Intensity-Modulated Proton and Carbon-Ion Radiation Therapy in the Management of Head and Neck Sarcomas

Abstract

Purpose: We report our experience of intensity-modulated proton and carbon-ion radiotherapy (IMPT/IMCT) for head and neck sarcomas (HNS).

Methods and materials: An analysis of the ongoing prospective data registry from the Shanghai Proton and Heavy Ion Center (SPHIC) for patients with HNS was conducted. The 12- and 24-month rates of local recurrence-free, overall, distant metastasis-free, progression-free survival (LRFS, OS, DMFS, and PFS), and acute/late toxicities were calculated. The prognostic factors for the effectiveness of the treatment were also analyzed.

Results: Between 7/2014 and 5/2018, 51 consecutive patients with HNS received definitive doses of IMCT (41 cases), IMPT (two cases), or their combination (eight cases). One patient had R0 resection and another treated on the Chinese Food and Drug Administration registration trial received IMPT only. Twenty-seven patients were treated according to various dose escalation trials or institutional protocols using IMCT or IMPT + IMCT boost. Twenty-two patients with locoregional recurrence (10 and four patients failed surgery or surgery followed by radiotherapy, respectively) or radiation-induced second primary sarcomas (eight patients) received salvage particle radiotherapy. With a median follow-up time of 15.7 months, four patients with second primary sarcoma died. The 1- and 2-year OS, PFS, LRFS, and DMFS rates for the entire cohort were 92.9% vs 90%, 73.6% vs 57.4%, 88.4% vs 78.9%, and 84.6% vs 76.5%, respectively. Those rates for patients without prior radiotherapy were 100% vs 100%, 82.1% vs 65.8%, 93.6% vs 85.3%, and 88.4% vs 79.5%, respectively. Multivariate analyses revealed that re-irradiation was an independent prognostic factor for both LRFS and PFS (P = 0.015 and 0.037, respectively). In addition, gross tumor volume (GTV) was an independent prognostic factor for PFS (P = 0.048). One patient experienced Grade 3 acute toxicity (oral mucositis); another experienced Grade 4 acute event (hemorrhage) which required embolization. He lately died from hemorrhage (Grade 5) at 3.4 months after the completion of treatment. No patient experienced radiation-induced acute/late toxicity of ≥ Grade 2 otherwise.

Conclusion: With few observed acute/late toxicities, IMPT/IMCT provided effective short-term tumor control in our patients with HNS. Further investigations, preferably in a prospective fashion, will be required to confirm the efficacy and toxicities of IMPT/IMCT in this group of patients.

Figure 1

A typical IMCT treatment plan of a patient with locoregionally advanced soft‐tissue sarcoma of nasopharynx

Figure 2

Local control, overall survival, distant metastasis‐free survival, and progression‐free survival according to clinical stages (clinical stage I ~ II vs clinical stage III ~ IV and recurrence) for the entire group of patients

Figure 3

Local control, overall survival, distant metastasis‐free survival, and progression‐free survival according to the GTV volumes (< vs ≥ median volume)

Figure 4

Local control, overall survival, distant metastasis‐free survival, and progression‐free survival according to initial vs re‐irradiation

Figure 5

Local control, overall survival, distant metastasis‐free survival, and progression‐free survival according to primary vs radiation‐induced second primary head and neck sarcomas