Search

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. Methods This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. Discussion PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. Trial Registration NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020–000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020–01, version 3.2, date 18.09.2020.

Background: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. Methods: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. Discussion: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. Trial Registration: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020–000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020–01, version 3.2, date 18.09.2020. [ABSTRACT FROM AUTHOR]

Background A post-operative MRI (MRIpost-op) performed within 72 h is routinely used for radiation treatment planning in glioblastoma (GBM) patients, with radiotherapy starting about 4–6 weeks after surgery. Some patients undergo an additional pre-radiotherapy MRI (MRIpre-RT) about 2–6 weeks after surgery. We sought to analyze the incidence of rapid early progression (REP) between surgery and initiation of radiotherapy seen on MRIpre-RT and the impact on radiation target volumes. Methods Patients with GBM diagnosed between 2018 and 2020 who had an MRIpost-op and MRIpre-RT were retrospectively identified. Criteria for REP was based on Modified RANO criteria. Radiation target volumes were created and compared using the MRIpost-op and MRIpre-RT. Results Fifty patients met inclusion criteria. The median time between MRIpost-op and MRIpre-RT was 26 days. Indications for MRIpre-RT included clinical trial enrollment in 41/50 (82%), new symptoms in 5/50 (10%), and unspecified in 4/50 (8%). REP was identified in 35/50 (70%) of patients; 9/35 (26%) had disease progression outside of the MRIpost-op-based high dose treatment volumes. Treatment planning with MRIpost-op yielded a median undertreatment of 27.1% of enhancing disease and 11.2% of surrounding subclinical disease seen on MRIpre-RT. Patients without REP had a 38% median volume reduction of uninvolved brain if target volumes were planned with MRIpre-RT. Conclusion Given the incidence of REP and its impact on treatment volumes, we recommend using MRIpre-RT for radiation treatment planning to improve coverage of gross and subclinical disease, allow for early identification of REP, and decrease radiation treatment volumes in patients without REP. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study is to provide real-world evidence in glioblastoma treatment and to compare overall survival after Stupp's regimen treatment today and a decade ago. A current consecutive cohort of histologically confirmed glioblastoma irradiated from 1/2014 to 12/2017 in our cancer center was compared with an already published historical control of patients treated in 1/2003–12/2009. A total of new 155 patients was analyzed, median age 60.9 years, 61% men, 58 patients (37%) underwent gross total tumor resection. Stupp's regimen was indicated in 90 patients (58%), 65 patients (42%) underwent radiotherapy alone. Median progression-free survival in Stupp's regimen cohort was 6.7 months, median OS 16.0 months, and 2-year OS 30.7%. OS was longer if patients were able to finish at least three cycles of adjuvant chemotherapy (median 23.3 months and 43.9% of patients lived at 2 years after surgery). Rapid early progression prior to radiotherapy was a negative prognostic factor with HR 1.87 (p = 0.007). The interval between surgery and the start of radiotherapy (median 6.7 weeks) was not prognostically significant (p = 0.825). The median OS in the current cohort was about 2 months longer than in the historical control group treated 10 years ago (16 vs. 13.8 months) using the same Stupp's regimen. Taking into account differences in patient's characteristics between current and historical cohorts, age, extent of resection, and ECOG patient performance status adjusted HR (Stupp's regimen vs. RT alone) for OS was determined as 0.45 (p = 0.002).

