Adjuvant Temozolamide Research Articles

Neurocognitive Function And Quality Of Life Assessment In Patients Receiving Whole Brain Radiotherapy With Adjuvant Temozolamide And Whole Brain Radiotherapy Alone: A Prospective Comparative Study

Neurocognitive Function And Quality Of Life Assessment In Patients Receiving Whole Brain Radiotherapy With Adjuvant Temozolamide And Whole Brain Radiotherapy Alone: A Prospective Comparative Study

GLIOMA-15 RETROSPECTIVE REVIEW OF GLIOBLASTOMA MULTIFORME CASES MANAGED AT A TERTIARY LEVEL HOSPITAL IN KENYA

Abstract Glioblastoma Multiforme(GBM) is one of the most aggressive tumors of the central nervous system. Though rare, it accounts for the commonest primary brain tumor in adults. Despite recent advances in the treatment of patients with GBM, it portends a poor prognosis. There is limited published data of GBM from sub-Saharan Africa(SSA). We performed a retrospective chart review of 24 patients seen in the Medical Oncology service at the Aga Khan University Hospital between January 2018 and December 2020. Clinical, radiological, pathological outcomes were investigated, analyzed and compared with data from the literature. A total of twenty-four patients were seen at the medical oncology clinic over the 3-year period. The median age of the patients was 54 years (IQR 44.7-65) and majority of patients (>80%) were of African descent. Of the 24 patients, 13(54.2%) were male and 11(45.8%) were female. Headaches were the commonest clinical presentation and frontal lobe was commonest tumor location on imaging. The median size of the tumor was 4.5cm (IQR 3.8-6.45). Following diagnosis, eighteen(75%) patients underwent maximal safe resection of the tumor with presence of residual tumor in thirteen (56%) of the post-operative scans. Nineteen patients(83%) were initiated on concurrent chemotherapy (Temozolamide) and Radiation therapy (CCRT) as part of adjuvant treatment. Of those initiated on adjuvant Temozolamide following CCRT, more than one-third completed one year of treatment. At 6 months following diagnosis, 25% of patients remained stable while 25% had disease progression. Our study adds to the literature which demonstrates that patients seen in SSA with GBM present at younger age, with bigger tumor size but tend to do better compared to those in the west. Understanding of the molecular alterations within the tumor and larger prospective studies are needed to define the behavior of GBM in SSA.

P17.18.B RADIOTHERAPY IN GLIOBLASTOMA MULTIFORME COULD BE PLANNED WITH MARGINS LESS THAN 2 CM WITH LESS THAN 1 CM FROM THE SURGICAL BED

Abstract BACKGROUND The administration of radiotherapy (Rt) plus adjuvant temozolamide (TMZ) with IMR and VMAT techniques has become an increasingly valuable tool in the local control of glioblastoma multiforme with a survival current Rt techniques allow specific conformation with the use of better radiological images that allow us greater precision. For many years large Rt field sizes have been associated with significant adverse effects.Although we continue to give very wide margins that lead us to irradiate non-compromised organs at risk, which translates into a higher rate of radionecrosis and acute and chronic neurological toxicity.Therefore, we consider it valid to ask ourselves if we could reduce the standard margins applied in the planning of Rt. MATERIAL AND METHODS Analysis of 98 GBM patients treatedat the barros luco hospital between 2021 and 2023 with surgery followed by adjuvant therapy, radiotherapy plus concomitant chemotherapy at the Institute. Nacional de Cáncer de Santiago de Chile we reviewed the time of recurrence and the location in relation to the surgical margins vs. radiotherapy margins or other nearby areas. RESULTS After the analysis, we can see that 65% of the recurrences presented a dominant failure pattern, within the field and less than 1cm from the margin between the surgical bed and the radiotherapy margin, evaluated with perfusion brain resonance imaging and spectroscopy CONCLUSION n the local control of GBM, the application of adjuvant therapy is essential in a period of not less than 2 months after surgery, in this institutional analysis we can observe a considerable number of patients under 40 years of age with this pathology, for which reason to consider reducing the diameter of Rt margins can be considered an option, in order to limit deleterious effects in healthy organs in the times that there are advanced Rt techniques, the increasingly frequent application of brain radiosurgery (SRS) thatIt can be used as a rescue method in case of recurrences at the edge of the margin, using radiological images (MRI with perfusion and spectroscopy/C-methionine PET/CT. Figure we can see the CTV and PTV to be treated with modulated intensity technique, evidencing the large field size that receives radiation between 54 to 60 Gy.Radiation oncology must continue to develop and improve the delivery, targeting, and dose of radiation therapy in the GBM to improve its survival and treatment-associated toxicity.

