Clinical Pathology - Research Publications
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ItemThe prevalence and clinicopathological features of programmed death-ligand 1 (PD-L1) expression: a pooled analysis of literatures(IMPACT JOURNALS LLC, 2016-03-22)BACKGROUND & AIMS: Programmed death-ligand 1 (PD-L1) has been recognized as a critical and promising target in therapies that direct immune escape of cancers. However, its association with aggressive clinicopathological features in solid tumors remains unclear. We investigated this question by synthesizing published articles. METHODS: Electronic databases were searched for relevant studies. Outcomes of interest included age, gender, tumor size, tumor size, lymph node metastasis and tumor cell differentiation. RESULTS: A total of 61 studies involving 17 types of malignancies were included. The overall expression rate of PD-L1 was 44.5% (95% CI, 37.5% to 51.6 %). Patients with regional lymph node metastases (OR 1.38; P < 0.01), large size tumor (OR 1.89; P < 0.01) or poor differentiated tumors (OR 1.71; P < 0.01) were associated with higher PD-L1 expression rate. However, no significant association was observed between young and elder patients (OR 1.04; P = 0.58), or male and female patients (OR 1.13; P = 0.06). A numerically higher PD-L1 expression rate was detected in polyclonal antibodies (57.2%) than monoclonal antibodies (39.6%). In addition, the PD-L1 expression rate reported by studies from Asian areas (52.3%) was numerically higher than those from non-Asian areas, namely Caucasians (32.7%). CONCLUSIONS: This meta-analysis indicated that patients with larger tumors, regional lymph node metastases, or poor-differentiated tumors were associated with a higher PD-L1 expression rate; in addition the expression rate of PD-L1 in Asians might be higher than that of Caucasians. This information might be useful in screening candidates for relevant tests and treatments.
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ItemAdoptive Immunotherapy in Postoperative Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis(PUBLIC LIBRARY SCIENCE, 2016-09-12)BACKGROUND: Adoptive immunotherapy (AI) has been applied in the treatment of non-small-cell lung cancer (NSCLC) patients, but the value of postoperative AI has been inconclusive largely as a result of the small number of patients included in each study. We performed a systematic review and meta-analysis to address this issue for patients with postoperative NSCLC. METHODS: Pubmed, Embase, Cochrane Library were searched for randomized controlled trials comparing adoptive immunotherapy with control therapies in postoperative NSCLC patients. The primary endpoint was overall survival. Hazard ratio (HR) was estimated and 95% confidence intervals (CI) were calculated using a fixed-effect model. RESULTS: Compared with control therapies, analyses of 4 randomized controlled trials (472 patients) showed a significant benefit of adoptive immunotherapy on survival (hazard ratio [HR] 0.61, 95% CI 0.45-0.84, p = 0.002), and a 39% reduction in the relative risk of death (no evidence of a difference between trials; p = 0.16, I² = 42%). In subgroup analyses by treatment cycles and treatment regimen, significant OS benefit was found in combination therapy of AI with chemotherapy, regardless of whether or not the treatment cycles were more than 10 cycles. CONCLUSION: Adoptive immunotherapy has the potential to improve overall survival in postoperative NSCLC. The findings suggest this is a valid treatment option for these patients. Further randomized clinical trials are urgently needed.
