Cycles Of Adjuvant Temozolomide Research Articles

Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis.

Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes. Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7-12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS. From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group. Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

A Phase II Trial of Concurrent Sunitinib, Temozolomide and Radiation Therapy Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients with an Unmethylated MGMT Gene Promoter

<h3>Purpose/Objective(s)</h3> Despite advances in treatment modalities, the overall prognosis of Glioblastoma remains dismal, particularly for patients with unmethylated MGMT promoter. In this phase II trial, we tested for the first time the combination of Sunitinib with radiotherapy and Temozolomide in newly diagnosed MGMT unmethylated Glioblastoma patients. We hypothesized that this combination therapy would be safe and yield superior survival outcomes than the current standard of care for MGMT unmethylated Glioblastoma patients. <h3>Materials/Methods</h3> 37 patients diagnosed with WHO-Grade IV Glioblastoma and unmethylated MGMT promoter, age 18-70 and KPS ≥70 were eligible from two institutions. Patients received 12.5 mg of daily Sunitinib for 7 days, followed by concurrent chemoradiation and 12.5 mg Sunitinib x6 weeks, then adjuvant Temozolomide x6 cycles. Primary objective was progression-free-survival (PFS) as per RANO criteria, secondary objectives were overall survival (OS), safety and Neutrophil-to-Lymphocyte ratio (NLR). <h3>Results</h3> Median follow-up time was 15.3 months (95% CI: 13.8-19.4). Median PFS was 7.15 months (95% CI: 5.4-10.5 months) and 6-month PFS was 54.0%. Median OS was 15.0 months (95% CI: 13.8-19.4 months) and 2-year OS was 17.1%. Having received >3 cycles of adjuvant Temozolomide and surgery at progression significantly predicted for better OS with hazard ratios of 0.32 (p=0.017) and 0.46 (p=0.049) respectively, whereas age >65 and post-treatment NLR>6 predicted for worse OS with hazard ratios of 3.92 (p=0.037) and 2.64 (p = 0.021) respectively. Grade ≥3 thrombocytopenia occurred in 22.9%, grade ≥3 neutropenia in 20% and grade ≥3 thromboembolic events in 14.3% of patients. There were no grade 5 events. <h3>Conclusion</h3> Addition of Sunitinib to RT and Temozolomide was safe and survival outcomes are promising compared to the standard of care for GBM patients with unmethylated MGMT promoter status.

A new approach to delineating clinical target volume for radiotherapy of glioblastoma: A phase II trial.

No consensus has currently been reached regarding the optimal radiation volume for radiotherapy of glioblastoma. Here, we have proposed a new delineation approach to delineating clinical target volume based on the relationship between the growth patterns of glioblastoma and neural pathways. Its safety and efficacy were evaluated in a phase II clinical trial. A total of 69 patients with histologically confirmed glioblastoma were enrolled. All patients underwent tumor resection, followed by focal radiotherapy and concomitant temozolomide (TMZ), and then received six cycles of adjuvant TMZ. The gross tumor volume (GTV) was defined as the surgical resection cavity plus any residual enhancing tumor, on contrast enhanced T1-weighted MRI. The clinical target volume (CTV) was delineated through our new approach. The median recurrence-free survival (RFS) and overall survival (OS) were 11.4 months and 18.2 months, which were better than the previous reports. Relapse was found in 47 patients, of whom 41 patients (87.2%) failed in central, two patients (4.3%) failed in field, and four patients (8.5%) failed in distance. No marginal recurrence was found. Our regimen showed a trend of lower rates of marginal recurrence, and the brain volume of high-dose radiation fields in our regimen was similar to that of EORTC (p = 0.257). We have proposed a novel method for the delineation of clinical target volume by referencing the nerve fiber bundles for radiotherapy of glioblastoma. The results of the present phase II clinical trial suggest that this approach may be feasible and effective.

Can Extended Chemotherapy Improve Glioblastoma Outcomes? A Retrospective Analysis of Survival in Real-World Patients.

