scholarly journals Temozolomide and Radiotherapy versus Radiotherapy Alone in High Grade Gliomas: A Very Long Term Comparative Study and Literature Review

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Salvatore Parisi ◽  
Pietro Corsa ◽  
Arcangela Raguso ◽  
Antonio Perrone ◽  
Sabrina Cossa ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Haematological Toxicity ◽  
High Grade ◽  
Term Survival ◽  
Long Time ◽  
Radiotherapy Alone ◽  
High Grade Gliomas ◽  
Time Basis ◽  
Grade 3

Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ.Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ.Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11.Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis.

Post-operative concomitant radiochemotherapy in the treatment of primitive CNS high grade gliomas. A retrospective analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 11528-11528
Author(s):  
P. Costa ◽  
F. Braga ◽  
C. Sottomayor ◽  
M. Honavar ◽  
M. Resende ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Haematological Toxicity ◽  
Small Sample ◽  
Routine Practice ◽  
High Grade ◽  
Tumour Control ◽  
Concomitant Radiochemotherapy ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
The Impact

11528 Background: The authors analyse retrospectively the impact on tumour control and toxicity of concomitant radiotherapy (RT) and Temozolomide (TMZ) in high grade gliomas (HGG) of the CNS, in patients treated in the Clínica de Radioterapia do Porto - Portugal. Methods: This cohort represents all patients with HGG treated between January 2002 and January 2006, with concomitant RT a median total dose of 60 Gy, 2 Gy per treatment given once daily 5-days/week and TMZ 75mg/m2 for 42 days, followed by adjuvant treatment with TMZ 5-days schedule every 28 days (150 mg/m2 for the first cycle increased to 200mg/m2). The cohort was retrospectively analyzed for gender distribution, age, extent of surgical resection, initial KPS, median overall survival (OS) and haematological toxicity. Results: 23 with HGG (6 females, 17 males) were treated with concomitant RT (44–72 Gy) and TMZ followed by adjuvant TMZ; median age was 58 (ranging from 17–72); median KPS was 80 (ranging from 40–90); 3 patients had complete resection, 17 partial resection and 3 biopsy. All patients except one, who had treatment interruption for thrombocytopenia, completed the concomitant phase of treatment; 19 patients continued to received adjuvant treatment with TMZ (median number of cycles was 5 (ranging from 1–20). Median OS (measured from the date of diagnosis to the date of death) was 20.4 month and 1 yr OS was 54%. During concomitant phase, one patient had grade 3–4 thrombocytopenia. During the adjuvant TMZ therapy 4 patients had grade 3–4 haematological toxicity (anaemia: 1; thrombocytopenia: 1; leucopoenia and thrombocytopenia: 2). Conclusions: The results of concomitant RT+TMZ followed by TMZ in these patients with HGG showed values in accordance with the latest data published on literature for this association. Differences observed might be due to the small sample size.RT+TMZ followed by adjuvant TMZ is a well tolerated treatment with better results in median OS comparatively with previous results of RT only treatment in HGG. Treatment related toxicity was within acceptable levels, and this approach became routine practice in this set of patients. No significant financial relationships to disclose.

Radiotherapy plus concomitant and adjuvant temozolamide for newly diagnosed pediatric high-grade astrocytoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9042-9042
Author(s):  
M. M. Abdel Wahab ◽  
H. El-Hosseini ◽  
L. R. Eezz El-Arab
Keyword(s):  
Overall Survival ◽  
Pediatric Patients ◽  
Combined Treatment ◽  
High Grade ◽  
Newly Diagnosed ◽  
Time To Progression ◽  
High Grade Astrocytoma ◽  
Significant Survival ◽  
Radiotherapy Alone ◽  
Grade 3

