Junling Li

Bio: Junling Li is an academic researcher from Peking Union Medical College. The author has contributed to research in topics: Lung cancer & Medicine. The author has an hindex of 12, co-authored 119 publications receiving 774 citations.

Molecular Epidemiology of EGFR Mutations in Asian Patients with Advanced Non-Small-Cell Lung Cancer of Adenocarcinoma Histology - Mainland China Subset Analysis of the PIONEER study.

Abstract: Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naive lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naive) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0-10 pack-year, OR 0.27, 95%CI: 0.17-0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29-0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged.

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients.

Abstract: Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSP-mediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 x 10(7) to 3.0 x 10(12) viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 x 10(12) VP and transient grade IV thrombocytopenia at the dose of 3.0 x 10(12) VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4(+) and CD8(+) T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis.

Abstract: Deciphering the correlation between immune-related adverse events (irAEs) categorized by organ system class and clinical benefit of immunotherapy is critical for clinical practice. The aim of this study is to investigate the incidence rates of irAEs and their correlations with objective response rate (ORR) in patients with advanced solid tumours treated with nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI). PubMed, Embase and Cochrane library were searched for eligible studies from January 1st, 2000 to May 1st 2019. Published clinical trials on NIVO or NIVO+IPI with reported irAEs were included. Logit transformation of the irAE incidences was applied for the generation of pooled estimate and Pearson correlation coefficient was calculated to evaluate the correlation between irAE and ORR. 48 clinical trials involving 7936 patients treated with NIVO or NIVO+IPI were included. Compared to NIVO, NIVO+IPI led to more all-grade and grade 3 or higher irAEs categorized by system organ class (P < 0.05). The ORR of NIVO was positively correlated with the incidence rate of skin (r = 0.79, P < 0.001), gastrointestinal (r = 0.56, P = 0.006) and endocrine irAEs (r = 0.44, P = 0.05), but not hepatic, pulmonary and renal irAEs. The ORR of NIVO+IPI was positively correlated with the incidence rate of skin (r = 0.54, P = 0.04), and gastrointestinal irAEs (r = 0.60, P = 0.02), but not endocrine, hepatic, pulmonary and renal irAEs. This meta-analysis summarizes the incidence rates of irAEs in patients with advanced solid tumours treated with NIVO or NIVO+IPI, and uncovers their correlations with ORR across multiple neoplasms. These findings highlight the potential of irAE to reflect response to NIVO or NIVO+IPI.

Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non–Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial

Abstract: Importance The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non–small cell lung cancer (NSCLC). Objective To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy. Design, Setting, and Participants The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020. Interventions Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy. Main Outcomes and Measures The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence–free survival (LRFS), distant metastasis–free survival, and toxic effects. Results In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09;P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rankP = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02;P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97;P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00;P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30;P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray testP = .04). No radiotherapy-related grade 4 or 5 adverse event was observed. Conclusions and Relevance In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed. Trial Registration ClinicalTrials.gov Identifier:NCT00880971

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

Abstract: Malignant melanoma is one of the most common malignancies. Its incidence grows rapidly at an annual rate of 3−5%. Although the incidence of melanoma remains low in China, it has increased rapidly, with approximately 20,000 new cases reported each year. The mortality of melanoma also has been increasing rapidly; in contrast, although the incidence of melanoma is also increasing in western countries, its mortality basically remains unchanged and does not rise along with the escalation in prevalence. Thus, there is still a wide gap between China and Western countries in the diagnosis and treatment of melanoma. Melanoma has become one of the diseases that pose a major threat to health of Chinese people. However, compared with other common malignant tumors, there is still a far way to go to achieve the standardized diagnosis and treatment of melanoma. In May 2007, the Chinese Society of Clinical Oncology (CSCO) formally established the CSCO Melanoma Panel with an attempt to promote the development of clinical oncology, facilitate the multidisciplinary standardized treatment for melanoma, advocate the active learning and application of currently available scientific evidences at home and abroad, and explore the development of Chinese guidelines on the clinical practices on melanoma. After consultations with multidisciplinary experts, the first edition of the Chinese Consensus on the Diagnosis and Treatment of Melanoma was released in 2008; in 2009, 2011, and 2013, three revisions of this consensus document were published after many multidisciplinary seminars. The past 5 years have witnessed several breakthroughs in the clinical treatment of melanoma. Melanoma has become one of the malignant tumors whose treatment patterns have changed rapidly. To adapt to the fast advances in melanoma treatment and make the clinical management of melanoma in China more standardized and internationalized, the 2015 edition of the Chinese Guidelines on the Diagnosis and Treatment of Melanoma was finalized after repeated and wide consultations with multidisciplinary experts and updated and added with much new information, with an attempt to provide the up-todated and reliable instructions on clinical practices based recent scientific evidences.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Abstract: Purpose The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). Patients and Methods In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). Results A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Conclusion Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation☆

Abstract: a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS2 index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS2 score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. Conclusion The 2 existing classification schemes and especially a new stroke risk index, CHADS2, can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Oncolytic viruses: a new class of immunotherapy drugs

Abstract: Oncolytic viruses can kill tumour cells through a dual mechanism of action; the direct lysis of cells, and the induction of an immune response. The first oncolytic virus has been approved in China, and another has been recommended for approval in the United States. This Review discusses the biology of oncolytic viruses as well as key oncolytic viruses in clinical development, and investigates the challenges associated with developing oncolytic viruses as a new therapeutic modality for cancer.