Standard treatment for glioblastoma multiforme (GBM) is surgery followed by radiotherapy plus concurrent chemotherapy with daily temozolomide (TMZ), and six subsequent TMZ 5/28-day cycles. Research has focused on identifying more effective alternatives to the current protocol, including extension of the number of adjuvant TMZ cycles. We performed a retrospective analysis of all GBM patients treated in our hospital (160 patients, 2011–2020). Median follow-up was 16.0 months. Analysis of prognostic factors was performed with a particular focus on the benefit of extending TMZ chemotherapy. Improved survival correlated with younger age, female gender, good performance status, absence of cognitive dysfunctions, no steroid use, and total tumor resection. Median progression-free survival (PFS) was 12 months and median overall survival (OS) was 20.0 months for the entire cohort. Median OS by adjuvant TMZ was 10.0 months if no adjuvant chemotherapy given (group 0), 15.0 months for patients that did not complete six TMZ cycles (group A), 24.0 months for those that did (group B), and 29.0 months for patients having received more than six cycles (group C) (p < 0.0001). At the three-year mark, 15.9% patients were alive in group A, 24.4% in group B and 38.1% in group C. Carefully selected GBM patients may derive benefit from extending the standard adjuvant chemotherapy beyond six TMZ cycles, but more data is required.

The use of temozolomide in a patient with chronic thrombocytopenia: A case report

Thrombocytopenia is commonly experienced with Temozolomide (TMZ) during treatment for Glioblastoma (GBM). With the increasing prevalence of obesity and associated Non-Alcoholic Steatohepatitis (NASH) worldwide, chronic thrombocytopenia is becoming increasingly common, and necessitates modifications in the standard of care treatment regimen for GBM. To date, no guidelines are present addressing this dilemma. We present a case of a patient with newly diagnosed GBM and NASH-associated cirrhosis with chronic thrombocytopenia and baseline platelet count of approximately 70,000/ μL. She received brain radiation alone followed by 6 cycles of adjuvant TMZ, initially with a 50% dose reduction and subsequent dose increase based on tolerability and stability of platelet counts. This case demonstrates the relative safety of TMZ in a patient whose platelets are affected by liver disease as opposed to bone marrow insufficiency.

Phase IB trial of pegylated arginine deiminase (ADI-PEG 20) plus radiotherapy and temozolomide in patients with newly diagnosed glioblastoma.

2057 Background: ADI-PEG 20 exploits the different metabolic ability for synthesizing arginine (Arg) between normal and neoplastic cells to reduce tumor cell growth. Preclinical and clinical studies have shown that cancers which are either Arg auxotrophic, with silencing of argininosuccinate synthetase ( ASS1), or Arg non-auxotrophic, respond to ADI-PEG 20 monotherapy or ADI-PEG 20 combined with various chemotherapies, respectively. ADI-PEG 20 has shown efficacy as monotherapy in ASS1 negative mouse glioblastoma (GBM) models and the combination of ADI-PEG 20 with temozolomide (TMZ) and with radiation (RT) in both ASS1 negative and ASS1 positive mouse GBM models. Based on these rationales, ADI-PEG 20 was added to standard RT + TMZ in patients with newly diagnosed GBM. This is the first clinical trial combining ADI-PEG 20 with RT. Methods: This phase IB, open-label, single-arm, standard 3+3 dose escalation with a recommended phase 2 dose (RP2D) expansion study (NCT04587830) was initiated in June 2020. Weekly ADI-PEG 20 is added to concurrent RT + TMZ and to 6 cycles of adjuvant TMZ (Stupp protocol). ADI-PEG 20 could be continued for up to 2 years. RANO criteria are used to determine response by evaluating MRI at 1, 3 and 6 months after RT, and every 3 months thereafter. Major eligibility criteria are age 20-75 years with newly diagnosed, histologically confirmed GBM with Karnofsky performance status ≥ 60. Endpoints include safety, pharmacodynamics, immunogenicity, progression free survival (PFS) and overall survival (OS). Results: Cohorts 1 (18 mg/m2) and 2 (36 mg/m2) were completed without dose limiting toxicity (DLT). Enrollment to cohort 3 (RP2D phase, 36 mg/m2) is ongoing with 23/26 patients. The major adverse events (AEs) were fatigue (52%), constipation (39%) and neutrophil decrease (39%). Dermatologic or allergic reactions occurred in 12/23 (52%), and all were grade 1-2 except for anaphylactic shock in 1 and vasculitis/rash in 1. 22/23 are alive, with median PFS = 9.5 months. The first 6 study patients are all alive for at least 11 months, with the longest at 1.5 years. 10 are off treatment due to progressive disease in 6, severe AE in 2, consent withdrawal in 1, and medical decision in 1. Mean peripheral blood Arg levels were suppressed ( &lt; 10uM) for 4-6 weeks in most subjects, with a reciprocal elevation of citrulline levels. Anti-ADI-PEG 20 antibodies tended to increase as peripheral Arg levels increased. Conclusions: The addition of ADI-PEG 20 to RT + TMX was safe, and no DLT was observed. The RP2D of ADI-PEG 20 was determined to be 36mg/m2. AEs were those typically seen with RT + TMZ, with perhaps an increase in rash reported with the addition of ADI-PEG 20. Anaphylaxis and vasculitis were seen (1 subject with each), and have been observed previously with ADI-PEG 20. The preliminary OS data are encouraging. A registration phase 2/3 trial of this triplet is being considered. Clinical trial information: NCT04587830.

