PO-0655: Stereotactic RT of recurrent high-grade glioma based on FET-PET and MRI: Initial results of a dose escalation trial

Purpose: The aims of the present study were to: 1- critically assess the utility of L-3,4- dihydroxy-6-18Ffluoro-phenyl-alanine (18F-DOPA) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) Positron Emission Tomography (PET)/Computed Tomography (CT) in patients with high grade glioma (HGG) and 2- describe the results of 18F-DOPA and 18F-FET PET/CT in a case series of patients with recurrent HGG. Methods: We searched for studies using the following databases: PubMed, Web of Science and Scopus. The search terms were: glioma OR brain neoplasm and DOPA OR DOPA PET OR DOPA PET/CT and FET OR FET PET OR FET PET/CT. From a mono-institutional database, we retrospectively analyzed the 18F-DOPA and 18F-FET PET/CT of 29 patients (age: 56 ± 12 years) with suspicious for recurrent HGG. All patients underwent 18F-DOPA or 18F-FET PET/CT for a multidisciplinary decision. The final definition of recurrence was made by magnetic resonance imaging (MRI) and/or multidisciplinary decision, mainly based on the clinical data. Results: Fifty-one articles were found, of which 49 were discarded, therefore 2 studies were finally selected. In both the studies, 18F-DOPA and 18F-FET as exchangeable in clinical practice particularly for HGG patients. From our institutional experience, in 29 patients, we found that sensitivity, specificity and accuracy of 18F-DOPA PET/CT in HGG were 100% (95% confidence interval- 95%CI - 81-100%), 63% (95%CI: 39-82%) and 62% (95%CI: 39-81%), respectively. 18F-FET PET/CT was true positive in 4 and true negative in 4 patients. Sensitivity, specificity and accuracy for 18F-FET PET/CT in HGG were 100%. Conclusion: 18F-DOPA and 18F-FET PET/CT have a similar diagnostic accuracy in patients with recurrent HGG. However, 18F-DOPA PET/CT could be affected by inflammation conditions (false positive) that can alter the final results. Large comparative trials are warranted in order to better understand the utility of 18F-DOPA or 18F-FET PET/CT in patients with HGG.

Download Full-text

External beam radiation dose escalation for high grade glioma

Cochrane Database of Systematic Reviews ◽

10.1002/14651858.cd011475.pub3 ◽

2020 ◽

Author(s):

Luluel Khan ◽

Hany Soliman ◽

Arjun Sahgal ◽

James Perry ◽

Wei Xu ◽

...

Keyword(s):

Radiation Dose ◽

Dose Escalation ◽

High Grade Glioma ◽

External Beam Radiation ◽

External Beam ◽

High Grade ◽

Beam Radiation

Download Full-text

RT-10 * DO WE NEED IMAGE-GUIDANCE OF GTV DEFINED BY FET-PET IN RADIOTHERAPY OF HIGH GRADE GLIOMA?

Neuro-Oncology ◽

10.1093/neuonc/nou270.7 ◽

2014 ◽

Vol 16 (suppl 5) ◽

pp. v189-v189

Author(s):

S. Engelholm ◽

J. Costa ◽

M. Lundemann ◽

I. Law ◽

P. M. a. Rosenschold ◽

...

Keyword(s):

Image Guidance ◽

High Grade Glioma ◽

High Grade ◽

Fet Pet

Download Full-text

External beam radiation dose escalation for high grade glioma

10.1002/14651858.cd011475 ◽

2015 ◽

Cited By ~ 1

Author(s):

Luluel Khan ◽

Hany Soliman ◽

Arjun Sahgal ◽

James Perry ◽

Wei Xu ◽

...

Keyword(s):

Radiation Dose ◽

Dose Escalation ◽

High Grade Glioma ◽

External Beam Radiation ◽

External Beam ◽

High Grade ◽

Beam Radiation

Download Full-text

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

Neuro-Oncology ◽

10.1093/neuonc/noz126.295 ◽

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.

Download Full-text

Phase I dose escalation of temozolomide with thiotepa and carboplatin with autologous hematopoietic cell reinfusion in patients with recurrent/refractory malignant brain tumors

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.2060 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 2060-2060 ◽

Cited By ~ 1

Author(s):

S. Gardner ◽

M. Fisher ◽

J. Belasco ◽

P. Phillips ◽

J. Finlay

Keyword(s):

