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.

Investigation of small lung lesion detection for lung cancer screening in low dose FDG PET imaging by deep neural networks.

Purpose: FDG PET imaging is often recommended for the diagnosis of pulmonary nodules after indeterminate low dose CT lung cancer screening. Lowering FDG injecting is desirable for PET imaging. In this work, we aimed to investigate the performance of a deep learning framework in the automatic diagnoses of pulmonary nodules at different count levels of PET imaging. Materials and methods: Twenty patients with 18F-FDG-avid pulmonary nodules were included and divided into independent training (60%), validation (20%), and test (20%) subsets. We trained a convolutional neural network (ResNet-50) on original DICOM images and used ImageNet pre-trained weight to fine-tune the model. Simulated low-dose PET images at the 9 count levels (20 × 106, 15 × 106, 10 × 106, 7.5 × 106, 5 × 106, 2 × 106, 1 × 106, 0.5 × 106, and 0.25 × 106 counts) were obtained by randomly discarding events in the PET list mode data for each subject. For the test dataset with 4 patients at the 9 count levels, 3,307 and 3,384 image patches were produced for lesion and background, respectively. The receiver-operator characteristic (ROC) curve of the proposed model under the different count levels with different lesion size groups were assessed and the areas under the ROC curve (AUC) were compared. Results: The AUC values were >0.98 for all count levels except for 0.5 and 0.25 million true counts (0.975 (CL 95%, 0.953-0.992) and 0.963 (CL 95%, 0.941-0.982), respectively). The AUC values were 0.941(CL 95%, 0.923-0.956), 0.993(CL 95%, 0.990-0.996) and 0.998(CL 95%, 0.996-0.999) for different groups of lesion size with effective diameter (R) <10 mm, 10-20 mm, and >20 mm, respectively. The count limit for achieving high AUC (≥0.96) for lesions with size R < 10 mm and R > 10 mm were 2 million (equivalent to an effective dose of 0.08 mSv) and 0.25 million true counts (equivalent to an effective dose of 0.01 mSv), respectively. Conclusion: All of the above results suggest that the proposed deep learning based method may detect small lesions <10 mm at an effective radiation dose <0.1 mSv. Advances in knowledge: We investigated the advantages and limitations of a fully automated lung cancer detection method based on deep learning models for data with different lesion sizes and different count levels, and gave guidance for clinical application.

Radiation oncology training in Singapore - A non-Australasian RANZCR training site.

The Radiation Oncology Department at The National Cancer Institute, Singapore (NCIS) and the Royal Australian and New Zealand College of Radiology (RANZCR) has had a well-established relationship that began as a partnership to grow a pool of local radiation oncologists to meet a nation's demand for radiotherapy services. This journey has surpassed its initial aims and now has produced a generation of radiation oncologists leading a national cancer institute. We recount the history and progress of this partnership here, as well as the unique success of its product; the only RANZCR-accredited radiation oncology training site outside of Australia and New Zealand since 2002. We outline the mutual benefits through many years of collaboration and deliberate efforts to grow the partnership. We also outline the distinctive specialist training path that our trainees take to meet both the local accreditation body as well as the RANZCR requirements.

Regional collaboration to improve quality of radiation therapy in Asia.

In Asia, several challenges hinder the delivery of high-quality cancer treatment, especially radiation therapy (RT). Many Asian countries face large-scale shortage of RT centres and treatment machines. Additionally, there is also a significant technological gap, with many RT centres in Asia still using outdated technology. There is an urgent need to improve radiation treatment quality in Asia. The Federation of Asian Organizations for Radiation Oncology (FARO) was set up to foster regional collaboration, which we believe can help to identify and solve some of these issues collectively. This report describes the background and rationale of starting FARO, and puts forth some of the early achievements of the group, including fact-finding and educational activities. Finally, we discuss future possibilities, including strategic proposals that may benefit the RT community and our patients in Asia.

Validation of low-dose lung cancer PET-CT protocol and PET image improvement using machine learning.

PURPOSE: To conduct a simplified lesion-detection task of a low-dose (LD) PET-CT protocol for frequent lung screening using 30% of the effective PETCT dose and to investigate the feasibility of increasing clinical value of low-statistics scans using machine learning. METHODS: We acquired 33 SD PET images, of which 13 had actual LD (ALD) PET, and simulated LD (SLD) PET images at seven different count levels from the SD PET scans. We employed image quality transfer (IQT), a machine learning algorithm that performs patch-regression to map parameters from low-quality to high-quality images. At each count level, patches extracted from 23 pairs of SD/SLD PET images were used to train three IQT models - global linear, single tree, and random forest regressions with cubic patch sizes of 3 and 5 voxels. The models were then used to estimate SD images from LD images at each count level for 10 unseen subjects. Lesion-detection task was carried out on matched lesion-present and lesion-absent images. RESULTS: LD PET-CT protocol yielded lesion detectability with sensitivity of 0.98 and specificity of 1. Random forest algorithm with cubic patch size of 5 allowed further 11.7% reduction in the effective PETCT dose without compromising lesion detectability, but underestimated SUV by 30%. CONCLUSION: LD PET-CT protocol was validated for lesion detection using ALD PET scans. Substantial image quality improvement or additional dose reduction while preserving clinical values can be achieved using machine learning methods though SUV quantification may be biased and adjustment of our research protocol is required for clinical use.