Reproducibility of outcomes in sequential trials using CMV-targeted dendritic cell vaccination for glioblastoma.

2005 Background: Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. Methods: To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with newly diagnosed GBM eligible to receive standard of care resection and adjuvant radiation therapy and temozolomide chemotherapy. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. Results: Our initial study was the phase II ATTAC study (NCT00639639; total n = 12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning ( P = 0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR = 0.820, P = 0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n = 24, unpulsed DC n = 19; 24h, P = 0.031 and 48h, P = 0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td ( P = 0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). Conclusions: We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM. Clinical trial information: NCT00639639, NCT02366728.

Efficacy and safety of extended adjuvant temozolomide compared to standard adjuvant temozolomide in glioblastoma: Updated systematic review and meta-analysis.

This study was designed to compare outcomes of extended adjuvant temozolomide (TMZ) vs standard adjuvant TMZ following radiotherapy (RT) plus concurrent TMZ in newly diagnosed glioblastoma. This systematic review and meta-analysis was carried out in accordance with Cochrane methodology. Only prospective clinical trials randomly assigning adults with newly diagnosed glioblastoma after concurrent RT/TMZ to 6 cycles of adjuvant TMZ (control arm) or extended (>6 cycles) adjuvant TMZ (experimental arm) were eligible. Primary outcome of interest was overall survival, while progression-free survival and toxicity were secondary endpoints. Hazard ratio (HR) for progression and death with corresponding 95% confidence interval (CI) were computed for individual primary study and pooled using random-effects model. Toxicity was defined as proportion of patients with ≥grade 3 hematologic toxicity and expressed as risk ratio (RR) with 95% CI. Any P-value <.05 was considered statistically significant. Systematic literature review identified five randomized controlled trials comparing standard (6 cycles) vs extended (>6 cycles) adjuvant TMZ in newly diagnosed glioblastoma. Outcome data could be extracted from 358 patients from four primary studies. Extended adjuvant TMZ was not associated with statistically significant reduction in the risk of progression (HR = 0.82, 95% CI: 0.61-1.10; P = .18) or death (HR = 0.87, 95% CI:0.60-1.27; P = .48) compared to standard adjuvant TMZ. Grade ≥3 hematologic toxicity though somewhat higher with extended adjuvant TMZ, was not significantly different between the two arms (RR = 2.01, 95% CI: 0.83-4.87; P = .12). There is low-certainty evidence that extended adjuvant TMZ is not associated with significant survival benefit or increased hematologic toxicity in unselected patients with newly diagnosed glioblastoma compared to standard adjuvant TMZ.

Glioblastoma with concomitant moyamoya vasculopathy in neurofibromatosis type 1: illustrative case.

BACKGROUNDIn a case of concurrent glioblastoma and moyamoya vasculopathy, it is arduous to safely perform surgery because the brain is highly vulnerable and collaterals are sometimes well developed. In addition, radiotherapy carries a risk of aggravating moyamoya vasculopathy, and chemotherapeutic agents also have a risk of interfering with collateral development.OBSERVATIONSA 48-year-old woman with neurofibromatosis type 1 was admitted because of left hemiparesis and hemispatial neglect. Brain imaging studies revealed a large mass with peripheral enhancement in the right frontal lobe and occlusion of the bilateral middle cerebral arteries with an abnormal vascular network at the base of the brain. Total tumor resection was performed, and the pathological diagnosis was isocitrate dehydrogenase–mutant glioblastoma. Radiotherapy with a total dose of 60 Gy was delivered with concurrent temozolomide, and thereafter six cycles of adjuvant temozolomide were given. Progression of moyamoya vasculopathy without symptoms was observed after the completion of each of radiotherapy and adjuvant temozolomide.LESSONSThe authors present the first adult case of glioblastoma with moyamoya vasculopathy. Careful consideration and attention should be given throughout treatment to avoiding moyamoya vasculopathy–related ischemic and hemorrhagic events. Although the patient did not exhibit neurological deterioration, progression of moyamoya vasculopathy occurred early after radiotherapy and continued thereafter.

