Irradiation Fields and Doses in Glioblastoma Multiforme: Are Current Standards Adequate?

2001 ◽  
Vol 87 (2) ◽  
pp. 85-90 ◽  
Author(s):  
Michele Reni ◽  
Cesare Cozzarini ◽  
Maria Grazia Panucci ◽  
Giovanni Luca Ceresoli ◽  
Andrés José María Ferreri ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Performance Status ◽  
Phase Iii ◽  
Control Group ◽  
Whole Brain ◽  
Female Ratio ◽  
Brain Irradiation ◽  
Impact On Survival ◽  
Prospective Trials ◽  
The Impact

Aims and background The optimum conventional radiotherapy in glioblastoma multiforme patients has not been clearly defined by prospective trials. To better characterize a standard radiotherapy in glioblastoma multiforme, the impact on survival of different fields and doses was analyzed in a retrospective single center series. Methods One hundred and forty-seven patients with glioblastoma multiforme, submitted to biopsy only (n = 15), subtotal (n = 48) or total resection (n = 82) and who completed the planned postsurgical radiotherapy, were considered. The median age was 57 years, the male/female ratio 1.5/1, and the performance status ≥70 in 76%. Whole brain irradiation, followed by a boost to partial brain, was used in 75 cases with a whole brain dose of 44–50 Gy (median, 46) and a partial brain dose of 56–70 Gy (median, 60 Gy). Partial brain irradiation alone was used in 72 patients with a dose of 56–70 Gy (median, 61 Gy). Ninety-eight patients received 56–60 Gy (median, 59 Gy) to partial brain whereas 49 patients received 61–70 Gy (median, 63 Gy). Results There was an almost significantly longer survival in patients irradiated to the partial brain alone with respect to those also receiving whole brain radiotherapy (P = 0.056). Doses <60 Gy significantly prolonged survival (P = 0.006). Multivariate analysis confirmed that the impact on survival of radiation dose was independent of age, performance status, extent of surgery, field of irradiation and the use of chemotherapy. The extent of irradiation field was not independently related to improved survival. Conclusions Our retrospective findings suggest that we reflect on the adequacy of the current standard irradiation parameters. Well-designed prospective trials are necessary to standardize the radiotherapy control group in patients with glioblastoma multiforme to be compared in phase III trials with innovative therapeutic approaches.

scholarly journals RADT-23. IMPACT OF REIRRADIATION UTILIZING STEREOTACTIC RADIOSURGERY ON RECURRENT GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
O’Dell Patrick ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
D Sun ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
High Performance ◽  
Performance Status ◽  
Treatment Options ◽  
Methylation Status ◽  
Initial Therapy ◽  
Recurrent Glioblastoma ◽  
Control Group ◽  
The Impact

Abstract BACKGROUND Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes. METHODS We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups. RESULTS We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P &lt; 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P&lt; 0.0001, HR for death 0.33 (95% CI 0.18-0.6)]. CONCLUSIONS In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.

scholarly journals TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030731 ◽  
Author(s):  
Jarad Martin ◽  
Paul Keall ◽  
Shankar Siva ◽  
Peter Greer ◽  
David Christie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Performance Status ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Dose ◽  
The Novel ◽  
Ecog Performance Status ◽  
Initial Portion ◽  
The Impact

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration ofNew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.Methods and analysisEligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.Ethics and disseminationNINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.Trial registration numberANZCTN 12615000223538.

Serum cathepsin B (CB) levels are prognostic in chemotherapy-naive patients (pts) with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18036-18036
Author(s):  
J. W. Singer ◽  
F. B. Oldham ◽  
B. Bandstra ◽  
L. Sandalic ◽  
J. Bianco ◽  
...  
Keyword(s):  
Median Survival ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Phase Iii ◽  
Serum Samples ◽  
Protein Levels ◽  
Lysosomal Cysteine Protease ◽  
Phase Iii Trials ◽  
And Performance ◽  
The Impact

