IMMU-27. LONG TERM STABILIZATION OF RECURRENT HIGH-GRADE GLIOMA WITH PD-1 INHIBITOR PEMBROLIZUMAB IN TWO CASES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi97-vi98
Author(s):  
Matthew Moldenhauer ◽  
Steven Du ◽  
Dan Fu ◽  
Joon Myung ◽  
Daniela Bota ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Case Reports ◽  
Single Agent ◽  
High Grade Glioma ◽  
High Grade ◽  
First Recurrence ◽  
One Year ◽  
Second Tumor ◽  
Tumor Debulking

Abstract INTRODUCTION Despite PD-1 inhibition having success in many cancers, it has uncertain effects in brain tumors. We report two cases of recurrent high-grade gliomas that have remained stable for over one year since starting pembrolizumab. CASE REPORTS Case 1: A 59-year-old male was diagnosed with glioblastoma (GBM) without MGMT methylation or IDH mutation in late 2018 after surgery. He received radiation and temozolomide (TMZ) followed by adjuvant TMZ before tumor progression. He underwent second tumor debulking with recurrent GBM on pathology with negative PD-L1 expression. He started carboplatin. Progression was noticed after 7 to 8 cycles. Pembrolizumab was added. Tumor was stabilized. Carboplatin was completed after total 12 cycles and the patient has continued single agent of pembrolizumab for more than one year with stable brain MRIs. The patient has survived for 24 months since recurrence and 30 months since diagnosis. Case 2: A 53-year-old male had a brain tumor discovered on MRI in 2012 and received no treatment until resection in 2014. In 2016, he underwent second tumor debulking and was diagnosed with anaplastic oligodendroglioma with negative PD-L1 expression. He received radiation followed by PCV regimen. 17 months since diagnosis, he had first tumor progression on PCV. TMZ was started. 22 months since diagnosis, bevacizumab was initiated due to further growth. 33 months since diagnosis, pembrolizumab was added due to new lesions after 12-months of bevacizumab therapy. His tumor was stabilized. Bevacizumab was eventually discontinued. He has continued single agent pembrolizumab for 6 months so far. His tumor has been stable for 22 months since starting pembrolizumab. Survival has been 38 months from first recurrence and 7 years since tissue diagnosis. DISCUSSION These cases demonstrate the potential effects of anti-PD-1 immunotherapy in stabilizing recurrent high-grade glioma with combination of other treatment agents followed by single agent as maintenance therapy.

Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.

1998 ◽  
Vol 16 (6) ◽  
pp. 2195-2201 ◽  
Author(s):  
B V Taylor ◽  
J C Buckner ◽  
T L Cascino ◽  
J R O'Fallon ◽  
P L Schaefer ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cognitive Performance ◽  
Mmse Score ◽  
Eastern Cooperative Oncology Group ◽  
High Grade Glioma ◽  
High Grade ◽  
Significant Deterioration ◽  
Term Survival ◽  
Number Of Patients

PURPOSE The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

scholarly journals HGG-12. A CASE OF PEDIATRIC SPINAL HIGH-GRADE GLIOMA WITH NTRK1 GENE FUSION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii346-iii346
Author(s):  
Tamaki Morisako ◽  
Daisuke Umebayashi ◽  
Kazuaki Kamata ◽  
Hiroyuki Yamamoto ◽  
Takumi Yamanaka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mr Imaging ◽  
Tumor Progression ◽  
Gene Fusion ◽  
High Grade Glioma ◽  
Gene Panel ◽  
Partial Resection ◽  
Low Grade ◽  
High Grade ◽  
Surgical Specimen

Abstract INTRODUCTION Tumors arising from the spinal cord are uncommon, especially high-grade tumors in pediatric patients. We report a case of high-grade glioma in the spinal cord harboring NTRK1 gene fusion, who received effective entrectinib therapy. CASE REPORT: A 5-year-old boy presented right hemiparesis and MR imaging revealed an intramedullary enhancing mass at the vertebral body level between C3 and Th1. He underwent microsurgical partial resection and the histological diagnosis was low-grade astrocytoma. After the first-line chemotherapy with vincristine and carboplatin, his right hemiparesis deteriorated and recurrent MR imaging showed growth of the tumor. He underwent microsurgical partial resection again and the histological examination was high-grade glioma with endothelial proliferation and necrosis. The chemoradiotherapy with temozolomide and focal irradiation of 50.4 Gy were given, and his neurological symptom slightly improved. One month later, he presented respiratory disturbance and required assisted ventilation with tracheostomy. MR imaging showed tumor progression invading upward to medulla oblongata. NTRK1 gene fusion was detected in the previous surgical specimen by a gene panel testing, and he received entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK). Since then, no tumor progression has been demonstrated for several months by MRI and he has been stable neurologically. CONCLUSION High-grade spinal cord tumors are rare and effective treatment strategies have not been addressed. Although the frequency of the gene fusion is very low in pediatric gliomas, identification of the driver gene aberration like in this case by a gene panel can provide potential targeted therapies for selected patients.