Tumor growth, angiogenesis, and invasion as clinical hallmarks of glioblastoma: A case report

The clinical hallmarks of tumor growth, angiogenesis, and invasion were identified in a patient with isocitrate dehydrogenase-1 wild-type glioblastoma at initial diagnosis and management issues were examined. The head magnetic resonance imaging (MRI) showed multiple solid and cystic contrast enhancements in the rostral portion of the tumor located within the left motor gyrus and the adjacent brain. Extensive tumor invasion was noted along the left corticospinal tract extending into the cerebral peduncle and pons. After an open craniotomy for tissue biopsy, the patient underwent external beam radiotherapy and concomitant temozolomide, and his motor deficit was stabilized with concurrent bevacizumab infusion while dexamethasone was weaned off. After two cycles of adjuvant temozolomide, the patient experienced worsening motor deficit in the right hand. A repeat gadolinium-enhanced head MRI revealed increased fluid-attenuated inversion recovery hyperintensity in the left cerebral peduncle indicating tumor progression. This case illustrates the extensive invasion from a glioblastoma that cannot be adequately quantified or effectively treated. A wider margin of radiation may be needed to cover microscopic and infiltrative tumor cells. The early use of bevacizumab can also reverse neurological deficits and obviate the long-term use of dexamethasone and insulin in this patient. This study was approved by the Institutional Review Board at Dana Farber Cancer Institute #12-519 onMay 5, 2020.

INNV-21. COMPLETE RESPONSE TO ADJUVANT TEPOTINIB IN A PATIENT WITH NEWLY DIAGNOSED DISSEMINATED GLIOBLASTOMA (GBM) HARBORING MET AMPLIFICATION

Abstract MET oncogene encodes a receptor-tyrosine-kinase which drives cell proliferation, invasion and angiogenesis in a number of solid cancers including GBM where the incidence of MET amplification is 2-5%. Tepotinib is a highly selective blood-brain-barrier penetrant oral c-MET inhibitor recently FDA approved for MET-exon-14 altered non-small cell lung cancer (NSCLC). Here, we report complete radiographic response to tepotinib in a patient with newly-diagnosed disseminated GBM harboring MET amplification. A 29-years-old male presented with progressive headache. MRI brain showed a large heterogeneously enhancing intraventricular mass with epicenter in the right lateral ventricular trigone and enhancing nodules in bilateral cerebellum. MRI spine showed multifocal enhancement along the periphery of the cervicothoracic spinal cord and cauda equina concerning for leptomeningeal disease. He underwent right temporal lobectomy and subtotal resection of the mass. His KPS was 90 post-surgery due to dizziness. Pathology was consistent with GBM, IDH wild-type, MGMT-unmethylated and MET amplification at 7q31.2. He completed proton craniospinal irradiation at 3600cGy followed by boost to the tumor bed at 2400cGy without concurrent temozolomide (TMZ) due to the large radiation field. He completed two cycles of adjuvant TMZ which was put on hold due to myelosuppression. He subsequently started tepotinib monotherapy at 1000mg daily obtained on a compassionate IND. MRIs after one month of therapy showed resolution of areas of enhancement in the brain and spine. He had grade 1 creatinine elevation and abdominal discomfort and dose was reduced to 500mg daily after two cycles. Nineteen weeks after initiation of tepotinib, his complete response persists, and he remains clinically stable with mild chronic dizziness. Trials of targeted therapy in molecularly-unselected GBM have been largely disappointing, however, this case demonstrates the promise of targeting MET using tepotinib in GBM. A clinical trial of tepotinib in MET-amplified GBM and NSCLC brain metastasis is currently underway at MD Anderson.

CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.

