scholarly journals ACTR-49. INITIAL EXPERIENCE WITH SCALP PRESERVATION AND RADIATION PLUS CONCURRENT ALTERNATING ELECTRIC TUMOR-TREATING FIELDS (SPARE) FOR GLIOBLASTOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi24-vi24 ◽  
Author(s):  
Andrew Song ◽  
Michele Ly ◽  
Voichita Bar-Ad ◽  
Maria Werner-Wasik ◽  
Jon Glass ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Synergistic Effects ◽  
Prospective Trial ◽  
Skin Toxicity ◽  
Concurrent Chemoradiation ◽  
Subtotal Resection ◽  
Initial Experience ◽  
Newly Diagnosed ◽  
Idh Mutations ◽  
Newly Diagnosed Glioblastoma

Abstract INTRODUCTION Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide with electric tumor treatment fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our initial experience evaluating toxicity and tolerability of scalp-preserving radiation with concurrent TTFields. METHODS We conducted a single arm pilot study. Adult patients (≥ 18 years old) with KPS ≥ 60 with newly diagnosed glioblastoma were included. All patients received concurrent scalp-preserving radiation (60 Gy in 30 fractions), standard temozolomide (75 mg/m2 daily), and TTFields (200 kHz; ≥ 18 hr daily). Maintenance therapy included standard temozolomide and TTFields. Radiation treatment was delivered through TTFields arrays. Our primary endpoint was safety and toxicity for concurrent TTFields with chemoradiation in newly diagnosed glioblastoma. RESULTS Here we report the first seven patients on the trial. Five were male, and 2 female, with median age 58 y/o (range 49–73). Median KPS was 90. Median follow-up was 5.2 months (range 1.4–11.2). MGMT status was unmethylated for 6 patients, and one unknown, and no IDH mutations. Four (57.1%) received gross total resection and three (42.9%) had subtotal resection. All patients completed concurrent chemoradiation plus TTFields without radiation or TTFields treatment interruption or discontinuation. There was no related Grade 3 or higher toxicity. Skin toxicity (erythema, dermatitis, pruritus) was noted in all patients, however, limited to Grade 1 or 2 which resolved spontaneously or responded to topical medications. All patients were alive at time of writing. Two (28.6%) patients had progression, of which one (at 9 months) continued TTFields and temozolomide with bevacizumab, while the other (at 4 months) discontinued TTFields and underwent re-resection with bevacizumab. CONCLUSIONS Concurrent TTFields with scalp-preserving chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trial is warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.

CTNI-19. CONCURRENT CHEMORADIATION AND TUMOR TREATING FIELDS (TTFields, 200 kHz) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF DISTANT RECURRENCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi63-vi63
Author(s):  
Ayesha S Ali ◽  
Muneeb Niazi ◽  
Voichita Bar-Ad ◽  
Maria Werner-Wasik ◽  
David Andrews ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Synergistic Effects ◽  
Secondary Analysis ◽  
Standard Of Care ◽  
Distant Recurrence ◽  
Concurrent Chemoradiation ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.

Scalp-sparing radiation with concurrent temozolomide and tumor treating fields (SPARE) for patients with newly diagnosed glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2056-2056
Author(s):  
Ryan C Miller ◽  
Andrew Jehyun Song ◽  
Ayesha Ali ◽  
Voichita C Bar-Ad ◽  
Nina Leyson Martinez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Treatment ◽  
Synergistic Effects ◽  
Standard Of Care ◽  
Treatment Interruption ◽  
Newly Diagnosed ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Constraints ◽  
Topical Medications

2056 Background: Standard of care for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our clinical trial evaluating safety and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. Methods: This is a single arm pilot study. Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of TTFields concurrent with chemoradiation in patients with newly diagnosed glioblastoma. Results: A total of 30 patients were enrolled in the trial. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). Median follow-up was 8.9 months (range 1.6 to 21.4 months). Twenty (66.7%) patients had unmethylated MGMT promotor status and ten (33.3%) patients had methylated promoter status. Median time from surgery to radiation was 34 days (26 to 49 days). Scalp dose constraints were achieved for all patients, with the mean dose having a median value of 8.3 Gy (range 4.3 to 14.8 Gy), the D20cc median was 26.1 Gy (range 17.7 to 42.8 Gy), and the D30cc median was 23.5 Gy (range 14.8 to 35.4 Gy). Skin adverse events (AEs; erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). Nineteen patients (63.3%) had progression, with a median PFS of 7.6 months (range 1.6 to 12.7 months). Overall survival was not reached. Conclusions: Concurrent TTFields (200 kHz) with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation. Clinical trial information: NCT03477110.

scholarly journals Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma

2020 ◽  
Author(s):  
Muayad F Almahariq ◽  
Thomas J Quinn ◽  
Jessica D Arden ◽  
P T Roskos ◽  
George D Wilson ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Verbal Learning ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Neurocognitive Function ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Clinical Series ◽  
Newly Diagnosed Glioblastoma

Abstract Background Pulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM). Methods This is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation. Results Twenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)–mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID. Conclusions Treatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.

