety, feasibility, and low rates of acute toxicity.

Technical challenges in proton therapy remain, including full understanding of depth of proton penetration and the biological activity in the distal Bragg peak. In addition, longer clinical followup is required to demonstrate reduction in late toxicities as compared to conventional photon-based radiation techniques.

In this review, we summarize the current clinical literature and areas of active investigation in proton therapy for adult central nervous system malignancies.

 

Multimodality Treatment of Skull Base Chondrosarcomas

Neurosurgery 81:520–530, 2017

Limited data exist to guide the multimodality management of chondrosarcomas (CSAs) arising in the skull base.

OBJECTIVE : To determine the impact of histological subtype/grade on progression-free survival (PFS) and the indications for surgery, radiation, and chemotherapy based on histology.

METHODS: A retrospective review was performed of 37 patients (conventional type: 81%, mesenchymal: 16.2%, dedifferentiated: 2.7%) treated at The University of Texas M.D. Anderson Cancer Center. Of the conventional subtype, 23% were grade 1, 63% were grade 2, and 14% were grade 3. In addition to surgery, mesenchymal/dedifferentiated CSAs (18% of the cohort) underwent neoadjuvant chemotherapy and 48.6% of the overall cohort received adjuvant radiotherapy. Histological grade/subtype and treatment factors were assessed for impact on median PFS (primary outcome).

RESULTS: Conventional subtype vs mesenchymal/dedifferentiated was positively associated with median PFS (166 vs 24 months, P < .05). Increasing conventional grade inversely correlated with median PFS (P < .05). Gross total resection positively impacted PFS in conventionalCSAs (111.8 vs 42.9months, P=.201) and mesenchymal/dedifferentiated CSAs (58.2 vs 1.0 month, P < .05). Adjuvant radiotherapy significantly impacted PFS in conventional grades 2 and 3 (182 vs 79 months, P < .05) and a positive trend with mesenchymal/dedifferentiated CSAs (43.5 vs 22.0 months). Chemotherapy improved PFS for mesenchymal/dedifferentiated CSAs (50 vs 9 months, P = .089).

CONCLUSION: There is a potential need for histological subtype/grade specific treatment protocols. For conventional CSAs, surgery alone provides optimal results grade 1 CSAs, while resection with adjuvant radiotherapy yields the best outcomefor grade 2 and 3 CSAs. Improvements in PFS seen with neoadjuvant therapy in mesenchymal/dedifferentiated CSAs indicate a potential role for systemic therapies. Larger studies are necessary to confirm the proposed treatment protocols.