scholarly journals Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Maria Saager ◽  
Christin Glowa ◽  
Peter Peschke ◽  
Stephan Brons ◽  
Rebecca Grün ◽  
...  

Abstract Background To determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations. Material and methods The rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16–99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD50-values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV). Results At six fractions, TD50-values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range. Conclusions This study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.

2016 ◽  
Vol 55 (12) ◽  
pp. 1512-1515 ◽  
Author(s):  
Maria Saager ◽  
Christin Glowa ◽  
Peter Peschke ◽  
Stephan Brons ◽  
Rebecca Grün ◽  
...  

2020 ◽  
Author(s):  
Liwen Zhang ◽  
Weiwei Wang ◽  
Jiyi Hu ◽  
Jiade Lu ◽  
Lin Kong

Abstract Background: We sought to establish a conversion curve to convert the RBE-weighted doses calculated by local effect model I (LEM) (LEM RBE-weighted doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the RBE-weighted doses calculated by microdosimetric kinetic model (MKM) (MKM RBE-weighted doses). We also converted the LEM dose constraints (RBE-weighted dose constraints in LEM plans) for the brain stem, spinal cord, and optic nerve based on this curve.Methods: Data from 20 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. The clinical target volume CTV1(GTV+5mm)was given 3 Gy (RBE) per fraction. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of conversion factors (i.e., the ratio of LEM RBE-weighted dose to MKM RBE-weighted dose) was then obtained by using an isovolumetric dose method. The LEM plan prescriptions (LEM prescription) and dose constraints of the organs at risk (OARs) (OAR constraints) were converted to the corresponding MKM prescriptions and dose constraints using this conversion curve. Results: For the CTV1 fractional RBE-weighted dose prescription of 3.00 Gy (RBE) and CTV2 of 2.70 Gy (RBE) in LEM plans, the conversion factors (LEM RBE-weighted dose/MKM RBE-weighted dose) were 1.37 (CI 95% 1.35–1.39) and 1.46 (1.41–1.51), respectively. The average conversion factors from 1.37(CI 95% 1.33–1.41) to 3.09 (2.94–3.24) corresponded to the LEM fractionated doses from 2.86 Gy (RBE) to 0.24 Gy (RBE), including the doses constraining upon OARs. LEM RBE-weighted doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM RBE-weighted doses of 16.64 Gy (RBE) and 30.72 Gy (RBE) in 16 fractions. Conclusions: This conversion curve could be used to convert LEM RBE-weighted doses to MKM RBE-weighted doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Liwen Zhang ◽  
Weiwei Wang ◽  
Jiyi Hu ◽  
Jiade Lu ◽  
Lin Kong

Abstract Background We sought to establish a conversion curve to convert the RBE-weighted doses calculated by local effect model I (LEM) (LEM RBE-weighted doses) in patients with locally recurrent nasopharyngeal carcinoma (rNPC) to the RBE-weighted doses calculated by microdosimetric kinetic model (MKM) (MKM RBE-weighted doses). We also converted the LEM dose constraints (RBE-weighted dose constraints in LEM plans) for the brain stem, spinal cord, and optic nerve based on this curve. Methods Data from 20 patients with rNPC receiving carbon-ion radiotherapy (CIRT) in our hospital were collected. LEM in Raystation (V8A, Raystation, Sweden) was used to generate treatment plans. The clinical target volume CTV1 (GTV + 5 mm) was given 3 Gy (RBE) per fraction. Ninety-nine percent of target volumes should be covered by 95% of the prescriptions; the maximum doses of the brainstem and spinal cord were < 45 Gy (RBE) and < 30 Gy (RBE), respectively. The doses covering 20% volumes of optical nerves/chiasms D20 were < 30 Gy (RBE). Then physical doses of the LEM plans were recalculated by using MKM in Raystation to generate MKM plans. A series of conversion factors (i.e., the ratio of LEM RBE-weighted dose to MKM RBE-weighted dose) was then obtained by using an isovolumetric dose method. The LEM plan prescriptions (LEM prescription) and dose constraints of the organs at risk (OARs) (OAR constraints) were converted to the corresponding MKM prescriptions and dose constraints using this conversion curve. Results For the CTV1 fractional RBE-weighted dose prescription of 3.00 Gy (RBE) and CTV2 of 2.70 Gy (RBE) in LEM plans, the conversion factors (LEM RBE-weighted dose/MKM RBE-weighted dose) were 1.37 (CI 95% 1.35–1.39) and 1.46 (1.41–1.51), respectively. The average conversion factors from 1.37 (CI 95% 1.33–1.41) to 3.09 (2.94–3.24) corresponded to the LEM fractionated doses from 2.86 Gy (RBE) to 0.24 Gy (RBE), including the doses constraining upon OARs. LEM RBE-weighted doses of 30 Gy (RBE) and 45 Gy (RBE) in 21 fractions were converted to MKM RBE-weighted doses of 16.64 Gy (RBE) and 30.72 Gy (RBE) in 16 fractions. Conclusions This conversion curve could be used to convert LEM RBE-weighted doses to MKM RBE-weighted doses for patients with rNPC receiving CIRT, providing dose references for re-irradiation therapy.


