Toward Improved Outcomes for Patients With Lung Cancer Globally: The Essential Role of Radiology and Nuclear Medicine.

PURPOSE: Key to achieving better population-based outcomes for patients with lung cancer is the improvement of medical imaging and nuclear medicine infrastructure globally. This paper aims to outline why and spark relevant health systems strengthening. METHODS: The paper synthesizes the global lung cancer landscape, imaging referral guidelines (including resource-stratified ones), the reliance of TNM staging upon imaging, relevant multinational health technology assessments, and precisely how treatment selection and in turn patient outcomes hinge upon imaging findings. The final discussion presents data on current global gaps in both diagnostics (including imaging) and therapies and how, informed by such data, improved population-based outcomes are tangible through strategic planning. RESULTS: Imaging findings are central to appropriate lung cancer patient management and can variably lead to life-prolonging interventions and/or to life-enhancing palliative measures. Early-stage lung cancer can be treated with curative intent but, unfortunately, most patients with lung cancer still present at advanced stages and many patients lack access to both diagnostics and therapies. Furthermore, half of lung cancer cases occur in low- and middle-income countries. The role of medical imaging and nuclear medicine in lung cancer management, as outlined herein, may help inform strategic planning. CONCLUSION: Lung cancer is the number one cancer killer worldwide. The essential role that medical imaging and nuclear medicine play in early diagnosis and disease staging cannot be overstated, pivotal in selecting the many patients for whom measurably improved outcomes are attainable. Prevention synergized with patient-centered, compassionate, high-quality lung cancer management provision mandate that strategic population-based planning, including universal health coverage strategies, should extend well beyond the scope of disease prevention to include both curative and noncurative treatment options for the millions afflicted with lung cancer.

Radiotherapy quality assurance of SBRT for patients with centrally located lung tumours within the multicentre phase II EORTC Lungtech trial: Benchmark case results.

PURPOSE: To report on the benchmark case (BC) study performed in the context of the European Organisation for Research and Treatment of Cancer prospective multicentre Lungtech trial of SBRT for patients with inoperable centrally located lung tumours. METHODS AND MATERIALS: Target volume and organs at risk (OARs) delineations first needed to be acceptable before the treatment plan was reviewed. Retrospectively, Dice similarity coefficients of the OARs and the target volumes were calculated and a set of gold standard contours adapted for each institution margins was applied on the accepted dose submissions to evaluate the influence of acceptable delineation variations on dosimetry. RESULTS: Twenty-five institutions participated. Five BCs were accepted at the first attempt. Twenty institutions had to revise their delineation at least once and seven had to revise their planning once. The V60 Gy dose coverage improved significantly (p = 0.05) between the first and final submissions from median (range) 94.8% (22.5-97.8) to 95.3% (70.5-99.3). The median Dice coefficient varied significantly between OARs: The lowest values were found for the brachial plexus 0.25 (0.01-0.54) and the highest for the spinal cord 0.89 (0.71-0.95). The mean PTV Dice coefficient was 0.82 (0.48-0.92). Applying the gold standard contours, only one institution remained compliant with the dose coverage criteria with V60 Gy median (range) of 83.4% (54.2-93.9). CONCLUSIONS: Clinical guidelines and radiotherapy protocols are not a substitute for timely radiotherapy quality assurance procedures, which improve dose coverage significantly. Delineation remains the main source of BC rejection and plan review without first reviewing delineation may not be efficient. Our results show that delineation variations seem to have a larger influence on PTV coverage than variations in planning and irradiation techniques and thus suggest that dose tolerance criteria should preferably take into account the accuracy of delineation.

Stereotactic Body Radiation Therapy as an Alternative Treatment for Patients with Hepatocellular Carcinoma Compared to Sorafenib: A Propensity Score Analysis.

BACKGROUND AND AIMS: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC. METHODS: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 centers in Germany and Switzerland. Medical records were reviewed including laboratory parameters, treatment characteristics and development of adverse events. Propensity score matching was performed to adjust for differences in baseline characteristics. The primary endpoint was overall survival (OS) and progression-free survival. RESULTS: Median OS of SBRT patients was 18.1 (10.3-25.9) months compared to 8.8 (8.2-9.5) in sorafenib patients. After adjusting for different baseline characteristics, the survival benefit for patients treated with SBRT was still preserved with a median OS of 17.0 (10.8-23.2) months compared to 9.6 (8.6-10.7) months in sorafenib patients. SBRT treatment of intrahepatic lesions in patients with extrahepatic metastases was also associated with improved OS compared to patients treated with sorafenib in the same setting (17.0 vs. 10.0 months, p = 0.012), whereas in patients with portal vein thrombosis there was no survival benefit in patients with SBRT. CONCLUSIONS: In this retrospective comparative study, SBRT showed superior efficacy in HCC patients compared to patients treated with sorafenib.

Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells.

AIM: To study short dsRNA oligonucleotides (siRNA) as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1 (NDRG1) gene induced under different physiological conditions (Normoxia and hypoxia) modulating NDRG1 transcription, mRNA stability and translation. METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 × 10(7) cells, nuclear extracts were prepared according to previous protocols. The pSUPER-NDRG1 vectors were designed, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on ß-actin and hypoxia-inducible factor (HIF)-1α mRNA sequences in GenBank. NDRG1 mRNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia (P < 0.05 was considered significant). RESULTS: siRNA- and iodoacetate (IAA)-mediated downregulation of NDRG1 mRNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results. CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it can represent a potential target for tumor treatment in human glioblastoma. The siRNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays.