Isotropic reconstruction of a 4-D MRI thoracic sequence using super-resolution.

PURPOSE: Four-dimensional (4D) thoracic magnetic resonance imaging (MRI) sequences have been shown to successfully monitor both tumor and lungs anatomy. However, a high temporal resolution is required to avoid motion artifacts, which leads to volumes with poor spatial resolution. This article proposes to reconstruct an isotropic 4D MRI thoracic sequence with minimum modifications to the acquisition protocols. This could be an important step toward the use of 4D MRI for thoracic radiotherapy applications. METHODS: In a postacquisition step, three orthogonal 4D anisotropic acquisitions are combined using super-resolution to reconstruct a series of isotropic volumes. A new phantom that simulates lung tumor motion is developed to evaluate the performance of the algorithm. The proposed framework is also applied to real data of a lung cancer patient. RESULTS: Subjective and objective evaluations show clear resolution enhancement and partial volume effect diminution. The isotropic reconstruction of patient data significantly improves both the visualization and segmentation of thoracic structures. CONCLUSIONS: The results presented here are encouraging and suggest that super-resolution can be regarded as an efficient method to improve the resolution of 4D MRI sequences. It produces an isotropic 4D sequence that would be impossible to acquire in practice. Further investigations will be required to evaluate its reproducibility in various clinical applications.

Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases.

BACKGROUND: The 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. OBJECTIVES: To 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 METHODS: We 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 CRITERIA: Randomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. DATA COLLECTION AND ANALYSIS: Two 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' CONCLUSIONS: There 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.

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

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.

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.

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally advanced nasopharyngeal carcinoma: interim results from 2 prospective phase 2 clinical trials.

BACKGROUND: The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC). METHODS: Patients with newly diagnosed NPC were accrued to 2 trials, 1 for patients with stage III disease and the other for patients with IVA/IVB disease. All patients received TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), and 5-FU 2500 mg/m(2) every 3 weeks for 3 cycles) followed by cisplatin 40 mg/m(2) per week concurrently with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy. RESULTS: From January 2007 to July 2011, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued. With a median follow-up of 32.9 months, the 3-year overall survival rates were 94.8% (95% confidence interval [CI], 87.6%-100%) and 90.2% (95% CI, 81.8%-98.6%) for the stage III NPC group and the IVA/IVB NPC group, respectively. The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 78.2% (95% CI, 64.6%-91.8%), 90.5% (95% CI, 79.7%-100%), and 93.9%(87.1%-100%), respectively, for patients with stage III NPC and 85.1% (95% CI, 75.1%-95.1%), 88% (95% CI, 78.6%-97.4%), and 100%, respectively, for patients with stage IVA/IVB NPC. The most common severe (grade 3/4) hematologic and nonhematologic adverse events were neutropenia (64 patients; 55.2%) and nausea/vomiting (23 patients; 19.8%). CONCLUSIONS: Neoadjuvant TPF followed by concurrent chemoradiation was well tolerated and produced encouraging outcomes in patients with locally advanced NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy.

Recombinant adenovirus-p53 (Gendicine) sensitizes a pancreatic carcinoma cell line to radiation.

OBJECTIVE: In this study, we examine the effects of recombinant adenovirus-p53 (rAd-p53) on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. METHODS: Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions (SF) were calculated. Dose survival curves were constructed and modeled for comparison. RESULTS: Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation (D0 for the experimental and control groups was 2.199 and 2.462, respectively). CONCLUSIONS: Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial.

Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence.

BACKGROUND: The characteristics of cervical lymphatic metastasis in nasopharyngeal carcinoma (NPC) are not completely understood. As such, radiotherapy to the entire lymphatic of the neck bilaterally has been empirically practiced even in early stage disease, although not supported by clinical evidence. We studied the pattern and probability of nodal metastasis through a meta-analysis of published evidences, with an aim to establish an evidence-based guideline for selecting and delineation of clinical target volume of neck lymphatics for conformation radiation for NPC. METHODS: A literature search yielded an initial 411 original articles, and 13 studies with 2920 NPC cases staged via MRI were included in this analysis. The occurrence of nodal metastasis was calculated and analyzed according to the respective regional nodal levels. RESULTS: 85% of NPC cases presented with lymphadenopathy. The most commonly involved regions include retropharyngeal (69%) and level II lymph nodes (70%). The overall probability of levels III, IV, and V nodal involvement are 45%, 11%, and 27%, respectively. Low-risk node groups included the supraclavicular, levels IA/IB and VI nodes, and parotid nodes with involvement rates at 3%, 0%, 3%, 0%, and 1%, respectively. Nodal metastases followed an orderly pattern and the probability of "skip" metastasis between levels varied between 0.5-7.9%. CONCLUSIONS: Lymph node metastasis in NPC follows a predictable and orderly pattern. The rarity of metastasis in certain nodal groups and "skip" metastasis suggest that reduced treatment volume is feasible in conformal radiotherapy for NPC.

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.

Concurrent chemoradiotherapy incorporating high-dose rate brachytherapy for locally advanced cervical carcinoma: survival outcomes, patterns of failure, and prognostic factors.

BACKGROUND: This is a retrospective study evaluating the survival outcomes, patterns of failure, and prognostic factors of chemoradiotherapy incorporating high-dose rate brachytherapy in the treatment of locally advanced cervical cancer. METHODS: A review of 120 consecutive patients with Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stages IB2 to IVA cervical cancer treated with concurrent cisplatin-based chemoradiotherapy between April 1999 and January 2005. Overall (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. RESULTS: The 5-year OS and DFS rates were, respectively, 65.0% (35.0% IB2, 65.7% IIA-B, 71.0% IIIA-B, and 40.0% IVA) and 57.3% (30.0% IB2, 58.2% IIA-B, 64.0% IIIA-B, and 40.0% IVA). Most patients had squamous cell carcinoma (89.2%) and belonged to FIGO stages IIB (40.8%) and IIIB (30.8%). All but 4 patients completed the planned radiotherapy regimen. There were 48 documented recurrences, of which 13 were locoregional only, 26 were distant only, and 9 were both sites. Five patients (4.2%) experienced late grade 3 to 4 gastrointestinal toxicity. On multivariate analysis, a preradiotherapy hemoglobin level of less than 10 g/dL and tumor size of 4 cm or greater or bulky on computed tomography were independently significant variables for OS, whereas a nadir hemoglobin level of less than 10 g/dL and presence of radiologically enlarged pelvic or paraaortic lymph nodes were independently significant variables for DFS. CONCLUSIONS: We conclude that this regimen is efficacious and feasible, but the safety profile about concurrent administration of high-dose rate brachytherapy and chemotherapy should be studied further. Finally, for cervical cancer patients selected for nonsurgical treatment, radiological assessment of tumor size and lymph node status can provide valuable prognostic information over and above FIGO staging alone.

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.

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.

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.

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.

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.

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.

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.