9042 Background: to evaluate the potential survival advantage of adding temozolamide (TMZ) concomitantly and adjuvant to radiotherapy (RT) as regard time to progression (TTP) and overall survival in addition to its safety and tolerability in pediatric high grade astrocytomas. Methods: A total of 29 pediatric patients newly diagnosed, histologically proven glioblastoma multiforme (GBM) or anaplastic astreocytoma (AA) were randomized, to radiotherapy alone (14 patients) or radiotherapy and concomitant (TMZ) 150mg/m2/d for 5 days every 28 days followed by up to 6 cycels of adjuvant TMZ (15 patients). Results: The median time to progression was significantly prolonged in patients treated with RT/TMZ compared to those treated with RT alone (14 months Vs 7 months respectively) (P<0.05). The median overall survival in the combined treatment Vs monotherapy was 23 months and 13 months respectively (P<0.01). Non hematologic adverse events were similar between both groups while grade 3 & 4 hematologic toxicities occurred in 20% only of the RT/TMZ arm (2 patients experienced grade 3 thrombocytopenia and 1 patient developed grade 4 neutropenia). Conclusions: This study demonstrate a significant survival benefit for the addition of TMZ to treatment of pediatric patients with high grade astrocytpoma and it’s safety, well tolerability which allows it to be given concurrently with RT, followed by additional adjuvant cycles. No significant financial relationships to disclose.

scholarly journals Long-Term Follow-Up of Children Treated for High-Grade Gliomas: Children's Oncology Group L991 Final Study Report

2012 ◽  
Vol 30 (9) ◽  
pp. 943-949 ◽  
Author(s):  
Stephen Alan Sands ◽  
Tianni Zhou ◽  
Sharon Helene O'Neil ◽  
Sunita K. Patel ◽  
Jeffrey Allen ◽  
...  
Keyword(s):  
Verbal Memory ◽  
Visual Memory ◽  
Neuropsychological Functioning ◽  
High Grade ◽  
Oncology Group ◽  
Term Survival ◽  
Patient Reported ◽  
High Grade Gliomas

Purpose High-grade gliomas of the CNS are characterized by poor treatment response and prognosis for long-term survival. The Children's Oncology Group (COG) L991 study investigated the neuropsychological, behavioral, and quality of life (QoL) outcomes after treatment on the Children's Cancer Group (CCG) trial for high-grade gliomas (CCG-945). Patients and Methods Fifty-four patients (29 males, 25 females) with a median age of 8.8 years at diagnosis (range, 0.2 to 19.5 years) were enrolled at 25 institutions in North America, representing 81% of available survivors; median length of follow-up was 15.1 years (range, 9.5 to 19.2 years), and median age at study evaluation was 23.6 years (range, 11.3 to 36 years). Standardized tests of neuropsychological functioning and QoL were performed. Descriptive statistics summarized principal findings, and one-way analysis of variance identified potential predictors of outcomes. Results With an average follow-up time of 15 years, survivors demonstrated intellectual functioning within the low-average range. Executive functioning and verbal memory were between the low-average and borderline ranges. In contrast, visual memory and psychomotor processing speed were between the borderline and impaired ranges, respectively. Approximately 75% of patient reported overall QoL within or above normal limits for both physical and psychosocial domains. Nonhemispheric tumor location (midline or cerebellum), female sex, and younger age at treatment emerged as independent risk factors. Conclusion These results serve as a benchmark for comparison with future pediatric high-grade glioma studies, in addition to identifying at-risk cohorts that warrant further research and proactive interventions to minimize late effects while striving to ensure survival.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

Palliative brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer: a nationwide survey in Japan

2021 ◽  
Author(s):  
Terufumi Kawamoto ◽  
Naoki Nakamura ◽  
Tetsuo Saito ◽  
Ayako Tonari ◽  
Hitoshi Wada ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
External Beam Radiotherapy ◽  
Nationwide Survey ◽  
External Beam ◽  
First Line ◽  
Term Survival ◽  
Radiotherapy Alone ◽  
Group Members ◽  
First Line Treatment

