Chemoradiotherapy for untreated Masaoka-Koga stage IVB thymic carcinoma: a single-center retrospective study.

BACKGROUND: Thymic carcinoma (TC) is a rare type of a malignant tumor. The optimal treatment for Masaoka-Koga stage IVB TC patients is controversial due to the rarity of the disease. Chemotherapy is still the preferred option, but the outcomes are unsatisfactory. Whether radiotherapy combined with chemotherapy could improve prognosis remains unclear. METHODS: Untreated stage IVB TC patients who have received first-line chemotherapy were included in the present study. The patients who have undergone surgery were excluded. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). RESULTS: Sixty-seven patients were included in the study. A total of 31 patients received chemoradiotherapy (ChemoRT cohort), and the remaining 36 patients only received chemotherapy (Chemo cohort). The median follow-up period was 40.3 months. The ORR for the ChemoRT and Chemo cohorts was 61.3 and 27.8%, respectively (P = 0.006). Furthermore, PFS (P = 0.003) and OS (P = 0.046) were significantly superior in the ChemoRT cohort. Radiotherapy maintained a significant favorable effect on PFS in multivariate analysis (P = 0.014), but the effect on OS was insignificant (P = 0.249). There was no advantage in PFS (P = 0.302) in the ChemoRT cohort in patients who received < 4 cycles of chemotherapy. In contrast, radiotherapy significantly improved PFS (P = 0.005) in patients who received ≥ 4 cycles of chemotherapy. CONCLUSIONS: Chemoradiotherapy used as the first-line treatment improved ORR and PFS in Masaoka-Koga stage IVB TC patients. Patients receiving more cycles of chemotherapy may have a better chance to benefit from chemoradiotherapy.

Left ventricular entropy is a novel predictor of major adverse cardiac events (MACE) in patients with coronary atherosclerosis: a multi-center study.

OBJECTIVES: To investigate the incremental prognostic value of left ventricular (LV) entropy in a large multi-center population with coronary atherosclerotic heart disease (CAD). BACKGROUND: Current risk stratification of patients with CAD is imprecise and not accurate enough. METHODS: A total of 314 CAD patients who underwent cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) at two medical centers in China between October 2015 and July 2022 were included in this study. Additionally, the 193 patients under 3.0-T field also underwent CMR T1 mapping. LV entropy and extracellular volume (ECV) were calculated from the LGE image of LV myocardium, and major adverse cardiac events (MACEs) were analyzed. RESULTS: Among 314 patients, 110 experienced MACE during a median follow-up of 13 months. The risk of MACE was significantly increased in the high entropy group (log-rank p < 0.001). Entropy maintained an independent association with MACE in a multivariable model including left ventricular ejection fraction (LVEF) and LGE (HR = 1.78; p = 0.001). In addition, the primary endpoint events prognostic value was significantly improved by adding LV entropy to the baseline multivariable model (C-statistic improvement: 0.785-0.818, Delong test: p = 0.001). Similarly, among 193 3.0-T field patients, adding LV entropy to the multivariable baseline model significantly improved the prognostic value of the model for MACE (C-statistic improvement: 0.820-0.898, Delong test: p = 0.004). CONCLUSION: CMR-assessed LV entropy is a powerful independent predictor of MACE in patients with CAD, incremental to common clinical and CMR risk factors, including LVEF, LGE, Native T1, and ECV. CLINICAL RELEVANCE STATEMENT: Left ventricular entropy is a powerful independent predictor of major adverse cardiac events in patients with coronary atherosclerotic heart disease, incremental to common clinical and cardiac magnetic resonance risk factors. KEY POINTS: • Left ventricular entropy, a novel cardiac magnetic resonance parameter of myocardial heterogeneity, demonstrated a robust prognostic association with major adverse cardiac events beyond guideline-based, clinical risk markers. • Entropy can have an important role in the primary prevention of major adverse cardiac events in patients with coronary atherosclerotic heart disease. • Compared with late gadolinium enhancement, extracellular volume, and native T1, entropy could be used to more comprehensively characterize the heterogeneity of left ventricular myocardium.

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.

The prognostic impact of immune checkpoint inhibitors for the treatment of pulmonary sarcomatoid carcinoma: A multicenter retrospective study.

Pulmonary sarcomatoid carcinoma (PSC) is an aggressive and poorly differentiated type of non-small cell lung carcinoma. Because of the rarity of PSC, the efficacy and toxicity of immunotherapy remain unclear. Hence, the aim of this study was to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) for the treatment of advanced PSC. The study cohort was limited to 33 patients with pathologically confirmed PSC treated with ICIs in four hospitals in China from March 2018 to March 2022. Expression of programmed death ligand 1 (PD-L1) was detected by immunohistochemical analysis. Categorical variables were compared with the Fisher exact test and survival analysis was conducted with the Kaplan-Meier method. Of the 33 PSC patients, 8 (24.2%) received monotherapy with ICIs and 25 (75.8%) received combination therapy with ICIs. The objective response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8%, respectively. The median durations of progression-free survival (PFS) and overall survival (OS) were 6.07 and 21.33 months, respectively. PD-L1 status in 16 available samples was assessed, which included 30.3% PD-L1-positive patients. The ORRs for PD-L1-positive vs. -negative patients were 50.0% and 90.0%, the DCR was 33.3% and 83.3%, and the median PFS was 17.50 and 6.07 months, respectively (p=0.812). The median OS was not reached in PD-L1-positive and -negative patients (p=0.655). The incidence of immune-related adverse (irAEs) was 48.5% and mainly included grade 1 or 2 (39.4%), while the incidence of grade 3 or 4 was 9.1%. Pneumonia (9.1%) and skin rash (9.1%) were the most frequent irAEs. Immunotherapy with ICIs was a promising regimen to improve the prognosis of patients with advanced PSC.