scholarly journals COT-21 EFFECT OF BEVACIZUMAB FOR PEDIATRIC HIGH GRADE GLIOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii44-ii44
Author(s):  
Yoshihiro Tsukamoto ◽  
Manabu Natsumeda ◽  
Masayasu Okada ◽  
Takeyoshi Eda ◽  
Junichi Yoshimura ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Therapeutic Agent ◽  
High Grade Glioma ◽  
Wound Complication ◽  
Symptomatic Improvement ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Rapid Progression ◽  
High Grade ◽  
Diffuse Midline Glioma ◽  
Pediatric High Grade Glioma

Abstract INTRODUCTION Bevacizumab (BEV) therapy has been used for pediatric high grade glioma,however the evidence and effectiveness are not understood yet. METHODS We report 7 cases (age 2 to 10 years old) of pediatric high grade glioma treated with BEV. One case is thalamic diffuse midline glioma H3K27 mutant (DMGH3K27M),one case is brain stem DMGH3K27M,one case is cerebellar high grade glioma,and 4 cases are diffuse intrinsic pontine glioma (DIPG) diagnosed clinically without biopsy. 5 cases were treated with BEV when diagnosed as recurrence after chemo-radiotherapy. One case was treated for rapid tumor progression during radiotherapy. One case was started on BEV therapy with radiation and concomitant temozolomide therapy. RESULT The number of times of BEV was 2 to 13 times (median 7 times). The period of BEV was 1 to 9 months (median 4 months). One case which was treated with BEV at rapid progression during radiation showed good response on imaging and improvement of symptoms. 4 of 5 cases who were treated at recurrence clinically showed mild symptomatic improvement. One case treated with BEV and radiotherapy initially was not evaluated. The adverse effects of BEV included wound complication of tracheostomy and rash. CONCLUSION BEV showed good response for rapid progression during radiotherapy,and mild response for recurrence cases. BEV is thought to be an effective therapeutic agent for pediatric HGG at recurrence and rapid tumor progression during radiotherapy.

scholarly journals P14.60 FET PET response upon radiochemotherapy followed by Tumor Treating Fields (TTFields) in a patient with progressive high-grade glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii81-iii81
Author(s):  
A F Keßler ◽  
J Weiland ◽  
T Linsenmann ◽  
R Ernestus ◽  
C Hagemann ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Treatment Response ◽  
High Grade Glioma ◽  
High Grade ◽  
Who Grade ◽  
Fet Pet ◽  
Tumor Treating Fields ◽  
Grade Ii ◽  
The Right ◽  
Pet Scans

Abstract BACKGROUND The addition of Tumor Treating Fields (TTFields) to the first-line therapy in glioblastoma (GBM) demonstrated significantly improved progression free survival, overall survival and longterm survival rates in the EF-14 phase 3 trial. However, responder analysis of patients with recurrent GBM (rGBM) treated with TTFields monotherapy (in the EF-11 trial) revealed delayed response monitored by MRI analysis. More recent data suggests that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET may add valuable information for monitoring therapy response of glioblastoma patients treated with TTFields. Here, we report on FET PET response in a patient with progressive anaplastic astrocytoma WHO grade III (AA) treated with TTFields in combination with temozolomide (TMZ) chemotherapy. METHODS We present a 38-year old patient with an initial diagnosis of a diffuse astrocytoma WHO grade II in 2011, and malignisation to an AA on progression. The treatment regimen included initially radio-chemotherapy (RCT) with TMZ. On further progression of the AA in 2017, TTFields were added to another 6 cycles of TMZ. Several FET PET scans for differentiation of tumor progression from treatment-related changes were performed over time. The definitive diagnosis (tumor progression and grading) was confirmed by histopathology after stereotactic biopsy (SB). RESULTS In 2012, the patient was first diagnosed with a low grade astrocytoma WHO grade II of the right frontal, temporal and parietal lobe including infiltration of thalamus and corpus was confirmed by SB, followed by irradiation. On progression in 2015, a FET PET Scan showed FET avidity in all tumor affected regions of the brain. SB confirmed an AA, while FET PET scans showed only a mild response in the temporoparietal region after 6 cycles of TMZ. In 2017, the next progression without further malignisation was confirmed by SB and treated RCT with 41.4 Gy and TMZ chemotherapy, followed by application of TTFields with an average usage rate of 85.7 % over 6 months. Thus, the TTFields adherence was well above the independent prognostic threshold of 75 %. No additional adverse events due to the combined therapy of TTFields and TMZ were observed. Due to a new contrast enhancing lesion in the right frontal lobe (10x7mm), another FET PET scan was performed 1.5 years later. In this scan, obtained after combined TTFields and RCT therapy a strong response regarding FET avidity was observed. CONCLUSION In summary, FET PET is able to add important additional information for evaluation of treatment response in high grade glioma patients, in particular for TTFields treated patients, while adding TTFields to radiochemotherapy might even enhance treatment response of high grade glioma. Further studies might elucidate the role of FET PET imaging for therapy monitoring in high grade glioma patients treated with TTFields.