Impact of Extended Adjuvant Temozolamide Beyond 6 Months in the Management of Glioblastoma Patients.

Our study aimed to assess the benefit of prolonging adjuvant temozolomide (TMZ) therapy beyond 6 cycles in glioblastoma multiform patients. The medical records of 329 patients in 2 cancer centers in Egypt were reviewed from January 2008 to December 2018 who were diagnosed with diffuse gliomas. Data were collected on patient demographics, presenting complaints, tumor size, treatment modalities (extent of surgery, radiotherapy dose and technique, concomitant TMZ, and the number of adjuvant TMZ cycles), and reported adverse events. In the studied cohort, 105 patients were treated with adjuvant TMZ, 33 patients received <6 cycles (TMZL), 41 patients received the standard 6 cycles (TMZS), and 31 patients received >6 cycles (TMZE). Our results showed the median overall survival in the TMZL arm was 8.47 months compared with 15.83 months in the TMZS arm and 27.33 months in the TMZE arm ( P < 0.001). Furthermore, a median progression-free survival of 6.35 months was reported in the TMZL group versus, 12.7 and 22.90 months in (TMZS) and (TMZE) groups, respectively( P < 0.001). In the multivariate analysis, the extended adjuvant TMZ with a hazard ratio of 3.106 (95% CI: 2.43-14.46; P < 0.001) was statistically significantly associated with a better outcome. Extended adjuvant TMZ therapy beyond 6 cycles may significantly improve the progression-free survival and overall survival in patients with glioblastoma multiform.

CSIG-29. TRIBBLES-1 (TRIB1) INCREASES TUMOR FORMATION IN AN ORTHOTOPIC MOUSE MODELS BY PROMOTING SURVIVAL OF GBM CELLS AND TREATMENT RESISTANCE

Abstract INTRODUCTION Glioblastoma (GBM) is the most aggressive CNS tumor with an average survival of about 15 months after diagnosis. The current gold standard therapy comprises radiation therapy (RT) and concurrent and adjuvant temozolamide (TMZ). Due to poor prognosis, novel therapeutic targets need to be identified for drug development. To this end, we identified TRIB1 through correlative studies using patient derived methylation data from an institutional cohort as a novel therapeutic target. TRIB1 is a Ser/Thr pseudokinase that functions as a scaffold for the degradation of its substrates and activates Akt and MEK oncogenic pathways. In this study, we show that TRIB1 promoted GBM progression by upregulating survival pathways and reducing RT/TMZ-induced cell death. MATERIALS AND METHODS In vitro functional validation was performed by overexpression and knockdown approaches. GBM patient derived (PDX) cell lines overexpressing the TRIB1 transgene were used to create an orthotopic tumor model for in vivo studies. Mice were monitored for changes in tumor volume and overall survival. Stable cell lines were generated by puromycin selection. Western blotting was utilized to detect protein levels. RESULTS Mice inoculated with PDX cells overexpressing TRIB1 transgene had increased tumor volume and worse overall survival compared to the empty vector control. We also observed that TRIB1 overexpression caused decreased apoptosis of PDX cell lines after RT/TMZ treatment. Additionally, an increase in the phosphorylation of ERK and Akt was also noted after TRIB1 overexpression. Consistent with these observations, TRIB1 knockdown sensitized the cells towards radiation and caused decreased Akt phosphorylation/activation as well. CONCLUSION TRIB1 overexpression decreases overall survival of xenograft bearing mice and promotes GBM cell survival by upregulating survival signaling pathways. This compromises the effects of RT/TMZ therapy, which is reversed after TRIB1 knockdown. Targeting of TRIB1 may reduce oncogenic signaling in GBM cells and therefore would sensitize them towards RT/TMZ therapy.

