An improved differential evolution algorithm for multi-modal multi-objective optimization.

Multi-modal multi-objective problems (MMOPs) have gained much attention during the last decade. These problems have two or more global or local Pareto optimal sets (PSs), some of which map to the same Pareto front (PF). This article presents a new affinity propagation clustering (APC) method based on the Multi-modal multi-objective differential evolution (MMODE) algorithm, called MMODE_AP, for the suit of CEC'2020 benchmark functions. First, two adaptive mutation strategies are adopted to balance exploration and exploitation and improve the diversity in the evolution process. Then, the affinity propagation clustering method is adopted to define the crowding degree in decision space (DS) and objective space (OS). Meanwhile, the non-dominated sorting scheme incorporates a particular crowding distance to truncate the population during the environmental selection process, which can obtain well-distributed solutions in both DS and OS. Moreover, the local PF membership of the solution is defined, and a predefined parameter is introduced to maintain of the local PSs and solutions around the global PS. Finally, the proposed algorithm is implemented on the suit of CEC'2020 benchmark functions for comparison with some MMODE algorithms. According to the experimental study results, the proposed MMODE_AP algorithm has about 20 better performance results on benchmark functions compared to its competitors in terms of reciprocal of Pareto sets proximity (rPSP), inverted generational distances (IGD) in the decision (IGDX) and objective (IGDF). The proposed algorithm can efficiently achieve the two goals, i.e., the convergence to the true local and global Pareto fronts along with better distributed Pareto solutions on the Pareto fronts.

Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients.

Background: Genome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported. Case presentation: In this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation. Conclusion: This case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.

Predicting outcomes of Lung Cancer using the modified glasgow prognostic score: A systematic review and meta-analysis.

Background & Objective: Previous studies have suggested that the modified Glasgow Prognostic Score (mGPS) could be a potential biomarker for lung cancer (LC). However, the association between mGPS and overall survival (OS) or progression-free survival (PFS) in lung cancer patients remains unclear. The purpose of our study was to investigate possible correlation between mGPS and OS or PFS in LC patients. Methods: An extensive search of PubMed, Cochrane Library, EMbase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Trip Database, Worldwide Science, and Google Scholar databases was done for relevant articles, published prior to May 30, 2021, that report correlation between mGPS and OS or PFS in LC patients. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used as the main parameters for evaluation. Results: A total of 28 studies involving 9,748 lung cancer patients were analysed. The pooled analysis revealed that elevated mGPS (≥ 0) was associated with poor OS (HR=1.54; 95% CI, 1.32-1.77) and PFS (HR=1.49; 95% CI, 1.17-1.82). Furthermore, a significant correlation between mGPS (1 or 2) and OS was observed. However, no significant correlation was found between mGPS (1 or 2) and PFS. Subgroup analysis based on ethnicity demonstrated that mGPS ≥ 0 was associated with worse OS compared to mGPS=0 in both Asian (HR=1.46; 95% CI, 1.04-1.89; p<0.05) and Caucasian (HR=1.64; 95% CI, 1.35-1.94; p<0.05) cohorts of LC patients. Conclusions: Our results demonstrate that positive mGPS is associated with poor survival results. Therefore, mGPS may be used as a biomarker for predicting prognosis in LC patients.

Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor.

Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in-depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: A multicenter pooled analysis.

Despite limited efficacy of immunotherapy for advanced non-small-cell lung cancer (NSCLC) with driver mutations, whether neoadjuvant immunotherapy could be clinically valuable in those patients warrants further investigation. We utilized 40 oncogene-mutant NSCLC treated with induction immunotherapy from a large consecutive multicenter cohort. Overall response rate was 62.5% while 2 patients had disease progression. Of 39 patients that received surgery, R0 resection rate was 97.4%. The major pathological response (MPR) rate was 37.5% and the pathological complete response (pCR) rate was 12.5%. Pre-treatment PD-L1 expression was not a predictive biomarker in these patients. Median disease-free survival for all oncogenic mutation and EGFR mutation was 28.5 months. Indirect comparison through integrating CTONG1103 cohort showed neoadjuvant immunotherapy plus chemotherapy yielded the most superior efficacy among erlotinib and chemotherapy for resectable EGFR-mutant NSCLC. No MPR patients were identified with neoadjuvant immunotherapy plus chemotherapy for uncommon EGFR insertion or point mutations. Our results indicated the potential clinical feasibility of neoadjuvant immunotherapy for resectable localized oncogene-mutant NSCLC especially for EGFR-mutant NSCLC.

