Yu Yang Soon

EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE EGFR TKIs alone have demonstrated activity against intracranial disease in EGFR mutant non-small cell lung cancer (NSCLC). This study aimed to determine if upfront cranial radiotherapy improves intracranial disease control and survival outcomes in EGFR mutant NSCLC with brain metastases relative to TKIs alone. MATERIALS AND METHODS We searched MEDLINE and various conference proceedings from 2008 to July 2014 for eligible studies where patients received upfront cranial radiotherapy or TKIs alone. Outcomes of interest were overall intracranial disease response rate (ORR), four-month intracranial disease progression-free survival (PFS), two-year overall survival (OS) and neurological adverse events (AE). We used random effects models to pool outcomes across studies and compared them using interaction tests. RESULTS We found 12 non-comparative observational studies (n=363) with severe methodological limitations. Upfront cranial radiotherapy results in similar intracranial disease ORR (relative risk (RR) 0.93, 95% confidence interval (CI) 0.82-1.06; interaction p value (p)=0.53), improved four-month intracranial disease PFS (RR 1.06, 95% CI 1.00-1.12; p=0.03), improved two-year OS (RR 1.33, 95% CI 1.00-1.77; p=0.05) but caused more neurological AEs than TKIs alone. CONCLUSION There is evidence, albeit of low quality, that upfront cranial radiotherapy may improve intracranial disease control and survival outcomes compared with TKI alone.

Postoperative chemo‐radiotherapy versus chemotherapy for resected gastric cancer: A systematic review and meta‐analysis

This study conducted a systematic review and meta‐analysis (direct and indirect) of published randomised controlled trials (RCTs) to compare the effects of postoperative chemo‐radiotherapy (ChRT) with chemotherapy (Ch) on overall and disease‐free survival (DFS) for patients with resectable gastric cancer.

Accuracy of 18 F-flurodeoxyglucose- positron emission tomography/computed tomography in the staging of newly diagnosed nasopharyngeal carcinoma: a systematic review and meta-analysis

Abstract Background. The specific role of 18F-flurodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in staging of nasopharyngeal carcinoma (NPC) remains to be validated. A systematic review and meta-analysis were performed to assess the accuracy of staging FDG-PET/CT for newly diagnosed NPC. Methods. We searched various biomedical databases and conference proceedings for relevant studies. We determined the pooled sensitivities and specificities, diagnostic odds ratios (DOR) and constructed summary receiver operating characteristic (SROC) curves using the hierarchical regression model. Results. 15 relevant studies including 851 patients were identified. Five addressed primary tumor (T), nine addressed regional lymph nodes (N) and seven addressed distant metastasis (M). The combined sensitivity estimate for FDG-PET/CT in T classification was 0.77 (95% confidence interval [CI] 0.59-0.95). For N classification, combined sensitivity was 0.84 (95% CI 0.76-0.91), specificity was 0.90 (95% CI 0.83-0.97), DOR was 82.4 (23.2-292.6) and Q*-index was 0.90. For M classification, the combined sensitivity estimate was 0.87 (95% CI 0.74-1.00), specificity was 0.98 (95% CI 0.96-1.00), DOR was 120.9 (43.0-340.0) and Q*-index was 0.89. Conclusion. FDG-PET/CT showed good accuracy in N and M but not T classification for newly diagnosed NPC. FDG-PET/CT, together with Magnetic resonance imaging (MRI) of the nasopharynx, should be part of the routine staging investigations

Palliative radiotherapy for gastric cancer: a systematic review and meta-analysis

Background/Purpose To review the efficacy and toxicity of palliative radiotherapy (RT) for symptomatic locally advanced gastric cancer (GC) and to determine the optimal RT schedule for symptom palliation. Methods We searched MEDLINE and CENTRAL for eligible studies published from 1995 to 2015. Outcomes of interest were relief of bleeding, pain and obstruction. RESULTS Seven non-comparative observational studies were included. There were large variations in RT dose and fractionation. The pooled overall response rates for bleeding, pain and obstruction symptoms were 74%, 67% and 68% respectively. There was no difference in response rate of bleeding between regimens with high biological equivalent dose (BED) of = 39Gy versus regimens with low BED<39Gy regimens (p value =0.39). Grade 3 to 4 toxicities occurred in up to 15% of patients for patients treated with RT alone and up to 25% of patients treated with chemoradiotherapy. Health-related quality of life (HRQL) outcomes were not reported. Conclusion More than two-thirds of patients receiving RT would have a clinical benefit. Low BED regimens appear to be adequate for symptom palliation. Toxicity rates appear acceptable for patients treated with RT alone. The optimal dose fractionation regimen for symptom palliation remains unclear. Prospective studies to determine the effects of palliative gastric RT on HRQL outcomes are warranted.