Additional Value of 18F-FDOPA Amino Acid Analog Radiotracer to Irradiation Planning Process of Patients With Glioblastoma Multiforme.

PurposeTo investigate the added value of 6-(18F]-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) PET to radiotherapy planning in glioblastoma multiforme (GBM).MethodsFrom September 2017 to December 2020, 17 patients with GBM received external beam radiotherapy up to 60 Gy with concurrent and adjuvant temozolamide. Target volume delineations followed the European guideline with a 2-cm safety margin clinical target volume (CTV) around the contrast-enhanced lesion+resection cavity on MRI gross tumor volume (GTV). All patients had FDOPA hybrid PET/MRI followed by PET/CT before radiotherapy planning. PET segmentation followed international recommendation: T/N 1.7 (BTV1.7) and T/N 2 (BTV2.0) SUV thresholds were used for biological target volume (BTV) delineation. For GTV-BTVs agreements, 95% of the Hausdorff distance (HD95%) from GTV to the BTVs were calculated, additionally, BTV portions outside of the GTV and coverage by the 95% isodose contours were also determined. In case of recurrence, the latest MR images were co-registered to planning CT to evaluate its location relative to BTVs and 95% isodose contours.ResultsAverage (range) GTV, BTV1.7, and BTV2.0 were 46.58 (6–182.5), 68.68 (9.6–204.1), 42.89 (3.8–147.6) cm3, respectively. HD95% from GTV were 15.5 mm (7.9–30.7 mm) and 10.5 mm (4.3–21.4 mm) for BTV1.7 and BTV2.0, respectively. Based on volumetric assessment, 58.8% (28–100%) of BTV1.7 and 45.7% of BTV2.0 (14-100%) were outside of the standard GTV, still all BTVs were encompassed by the 95% dose. All recurrences were confirmed by follow-up imaging, all occurred within PTV, with an additional outfield recurrence in a single case, which was not DOPA-positive at the beginning of treatment. Good correlation was found between the mean and median values of PET/CT and PET/MRI segmented volumes relative to corresponding brain-accumulated enhancement (r = 0.75; r = 0.72).Conclusion 18FFDOPA PET resulted in substantial larger tumor volumes compared to MRI; however, its added value is unclear as vast majority of recurrences occurred within the prescribed dose level. Use of PET/CT signals proved to be feasible in the absence of direct segmentation possibilities of PET/MR in TPS. The added value of 18FFDOPA may be better exploited in the context of integrated dose escalation.

Cost-Effectiveness of Temozolamide for Treatment of Glioblastoma Multiforme in India.

PURPOSEGlioblastoma multiforme (GBM) has poor outcomes following surgery and radiation. Adjuvant temozolamide along with radiation therapy has been shown to improve survival. In this paper, we evaluate the cost-effectiveness of concomitant temozolamide with radiation and maintenance temozolamide for 6 months of treatment for GBM in India.MATERIALS AND METHODSWe used a Markov model to evaluate the lifetime costs and consequences of treating GBM with radiation alone versus radiation with adjuvant temozolamide. The model was calibrated using the published evidence from European Organisation for Research and Treatment of Cancer-NCIC trial on progression-free survival and overall survival to estimate the life years (LYs) and quality-adjusted LYs (QALYs). Cost of treatment and management of complications were estimated using the data from the National Health System Cost Database and Indian studies. Future cost and consequences were discounted at 3%. Incremental cost per QALY gained with temozolamide was estimated to assess cost effectiveness.RESULTSTemozolamide resulted in an increase of 0.59 (0.53-0.66) LY and 0.33 (0.29-0.40) QALY per person at an incremental cost of ₹75,120 in Indian national rupee (INR) (59,337-93,960). Overall, the use of temozolamide incurs an incremental cost of ₹212,020 INR (138,127-401,466) per QALY gained, which has a 4.7% probability to be cost-effective at 1-time per capita Gross Domestic Product (GDP) threshold. In case the current price of temozolamide could be decreased by 90%, the probability of its use for GBM being cost-effective increases to 80%.CONCLUSIONTemozolamide is not cost-effective for treatment of patients with GBM in India. This evidence should be used while framing guidelines for treatment and price regulation.

