Publications by authors named "Jacky Li"

7 Publications

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Effect of the underlying malignancy on critically ill septic patient's outcome.

Asia Pac J Clin Oncol 2021 Nov 24. Epub 2021 Nov 24.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong.

Background: Sepsis is an important cause of mortality and morbidity among critically ill patients with underlying malignancy.

Methods: Patients with sepsis admitted to the intensive care unit (ICU) of the Pamela Youde Nethersole Eastern Hospital from January 1, 2010 to April 30, 2019 were recruited. Demographics, laboratory parameter, and outcome were analyzed. Those with underlying malignancy were matched with those without malignancy based on their severity of organ failure (defined by the sequential organ failure assessment [SOFA] score) and septic source.

Results: Two hundred sixty-three patients with underlying active malignancy were matched with 259 patients without malignancy. Those with malignancy had higher APACHE IV score (89 vs. 83), lower albumin (22.1 vs. 24.4), neutrophil count (6.0 vs. 9.3), hemoglobin (8.0 vs. 9.8), platelet count (113 vs. 133), less use of mechanical ventilation (35.7% vs. 45.9%), renal replacement therapy (22.1% vs. 28.2%) and vasopressor (66.2% vs. 74.9%), higher 30-day (34.2% vs. 24.3%) ICU (22.4% vs. 18.9%), and 1-year (62.4% vs. 36.7%) mortality compared with those without malignancy. A higher APACHE IV score and pulmonary sepsis were predictors of 30-day mortality by Cox regression analysis.

Conclusion: Disease severity and pulmonary sepsis, but not underlying malignancy, predicted short-term mortality among critically ill septic patients.
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http://dx.doi.org/10.1111/ajco.13638DOI Listing
November 2021

ATOM: A phase II study to assess efficacy of preemptive local ablative therapy to residual oligometastases of NSCLC after EGFR TKI.

Lung Cancer 2020 04 11;142:41-46. Epub 2020 Feb 11.

Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Objectives: NSCLC patients harboring EGFR mutation invariably developed resistance to EGFR TKI. We postulated that oligoresidual disease (ORD) after initial TKI might harbor resistant clones. This study aimed to test if preemptive local ablative therapy (LAT) can improve progression free survival (PFS) or not compared to historic data.

Materials And Methods: Patients indicated for EGFR TKI who possessed ORD (≤ 4 PET-avid lesions) after an initial 3-month TKI therapy were enrolled. After screening PET-CT, eligible patients with PET-avid ORDs were treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians' discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was repeated on the 3rd and 12th month post-LAT (or at progression) apart from regular imaging. Further LAT was allowed in oligoprogressive disease. Primary endpoint was PFS rate at one-year from enrollment. Overall survival (OS), PFS and treatment safety were secondary endpoints. A post hoc comparison with screen failure cohort was performed.

Results: Eighteen patients were enrolled from 2014-17. Recruitment was stopped before the planned number (34) due to slow accrual. Two were excluded due to consent withdrawal and significant protocol violation. Median follow up was 39.1 months. Among the 16 analyzed patients, the one-year PFS rate (i.e. 15 month post TKI) was 68.8 %. Median OS was 43.3 months. All LAT were done by SABR, and none experienced ≥ grade 3 SABR related toxicities. Compared with screen failure cohort (n = 48), pre-emptive LAT effectively reduced risk of progression (HR 0.41, p = 0.0097).

Conclusion: Preemptive LAT in ORD appeared to be safe and feasible. The 1-year PFS rate was encouraging. However, potential biases and the limitations of the study should not be overlooked. Further randomized studies are warranted.
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http://dx.doi.org/10.1016/j.lungcan.2020.02.002DOI Listing
April 2020

Tissue Determinants of Human NK Cell Development, Function, and Residence.

Cell 2020 02 13;180(4):749-763.e13. Epub 2020 Feb 13.

Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address:

Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2020.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194029PMC
February 2020

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer.

Oncotarget 2018 Nov 20;9(91):36344-36357. Epub 2018 Nov 20.

ACT Genomics, Co. Ltd., Taipei, Taiwan.

Purpose: The identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC.

Results: Of the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset.

Conclusions: The genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact.

Materials And Methods: Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.
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http://dx.doi.org/10.18632/oncotarget.26349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284742PMC
November 2018

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.

N Engl J Med 2018 11 25;379(21):2027-2039. Epub 2018 Sep 25.