Phase II trial of sunitinib malate in patients with temozolomide refractory recurrent high-grade glioma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2038-2038 ◽  
Author(s):  
B. Neyns ◽  
C. Chaskis ◽  
M. Dujardin ◽  
H. Everaert ◽  
J. Sadones ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cerebral Blood Volume ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
High Grade Glioma ◽  
Gene Copy ◽  
Dynamic Susceptibility ◽  
High Grade ◽  
Antiangiogenic Effect ◽  
Daily Dose

2038 Background: High-grade gliomas (HGG) are characterized by neo-angiogenesis. Sunitinib is a small molecule tyrosine kinase inhibitor that inhibits multiple receptors (including VEGFR, PDGFR, and c-Kit). We investigated sunitinib for the treatment of patients (pts) with temozolomide (TMZ) refractory recurrent HGG. Methods: Pts were recruited according to a 2-stage phase II design and received a daily dose of 37.5 mg sunitinib. T1 ± Gd and T2 weighted MRI images were obtained after 4 and 8 weeks of sunitinib and q8 weeks thereafter. We assessed the antiangiogenic effect by calculating the cerebral blood volume (CBV) and cerebral blood flow (CBF) from dynamic susceptibility (DSC) based perfusion MRI and determined the lesion-to-normal-white matter CBV (CBVLTN) and CBF (CBFLTN) ratios. Uptake of fluorinated fenyl-methyl-alanine within the CNS was assessed by PET at baseline and reassessed in responding pts. Results: 21 pts were enrolled (median age 43 [range 34–71]; M/F 15/6; KPS 90–80: 11 pts, KPS 70–60: 10 pts). All pts had PD following surgery, RT and TMZ. A total of 142 treatment weeks (range 2–84) were evaluated; 81% of the administrations were at the 37,5 mg-, 19% at the 25 mg dose level. Most frequent AEs were: skin toxicity (gr2, n = 1; gr 3, n = 1), fatigue (gr 2, n = 4), hypertension (gr 2, n = 3), diarrhea (gr 2, n = 2), mucositis (gr 3; n = 1), afebrile- (gr 2, n = 3) and febrile neutropenia (gr 3, n = 1; gr 4, n = 1), thrombocytopenia (gr 2, n = 4; gr 3, n = 1; gr 4, n = 1), and lymphocytopenia (gr 2, n = 2; gr 3, n = 4). Decrease in CBVLTN and CBFLTN was observed in 6/14 evaluable pts after 4 weeks of sunitinib, 5/19 evaluable pts had SD on T1±Gd after 8 weeks; one pt experienced a marked clinical improvement with a reduction in the tumor metabolism on PET. After a median follow-up of 11 months, median TTP and -OS are1,6 and 3,8 months respectively. Three pts with a secondary glioblastoma (age <40 year) had an objective PR when administered CCNU at PD under sunitinib (with a TTP of 2, 8 and +9 mths respectively). Characterization of the VEGFR, PDGFR, and Kit gene copy numbers and protein expression in the tumors is ongoing. Conclusions: Sunitinib at a continuous daily dose of 37.5 mg has a transient antiangiogenic effect in pts with recurrent HGG but is of insufficient clinical benefit to warrant further investigation as a single agent. [Table: see text]

Long-term follow-up of patients with follicular lymphoma (FL) receiving single agent rituximab at two different schedules in study SAKK 35/98

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8512-8512 ◽  
Author(s):  
M. E. Ghielmini ◽  
S. Hsu Schmitz ◽  
G. Martinelli ◽  
F. Peccatori ◽  
U. Hess ◽  
...  
Keyword(s):  
Cox Regression ◽  
Single Agent ◽  
Previous Treatment ◽  
Fc Receptor ◽  
Significant Prognostic Factor ◽  
Short Course ◽  
Long Term Follow Up ◽  
Second Tumor