An evolutionary algorithm based on approximation method and related techniques for solving bilevel programming problems.

In the engineering and economic management fields, optimisation models frequently involve different decision-making levels. These are known as multi-level optimisation problems. Because the decision-making process of such problems are hierarchical, they are also called a hierarchical optimisation problems. When the problem involves only two-level decision-making, the corresponding optimisation model is referred to as a bilevel programming problem(BLPP). To address the complex nonlinear bilevel programming problem, in this study, we design an evolutionary algorithm embedded with a surrogate model-that it is a approximation method and correlation coefficients. First, the isodata method is used to group the initial population, and the correlation coefficients of the individuals in each group are determined based on the rank of the leader and follower objective functions. Second, for the offspring individuals produced by the evolutionary operator, the surrogate model is used to approximate the solution of the follower's programming problem, during which the points in the population are screened by combining the correlation coefficients. Finally, a new crossover operator is designed by the spherical search method, which diversifies the generated offspring. The simulation experimental results demonstrate that the proposed algorithm can effectively obtain an optimal solution.

Treatment outcomes and prognosis of patients with primary and acquired BRAF-mutated non-small cell lung cancer: A multicenter retrospective study.

The incidence of primary and acquired BRAF mutations is low in non-small cell lung cancer (NSCLC), with limited demographic and treatment outcome data available for this patient population. We evaluated lung cancer samples with programmed cell death ligand 1 (PD-L1) information extracted from 12 051 cases (cohort A) of lung cancer from OncoPanscan™-based sequencing of tissue (Genetron Health) and conducted retrospective multicenter data analysis using the database of Zhejiang Cancer Hospital and four other centers (cohort B, including 73 primary BRAF mutation and 14 acquired BRAF mutation cases) to compare treatment outcomes of patient groups with primary and acquired BRAF mutations. In cohort A, after propensity score analysis, 165 samples of NSCLC with BRAF mutations were screened along with 165 paired non-BRAF mutation samples. We observed no significant differences in the proportion of samples with ≥1% PD-L1 between BRAF and non-BRAF mutant groups. The median progression-free survival (mPFS) period in 13 patients with primary BRAF mutations receiving BRAF tyrosine kinase inhibitors (BRAF-TKIs) was 7.0 months. The group with primary BRAF mutations receiving immune checkpoint inhibitor (ICI) combination chemotherapy had better PFS than those administered ICI monotherapy (14.77 months vs. 5.0 months, p = 0.025) and similar results were obtained for OS (unreached vs. 20.3 months, p = 0.013). For acquired BRAF mutations, mPFS of BRAF-TKI, ICI-based, and chemotherapy-based regimens were 3.8, 1.5, and 1.9 months, respectively. Therefore, for patients with the primary BRAF V600E mutation, targeted therapy or immunochemotherapy could serve as effective treatment choices, while for those with acquired BRAF V600E, targeted drug therapy may remain the preferred solution in China.

Clinicopathological features and resistance mechanisms in HIP1-ALK-rearranged lung cancer: A multicenter study.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) respond well to ALK tyrosine kinase inhibitors (TKIs), and echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged NSCLC accounts for the majority of those patients. However, few studies have evaluated ALK-TKIs treatment for patients with huntingtin-interacting protein 1 (HIP1)-ALK fusions. This retrospective study evaluated the clinicopathological characteristics, genomic features, response to ALK-TKIs, and resistance mechanisms in 11 cases with HIP1-ALK fusions from five Chinese centers. Patients who received crizotinib at the Chinese centers had an objective response rate of 90% [9/10 cases, 95% confident index (CI): 54.1%-99.5%], median progression-free survival of 17.9 months (95% CI: 5.8-NA months), and median overall survival of 58.8 months (95% CI: 24.7-NA months). One patient who received first-line lorlatinib treatment achieved partial response for > 26.5 months. Despite the small sample size, HIP1-ALK (H21:A20) variant was the most common variant (four of 11 cases, 36.4%) and associated with better outcomes. Among the 11 cases, there were eight patients having available specimens for genetic testing before ALK-TKIs treatment and four patients undergoing biopsy after ALK-TKIs failure. The most common coexisting gene was TP53 among 11 patients and two of four patients after crizotinib failure harbored acquired ALK mutations (e.g., L1152V/Q1146K and L1196M). Brigatinib treatment appeared to be effective for a patient who failed crizotinib treatment because of the L1152V/Q1146K mutations, which might be related to increased binding affinity to these mutants. Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation. Larger studies are needed to evaluate the significance of HIP1-ALK-rearranged NSCLC.

Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited. PATIENTS AND METHODS: We retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed. RESULTS: We included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16-36%), the median PFS was 3.3 months (95% CI, 2.2-4.4), and the median OS was 13.9 months (95% CI, 11.4-16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2-5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3-14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14-61%), the median PFS was 3.3 months (95% CI, 2.6-4.0), and the median OS was 13.4 months (95% CI, 0-27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations. CONCLUSIONS: Our results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.

Genomic alterations and clinical outcomes in patients with lung adenocarcinoma with transformation to small cell lung cancer after treatment with EGFR tyrosine kinase inhibitors: A multicenter retrospective study.

BACKGROUND: Transformation to small cell lung cancer (SCLC) is a resistance mechanism to tyrosine kinase inhibitor (TKI) treatment that develops in lung adenocarcinoma. The genomic and treatment outcomes in these populations have not been comprehensively reported in China. METHODS: We performed a retrospective study analyzing patients with advanced non-SCLC (NSCLC) from eight sites who were diagnosed with SCLC transformation after receiving epidermal growth factor receptor (EGFR)-TKI treatment including first/second- or third-generation EGFR-TKIs. We assessed the genomic features and clinical prognosis in these patients with EGFR-mutated lung cancer. RESULTS: Thirty-two eligible patients with EGFR mutations were identified, 25 of whom had sufficient tumor tissues for detection of genes by next-generation sequencing. The median progression free survival (mPFS) for first/second-generation TKIs was 14.0 months. The most common mutations identified in samples with transformation to SCLC were in TP53 (17/25, 68.0 %), RB1 (9/25, 36.0 %), and PIK3CA (3/25, 12.0 %), and the incidence rates of RB1 and TP53 mutations were similar between patients receiving first/second-generation and third-generation TKI treatment. The estimated median time to SCLC transformation was 17.0 months. After SCLC transformation, platinum-etoposide was the most common treatment regimen, and the mPFS after platinum-etoposide treatment was 3.5 months. Anlotinib showed good efficacy in these patients (overall response rate, 66.7 %; mPFS, 6.2 months). The median overall survival after the initial diagnosis of metastatic lung cancer was 34.5 months, and patients with small cell transformation after third-generation TKI treatment had better prognosis than patients with transformation after first/second-generation treatment (49.4 months vs. 20.0 months, P = 0.013). CONCLUSION: We observed that TP53 and RB1 mutations were common in Chinese patients with SCLC transformation, regardless of whether first/second-generation or third-generation EGFR-TKI treatments were used. Earlier occurrence of small cell transformation after EGFR-TKI treatment was associated with poorer prognosis of patients. After the standard chemotherapy regimens for the management of primary SCLC, anlotinib may be a therapeutic option.

Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

Hepatoid adenocarcinoma of the lung (HAL) is a rare malignant tumor that is defined as a primary alpha-fetoprotein (AFP)-producing lung carcinoma. We aimed to identify prognostic factors associated with the survival of patients with HAL using data from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients diagnosed with HAL, adenocarcinoma (ADC), and squamous cell carcinoma (SCC) of the lung between 1975 and 2016 from the SEER database. The clinical features of patients with ADC and SCC of the lung were also analyzed. The clinical features of HALs were compared to ADCs and SCCs. A chi-square test was used to calculate the correlations between categorical variables, and a t test or Mann-Whitney U test was used for continuous variables. The Kaplan-Meier method and Cox regression analysis were used to identify the prognostic factors for the overall survival (OS) of HALs. Two-tailed p values < 0.05 were considered statistically significant. Sixty-five patients with HAL, 2,84,379 patients with ADC, and 1,86,494 with SCC were identified from the SEER database. Fewer males, advanced stages, and more chemotherapy-treated HALs were found. Compared to patients with SCC, patients with HAL were less likely to be male, more likely to be in an advanced stage, and more likely to receive chemotherapy (p < 0.05). The American Joint Committee on Cancer staging was the only prognostic factor for OS in patients with HAL, and stage IV was significantly different from other stages (hazard ratio = 0.045, 95% confidence interval: 0.005-0.398, p = 0.005). Males with HAL were more likely to receive radiotherapy compared to females with HAL (61.8 vs 31.5%, p = 0.034). Younger patients with HAL were more likely to receive chemotherapy (59.4 + 10.2 years vs 69 + 11.3 years, p = 0.001). The primary tumor size of HAL was associated with the location of the primary lesion (p = 0.012). No conventional antitumor therapies, including surgery, chemotherapy, and radiotherapy, were shown to have a significant survival benefit in patients with HAL (p > 0.05). This study showed that stage IV was the only prognostic factor for OS in HALs compared to other clinicopathologic factors. Conventional antitumor therapies failed to show survival benefit; thus, a more effective method by which to treat HAL is needed. Interestingly, the clinical features and the location of the primary lesion were shown to be associated with primary tumor size and treatment in patients with HAL, which have not been reported before.

A Novel Oncogenic Driver in a Lung Adenocarcinoma Patient Harboring an EGFR-KDD and Response to Afatinib.

Introduction: Oncogenic mutations in the epidermal growth factor receptor (EGFR) occur frequently in patients with lung cancer. These mutations may serve as critical predictive biomarkers in patients with non-small cell lung cancer (NSCLC). Among them, EGFR exon 18-25 kinase domain duplication (EGFR-KDD) mutations have been identified as a novel EGFR gene subtype in NSCLC. Case Presentation: We reported a rare case of a 59-year-old male diagnosed with adenocarcinoma. A biopsy revealed an EGFR-KDD identified by the next generation sequencing (NGS). Effective treatment outcome has been observed after administration with afatinib. Conclusion: This case highlights that comprehensive NGS technique is valuable in detecting novel genetic mutations in tumors.

PD-L1 expression level in different thymoma stages and thymic carcinoma: a meta-analysis.

BACKGROUND: The immune checkpoint ligand, programmed cell death 1 ligand 1 (PD-L1), is expressed in various tumors and associated with response to drugs that target programmed cell death protein 1. Previous studies have estimated the level of PD-L1 expression among different stages of thymoma and thymic carcinoma to evaluate its potential use as a diagnostic factor; however, its varying expression level has been problematic. We conducted this meta-analysis of published literature to evaluate PD-L1 expression in thymomas and thymic carcinomas. METHODS: We analyzed 12 studies that included 320 patients with type A/AB/B1 thymoma, 225 patients with type B2/B3 thymoma, and 180 patients with thymic carcinoma. RESULTS: No difference in PD-L1 expression level was found between the B2/B3 vs C groups (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.26, 1.76; p = 0.42). However, the heterogeneity was very high (I2 = 78%), and a significant difference was found between groups A/AB/B1 and B2/B3 (OR, 0.22; 95% CI, 0.12, 0.41; p < 0.001), with a relatively low heterogeneity (I2 = 55%). CONCLUSION: PD-L1 positivity might be a useful factor to differentiate type A/AB/B1 thymoma from type B2/B3 and thymic carcinoma. This result might be valuable for potential anti PD-L1 treatment in thymoma and thymic carcinoma.

Association Between RET Fusions and Efficacy of Pemetrexed-based Chemotherapy for Patients With Advanced NSCLC in China: A Multicenter Retrospective Study.

