Unresectable Chondrosarcomas Treated With Carbon Ion Radiotherapy: Relationship Between Dose-averaged Linear Energy Transfer and Local Recurrence.

BACKGROUND/AIM: The local control rate of chondrosarcomas treated with carbon-ion radiotherapy (CIRT) worsens as tumour size increases, possibly because of the intra-tumoural linear energy transfer (LET) distribution. This study aimed to evaluate the relationship between local recurrence and intra-tumoural LET distribution in chondrosarcomas treated with CIRT. PATIENTS AND METHODS: Thirty patients treated with CIRT for grade 2 chondrosarcoma were included. Dose-averaged LET (LETd) distribution was calculated by the treatment planning system, and the relationship between LETd distribution in the planning tumour volume (PTV) and local control was evaluated. RESULTS: The mean LETd value in PTV was similar between cases with and without recurrence. Recurrence was not observed in cases where the effective minimum LETd value exceeded 40 keV/µm. CONCLUSION: LETd distribution in PTV is associated with local control in chondrosarcomas and patients treated with ion beams of higher LETd may have an improved local control rate for unresectable chondrosarcomas.

Proton therapy for brain tumours in the area of evidence-based medicine.

ADVANCES IN KNOWLEDGE: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.

A prospective clinical trial of proton therapy for chordoma and chondrosarcoma: Feasibility assessment.

BACKGROUND/OBJECTIVES: Proton therapy (PRT) has emerged as a treatment option for chordomas/chondrosarcomas to escalate radiation dose more safely. We report results of a phase I/II trial of PRT in patients with chordoma/chondrosarcoma. METHODS: Twenty adult patients with pathologically confirmed, nonmetastatic chordoma or chondrosarcoma were enrolled in a single-institution prospective trial of PRT from 2010 to 2014. Seventeen patients received adjuvant PRT and three received definitive PRT. Median dose was 73.8 Gy(RBE; range 68.4-79.2 Gy) using PRT-only (n = 6) or combination PRT/intensity-modulated radiotherapy (IMRT) (n = 14). Quality-of-life (QOL) and fatigue were assessed weekly and every 3 months posttreatment with the Functional Assessment of Cancer Therapy - Brain (FACTBr) and Brief Fatigue Inventory. Primary endpoint was feasibility (90% completing treatment with < 10 day treatment delay and ≤ 20% unexpected acute grade ≥ 3 toxicity). RESULTS: Tumors included chordomas of the skull base (n = 10), sacrum (n = 5), and cervical spine (n = 3), and skull base chondrosarcomas (n = 2). Median age was 57. The 80% had positive margins/gross disease. Median follow-up was 37 months. Feasibility endpoints were met. The 3-year local control and progression-free survival was 86% and 81%. There were no deaths. Two patients had acute grade 3 toxicity (both fatigue). One had late grade 3 toxicity (epistaxis and osteoradionecrosis). There were no significant differences in patient reported fatigue or QOL from baseline to the end-of-treatment. CONCLUSIONS: We report favorable local control, survival, and toxicity following PRT.

The use of proton therapy in the treatment of head and neck cancers.

External beam radiation therapy is a commonly utilized treatment modality in the management of head and neck cancer. Given the close proximity of disease to critical normal tissues and structures, the delivery of external beam radiation therapy can result in severe acute and late toxicities, even when delivered with advanced photon-based techniques, such as intensity-modulated radiation therapy. The unique physical characteristics of protons make it a promising option in the treatment of advanced head and neck cancer, with the potential to improve sparing of normal tissues and/or safely escalate radiation doses. Clinical implementation will require the continued development of advanced techniques such as intensity-modulated proton therapy, using pencil beam scanning, as well as rigorous methods of quality assurance and adaptive techniques to accurately adjust to changes in anatomy due to disease response. Ultimately, the widespread adaptation and implementation of proton therapy for head and neck cancer will require direct, prospective comparisons to standard techniques such as intensity-modulated radiation therapy, with a focus on measures such as toxicity, disease control, and quality of life.

Proton therapy for sarcomas.

Sarcomas are a heterogeneous group of tumors that can occur in a wide array of anatomic sites and age ranges with varying histologies. Proton beam therapy, as compared with advanced x-ray radiation therapy techniques, can substantially lower dose to nontarget tissues. This dosimetric advantage can potentially allow for improvement of the therapeutic ratio in the treatment of many of the sarcomas by either increasing the local control, via increased dose to the target, or by decreasing the normal tissue complications, via lowered dose to the avoidance structures. This article reviews the key dosimetric studies and clinical outcomes published to date documenting the potential role proton beam therapy may play in the treatment of sarcomas.

Electrophysiological monitoring in patients with tumors of the skull base treated by carbon-12 radiation therapy.

PURPOSE: To report the results of short-term electrophysiologic monitoring of patients undergoing (12)C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery. METHODS AND MATERIALS: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision. RESULTS: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline. CONCLUSIONS: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may help predict, possible late toxicity.

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

UNLABELLED: PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. PATIENTS AND METHODS: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. RESULTS: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. CONCLUSIONS: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.

Increased efficacy of radiation therapy by use of proton beam.

Proton beam treatment techniques provide a powerful approach to improving dose distribution (decrease treatment volume towards target volume) and hence increasing dose to target with resultant higher tumor control rates and lesser morbity. To achieve these dose distributions in patients requires use of modern imaging techniques, rigid immobilization systems, confirmation of target position vis a vis the proton beam at each treatment session, treatment planning which feature beam's eye view, displays of uncertainty, dose at each anatomic point, boli based on accurate assessment of density along each pixel, etc. Experience at MGH/MEEI/HCL has yielded a disease-free survival of 78% for patients with chordoma/chondrosarcoma of base of skull. Local control is achieved by 98% of patients treated for choroidal melanoma.