SYST-08. A phase II trial of concurrent Sunitinib, Temozolomide and Radiation Therapy followed by adjuvant Temozolomide for newly diagnosed Glioblastoma patients with an unmethylated MGMT gene promoter (A01-M121-11A, McG1132)

INTRODUCTIONDespite advances in treatment modalities, the overall prognosis of GBM remains dismal, particularly for patients with unmethylated MGMT promoter. Thus, alternative treatment strategies are warranted. Our group has previously shown that addition of Sunitinib (SU11248) to standard therapy significantly improved the response of unmethylated MGMT cells through decreased angiogenicity and tumorigenicity. In this phase II trial, we tested for the first time the combination of Sunitinib with RT and Temozolomide in newly diagnosed MGMT unmethylated GBM patients.METHODSPatients with histologically confirmed WHO Grade IV GBM and MS-PCR confirmed unmethylated MGMT promoter, age 18-70, KPS ≥70, life expectancy ≥6 months were eligible. 41 patients treated between 2012 and 2017 were screened, 37 of which were eligible. Patients received 12.5 mg of daily Sunitinib for 7 days, followed by concurrent RT, Temozolomide and 12.5 mg Sunitinib for 6 weeks, then adjuvant Temozolomide x6 cycles. RT and Temozolomide doses were as per standard of care. Primary objective was PFS as assessed by RANO criteria, secondary objectives were OS and safety.RESULTSMedian follow-up time was 15 months. Median PFS was 7 months (95%CI, 6.7-7.2) and 6-month PFS was 59.3%. Median OS was 13 months (95%CI, 12.62-13.37) and 2-year OS was 17.8%. Two patients had OS >50 months, with one surviving 71 months. Having received >3 cycles of adjuvant Temozolomide, surgery at progression or age ≤65 significantly predicted for better OS, with hazard ratios of 0.184 (p=0.001), 0.402 (p=0.026) and 10.017 (for age >65, p=0.002) respectively. Grade ≥3 thrombocytopenia occurred in 18.9% of patients, grade ≥3 neutropenia in 10.8% and grade ≥3 thromboembolic events in 13.5%. There were no grade 5 evens.CONCLUSIONAddition of Sunitinib to RT and Temozolomide was well tolerated and survival outcomes compared favorably to the current standard of care for GBM patients with unmethylated MGMT promoter status.

Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study).

PurposeThe KNOG-1101 study showed improved 2-year progression-free survival (PFS) with temozolomide during and after radio-therapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).Materials and MethodsIn this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B).ResultsOf the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33).ConclusionThe addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of PFS for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Survival and Prognostic Factors in Patients with Glioblastoma Multiforme Receiving Radiation and Temozolomide – A Retrospective Study

Introduction: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The standard treatment is surgical excision, followed by concomitant chemoradiation and adjuvant treatment with temozolomide. The standard radiation dose is 60Gy/ 30 fractions 2 Gy per fraction. Temozolomide is an alkylating agent and dosage is 75mg/m2 concurrent with radiation and 150-200mg/m2 as adjuvant treatment. This study aims at studying the median survival and the various prognostic factors. Materials and Methods: This is a retrospective study conducted in Government Medical College, Alappuzha, of 44 patients with GBM from March 2015-2017, who underwent surgery followed by chemoradiation with temozolomide and six cycles of adjuvant temozolomide. Result: Out of 44 patients, 26 were males and 18 females. There were 28(64%) patients with an ECOG performance status (PS) of 0-1 and had a median survival (MS) of 21months and 16(36%) patients with PS of 2 who had a MS of 10 months (p value &lt;0.001). In this study 30(68%) patients had complete or near complete excision and had a MS of 20 months and 14 (32%) patients had only a partial excision who had a MS of 10 months(p value &lt;0.001). There were 25(57%) patients below 50 years who had a MS of 20 months and 19(43%) patients above 50 years who had a MS of 12 months (p value &lt;0.01). Conclusion: The prognostic factors detected were age, performance status and extent of resection. The triple modality of treatment of concurrent chemoradiation with temozolomide followed by adjuvant temozolomide continues to be the standard treatment. Keywords: Glioblastoma multiforme, Temozolomide, chemoradiation.

