Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM)

Neurosurgery ◽  
2018 ◽  
Vol 84 (5) ◽  
pp. 1133-1137
Author(s):  
Stefanie Brehmer ◽  
Mario Alexander Grimm ◽  
Alex Förster ◽  
Marcel Seiz-Rosenhagen ◽  
Grit Welzel ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Gamma Knife Radiosurgery ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Open Label ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

scholarly journals RBTT-11. NRG ONCOLOGY NRG-BN006: A PHASE II/III RANDOMIZED, OPEN-LABEL STUDY OF TOCA 511 AND TOCA FC WITH STANDARD OF CARE COMPARED TO STANDARD OF CARE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi220-vi221
Author(s):  
Manmeet Ahluwalia ◽  
Stephanie Pugh ◽  
Benjamin Ellingson ◽  
Rupesh Kotecha ◽  
Timothy Cloughesy ◽  
...  
Keyword(s):  
Objective Response ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Immune Monitoring ◽  
Newly Diagnosed ◽  
Open Label ◽  
Presumptive Diagnosis ◽  
Newly Diagnosed Glioblastoma

Abstract The standard of care (SOC) in newly diagnosed glioblastoma (nGBM) includes resection and chemoradiotherapy. With a median overall survival (OS) of only 16–18 months for well-selected patients in clinical trials, better therapeutic options are needed. Toca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding a codon optimized, heat stabilized cytosine deaminase that converts Toca FC (extended-release 5- fluorocytosine,5-FC) into 5-fluorouracil. Preclinical evidence demonstrates that Toca 511 & 5-FC kill cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, leading to durable antitumor immune responses. Three phase (P) 1 studies in patients with recurrent high grade glioma have demonstrated tolerable safety profile and encouraging efficacy. NRG-BN006 is a randomized P2/3 trial of Toca 511 & Toca FC with SOC versus SOC for patients with nGBM. Optune use is allowed on the SOC arm, but not on the experimental arm. Patients will be stratified by age and KPS score for 1:1 randomization. The primary endpoint is progression-free survival for P2 and OS for P3. The secondary endpoints include objective response rate in patients with measurable disease and safety. Key inclusion criteria include presumptive diagnosis of glioblastoma with anticipated 80% resection, unifocal tumor, and KPS≥70. Immune monitoring and molecular profiling will be performed. P2 has 90% power to detect a hazard ratio (HR)=0.67 in 250 nGBM patients. P3 has 85% power to detect a HR=0.75 in 720 nGBM patients. Since patients are enrolled prior to surgery and confirmatory diagnosis of GBM, approximately 900 patients will be enrolled, and two interim analyses are planned for OS. In addition, two interim safety analyses will be conducted for the experimental treatment, with the first 15 and 30 eligible and analyzable patients randomized to the experimental arm. NRG-BN006 is anticipated to start enrollment in Q4 2019. Supported by grants U10CA180868, U10CA180822 from NCI and Tocagen.

scholarly journals P14.124 EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii98-iii98 ◽  
Author(s):  
P Roth ◽  
J Reijneveld ◽  
T Gorlia ◽  
F Dhermain ◽  
F De Vos ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND The standard of care for patients with newly diagnosed glioblastoma includes maximal debulking surgery followed by radiotherapy (RT), and concomitant as well as maintenance therapy with the alkylating agent, temozolomide (TMZ). However, the prognosis remains poor and novel treatment strategies are urgently needed. Targeting the proteasome has been considered a promising anti-cancer approach for several years. Marizomib is a novel, irreversible and pan-proteasome inhibitor, which crosses the blood-brain barrier and has been assessed in phase I trials in patients with newly diagnosed or recurrent glioblastoma. MATERIAL AND METHODS EORTC 1709/CCTG CE.8 is a randomized, controlled, open label phase III superiority trial. Patients with histologically confirmed newly diagnosed glioblastoma and a performance status >70 are eligible. Patients are randomized in a 1:1 ratio to receive standard of care (TMZ/RT→TMZ) alone or TMZ/RT→TMZ plus marizomib. The study aims at enrolling 750 patients. Stratification factors include study site, age, performance status and extent of resection. The primary objective of this trial is to compare overall survival in patients receiving marizomib in addition to standard of care with those receiving standard treatment only. The testing strategy specifies the determination of this objective in the intent-to-treat population as well as the subgroup of patients with MGMT-unmethylated tumors. Secondary endpoints include progression-free survival, safety, neurocognitive function and quality of life. A translational research program has been set up. The study will be activated at approximately 50 EORTC sites across Europe, 25 sites in Canada and additional sites in the US. Patient recruitment started in June 2018 and as of April 29, 2019, a total of 164 patients have been randomized. An update on the enrolment status will be provided at the EANO meeting. ClinicalTrials.gov Identifier: NCT03345095

scholarly journals C-methionine-PET-guided Gamma Knife radiosurgery boost as adjuvant treatment for newly diagnosed glioblastomas

