Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus

Lambrecht, Maarten; Eekers, Daniëlle; Alapetite, Claire; Burnet, N.G.; Calugaru, Valentin; Coremans, I.; Fossati, Piero; Høyer, Morten; Langendijk, Johannes A.; Romero, Alejandra Méndez; Paulsen, Frank; Perpar, Ana; Renard, Laurette; Ruysscher, Dirk De; Timmermann, Beate; Vítek, Pavel; Weber, Damien Charles; Weide, Hiske L van der; Whitfield, Gillian A; Wiggenraad, Ruud; Roelofs, Erik; Nyström, Petra Witt; Troost, Esther G.C.

doi:10.1016/j.radonc.2018.05.001

Cited by 129 publications

(101 citation statements)

References 127 publications

(210 reference statements)

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“…It was considered that there might be some relationship between the incidence of hearing loss and the combination of WBRT and ALK-TKI. Sensorineural hearing loss is one of the serious complications of the inner ear induced by radiation, which occurs 1.5-5 years after radiotherapy and is irreversible (30).…”

Section: Discussionmentioning

confidence: 99%

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

Nakashima

Nonoshita

Hirata

et al. 2019

In Vivo

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Background: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK. Patients and Methods: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both wholebrain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT. Results: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wildtype cases (p=0.013), respectively. Conclusion: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC. Anaplastic lymphoma kinase gene rearrangement (ALKr) is a significant driver of gene mutation for novel moleculartargeted therapy in lung cancer, and is identified in about 2-7% of non-small cell lung cancer (NSCLC) cases (1). The predominant histological subtype in ALKr NSCLC is adenocarcinoma, and ALKr is rarely seen in other histological subtypes, including small-cell lung cancer. In addition, unlike mutation of epidermal growth factor receptor (EGFR), which differs in humans according to race, there is no race-related difference in the frequency of ALKr. With regard to the prognostic significance of ALKr, some investigations have reported ALKr itself to be a favorable prognostic factor (2). The existence of brain metastases (BMs) is a major factor leading to poor survival outcome in NSCLC, with the median survival of patients with BMs ranging from 3 to 14.8 months according to diagnosis-specific graded prognostic assessment (3). The incidence of BMs from ALKr NSCLC ranges from approximately 25% to 35%; it is greater than that for those with wild-type NSCLC, and slightly higher or equivalent to that of NSCLC with EGFR mutation (4). BMs seem to be more commonly detected at initial diagnosis in those with ALKr NSCLC compared with those with wildtype NSCLC. Many previous clinical trials reported that multi-targeted receptor tyrosine kinase inhibitors (TKIs) of ALK, such as crizotinib, alectinib and ceritinib, achieved better local control of BMs and intracranial progression-free survival (IPFS) in ALKr NSCLC (5-7). Crizotinib, a first-generation ALK-TKI, was associated with a median IPFS of 7 months in patients with BMs that was previously untreated in the analysis of PROFILE 1005 and 1007 (8). After the experience of progression with a single ALK-TKI, it is promising to consider sequential therapy with multiple ALK-TKI (9-12). Regardless of the efficacy of ALK-TKI for BMs, it is concerning that many patients invariably develop progression of intracranial disease. Therefore, radiotherapy such as whole-brain radioth...

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Section: Discussionmentioning

confidence: 99%

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

Nakashima

Nonoshita

Hirata

et al. 2019

In Vivo

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“…This will enable upfront assessment of a patient's likelihood to benefit from particle treatment. Uniform delineation and consensus on the tolerance on OARs are the first steps to achieve this besides a structured follow up including uniform neuro-cognitive tests [18,48]. This potentially improved quality of life ought to be outweighed against the additional costs of particles (protons, carbon ions) over technically advanced photon treatments.…”

Section: Discussionmentioning

confidence: 99%

Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial

et al. 2018

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Background and purpose: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. Material and methods: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. Results: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (D mean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. Discussion: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.

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“…Therefore, EPTN is an official task force of the European Society for Radiotherapy and Oncology (ESTRO). The seven working groups have already produced a series of recommendations and whitepapers, and more activities are expected in the coming years (Bolsi et al, 2018;Dosanjh et al, 2018b;Eekers et al, 2018;Grau et al, 2018;Lambrecht et al, 2018;Langendijk et al, 2018b;Weber et al, 2018Weber et al, , 2019.…”

Section: Collaborative Networkmentioning

confidence: 99%

Particle therapy in Europe

et al. 2020

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Particle therapy using protons or heavier ions is currently the most advanced form of radiotherapy and offers new opportunities for improving cancer care and research. Ions deposit the dose with a sharp maximum – the Bragg peak – and normal tissue receives a much lower dose than what is delivered by X‐ray therapy. Particle therapy has also biological advantages due to the high linear energy transfer of the charged particles around the Bragg peak. The introduction of particle therapy has been slow in Europe, but within the last decade, more than 20 clinical facilities have opened and facilitated access to this frontline therapy. In this review article, the basic concepts of particle therapy are reviewed along with a presentation of the current clinical indications, the European clinical research, and the established networks.

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Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus

Cited by 129 publications

References 127 publications

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial

Particle therapy in Europe

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