A prospective clinical trial of proton therapy for chordoma and chondrosarcoma: Feasibility assessment

Abstract

Background/Objectives Proton therapy (PRT) has emerged as a treatment option for chordomas/chondrosarcomas to escalate radiation dose more safely. We report results of a phase I/II trial of PRT in patients with chordoma/chondrosarcoma. Methods Twenty adult patients with pathologically confirmed, nonmetastatic chordoma or chondrosarcoma were enrolled in a single‐institution prospective trial of PRT from 2010 to 2014. Seventeen patients received adjuvant PRT and three received definitive PRT. Median dose was 73.8 Gy(RBE; range 68.4‐79.2 Gy) using PRT‐only (n = 6) or combination PRT/intensity‐modulated radiotherapy (IMRT) (n = 14). Quality‐of‐life (QOL) and fatigue were assessed weekly and every 3 months posttreatment with the Functional Assessment of Cancer Therapy ‐ Brain (FACTBr) and Brief Fatigue Inventory. Primary endpoint was feasibility (90% completing treatment with < 10 day treatment delay and ≤ 20% unexpected acute grade ≥ 3 toxicity). Results Tumors included chordomas of the skull base (n = 10), sacrum (n = 5), and cervical spine (n = 3), and skull base chondrosarcomas (n = 2). Median age was 57. The 80% had positive margins/gross disease. Median follow‐up was 37 months. Feasibility endpoints were met. The 3‐year local control and progression‐free survival was 86% and 81%. There were no deaths. Two patients had acute grade 3 toxicity (both fatigue). One had late grade 3 toxicity (epistaxis and osteoradionecrosis). There were no significant differences in patient reported fatigue or QOL from baseline to the end‐of‐treatment. Conclusions We report favorable local control, survival, and toxicity following PRT.

A nomogram to predict the progression-free survival of clival chordoma

“…Radiotherapy, especially proton therapy, has been reported to improve local control and PFS of chordoma. 2 In our study, the multivariate Cox regression analysis showed that radiotherapy has no relation with PFS. This indicates that chordoma is resistant to radiotherapy, and more studies are needed to explore its role in prolonging PFS.…”

Sacral chordoma: do the width of surgical margin and the use of photon/proton radiotherapy affect local disease control?

“…The effect of proton radiotherapy in an adjuvant setting has been unclear, whereas recent studies have reported favourable early results with proton radiotherapy as definitive treatment, with local control rates of over 90% at 3 years [15,19]. As an adjuvant treatment, proton radiotherapy was reported to result in a local control rate of 33-95% with a relatively short follow-up (Table 5) [15,19,34,35,38]. The wide range of local control rates among these studies might be attributed to the heterogeneous settings among the study cohorts, such as margin status and pre-/postoperative use of proton radiotherapy, which hinder effective comparisons of the outcomes associated with the adjuvant use of conventional photon radiotherapy [40].…”

“…These inconsistencies might be attributed to the unstandardized treatment paradigms among multiple institutions, such as timing of treatment (pre-or post-operative), type of radiotherapy (photon, proton, or carbon ion), and radiation dose. Notably, the benefits of proton radiotherapy in an adjuvant setting have been unclear [34][35][36], while carbon ion [15,18,37] or proton radiotherapy [12,15,18,38] plays a role in unresectable cases.…”

Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models

“…Moreover, hypoxia is a cause of treatment failure, and new radiotherapeutic strategies aim at delivering a stronger dose to hypoxic tumor zones to eliminate chordoma tumors [13,42]. In the same intent of improving chordoma patient response to radiotherapy, proton irradiations are used in chordomas in recent clinical trials and show better results than X-rays [43,44]. Even though proton therapy is still poorly accessible, it could be interesting to study the response of our spheroids to this kind of treatment.…”