Effect of temozolomide chronotherapy in patients with high-grade glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14525-e14525 ◽  
Author(s):  
Himachandana Atluri ◽  
Jian Li Campian ◽  
Grayson Talcott ◽  
Melissa Meyer ◽  
Emily Slat ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Biological Rhythms ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Well Being ◽  
Current Therapy ◽  
High Grade ◽  
Who Grade ◽  
Significant Difference ◽  
Morning Administration

e14525 Background: High grade gliomas (HGG) (the most common being glioblastoma) are the most common primary CNS malignancy in adults. Mainstay of therapy is surgical resection followed by concurrent radiation and temozolomide (TMZ) followed by adjuvant TMZ. Unfortunately, prognosis remains poor and optimization of current therapy is critical. Chronotherapy is defined as improvement in treatment outcomes by maximizing treatment efficacy and minimizing toxicity by administering medications in accordance with biological rhythms of the patient. In a mouse model, there was greater anti-tumor efficacy during morning administration of TMZ. This trial was designed to determine the feasibility and potential clinical impact of chrono-therapeutically administering TMZ in patients with HGG. Methods: Adult patients ( > 18 years) with HGG (WHO Grade III/IV) were eligible. Patients were screened and consented prior to initiation of monthly TMZ therapy. Eligible patients were randomized to TMZ in the morning (AM) before 10AM or in the evening (PM) after 8PM. Pill diaries were recorded for drug administration time and compliance. Fact-Br Quality of Life (QoL) surveys were administered to patients at the time of enrollment in the trial and at the end of treatment to measure differences in QoL in both groups. Circadian rhythm was recorded by Actiwatch. Adverse events (AE), overall survival (OS) and progression free survival (PFS) were measured for each group. Results: At the time of submission, a total of 28 patients were evaluated. 15 patients were in AM group and 13 in PM group. It is feasible for participants to take TMZ per study assignment. There was no significant difference in the QoL based on the Fact-Br dataset in the four main categories of physical well-being, social/family well-being, functional well-being and emotional well-being. The Friedman’s two-way nonparametric ANOVA tests were used to analyze the differences across time points. Cytopenias are a known adverse effect of TMZ. There was a trend towards worsening lymphocyte counts in the AM group compared to PM group, although not statistically significant. There was no statistical significance in PFS or OS in patients with newly diagnosed glioblastoma. Conclusions: Chronotherapy with TMZ is feasible. A trend of worsening lymphocyte counts is noted in AM treatment group compared to PM group but was not statistically significant. No difference in OS or PFS was noted, although sample size was too small to effectively assess this. A larger study will need to be conducted to effectively assess the effect of chronotherapy on survival. Clinical trial information: NCT02781792.

scholarly journals The Biological Behavior of High-Grade Glioma in H3K27M Mutant Circumscribed Midline Gliomas

2021 ◽  
Author(s):  
Hainan Li ◽  
Jieyun Tan ◽  
Mingyao Lai ◽  
Wendan Chen ◽  
Minting Liu ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Clinicopathological Characteristics ◽  
Biological Behavior ◽  
High Grade ◽  
Who Grade ◽  
Significant Difference ◽  
Prognostic Stratification ◽  
Grade 3 ◽  
Elder Adults ◽  
H3k27m Mutation

Abstract Purpose Due to the prognosis of circumscribed middle gliomas（CMGs）with H3K27M mutation is still unclear. This study explored the prognostic stratification of （CMGs） with H3K27M mutation.Methods: One hundred and sixty middle gliomas（MGs）were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and P53, and Sanger sequencing performed for IDH and H3 genes. The clinicopathological characteristics were reviewed and survival analysis performed.Results: 1. H3K27M mutation was associated with a poor prognosis (p = 0.00017) for brainstem gliomas, but not for thalamic gliomas (p = 0.3). In the elder adults (≥40 years), there was no correlation between H3K27M mutation and the prognosis for MGs (p = 0.49).2. For H3K27M mutant MGs, there was no difference in prognosis between diffuse midline gliomas (DMGs) and CMGs (p = 0.211), also between the CNS WHO grades.3. The prognosis of H3K27M mutant CMGs of CNS WHO grade 1 was worse than that of H3K27M wild-type CMGs (p = 0.0024), even worse than of DMGs without H3K27M mutation of CNS WHO grade 2(p = 0.0066). There was no significant difference in prognosis from DMGs with histological grades CNS WHO grade 3 and 4 (p = 0.46).Conclusions: The weight value of H3K27M affecting prognosis is affected by location and age. CMGs with H3K27M mutation have biological behavior similar to high-grade gliomas. It is recommended that Treatment management was referenced to high-grade glioma for CMGs with H3K27 mutation.