The aim of this retrospective study is to provide real-world evidence in glioblastoma treatment and to compare overall survival after Stupp's regimen treatment today and a decade ago. A current consecutive cohort of histologically confirmed glioblastoma irradiated from 1/2014 to 12/2017 in our cancer center was compared with an already published historical control of patients treated in 1/2003–12/2009. A total of new 155 patients was analyzed, median age 60.9 years, 61% men, 58 patients (37%) underwent gross total tumor resection. Stupp's regimen was indicated in 90 patients (58%), 65 patients (42%) underwent radiotherapy alone. Median progression-free survival in Stupp's regimen cohort was 6.7 months, median OS 16.0 months, and 2-year OS 30.7%. OS was longer if patients were able to finish at least three cycles of adjuvant chemotherapy (median 23.3 months and 43.9% of patients lived at 2 years after surgery). Rapid early progression prior to radiotherapy was a negative prognostic factor with HR 1.87 (p = 0.007). The interval between surgery and the start of radiotherapy (median 6.7 weeks) was not prognostically significant (p = 0.825). The median OS in the current cohort was about 2 months longer than in the historical control group treated 10 years ago (16 vs. 13.8 months) using the same Stupp's regimen. Taking into account differences in patient's characteristics between current and historical cohorts, age, extent of resection, and ECOG patient performance status adjusted HR (Stupp's regimen vs. RT alone) for OS was determined as 0.45 (p = 0.002). [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of two fractionation regimens on survival in patients with Grade IV gliomas depending on rapid early progression (REP)., Material and Methods: Fractionation with prescribed doses of 2 and 3 Gy was alternately used in 140 patients with morphologically confirmed Grade IV glioma using a pairwise modeling strategy., Results: REP was diagnosed in 60 (42.9%) out of 140 patients with Grade IV gliomas and 55 (45.5%) out of 121 patients with glioblastomas. Fatal outcome was observed in 111 (79.3%) patients, 99 (70.7%) ones died from progression of glioma. In case of no REP, the median overall survival as of December 2023 was 32.20 (95% CI 25.7-38.7) months, with REP - only 16.03 (95% CI 13.5-18.6) months ( p <0.0001). Median survival was slightly lower in patients with glioblastoma - 28.2 and 16.5 months, respectively ( p <0.0001)., In patients with Grade IV gliomas and no REP, 3 Gy ( n =40) fractionation regimen was followed by median overall survival 44.98 (95% Cl 15.3-74.6) months, 2 Gy ( n =40) - 20.99 (95% CI 9.2-32.7) months ( p =0.027). In case of glioblastoma, differences between fractionation regimes lose significance - medians 33.7 and 19.7 months, respectively ( p =0.081). According to multivariate analysis, 3 Gy fractionation regimen is more effective than standard radiotherapy ( p =0.009) in patients without REP, while significance of isoeffective doses <59.5Gy≥ is slightly lower ( p =0.020). Radiotherapy on the background of temozolomide is equally important ( p =0.007)., In patients with grade 4 gliomas and REP, 3 Gy ( n =30) fractionation regimen was followed by median overall survival 17.18 (95% CI 14.2-20.2) months, 2 Gy ( n =30) - 12.88 (95% CI 5.4-20.3) months ( p =0.849). In case of glioblastoma, Cox model classification matrix looks as follows: fractionation variant ( p =0.423), isoeffective dose <59.5Gy≥ ( p <0.0001), temozolomide during radiotherapy ( p =0.701), functional status ( p =0.485)., Conclusion: In patients with Grade IV gliomas and no REP, 3 Gy fractionation regimen has significant advantages over standard radiotherapy regarding overall survival. In case of more aggressive course of tumor (REP), higher single dose does not improve treatment outcomes. Isoeffective dose ≥59.5Gy is of great importance.

Background: The aim of this retrospective study is to assess the incidence, localization, and potential predictors of rapid early progression (REP) prior to initiation of radiotherapy in newly diagnosed glioblastoma patients and to compare survival outcomes in cohorts with or without REP in relation to the treatment. Methods: We assessed a consecutive cohort of 155 patients with histologically confirmed irradiated glioblastoma from 1/2014 to 12/2017. A total of 90 patients with preoperative, postoperative, and planning MRI were analyzed. Results: Median age 59 years, 59% men, and 39 patients (43%) underwent gross total tumor resection. The Stupp regimen was indicated to 64 patients (71%); 26 patients (29%) underwent radiotherapy alone. REP on planning MRI performed shortly prior to radiotherapy was found in 46 (51%) patients, most often within the surgical cavity wall, and the main predictor for REP was non-radical surgery (p < 0.001). The presence of REP was confirmed as a strong negative prognostic factor; median overall survival (OS) in patients with REP was 10.7 vs. 18.7 months and 2-year survival was 15.6% vs. 37.7% (hazard ratio HR 0.53 for those without REP; p = 0.007). Interestingly, the REP occurrence effect on survival outcome was significantly different in younger patients (≤ 50 years) and older patients (> 50 years) for OS (p = 0.047) and non-significantly for PFS (p = 0.341). In younger patients, REP was a stronger negative prognostic factor, probably due to more aggressive behavior. Patients with REP who were indicated for the Stupp regimen had longer OS compared to radiotherapy alone (median OS 16.0 vs 7.5; HR = 0.5, p = 0.022; 2-year survival 22.3% vs. 5.6%). The interval between surgery and the initiation of radiotherapy were not prognostic in either the entire cohort or in patients with REP. Conclusion: Especially in the subgroup of patients without radical resection, one may recommend as early initiation of radiotherapy as possible. The phenomenon of REP should be recognized as an integral part of stratification factors in future prospective clinical trials enrolling patients before initiation of radiotherapy.