From the University of Colorado Cancer Center, Aurora (D.R.C.); Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine (H.R.K.), Samsung Medical Center (M.-J.A.), and Seoul National University Hospital (D.-W.K.), Seoul, National Cancer Center, Goyang (J.-Y.H.), Seoul National University Bundang Hospital, Seongnam (J.-S.L.), and Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju (K.H.L.) - all in South Korea; National Taiwan University Hospital (J.C.-H.Y.) and the Faculty of Medicine, School of Medicine, National Yang-Ming University (G.-C.C.), Taipei, and the Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung (G.-C.C.) - all in Taiwan; the Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna (M.J.H.); Queen Elizabeth Hospital, Kowloon, Hong Kong (J.Y.-C.L.); Azienda Ospedaliera S. Giuseppe Moscati, Avellino (C.G.), the Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola (A.D.), Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS Struttura Operativa Complessa Oncologia Medica A, Aviano (A.B.), Thoracic Medical Oncology, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples (A.M.), and the Medical Oncology Unit, University Hospital of Parma, Parma (M.T.) - all in Italy; Complejo Hospitalario Universitario de A Coruña, Coruña (R.G.C.), and Vall d'Hebron University Hospital, Barcelona (E.F.) - both in Spain; the Department of Hematology and Oncology, University Department of Internal Medicine-Oncology, Pius-Hospital Medical Campus, University of Oldenburg, Oldenburg, Germany (F.G.); the Department of Medical Oncology, Christie NHS Foundation Trust, and Division of Cancer Sciences, University of Manchester, Manchester (R.C.), and Guy's and St. Thomas' NHS Foundation Trust (S.G.) and Royal Marsden Hospital and the National Heart and Lung Institute, Imperial College London (S.P.), London - all in the United Kingdom; Virginia Cancer Specialists Research Institute and US Oncology Research, The Woodlands, TX (A.S.); Yale Cancer Center, New Haven, CT (S.N.G.); and Millennium Pharmaceuticals, Cambridge, MA (N.G., J.H., D.K.).

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.

Methods: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred.

Results: A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted.

Conclusions: Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).
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http://dx.doi.org/10.1056/NEJMoa1810171DOI Listing
November 2018

T790M mutant copy number quantified via ddPCR predicts outcome after osimertinib treatment in lung cancer.

Oncotarget 2018 Jun 15;9(46):27929-27939. Epub 2018 Jun 15.

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR.

Osimertinib prolongs progression-free survival (PFS) in patients with metastatic, epidermal growth factor receptor (EGFR) T790M-mutated, non-small cell lung cancer (NSCLC) after failure of EGFR tyrosine kinase inhibitor (TKI) therapy. We investigated the utility of T790M mutant copy number quantification in a plasma cell-free DNA (cfDNA) assay for predicting clinical outcomes of osimertinib treatment. We retrospectively examined 161 patients who underwent plasma EGFR testing using a digital droplet polymerase chain reaction (ddPCR) technique after EGFR-TKI failure. Of the 74 (46%) patients with detectable T790M mutations in plasma, 55 received osimertinib treatment. Patients who achieved partial response had a higher plasma mutant copy levels than those with progressive disease. Patients who achieved stable disease also tended to have higher plasma mutant copy levels than those with progressive disease. High mutant copy number (≥ 105 per mL of plasma) was associated with shorter PFS (median: 5.5 months vs. not reached) and overall survival (median: 9.1 months vs. NR). Quantitative measurements of T790M mutant copy number in plasma cfDNA by ddPCR thus predicted treatment response and survival outcomes after osimertinib in NSCLC patients resistant to EGFR TKI.
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http://dx.doi.org/10.18632/oncotarget.25332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021335PMC
June 2018

Attitudes, knowledge, and actions with regard to organ donation among Hong Kong medical students.

Hong Kong Med J 2008 Aug;14(4):278-85

Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.

Objective: To study attitudes, knowledge, and actions of local medical students with regard to organ donation and self-perceived confidence and competence in approaching potential organ donors.

Design: Cross-sectional questionnaire survey.

Setting: Faculty of Medicine, The University of Hong Kong, Hong Kong.

Participants: Medical students, years 1-5.

Main Outcome Measures: Knowledge on various aspects of organ donation was assessed, and students' self-evaluated competence and confidence about counselling for organ donation was evaluated. Factors influencing attitudes and actions were determined.

Results: The response rate was 94% (655/694). A majority (85%) had a 'positive' attitude, but only a small proportion (23%) had signed the organ donation card. Inconvenience and lack of knowledge about organ donor registration, and concerns about premature termination of medical treatment accounted for such discrepancies. Socio-cultural factors such as the traditional Chinese belief in preservation of an intact body after death, unease discussing death-related issues, and family objections to organ donation were significantly associated with a 'negative' attitude. Knowledge and action increased with medical education yet only a small proportion of medical students felt competent and confident in counselling patients on organ donation.

Conclusions: The medical curriculum should increase medical students' awareness of the organ shortage problem. The donor registration system should be made more convenient and public education is recommended to correct misconceptions.
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August 2008
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