Dataset Information

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis.

ABSTRACT:

Objective

We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM).

Methods

Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events.

Results

Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia.

Conclusion

Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage.

SUBMITTER: Zhao Q

PROVIDER: S-EPMC4773042 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis.

Zhao Qian Q Qin Qin Q Sun Jinglong J Han Dan D Wang Zhongtang Z Teng Junjie J Li Baosheng B

PloS one 20160301 3

<h4>Objective</h4>We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM).<h4>Methods</h4>Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Second ...[more]

PMID: 26930609

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Project description:BackgroundThe benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear.ObjectivesTo compare the efficacy and safety of surgery or SRS plus WBRT with that of surgery or SRS alone for treatment of brain metastases in patients with systemic cancer.Search methodsWe searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL) up to May 2013 and annual meeting proceedings of ASCO and ASTRO up to September 2012 for relevant studies.Selection criteriaRandomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases.Data collection and analysisTwo review authors undertook the quality assessment and data extraction. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), health related quality of life (HRQL) and neurological adverse events. Hazard ratios (HR), risk ratio (RR), confidence intervals (CI), P-values (P) were estimated with random effects models using Revman 5.1 MAIN RESULTS: We identified five RCTs including 663 patients with one to four brain metastases. The risk of bias associated with lack of blinding was high and impacted to a greater or lesser extent on the quality of evidence for all of the outcomes. Adding upfront WBRT decreased the relative risk of any intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to 0.66, P value < 0.0001, I(2) =34%, Chi(2) P value = 0.21, low quality evidence) but there was no clear evidence of a difference in OS (HR 1.11, 95% CI 0.83 to 1.48, P value = 0.47, I(2) = 52%, Chi(2) P value = 0.08, low quality evidence) and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I(2) = 16%, Chi(2) P value = 0.28, low quality evidence). Subgroup analyses showed that the effects on overall survival were similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The evaluation of the impact of upfront WBRT on NF, HRQL and neurological adverse events was limited by the unclear and high risk of reporting, performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.Authors' conclusionsThere is low quality evidence that adding upfront WBRT to surgery or SRS decreases any intracranial disease progression at one year. There was no clear evidence of an effect on overall and progression free survival. The impact of upfront WBRT on neurocognitive function, health related quality of life and neurological adverse events was undetermined due to the high risk of performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.

Project description:OBJECTIVE:The immune modulatory drug chloroquine (CQ) has been demonstrated to enhance survival following radiotherapy in patients with high-grade glioma in a clinical trial, but the efficacy in patients with brain metastases is unknown. We hypothesized that short-course CQ during whole brain radiotherapy (WBRT) would improve response to local therapy in patients with brain metastases. METHODS:A prospective, single-cohort study was performed combining WBRT with concurrent CQ to assess both the feasibility of and intracranial response to combined therapy in patients with brain metastases. Safety, tolerability and overall survival of this combination was also examined, along with allelic status of IDO2 (indoleamine 2,3-dioxygenase 2), an immune modulatory enzyme inhibited by chloroquine that may affect survival outcomes. CQ therapy (250 mg by mouth daily) was initiated 1 week before WBRT (37.5 Gy in 2.5 Gy daily fractions) in patients with newly diagnosed brain metastases from biopsy-proven, primary lung, breast or ovarian solid tumors (n=20). The primary endpoint was radiologic response 3 months after combined CQ and WBRT therapy. Secondary endpoints included toxicity and overall survival. Patients were stratified by IDO2 allelic status. RESULTS:After a median clinical follow up of 5 months (range, 0.5-31), 16 patients were evaluable for radiologic response which was complete response in two patients, partial response in 13 patients and stable disease in one patient. There were no treatment-related grade?3 toxicities or treatment interruption due to toxicity. Median and mean overall survival was 5.7 and 8.9 months, respectively (range, 0.8-31). A trend toward increased overall survival was observed in patients with wild-type IDO2 compared to patients with heterozygous or homozygous configurations that ablate IDO2 enzyme activity (10.4 mos vs. 4.1 mos.; p=0.07). CONCLUSIONS:WBRT with concurrent, short-course CQ is well tolerated in patients with brain metastases. The high intracranial disease control rate warrants additional study.

Project description:Abstract Our previous data showed that WHO grade II/III gliomas with isocitrate dehydrogenase wide-type (IDH-wt) and telomerase reverse transcriptase promoter mutation (TERTp-mut) have dismal prognosis as glioblastoma. This study compared concurrent chemoradiotherapy(CRT) with radiotherapy(RT) alone on the outcome of these patients. Between September 2016 and November 2018, 30 eligible grade II/III glioma patients with IDH-wt and TERTp-mut were randomly assigned to receive either RT (60 Gy in 30 daily fractions for 6 weeks) alone (n=15) or concurrent CRT with daily temozolomide and adjuvant temozolomide (n=15). The median follow-up duration was 15.5 months. The median age was 51 years (range, 24–66 years). The median Karnofsky performance status (KPS) score at randomization was 80 (range, 60–80). Surgery was the primary treatment. The characteristics of the two treatment groups were well balanced at baseline. The 1-year OS rate was significant difference between CRT group (92.3%; 95% CI: 77.8–100) and RT alone group(71.1%; 95% CI: 47.0–95.2) (p = 0.019). Local, distant, and combined tumor recurrence patterns were observed in 4 (26.7%), 1 (6.7%), and 3 patients (20%) in the CRT group and 4 (26.7%), 3 (20%), and 3 patients (20%) in the RT alone group. Those treated with RT alone had shorter median PFS (9 vs 18 months, HR: 0.517; 95% CI: 0.193 to 1.386; p = 0.19). CRT with temozolomide and extent of resection were statistically significant predictors for survival on univariate analysis. Multivariate analysis showed that CRT was associated with a significantly better OS compared with RT alone (OR=0.195; 95% CI, 0.044 to 0.867; p=0.032). Consequently, concurrent CRT with daily temozolomide and adjuvant temozolomide for newly diagnosed IDHwt/TERTp-mut grade II/III gliomas had significantly better OS compared with RT alone. A large multi-center prospective randomized trial is warranted. The trial has been registered at ClinicalTrials.gov (NCT02766270).

Dataset Information

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis.

Objective

Methods

Results

Conclusion

Publications

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis.

Similar Datasets

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