Hypofractionated Radiotherapy Using Simultaneous Integrated Boost Technique with Concurrent and Adjuvant Temozolomide for Glioblastoma

Aim: This study was conducted to assess the safety and efficacy of postoperative hypofractionated radiotherapy (HRT) using simultaneous integrated boost (SIB) technique for glioblastoma (GBM) compared to conventional radiotherapy (CRT).&#x0D; Study Design: This was a prospective study with historical control arm.&#x0D; Place and Duration of the Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019.&#x0D; Methods: The intervention (HRT) group included 30 patients who received 3D conformal HRT with SIB using field in field (FIF) technique to deliver a differential radiation dose to different targets. Planning target volume 60 (PTV60) includes the gross target volume (GTV) plus a 5-mm margin, and PTV45 includes the GTV plus a 15-mm margin. PTV60 will receive 60 Gy in 20 fractions, and PTV45 will receive 45 Gy in the same 20 fractions (one fraction daily and 5 days per week).The CRT group included 30 patients who received 3D conformal CRT with total dose 60 Gy in 2-Gy fractions delivered over 6 weeks. Both groups was planned to receive concurrent and adjuvant temozolamide.&#x0D; Results: The median PFS was 10 months in both groups. The median OS was 13 months in HRT group versus 12 months in CRT group which is statistically non significant. The toxicities were mild and acceptable. Performance status and adjuvant temozolamide were significant predictors that affect the overall survival.&#x0D; Conclusions: HRT with SIB using 3D conformal RTH with (FIF) technique in patients with GBM is a feasible and safe treatment and its results is comparable to the conventional radiotherapy.

3D Conformal Re-Irradiation with Temozolamide for Recurrent Glioblastoma: A Prospective Cohort Study

Introduction and objectives: Salvage treatment of recurrent Glioblastoma (GBM) is one of the most challenging tasks in neuro-oncology. There is no standard treatment for recurrent GBM as options include resection, chemotherapy, and re-irradiation either separate or in combination. Role of concomitant temozolamide with re-irradiation in recurrent disease is still debatable. Therefore, this study evaluates efficacy of concurrent and adjuvant temozolamide with re-irradiation in management of recurrent GBM. Patients and methods: Twenty two patients with recurrent glioblastoma were eligible. Patients were treated with 3 D conformal radiotherapy. The dose ranged from 30 to 40 Gy in 1.6 to 1.8 Gy per fraction for 5 days per week. Temozolamide was administrated at 50 mg/m2 daily dose during radiation therapy. Adjuvant Temozolomide (200 mg/m2) was given orally for five days every four weeks for 4 - 6 cycles for patients who did not receive temozolamide before, and 150 mg/m2 for pretreated patients. Results: 22 patients received re-irradiation with median dose 38 Gy (range 33 - 40 Gy), concurrent with temozolamide. The time interval between primary and re-irradiation ranged from 6 to 23 months with median 12 months. The re-irradiated volume, median was 101.95 cm3 (range 30 - 375 cm3). The median cumulative maximum dose to optic system and brain stem were 53.5 Gy (range 42 - 63 Gy), and 60 Gy (range 54 - 73 Gy), respectively. Response rate was 72.7%, one patient showed complete response (4.5%), partial response and stable disease registered in 22.7% and 45.5%, respectively. The median overall survival (OS) was 10 months (range 4 - 13 months), and median progression-free (PFS) survival was 7.5 months (range 2 - 11 months). The 6 and 12 months OS rate was 100% and 56.6% respectively, and the 6 months PFS rate was 93.3%. No major acute toxicity was observed. About 70% of patients experienced grade 2 toxicity in the form of headache, nausea & vomiting, skin erythema and alopecia. The late toxicity was minimal as GI & II. Symptoms of radiation necrosis were not recorded in any patient. Conclusion: 3D conformal re-irradiation concomitant with temozolamide and adjuvant temozolamide appears effective treatment in recurrent glioblastoma. The treatment protocol is safe, feasible treatment with limited rate of toxicity and improve survival outcome.

