11 research outputs found
The risk of secondary malignancies over 30 years after the treatment of non‐Hodgkin lymphoma
No full textComparison of the cell lines used in meningoma research
No full textmanuscriptBackground: Immortal cell lines and cell lines derived from operative specimens transplanted into animal models are used in meningioma research. We address two criticisms of the mouse xenograft flank tumor model: Why are tumor induction rates derived from operative specimens low and inconsistent? Are flank tumors meningiomas? Methods: Meningioma cell cultures were processed for Giemsa-band karyotyping and flow cytometry. Mouse flank tumors induced subcutaneously were analyzed microscopically, immunohistochemically, and ultrastructurally. G-band studies identified meningiomas with simple karyotype (≤ 1 chromosomal abnormality) or complex karyotype (multiple chromosomal abnormalities). Results: Cell cultures with complex karyotypes (IOMM-Lee, CH-157 MN, 2 operative specimens) grew rapidly in vitro and induced tumors in 49/50 (98%) animals. Meningioma cell cultures with simple karyotypes grew slowly in vitro and showed small, non-growing tumors in mouse flanks (10/10). Meningioma flank tumors were vimentin positive with ultrastructural features consistent with meningiomas. Cell cultures with complex karyotypes grew faster in cell culture and consistently induced flank tumors, unlike meningiomas with simple karyotypes. Conclusions: Meningioma cell lines transplanted into flanks of nude mice exhibit microscopic, immunohistochemical, and ultrastructural features of meningiomas. The ease of monitoring tumor growth in the subcutaneous mouse flank model is its primary advantage, although we recognize an intracranial location is more biologically desirable
The Early Social Cognition Inventory (ESCI): An examination of its psychometric properties from birth to 47 months.
No full textSocial cognition refers to a broad range of cognitive processes and skills that allow individuals to interact with and understand others, including a variety of skills from infancy through preschool and beyond, e.g., joint attention, imitation, and belief understanding. However, no measures examine socio-cognitive development from birth through preschool. Current test batteries and parent-report measures focus either on infancy, or toddlerhood through preschool (and beyond). We report six studies in which we developed and tested a new 21-item parent-report measure of social cognition targeting 0-47 months: the Early Social Cognition Inventory (ESCI). Study 1 (N = 295) revealed the ESCI has excellent internal reliability, and a two-factor structure capturing social cognition and age. Study 2 (N = 605) also showed excellent internal reliability and confirmed the two-factor structure. Study 3 (N = 84) found a medium correlation between the ESCI and a researcher-administered social cognition task battery. Study 4 (N = 46) found strong 1-month test-retest reliability. Study 5 found longitudinal stability (6 months: N = 140; 12 months: N = 39), and inter-observer reliability between parents (N = 36) was good, and children's scores increased significantly over 6 and 12 months. Study 6 showed the ESCI was internally reliable within countries (Australia, Canada, United Kingdom, United States, Trinidad and Tobago); parent ethnicity; parent education; and age groups from 4-39 months. ESCI scores positively correlated with household income (UK); children with siblings had higher scores; and Australian parents reported lower scores than American, British, and Canadian parents. [Abstract copyright: © 2021. The Author(s).
