Impact of programmed death-ligand 1 expression on the patients of stage IV non-small cell lung cancer harboring epidermal growth factor receptor mutation: a systematic review and meta-analysis.

BACKGROUND: To determine the impact of programed death-ligand 1 (PD-L1) expression on progression-free survival (PFS) outcomes in stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with first-line EGFR tyrosine kinase inhibitors (TKIs). MATERIAL AND METHODS: We searched biomedical databases for studies comparing PFS outcomes of PD-L1-positive versus (vs) PD-L1-negative tumors. We assessed the methodological quality of eligible studies using ROBINS-I tool. We employed a two-staged meta-analysis approach by reconstructing individual patient data of each study from the published Kaplan-Meier curves and then pooling the individual hazard ratios (HRs) and weighted mean differences (WMDs) for restricted mean PFS time at 6 (RMPFST6) and 12 (RMPFST12) months using random-effect models. We assessed the quality of summarized evidence using GRADE approach. RESULTS: We identified five non-randomized comparative studies including 435 patients. The overall risk of bias in the methodological quality of included studies was moderate. PD-L1-positive tumors were associated with significantly worse PFS outcomes compared to PD-L1-negative tumors (HR: 2.41, 95% confidence interval (CI): 1.59-3.66, p < .001; WMD in RMPFST6: -1.01, 95% CI: -1.65 to -0.37, p = .002; WMD in RMPFST12: -2.64, 95% CI: -4.40 to -0.88, p = .003). Subgroup analysis showed that the effect of PD-L1 expression on PFS outcomes was greater for studies using older-generation rather than third-generation TKIs (HR: 2.69 vs 1.22, p = .069; WMD in RMPFST6: -1.23 vs -0.07, p = .005; WMD in RMPFST12: -3.29 vs -0.12, p = .003). The quality of summarized evidence was judged to be low. CONCLUSION: There is low certainty in the evidence to suggest that positive PD-L1 expression is associated with inferior disease control and survival outcomes in patients with stage IV EGFR-mutated NSCLC treated with first-line EGFR TKIs.

Pushing the limits of immune-related response: a case of "extreme pseudoprogression".

The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena in both tumor responses and toxicities. We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments. He was eventually started on nivolumab-the anti-programmed death receptor-1 monoclonal antibody approved for the treatment of advanced RCC. Clinical deterioration was observed soon after a 100 mg dose of nivolumab, with onset of acute renal failure and declining performance status. Radiologic progression was documented in multiple sites including worsening tumor infiltration of his residual kidney. The patient was on palliative treatment and visited by the home hospice team in an end-of-life situation. The patient unexpectedly improved and went on to achieve a durable tumor response. The case is illustrative of an extreme manifestation of pseudoprogression, and impels us to probe the assumptions and controversies surrounding this phenomenon.

Chemoradiotherapy versus chemoradiotherapy plus surgery for esophageal cancer.