RADT-13. SPARE TRIAL: SCALP-SPARING RADIATION WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATING FIELDS FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi43-vi44
Author(s):  
Ryan Miller ◽  
Andrew Song ◽  
Ayesha S Ali ◽  
Voichita Bar-Ad ◽  
Nina, L Martinez ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Methylation Status ◽  
Treatment Interruption ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Prospective Trials ◽  
Dose Constraints ◽  
Topical Medications

Abstract INTRODUCTION Current adjuvant treatment for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). We report our clinical trial evaluating feasibility and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. METHODS Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma with a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment. RESULTS Thirty patients were enrolled. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median follow-up was 10.8 months (range 1.6 to 21.3 months). Twenty (66.7%) patients had unmethylated MGMT promotor and ten (33.3%) patients had methylated promoter. Scalp dose constraints were achieved for all patients. Skin adverse events (erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). The median PFS for the entire cohort was 9.1 months (at least 8.5 months, 95% confidence). The median PFS for patients with MGMT promoter methylation status was 11.4 months (at least 9.5 months, 95% confidence). Overall survival was not reached. CONCLUSIONS Concurrent TTFields with scalp-sparing chemoradiation is feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.

scholarly journals Phase II Study of Iniparib with Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma

2018 ◽  
Vol 25 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Jaishri O. Blakeley ◽  
Stuart A. Grossman ◽  
Andrew S. Chi ◽  
Tom Mikkelsen ◽  
Myrna R. Rosenfeld ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Concurrent Chemoradiation ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

scholarly journals Impact of Timing of Concurrent Chemoradiation for Newly Diagnosed Glioblastoma

Neurosurgery ◽  
2015 ◽  
Vol 62 (CN_suppl_1) ◽  
pp. 160-165 ◽  
Author(s):  
Seunggu J. Han ◽  
Dario J. Englot ◽  
Harjus Birk ◽  
Annette M. Molinaro ◽  
Susan M. Chang ◽  
...  
Keyword(s):  
Concurrent Chemoradiation ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

scholarly journals P14.71 Tumor Treating Fields combined with radiotherapy and temozolomide for newly diagnosed glioblastoma: final safety and efficacy results from a pilot study

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii84-iii84
Author(s):  
R Grossman ◽  
F Bokstein ◽  
D Blumenthal ◽  
C Ben Harush ◽  
D Limon ◽  
...  
Keyword(s):  
Pilot Study ◽  
Electric Fields ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Sensitizing Effect

Abstract BACKGROUND Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment consisting of low intensity alternating electric fields. The combination of TTFields with maintenance temozolomide significantly improved survival versus temozolomide alone in the phase 3 EF-14 study in newly diagnosed glioblastoma (ndGBM). In preclinical studies, TTFields increased the number of glioma cells undergoing cellular death following radiotherapy (RT) by inhibiting DNA damage repair, suggesting a radio-sensitizing effect of TTFields. This pilot study is the first to evaluate the safety and feasibility of administering TTFields concomitant to RT and TMZ in ndGBM patients. MATERIAL AND METHODS Patients diagnosed with ndGBM were treated with TTFields/RT/TMZ followed by maintenance TMZ and TTFields for up to 24 months. TTFields (200kHz) were delivered for >18 hours/day while the transducer arrays were removed during delivery of RT. TMZ was administered at a dose of 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined TTFields/RT/TMZ; secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Adverse events (AEs) were graded according to CTCAE V4.0. RESULTS 10 ndGBM patients that recovered from maximal debulking surgery or biopsy were enrolled at a single center in Israel between April and December 2017. Five patients (50%) had undergone gross total resection while the rest had biopsy only. Eight of the patients were male, median age was 59, median KPS was 80 and median dose of RT was 60 Gy. Six patients (60%) reported at least one AE. The most common AE was TTFields-related skin toxicity, reported in four patients (40%), all of which were grade 1–2 in severity. Two patients reported serious AEs (seizures and general deterioration) that were considered unrelated to TTFields. Median PFS with RT/TMZ/TTFields was 10.5 months. Median OS has not yet been reached. CONCLUSION The proportion of patients with TTFields-related skin toxicity was similar to that reported in ndGBM patients in the randomized Phase III study (52%), where patients started TTFields at least 4 weeks after RT. No other TTFields-related toxicities were reported and there were no increase in RT- or TMZ-related toxicities as a result of combining TTFields with RT in addition to TMZ. Based on the safety and preliminary efficacy results of this pilot study, a phase II randomized study has been initiated to investigate the efficacy of concomitant RT/TMZ/TTFields in 60 ndGBM patients.

Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2009-2009 ◽  
Author(s):  
Elizabeth Robins Gerstner ◽  
Kyrre E. Emblem ◽  
Andrew S. Chi ◽  
April F. Eichler ◽  
Fred Hochberg ◽  
...  
Keyword(s):  
Blood Flow ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Tumor Blood Flow ◽  
Phase Ib ◽  
Entire Cohort ◽  
Radiographic Response ◽  
Newly Diagnosed Glioblastoma

2009 Background: Anti-angiogenic therapy is hypothesized to synergize with radiation and chemotherapy by improving tumor blood flow. We evaluated the tolerability, efficacy and potential mechanism of action of radiation, temozolomide, and cediranib in newly diagnosed glioblastoma patients. Methods: Newly diagnosed glioblastoma patients were treated with radiation, temozolomide, and cediranib followed by monthly temozolomide for 6 cycles and daily cediranib until tumor progression or toxicity as part of an IRB-approved, Phase Ib/II clinical trial. MRI scans including measurement of cerebral blood flow were performed at baseline, weekly during the 6 weeks of chemoradiation and then monthly. Radiographic response was determined by RANO criteria. Results: Six patients were enrolled in the phase Ib part of the study with cediranib 30 mg daily in combination with temozolomide and radiation. No dose-limiting toxicities were identified. Forty patients were enrolled in the phase II part of the study. Among the entire cohort of 46 patients, median age was 57 (range 35-74), median KPS was 90% (60-100), 36 patients underwent a subtotal resection and 10 underwent biopsy. 26/30 patients taking corticosteroids were able to taper corticosteroids during chemoradiation. Off study reasons included toxicity (14), disease progression (18), and patient preference (2). Five patients remain on study without disease progression and 20 patients have died. Median duration on study was 158 days. Median progression free survival was 288 days (95%CI 240,∞) and median overall survival was 786 days (95%CI 411 ,∞). Best radiographic response in patients who completed chemoradiation was CR in 2 patients, PR in 20 patients, and SD in 15 patients. Patients with increased tumor perfusion during chemoradiation survived nearly 1 year longer (mean OS=611 days) than patients with decreased perfusion (mean OS=269 days). Conclusions: Cediranib was well tolerated and led to improved PFS and OS compared to historical controls, particularly in those with improved perfusion. This combination is being evaluated in an ongoing randomized trial (RTOG 0837).

Final results of a single-arm phase II study of bevacizumab and temozolomide following radiochemotherapy in newly dignosed adult glioblastoma patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2076-2076 ◽  
Author(s):  
Martin Kelly Nicholas ◽  
Rimas Vincas Lukas ◽  
Christine Amidei ◽  
Nicholas Vick ◽  
Nina Paleologos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Treatment ◽  
Treatment Phase ◽  
Progression Free Survival ◽  
Concomitant Administration ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Intention To Treat ◽  
Newly Diagnosed Glioblastoma ◽  
Post Radiation

2076 Background: This study evaluated efficacy and safety of bevacizumab (BEV) added to the post-radiation treatment phase for patients with newly diagnosed glioblastoma (GBM). Methods: Sixty-two participants with newly diagnosed GBM were enrolled between May 2007 and June 2010. Participants received standard radiation therapy (RT) within 6 weeks of surgery, and concomitant administration of temozolomide (TMZ). Four weeks after radiation, treatment with TMZ (Days 1-5 of a 28 day cycle) with BEV, (days 1 and 15 of a 28 day cycle) was started, and continued until disease progressed or adverse effects indicated need to stop treatment. Analyses were completed for all participants by intention to treat (ITT), with progression-free survival (PFS) and overall survival (OS) serving as primary and secondary endpoints respectively. Results: Subbjects completed a mean of 7.7 (range 0-29) cycles of post-RT with BEV and TMZ. Twenty participants (32%) were unable to proceed to the post-RT phase. The forty-two participants who did proceed to the post-RT phase completed a mean of 11.5 cycles of treatment. Thirty-eight participants (61%) stopped the study due to disease progression; 6 participants (14%) voluntarily discontinued treatment after 24 cycles with at least stable disease. At a median follow-up time of 24 months, median progression-free survival (PFS) for all participants was 8.8 months while median overall survival (OS) was 16.5 months for all participants. Ly with These results also compare favorably with recently reported results from the AVAglio study (PFS = 10.6 mo.). The toxicity profile was consistent with that reported in similar studies. MGMT promoter methtion.ylation status is under investiga Conclusions: Participants in this study demonstrated a median 1.9 month PFS benefit as compared to the 6.9 median OS reported by Stupp, et al. (2005) and a median 1.9 month OS benefit as compared to the 14.6 month median OS reported by Stupp, et al. (2005). Results suggest that the addition of bevacizumab to the post-RT phase of treatment improves both PFS and OS for persons with GBM despite the high percentage of participants being unable to progress to post-radiation treatment. Clinical trial information: NCT005906.

Sign in / Sign up

Export Citation Format

Share Document