scholarly journals Radiotherapy versus combination radiotherapy-bevacizumab for the treatment of recurrent high-grade glioma: a systematic review

2021 ◽  
Author(s):  
Daniel P. Kulinich ◽  
John P. Sheppard ◽  
Thien Nguyen ◽  
Aditya M. Kondajji ◽  
Ansley Unterberger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Target Volume ◽  
Adult Brain ◽  
High Grade ◽  
Who Grade ◽  
Fractionated Radiotherapy ◽  
Meta Analyses

Abstract Background High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination of re-irradiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. Objective To assess clinical outcomes after reRT ± BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypofractionated radiosurgery (HFSRT), or fully fractionated radiotherapy (FFRT). Methods We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT ± BVZ. Cohorts were stratified by BVZ treatment status and re-irradiation modality (SRS, HFSRT, and FFRT). Outcome variables were overall survival (OS), progression-free survival (PFS), and radiation necrosis (RN). Results Data on 1399 patients was analyzed, with 954 patients receiving reRT alone and 445 patients receiving reRT + BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO grade, RT dosing, reRT fractionation regimen, time between primary and re-irradiation, and re-irradiation target volume, BVZ therapy was associated with significantly improved OS (2.51, 95% CI [0.11, 4.92] months, P = .041) but no significant improvement in PFS (1.40, 95% CI [− 0.36, 3.18] months, P = .099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 6.5%, P < .001). Conclusions Combination of reRT + BVZ may improve OS and reduce RN rates in recurrent HGG, but further controlled studies are needed to confirm these effects.

scholarly journals Phase III Study of Enzastaurin Compared With Lomustine in the Treatment of Recurrent Intracranial Glioblastoma

2010 ◽  
Vol 28 (7) ◽  
pp. 1168-1174 ◽  
Author(s):  
Wolfgang Wick ◽  
Vinay K. Puduvalli ◽  
Marc C. Chamberlain ◽  
Martin J. van den Bent ◽  
Antoine F. Carpentier ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Objective Response ◽  
Progression Free Survival ◽  
Well Being ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Serious Adverse Events ◽  
Who Grade

PurposeThis phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4).Patients and MethodsPatients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m2, day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025.ResultsEnrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P ≤ .001).ConclusionEnzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.

scholarly journals RADT-33. RADIOSURGERY VERSUS COMBINATION RADIOSURGERY-BEVACIZUMAB FOR THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMA: A SYSTEMATIC REVIEW

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii188-ii188
Author(s):  
Daniel Kulinich ◽  
John Sheppard ◽  
Thien Nguyen ◽  
Aditya Kondajji ◽  
Ansley Unterberger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Target Volume ◽  
Adult Brain ◽  
High Grade ◽  
Who Grade ◽  
Reported Data ◽  
Meta Analyses

Abstract BACKGROUND High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination re-radiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. OBJECTIVE To assess clinical outcomes after reRT±BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypo-fractionated (HFSRT), or fully fractionated RT (FSRT). METHODS We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT±BVZ. Cohorts were stratified by BVZ treatment status and reRT modality (SRS, HFSRT, and FSRT). Outcome variables were overall survival (OS), and progression-free survival (PFS). RESULTS 34 of 1,742 identified articles survived inclusion criteria (2%) and reported data on 954 patients receiving reRT alone and 445 patients receiving reRT+BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO Grade, RT dosing, reRT fractionation regimen, time between primary and reRT, and reRT target volume, BVZ therapy was associated with significantly improved OS (2.51 [0.11, 4.92] months, P=.041) but no significant improvement in PFS (1.40 [-0.36, 3.18] months, P=.099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 9.5%, P &lt; .001). CONCLUSIONS Combination reRT+BVZ may improve OS and reduce rates of RN in recurrent HGG, but further controlled studies are needed to confirm these effects.

scholarly journals Self-reported morbidities, nutritional characteristics, and associated factors in institutionalized and non-institutionalized older adults