Bevacizumab for progressive glioblastoma multiforme: a case of treading the tightrope

Until March 2013, Bevacizumab had been funded through the National Cancer Drugs Fund (CDF) for the treatment of recurrent/progressive Glioblastoma multiforme (GBM). Although the CDF concluded at the time that there was insufficient evidence around the effectiveness of the Bevacizumab on overall survival and quality of life, there is evidence that a small number of individual patients may significantly benefit from it. We present a case of a 40-year old man with GBM (IDH-1 wild-type, MGMT <10% methylated) who, following surgical debulking, was treated as per the Stupp regime. 2 months after completing adjuvant Temozolamide, he developed clinical and radiological progression. He was commenced on Bevacizumab and Irinotecan, which at the time was funded through the CDF. Following 4 cycles of treatment, his symptoms resolved, and at minimum, good partial radiological response was achieved. After 34 cycles the Irinotecan was stopped due to debilitating diarrhoea. After 44 cycles, the Bevacizumab was suspended for 4 weeks because the patient developed a perianal abscess and fistula, which were treated surgically with incision, drainage, and Seton insertion. At this point, discussions with the patient regarding stopping Bevacizumab were held, and his choice was to continue despite the risks. To date (March 2017) he has received 101 cycles of Bevacizumab, equating to 4 years of treatment, with no evidence of radiological or clinical progression. He has developed mild hypertension, for which he has declined antihypertensive treatment. His perianal fistula has completely healed. To our knowledge, this patient is one of the longest survivors on Bevacizumab given at progression. This case has posed, and still poses, important questions in relation to patient choice and risk-benefit conversations; in particular relating to the potential risks of protracted treatment vs its benefit, and the possibility of “drug holidays”.

Glioblastoma multiforme with gliosarcoma with metastasis to lung

Abstract A 51 year old female presented with headache and projectile vomiting of 1 month duration, and her systemic examination was non-contributory. Blood and urine investigations were normal. MRI brain identified a mass lesion in the right frontal lobe and anterior body of corpus callosum with areas of peri-lesional edema. Craniotomy was performed with right frontal lobectomy and tumour excised. Biopsy confirmed Glioblastoma multiforme with gliosarcomatous areas. Adjuvant external beam irradiation with concurrent temozolamide was administered followed by adjuvant temozolamide. Subject developed breathlessness 8 months after surgery, and PET scan performed revealed mildly enhancing metabolically active area in genu of corpus callosum and metabolically active left sided pleural based masses with left pleural effusion. Biopsy from the pleural based lesion was consistent with metastatic disease from Glioblastoma Multiforme. Extra-cranial metastasis in a case of glioblastoma multiforme is uncommon.

A Retrospective Study Evaluating Effectiveness of Concurrent And Adjuvant Temozolamide in Newly Diagnosed Glioblastoma Multiforme in Indian Population.

A Retrospective Study Evaluating Effectiveness of Concurrent And Adjuvant Temozolamide in Newly Diagnosed Glioblastoma Multiforme in Indian Population.

