methods Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. results A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.

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Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nelia and Amadeo Barletta Foundation, Schering-Plough.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(09)70025-7.pdf

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial

Approximately 5% of patients with malignant gliomas have a family history of gliomas. Some of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot’s syndrome (intestinal polyposis and brain tumors). 10 However, most familial cases have

Malignant Gliomas in Adults

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Purpose We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial. Patients and Methods One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m2 or 125 mg/m2 (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival. Results In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticoste...

Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

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A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse

The roles of cd8+ ctls, cd163+ tams, pdl1 in tumor microenvironment in the prognosis of primary central nervous system

Objective: The effectiveness and prognosis of a BTki-containing regimen in first-line treatment and relapsed/refractory patients were assessed in this study. Methods: There were 26 patients with DLBCL. BTKi was administered to patients with newly diagnosed, relapsed, refractory primary PCNSL and high-risk/refractory systemic DLBCL, and the effectiveness and PFS were evaluated. Results: The BTKi therapy study included 26 participants (16 PCNSL, 10 DLBCL). Among PCNSL,3 patients who had achieved PR following MTX-based first-line chemotherapy were given BTKi as a monotherapy for disease recurrence. BTKi patients lived for an average of 5 (1–8) months before dying from disease progression, which is 5 months longer than the typical patient survival period following chemotherapy recurrence. After three rounds of MTX-based chemotherapy, none of the six patients with refractory PCNSL achieved PR. After BTKi was utilized as second-line therapy, the average survival time was increased by 12 (2–21) months. Three patients received early treatment, while the remaining three received BTKi after the third round of medicine. Early patients had a longer average survival period than late ones (11 months vs. 10 months). The remaining seven high-risk patients received first-line chemotherapy and BTKi treatment. The median follow-up duration was 5 months, the ORR was 100%, and neither the median PFS nor the median OS were achieved. The mean maintenance time was 8 months. Among 10 patients with DLBCL, 8 of them are high risk group, and 2 had refractory disease. When the disease of two SCNSL patients advanced, BTKi was used in conjunction with chemotherapy as a salvage treatment, and BTKi was kept up for an average of 5 months. The efficacy was evaluated as PD. The ORR was 80% (4/5, 1 case was not assessed) and CR rate was 100% in high risk group. Four of these CNS-IPI high-risk DLBCL patients had adrenal involvement and a high IPI score, with BTKi maintained for an average of 6 months, two of them achieved CR, one of PD, and 1 case was not evaluated. The efficacy evaluation was CR in the other two high-risk CD5+ patients, whose BTKi was sustained for 12 months and 6 months, respectively. After receiving standard chemotherapy, the remaining 2 refractory patients kept getting worse. One patient with hepatitis B cirrhosis had elevated AST and ALT levels after one course of medication, so BTKi was stopped. The other patient was kept on BTKi alone for 4 months, but the efficacy was still PD. Patients with PCNSL have a dismal prognosis, in particular, the average survival time for R/R patients is less than two months. The research was funded by: National Natural Science Foundation of China (8226010026), Natural Science Foundation of Gansu Province (22JR11RA053) Keywords: aggressive B-cell non-Hodgkin lymphoma, molecular targeted therapies, combination therapies No conflicts of interests pertinent to the abstract. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hon.3165_548

N. Yue

Papers

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse

The roles of cd8+ ctls, cd163+ tams, pdl1 in tumor microenvironment in the prognosis of primary central nervous system

Btk inhibitors in cnsl and high‐risk/refractory dlbcl patients: a real‐world study