Discovery of pre-therapy 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography-based radiomics classifiers of survival outcome in non-small-cell lung cancer patients.

PURPOSE: The aim of this multi-center study was to discover and validate radiomics classifiers as image-derived biomarkers for risk stratification of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Pre-therapy PET scans from a total of 358 Stage I-III NSCLC patients scheduled for radiotherapy/chemo-radiotherapy acquired between October 2008 and December 2013 were included in this seven-institution study. A semi-automatic threshold method was used to segment the primary tumors. Radiomics predictive classifiers were derived from a training set of 133 scans using TexLAB v2. Least absolute shrinkage and selection operator (LASSO) regression analysis was used for data dimension reduction and radiomics feature vector (FV) discovery. Multivariable analysis was performed to establish the relationship between FV, stage and overall survival (OS). Performance of the optimal FV was tested in an independent validation set of 204 patients, and a further independent set of 21 (TESTI) patients. RESULTS: Of 358 patients, 249 died within the follow-up period [median 22 (range 0-85) months]. From each primary tumor, 665 three-dimensional radiomics features from each of seven gray levels were extracted. The most predictive feature vector discovered (FVX) was independent of known prognostic factors, such as stage and tumor volume, and of interest to multi-center studies, invariant to the type of PET/CT manufacturer. Using the median cut-off, FVX predicted a 14-month survival difference in the validation cohort (N = 204, p = 0.00465; HR = 1.61, 95% CI 1.16-2.24). In the TESTI cohort, a smaller cohort that presented with unusually poor survival of stage I cancers, FVX correctly indicated a lack of survival difference (N = 21, p = 0.501). In contrast to the radiomics classifier, clinically routine PET variables including SUVmax, SUVmean and SUVpeak lacked any prognostic information. CONCLUSION: PET-based radiomics classifiers derived from routine pre-treatment imaging possess intrinsic prognostic information for risk stratification of NSCLC patients to radiotherapy/chemo-radiotherapy.

Letter to the Editor in response to the Position statement and best practice recommendations on the imaging use of ultrasound from the European Society of Radiology ultrasound subcommittee.

This letter to the editor is in response to the consensus statement from the Ultrasound Subcommittee of the European Society of Radiology, the European Union of Medical Specialists (UEMS) Section of Radiology, and the European Federation of Societies for Ultrasound in Medicine and Biology. It highlights the role of the non-medical sonographer in the UK and the evidence underpinning this safe and effective practice.

Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic.

The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency. The National COVID-19 Chest Imaging Database, led by NHSX, British Society of Thoracic Imaging, Royal Surrey NHS Foundation Trust and Faculty, is an example of such a national initiative. Here, we summarise the experiences and challenges of setting up the National COVID-19 Chest Imaging Database, and the implications for future ambitions of national data curation in medical imaging to advance the safe adoption of artificial intelligence in healthcare.

Continuous hyperfractionated accelerated radiotherapy - Escalated dose (CHART-ED): A phase I study.

INTRODUCTION: Patients who present with locally advanced inoperable non-small cell lung cancer (NSCLC) may be suitable for radical radiotherapy. A randomised trial of 563 patients compared CHART and conventional radical radiotherapy (60 Gy/30f) given over 6 weeks and suggested that CHART resulted in a 9% improvement in 2-year survival (Saunders et al., 1999). RT dose escalation for both conventional and CHARTWEL (CHART-WeekEndLess) - fractionation schedules is feasible with modern 3-dimensional CT-based planning techniques and we initiated a phase I CHART dose escalation study in 2009. METHODS: Patients with WHO performance status 0-2 histologically confirmed, inoperable, stage I-III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6G y (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15-16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15-17, Group 3). RESULTS: Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia - classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed. CONCLUSIONS: CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies.

Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial.

PURPOSE: Venous thromboembolism (VTE) is common in cancer patients. Evidence has suggested that low molecular weight heparin (LMWH) might improve survival in patients with cancer by preventing both VTE and the progression of metastases. No trial in a single cancer type has been powered to demonstrate a clinically significant survival difference. The aim of this trial was to investigate this question in patients with lung cancer. PATIENTS AND METHODS: We conducted a multicenter, open-label, randomized trial to evaluate the addition of a primary prophylactic dose of LMWH for 24 weeks to standard treatment in patients with newly diagnosed lung cancer of any stage and histology. The primary outcome was 1-year survival. Secondary outcomes included metastasis-free survival, VTE-free survival, toxicity, and quality of life. RESULTS: For this trial, 2,202 patients were randomly assigned to the two treatment arms over 4 years. The trial did not reach its intended number of events for the primary analysis (2,047 deaths), and data were analyzed after 2,013 deaths after discussion with the independent data monitoring committee. There was no evidence of a difference in overall or metastasis-free survival between the two arms (hazard ratio [HR], 1.01; 95% CI, 0.93 to 1.10; P = .814; and HR, 0.99; 95% CI, 0.91 to 1.08; P = .864, respectively). There was a reduction in the risk of VTE from 9.7% to 5.5% (HR, 0.57; 95% CI, 0.42 to 0.79; P = .001) in the LMWH arm and no difference in major bleeding events but evidence of an increase in the composite of major and clinically relevant nonmajor bleeding in the LMWH arm. CONCLUSION: LMWH did not improve overall survival in the patients with lung cancer in this trial. A significant reduction in VTE is associated with an increase in clinically relevant nonmajor bleeding. Strategies to target those at greatest risk of VTE are warranted.