BACKGROUND: Rearranged during transfection (RET) proto-oncogene gene fusions are rare in non-small-cell lung cancer (NSCLC). We compared the efficacy of pemetrexed-based chemotherapy with other chemotherapy regimens in patients with NSCLC with different RET fusion subtypes. PATIENTS AND METHODS: A retrospective, multicenter study of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas was conducted. RET rearrangements were detected using next generation sequencing. We analyzed the clinical characteristics of patients with RET-rearranged NSCLC and the efficacy of chemotherapy regimens. We also evaluated the efficacy between groups of patients with and without KIF5B-RET-rearranged lung cancer. RESULTS: We evaluated 62 patients with NSCLC and RET rearrangements, including 41 with KIF5B-RET, 15 with CCDC6-RET, and 6 with other rare fusion subtypes. Of these 62 patients, 50 had stage IIIB/IV. We also evaluated 40 patients with first-line chemotherapy information available. The median progression-free survival was significantly different between those receiving pemetrexed-based chemotherapy and those receiving other chemotherapy regimens (9.2 vs. 5.2 months; P = .007). The median progression-free survival for patients with KIF5B-RET fusion and non-KIF5B-RET fusion was not significantly different statistically (7.8 vs. 11.2 months; P = .847). For second-line chemotherapy, a statistically significant difference was found between the chemotherapy regimens (4.9 vs. 2.8 months; P = .049). Survival follow-up data were available for 38 patients with advanced NSCLC. The median overall survival was 26.4 months. The overall survival of the patients with RET-rearranged NSCLC who had received pemetrexed-based chemotherapy versus no pemetrexed-based chemotherapy was 35.2 versus 22.6 months (P = .052). No difference in survival was observed between the patients with KIF5B-RET and non-KIF5B-RET rearrangements. CONCLUSIONS: Pemetrexed-based treatment should be considered first when selecting the chemotherapy regimen for patients with NSCLC and RET rearrangements.

A novel SOS1-ALK fusion variant in a patient with metastatic lung adenocarcinoma and a remarkable response to crizotinib.

OBJECTIVES: Transforming anaplastic lymphoma kinase (ALK) gene rearrangements are well known as a unique subset of non-small cell lung cancer (NSCLC) with mutations other than EGFR. Currently, crizotinib is the standard first-line treatment for ALK-positive NSCLC. MATERIALS AND METHODS: With advances in detection methods, more and more uncommon ALK fusion partners have been identified. Herein we present a novel SOS1-ALK fusion and the efficacy of crizotinib in an advanced NSCLC patient harboring this type of fusion. RESULTS: A 52-year-old Chinese man had left upper lobe primary NSCLC and synchronous multiple lung metastases (cT2N3M1, stage IV). The ultrasound-guided fine-needle aspiration cytology of palpable left supraclavicular lymph nodes and the results of immunohistochemistry staining supported the diagnosis of metastatic lung adenocarcinoma. Using a next-generation sequencing assay (NGS), we showed that the tumor had a SOS1-ALK fusion which the breakpoints was (S2, A20) rather than other actionable mutations. Therefore, the patient received first-line crizotinib and experienced a remarkable tumor response and has tolerated crizotinib well until this writing. CONCLUSION: Considering this rare SOS1-ALK fusion and remarkable response to an ALK-inhibitor, it is important to be aware of the presence of SOS1-ALK fusions in patients with advanced NSCLC to better guide targeted therapy. Precision methods, such as NGS for oncogenic alteration detection, should also be encouraged in clinical practice.

Eye metastasis in lung adenocarcinoma mimicking anterior scleritis: A case report.

BACKGROUND: The eye is a rare site for lung cancer metastasis. Indeed, ocular metastasis is one of the greatest challenges to quality of life in a cancer patient. Here we present a patient with lung adenocarcinoma and ocular metastasis. CASE SUMMARY: The patient was a 70-year-old man diagnosed with lung adenocarcinoma who developed eye metastasis mimicking anterior scleritis. Brain magnetic resonance imaging showed an abnormal signal in the right eye. Based on next generation sequencing of the surgical specimen, the patient was shown to have a KRAS point mutation (p.G12D). CONCLUSION: Multidiscipline expertise collaboration is needed to make the early diagnosis and determine the prompt treatment in patients. We hope to increase the awareness of the possibility of lung cancer metastasizing to the eye.

A prostate cancer patient with isolated lung metastases: a case report.

