Sebastian Adeberg1, Denise Bernhardt2, Semi Ben Harrabi3, Matthias Uhl2, Angela Paul3, Nina Bougatf4, Vivek Verma5, Andreas Unterberg6, Wolfgang Wick7, Thomas Haberer4, Stephanie E Combs8, Klaus Herfarth3, Juergen Debus3, Stefan Rieken3. 1. University Hospital of Heidelberg, Department of Radiation Oncology, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Germany; Heidelberg Institute for Radiation Oncology (HIRO), Germany. Electronic address: Sebastian.adeberg@med.uni-heidelberg.de. 2. University Hospital of Heidelberg, Department of Radiation Oncology, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Germany; Heidelberg Institute for Radiation Oncology (HIRO), Germany. 3. University Hospital of Heidelberg, Department of Radiation Oncology, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center (HIT), Germany; Heidelberg Institute for Radiation Oncology (HIRO), Germany. 4. Heidelberg Ion-Beam Therapy Center (HIT), Germany; Heidelberg Institute for Radiation Oncology (HIRO), Germany. 5. Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, USA. 6. University Hospital of Heidelberg, Department of Neurosurgery, Germany. 7. University Hospital of Heidelberg, Department of Neurooncology, Germany. 8. Technische Universität München, Department of Radiation Oncology, Germany; Institut für Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Germany.
Abstract
PURPOSE: To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG). METHOD AND MATERIALS: Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofsky's performance status, PTV size, temozolomide therapy (each p > 0.1). The study assessed progression-free survival (PFS), overall survival (OS), acute treatment-related toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria). RESULTS: Median PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2-39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV of the proton boost was significantly smaller than the photon plan PTVs (each p < 0.001). Acute toxicity was mild. Toxicity ≥grade 2 was observed in 6 patients (9%) receiving bimodality RT and 9 patients (14%) receiving photon-only RT. Two types of severe adverse events (CTCAE grade 3) occurred solely in the photon-only group: severe increase in intracranial pressure (5%); and generalized seizures (3%). Pseudoprogression was rare, occurring on average 6 weeks after radiotherapy, and was balanced in both treatment groups (n = 4 each; 8%). CONCLUSION: Delivering a proton boost to significantly smaller target volumes when compared to photon-only plans, yielded comparable progression and survival rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred rarely and evenly distributed in both treatment groups. Thus, bimodality RT was at least equivalent regarding outcome and potentially superior with respect to toxicity in patients with HGG. SUMMARY: Treating patients with HGG with 50.0 Gy photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0 Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity and pseudoprogression were rare in both treatment groups. Therefore, in this clinical setting, combined proton radiotherapy might be beneficial in terms of further risk reduction for treatment-related side effects. Interestingly, treatment volume reduction using a proton boost led to comparable survival and progression rates with decreased severe treatment-related toxicity compared to conventional photon radiotherapy.
PURPOSE: To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG). METHOD AND MATERIALS: Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofsky's performance status, PTV size, temozolomide therapy (each p > 0.1). The study assessed progression-free survival (PFS), overall survival (OS), acute treatment-related toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria). RESULTS: Median PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2-39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV of the proton boost was significantly smaller than the photon plan PTVs (each p < 0.001). Acute toxicity was mild. Toxicity ≥grade 2 was observed in 6 patients (9%) receiving bimodality RT and 9 patients (14%) receiving photon-only RT. Two types of severe adverse events (CTCAE grade 3) occurred solely in the photon-only group: severe increase in intracranial pressure (5%); and generalized seizures (3%). Pseudoprogression was rare, occurring on average 6 weeks after radiotherapy, and was balanced in both treatment groups (n = 4 each; 8%). CONCLUSION: Delivering a proton boost to significantly smaller target volumes when compared to photon-only plans, yielded comparable progression and survival rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred rarely and evenly distributed in both treatment groups. Thus, bimodality RT was at least equivalent regarding outcome and potentially superior with respect to toxicity in patients with HGG. SUMMARY: Treating patients with HGG with 50.0 Gy photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0 Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity and pseudoprogression were rare in both treatment groups. Therefore, in this clinical setting, combined proton radiotherapy might be beneficial in terms of further risk reduction for treatment-related side effects. Interestingly, treatment volume reduction using a proton boost led to comparable survival and progression rates with decreased severe treatment-related toxicity compared to conventional photon radiotherapy.
Authors: Maria Waltenberger; Jennifer Furkel; Manuel Röhrich; Patrick Salome; Charlotte Debus; Bouchra Tawk; Aoife Ward Gahlawat; Andreas Kudak; Matthias Dostal; Ute Wirkner; Christian Schwager; Christel Herold-Mende; Stephanie E Combs; Laila König; Jürgen Debus; Uwe Haberkorn; Amir Abdollahi; Maximilian Knoll Journal: Front Oncol Date: 2022-09-20 Impact factor: 5.738
Authors: Rainer J Klement; Ilinca Popp; David Kaul; Felix Ehret; Anca L Grosu; Bülent Polat; Reinhart A Sweeney; Victor Lewitzki Journal: J Neurooncol Date: 2021-12-23 Impact factor: 4.130