Concurrent chemoradiation in the management of newly diagnosed glioblastoma multiforme: Retrospective review of single center experience over a period of 10 years.

e14028 Background: Glioblastoma Multiforme (GBM) is the most common primary intracranial tumour of the brain. The standard of care first line management is maximum safe debulking followed by concurrent chemo radiation (Stupp et al, 2005). In spite of further recent advances, median survival still remains poor and ranges between 14 to 21 months, especially in the MGMT unmethylated group. There are no randomised trials investigating less than 6 cycles of adjuvant temozolomide (TMZ). In our study we retrospectively analyse the impact on overall survival (OS) and progression free survival (PFS) in cases where adjuvant treatment has been discontinued due to toxicity or patient’s fitness Methods: We collected data from 2007 to 2016 for a cohort of patients who underwent adjuvant treatment for GBM following histological diagnosis. The final analyses included patient’s who completed concurrent chemoradiotherapy to a dose of 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ chemotherapy Results: Of 110 patient cohorts, 57% of patients completed adjuvant chemo radiotherapy followed by 4-6 cycles of adjuvant TMZ, 43% received 3 or less cycles of TMZ. Overall PFS was 11.9 months. Those that completed 4 or more cycles of adjuvant TMZ had an improved PFS (Log rank test P-value 0.001) versus those that completed 3 or less cycles. On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Median overall survival was 16 months for the whole group, but was 10 vs. 20 months for the two groups. On cox analysis we also identified second line chemotherapy had a significant impact on OS (cox model P-value 0.002) Conclusions: We identified patients receiving three or fewer cycles of adjuvant TMZ had poorer outcomes. Second-line chemotherapy improved outcomes at relapse regardless of redo surgery.

COVD-29. CONTINUATION OF TEMOZOLOMIDE CHEMOTHERAPY IN A GLIOBLASTOMA PATIENT AFTER RESOLUTION OF COVID-19 PNEUMONIA

We present a case of a 33 year-old patient with glioblastoma (IDH wild type, MGMT unmethylated) who was diagnosed with COVID-19 pneumonia while undergoing chemotherapy. The patient did not have any medical comorbidities. He was clinically asymptomatic following surgery, completed concurrent phase of combined chemotherapy and radiation and was undergoing treatment with adjuvant temozolomide. He had radiographic improvement of the brain tumor (decreased size, contrast enhancement and T2 flair) after three cycles of adjuvant temozolomide. However, after cycle three the patient developed fever and abdominal pain. Evaluation in the emergency room revealed low absolute lymphocyte count (0.7 K/MM3), positive COVID-19 point of care test and CT chest revealed patchy peripheral bibasilar ground glass and consolidative opacities compatible with pulmonary infection, with viral etiology such as COVID. Symptoms resolved after 2 weeks. Due to active infection and leucopenia temozolomide was on hold for 1 month. He was considered cleared of infection after resolution of symptoms. Temozolomide was initiated after resolution of leucopenia. Patient continued to do well after administration of subsequent temozolomide cycles and repeat CT chest after 2 months revealed resolution of consolidation and no new areas of consolidation. Temozolomide was safely administered in this patient without reactivation of COVID-19 infection. He did not have any thrombotic events.

NCOG-42. INITIAL PRESENTATION AND OUTPATIENT VISIT COMPLIANCE OF INMATES WITH BRAIN TUMORS

Abstract INTRODUCTION While advocacy for inmates with cancer has recently gained momentum, little is known about management of brain tumors in inmates. Delays in acknowledging or recognizing nonspecific initial symptoms can lead to delayed diagnosis and treatment. Inmates with cancer are reported to either be ignored or receive substandard care due in part to cost or logistics (American Civil Liberties Union; ASCO Post 2018). METHODS In this retrospective study, we identified inmates with gliomas seen in the Ohio State University Neuro-oncology Center between 1/1/2010-4/20/2019. RESULTS Twelve patients were identified. Median age at presentation was 39.5 years (range 28-62). Eleven patients were Caucasian and one was African American. Diagnoses included glioblastoma (GBM) (n=6), anaplastic astrocytoma (n=1), anaplastic oligodendroglioma (n=1), low-grade astrocytoma (n=3) and anaplastic pleomorphic xanthroastrocytoma (n=1). Patients were more likely to present early after seizures or focal neurologic deficits (9/12) than after headaches alone. Patients with GBM started RT 12-71 days after surgery (median 34.5). One patient’s post-RT MRI was delayed by a month and another with GBM had treatment held after 4 cycles of adjuvant temozolomide (TMZ) due to “incarceration issues”. For one patient who received adjuvant TMZ, the facility failed to communicate with the primary team throughout treatment. Two patients suffered significant nausea while on chemotherapy due to inability to obtain ondansetron in prison, or due to wrong timing. 7/12 (58%) patients were lost to follow-up for periods of 3-15 months during treatment. Three patients refused adjuvant treatment. CONCLUSIONS Although this is a small series, our results highlight the inequities and challenges faced by inmates with gliomas who are more likely to forego treatments or whose incarceration prevents them from keeping appropriate treatment and follow-up schedules. Additional studies are needed to define and address these deficiencies in the care of inmates with brain tumors and other cancers.

