140 research outputs found
Treatment optimization of nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy (IMRT)
No full textNasopharyngeal carcinoma (NPC) is an endemic malignancy in Hong Kong, southern China, Taiwan, Singapore and Malaysia, well known for its strong association with genetic predisposition and Epstein-Barr virus (EBV). Recently intensity modulated radiation therapy (IMRT) has developed itself as key player in this battlefield against this radio-sensitive and radio-responsive malignancy for the past 15 years. Numerous studies have confirmed its superiority over traditional techniques for both untreated or locally recurrent diseases. By the use of multiple beams directing to the tumors at numerous angles, together with its further intensity modulation within each beam by the movement and positions of the leaves in the multileaf collimators driven by contemporary linear accelerators, a high radiation dose to the tumor and dose sparing to adjacent organs-at-risk (OARs) can be achieved. Nevertheless, IMRT still gives rise to significant though manageable acute and chronic side effects including nausea/vomiting, xerostomia, impaired hearing ability, dysphagia, etc. Although the dose tolerance to the concerned organs or structures responsible for xerstomia, impaired hearing and dysphagia has been recognized, there are still others organs/structures which can be further explored so the aim of less radiation-related toxicities can be achieved.
Apart from that, post-treatment tumor response evaluation is a major component to demonstrate the superiority of IMRT as compared to other techniques. Imaging tools including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography with integrated computed tomography (PET-CT) may not be sensitive and specific enough to differentiate between recurrent tumors and post-radiation changes. Biomarkers have been developed rapidly as non-invasive and accurate predictors or prognosticators of this disease. It is hoped that biomarkers can complement imaging tools as reliable instruments in diagnosis, surveillance and prognostication.
In this thesis, I first focused on the effect of CT contrast on radiation dose calculation during IMRT treatment planning with emphasis on the dose to the carotid arteries and thyroid which are readily contrast enhancing. Our results showed that contrast injection resulted in an insignificant and clinically negligible dose reduction to the carotid arteries and the thyroid. We then identified that radiation dose to the vestibules in the inner ears are responsible for the development of radiation-induced acute nausea in patients treated with IMRT alone. Furthermore, we investigated the role of plasma EBV deoxyribonucleic acid (DNA) in predicting local clinical remission immediately after IMRT as well as long-term survival outcomes. We demonstrated that though plasma EBV DNA did not correlate well with local clinical remission after completion of IMRT with or without adjunct chemotherapy, it is significantly and strongly prognostic of all prespecified 3-year survival endpoints. Finally we revealed that hyperfractionated IMRT showed a trend of better local failure-free survival and fewer incidences of treatment-related hemorrhage compared to standard-fractionated IMRT as a second-course radiation therapy for locally recurrent NPC.
In summary, this thesis has provided new insights on treatment optimization of NPC in the era of IMRT and it is believed our study results shall benefit the next generation of patients who suffer from this highly curable malignancy.published_or_final_versionClinical OncologyMasterDoctor of Medicin
Supporting data for "Preclinical study of ATM inhibitor AZD1390 on nasopharyngeal carcinoma"
No full textComprehensive in vitro drug testing of small molecule inhibitor on nasopharyngeal carcinoma cell lines from transcription to protein level regarding cell cycle, proliferation, cell death and clonogenicity and migration using AVPI, cell cycle analysis, cell proliferation, XTT cell viability, colony formation, qPCR, proteomics, SA-β-gal staining, ICC wound healing, western blot and morphological examination.</p
Overall Survival Benefits of First-Line Treatments for Asian Patients with Advanced Epidermal Growth Factor Receptor-Mutated NSCLC Harboring Exon 19 Deletion: A Systematic Review and Network Meta-Analysis
