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Δευτέρα 5 Σεπτεμβρίου 2022

P18.11.A Active beam scanning proton therapy for large skull base benign meningiomas: long-term results

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Purpose
To report long-term results of active beam scanning proton therapy (PT) for large skull base benign meningiomas
Material and Methods
Eighty-two patients (pts) with large skull base meningiomas were treated with PT between April 2015 and December 2021. Median age was 62 years (range, 48-82) while KPS ranged between 60 and 100 (median 90); 60 were female (73%), and 22 were male (27%). Thirty-two pts (39%) had histologically proven World Health Organization (WHO) Grade I tumors. In remaining pts diagnosis was based on the typical imaging appearance of benign meningioma. All patients received PT for residual, progressive or non-operable lesions. Newly diagnosed tumors received total dose of 50 GyRBE (RBE: relative biologic effectiveness) while progressing meningiomas 54 GyRBE. All the treatments were delivered at 2 GyRBE per fraction. All pts were treated with active beam scanning PT using 3 fields with single field optimiz ation technique. Treatment planning was based on morphological magnetic resonance imaging (MRI) with contrast enhancement medium administration. All pts received also 68-Ga-DOTATOC-PET. Gross tumor volume ranged from 21 to 64 cc. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Median follow-up time was 40 months (range, 3-83).
Results
All pts completed the treatment without breaks. Registered acute side effects include grade 1 (19%) and grade 2 (8%) skin erythema, grade 1 (5%) and grade 2 (5%) alopecia, grade 1 (40%) fatigue, grade 1 (5%) and grade 2 (10%) conjunctivitis, grade 1 (10%) pain, grade 1 (5%) blurred vision, grade 1 (10%) headache, and grade 2 (5%) skin hyperpigmentation. One pts (1%) experienced grade 3 pain. There were no further grade 3 or higher acute toxicities. Registered late side effects include grade 1 (2%) and grade 2 (5%) alopecia, grade 1 (21%) fatigue, grade 1 (5%) and grade 2 (5%) headache, grade 1 (6% ) dizziness, grade 1 (3%) blurred vision, grade 1 (3%) and grade 2 (6%) pain, grade 1 (2%) dry eye, and grade 1 (5%) skin hyperpigmentation. Two pts (2%) experienced grade 3 pain. Two further pts (2%) experienced grade 3 optic neuropathy. There were no further grade 3 or higher late toxicities. During follow-up one pts (1%) with cavernous sinus meningioma experienced complete obstruction of intracavernous carotid artery with mild transient symptoms that resolved in few days and brain tissue ischemia detected at MRI (grade 2). Before irradiation this pts already had a meningioma-related near-complete obstruction of the intracavernous carotid artery and received a vascular surgery evaluation. Currently, absolute tumor control is 99%. Moreover, relief of symptoms recorded before irradiation occurred in 40% of pts.
Conclusion
PT is safe and effective treatment for pts with large skull base benign meningiomas.
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P11.29.B Risk factors associated with the presence of brain metastasis at the moment of diagnosis in non-small cell lung cancer patients. Retrospective case series

