High control rates of proton‐ and carbon‐ion–beam treatment with intensity‐modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center

Mattke, Matthias; Vogt, Kira; Bougatf, Nina; Welzel, Thomas; Oelmann-Avendano, Jan Tobias; Hauswald, Henrik; Jensen, Alexandra; Ellerbrock, M.; Jäkel, Oliver; Haberer, Thomas; Herfarth, Klaus; Debus, Jürgen; Uhl, Matthias

doi:10.1002/cncr.31298

Cited by 57 publications

(43 citation statements)

References 29 publications

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“…In support of the hypothesis of dose homogeneity and HSV coverage driving improved LC, it has been shown that there are no significant differences in LC between doses greater than and doses less than or equal to 85 BED 10 , GyRBE . Furthermore, a modern trial using protons with a median dose of 70 Gy to treat chondrosarcoma at the Heidelberg Ion Beam Therapy Center found 4‐year OS and LC rates of 100% with modern techniques in particle therapy, albeit only for 22 patients . These findings are important because further dose escalation may have only a limited benefit as the prescribed dose has not been predictive of LC in a large experience .…”

Section: Discussionmentioning

confidence: 94%

“…29 Furthermore, a modern trial using protons with a median dose of 70 Gy to treat chondrosarcoma at the Heidelberg Ion Beam Therapy Center found 4-year OS and LC rates of 100% with modern techniques in particle therapy, albeit only for 22 patients. 30 These findings are important because further dose escalation may have only a limited benefit as the prescribed dose has not been predictive of LC in a large experience. 27 Because the treatment field size tends to inversely correlate with dose homogeneity, other prognostic factors such as a GTV < 25 cc 13,17,31 and a planning target volume ≤ 70 cc 29 have been associated with improved LC, and this helps to emphasize the importance of gross total resection before PRT.…”

Section: Discussionmentioning

confidence: 99%

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The role of dose escalation and proton therapy in perioperative or definitive treatment of chondrosarcoma and chordoma: An analysis of the National Cancer Data Base

Palm

Oliver

Yang

et al. 2019

Cancer

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Background Chordomas and chondrosarcomas are a rare but challenging subset of tumors to treat; however, previous studies have shown benefits from proton therapy, which are thought to be primarily driven by prescription conformality permitting homogeneous tumor dosing and the allowance of higher doses. No retrospective studies to date have directly compared the outcomes of conventional and particle therapy or examined the role of high doses (specifically ≥70 Gy) in definitive radiotherapy (DRT) or perioperative radiotherapy (PRT) for both types of malignancies. Methods A total of 863 patients with chondrosarcoma and 715 patients with chordoma treated with nonpalliative proton or conventional radiation therapy with a dose range of 20 to 80 Gy and at least 15 months of follow‐up were identified from the National Cancer Data Base for the years 2003‐2014. The primary endpoint of overall survival (OS) was evaluated, and clinical features, including age, sex, grade, clinical stage, and Charlson‐Deyo comorbidity index, were compared. Results Patients receiving DRT were older and had more advanced disease. In DRT for chondrosarcoma, a high dose (40.6% vs 16.9%; P = .006) and proton therapy (75.0% vs 19.1%; P = .046) were associated with improved OS at 5 years in a multivariate analysis. In DRT for chordoma, proton therapy was associated with improved OS at 5 years in a multivariate analysis (100% vs 34.1%; P = .031), and a high dose for chordoma was significant for improved OS in a univariate analysis with both DRT (79.0% vs 54.1%; P = .027) and PRT (83.3% vs 77.4%; P = .007). Conclusions In the largest retrospective series to date, dose escalation and proton radiotherapy were associated with improved OS in patients with chondrosarcoma and chordoma despite limited follow‐up and access to particle therapy.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The role of dose escalation and proton therapy in perioperative or definitive treatment of chondrosarcoma and chordoma: An analysis of the National Cancer Data Base

Palm

Oliver

Yang

et al. 2019

Cancer

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“…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). Most of the other papers included substantial cases of chordoma of the cervical spine or skull base, a condition that has a significantly different biological behavior from bone and soft-tissue sarcomas (18,26,27).…”

Section: Discussionmentioning

confidence: 98%

“…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).…”

Section: Discussionmentioning

confidence: 99%

Particle Beam Radiation Therapy for Skull Base Sarcomas

Yang¹,

Hu²,

Guan³

et al. 2020

Front. Oncol.

