Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum

Abstract

OBJECTIVE Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies. METHODS The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities. RESULTS Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%–82%, PFS 31%–57%, and DFS 52%–62%; metastases occurred in 17%–18% and acute toxicities in 3%–100% of cases; combined proton/photon therapy, local control 62%–85%, OS 78%–87%, PFS 90%, and DFS 61%–72%; metastases occurred in 12%–14% and acute toxicities in 84%–100% of cases; and carbon ion therapy, local control 53%–100%, OS 52%–86%, PFS (only reported for 3 years) 48%–76%, and DFS 50%–53%; metastases occurred in 2%–39% and acute toxicities in 26%–48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups. CONCLUSIONS The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.

The Role of En Bloc Resection in the Modern Era for Primary Spine Tumors

“…One such study, published in 2019, reported an 89.9% five-year local recurrence-free survival rate for patients receiving stereotactic radiosurgery in the form of 24 Gy in a single fraction for primary sacral or mobile spine chordoma 78 . A recent systematic review of definitive charged particle therapy found five-year local control rates of 56% to 68% for protons alone, 62% to 85% for mixed proton/photon therapy, and 53% to 100% for carbon ion radiotherapy 79 …”

Management of Chordoma of the Sacrum and Mobile Spine

“…Despite these encouraging preliminary studies, the overall data of proton and carbon ion RT are quite limited. The superiority of these modalities in the definitive or adjuvant setting has not been demonstrated by systematic reviews, with charged particle therapy offering similar local control to modern photon therapy in the adjuvant setting 78 . In addition, access to proton beam therapy in the United States is still limited and typically only available in large metropolitan areas.…”

“…Houdek et al examined 193 patients with primary sacrococcygeal chordomas and found no improvement of oncologic outcomes with the addition of low-dose RT to en bloc resection, but rather was associated with an increased risk of local complications 71 . However, recent innovations in radiation modalities and charged particle therapy have improved delivery precision and efficacy while minimizing toxicity 66,67,[72][73][74][75][76][77][78][79][80] .…”

Behandlungsalternativen für sakrale Chordome

“…Der Vorteil der Partikeltherapie besteht darin, dass mit Abgabe der Energie im Zielbereich, die umgebenden Strukturen geschont werden. Ein systematisches Review zeigt keinen relevanten Unterschied zwischen verschiedenen Partikeln und kann bei Verwendung einer Partikeltherapie als primäre Behandlung und historischen chirurgischen Kohorten vergleichbar sein [28]. Eine Carbon-Ionentherapie kann auch für Patienten mit Resektionsrand-positiven Resektionen verwendet werden und könnte im Vergleich zu Photontherapie einen Vorteil haben [29].…”