2020 ◽  
Author(s):  
Thomas Welzel ◽  
Alina Leandra Bendinger ◽  
Christin Glowa ◽  
Inna Babushkina ◽  
Manfred Jugold ◽  
...  

Abstract Background Radiation-induced myelopathy is a severe and irreversible complication that occurs after a long symptom-free latency time if the spinal cord was exposed to a significant irradiation dose during tumor treatment. As carbon ions are increasingly investigated for tumor treatment in clinical trials, their effect on normal tissue needs further investigation to assure safety of patient treatments. Magnetic resonance imaging (MRI)-visible morphological alterations could serve as predictive markers for medicinal interventions to avoid severe side effects. Thus, MRI-visible morphological alterations in the rat spinal cord after high dose photon and carbon ion irradiation and their latency times were investigated.MethodsRats whose spinal cords were irradiated with iso-effective high photon (n = 8) or carbon ion (n = 8) doses as well as sham-treated control animals (n=6) underwent frequent MRI measurements until they developed radiation-induced myelopathy (paresis II). MR images were analyzed for morphological alterations and animals were regularly tested for neurological deficits. In addition, histological analysis was performed of animals suffering from paresis II compared to controls.ResultsFor both beam modalities, first morphological alterations occurred outside the spinal cord (bone marrow conversion, contrast agent accumulation in the musculature ventral and dorsal to the spinal cord) followed by morphological alterations inside the spinal cord (edema, syrinx, contrast agent accumulation) and eventually neurological alterations (paresis I and II). Latency times were significantly shorter after carbon ions as compared to photon irradiation.Conclusions Irradiation of the rat spinal cord with photon or carbon ion doses that lead to 100% myelopathy induced a comparable fixed sequence of MRI-visible morphological alterations and neurological distortions. However, at least in the animal model used in this study, the observed MRI-visible morphological alterations in the spinal cord are not suited as predictive markers to identify animals that will develop myelopathy as the time between MRI-visible alterations and the occurrence of myelopathy is too short to intervene with protective or mitigative drugs.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Thomas Welzel ◽  
Alina L. Bendinger ◽  
Christin Glowa ◽  
Inna Babushkina ◽  
Manfred Jugold ◽  
...  

Abstract Background Radiation-induced myelopathy is a severe and irreversible complication that occurs after a long symptom-free latency time if the spinal cord was exposed to a significant irradiation dose during tumor treatment. As carbon ions are increasingly investigated for tumor treatment in clinical trials, their effect on normal tissue needs further investigation to assure safety of patient treatments. Magnetic resonance imaging (MRI)-visible morphological alterations could serve as predictive markers for medicinal interventions to avoid severe side effects. Thus, MRI-visible morphological alterations in the rat spinal cord after high dose photon and carbon ion irradiation and their latency times were investigated. Methods Rats whose spinal cords were irradiated with iso-effective high photon (n = 8) or carbon ion (n = 8) doses as well as sham-treated control animals (n = 6) underwent frequent MRI measurements until they developed radiation-induced myelopathy (paresis II). MR images were analyzed for morphological alterations and animals were regularly tested for neurological deficits. In addition, histological analysis was performed of animals suffering from paresis II compared to controls. Results For both beam modalities, first morphological alterations occurred outside the spinal cord (bone marrow conversion, contrast agent accumulation in the musculature ventral and dorsal to the spinal cord) followed by morphological alterations inside the spinal cord (edema, syrinx, contrast agent accumulation) and eventually neurological alterations (paresis I and II). Latency times were significantly shorter after carbon ions as compared to photon irradiation. Conclusions Irradiation of the rat spinal cord with photon or carbon ion doses that lead to 100% myelopathy induced a comparable fixed sequence of MRI-visible morphological alterations and neurological distortions. However, at least in the animal model used in this study, the observed MRI-visible morphological alterations in the spinal cord are not suited as predictive markers to identify animals that will develop myelopathy as the time between MRI-visible alterations and the occurrence of myelopathy is too short to intervene with protective or mitigative drugs.


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