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Lung cancer is the second most frequent neoplasm worldwide and the leading cause of cancer death in both sexes. Furthermore, it is the most common origin of brain metastases. The aim of this study is to identify clinical, histological, and molecular variables associated with a higher risk of presenting brain metastases at the moment of diagnosis in patients with lung cancer.
Material and Methods
A single-center retrospective case series analysis of patients with a new diagnosis of lung cancer (from January 2015 to December 2018) was performed. A total of 723 total patients with a new diagnosis of non-small cell lung cancer (NSCLC) were identified. Only patients with a brain imaging study at the time of diagnosis were included in the analysis. Non-parametric statistical tests were used to compare patients with or without metastases at the moment of diagnosis. A uni- and multivariate analysis were performed to identify risk factors associated with the presence of brain metastases at NSCLC diagnosis. Statistical significance was considered when p<0.05.
Results
We included 135 patients with a new diagnosis of lung cancer and with brain imaging study at the time of diagnosis (mean age at diagnosis of 64.69 years [SD= 10.34]; 71.9% men). The most common histology was adenocarcinoma (67.1%) followed by squamous carcinoma (25.2%). Brain metastases were present in 40% of patients at diagnosis. No significant differences in clinical, histological and molecular variables was identified between patients with or without brain metastases. In any case, as expected, the survival analysis showed that brain metastasis at diagnosis was associated with a worse overall survival (Log-Rank test, p<0.01).The univariate analysis showed that presenting neurological symptoms (OR=19.5, p<0.0001 CI [7.895-47.65]), histology of adenocarcinoma (OR= 2.113, p<0.014 CI [1.160-3.849]) and the presence of vis ceral metastases (OR= 14.444, p<0.0001 CI [6.161-33.86]) were associated to the presence of brain metastases at diagnosis. The presence of metastases limited to the thorax (OR= 0.019, p<0.001 CI [0.003-0.146] was associated to be free of brain metastasis at NSCLC diagnosis. However, only neurological symptoms (OR= 20.290, p<0.0001 CI [4.953-83.118]), presenting visceral metastases (OR= 4.451, p<0.010 CI [1.458-13.777]) and/or metastases limited to the thorax (OR= 0.066, p<0.024 CI [0.006-0.010]) reached statistical significance in the multivariate analysis.
Conclusion
Neurological symptoms and the presence of visceral metastases are independent predictors or presenting brain metastasis at the moment of diagnosis in lung cancer patients. On the other hand, the presence of lung cancer disease confined in the thoracic cavity is associated with a lower risk to present brain metastasis
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P02.01.B The telomere maintenance mechanism spectrum and its dynamics in gliomas

alexandrossfakianakis shared this article with you from Inoreader
Abstract
The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation indicates alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. Here, we show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined in the dichotomy of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation and ATRX mutation. Moreover, we observed that a considerable proportion of gli omas lack both telomerase activity and ALT (Neither group). And this Neither group exhibited evidence of slow growth potential. From a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed but changes with glioma progression. Collectively, these results suggest that the TMM is a dynamic entity and that reflects the plasticity of the oncogenic biological status of tumor cells and that the TMM should be defined by the direct measurement of telomerase enzyme activity and evidence of ALT.
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P17.09.A Regorafenib and Re-irradiation: analysis of clinical outcomes and toxicities in patients with recurrent glioblastomas