Abstract Background International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. Methods Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. Results Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. Conclusions Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

scholarly journals Efficacy and Safety of Blinatumomab for Relapsed or Refractory Pediatric ALL Patients: A Systematic Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Anam Khan ◽  
Atif Irfan Khan ◽  
Sana Irfan Khan ◽  
Sobia Aamir ◽  
Usman Ali Akbar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
T Cells ◽  
Complete Remission ◽  
Adverse Outcomes ◽  
Term Survival ◽  
Paediatric Patients ◽  
Grade 3

Background Most children with Acute Lymphoblastic Leukaemia achieve complete remission and subsequent cure after chemotherapy. But, ALL relapse is the leading cause of treatment failure in paediatric patients, causing long term survival to below. Chemotherapy along with targeted therapies have been explored in relapsed/refractory ALL (R/R ALL) patients. One such targeted therapy is Blinatumomab (Blin), a bi-specific T-cell engagers (BiTEs) antibody, it binds to CD3 receptors on T-cells and CD19 receptors on B-cells thereby re-directing T-cells to exert their cytotoxic effect on malignant as well as non-malignant B-cells. Blin was approved by FDA in March 2018 for the treatment of B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1%. This approval was based on BLAST trial conducted on ≥18-year-old ALL patients. The drug has been studied in children (1-18 years) with five clinical trials exclusively in children of which two have reported their results and three are ongoing. In this systematic review, we evaluated the safety and efficacy of Blin as a monotherapy in paediatric R/R ALL patients. Material/Methods We performed a search on PubMed, Embase, Clinical Trials, Web of Science and Cochrane. We used Mesh Terms "ALL" and "Blinatumomab" without any filters. After screening of 1199 articles, 5 clinical trial, 3 retrospective studies and 1 case series were included. These studies included only paediatric patients (&lt;18yrs) evaluating the role of Blin as monotherapy in R/R ALL. We followed the PRISMA guidelines for literature search and selection of studies RESULTS: A total number of patients who received Blin was 320, all were &lt;18 years. The preceding treatment regimens included multi-agent chemotherapy with or without hematopoietic stem cell transplant (HSCT). Five studies included only those patients with more than ≥5% bone marrow blasts. Though many combination monoclonal antibody therapies are available, we included only patients given Blin as monotherapy. Blin therapy was a 4 weeks continuous infusion at a dosage of 5 or 15μg/m2/day followed by 2 weeks of treatment-free interval as one cycle, in the studies, the number of treatment cycles ranged from 1-18. A median follow up in the studies ranged from 6 months to 5 years. Overall, complete response (CR) was found to be 58% (n=184) ranging between 31% to 100%. Following CR with Blin relapse rate was 40% (n=66). The overall median survival ranged from 4.3 to 22 months amongst 5 of the nine studies, while it was reported to be 80% (n=9) survival at the end of 12 months by Elitzur et al and 33.3% (n=3) at the end of two cycles of blin by Schlegel, P et al, the remaining two studies did not mention the duration of overall survival. The cumulative hematologic adverse outcomes of ≥grade 3 amongst the studies reported were neutropenia 22% (n=70), Anemia 27.7%(n=55), thrombocytopenia as reported in four studies was 21.5% (n=30). Fuster J et al. reported a cumulative non-hematologic adverse outcome of 40%(n=6) while other studies reported ≥ grade 3 non-hematologic adverse outcomes with increased liver enzymes, neurologic problems and fever to be most common. Cumulative cytokine release syndrome was reported as 4.7% (n=14) in 6 out of 9 studies. Elitzur et al. reported no non-hematologic adverse effect. We found total cumulative death reported as 17% of cases (n=34). Conclusion Blinatumomab use for R/R ALL paediatric patients treatment showed promising outcomes with more than half of the patients achieving CR. Overall survival has been good with median patient surviving disease-free between 4 to 22 months at large. Though, low mortality indicated long term survival, a high relapse rate points that Blin with combination therapy may show better outcomes. Fifteen ongoing clinical trials are testing Blin currently, three of which are on paediatric R/R ALL group. One trial is testing a combination of Blin and pembrolizumab. The results of these trials will further provide information on its effectiveness in combination therapy. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

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