Brain Tumors ◽

Dose Level ◽

Dose Escalation ◽

Standard Dose ◽

Treatment Options ◽

High Grade Glioma ◽

High Dose ◽

High Grade ◽

Malignant Brain Tumors ◽

Dose Limiting Toxicity

2060 Background: The prognosis for most patients with recurrent malignant brain tumors is dismal. Treatment options are limited especially for patients who have already received irradiation. TMZ is an oral alkylating agent which is approved for use in patients with high grade glioma and has also been shown to have activity in patients with recurrent medulloblastoma. It’s primary dose-limiting toxicity is non- cumulative bone marrow suppression. In the present study, TMZ is given in a dose escalation fashion with fixed doses of high dose thiotepa and carboplatin with AHCR in the treatment of patients with recurrent or refractory malignant brain tumors. Methods: Treatment consisted of TMZ twice daily on days -10 to -6 followed by thiotepa 300 mg/m2/day and carboplatin AUC=7/day on days -5 to -3 with AHCR on day 0. Filgrastim was given day +1 and continued until engraftment. Results: 27 patients (18M; 9F) ages 3–46 years were treated from 11/00 until 10/04. Diagnoses included high grade glioma (n=12); medulloblastoma/PNET (n=9); CNS germ cell tumor (GCT) (n=4); and 1 each ependymoma and spinal cord PNET. TMZ doses ranged from 50 mg/m2 twice daily (100 mg/m2/day) to 200 mg/m2 twice daily (400 mg/m2/day) for 5 days. One patient had dose limiting toxicity consisting of reversible veno-occlusive disease at dose level 3 (TMZ 100 mg/m2 twice daily). Two patients had dose limiting toxicity at dose level 7 (TMZ 200 mg/m2 twice daily) consisting of transient encephalopathy (n=1) and severe mucositis (n=1). Additional toxicities included bacteremia (n=11), C. difficile enteritis (n=6) and grade 4 elevation of bilirubin and/or liver transaminases (n=2). There were no toxic deaths. Survival included 3 patients with glioma (38–48 months); two of whom had relapsed following standard dose TMZ; 3 patients with PNET/MB (48–72 months) and 3 patients with CNS GCT (26–71 months). Conclusions: Increased doses of TMZ are feasible when given with AHCR. There is presently a phase II study underway through the Pediatric Blood and Marrow Transplant Consortium evaluating the efficacy of TMZ at a dose of 175 mg/m2/day twice daily for 5 days with high dose thiotepa and carboplatin and AHCR. No significant financial relationships to disclose.

Download Full-text

Prognostic Significance of Dynamic 18F-FET PET in Newly Diagnosed Astrocytic High-Grade Glioma

Journal of Nuclear Medicine ◽

10.2967/jnumed.114.144675 ◽

2014 ◽

Vol 56 (1) ◽

pp. 9-15 ◽

Cited By ~ 94

Author(s):

N. L. Jansen ◽

B. Suchorska ◽

V. Wenter ◽

C. Schmid-Tannwald ◽

A. Todica ◽

...

Keyword(s):

Prognostic Significance ◽

High Grade Glioma ◽

High Grade ◽

Newly Diagnosed ◽

Fet Pet

Download Full-text

Differentiation of treatment-related changes from high-grade glioma progression: A direct comparison between FET PET and ADC values obtained by DWI MRI

10.1055/s-0039-1683523 ◽

2019 ◽

Author(s):

J Werner ◽

G Stoffels ◽

T Lichtenstein ◽

J Borggrefe ◽

G Ceccon ◽

...

Keyword(s):

High Grade Glioma ◽

High Grade ◽

Fet Pet ◽

Adc Values ◽

Glioma Progression

Download Full-text

A phase I study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activities of daily oral BAL101553, a novel tumor checkpoint controller (TCC) in adult patients with progressive or recurrent glioblastoma (GBM) or high-grade glioma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps2601 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS2601-TPS2601

Author(s):

Alvaro Henrique Ingles Garces ◽

Elizabeth R. Plummer ◽

Juanita Suzanne Lopez ◽

Rebecca Sophie Kristeleit ◽

Julie MacDonald ◽

...

Keyword(s):

Antitumor Activity ◽

Dose Escalation ◽

Spindle Assembly Checkpoint ◽

Phase 1 ◽

High Grade Glioma ◽

Low Grade ◽

High Grade ◽

Tumor Cell Death ◽

Antitumor Activities ◽

Dose Escalation Study

TPS2601 Background: BAL101553 (prodrug of BAL27862) is a novel TCC that promotes tumor cell death by modulating the spindle assembly checkpoint. BAL27862 is a lipophilic, small molecule (MW 387) shown in rats to penetrate the brain (1:1 plasma ratio) and has shown promising antitumor activity in orthotopic preclinical models of GBM as monotherapy or in combination with radiotherapy (RT) with/without chemotherapy. In a completed Phase 1 study with 2-h IV infusions (Days 1, 8, 15, q28d, NCT01397929 , CDI-CS-001, Lopez et al. J Clin Oncol 34, 2016 suppl; 2525), dose-limiting vascular effects were observed and appeared Cmax related. Preclinical data suggest that antiproliferative effects of BAL101553/27862 are driven by exposure (AUC); thus vascular toxicity and antitumor activity are mediated by different PK drivers. In this ongoing study (NCT02490800, CDI-CS-002), daily oral BAL101553 was initially examined in solid-tumor patients; no vascular toxicities were observed at doses up to the MAD of 30 mg QD. Given this absence, the study was amended to enroll separate cohorts of patients with progressive or recurrent GBM or high-grade glioma. Methods: This is an ongoing multicenter, open-label, Phase 1 dose-escalation study using a 3+3 design to determine the MTD, characterize dose-limiting toxicities and assess the PK, PD and antitumor activities of daily oral administration of BAL101553 in consecutive 28-day cycles at a starting dose of 8 mg QD. Patients with histologically-confirmed GBM or high-grade glioma, with progressive or recurrent disease after prior RT with/without chemotherapy, are eligible for enrollment. This includes patients with histologically-confirmed low-grade glioma with unequivocal evidence by imaging of transformation to high-grade glioma. Adverse events are assessed using CTCAEv4; tumor response by RANO (every 2 cycles). The dose escalation allows for doubling of dose levels depending on observed toxicities. PD assessments include circulating tumor cells. PK profiles are assessed throughout the first two treatment cycles. Clinical trial information: NCT02490800.

Download Full-text