BACKGROUND: Please see Appendix 4 for a glossary of terms.The outcome of patients with esophageal cancer is generally poor. Although multimodal therapy is standard, there is conflicting evidence regarding the addition of esophagectomy to chemoradiotherapy. OBJECTIVES: To compare the effectiveness and safety of chemoradiotherapy plus surgery with that of chemoradiotherapy alone in people with nonmetastatic esophageal carcinoma. SEARCH METHODS: We performed a computerized search for relevant studies, up to Feburary 2017, on the CENTRAL, MEDLINE, and Embase databases using MeSH headings and keywords. We searched five online databases of clinical trials, handsearched conference proceedings, and screened reference lists of retrieved papers. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing chemoradiotherapy plus esophagectomy with chemoradiotherapy alone for localized esophageal carcinoma. We excluded RCTs comparing chemotherapy or radiotherapy alone with esophagectomy. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data, and assessed risk of bias and the quality of the evidence, using standardized Cochrane methodological procedures. The primary outcome was overall survival (OS), estimated with Hazard Ratio (HR). Secondary outcomes, estimated with risk ratio (RR), were local and distant progression-free survival (PFS), quality of life (QoL), treatment-related mortality and morbidity, and use of salvage procedures for dysphagia. Data were analyzed using a random effects model in Review Manager 5.3 software. MAIN RESULTS: From 2667 references, we identified two randomized studies, in six reports, that included 431 participants. All participants were clinically staged to have at least T3 and/or node positive thoracic esophageal carcinoma, 93% of which was squamous cell histology. The risk of methodological bias of the included studies was low to moderate.High-quality evidence found the addition of esophagectomy had little or no difference on overall survival (HR 0.99, 95% CI 0.79 to 1.24; P = 0.92; I² = 0%; two trials). Neither study reported PFS, therefore, freedom from loco-regional relapse was used as a proxy. Moderate-quality evidence suggested that the addition of esophagectomy probably improved freedom from locoregional relapse (HR 0.55, 95% CI 0.39 to 0.76; P = 0.0004; I² = 0%; two trials), but low-quality evidence suggested it may increase the risk of treatment-related mortality (RR 5.11, 95% CI 1.74 to 15.02; P = 0.003; I² = 2%; two trials).The other pre-specified outcomes (quality of life, treatment-related toxicity, and use of salvage procedures for dysphagia) were reported by only one study, which found very low-quality evidence that use of esophagectomy was associated with reduced short-term QoL (MD 0.93, 95% CI 0.24 to 1.62), and low-quality evidence that it reduced use of salvage procedures for dysphagia (HR 0.52, 95% CI 0.36 to 0.75). Neither study compared treatment-related morbidity between treatment groups. AUTHORS' CONCLUSIONS: Based on the available evidence, the addition of esophagectomy to chemoradiotherapy in locally advanced esophageal squamous cell carcinoma, provides little or no difference on overall survival, and may be associated with higher treatment-related mortality. The addition of esophagectomy probably delays locoregional relapse, however, this end point was not well defined in the included studies. It is undetermined whether these results can be applied to the treatment of adenocarcinomas, tumors involving the distal esophagus and gastro-esophageal junction, and to people with poor response to chemoradiation.

Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups. ETHICS AND DISSEMINATION: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION: CRD42022330532.

Prophylactic irradiation of tracts in patients with malignant pleural mesothelioma: A systematic review and meta-analysis of randomized trials.

INTRODUCTION: The role of prophylactic irradiation of tracts (PIT) to prevent tumor seeding at the site of a diagnostic or therapeutic intervention in patients with malignant pleural mesothelioma (MPM) is controversial. This study aimed to determine the efficacy of PITs in preventing procedure tract metastases (PTM) after a chest wall procedure in MPM. MATERIALS AND METHODS: We searched various databases from inception date to April 2020 for randomized controlled trials (RCTs) comparing PIT with no PIT in patients who had a chest wall procedure for MPM. We assessed the risk of bias of individual RCT using the RoB2 tool. The primary outcome was the occurrence of PTM. Meta-analysis was performed using random-effects model. We employed the GRADE approach to assess the certainty of the evidence. RESULTS: We identified five RCTs including 737 patients. Two RCTs had a low risk of bias. PIT was associated with a significant reduction in the odds of PTM (odd ratio, 0.55; 95 % confidence interval, 0.32 to 0.95; P-value = 0.03; I2 = 13 %; GRADE: moderate certainty). One RCT reported no difference in overall survival outcome with the use of PIT. None of the RCTs performed subgroup analyses. Sensitivity analyses showed similar results when limited to RCTs with low risk of bias. CONCLUSION: PIT significantly reduces the occurrence of PTM in patients with MPM who had a diagnostic or therapeutic chest wall procedure.

Atypical Response Patterns in Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors-Navigating the Radiologic Potpourri.

BACKGROUND: Atypical response patterns have been a topic of increasing relevance since the advent of immune checkpoint inhibitors (ICIs), challenging the traditional RECIST (Response Evaluation Criteria in Solid Tumors) method of tumor response assessment. Newer immune-related response criteria can allow for the evolution of radiologic pseudoprogression, but still fail to capture the full range of atypical response patterns encountered in clinical reporting. METHODS: We did a detailed lesion-by-lesion analysis of the serial imaging of 46 renal cell carcinoma (RCC) patients treated with ICIs with the aim of capturing the full range of radiologic behaviour. RESULTS: Atypical response patterns observed included pseudoprogression (n = 15; 32.6%), serial pseudoprogression (n = 4; 8.7%), dissociated response (n = 22; 47.8%), abscopal response (n = 9; 19.6%), late response (n = 5; 10.9%), and durable response after cessation of immunotherapy (n = 2; 4.3%). Twenty-four of 46 patients (52.2%) had at least one atypical response pattern and 18 patients (39.1%) had multiple atypical response patterns. CONCLUSIONS: There is a high incidence of atypical response patterns in RCC patients receiving ICIs and the study contributes to the growing literature on the abscopal effect. The recognition of these interesting and overlapping radiologic patterns challenges the oncologist to tweak treatment options such that the clinical benefits of ICIs are potentially maximized.