18036 Background: CB is an estrogen-influenced lysosomal cysteine protease produced by tumor cells and tumor-associated macrophages; tumor tissue CB protein levels and proteolytic activity are prognostic in NSCLC (Anticancer Res. 2004; 24:4147–61). The prognostic value of serum CB has not previously been evaluated in NSCLC. Here we evaluate the impact of pretreatment CB levels on survival in pts from 2 phase III trials in advanced NSCLC, STELLAR 3 and 4. These trials compared paclitaxel poliglumex (PPX) against commonly used regimens. As the intratumoral metabolic pathway of PPX is characterized by the CB-mediated release of paclitaxel (P) from a polymeric backbone (Ca Chemother Pharm. 2006. Epub ahead of print), correlation of CB levels with PPX efficacy was assessed as well. Methods: Pretreatment serum samples from 450 chemo-naive pts with advanced NSCLC and PS 2 enrolled in STELLAR 3 (P + carboplatin (C) v. PPX + C) (N=315) and STELLAR 4 (vinorelbine or gemcitabine v. PPX) (N=135) were assayed for CB by ELISA (ICON Labs). Values were assessed by quartiles and there was a clear breakpoint at the median. Pts were categorized as high or low CB based on values above or below the median (64 ng/ml). The effect of CB levels on survival was evaluated by log rank for pooled pts from the studies. Results: As detailed in the table , median survival for non-PPX-treated pts was worse if CB was high; in contrast, median survival for PPX-treated pts did not differ by CB level. Pts with high CB receiving PPX showed a trend towards better survival compared to those receiving control regimens. Conclusions: The data suggest that serum CB may be prognostic biomarker for NSCLC. Retrospective analysis suggests a trend towards improved survival in patients with high CB receiving PPX; prospective studies are required to confirm this observation. [Table: see text] No significant financial relationships to disclose.

A randomized phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable and metastatic pancreatic cancer (PC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4601-4601 ◽  
Author(s):  
T. Buanes ◽  
J. Maurel ◽  
W. Liauw ◽  
M. Hebbar ◽  
J. Nemunaitis
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Locally Advanced ◽  
Peptide Vaccine ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Delayed Treatment ◽  
Sequential Combination ◽  
The Impact

4601 Background: A phase I/II study with GV1001, a telomerase peptide vaccine, showed a median overall survival (OS) of 8.6 months in non-resectable PC (Bernhardt SL et al, Br J Cancer. 2006;95:1474–1482). This phase III trial was conducted to determine the impact on overall survival of G monotherapy vs. GV1001 in sequential combination with G in unresectable and metastatic PC. Methods: Eligible patients (pts) had chemotherapy-naive, advanced PC and ECOG performance status 0–1. Pts were randomized 1:1 to receive arm A: G (1,000 mg/m2 30 min i.v.) weekly for 7 weeks (w), 1w off and then 3w during 4-weekly cycles, or arm B: GV1001 0.56 mg s.c. plus GM-CSF as immune adjuvant on days 1, 3, 5, 8, 15, 22, 36, then every 4 weeks. Patients who progressed clinically or radiologically during GV1001 continued on GV1001 and concomitant gemcitabine. CT scans were performed every 8 weeks. The primary end-point was OS. A sample size of 520 patients allowed the detection of a hazard ratio (HR) of 0.73 (B/A), with 2α = 0.05 and 90% power. Results: Between June 2006 and May 2008, 365 pts were enrolled (A / B; 182 / 183). The study was stopped prematurely due to a preliminary analysis with 178 events showing no survival benefit of GV1001. Pts were well balanced for baseline characteristics: male 59.3% / 62.8%; median age 61y / 61y; ECOG PS 0 34.3% / 36.7%; locally advanced 22.4% / 20.7%. As of August 2008, 238 pts (A / B : 114 / 124) had died. Median OS was 7.3 / 5.9 months (HR 0.8; 95% CI 0.6–1.0). Median progression-free survival (PFS) was 3.7 / 1.9 months (HR 0.5; 95%CI 0.4–0.7). Grade 3–4 AEs: gastrointestinal 6% / 8%, infection 5% / 5%, vascular disorders 2% / 3%, neutropenia 6% / 3%. Conclusions: GV1001 did not show efficacy in sequential combination with G in advanced PC. The advantage of G monotherapy over the sequential combination may be due to the delayed treatment with G in arm B. [Table: see text]

Nomogram to estimate the activity of second-line therapy for advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4524-4524
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Neeraj Agarwal ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Performance Status ◽  
Phase Iii ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
The Impact

4524 Background: Prognostic factors may impact on endpoints used in phase II trials of second-line therapy for advanced UC. We aimed to study the impact of prognostic factors (liver metastasis [LM], anemia [Hb<10 g/dl], ECOG-performance status [PS] ≥1, time from prior chemotherapy [TFPC]) on PFS6 and RR. Methods: Twelve phase II trials evaluating second-line chemotherapy and/or biologics (n=748) in patients with progressive disease were pooled. PFS was defined as tumor progression or death from any cause. PFS6 was defined from the date of registration and calculated using the Kaplan-Meier method. RR was defined using RECIST 1.0. A nomogram predicting PFS6 was constructed using the RMS package in R (www.r-project.org). Results: Data regarding progression, Hb, LM, PS and TFPC were available from 570 patients. The mean age was 65.1 years, 45.3% had ECOG-PS ≥1, 30.2% had LM, 14.6% had anemia and TFPC was <6 months (mo) in 60.2%. The overall median PFS was 2.7 mo, PFS6 was 22.2% (95% CI: 18.8-25.9) and RR was 17.5% (95% CI: 14.5%-20.9%). For every unit increase in risk group, the hazard of progression increased by 41% and the odds of response decreased by 48% (Table). A nomogram was constructed to predict PFS6 on an individual patient level. Conclusions: PFS6 and RR vary as a function of prognostic factors in patients receiving second-line therapy for advanced UC. A nomogram incorporating prognostic factors might facilitate the evaluation of activity across phase II trials enrolling heterogeneous populations and can help to select and stratify patients for phase III evaluation of suitable agents. [Table: see text]

Impact of concomitant bone-targeted therapies (BTT) on outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) without prior chemotherapy (ctx) treated with abiraterone acetate (AA) or prednisone (P).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5037-5037 ◽  
Author(s):  
Fred Saad ◽  
Karim Fizazi ◽  
Matthew R. Smith ◽  
Thomas W. Griffin ◽  
Anil Londhe ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Cox Regression ◽  
Performance Status ◽  
Phase Iii ◽  
End Points ◽  
Opiate Use ◽  
Potential Clinical Benefit ◽  
Ecog Ps ◽  
Post Hoc ◽  
The Impact

5037 Background: BTT can delay symptomatic progression in cancer pts with bone metastases. In a post hoc analysis, we assessed the impact of concomitant BTT on outcomes in a recent large, multinational study in mCRPC pts without prior ctx. Methods: COU-AA-302 was a phase III trial in asymptomatic/mildly symptomatic pts with progressive mCRPC and no prior ctx. 1,088 pts were stratified by ECOG performance status (ECOG-PS, 0 vs 1) and randomized 1:1 to AA 1 g or placebo QD, plus prednisone 5 mg BID. Radiographic progression-free survival (rPFS) and overall survival (OS) were primary end points; secondary end points were times to opiate use, ctx, ECOG-PS deterioration, and PSA progression. The effect of concomitant use of BTT on all end points was assessed retrospectively using a stratified Cox regression model with factors for treatment, concomitant BTT, interaction of treatment and BTT, and baseline covariates. All data were obtained from a prespecified interim analysis at 55% OS events. Results: Median follow-up at the time of analysis was 27.1 mos. Among intent-to-treat (ITT) pts, 184/546 AA and 169/542 P pts received concomitant BTT for treatment of bone metastases, either zoledronic acid (n = 330), other bisphosphonates (n = 16), denosumab (n = 22), and/or other BTT (n = 5). In these pts, concomitant BTT use was associated with improved OS, time to opiate use for cancer pain, and time to ECOG-PS deterioration (Table). Results were similar in a sensitivity analysis including only ITT pts with bone metastases at baseline. Conclusions: In this post hoc, exploratory analysis, concomitant BTT use was associated with delayed symptomatic progression in asymptomatic/mildly symptomatic mCRPC pts. This potential clinical benefit should be investigated in prospective studies. Clinical trial information: NCT00887198. [Table: see text]

scholarly journals Does Stereotactic Radiosurgery Have a Role in the Management of Patients Presenting With 4 or More Brain Metastases?

Neurosurgery ◽  
2018 ◽  
Vol 84 (3) ◽  
pp. 558-566 ◽  
Author(s):  
Michael H Soike ◽  
Ryan T Hughes ◽  
Michael Farris ◽  
Emory R McTyre ◽  
Christina K Cramer ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Performance Status ◽  
Phase Iii ◽  
Whole Brain Radiation ◽  
Multiple Phase ◽  
Phase Iii Trials ◽  
Prospective Trials ◽  
Level I ◽  
Brain Radiation

Abstract Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are effective treatments for management of brain metastases. Prospective trials comparing the 2 modalities in patients with fewer than 4 brain metastases demonstrate that overall survival (OS) is similar. Intracranial failure is more common after SRS, while WBRT is associated with neurocognitive decline. As technology has advanced, fewer technical obstacles remain for treating patients with 4 or more brain metastases with SRS, but level I data supporting its use are lacking.  Observational prospective studies and retrospective series indicate that in patients with 4 or more brain metastases, performance status, total volume of intracranial disease, histology, and rate of development of new brain metastases predict outcomes more accurately than the number of brain metastases. It may be reasonable to initially offer SRS to some patients with 4 or more brain metastases. Initiating therapy with SRS avoids the acute and late sequelae of WBRT. Multiple phase III trials of SRS vs WBRT, both currently open or under development, are directly comparing quality of life and OS for patients with 4 or more brain metastases to help answer the question of SRS appropriateness for these patients.

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