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.

Biological Guided Carbon-Ion Microporous Radiation to Tumor Hypoxia Area Triggers Robust Abscopal Effects as Open Field Radiation

“…Ionization radiation beams of higher LET have been shown to induce more complex DNA damage, despite reportedly more effective in eradicating tumor cells under hypoxic environment, as compared to those with lower LET (23)(24)(25)(26)(27). Theoretically, the physical and biological advantages of carbon ion radiation therapy (CIRT) make it more appropriate in the management of bulky or radio-resistant tumors (28)(29)(30). Results of pre-clinical or retrospective studies have confirmed its advantages in tumor proliferation and metastasis over photon (31)(32)(33).…”

Particle Beam Radiation Therapy for Skull Base Sarcomas

“…Also, particle beams with higher linear energy transfer (e.g., carbon ion) produces significantly higher biological effectiveness as compared with photon beams (23), a clear advantage for radioresistant histologies such as most subtypes of sarcomas. Clinical data from several retrospective studies showed that PBRT could achieve favorable disease control for head and neck sarcomas or base of skull tumors, including chordoma and chondrosarcoma, even in patients with unresected or recurrent diseases (24)(25)(26)(27)(28)(29). In our previous studies, PBRT for head and neck sarcomas, including those involving skull base, produced effective tumor controls, and overall survivals in both primary and recurrent patients; the 1/2-year OS and LRFS for the entire cohort were 92.9/90.0 and 88.4/78.9%, respectively (24,25).…”

“…Clinical data from several retrospective studies showed that PBRT could achieve favorable disease control for head and neck sarcomas or base of skull tumors, including chordoma and chondrosarcoma, even in patients with unresected or recurrent diseases ( 24 – 29 ). In our previous studies, PBRT for head and neck sarcomas, including those involving skull base, produced effective tumor controls, and overall survivals in both primary and recurrent patients; the 1/2-year OS and LRFS for the entire cohort were 92.9/90.0 and 88.4/78.9%, respectively ( 24 , 25 ). For chondrosarcoma of the skull base, PBRT attained more favorable outcomes; results from Heidelberg Ion Beam Therapy Center reported both the 5-year OS, and local controls were over 90% and over 85%, respectively ( 26 , 28 ).…”

Carbon Ion Dose Constraints in the Head and Neck and Skull Base: Review of MedAustron Institutional Protocols

“…The CIRT has been used to treat several tumors of the head and neck area. It has not been employed for squamocellular carcinoma-the most common entity-but rather, for other, radioresistant histologies, such as salivary gland tumors [15][16][17][18][19][20][21][22], paranasal sinuses tumors (including sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, intestinal-type adenocarcinoma, and esthesioneuroblastoma, among others) [15,23], mucosal melanoma [24][25][26][27][28], lacrimal gland tumors [29][30][31], and bone and soft tissue sarcoma (including tumors of the skull base and cervical spine [32][33][34][35][36][37][38] At MedAustron, CIRT was begun in July 2019. Until September 2020, 91 patients have been treated and 42 of them had tumors in the head and neck.…”