Navigating the challenges of the COVID-19 outbreak: Perspectives from the radiation oncology service in Singapore.

In December 2019, pneumonia of unknown cause was reported by China to WHO. The outbreak was found to be caused by a coronavirus which was officially named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), and the disease caused by it was named 'COVID-19'. The first case in Singapore was confirmed on 23rd January 2020. With lessons learnt from the SARS epidemic in 2003 and the H1N1 flu pandemic in 2009, Singapore was much better prepared to deal with the virus outbreak. The government has taken swift measures to contain and break the chain of transmission. Healthcare workers face the challenge of keeping patients and staff safe from the disease. There is a higher risk of mortality of COVID-19 in cancer patients and hence unique considerations for a radiation oncology department operating in an infectious disease outbreak. This article is the recommendations and adapted workflow from the two National Cancer Centres in Singapore with the endorsement by the working committee of the Chapter of Radiation Oncology, Academy of Medicine, Singapore. It highlights the challenges that radiation oncology departments in Singapore face and the appropriate recommended responses. This includes interventions, business continuity plans and workflow in managing a COVID-19 positive patient on radiotherapy.

Discordance of epidermal growth factor receptor mutation between primary lung tumor and paired distant metastases in non-small cell lung cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the rate of discordance of epidermal growth factor receptor (EGFR) mutation between primary lung tumor and paired distant metastases in non-small-cell lung cancer (NSCLC). METHODS: We performed a meta-analysis of 17 studies (518 cases) assessing discordance rates of EGFR mutation in primary tumors and paired distant metastases. We performed subgroup analyses based on EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system (CNS) or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis (synchronous or metachronous). RESULTS: The overall discordance rate in EGFR mutation was low at 10.36% (95% CI = 4.23% to 18.79%) and varied widely between studies (I2 = 83.18%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001). Subgroup analyses did not demonstrate any significant effect modification on the discordance rates by the EGFR mutation status in primary lung tumor, methods of testing and timing of metastasis. CONCLUSION: The overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases. Future studies assessing the impact of EGFR mutation discordance on treatment outcomes are required.

Are heart doses associated with survival in patients with non-small cell lung cancer who received post-operative thoracic radiotherapy?: A national population-based study.

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

Spontaneous regression of locally advanced nonsmall cell lung cancer: A case report.

RATIONALE: Spontaneous regression of non-small cell lung cancer is exceptionally rare. PATIENT CONCERNS: Treatment-related toxicity. DIAGNOSES: We report a case of a patient diagnosed with locally advanced non-small cell lung cancer. INTERVENTIONS: The patient declined potentially curative treatment, and did not receive any anti-cancer treatment. OUTCOMES: He has survived more than two years since his initial diagnosis, maintaining his good performance status. Serial imaging with computed tomography scans showed tumour regression and near-complete resolution of his disease. LESSONS: Spontaneous regression of non-small cell lung cancer, by virtue of its scarcity, has not been well-studied and is poorly understood. Further studies are required, in order to clarify the mechanisms by which spontaneous regression occurs, and possibly identify new targets for cancer treatment.

Adoption of prophylactic cranial irradiation (PCI) for extensive stage small cell lung cancer (ES-SCLC): a population based outcome study.

