Early results and volumetric analysis after spot-scanning proton therapy with concomitant hyperthermia in large inoperable sacral chordomas

Abstract

Objective: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). Methods: Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. Results: Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369–1142). All patients completed PT and received a median of 5 HT sessions (range, 2–6). Median follow-up was 18 months (range, 9–26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9–72). All patients experienced acute Grade 2–3 local pain. One patient presented with a late Grade 3 iliac fracture. Conclusion: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. Advances in knowledge: This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses

“…Combining HT with proton therapy has a thermoradiobiological rationale (299). Early results with proton HTRT in unresectable sacral chordomas and soft tissue sarcomas are promising (266,305). Confirmation of the hypothesis that proton HTRT is analogous to 12 C ions could result in major savings over investments in 12 C ion therapy.…”

“…Protons supplemented with the high LET features of HT could mimic 12 C ion therapy and thus be a cost-effective alternative to 12 C ions (299-303) (Figure 4). Proton HTRT has shown promising results in experimental choroidal melanomas and inoperable large sacral chordomas (304,305). Presently proton HTRT is under investigation in inoperable soft tissue sarcoma (266,299).…”

Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature–time area under the curve (AUC)

“…A number of phase III randomized trials, pairwise meta-analyses and network meta-analyses have shown the efficacy of HT in a wide range of malignancies [7,8,20,[32][33][34][35][36]. Thermoradiobiologically, HT with photons is analogous to that of neutrons but devoid of any added acute or late morbidity while with protons it mimics 12 C beam therapy [37][38][39][40]. In phase III randomized study, HT with CT has improved survival outcomes in soft tissue sarcoma [41].…”

Hyperthermia with photon radiotherapy is thermoradiobiologically analogous to neutrons for tumors without enhanced normal tissue toxicity

“…Thus the thermoradiobiological advantages of HT coupled with the physical dose distribution of protons enables proton HTRT to mimic 12 C ion therapy [13] ( Figure 3). Early clinical studies have demonstrated the feasibility and effectivity of proton HTRT in radioresistant unresectable soft tissue sarcomas and large unresectable chordomas, both of which respond poorly to conventional photons or protons [42,43].…”