Emerging radiotherapy technologies and trends in nasopharyngeal cancer.

Technology has always driven advances in radiotherapy treatment. In this review, we describe the main technological advances in radiotherapy over the past decades for the treatment of nasopharyngeal cancer (NPC) and highlight some of the pressing issues and challenges that remain. We aim to identify emerging trends in radiation medicine. These include advances in personalized medicine and advanced imaging modalities, standardization of planning and delineation, assessment of treatment response and adaptive re-planning, impact of particle therapy, and role of artificial intelligence or automation in clinical care. In conclusion, we expect significant improvement in the therapeutic ratio of radiotherapy treatment for NPC over the next decade.

Supervised learning with cyclegan for low-dose FDG PET image denoising.

PET imaging involves radiotracer injections, raising concerns about the risk of radiation exposure. To minimize the potential risk, one way is to reduce the injected tracer. However, this will lead to poor image quality with conventional image reconstruction and processing. In this paper, we proposed a supervised deep learning model, CycleWGANs, to boost low-dose PET image quality. Validations were performed on a low dose dataset simulated from a real dataset with biopsy-proven primary lung cancer or suspicious radiological abnormalities. Low dose PET images were reconstructed on reduced PET raw data by randomly discarding events in the PET list mode data towards the count level of 1 million. Traditional image denoising methods (Non-Local Mean (NLM) and block-matching 3D(BM3D)) and two recently-published deep learning methods (RED-CNN and 3D-cGAN) were included for comparisons. At the count level of 1 million (true counts), the proposed model can accurately estimate full-dose PET image from low-dose input image, which is superior to the other four methods in terms of the mean and maximum standardized uptake value (SUVmean and SUVmax) bias for lesions and normal tissues. The bias of SUV (SUVmean, SUVmax) for lesions and normal tissues are (-2.06±3.50%,-0.84±6.94%) and (-0.45±5.59%, N/A) in the estimated PET images, respectively. However, the RED-CNN achieved the best score in traditional metrics, such as structure similarity (SSIM), peak signal to noise ratio (PSNR) and normalized root mean square error (NRMSE). Correlation and profile analyses have successfully explained this phenomenon and further suggested that our method could effectively preserve edge and also SUV values than RED-CNN, 3D-cGAN and NLM with a slightly higher noise.

Defining a cohort of oligometastatic nasopharyngeal carcinoma patients with improved clinical outcomes.

OBJECTIVES: To compare the clinical outcomes of oligometastatic versus widely metastatic NPC patients. MATERIALS AND METHODS: Retrospective review of 157 patients with metastatic NPC at a tertiary hospital was performed. Multivariate analysis was carried out to compare the overall and progression-free survival (OS and PFS) of these two cohorts of NPC patients. The number of organ involvement and discrete metastatic lesions associated with improved OS and PFS were ascertained. RESULTS: Patients with oligometastatic NPC (single organ, less than six discrete metastatic lesions) had a better median OS than patients with widespread metastasis (24.8 versus 12.8 months, P < .001). Similarly, the median PFS of oligometastatic NPC was better than that of polymetastatic NPC (11.7 versus 7.3 months, P < .001). CONCLUSION: Single organ disease with less than six discrete lesions is a good indicator of limited metastatic load in NPC, and is associated with improved survival.

Quantitative accuracy of radiomic features of low-dose 18F-FDG PET imaging.

BACKGROUND: 18F-FDG PET based radiomics is promising for precision oncology imaging. This work aims to explore quantitative accuracies of radiomic features (RFs) for low-dose 18F-FDG PET imaging. METHODS: Twenty lung cancer patients were prospectively enrolled and underwent 18F-FDG PET/CT scans. Low-dose PET situations (true counts: 20×106, 15×106, 10×106, 7.5×106, 5×106, 2×106, 1×106, 0.5×106, 0.25×106) were simulated by randomly discarding counts from the acquired list-mode data. Each PET image was created using the scanner default reconstruction parameters. Each lesion volume of interest (VOI) was obtained via an adaptive contouring method with a threshold of 50% peak standardized uptake value (SUVpeak) in the PET images with full count data and VOIs were copied to the PET images at the reduced count level. Conventional SUV measures, features calculated from first-order statistics (FOS) and texture features (TFs) were calculated. Texture based RF include features calculated from gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level size zone matrix (GLSZM), neighboring gray-level dependence matrix (NGLDM) and neighbor gray-tone difference matrix (NGTDM). Bias percentage (BP) at different count levels for each RF was calculated. RESULTS: Fifty-seven lesions with a volume greater than 1.5 cm3 were found (mean volume, 25.7 cm3, volume range, 1.5-245.4 cm3). In comparison with normal total counts, mean SUV (SUVmean) in the lesions, normal lungs and livers, Entropy and sum entropy from GLCM, busyness from NGTDM and run-length non-uniformity from GLRLM were the most robust features, with a BP of 5% at the count level of 1×106 (equivalent to an effective dose of 0.04 mSv) RF including cluster shade from GLCM, long-run low grey-level emphasis, high grey-level run emphasis and short-run low grey-level emphasis from GLRM exhibited the worst performance with 50% of bias with 20×106 counts (equivalent to an effective dose of 0.8 mSv). CONCLUSIONS: In terms of the lesions included in this study, SUVmean, entropy and sum entropy from GLCM, busyness from NGTDM and run-length non-uniformity from GLRLM were the least sensitive features to lowering count.