BACKGROUND: The survival benefit of PCI in ES-SCLC reported by a European randomized trial (RCT) in 2007 was not replicated by a Japanese RCT published in 2017. This study aimed to evaluate the uptake of PCI before and after publication of the European RCT and its association with survival in ES-SCLC. METHODS: We identified eligible patients in the only two Singapore national cancer centres from 2003 to 2010. We linked their electronic medical records to the national death registry. We described the utilization of PCI in patients diagnosed from 2003 to 2006 (pre-adoption cohort) with patients diagnosed from 2007 to 2010 (post-adoption cohort). We performed univariable and multivariable Cox regression analysis to assess the association between PCI and survival. RESULTS: We identified 224 patients with ES-SCLC with no brain metastases. Among the 71 patients who had at least stable disease after first line chemotherapy, there was an increase in the use of PCI from the period 2007 to 2010 compared with 2003 to 2006 (32% versus 10%, P = 0.044). PCI was associated with improved OS (hazard ratio 0.22, 95% CI 0.10 to 0.47, P < 0.001) compared to no PCI in the multivariable analysis. CONCLUSION: There was an increase in the adoption of PCI for ES-SCLC since 2007. PCI was associated with improved survival in patients who did not have mandatory MRI brain imaging prior to PCI and had stable disease or better after first line chemotherapy, suggesting that the results of the European RCT are reproducible in the real-world practice.

Outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery for locally advanced rectal cancer: a single-institution experience.

INTRODUCTION: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) surgery for locally advanced rectal cancer has been shown to improve local control and reduce toxicity, as compared to adjuvant CRT. We reported the outcomes of our patients with locally advanced rectal cancer treated at National University Hospital, Singapore. METHODS: From April 2002 to December 2014, 117 patients with T3/4, N0/+, M0 rectal cancer received neoadjuvant CRT followed by TME surgery. The treatment regimen comprised a total radiotherapy dose of 50.4 Gy in 28 daily fractions delivered concurrently with 5-fluorouracil or capecitabine chemotherapy over 5.5 weeks. All patients were planned for TME surgery. Local control, disease-free survival, overall survival and treatment toxicities were analysed. RESULTS: Median follow-up was 34 (range 2-122) months. 11.5% (13/113) of patients achieved a pathological complete response (pCR) and 72.6% (85/117) had either tumour or nodal downstaging following neoadjuvant CRT. 5.2% (5/96) of patients had Grade 3 acute toxicities (dermatitis and diarrhoea) and 3.1% (3/96) had Grade 3 late toxicities (fistula and stricture). There was no Grade 4 toxicity noted. The five-year local recurrence, disease-free survival and overall survival rates were 4.5%, 65.7% and 80.6%, respectively. Multivariate analysis showed that nodal positivity was a predictor of poor disease-free survival and poor overall survival. Tumour downstaging and pCR did not improve outcomes. CONCLUSION: Our outcomes were comparable to internationally published data, and this treatment regimen remains the standard of care for locally advanced rectal cancer in our local population.

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.

The role of palliative radiation therapy in symptomatic locally advanced gastric cancer.

PURPOSE: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. METHODS AND MATERIALS: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at The Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). RESULTS: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. CONCLUSION: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer.

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0. Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery. At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis. Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.

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.

Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis.

BACKGROUND: To determine if the presence of epidermal growth factor receptor (EGFR) sensitizing mutations improves tumor control and survival outcomes in patients with non-metastatic non-small cell lung cancer (NSCLC) who received definitive thoracic radiation therapy (TRT) with or without chemotherapy. MATERIALS AND METHODS: We searched MEDLINE for eligible comparative studies which compared the outcomes of patients treated with definitive TRT according to EGFR mutation status. Meta-analysis was performed using random effects model. Outcomes of interest were tumor overall response rate (ORR), loco-regional (LRR), distant recurrence rates (DRR), relapse-free survival (RFS), overall survival (OS) and adverse events (AE). RESULTS: We found seven studies including 537 patients with stage III NSCLC. Up to 45% of patients in the studies had mutations in exon 19 and 21. Patients harbouring EGFR sensitizing mutations had a trend towards improvement in ORR (risk ratio 1.17, 95% confidence interval 0.99-1.37, P = 0.06) compared to EGFR wild type status. There were no significant differences in LRR, DRR, RFS, OS and AE outcomes between the EGFR mutant and EGFR wild type groups. CONCLUSIONS: The presence of EGFR sensitizing mutations may improve tumour response rate but not survival in patients with localized NSCLC treated with definitive thoracic radiation therapy with or without chemotherapy.

Efficacy of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice.

PURPOSE: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. METHODS AND MATERIALS: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. RESULTS: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p = 0.0005) and RO performance (7.6-7.9 of 8, p = 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p = 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. CONCLUSION: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

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.