2021 ◽  
Vol 12 ◽  
pp. 247
Author(s):  
Javier A. Jacobo ◽  
Masao Buentello ◽  
Ramiro Del Valle
Keyword(s):  
Gamma Knife ◽  
External Beam Radiotherapy ◽  
Gamma Knife Radiosurgery ◽  
Progression Free Survival ◽  
Magnetic Resonance Images ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Glial Tumor ◽  
Beneficial Role ◽  
Stupp Protocol

Background: The most common glial tumor is the glioblastoma, and the prognosis remains dismal despite a multimodal therapeutic approach. The role of radiosurgery for the treatment of glioblastomas has been evaluated in several studies with some benefit at the recurrent stage. We evaluate the results of the protocol administered at the Gamma Knife unit administering radiosurgery as a boost to metabolic active parts of the tumor after the patient had completed traditional external beam radiotherapy (XBRT) as part of the Stupp protocol for high-grade gliomas. Methods: This is a retrospective analysis of seven patients with newly diagnosed glioblastomas who were treated with Gamma Knife radiosurgery as a boost after receiving XBRT as part of the Stupp protocol. The target of radiation was determined according to the findings of the C-methionine PET scan in relation to magnetic resonance images. The primary end point of this study was to determine the progression-free survival (PFS) from the time of diagnosis. Results: The median age of patients was 48.8 years and the mean Karnofsky performance score was 92.8%. The median PFS was 12.4 months. No radiation adverse effects were documented. Conclusion: Stereotactic radiosurgery is safe to use in the upfront treatment for these patients and appears to have a beneficial role in improving the PFS. This beneficial role seems to be conditioned not only by the time the treatment is administered but also where the radiation dose is targeted to.

scholarly journals Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kuo-Chen Wei ◽  
Peng-Wei Hsu ◽  
Hong-Chieh Tsai ◽  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Newly Diagnosed ◽  
Open Label ◽  
Free Survival ◽  
Asian Patients ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints

AbstractAsunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

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).

scholarly journals Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival

2016 ◽  
Vol 124 (4) ◽  
pp. 998-1007 ◽  
Author(s):  
Ranjith Babu ◽  
Jordan M. Komisarow ◽  
Vijay J. Agarwal ◽  
Shervin Rahimpour ◽  
Akshita Iyer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Median Survival ◽  
Standard Of Care ◽  
Extent Of Resection ◽  
Older Age ◽  
Karnofsky Performance Scale ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Complication Risk

OBJECT The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02–1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95–0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31–0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.

RTID-05. THE MULTI-ARM GLIOBLASTOMA AUSTRALASIA (MAGMA) TRIAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi193-vi194
Author(s):  
Benjamin Kong ◽  
Hao-Wen Sim ◽  
Eng-Siew Koh ◽  
Hui Gan ◽  
Elizabeth H Barnes ◽  
...  
Keyword(s):  
Data Collection ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Future Design ◽  
Multiple Treatment ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Survival outcomes for patients with newly diagnosed glioblastoma have not changed significantly since the introduction of concurrent temozolomide with post-surgical radiation followed by adjuvant temozolomide. METHODS Multi-Arm Glioblastoma Australasia (MAGMA) is a recently initiated phase III multi-arm, multi-centre randomized trial for patients with newly diagnosed glioblastoma, led by the Australian Cooperative Trials Group for Neuro-Oncology (COGNO), that will concurrently test multiple treatment questions. Initially, a partial factorial design will be implemented to compare the current standard of care with either or both of (1) neoadjuvant temozolomide and (2) aduvant temozolomide continued beyond six months until progression. MAGMA will transition to a multi-arm multi-stage (MAMS) design as additional tratment question are introduced. Treatment allocation to each question will be balanced (1:1) using minimisation over several stratification factors, including study site, age, IDH-mutation status, surgical extent and randomization to the prior treatment question(s). The primary outcome is overall survival. Secondary outcomes include progression-free survival (measured by mRANO), time to first non-temozolomide systemic treatment, clinically significant toxicity as measured by Grade 2/4 adverse events, and health-related quality of life measures. Parsimonious data collection and a streamlined assessment schedule have been incorporated to mitigate the burden of data collection (such as low grade toxicity from temozolomide), and to encourage participation in regional and rural settings. A consortium model has been adopted to foster neuro-oncology expertise and infrastructure and share academic credit and future design opportunities. PROGRESS Recruitment commenced in September 2020. To date, 60 patients have been recruited from an initial sample size target of 250 patients for each of these initial two treatment questions. Of these 60 patients, 45 have been randomized in Question 1 (neoadjuvant chemotherapy) whilst 50 randomized in Question 2 (prolonged adjuvant chemotherapy). To date, 14 of the 27 intended sites are open to recruitment.