Prevalence and predictors of bias in the reporting of primary efficacy and toxicity endpoints in randomized clinical trials of radiation oncology.

To determine the prevalence and predictors of bias in reporting of primary efficacy and toxicity endpoints in randomized trials (RCTs) of radiation oncology.

Long‐term outcomes after reirradiation in nasopharyngeal carcinoma with intensity‐modulated radiotherapy: A meta‐analysis

The purpose of this clinical review was to summate the published data for the long‐term outcomes of reirradiation with intensity‐modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC).

Induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A systematic review and meta-analysis

PURPOSE To determine if the addition of induction chemotherapy (IC) to concurrent chemoradiation (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) can improve survival. METHODS We performed a meta-analysis of both randomized controlled trials (RCTs) and observational studies (OBS) to compare the effects of addition of IC to CCRT versus (vs) CCRT alone on overall survival (OS), progression free survival (PFS), distant metastasis-free survival (DMFS) and adverse events (AE) in LA-NPC. We searched MEDLINE for eligible studies comparing IC plus CCRT vs CCRT for LA-NPC from Jan 1996 to May 2017. We selected RCTs and OBS that included patients with non-metastatic, LA-NPC who received IC followed by CCRT or CCRT alone. Three reviewers independently assessed the abstracts for eligibility. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model. We used the GRADE approach to appraise the quality of evidence from RCTs. The primary outcome was OS; secondary outcomes included PFS, DMFS and AE. RESULTS We found six RCTs and five OBS including 2802 patients with low to moderate risk of bias in their methodological quality. There was high quality evidence from the RCTs that IC improved PFS (HR 0.69, 95% CI 0.57-0.84, P = 0.0003, I2 = 0%) and OS (HR 0.77, 95% CI 0.60-0.98, P = 0.03, I2 = 0%) significantly and was associated with more frequent AE. The estimates of IC effects from RCTs and OBS were similar (PFS HR 0.69 vs 0.71, interaction P (IP) = 0.92; OS HR 0.77 vs 0.58, IP = 0.27). CONCLUSIONS IC delays disease progression and improves survival significantly for LA-NPC treated with CCRT, and was associated with more toxicity. There were no divergent results between RCTs and OBS. IC followed by CCRT can be considered one of the standard treatment options for LA-NPC.

Outcomes of Asian patients with localized prostate cancer treated with combined intensity modulated radiation therapy (IMRT) and high dose rate (HDR) brachytherapy: A single institution experience

External beam radiotherapy (EBRT) followed by high dose rate (HDR) brachytherapy boost has demonstrated minimal toxicities and improved disease control rate compared with EBRT alone in observational and randomized studies with predominantly Caucasian patients. This study aims to report the outcomes of patients treated with this approach in our predominantly Asian population.

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer

BackgroundGood radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer.MethodsWe searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting.ResultsWe found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria.ConclusionThere is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Association between radiation heart dosimetric parameters, myocardial infarct and overall survival in stage 3 non-small cell lung cancer treated with definitive thoracic radiotherapy

OBJECTIVES The aim of this retrospective observational study is to assess the association between various radiation heart dosimetric parameters (RHDPs) and acute myocardial infarct (AMI) and overall survival (OS) outcomes in stage III non-small cell lung cancer (NSCLC) treated with definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS We identified eligible patients treated at two institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. We performed univariable and multivariable Cox regressions analysis to assess the association between various RHDPs, AMI and OS. RESULTS 120 eligible patients were included with a median follow-up of 17.6 months. Median age was 65.5 years. Median prescription dose was 60 Gy. Median mean heart dose (MHD) was 12.6 Gy. Univariable analysis showed that higher MHD (hazard ratio (HR), 1.03; 95% confidence interval (CI), 1.01-1.06; P = .008) and volume of heart receiving at least 5 Gy (V5) (HR, 1.01; 95% CI, 1.00-1.03; P = .042) were associated with increased hazards for AMI. Univariable analysis showed that higher MHD, V5, V25, V30, V40, V50 and dose to 30% of heart volume were associated with increased hazards for death. Multivariable analysis showed that there was no statistically significant association between various RHDPs and OS. CONCLUSION The incidence of AMI is low among stage III NSCLC treated with definitive radiotherapy with or without chemotherapy. There is insufficient evidence to conclude that RHDPs are associated with AMI or OS in our study.