Relative thrombocytosis following chemoradiation of patients with glioblastoma to predict survival.

e13527 Background: Thrombocytosis is associated with poor survival in several malignancies and is both triggered by and promoting of tumor growth. We hypothesized that an increase in circulating platelets following standard temozolamide (TMZ) CRT and/or adjuvant TMZ would predict for decreased survival in patients with glioblastoma (GBM). Methods: We reviewed data of 122 patients with newly diagnosed, pathological-proven GBM from 2007 to 2016 with documented complete blood counts before the start of CRT, after CRT, before adjuvant TMZ, and after a minimum 2 cycles of adjuvant TMZ. The association between changes in blood count levels and patient survival was analyzed by log-rank test. Multivariate analysis was performed using known prognostic co-variates, including MGMT methylation, patient age, and performance status (PS). Results: The mean change in platelets before and after CRT was -46 k/µl (range -387 to 179 k/µl) and before and after adjuvant TMZ was -25 k/µl (range -408 to 143 k/µl). As a reference, the mean change in lymphocytes was -5.7 k/µl (range -0.7 to 1.3 k/µl) and -0.0 k/µl (range -1.6 to 0.9 k/µl) for CRT and adjuvant TMZ, respectively. Patients were dichotomized based on the relative change in platelets and lymphocytes from baseline (≤30% increase, “low”, n = 101 vs &gt; 30% increase, “high”, n = 12). The median survival of low patients vs. high patients was 30 vs 13 months (p = 0.006). Potential confounders, such as infection or thrombosis, were not associated with the high group. However, no significant survival difference was observed between groups based on platelet changes during adjuvant TMZ. Similarly, changes in lymphocyte counts were not significantly prognostic. In multivariate analysis, extent of resection, MGMT status, PS and the increase in platelets after CRT were significantly associated with survival (HR for platelets 4.0, 95% CI 1.6-10.1). Conclusions: Increased platelet counts after CRT predict for poor survival in patients with GBM. The effect is platelet specific and does not reflect general bone marrow changes, as lymphocyte changes were not significantly prognostic. These results suggest a potential interaction between platelets and tumor aggressiveness.

350P - Extended adjuvant temozolamide as prognostic factor of longer overall and progression-free survival in glioblastoma multiforme

350P - Extended adjuvant temozolamide as prognostic factor of longer overall and progression-free survival in glioblastoma multiforme

Association Between Perioperative Hyperglycemia and Survival in Patients With Glioblastoma.

Several studies have examined the association between hyperglycemia in the first 10 to 12 weeks following surgery and postoperative survival in glioblastoma multiforme (GBM) patients. We hypothesize that episodes of hyperglycemia before, during and/or following surgery for primary GBM are independent predictors of disease progression and mortality. A total of 162 adult patients were included in the analysis. All patients received adjuvant temozolamide. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5 years were analyzed using different glycemic cutoff values. Multivariate analyses were conducted to test the association between preoperative, intraoperative and postoperative hyperglycemia with PFS and OS. Kaplan-Meier curves revealed a trend toward increased PFS and OS with lower glucose concentrations with the exception of glucose concentrations >180 mg/dL in the intraoperative/postoperative day 0 time period. Univariate analysis of blood glucose levels did not demonstrate a statistically significant effect on PFS in any time period, however hyperglycemia was statistically significant for OS in the preoperative time period. Although, multivariate analysis showed no statistically significant association with hyperglycemia on PFS, a statistically significant decrease in OS was seen for plasma glucose concentrations >112 mg/dL (P=0.01) and >180 mg/dL (P=0.01) in the preoperative period. There was a decreasing effect on OS with blood glucose concentrations greater than the median in multiple time periods (P=0.02). Preoperative hyperglycemia is associated with poor OS after GBM surgery.

ATNT-29TREATMENT OF GLIOBLASTOMA: USE OF BEVACIZUMAB AFTER FIRST PROGRESSION. EXPERIENCE OF 20 DE NOVIEMBRE ISSSTE MEDICAL CENTER, MEXICO CITY