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Background: To report the clinical experience of carbon-ion and proton radiation therapy for skull base sarcomas. Methods: An analysis of the retrospective data registry from the Shanghai Proton and Heavy Ion Center for patients with skull base sarcomas was conducted. The 1-/2-year local relapse-free, distant metastasis-free, progression-free, and overall survival (LRFS, DMFS, PFS, OS) rates as well as associated prognostic indicators were analyzed. Radiotherapy-induced acute and late toxicities were summarized. Results: Between 7/2014 and 5/2019, 62 patients with skull base sarcomas of various subtypes received carbon-ion radiation therapy (53), proton radiation therapy (5), or proton radiation therapy + carbon-ion boost (4). With a median follow-up of 20.4 (range 2.73-91.67) months, the 1-/2-year OS, LRFS, DMFS, and PFS rates were 91.2%/80.2%, 89.2%/80.2%, 86.0%/81.1%, and 75.8%/62.9%, respectively. Grade 3 mucositis and grade 4 hemorrhage were observed in 1 patient for each. Only grade 1 and grade 2 toxicities were observed except for the same patient with grade 4 acute toxicity died of severe hemorrhage (grade 5). Multivariate analyses revealed the lack of prior RT was an independent favorable prognostic factor for OS, PFS, and LRFS, age under 40 was associated with improved OS, early T-disease (T1/2) showed a significant association with better PFS. Conclusion: With few observed acute and late toxicities, particle beam radiation therapy provided effective tumor control and overall survival for patients with skull base sarcomas.

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“…However, a recent publication suggests that equivalent control rates and outcomes were achieved by 101 patients with skull-based chondrosarcomas who received either protons or carbon ions using intensity-modulated, active raster scanning. 22 Furthermore, the published evidence for long-term late effects from these and other therapies is sparse. There is the potential for considerable variability in the RBE of CIRT used clinically and, to a lesser degree, of protons, depending on the biologic models, treatment planning protocols, and treatment volumes currently in use.…”

Section: Introductionmentioning

confidence: 99%

Clinical trials involving carbon‐ion radiation therapy and the path forward

Lazar

Schulte

Faddegon

et al. 2018

Cancer

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To describe the international landscape of clinical trials in carbon ion radiotherapy (CIRT), we reviewed the current status of 63 ongoing clinical trials (median: 47 subjects) involving CIRT identified from the clinicaltrials.gov trial registry and World Health Organization International Clinical Trials Platform Registry. We evaluated the potential for these trials to define the role of this modality in the treatment of specific cancer types, and to identify major challenges and opportunities to advance this technology. A significant body of literature suggests the potential for advantageous dose distributions and in preclinical biologic studies the enhanced effectiveness for CIRT compared to photons and protons. Additionally, clinical evidence, though limited, from phase I/II trials indicates the potential for CIRT to improve cancer outcomes. However, at present, high level phase III randomized clinical trial evidence does not exist. While there has been an increase in the number of trials investigating CIRT since 2010, and the number of countries and sites offering CIRT is slowly growing, this progress has excluded other countries. We propose several recommendations to study this modality in order to accelerate progress in the field, including to (1) increase the number of multi-national randomized clinical trials (2) leveraging existing CIRT facilities to launch larger multi-national trials directed at common cancers combined with high level quality assurance; and (3) developing more compact and less expensive “next generation” treatment systems integrated with radiobiological research and pre-clinical testing.

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High control rates of proton‐ and carbon‐ion–beam treatment with intensity‐modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center

Abstract: No significant difference between carbon ions and protons in the therapy of skull base chondrosarcoma could be detected in these initial retrospective results. Cancer 2018;124:2036-44. © 2018 American Cancer Society.

Cited by 57 publications

References 29 publications

The role of dose escalation and proton therapy in perioperative or definitive treatment of chondrosarcoma and chordoma: An analysis of the National Cancer Data Base

The role of dose escalation and proton therapy in perioperative or definitive treatment of chondrosarcoma and chordoma: An analysis of the National Cancer Data Base

Particle Beam Radiation Therapy for Skull Base Sarcomas

Clinical trials involving carbon‐ion radiation therapy and the path forward

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