No full textSIMPLE SUMMARY: Survival benefits and clinical responsiveness have been exhibited by various generations of EGFR-tyrosine kinase inhibitors (TKIs) in numerous randomized-controlled trials for EGFR-mutated advanced non-small-cell lung cancer (NSCLC) over the past two decades. However, the efficacy, especially long-term overall survival (OS) for Asians harboring an exon 19 deletion (19del) in their NSCLC, remains uncertain. This systematic review and network meta-analysis evaluate the efficacy of all first-line treatments in Asian patients with advanced EGFR-mutated NSCLC harboring 19del. EGFR-TKIs and combination treatments demonstrated no OS benefits in comparison with standard chemotherapy treatments, although progression-free survival (PFS) benefits were revealed. Erlotinib plus bevacizumab, ramucirumab plus erlotinib, and osimertinib are the optimal regimens to prolong PFS for Asians with 19del. Further studies are warranted to investigate the resistance mechanisms and possible strategies for individuals harboring this common mutation. ABSTRACT: (1) Background: Randomized controlled trials (RCTs) have explored various primary treatments for individuals diagnosed as having later-stage epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. Nevertheless, the extent to which such treatments are efficacious, particularly with regard to overall survival (OS) rates of patients from Asia with exon 19 deletion (19del), has yet to be clarified. (2) Methods: A systematic review and frequentist network meta-analysis were conducted by obtaining pertinent studies from PubMed/MEDLINE Ovid, Embase, Cochrane Library, and trial registries, as well as various other sources. RCTs in which two or multiple treatments in the primary setting for patients from Asia with EGFR 19del were compared were included. This research has been recorded in the Prospective Register of Systematic Reviews (CRD 42022320833). (3) Results: A total of 2715 patients from Asia participated in 18 trials in which 12 different treatments were administered, which included: EGFR tyrosine kinase inhibitors (TKIs) (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed-based chemotherapy, pemetrexed-free chemotherapy, and combination treatments (gefitinib plus apatinib, erlotinib plus ramucirumab, erlotinib plus bevacizumab, and gefitinib plus pemetrexed-based chemotherapy). Such treatments were not significantly beneficial in terms of OS for patients from Asia who had 19del. It was demonstrated that erlotinib plus bevacizumab, ramucirumab plus erlotinib, and osimertinib consistently yielded the greatest benefits regarding progression-free survival benefit (P-scores = 94%, 84%, and 80%, respectively). Combination treatments resulted in increased toxicity, particularly gefitinib plus apatinib and erlotinib plus bevacizumab, causing the highest prevalence of grade ≥ 3 adverse events. Icotinib and osimertinib had the fewest grade ≥ 3 adverse events. Specific treatments were associated with a wide range of toxicity levels. (4) Conclusions: In patients from Asia with 19del, both EGFR-TKIs and treatments in which therapies were combined exhibited no OS benefits in comparison with standard chemotherapy treatments. Additional research is required to study TKIs’ resistance mechanisms and possible combined approaches for individuals harboring this common mutation
Nasopharynx Battlefield: Cellular Immune Responses Mediated by Midkine in Nasopharyngeal Carcinoma and COVID-19
No full textClinical evidence suggests that the severe respiratory illness coronavirus disease 2019 (COVID-19) is often associated with a cytokine storm that results in dysregulated immune responses. Prolonged COVID-19 positivity is thought to disproportionately affect cancer patients. With COVID-19 disrupting the delivery of cancer care, it is crucial to gain momentum and awareness of the mechanistic intersection between these two diseases. This review discusses the role of the cytokine midkine (MK) as an immunomodulator in patients with COVID-19 and nasopharyngeal carcinoma (NPC), both of which affect the nasal cavity. We conducted a review and analysis of immunocellular similarities and differences based on clinical studies, research articles, and published transcriptomic datasets. We specifically focused on ligand–receptor pairs that could be used to infer intercellular communication, as well as the current medications used for each disease, including NPC patients who have contracted COVID-19. Based on our findings, we recommend close monitoring of the MK axis to maintain the desirable effects of therapeutic regimens in fighting both NPC and COVID-19 infections
Abstract P186: Preclinical evaluation of the proteasome inhibitor ixazomib (MLN2238) on nasopharyngeal cacinoma (NPC)
No full textComplications of Central Venous Access Devices Used in Palliative Care Settings for Terminally Ill Cancer Patients: A Systematic Review and Meta-Analysis
