Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma

Abstract

Purpose To evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma. Materials and Methods We reviewed the medical records of patients with skull-base chordoma treated with definitive or adjuvant high-dose PT and updated their follow-up when feasible. We assessed overall survival, disease-specific survival, local control, and freedom from distant metastasis. Radiotherapy toxicities were scored using the Common Terminology Criteria for Adverse Events, version 4.0. Results A total 112 patients were analyzed, of whom 105 (94%) received PT and 7 (6%) received combined proton-photon therapy between 2007 and 2019. Eighty-seven patients (78%) underwent a subtotal resection, 22 (20%) a gross total resection, and 3 (3%) a biopsy alone. The median radiotherapy dose was 73.8 Gy radiobiologic equivalent (GyRBE; range, 69.6-74.4). Ninety patients (80%) had gross disease at radiotherapy and 7 (6%) were treated for locally recurrent disease following surgery. Median follow-up was 4.4 years (range, 0.4-12.6); for living patients, it was 4.6 years (range, 0.4-12.6), and for deceased patients, 4.1 years (range, 1.2-11.2). At 5 years after radiotherapy, the actuarial overall survival, disease-specific survival, local control, and freedom from distant metastasis rates were 78% (n = 87), 83% (n = 93), 74% (n = 83), and 99% (n = 111), respectively. The median time to local progression was 2.4 years (range, 0.8-7). Local control and disease-specific survival by resection status was 95% versus 70% (P = 0.28) and 100% versus 80% (P = 0.06) for gross total, versus subtotal, resection or biopsy alone, respectively. There were no serious acute toxicities (grade ≥ 3) related to radiotherapy. Conclusion High-dose PT alone or after surgical resection for skull-base chordoma reaffirms the favorable 5-year actuarial local control rate compared with conventional techniques with acceptable late-complication–free survival. Outcomes following gross total resection and adjuvant PT were excellent. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection

“…This multicenter study underscores the efficacy of proton therapy as a potent adjuvant to resection when dealing with chordomas, presenting compelling evidence of its superiority over traditional photon radiotherapy in curbing recurrence. 15 Notably, logistic regression analysis accentuated a significant reduction in the risk associated with recurrence in cases managed with proton therapy.…”

“…Our findings are in accordance with earlier studies suggesting the efficacy of proton therapy in managing chordomas. 15,[17][18][19] Yet, what distinguishes our study from these earlier ones is the incorporation of tree-based machine learning models, shedding light on crucial predictive variables.…”

Risk Factors for Radiation Necrosis and Local Recurrence after Proton Beam Therapy for Skull Base Chordoma or Chondrosarcoma

“…For three-fraction SRS for brain metastases, normal brain tissue V18 < 30 cc and V23 < 7 cc were associated with <10% risk of brain necrosis. Finally, we evaluate the results of this study based on the latest reports [14,[21][22][23]31,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. According to the latest reports, the 5-year local recurrence rate for chordoma was about 15 to 35%, while for chondrosarcoma, it was less than 10%.…”

Proton beam therapy for clival chordoma: Optimising rare cancer treatments in Australia

“…[42][43][44][45][46] Other significant series are summarised in Table 1. 15,37,[47][48][49] To date, there have been no randomised studies comparing proton therapy and photon therapy. In a meta-analysis spanning the years 1999 to 2010, Di Maio et al 50 concluded that there was no significant difference in 5-year overall survival based on the adjuvant radiation modality, whether it be proton therapy, carbon ion therapy, Gamma knife radiosurgery, or fractionated photon radiation.…”

“…Several excellent reviews of the literature for proton therapy in skull base chordomas have been published recently including systematic reviews 42–46 . Other significant series are summarised in Table 1 15,37,47–49 …”