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Glioblastoma is the most common and aggressive primary brain tumor in adults.The aggressiveness and poor prognosis related to this disease join to the limited available treatment options. The current standard of care involves surgical resection followed by concomitant radiotherapy and chemotherapy. At recurrence, no standard treatment exists and there are no guidelines to facilitate decisions in the recurrent setting. Available options include re-operation, re-irradiation, systemic therapy, alone or in combination. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. Regorafenib (Stivarga) is an inhibitor of several kinases involved in the mechanisms that regulate neoangiogenesis processes, through the inhibition vascular endothelial growth factor (VEGF) receptors and the modifications of the tumor microenvironment; specifically, Regorafenib binds an d stabilizes PSAT1 (phosphoserine aminotransferase 1). The dual regulatory mechanism underlying PSAT1-induced autophagy arrest accounts for the superior anti-GBM effect of Regorafenib compared with Temozolomide.
Material and Methods
15 patients with documented disease progression after surgery followed by RT and TMZ were assigned to receive regorafenib (REG) 160 mg once daily for the first 3 weeks of each 4-week cycle. All patients received prior radiation therapy (RT) to a median dose of 60 Gy (range 40.05 -60). Median time to retreatment after prior RT was 16 months (range 14-33). Tumor volumes ranged from 81.7 cm3 to 422.4 cm3 (CTV) and from 112.7 cm3 to 422.4 cm3 (PTV).3 patients (20%) received concomitant reirradiation with a radiation dose of 37.5 Gy in 15 fractions of 2.5 Gy.
Results
the median follow-up was 9.5 months (range 5-22). The overall survival and the progression-free survival rates were 53,8 %, and 46,6 % respectively at 2 years. In 53% the sympto ms were stable. Only one patient developed late toxicity: acute pancreatitis (Grade I) regressed on interruption of Regorafenib. No other neurological deficits occurred during follow-up. At last follow up 60% of patients were alive.
Conclusion
we report our experience with Regorafenib, administered in patients with rapid progression after the end of postoperative radio chemotherapy treatment. Regorafenib might be a new potential treatment option for recurrent glioblastoma: it was well tolerated also in cases of combined treatment with reirradiation and appeared effective. Other studies will be necessary to evaluate and confirm the role of Regorafenib in glioblastoma patients and the potential effectiveness of the combined therapeutic strategy: Regorafenib-reirradiation.
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KS05.5.A Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
In glioma patients, multimodal therapy and recurrent tumor result in local brain tissue changes, characterized by pathologic findings in structural MRI and metabolic PET images. Little is known about these different lesion types' impact on the local white matter fiber architecture and clinical outcome.
Patients and Methods
This study included data from 121 pretreated patients (median age, 52 years; ECOG, 01) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median time of 14 months (range, 1-214 months), post-therapeutic structural and metabolic findings were evaluated using anatomical MRI and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET acquired on a 3T hybrid PET/MR scanner. Local fiber densi ty was estimated from tractography based on highangular resolution diffusion-weighted imaging. A cohort of 121 healthy subjects selected from the 1000BRAINS study and matched for age, gender and education served as a control group.
Results
The median volume of resection cavities, contrast-enhancing regions, regions with pathologically increased FET uptake, and T2/FLAIR hyperintense regions amounted to 20.9, 7.9, 30.3, and 53.4 mL, respectively. Compared to the control group, the average local fiber density in these regions was significantly reduced (p<0.001). Resection cavities showed the highest reduction, followed by contrast-enhancing lesions and metabolically active tumors on FET PET (relative fiber density reduction, -87%, -65%, -55%, respectively). The local fiber density was inversely related (p=0.005) to the FET uptake in recurrent tumors. T2/FLAIR hyperintense lesions, either assigned to peritumoral edema in recurrent glioma or radiation-induced gliosis, had a c omparable impact on reducing fiber density (48% and 41%, respectively). The total fiber loss (average fiber loss multiplied by lesion volume) associated with contrast-enhancing lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on the general performance status of the patients (ECOG score).
Conclusions
Our results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance due to the larger volume affected.
Funding
Funded by the 1000BRAINS study (INM, Research Centre Juelich, Germany), Horizon 2020 (Grant No. 945539 (HBP SGA3; SC)), and Heinz Nixdorf Foundation.
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Favipiravir in patients with early mild-to-moderate COVID-19: a randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Despite vaccination, many remain vulnerable to COVID-19 and its complications. Oral antivirals to prevent COVID-19 progression are vital. Based upon perceived potency and clinical efficacy, favipiravir is widely used to treat COVID-19. Evidence from large randomized controlled trials (RCT) is lacking.
Methods
In this multicenter double-blinded placebo-controlled RCT, adults with early mild-to-moderate COVID-19 were 1:1 randomized to favipiravir or placebo. The study evaluated time to sustained clinical recovery (TT-SCR), COVID-19 progression, and cessation of viral shedding.
Results
Of 1187 analyzed patients across 40 centers, 83.3% were Hispanic, 89.0% unvaccinated, 70.3% SARS-CoV-2 seronegative, and 77.8% had risk factors for COVID-19 progression. The median time from symptom presentation and from positive test to randomization was three and two days, respectively. There was no difference in TT-SCR (median of 7 days for both groups; p = 0.80), COVID-19 progression [11 patients each (1.9% vs. 1.8%); p = 0.96], time to undetectable virus [median = 6 days, 95% CI (6-8) vs. 7 days, 95% CI (6-9)], or in undetectable virus by end of therapy (73.4% vs. 72.3%; p = 0.94). Outcomes were consistent across the analyzed sub-groups. Adverse events were observed in 13.8% and 14.8% of favipiravir-treated and placebo-treated subjects, respectively. Uric acid elevation was more frequent among favipiravir-treated subjects (19.9% vs. 2.8%).
Conclusions
Favipiravir was well tolerated but lacked efficacy in TT-SCR, progression to severe COVID-19, or cessation of viral shedding and should not be used to treat patients with COVID-19.
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