Relationship between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiation reactions: a comparison of training and validation cohorts of breast cancer patients.

BACKGROUND AND PURPOSE: Using pulsed field gel electrophoresis (PFGE) a significant correlation was demonstrated between residual DNA double-strand breaks (dsbs) and the development of late radiation fibrosis in a group of 39 breast cancer patients studied retrospectively. This group formed a training cohort generating a hypothesis that there is a relationship between residual radiation-induced DNA dsbs in cultured fibroblasts and late radiotherapy reactions in breast cancer patients. The aim of this study was to retest and validate the hypothesis. MATERIALS AND METHODS: The study was retrospective. Skin biopsies were taken from a validation cohort of 50 breast cancer patients and PFGE was used to examine residual radiation-induced dsbs in cultured fibroblasts. Late morbidity was measured clinically as fibrosis and using the late effects on normal tissues scales that incorporate subjective, objective management and analytic data (LENT SOMA). RESULTS: PFGE data were obtained for 49 biopsies. In the 49 patients there was no correlation between residual DNA damage and either fibrosis (r=-0.027, P=0.85) or LENT SOMA (r=-0.10, P=0.48) scores. There was no significant relationship between residual damage and fibrosis for the combined training and validation cohorts of 88 patients (r=0.20, P=0.063). CONCLUSIONS: This study did not validate the hypothesis that there is a relationship between fibroblast residual DNA damage and late morbidity in breast cancer patients. The PFGE assay on fibroblasts is not a suitable test of the degree of late radiation-induced fibrosis in the breast.

FDG injection site extravasation: potential pitfall of misinterpretation and missing metastases.

18F-FDG PET/CT plays an important role in the management of non-small-cell lung cancers (NSCLC). The treatment options for NSCLC depend upon the initial staging of the disease. The authors report a case with a potential pitfall of overlooking a site of FDG uptake as radiopharmaceutical extravasation at an injection site. The PET/CT demonstrated a T2a N2 bronchial carcinoma, with a solitary focus of FDG uptake at the left antecubital fossa where FDG was administered. Careful interpretation of the images reveals a solitary skeletal metastasis in the left proximal ulna, which makes the disease stage IV rather than IIIA, leading to a significant difference in treatment.

Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy and 3-dimensional, conformal, accelerated radiotherapy in locally advanced nonsmall cell lung cancer.

BACKGROUND: The objective of this study was to evaluate prospectively the acute and late adverse effects of taxane/carboplatin neoadjuvant chemotherapy and 3-dimensional, conformal radiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). METHODS: Forty-two patients were entered into a nonrandomized Phase II study of continuous, hyperfractionated, accelerated radiotherapy (CHART) week-end less (CHARTWEL) to a dose of 60 grays (Gy). Three cycles of chemotherapy were given over 9 weeks before radiotherapy. Dose escalation with paclitaxel was from 150 mg/m2 to 225 mg/m2. Systemic toxicity to chemotherapy was monitored throughout. Radiation-induced, early, adverse effects were assessed during the first 9 weeks from the start of radiotherapy, and late effects were assessed from 3 months onward. Overall survival, disease-free survival, and locoregional tumor control also were monitored. RESULTS: Twenty percent of patients failed to receive chemotherapy as planned, primarily because of neutropenia. The incidence of Dische Dictionary Grade >or=2 and Grade >or=3 dysphagia was 57.5% and 10%, respectively, with an average duration of 1.2 weeks and 1.5 days, respectively. By 9 weeks, <3% of patients were symptomatic; and, eventually, all acute reactions were healed, and there has been no evidence of consequential damage. At 6 months, the actuarial incidence of moderate-to-severe pneumonitis was 10%. During this time, all patients were free of severe pulmonary complications. Actuarial estimates of Grade >or=2 late lung dysfunction were 3% at 1 year, 10% at 2 years, and remained at this level thereafter. The actuarial 3-year locoregional control and overall survival rates were 54% and 45%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy followed by 3-dimensional, conformal CHARTWEL 60-Gy radiotherapy in patients with advanced NSCLC was feasible and was tolerated well. Historic comparisons indicated that locoregional tumor control is not compromised by the use of conformal techniques.