Pulmonary involvement has been reported in >40% of autopsy series in patients with metastatic prostate cancer; however, isolated lung metastases have been documented in <1% of cases and 43.5% (10/23) cases underwent surgical resection and most of them have good outcome. We present a 74-year-old male Gleason high-grade prostate cancer patient with initially negative PSA and isolated pulmonary lesion which was confirmed as lung metastasis by resection. This patient received first-line endocrine therapy with leuprolide and bicalutamide endocrine and had a long-term disease-free follow-up of 3 years. The present patient had isolated lung metastasis with negative PSA, which was very rare in literature. Unexpected long-term disease-free survival was achieved after first-line endocrine therapy in this case with Gleason score of 8 metastatic prostate cancer. Whether or not the path of metastasis in this case was via lymph node jumping (negative lymph node dissection) or hematogenous (usually multiple, in bilateral lungs and lower lung fields) requires further investigation.

A Real-World Study in Advanced Non-Small Cell Lung Cancer with KRAS Mutations.

BACKGROUND: KRAS gene mutations are well known as a key driver of advanced non-small cell lung cancer (NSCLC). The impact of KRAS-mutant subtypes on the survival benefit from salvage chemotherapy is controversial. Here, we present a real-world study in patients across China with advanced NSCLC with KRAS mutations using a website-based patient self-report system. METHODS: We identified a total of 75 patients diagnosed with KRAS-mutant (determined by molecular sequencing) advanced NSCLC between 2014/5/9 and 2019/5/30. KRAS mutation subtypes were divided into G12C and non-G12C groups for statistical analysis. The clinicopathological characteristics and treatment survival benefit in all patients with a KRAS mutation were evaluated. Programmed death-ligand 1 (PD-L1) expression data were collected from 30 patients in the same cohort. RESULTS: In this study, 23 patients with stage IIIB NSCLC and 52 patients with stage IV NSCLC were enrolled with 58 men and 17 women; the median age was 60 years (39-84). All patients received regular chemotherapy/radiotherapy/targeted therapy/immune therapy as per the disease condition. Four main KRAS mutation subtypes were detected: G12C (33%), G12V (19%), G12A (12%), and G12D (12%). Three predominant KRAS comutations were detected: TP53-KRAS (31%), EGFR-KRAS (11%), and STK11-KRAS (8%). Compared with the KRAS non-G12C mutation subtype, patients with the KRAS G12C mutation had potentially longer progression-free survival (PFS) after first-line chemotherapy (4.7 vs. 2.5 months, p < 0.05). Pemetrexed-based chemotherapy appeared to be superior to taxanes- and gemcitabine-based chemotherapies in all patients (PFS: 5.0 vs. 1.5 and 2.3 months, respectively, p > 0.05). Cox regression analysis showed that the KRAS G12C mutation and pemetrexed-based first-line chemotherapy were positive influencers for PFS after first-line (hazard ratios = 0.31 and 0.55, respectively, P < 0.05), but not second-line chemotherapies. CONCLUSION: The KRAS G12C mutation could be a predictive biomarker for better survival benefit from first-line chemotherapy in patients with advanced NSCLC and KRAS mutations. The first-line chemotherapy regimen could possibly influence the outcome in patients with KRAS mutations. Larger and prospective clinical trials are warranted to confirm our conclusions.

Ginsenoside compound K inhibits growth of lung cancer cells via HIF-1α-mediated glucose metabolism.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Compound K, an active metabolite of ginsenosides, is reported to exhibit anti-cancer property in various types of human malignancies. The present study investigated the role of compound K on glucose metabolism in NSCLC cells and its underlying mechanism. Our study found that compound K dose-dependently inhibited the cell viability of NSCLC cells. Moreover, administration with compound K decreased glucose uptake and lactate secretion under normoxic and hypoxic conditions. Consistently, the expression of key enzymes (HK II, PDK1 and LDHA) involved in glucose metabolism were inhibited in compound K-treated tumor cells. In addition, compound K inhibited the expression of HIF-1α and its downstream gene GLUT1. On the contrary, overexpression of HIF-1α elevated metabolic reactions and partly attenuated the inhibitory role of compound K on NSCLC cell growth. These results demonstrate that compound K suppresses NSCLC cell growth via HIF-1α mediated metabolic alteration, contributing to novel anticancer therapy by targeting glucose metabolism.