COVD-20. COVID-19 INFECTION DURING CHEMOTHERAPY FOR MALIGNANT GLIOMA: OUTCOMES AMONG 3 PATIENTS

BACKGROUNDChemotherapy may increase risk of SARS-COV-2 infection and COVID-19 severity.METHODSA patient developed COVID-19 during chemotherapy for glioma. We retrospectively identified others diagnosed with COVID-19 during temozolomide or lomustine for glioma.RESULTS(1) A 64 year-old woman (index patient) with anaplastic oligodendroglioma received PCV 22 months previously. Baseline White Blood Cell (WBC) count was 4.2 and Absolute Neutrophil Count (ANC) was 2.7 K/uL. KPS was 90 without comorbidities. For recurrence she initiated temozolomide but developed fever on cycle 1 day 2. SARS-COV-2 PCR was positive. Further temozolomide was held. She is recovering as an outpatient. (2) A 27 year-old man with anaplastic astrocytoma received concurrent RT/temozolomide then 1 cycle of adjuvant temozolomide. Baseline WBC was 8.3, ANC 5.2, and KPS 90. Obesity, asthma, and pre-diabetes were comorbidities. Hyposmia/hypogeusia and low-grade fever began, in retrospect, during concurrent RT/temozolomide. PCR for SARS-COV-2 was negative 2 months after symptom onset; serology detected both IgG and IgM when WBC was 6.6 and ANC 4.0. Cycle 2 of adjuvant temozolomide was held until fever resolved (spontaneously); hyposmia/hypogeusia persist. (3) A 53 year-old man with glioblastoma previously received RT/temozolomide, then lomustine and bevacizumab for progression. WBC was 5.1, ANC 4.0, and KPS 60. He was obese. Fever, chills, and dyspnea developed on lomustine cycle 2 day 38. SARS-COV-2 PCR was positive. He was hospitalized and chemotherapy held; symptoms resolved 12 days after onset, but PCR continued to show detectable virus 32 days later. PCR became negative after 50 days total, and treatment resumed uneventfully.DISCUSSIONAll 3 patients recovered from SARS-COV-2 infection despite active temozolomide or lomustine chemotherapy. Normal ANC, high KPS, and early detection may have contributed to limited symptom severity and duration, despite obesity and other comorbidities in 2 cases. Detection changed management by delaying additional cycles of immunosuppressive chemotherapy until recovery.

Clinical characterization of glioblastoma patients living longer than 2 years: A retrospective analysis of two Italian institutions.

Despite the advances in surgery and radio-chemotherapy, the prognosis of glioblastoma (GBM) remains poor with about 13% of patients alive at 24 months. A total of 75 long-term survivors (LTS), defined as alive at least 24 months from diagnosis, were retrospectively analyzed. Overall survival (OS) and recurrence-free-survival (RFS) were calculated and related to patient characteristics and treatment received. Median age and Karnofsky performance status (KPS) were 56 years and 100%, respectively. After surgery (gross tumor resection-GTR in 62, 83% patients), all LTS received concomitant temozolomide (TMZ) with radiotherapy and 70 (93%) adjuvant TMZ. Of these, 10 (13%) discontinued TMZ prior the completion of 6 cycles, 37 (49%) received 6 cycles and 23 (31%)>6 cycles. Sixty-nine (92%) patients experienced a first tumor recurrence at a median time of 21 months. Of these, 32 (46%) were submitted to a second surgery, 34 (49%) to other no-surgical treatments and 3 (5%) only supportive care. At multivariate analysis, OS was significantly improved by second surgery after first recurrence (P=0.0032) and by cycles of adjuvant TMZ>6versus ≤6 (P=0.05). More than six cycles of TMZ significantly conditioned also first RFS (P=0.011) and second RFS (P=0.033). The large majority of LTS had<65 years, had a high KPS and received GTR. OS and RFS resulted significantly related to an extended administration of adjuvant TMZ (>6 cycles) and a second surgery in case of recurrence.