A Randomized Phase II Study of Everolimus in Combination With Chemoradiation in Newly Diagnosed Glioblastoma: Results of NRG Oncology RTOG 0913
No full textBackground This phase II study was designed to determine the efficacy of the mammalian target of rapamycin (mTOR) inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma. Methods Patients were randomized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS) and treatment-related toxicities. Results A total of 171 patients were randomized and deemed eligible for this study. Patients randomized to receive everolimus experienced a significant increase in both grade 4 toxicities, including lymphopenia and thrombocytopenia, and treatment-related deaths. There was no significant difference in PFS between patients randomized to everolimus compared with control (median PFS time: 8.2 vs 10.2 mo, respectively; P = 0.79). OS for patients randomized to receive everolimus was inferior to that for control patients (median survival time: 16.5 vs 21.2 mo, respectively; P = 0.008). A similar trend was observed in both O 6-methylguanine-DNA-methyltransferase promoter hypermethylated and unmethylated tumors. Conclusion Combining everolimus with conventional chemoradiation leads to increased treatment-related toxicities and does not improve PFS in patients with newly diagnosed glioblastoma. Although the median survival time in patients receiving everolimus was comparable to contemporary studies, it was inferior to the control in this randomized study
NRG/RTOG 1122: A phase 2, double‐blinded, placebo‐controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma
No full textGermline polymorphisms in MGMT associated with temozolomide-related myelotoxicity risk in patients with glioblastoma treated on NRG Oncology/RTOG 0825
No full textBACKGROUND: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma. METHODS: Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity. RESULTS: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 stopped treatment due to toxicity. Among those who continued therapy (n = 26), 11 experienced myelotoxicity again. The final multivariable clinical factor model included treatment arm, gender, and anticonvulsant status and had low prediction accuracy (area under the curve [AUC] = 0.672). The final extended risk prediction model including four polymorphisms in MGMT had better prediction (AUC = 0.827). Receiving combination chemotherapy (OR, 1.82; 95% CI, 1.02–3.27) and being female (OR, 4.45; 95% CI, 2.45–8.08) significantly increased myelotoxicity risk. For each additional minor allele in the polymorphisms, the risk increased by 64% (OR, 1.64; 95% CI, 1.43–1.89). CONCLUSIONS: Myelotoxicity during concurrent chemoradiation with temozolomide is an uncommon but serious event, often leading to treatment cessation. Successful prediction of toxicity may lead to more cost-effective individualized monitoring of at-risk subjects. The addition of genetic factors greatly enhanced our ability to predict toxicity among a group of similarly treated glioblastoma patients
Influence of Residual Disease Following Surgical Resection in Newly Diagnosed Glioblastoma on Clinical, Neurocognitive, and Patient Reported Outcomes
No full textInfluence of Residual Disease Following Surgical Resection in Newly Diagnosed Glioblastoma on Clinical, Neurocognitive, and Patient Reported Outcomes
No full textBACKGROUND: The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown.
OBJECTIVE: To examine these uncertainties.
METHODS: NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan-Meier method.
RESULTS: A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test-Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures.
CONCLUSION: STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients
Clinical and Genetic Markers of Vascular Toxicity in Glioblastoma Patients: Insights From Nrg Oncology Rtog-0825
No full textBackground: Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment.
Methods: In total, 591 non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N = 367) by occurrence of thrombosis or hypertension (grade ≥ 2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the clinical model as a single nucleotide polymorphism (SNP)-dose-effect variable to produce the final genetic models.
Results: Thrombosis and hypertension were experienced by 62 (11%) and 59 (10%) patients, respectively. Patients who experienced hypertension displayed improved survival over those without hypertension (median overall survival: 25.72 vs. 15.47 months, p = 0.002). The genetic model of thrombosis included corticosteroid use (odds ratio [OR]: 7.13, p = 0.02), absolute neutrophil count (OR: 1.008, p = 0.19), body surface area (OR: 18.87, p = 0.0008), and SNP-dose effect (3 variants; OR: 3.79, p \u3c 0.0001). The genetic model of hypertension included bevacizumab use (OR: 0.97, p = 0.95) and the SNP-dose effect (6 variants; OR: 4.44, p \u3c 0.0001).
Conclusions: In this study, germline variants were superior in predicting hypertension than clinical variables alone. Additionally, corticosteroid use was a considerable risk factor for thrombosis. Future investigations should confirm the hazard of corticosteroid use on thrombosis and the impact of bevacizumab in other malignancies after accounting for the genetic risk of hypertension
Short delay in initiation of radiotherapy for patients with glioblastoma-effect of concurrent chemotherapy: a secondary analysis from the NRG Oncology/Radiation Therapy Oncology Group database
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