Ion therapy guideline (Version 2020)

The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT). We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients. Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC. • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted.

BackgroundThe usefulness of particle therapy for skull base chordoma has not been established. The aim of this retrospective study was to analyse the treatment outcomes of proton therapy (PT) and carbon ion therapy (CIT) in patients with skull base chordoma at a single institution.MethodsAll patients who underwent PT or CIT with curative intent between 2003 and 2014 at Hyogo Ion Beam Medical Center were included in this study. Twenty-four patients were enrolled. Eleven (46%) received PT and 13 (54%) received CIT. Overall survival (OS), progression-free survival (PFS) and local control (LC) were calculated using the Kaplan–Meier method. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.ResultsThe median follow-up was 71.5 months (range, 14–175 months). The five-year LC, PFS and OS rates were 85, 81, and 86%, respectively. The LC (P = 0.048), PFS (P = 0.028) and OS (P = 0.012) were significantly improved in patients who had undergone surgery before particle therapy. No significant differences were observed in the LC rate and the incidence of grade 2 or higher late toxicities between patients who received PT and CIT.ConclusionsBoth PT and CIT appear to be effective and safe treatments and show potential to become the standard treatments for skull base chordoma. To increase the local control, surgery before particle therapy is preferable.

Proton therapy (PT) and carbon-ion therapy (CIT) differ not only in their physical dose characteristics but also in their biological effects, attributable to variations in fractionation protocols and linear energy transfer (LET). These differences make direct comparisons challenging. This study aims to comprehensively compare the treatment planning of protons and carbon ions for head and neck cancer by incorporating LET-dependent variable α/β ratios into the calculations of equivalent dose in 2 Gy fractions (EQD2) and normal tissue complication probability (NTCP). We retrospectively created treatment plans for nine head and neck cancer patients using proton therapy and carbon-ion therapy. Variable α/β ratios, calculated via the microdosimetric kinetic model, were integrated into EQD2 calculations. NTCP assessments for both late and acute toxicities utilized the Lyman-Kutcher-Burman model. In addition to comparing EQD2 and NTCP outcomes between protons and carbon ions, we conducted robustness evaluations that considered a 2 mm positioning error and a 3.5% range uncertainty. The α/β ratio for protons remained consistent at approximately 3 Gy across all tissues. In contrast, the α/β ratio for carbon ions varied significantly, reaching up to 20 Gy along the beam path. This variability in α/β ratios showed that carbon ions achieved lower EQD2 values for organs at risk (OARs) such as the brain, skin, and oral mucosa compared to protons. Furthermore, NTCP analysis revealed a significant reduction in acute toxicities, particularly dermatitis, with carbon-ion therapy. Both treatment modalities effectively minimized the probability of late toxicities. No significant differences in robustness were observed between proton therapy and carbon-ion therapy. EQD2 calculations incorporating variable α/β ratios revealed that carbon ions offer a dosimetric advantage over protons for certain OARs. However, this difference was relatively minor and did not suggest a clinically significant impact beyond acute toxicities.

Cost analysis of radiotherapy, carbon ion therapy, proton therapy and BNCT in Japan

Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT), proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80–90% and 40–50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation.

BackgroundSome cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy.MethodsThe ETOILE study is a multicenter prospective randomized phase III trial comparing carbon ion therapy to either advanced photon or proton radiotherapy for inoperable or macroscopically incompletely resected (R2) radioresistant cancers including sarcomas and adenoid cystic carcinomas.In the experimental arm, carbon ion therapy will be performed at the National Center for Oncological Hadrontherapy (CNAO) in Pavia, Italy. In the control arm, photon or proton radiotherapy will be carried out in referent centers in France.The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival and local control, toxicity profile, and quality of life. In addition, a prospective health-economic study and a radiobiological analysis will be conducted.To demonstrate an absolute improvement in the 5-year PFS rate of 20% in favor of carbon ion therapy, 250 patients have to be included in the study.DiscussionSo far, no clinical study of phase III has demonstrated the superiority of carbon ion therapy compared to conventional radiotherapy, including proton therapy, for the treatment of radioresistant tumors.Trial registrationClinicalTrials.gov identifier: NCT02838602. Date of registration: July 20, 2016. The posted information will be updated as needed to reflect protocol amendments and study progress.

Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

Mapping of RBE-Weighted Doses Between HIMAC– and LEM–Based Treatment Planning Systems for Carbon Ion Therapy

Radiation pneumonitis is a major dose-limiting complication in thoracic radiation therapy (RT) and presents clinically in the first few months after RT. We evaluated the feasibility of quantifying pulmonary parenchymal glycolysis (PG) as a surrogate of global lung inflammation and radiation-induced pulmonary toxicity using a novel semiautomatic lung segmentation technique in non-small-cell lung cancer (NSCLC) patients and compared PG in patients treated with photon or proton RT. We evaluated 18 consecutive locally advanced NSCLC patients who underwent pretreatment and post-treatment F-FDG PET/CT treated with definitive (median: 66.6 Gy; 1.8 Gy fractions) photon or proton RT between 2010 and 2014. Lung volume segmentation was conducted using 3D Slicer by performing simple thresholding. Pulmonary PG was calculated by summing F-FDG uptake in the whole lung. In nine patients treated with photon RT, significant increases in PG in both ipsilateral (mean difference: 1400±510; P=0.02) and contralateral (mean difference: 1200±450; P=0.03) lungs were noted. In nine patients treated with proton therapy, no increase in pulmonary PG was observed in either the ipsilateral (P=0.30) or contralateral lung (P=0.98). We observed a significant increase in global lung inflammation bilaterally as measured by quantification of PG. However, no significant change in global lung inflammation was noted after proton therapy. Future larger studies are needed to determine whether this difference correlates with lower risks of radiation pneumonitis in NSCLC patients treated with proton therapy.

A study was undertaken to evaluate the clinical outcome of particle therapy for stage I nonsmall cell lung cancer (NSCLC). From April 2003 to April 2007, 80 patients with stage I NSCLC were treated with proton therapy or carbon-ion therapy (57 with proton therapy and 23 with carbon-ion therapy) using 3 treatment protocols. In the first protocol, 80 gray equivalents (GyE) of proton therapy was given in 20 fractions, and the second proton therapy protocol used 60 GyE in 10 fractions. For carbon-ion therapy, 52.8 GyE was given in 4 fractions. After achieving promising preliminary results for the first protocol, the authors started to use the second proton therapy protocol to shorten the overall treatment time. Carbon-ion therapy was started in 2005, and thereafter, both proton and carbon-ion therapy plans were made for each patient, and the 1 that appeared superior was adopted. Patient age ranged from 48 to 89 years (median, 76 years). Thirty-seven patients were medically inoperable, and 43 refused surgery. Forty-two patients had T1 tumors, and 38 had T2 tumors. The median follow-up period for living patients was 35.5 months. For all 80 patients, the 3-year overall survival, cause-specific survival, and local control rates were 75% (IA: 74%; IB: 76%), 86% (IA: 84%; IB: 88%), and 82% (IA: 87%; IB: 77%), respectively. There were no significant differences in treatment results among the 3 protocols. Grade 3 pulmonary toxicity was observed in only 1 patient. Proton therapy and carbon-ion therapy are safe and effective for stage I NSCLC. Further investigation of particle therapy for stage I NSCLC is warranted.

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies.This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. The lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI.The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy.Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.

Dose–response curves for MRI-detected radiation-induced temporal lobe reactions in patients after proton and carbon ion therapy: Does the same RBE-weighted dose lead to the same biological effect?

Phase II Trial of Intensity-Modulated Photon or Scanning Beam Proton Therapy Both with Simultaneous Integrated Boost Dose Escalation to the Gross Tumor Volume with Concurrent Chemotherapy for Stage II/III Non-Small Cell Lung Cancer - Interim Analysis

Preliminary result of proton beam therapy for malignancies of the nasal cavity and paranasal sinus-with special reference to adverse effects on optic pathways

Examination of GyE system for HIMAC carbon therapy