In Mexico the incidence of brain tumors was 4786 cases in 2012, 18% of these tumors are glioblastoma, The study was conducted January 2007 to April 2015, with patients diagnosed with glioblastoma, included in the study, after standard treatment (CT/RT) and adjuvant temozolamide. Patients remained under surveillance with IMR. If progression was detected, bevacizumab was initiated at 10mg/Kg until progression; if patient had a good performance after the use of bevacizumab, we added Irinotecan and continued bevacizumab. The primary end point was progression-free survival, the secondary objective was overall survival. Inclusion criteria: Patients diagnosed with glioblastoma, age ≥ 18 years, ECOG 0-2, Karnofsky> 70. Exclusion criteria: Patients without diagnosis of glioblastoma ECOG 3. MATERIALS AND METHODS: 84 cases diagnosed with brain tumors, only 24 patients have glioblastoma. RESULTS: Age was 50 years, 10 women and 14 men, 2 patients with complete resection, 1 with biopsy and 21 remaining with partial resections were 40-80% of the tumor, DFS was 12. 7 months, with an overall survival of 31 months, 8 patients continued bevacizumab and irinotecan after second progression. DISCUSSION: This is the first Mexican study of reported experience with the use of bevacizumab, median overall survival 31 months, with a mean PFS of 12.7 months. We do not make the determination of IDH1, but the benefit of use of bevacizumab after the first progression and continue after second progression exist. we need a biomarker and clinical parameter. CONCLUSIONS: The use of bevacizumab in patients with glioblastoma has free survival similar to other reports, is safe in Mexican population, and some patients receive CT and continue to bevacizumab with increase of OS.

Impact of oligodendroglial component in glioblastoma (GBM-O): Is the outcome favourable than glioblastoma?

BackgroundPrognosis of patients with glioblastoma with oligodendroglial component (GBM-O) is not well defined. We report our experience of patients of GBM-O treated at our center. MethodsBetween January 2007 and August 2013, out of 817 consecutive patients with glioblastoma (GBM), 74 patients with GBM-O were identified in our prospectively maintained database. An experienced neuropathologist revaluated the histopathology of all these 74 patients and the diagnosis of GBM-O was eventually confirmed in 57 patients. Patients were uniformly treated with maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolamide (TMZ). ResultsAt a median follow up of 16 months, median overall survival (OS) and progression free survival (PFS) of the entire cohort was 23 months and 13 months respectively. Near total excision was performed in 30/57 (52.6%). On univariate analysis, age<50 years was a significant favourable prognostic factor for OS (p=0.009) and PFS (p=0.017), while patients with near total resection had a significantly better PFS (p=0.017), patients who completed a minimum of 6 cycles of adjuvant TMZ had significantly better OS (p=0.000) and PFS (p=0.003). On multivariate analysis, none of the above factors were significant except for patient who had completed a minimum of 6 cycles of TMZ (OS; p=0.000 & PFS; p=0.015). A comparative analysis of GBM-O patients with a similarly treated cohort of 105 GBM patients during the same period revealed significantly better median OS in favour of GBM-O (p=0.01). ConclusionsOur experience suggests patients with GBM-O have a more favourable clinical outcome as compared to GBM.

RT-04 * STEREOTACTIC RADIOSURGERY (SRS) IN RECURRENT HIGH-GRADE GLIOMA

Despite the failure of the RTOG 9305 randomized trial to demonstrate the efficacy of SRS in newly diagnosed glioblastoma, this treatment was reported in several institutional series to be modestly effective, particularly in the setting of limited focally recurrent disease. This is a retrospective review of 55 SRS treatments in 47 patients with recurrent high-grade glioma treated at our institution between 2004 to 2013. Thirty-two (63%) patients suffered from glioblastoma and 15 from high-grade glioma. The median age was 53.3 years (24-86). The initial non-surgical treatment included Stupp protocol in 35 (74.5%), adjuvant temozolamide after RT in 3, PCV or other chemotherapy in 4 patients and in 5 patients SRS was the only postoperative intervention. The indication for SRS was locally progressing lesions in 32 (68%) patients and a new distant lesion in 15 (32%). Eight (17%) patients received a second salvage SRS treatment for a new focus. None of the repeat SRS treated patients experienced treatment related toxicity. The median target volume was 2.1 cc (0.2-9.5cc) and the median prescription dose for LINAC-based SRS treatment was 18 Gy (14-24Gy). Median time to progression was 5.1 months (1.0-96.4). Longstanding responses (> 12 months) were observed in 8 (17%) patients. One patient developed clinically significant radiation necrosis 3 months after SRS and required a surgical resection, but remained asymptomatic and without radiological evidence of active disease for more than 51 months thereafter. One additional patient developed biopsy -proven RN, which was resolved conservatively. No other treatment associated side effects were observed. Median survival time after SRS was 15.5 months (0.2-109.3) and overall median survival (since diagnosis) was 39.0 months (10.7-193.6 months). In conclusion, SRS may be considered an effective salvage procedure in selected patients with recurrent high-grade gliomas, providing long term responses in almost 20% of the cases.