A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes.

Background Patients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT. Patients and methods Patients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed. Results Seventy-four patients were included in this analysis. The median follow up was 3 years (0.7-16 years). Fifty-eight percent of patients had stage I-II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57-83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS. Conclusions The outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

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.

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.

Palliative radiotherapy in symptomatic locally advanced gastric cancer: A phase II trial.

To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10-point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ-C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ-C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients.

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.

Implementation of temporal lobe contouring protocol in head and neck cancer radiotherapy planning: A quality improvement project.

Temporal lobe necrosis as result of radiation for nasopharyngeal cancer (NPC) occurs up to 28% of NPC patients. The only effective mitigation is by strict adherence to temporal lobe dose tolerances during radiotherapy planning, which in turn hinges on accurate temporal lobe delineation. We aim to improve the accuracy and to standardize temporal lobe contouring for patients receiving head and neck radiotherapy for NPC in a tertiary teaching hospital in Singapore.The baseline data were obtained from 10 patients in the diagnostic phase and the effect of interventions were measured in 37 patients who underwent head and neck radiotherapy over a 6-month period.We conducted the project based on the Clinical Practice Improvement Program methodology. The baseline pooled mean percentage variation in temporal lobe contouring was 39.9% (0.8%-60.2%). There was a low level of temporal lobe contouring concordance and this provided the impetus for implementation of strategies to improve the accuracy and reproducibility of temporal lobe contouring. The interventions included supervision and training of radiation therapists and residents in temporal lobe contouring, and standardization of temporal lobe contouring with a protocol and contouring atlas.Thirty-seven patients were treated during the study period from June to November 2014. Following implementation of the first set of interventions, the pooled mean percentage variation in temporal lobe contouring decreased but was not sustained. The implementation of the second set of interventions resulted in a decrease from 39.9% (January to September 2014) to 17.3% (October to November 2014) where P = .004 using t test. Weekly variation was seen throughout the study period but the decrease was sustained after standardizing and providing a contouring atlas for temporal lobe contouring.Temporal lobe contouring can be standardized through effective implementation of a temporal lobe contouring protocol and atlas.

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.

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.

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

BACKGROUND: 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). METHODS: We searched biomedical literature databases for eligible studies published from January 2005 to September 2016. Outcomes of interests were 5-year local failure-free survival, distant failure-free survival, overall survival (OS), and toxicities. Meta-analysis was performed using a random effects model. RESULTS: We found 4 comparative and 8 noncomparative studies (n = 1768). Reirradiation was associated with pooled event rates of 72% (95% confidence interval [CI] 66%-78%; I2 = 84%), 85% (95% CI 82%-88%; I2 = 69%), and 41% (95% CI 36%-47%; I2 = 80%) for 5-year local failure-free survival, distant failure-free survival, and OS, respectively, with significant heterogeneity among the study results. The pooled event rate for grade 5 toxicities was 33% (95% CI 30%-35%; I2 = 0%) with minimal heterogeneity. CONCLUSION: Reirradiation with IMRT for locally recurrent NPC could confer long-term disease control and survival but is associated with significant mortality.

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.

Prognostic stratification of patients with metastatic nasopharyngeal carcinoma using a clinical and biochemical scoring system.

PURPOSE: Metastatic nasopharyngeal cancer (NPC) is known to have poor survival outcomes. Clinical and biochemical parameters may impact survival outcomes among patients with metastatic NPC and may be used for prognostication. METHODS: One-hundred and fifty-eight patients with metastatic NPC treated at a single tertiary institution were analyzed retrospectively. Multivariate analysis was carried out on patients who were given disease control treatment (n = 135). A numerical score derived from the regression coefficients of each identified independent variable was used to create prognostic groups (PG). A p value of less than 0.05 was considered significant. RESULTS: Independent negative prognostic factors included ECOG status >1, LDH level >580 U/L, hemoglobin level <12.0 g/dL and having more than one metastatic organ involvement. Three PGs were obtained: low risk (total score = 0), intermediate risk (1-2) and high risk (3-4). Median survivals of the 3 groups (low, intermediate and high risk) were 57.1, 18.1 and 8.0 months for the three different risk groups, respectively (p < 0.001). CONCLUSION: Risk stratification of patients with metastatic nasopharyngeal cancer is possible using a prognostic scoring system based on clinical and biochemical parameters. Patients with low-risk score may achieve good metastatic survival and may benefit from additional therapy for disease control.