8512 Background: In FL, rituximab as a single agent obtains a response rate of 50–70% with an EFS of 1–3 years depending on the population studied. Some patients respond to this treatment for a prolonged time, so we investigated, in a clinical trial, the proportion of long-term responders and the characteristics predicting long-term response. Methods: Between 1998 and 2002, chemotherapy naïve (n = 64) or pre-treated (n = 138) FL patients received 4 weekly doses of rituximab: those responding or with stable disease were randomized to either no further treatment (observation, n = 78) or 4 additional doses of rituximab given at 2 months intervals (consolidation, n = 73). Results: At a median follow up of 8.9 years, and with all living patients having been followed for at least 5 years, the median event-free survival (EFS: time until progression, relapse, second tumor or death) is 13 months for the observation and 24 months for the consolidation arm (p=0.0012). In the observation arm 10% had no event at 5-years, the figure dropping to 4% (3/78) at 8 years, while in the consolidation arm the EFS was 26% at 5 years and remained 18% (13/73) at 8 years. The only significant prognostic factor for EFS in a multivariate Cox regression was having received consolidation rituximab (hazard ratio = 0.58, CI = 0.44–0.87, p = 0.008), whereas being chemotherapy naïve, presenting with stage < IV and showing a VV phenotype at position 158 of the Fc receptor RIIIA were not any more significantly prognostic in this long term analysis, in contrast to previous data with shorter follow-up. No long-term toxicity from treatment was observed. There were 21 cases of second malignancy: 11 on observation, 10 receiving the consolidation arm. Conclusions: It appears that the EFS advantage of prolonged versus short course rituximab continues for many years after the end of treatment. This seems to hold true independently from previous treatment, stage or 158-phenotype of the Fc receptor. Patients treated with 8 doses of rituximab over 1 year have approximately 25% and 20% chance to remain in remission at 5 and 8 years respectively. [Table: see text]

ONC201 in previously irradiated pediatric H3 K27M-mutant glioma or newly diagnosed DIPG.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3619-3619
Author(s):  
Sharon L. Gardner ◽  
Carl Johannes Koschmann ◽  
Rohinton Tarapore ◽  
Jeffrey C. Allen ◽  
Wafik Tharwat Zaky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Single Agent ◽  
High Grade Glioma ◽  
Biologically Active ◽  
High Grade ◽  
Newly Diagnosed ◽  
Preclinical Models ◽  
Open Label ◽  
The Impact

3619 Background: ONC201 is a first-in-class DRD2 antagonist and ClpP agonist that has demonstrated promising activity in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 in recurrent H3 K27M-mutant glioma patients . The recommended phase 2 dose (RP2D) of 625mg ONC201 orally once a week has been established in adult patients as well tolerated and biologically active. ONC201 efficacy has been shown in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. We report results from the first Phase I pediatric clinical trial of ONC201. Methods: This open-label, multi-center trial for pediatric H3 K27M-mutant glioma or non-biopsied DIPG employed a 3+3 dose-escalation and dose-expansion design with 6 arms. Arms A and E, which have completed accrual, determined the RP2D of ONC201 using oral capsule and liquid formulations in post-radiation pediatric H3 K27M-mutant glioma patients ONC201, respectively. Arm B aims to determine the RP2D for ONC201 in combination with radiotherapy in patients with newly diagnosed DIPG. Arms C and D aim to measure intratumoral ONC201 concentrations in midline glioma patients and the impact of ONC201 on H3 K27M DNA levels in CSF, respectively. Arm F was recently opened to study ONC201 as a single agent in patients with progressive H3 K27M-mutant tumors (excluding DIPG and spinal cord tumors) following radiotherapy. After determining the RP2D, a dose-expansion cohort will evaluate the safety, radiographic response, and activity of ONC201. Results: An RP2D of weekly 625mg ONC201 scaled by body weight as a capsule or in liquid formulation was established in the primary endpoints of arms A, B and E alone or in combination with radiation, without incidence of dose-limiting toxicity (DLT). Pharmacokinetic profiles were similar to those observed in adults (T1/2: 8.4h; Tmax: 2.1h; Cmax: 2.3ug/mL; AUC0-tlast: 16.4ug/mL), with similar exposure across body weights. Conclusions: ONC201 was well tolerated without DLTs at the same adult RP2D scaled by body weight as monotherapy or in combination with radiotherapy in pediatric H3 K27M-mutant glioma patients. Further investigation of ONC201 to treat H3 K27M-mutant glioma and DIPG is warranted. Clinical trial information: NCT03416530 .

scholarly journals EP-1209: Long-term outcomes following conventionally fractionated stereotactic boost for high-grade glioma

2018 ◽  
Vol 127 ◽  
pp. S673 ◽  
Author(s):  
M. Repka ◽  
S. Lei ◽  
L. Campbell ◽  
S. Suy ◽  
J. Voyadzis ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
High Grade ◽  
Long Term Outcomes ◽  
Conventionally Fractionated
Sign in / Sign up

Export Citation Format

Share Document