Conectar
by Dong Min Jung, Yong Jae Kwon, Yong Wan Cho, Jong Geol Baek, Dong Jae Jang, Yongdo Yun, Seok-Ho Lee, Gahee Son, Hyunjong Yoo, Min Cheol Han, Jin Sung Kim
Volumetric modulated arc therapy (VMAT) for lung cancer involves complex multileaf collimator (MLC) motion, which increases sensitivity to interplay effects with tumour motion. Current dynamic conformal arc methods address this issue but may limit the achievable dose distribution optimisation compared with standard VMAT. This study examined the clinical utility of a VMAT technique with monitor unit limits (VMATliMU) to mimic conformal arc delivery and reduce interplay effects while maintaining plan quality. VMATliMU was implemented by applying monitor unit limitations during VMAT reoptimisation to minimise MLC encroachment into target volumes. Using mesh-type reference computational phantom CT images, treatment plans were generated for a simulated stage I lung cancer case prescribed to 45 Gy in three fractions. VMATliMU, conventional VMAT, VMAT with leaf speed limitations, dynamic conformal arc therapy, and constant dynamic conformal arc therapy were compared. Plans were optimised for multiple isodose line prescriptions (50%, 60%, 70%, 80%, and 90%) to investigate the impact of dose distribution. Evaluation parameters included MLC positional accuracy using area difference ratios, dosimetric indices, gradient metrics, and organ-at-risk doses. VMATliMU prevented MLC encroachment into the internal target volume across 60%–90% isodose lines, showing superior MLC accuracy compared with other methods. At the challenging 50% isodose line, VMATliMU had 4.5 times less intrusion than VMAT with leaf speed limits. VMAT plans had better dosimetric indices than dynamic conformal arc plans. VMATliMU reduced monitor units by 5.1%–19.2% across prescriptions. All plans met the clinical dose constraints, with the aortic arch below tolerance and acceptable lung doses. VMATliMU combines VMAT’s dosimetric benefits with the dynamic conformal arcs’s simplicity, minimising MLC encroachment while maintaining plan quality. Reduced monitor units lower low-dose exposure, treatment time, and interplay effects. VMATliMU is usable in existing planners with monitor unit limits, offering a practical solution for lung stereotactic body radiation therapy.
by Xuanqi Pan, Katerina Togka, Hilde ten Berge, Lisa de Jong, Harry Groen, Maarten J. Postma, Eleftherios Zervas, Ioannis Gkiozos, Christoforos Foroulis, Kyriaki Tavernaraki, Sofia Lampaki, Georgia Kourlaba, Antonios Moraris, Sofia Agelaki, Konstantinos Syrigos
ObjectiveThis study aimed to assess the cost-effectiveness of lung cancer screening (LCS) employing volume-based low-dose computed tomography (LDCT) in contrast to the absence of screening, targeting an asymptomatic high-risk population in Greece, leveraging the outcomes derived from the NELSON study, the largest European randomized control trial dedicated to LCS.
MethodsA validated model incorporating a decision tree and an integrated state-transition Markov model was used to simulate the identification, diagnosis, and treatments for a population at high risk of developing lung cancer, from a healthcare payer perspective. Screen-detected lung cancers, costs, life years (LYs), quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. Sensitivity and scenario analyses were conducted to assess the robustness and reliability of the model’s outcomes under varying parameters and hypothetical situations.
ResultsAnnual LCS with volume-based LDCT detected 17,104 more lung cancer patients at early-stage among 207,885 screening population, leading to 8,761 premature lung cancer deaths averted. In addition, in contrast to no screening, LCS yielded 86,207 LYs gained and 50,207 incremental QALYs at an additional cost of €278,971,940, resulting in an ICER of €3,236 per LY and €5,505 per QALY, over a lifetime horizon. These estimates were robust in sensitivity analyses.
ConclusionsLCS with volume-based LDCT, targeting an asymptomatic high-risk population, is highly cost-effective in Greece. Implementing LCS ensures efficient allocation of public healthcare resources while delivering substantial clinical benefits to lung cancer patients.
by Vivian Y. Tat, Aleksandra K. Drelich, Pinghan Huang, Kamil Khanipov, Jason C. Hsu, Steven G. Widen, Chien-Te Kent Tseng, George Golovko
Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.
by Chanel Avenant, Mandisa Singata-Madliki, Alexis J. Bick, Donita Africander, Yusentha Balakrishna, Karl-Heinz Storbeck, Johnson M. Moliki, Sigcinile Dlamini, Salndave Skosana, Jenni Smit, Mags Beksinska, Ivana Beesham, Ishen Seocharan, Joanne Batting, George J. Hofmeyr, Janet P. Hapgood
HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018–2019, randomized HIV-negative women aged 18–40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214–218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p
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