Pediatric Supratentorial Ependymoma: Surgical, Clinical, and Molecular Analysis

Neurosurgery ◽  
2018 ◽  
Vol 85 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Jock C Lillard ◽  
Garrett T Venable ◽  
Nickalus R Khan ◽  
Ruth G Tatevossian ◽  
James Dalton ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Bivariate Analysis ◽  
Subtotal Resection ◽  
Behavioral Differences ◽  
Negative Prognostic Factor ◽  
Clinically Significant

Abstract BACKGROUND Pediatric supratentorial ependymomas (SEs) have distinct molecular and behavioral differences from their infratentorial counterparts. OBJECTIVE To present our experience with pediatric SEs over a 24-yr period. METHODS Clinical, operative, and radiographic information was abstracted retrospectively. Our primary outcomes were progression-free survival (PFS) and overall survival (OS). Detection of C11orf95-RELA rearrangement was performed using interphase fluorescence in situ hybridization (iFISH). RESULTS Seventy-three patients were identified (41 female, 32 male); median age was 6.7 yrs (range, 1 mo-18.8 yr); median follow-up was 8.3 yrs (range, 2.0-26.3). Fifty-eight (79.5%) of 73 patients underwent gross total resection (GTR); no patient with subtotal resection had greater than 1 cm3 of residual tumor; 42 patients (57.5%) experienced subsequent disease progression with 17 patients ultimately dying of their disease. Median PFS was 3.7 yrs. Molecular analysis was available for 51 patients (70%). On bivariate analysis, PFS and OS were not statistically affected by age, tumor grade, or extent of resection, although there was a clinically significant trend for the latter in favor of aggressive resection on PFS (P = .061). Children with RELA fusion had significantly higher PFS (P = .013) than those without, although there was no difference in OS when compared with those with no C11orf95-RELA fusion or C11orf95 gene rearrangement alone. CONCLUSION In our series, GTR may be associated with better PFS, but did not impact OS. Surprisingly, RELA fusion was not found to be a negative prognostic factor, raising the possibility that the deleterious effects may be overcome by aggressive resection.

scholarly journals RADT-25. EVALUATING LYMPHOCYTE COUNTS IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS RECEIVING CHEMORADIATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii187
Author(s):  
Lubna Hammoudeh ◽  
Mary Jane Lim-Fat ◽  
Daniel Cagney ◽  
Ayal A Aizer ◽  
Shyam Tanguturi ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Total Resection ◽  
Free Survival ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Glioblastoma (GBM) patients are treated with chemotherapy, radiation therapy (RT) and often corticosteroids, which can all contribute to lymphopenia. We examined lymphopenia with respect to incidence, predictors, and association with progression-free survival (PFS) and overall survival (OS). METHODS We reviewed 349 newly diagnosed adult GBM patients treated at our institution in the temozolomide (TMZ) era with available lymphocyte and RT records. Data was reviewed from diagnosis through the chemoradiation (CRT) phase, defined as the period upto 6 weeks after RT. Linear regression and Cox proportional hazards modeling were used to evaluate outcomes. RESULTS Median age was 60 years (range, 19-90); 86% had KPS ≥ 70, 30% had gross total resection (GTR), and 91% received TMZ. Prior to RT, 60% (205/341) patients had a lymphocyte measurement &lt; 1.0 x 1000 cells [K]/μL and 15% (50/341) had &lt; 0.5 K/μL. During the CRT phase of therapy, 83% (270/324) had at least one lymphocyte measurement &lt; 1.0 K/μL, 42% (135/324) &lt; 0.5 K/μL, and 5% (16/324) &lt; 0.2 K/μL. Older age was associated with lower lymphocytes pre-RT, while subtotal resection, TMZ use, and RT dose was associated with lower lymphocyte counts during CRT (p&lt; 0.05). On multivariable analysis (MVA), age (AHR 1.03, p&lt; 0.01), KPS &gt; 70 (AHR 0.35, p&lt; 0.01), MGMT status (AHR 0.47, p&lt; 0.01), GTR (AHR 0.67, p=0.03), TMZ (AHR 0.27, p&lt; 0.01) and lymphopenia during CRT (AHR 1.80, p&lt; 0.01) were significantly associated with OS. Pre-RT lymphocyte level was associated with PFS on UVA (HR 0.81, p=0.03) but not on MVA (p=0.27). Lymphocyte count during CRT was not associated with PFS (p=0.24). CONCLUSION Lymphopenia is common in GBM, and chemoradiation-related lymphopenia was associated with inferior OS relative to patients without lymphopenia. Further characterization of the mechanism and optimal treatment of patients with lymphopenia are warranted to improve outcomes.

Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix

2011 ◽  
Vol 29 (13) ◽  
pp. 1678-1685 ◽  
Author(s):  
Alfonso Dueñas-González ◽  
Juan J. Zarbá ◽  
Firuza Patel ◽  
Juan C. Alcedo ◽  
Semir Beslija ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Randomized Study ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Current Standard ◽  
Open Label ◽  
Grade 3

Purpose To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer. Patients and Methods Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m2 and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1,000 mg/m2 on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A). Results Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. Conclusion Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

Sign in / Sign up

Export Citation Format

Share Document