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Item[Propensity Score Matching Analysis of VATS Lobectomy and Sublobar Resection for Stage I Lung Adenocarcinoma].( 2017-01-20)BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend video-assisted thoracoscopic surgery (VATS) anatomical lobectomy as the first choice for the treatment of resectable lung cancer. However, sublobar resection offers significantly better functional preservation compared with lobectomy for stage I lung cancer. At present, the inferiority of sublobar resection to lobectomy is still uncertain. Herein, we compared the prognoses of these two types of surgical treatment for stage I lung adenocarcinoma. METHODS: Retrospective research was conducted on 258 patients with stage I lung adenocarcinomas who underwent VATS lobectomy and sublobar resection at the First Affiliated Hospital of Guangzhou Medical University between January 2009 and December 2011. VATS lobectomy was performed on 222 patients, and VATS sublobe resection was performed on 36 patients. Propensity score matching analyses were conducted on the two groups. RESULTS: A total of 70 patients were matched in the two groups. No significant difference was observed between the lobectomy and sublobar resection groups after matching (P=0.137). The disease-free survival (DFS) of the two groups were 49.3 and 42.7 months, and their overall survival (OS) were 50.3 and 49.0 months (P=0.122). Further, stratified analysis showed no significant differences in DFS and OS between the two groups with stage Ia lung adenocarcinoma. Nevertheless, the DFS and OS of the two groups significantly differed in matched patients with stage Ib lung adenocarcinomas. CONCLUSIONS: Sublobar resection could achieve a similar prognosis to VATS lobectomy for stage Ia lung adenocarcinoma. Lobectomy should still be the first choice for the treatment of stage Ib lung adenocarcinoma.
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ItemImpact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non-Small-Cell Lung Cancer: A Population Study of the US SEER Database and a Chinese Multi-Institutional Registry(AMER SOC CLINICAL ONCOLOGY, 2017-04-10)Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non-small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institutional registry and the US SEER database on stage I to IIIA resected NSCLC (2001 to 2008) were analyzed for the relationship between the ELN count and stage migration and overall survival (OS) by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. The selected cut point was validated with the SEER 2009 cohort. Results Although the distribution of ELN count differed between the Chinese registry (n = 5,706) and the SEER database (n = 38,806; median, 15 versus seven, respectively), both cohorts exhibited significantly proportional increases from N0 to N1 and N2 disease (SEER OR, 1.038; China OR, 1.012; both P < .001) and serial improvements in OS (N0 disease: SEER HR, 0.986; China HR, 0.981; both P < .001; N1 and N2 disease: SEER HR, 0.989; China HR, 0.984; both P < .001) as the ELN count increased after controlling for confounders. Cut point analysis showed a threshold ELN count of 16 in patients with declared node-negative disease, which were examined in the derivation cohorts (SEER 2001 to 2008 HR, 0.830; China HR, 0.738) and validated in the SEER 2009 cohort (HR, 0.837). Conclusion A greater number of ELNs is associated with more-accurate node staging and better long-term survival of resected NSCLC. We recommend 16 ELNs as the cut point for evaluating the quality of LN examination or prognostic stratification postoperatively for patients with declared node-negative disease.
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ItemSystematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour(BMJ PUBLISHING GROUP, 2018-09)OBJECTIVE: Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments. DESIGN: Literature review, pooling analysis and correlation analysis. DATA SOURCES: PubMed, from 1 January 2010 to 30 June 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments. RESULTS: Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29). CONCLUSIONS: No systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
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ItemErratum to updated statistics of lung and bronchus cancer in United States (2018) (vol 10, pg 1158, 2018)(AME Publishing, 2019-03)Updated statistics of lung and bronchus cancer in United States (2018)
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ItemThe impact of epidermal growth factor receptor mutations on the prognosis of resected non-small cell lung cancer: a meta-analysis of literatures(AME Publishing, 2019-04-20)BACKGROUND: Epidermal growth factor receptor (EGFR) mutation represents a good response to EGFR-tyrosine kinase inhibitor and an advantageous prognostic factor in advanced-stage non-small cell lung cancer (NSCLC). However, the predictive value of EGFR mutation for prognosis in NSCLC patients after complete surgery, which more reflective of natural process, remains controversial. We sought to examine the predictive value of EGFR mutation in NSCLC. Several studies with small sample sizes have been reported but small studies bring bias especially in a postoperative setting. Therefore, we sought to pool all current evidence to show the true effects. METHODS: Electronic databases were used to search the relevant articles. Disease-free survival (DFS), which will be less effected by subsequent treatments after recurrence, was the primary endpoint. The DFS between EGFR mutated and wild-type patients were compared focus on stage I patients who are rarely received adjuvant therapy. Besides, the DFS of patients with 19 exon deletion (19del) and 21 exon L858R mutation (L858R) were compared. A random effects model was used. RESULTS: A total of 19 relevant studies which involved 4,872 cases were enrolled and 2,086 patients were EGFR-mutated. The majority of studies used PCR-based methods to detect EGFR mutations. Through meta-analysis, we observed the DFS of EGFR-mutated patients were similar to wild type patients in overall population (HR 0.93, 95% CI: 0.74 to 1.17). Similar results were observed in stage I subgroup (HR 0.82, 95% CI: 0.50 to 1.33). DFS of 19 del patients were potentially inferior to L858R patients but the difference was not significant (HR 1.38, 95% CI: 0.76 to 2.52). CONCLUSIONS: There was no significant difference in postoperative DFS between EGFR-mutant patients and wild-type with resected NSCLC. In addition, there is still insufficient evidence to support different postoperative treatment strategies (especially for stage I) for both mutated and wild-type patients. However, 19 del may be a negative factor, which may require more strict management. Thus, we strongly encourage reporting specific prognostic impacts of different mutation types.