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abdelhafid Benksim ◽  
Rachid Ait Addi ◽  
Elhassania Khalloufi ◽  
Aziz Habibi ◽  
Mohamed Cherkaoui
Keyword(s):  
Older Adults ◽  
Health Insurance ◽  
Nutritional Status ◽  
Statistical Significance ◽  
Well Being ◽  
Public Institution ◽  
Subjective Well Being ◽  
Number Of Children ◽  
Significant Difference ◽  
Nutritional Characteristics

Abstract Background As the world’s population ages and people live longer, it seems important to ensure that older people have a good quality of life and positive subjective well-being. The objective of this study is to determine socio-economic, health and nutritional characteristics of institutionalized and non-institutionalized elders in the province of Marrakech. Methods This study was conducted among 368 older adults in the province of Marrakech between March 2017 and June 2019. Of all participants, 180 older adults reside in a public institution and 188 of them live in their own homes. Data on health conditions, nutritional status, functional and socio-economic characteristics were collected. Data was analyzed using SPSS Statistics for Windows, Version 16.0. Statistical significance was set at p < 0.05. Results Institutionalized elders were illiterate (80.0%), had low incomes (95.5%), and unmarried (73.3%), they reported also no children (56.1%) and no health insurance (98.9%). Institutional residents suffered from malnutrition (22.2%), hearing impairments (35.6%) and severe edentulism (43.3%). There was no significant difference between both groups on daily activities and depression. A multivariate analysis identified a model with three significant variables associated with non-institutionalized elders: health insurance (P = 0.001; OR = 107.49), number of children (P = 0.001; OR = 1.74) and nutritional status (p = 0.001; OR = 3.853). Conclusions This study shows that the institutionalization of older adults is considerably induced by various factors such as nutritional problems, lack of health insurance and family structure. To mitigate the effects of this phenomenon, home care strategies and preventive actions should be implemented to delay the institutionalization of older adults and therefore keep them socially active in their own homes.

scholarly journals A descriptive analysis of end-of-life discussions for high-grade glioma patients

2021 ◽  
Author(s):  
Ai Chikada ◽  
Sayaka Takenouchi ◽  
Yoshiki Arakawa ◽  
Kazuko Nin
Keyword(s):  
End Of Life ◽  
Health Care Providers ◽  
Patient Participation ◽  
High Grade Glioma ◽  
Team Approach ◽  
High Grade ◽  
Care Providers ◽  
Patient Goals ◽  
Significant Difference ◽  
Eol Care

Abstract Background End-of-life discussions (EOLDs) in patients with high-grade glioma (HGG) have not been well described. Therefore, this study examined the appropriateness of timing and the extent of patient involvement in EOLDs and their impact on HGG patients. Methods A cross-sectional survey was conducted among 105 bereaved families of HGG patients at a university hospital in Japan between July and August 2019. Fisher’s exact test and the Wilcoxon rank-sum test were used to assess the association between patient participation in EOLDs and their outcomes. Results In total, 77 questionnaires were returned (response rate 73%), of which 20 respondents replied with refusal documents. Overall, 31/57 (54%) participated in EOLDs at least once in acute hospital settings, and a significant difference was observed between participating and nonparticipating groups in communicating the patient’s wishes for EOL care to the family (48% vs 8%, P = .001). Moreover, &gt;80% of respondents indicated that the initiation of EOLDs during the early diagnosis period with patients and families was appropriate. Most EOLDs were provided by neurosurgeons (96%), and other health care providers rarely participated. Additionally, patient goals and priorities were discussed in only 28% of the EOLDs. Patient participation in EOLDs was not associated with the quality of EOL care and a good death. Conclusions Although participation in EOLDs is relatively challenging for HGG patients, this study showed that participation in EOLDs may enable patients to express their wishes regarding EOL care. It is important to initiate EOLDs early on through an interdisciplinary team approach while respecting patient goals and priorities.

scholarly journals CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii34
Author(s):  
Macarena De La Fuente ◽  
Tulay Koru-Sengul ◽  
Deborah Heros ◽  
Feng Miao ◽  
Alain Fernandez Marrero ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Rna Sequencing ◽  
Tumor Antigens ◽  
High Grade Glioma ◽  
Treatment Discontinuation ◽  
Sequencing Analysis ◽  
High Grade ◽  
Who Grade ◽  
Cytokine Levels ◽  
Grade 3

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.