CN-20 * BEVACIZUMAB CAUSING RECURRENT CEREBRAL INFARCTION IN A PATIENT WITH GLIOBLASTOMA: A PREVIOUSLY UNDOCUMENTED PHENOMENON

BACKGROUND: Bevacizumab, an anti-angiogenic VEGF antibody, is utilized for various malignancies, including glioblastoma multiforme (GBM). There has long been a correlation between bevacizumab therapy and CNS complications, including ischemic stroke and intracranial hemorrhage. Data on the pathophysiology of this correlation are scarce, and it has proven difficult to ascribe causality. To our knowledge there has never been a documented case of recurrent ischemia temporally associated with recurrent bevacizumab therapy. RESULTS: SS is a 70 year-old man with GBM. He received concomitant radiation and temozolamide (TMZ), followed by adjuvant TMZ and bevacizumab. After 5 cycles of TMZ/bevacizumab, he developed acute-onset left hemiparesis, upon which an MRI demonstrated an acute ischemic infarction. Angiography demonstrated mild attenuation of distal branches within the tumor bed. Chemotherapy was temporarily suspended, but after nearly two months, he had clinically recovered somewhat from the infarction. His TMZ/bevacizumab was restarted as his MRIs had been favorable to that point, with little disease progression. However, shortly thereafter, he had acute recurrence of his hemiparesis, and MRI again demonstrated acutely restricted diffusion. He was therefore switched to an alternative regimen that did not include bevacizumab. CONCLUSIONS: Here we describe a case of an ischemic stroke with radiographic correlate while on bevacizumab, with clinical improvement arrested by the development of a recurrent stroke when bevacizumab was restarted. Interestingly, the distal arteries within the stroke bed appeared somewhat attentuated, suggestive of radiation vasculopathy. This case, describing a previously undocumented phenomenon, raises the possibility of a synergistic effect of bevacizumab and radiation vasculopathy. It may be that radiation vasculoapthy alone is typically insufficient to cause ischemia, but the addition of bevacizumab may precipitate a sufficiently anti-vascular milieu as to cause frank and sudden-onset ischemia. In implicating bevacizumab, future directions may include large-scale studies to explore the temporal association of bevacizumab and ischemic stroke.

Continuous metronomic temozolamide with propranolol and etodolac in recurrent globlastoma: A pilot study.

e13005 Background: Glioblastoma is a extremely difficult disease to treat and recurrences are extremely high. Salvage treatment is of limited value. This remains an unmet need in oncology. Methods: Since 2003 to 2012, 32 patients of recurrent glioblastoma, post radiotherapy (concomitant with Temozolamide, followed by adjuvant Temozolamide) were taken. 32 patients were above the age of 65years and of the 32 in 9 patients it was partially resected. Patients were randomized to 2 groups, Arm A - with metronomic therapy with temozolamide and Arm B - of metronomic temozolamide combined with propranolol (eccentric dosing) and etodolac, (VT-122). Propranolol was titrated to maintain heart rate around 80 per minute. The primary end point was progression free survival at 6 months. Patients were assessed by MRI using Mac Donalds criteria. DWI criteria for vascularization was used. Results: The median time to progression was 5.2 months in Arm A and in Arm B it was 8.8 months. 6 months survival was 40% and 63% respect...