Objective: To investigate the impact of resection quality on subsequent survival of patients with glioblastoma., Material and Methods: There were 141 patients with morphologically confirmed glioblastoma (grade 4). Fractionation with the prescribed dose of 2 and 3 Gy was alternately used (pairwise modeling strategy). Total resection was performed in 29.8% of patients (EOR: 100%; n =42), subtotal - 56.7% (EOR: 70-99%; n =80). Extent of resection 1-69% was registered in 19 patients (13.5%)., Results: As of December 2022, 124 out of 141 patients (87.9%) were diagnosed with primary progression, 101 (71.6%) ones died. We analyzed the threshold role of EOR. The most informative level was 70% ( p =0.002). EOR 100% was followed by median overall survival about 32.2 months (95% Cl: 15.3-49.1), EOR 70-99% - 21.3 months (95% Cl: 15.1-27.5), EOR 1-69% - 10.3 months (95% Cl: 3.8-16.9; p =0.003). Fractionation mode with the prescribed dose of 3 Gy partially eliminated significance of EOR ( p =0.148) in contrast to standard fractionation ( p =0.015). Tumor growth in the interval between surgery and radiotherapy (REP) reduces significance of EOR ( p =0.042). Inclusion of second-line therapy with bevacizumab in multivariate analysis model (OR=0.488; p =0.002) makes EOR less significant (OR=0.749; p =0.085) in contrast to REP (OR=2.482; p <0.0001)., Conclusion: To date, the principle of maximum safe resection remains fundamental in neurosurgery. EOR about 70% is sufficient regarding overall survival, but total resection should be sought if possible.

Background: The aim of this retrospective study is to assess the incidence, localization, and potential predictors of rapid early progression (REP) prior to initiation of radiotherapy in newly diagnosed glioblastoma patients and to compare survival outcomes in cohorts with or without REP in relation to the treatment. Methods: We assessed a consecutive cohort of 155 patients with histologically confirmed irradiated glioblastoma from 1/2014 to 12/2017. A total of 90 patients with preoperative, postoperative, and planning MRI were analyzed. Results: Median age 59 years, 59% men, and 39 patients (43%) underwent gross total tumor resection. The Stupp regimen was indicated to 64 patients (71%); 26 patients (29%) underwent radiotherapy alone. REP on planning MRI performed shortly prior to radiotherapy was found in 46 (51%) patients, most often within the surgical cavity wall, and the main predictor for REP was non-radical surgery (p < 0.001). The presence of REP was confirmed as a strong negative prognostic factor; median overall survival (OS) in patients with REP was 10.7 vs. 18.7 months and 2-year survival was 15.6% vs. 37.7% (hazard ratio HR 0.53 for those without REP; p = 0.007). Interestingly, the REP occurrence effect on survival outcome was significantly different in younger patients (≤ 50 years) and older patients (> 50 years) for OS (p = 0.047) and non-significantly for PFS (p = 0.341). In younger patients, REP was a stronger negative prognostic factor, probably due to more aggressive behavior. Patients with REP who were indicated for the Stupp regimen had longer OS compared to radiotherapy alone (median OS 16.0 vs 7.5; HR = 0.5, p = 0.022; 2-year survival 22.3% vs. 5.6%). The interval between surgery and the initiation of radiotherapy were not prognostic in either the entire cohort or in patients with REP. Conclusion: Especially in the subgroup of patients without radical resection, one may recommend as early initiation of radiotherapy as possible. The phenomenon of REP should be recognized as an integral part of stratification factors in future prospective clinical trials enrolling patients before initiation of radiotherapy. [ABSTRACT FROM AUTHOR]