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ItemEndpoint surrogacy in oncology Phase 3 randomised controlled trials(SPRINGERNATURE, 2020-08-04)Endpoint surrogacy is an important concept in oncology trials. Using a surrogate endpoint like progression-free survival as the primary endpoint-instead of overall survival-would lead to a potential faster drug approval and therefore more cancer patients with an earlier opportunity to receive the newly approved drugs.
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ItemGeneralizability of COVID-19 Mortality Risk Score Model.(Elsevier, 2020-12)It is with deep appreciation that we read the research by Yu et al.1 investigating the risk factors for mortality among 1,663 patients hospitalized with the novel coronavirus disease 2019 (COVID-19) in a Wuhan (China) hospital that utilized clinical characteristics in the development of a statistical model that predicts death risk.1 Given that the ongoing pandemic has placed great pressure on healthcare systems worldwide, we consider prediction models to be of high utility in assessing which patients with COVID-19 have higher mortality risk to optimize healthcare resources.
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ItemHIV and tuberculosis co-infection in East Asia and the Pacific from 1990 to 2017: results from the Global Burden of Disease Study 2017(AME Publishing, 2019-09-30)BACKGROUND: Periodic surveillance is crucial to provide information for resource allocation to control HIV/AIDS, tuberculosis (TB), and their co-infection, especially in areas with high morbidity and mortality like East Asia and the Pacific. Therefore, we examined the morbidity and mortality of HIV/AIDS and TB co-infection in this region from 1990 to 2017. METHODS: Utilizing the Global Burden of Disease (GBD) Study 2017, we obtained incidence, prevalence, and mortality numbers and rates of HIV/AIDS and TB co-infection, including HIV and drug-susceptible TB (DS-TB), multidrug-resistant TB without extensive drug resistance (MDR-TB without XDR), and extensive drug-resistant TB (XDR-TB). The trends in incidence, prevalence, and mortality from 1990 to 2017 for each co-infection type were analyzed using join-point regression modelling. RESULTS: In 2017, there were 238,372, 4,294, and 392 new cases of HIV-infected DS-TB, HIV-infected MDR-TB without XDR, and HIV-infected XDR-TB, respectively. The number of prevalent cases and deaths were 383,809 and 12,197 of HIV-infected DS-TB, 7,811 and 1,168 of HIV-infected MDR-TB without XDR, and 713 and 282 of HIV-infected XDR-TB. From 1990 to 2017, the age-standardized incidence rate and prevalence rate of HIV-infected DS-TB, and the prevalence rate of HIV-infected XDR-TB continuously increased; the incidence rate of HIV-infected XDR-TB increased from 1990 to 2005 before stabilizing. However, the incidence and prevalence rates of HIV-infected MDR-TB without XDR-as well as the mortality rates of all co-infection types-have decreased in the last 5 years. CONCLUSIONS: Even though the mortality rates of all HIV and TB co-infection types have decreased recently, the overall trends in both incidence and prevalence rates of HIV-infected DS-TB and XDR-TB have been increasing since 1990. Efforts to control co-infection across drug resistance types should be continued and further strengthened.