No full text(1) Background: Central venous access devices (CVADs) have been commonly employed during various courses of anticancer treatment. Currently, there are a few types of clinically available CVADs, which are associated with short-term and long-term complications. However, little is known about the complication rates when CVADs are used only in palliative care settings. We therefore performed a systematic review and meta-analysis of all the published literature to evaluate the complication rates of CVADs in this clinical setting. (2) Methods: A systematic review and meta-analysis were conducted to identify publications from PubMed/MEDLINE, Embase (Ovid), Scopus, Cochrane Library, CINAHL, Google Scholar, and trial registries. Publications reporting the complication rates of PICCs, central lines, and PORTs in palliative settings for terminally ill cancer patients were included, while those on the use of systemic anticancer therapy and peripheral venous catheters were excluded. The outcome measures included overall complication rate, rate of catheter-related bloodstream infection (CRBSI), and rate of thromboembolism (TE). This systematic review was registered with PROSPERO (CRD42023404489). (3) Results: Five publications with 327 patients were analyzed, including four studies on PICCs and one study on central lines. No studies on PORTs were eligible for analysis. The overall complication rate for PICCs (pooled estimate 7.02%, 95% CI 0.27–19.10) was higher than that for central lines (1.44%, 95% CI 0.30–4.14, p = 0.002). The risk of CRBSI with PICCs (2.03%, 95% CI 0.00–9.62) was also higher than that with central lines (0.96%, 95% CI 0.12–3.41, p = 0.046). PICCs also had a trend of a higher risk of TE (2.10%, 95% CI 0.00–12.22) compared to central lines (0.48%, 95% CI 0.01–2.64, p = 0.061). (4) Conclusions: PICCs for palliative cancer care were found to have greater complications than central lines. This might aid in the formulation of future recommendation guidelines on the choice of CVAD in this setting
Learning Robust Shape Regularization for Generalizable Medical Image Segmentation
No full textGeneralizable medical image segmentation enables models to generalize to unseen target domains under domain shift issues. Recent progress demonstrates that the shape of the segmentation objective, with its high consistency and robustness across domains, can serve as a reliable regularization to aid the model for better cross-domain performance, where existing methods typically seek a shared framework to render segmentation maps and shape prior concurrently. However, due to the inherent texture and style preference of modern deep neural networks, the edge or silhouette of the extracted shape will inevitably be undermined by those domain-specific texture and style interferences of medical images under domain shifts. To address this limitation, we devise a novel framework with a separation between the shape regularization and the segmentation map. Specifically, we first customize a novel whitening transform-based probabilistic shape regularization extractor namely WT-PSE to suppress undesirable domain-specific texture and style interferences, leading to more robust and high-quality shape representations. Second, we deliver a Wasserstein distance-guided knowledge distillation scheme to help the WT-PSE to achieve more flexible shape extraction during the inference phase. Finally, by incorporating domain knowledge of medical images, we propose a novel instance-domain whitening transform method to facilitate a more stable training process with improved performance. Experiments demonstrate the performance of our proposed method on both multi-domain and single-domain generalization
Does HCC Etiology Impact the Efficacy of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma? An Asian Liver Radiation Therapy Group Study
No full textBackground/purpose: The Asian Liver Radiation Therapy Study Group has formed a large and detailed multinational database of outcomes following stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Here, we explored the potential impact of HCC etiology on SBRT efficacy. Tumor control probability (TCP) models were established to estimate the likelihood of local control (LC).
Methods: Data from 415 patients who were treated with SBRT for HCC were reviewed. Cox proportional hazards models were used to identify key predictors of LC. TCP models accounting for biologic effective dose (BED) and tumor diameter were generated to quantify associations between etiology and LC.
Results: Cox models demonstrated that hepatitis C virus (HCV) infection was associated with favorable LC following SBRT (HR=0.52, 95% CI 0.04-0.96, p=0.036). The 2-year LC rate for patients with HCV etiology was 88%, compared to 78% for other patients. Small tumor and high BED were also associated with favorable LC. TCP models demonstrated a 10-20% absolute increase in predicted LC across the range of SBRT doses and tumor sizes.
Conclusion: We found a novel association between HCV status and LC after SBRT for HCC that warrants further exploration. If validated in other datasets, our findings could help clinicians tailor SBRT schedules.ope
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