CTNI-22. A PHASE 0/1 ‘TRIGGER’ TRIAL OF RIBOCICLIB PLUS EVEROLIMUS IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi64-vi64
Author(s):  
Nader Sanai ◽  
An-Chi Tien ◽  
Jun Jiang ◽  
Yu-Wei Chang ◽  
Chelsea Pennington-Krygier ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
High Grade ◽  
Mtor Inhibition ◽  
Who Grade ◽  
Expansion Phase ◽  
Pik3ca Mutations ◽  
Pten Loss ◽  
Drug Concentrations ◽  
Phase 0 ◽  
Unbound Concentration

Abstract BACKGROUND mTOR activation is a mechanism of resistance in CDK4/6 targeting. We evaluated tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of combined CDK4/6 and mTOR inhibition in recurrent high-grade glioma (HGG) patients. METHODS Recurrent HGG patients with (1) intact RB, (2) CDKN2A/B deletion or CDK4/6 amplification, and (3) PTEN loss or PIK3CA mutations receive five days of presurgical ribociclib plus everolimus prior to resection at 2, 8 or 24 hours after the final dose. Beginning at 400mg QD ribociclib plus 2.5mg QD everolimus, six dose-escalations summit at 600mg QD plus 60mg QW. Gadolinium [Gd]-enhancing and nonenhancing tumor regions, CSF, and plasma are collected. Total and unbound drug concentrations are determined using validated LC-MS/MS methods. RB and S6 phosphorylation are compared to matched archival tissue. To select patients for a therapeutic expansion phase of combined drug therapy, the protocol includes a PK ‘trigger’ (i.e., for each drug, unbound concentration in Gd-nonenhancing tumor &gt; 5-fold biochemical IC50) and a PD ‘trigger’ (i.e., for each tumor, &gt; 30% decrease in pRB and pS6). RESULTS 21 patients with WHO Grade III (n=2) and IV (n=19) gliomas were enrolled into the Phase 0 component of the study. No dose-limiting toxicities were observed. In Gd-nonenhancing tumor regions, the median unbound concentration of ribociclib was 719 nM, whereas unbound everolimus tumor concentrations were undetectable. Across all dose-levels, 62% (13/21) and 22% (5/21) of tumors demonstrated decreased tumor RB and S6 phosphorylation, respectively. Tumor proliferation (MIB-1) was decreased in 67% (14/21) of all patients. No patients qualified for the therapeutic expansion phase. CONCLUSION In adult HGG, ribociclib achieves pharmacologically-relevant concentrations in Gd-nonenhancing tumor whereas everolimus exhibits no meaningful tumor penetration. These findings support further clinical development of ribociclib, but not everolimus, for the treatment of high-grade glioma patients.

scholarly journals High-grade glioma with anterior skull base erosion and intranasal extension: case report

2017 ◽  
Vol 126 (5) ◽  
pp. 1484-1487 ◽  
Author(s):  
Matthew T. Stib ◽  
Michael Johnson ◽  
Alan Siu ◽  
M. Isabel Almira-Suarez ◽  
Zachary Litvack ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Skull Base ◽  
Radiation Treatment ◽  
High Grade Glioma ◽  
Brain Parenchyma ◽  
Anterior Skull Base ◽  
High Grade ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

The authors describe the case of a large WHO Grade III anaplastic oligoastrocytoma extending through the anterior skull base and into the right nasal cavity and sinuses. Glial neoplasms are typically confined to the intracranial compartment within the brain parenchyma and rarely extend into the nasal cavity without prior surgical or radiation therapy. This 42-year-old woman presented with progressive headaches and sinus congestion. MR imaging findings revealed a large intracranial lesion with intranasal extension. Endoscopic nasal biopsy revealed pathology consistent with an infiltrating glioma. The patient subsequently underwent a combined transcranial/endonasal endoscopic approach for resection of this lesion. Pathological diagnosis revealed a WHO Grade III oligoastrocytoma. This report reviews the mechanisms of extradural glioma extension. To the authors' knowledge, it is the second report of a high-grade glioma exhibiting nasal extension without prior surgical or radiation treatment.

scholarly journals An Observational Study of the First Experience with Bevacizumab for the Treatment of Patients with Recurrent High-Grade Glioma in Two Belgian University Hospitals

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Huylebrouck ◽  
S. Lv ◽  
J. Duerinck ◽  
A. Van Binst ◽  
I. Salmon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Response ◽  
Metabolic Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
University Hospitals ◽  
Phase Ii Trials ◽  
Antiangiogenic Effect

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials.Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals.Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1–31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7–39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment.Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

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