Potential mechanism of primary resistance to icotinib in patients with advanced non-small cell lung cancer harboring uncommon mutant epidermal growth factor receptor: A multi-center study.

The incidence of epidermal growth factor receptor uncommon mutation (EGFRum) is relatively low and patients harboring EGFRum are resistant to the first-generation tyrosine kinase inhibitors (TKI). However, the mechanism of primary resistance remains unclear. Medical records of 98 patients who had never been treated by TKI and who accepted icotinib treatment were collected and followed. The circulating tumor DNA (ctDNA) were detected and analyzed using the next-generation sequencing (NGS) platform after progression on icotinib. The potential primary resistance mechanism of icotinib was explored. A total of 21 (21.4%) and 48 (49%) patients developed primary and acquired resistance to icotinib, respectively. The median progression-free survival (PFS) of primary resistance patients was 1.8 months (0.5-2.3, 95% CI = 1.50-2.10). Before treatment, 52.4% (11/21) of patients carried S768I, 23.8% (5/21) L861Q, 14.3% (3/21) G719X and 14.3% (3/21) exon 20-ins mutations. Approximately 23.8% (5/21) of patients harbored the combined pattern mutations and 76.2% (16/21) of patients harbored the single pattern mutations. The combined pattern with EGFR classical mutation (EGFRcm) had worse PFS than the combined with EGFRum and single pattern (P < .05). There were 6 (28.57%) patients with acquired EGFR extracellular domain mutation, 5 (23.81%) with BCL2L11 loss (BIM deletion polymorphism), 3 (14.29%) with MET amplification, 1 (4.76%) with ERBB2 amplification, 1 (4.76%) with MYC amplification, 1 (4.76%) with PTEN mutation, 1 (4.76%) with PIK3CA mutation and 3 (14.29%) with unknown status. EGFR extracellular domain mutation, BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN and PIK3CA mutations), MET amplification, ERBB2 amplification or MYC amplification might contribute to molecular mechanisms of primary resistance to icotinib in patients with advanced non-small cell lung cancer harboring uncommon mutant epidermal growth factor receptor. Combined targeted therapy or chemotherapy should be considered in this population.

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.

Simultaneous VENTANA IHC and RT-PCR testing of ALK status in Chinese non-small cell lung cancer patients and response to crizotinib.

BACKGROUND: ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements. METHODS: A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent. RESULTS: Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion. CONCLUSIONS: VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib.

Association between BIM polymorphism and lung cancer outcomes: a meta-analysis.

Accumulating evidences have indicated that BIM expression largely decides the development of lung cancer and outcome of EGFR-mutant lung cancers after TKI treatments. BIM polymorphism is a 2,903-bp deletion in the second exon. To clarify the relationship between this BIM polymorphism and clinical outcomes of lung cancers, we conducted this meta-analysis and observed the survival and responses to TKIs. Sixteen cohort studies, covering 4393 WT and 916 BIM deletion patients were included. Overall, BIM deletion polymorphism was associated with significantly shorter progression-free survival (PFS) and slightly shorter overall survival (OS), compared to the WT group. Moreover, patients with BIM deletion polymorphism showed significantly inferior response to EGFR TKIs. In conclusion, our analysis confirmed that lung cancer patients harboring the BIM deletion have inferior survival and TKI responses. Examination of the novel biomarker BIM deletion in lung cancer patients, especially for the EGFR mutant cohort, could provide some prognostic utility.

A meta-analysis of association between serum iron levels and lung cancer risk.

Many studies conducted on the relationship between serum iron levels and lung cancer risk had produced inconsistent results. We therefore conducted a meta-analysis to determine whether serum iron levels were lower in lung cancer patients compared to those in controls.A literature survey was conducted by searching the PubMed, WanFang, CNKI, and SinoMed databases for articles published as of Mar 1, 2018. Standard mean differences (SMD) with the corresponding 95% confidence intervals (CI) were executed by Stata 12.0 software. A total of 13 publications involving 1118 lung cancer patients and 832 controls were included in our study. The combined results showed that serum iron levels in lung cancer cases had no significantly lower when compared to those in controls [summary SMD = -0.125, 95%CI= -0.439, 0.189, Z = 0.78, p for Z test= 0.435], with high heterogeneity (I2= 89.9%, P< 0.001) found. In the stratified analysis by geographic locations, consistent results were found for serum iron levels between lung cancer patients and controls both in Asian populations [summary SMD = -0.113, 95%CI= -0.471, 0.245] and European populations [summary SMD = -0.215, 95%CI= -0.835, 0.404]. Publication bias was not found when evaluated by Begg's funnel plot and Egger's regression asymmetry test.In summary, the current study showed that serum iron levels had no significant association on lung cancer risk.

Combined detection of CEA and CA125 for the diagnosis for lung cancer: A meta-analysis.

This study aimed to systematically evaluate the value of combined detection of serum CEA and CA125 concentrations for the diagnosis of lung cancer. Related studies regarding the diagnosis of lung cancer were searched in PubMed, Embase, CNKI, and Wanfang using a computer. The number of patients who were true-positive, false-positive, false-negative, and true-negative were extracted from each study. Meta-analysis was performed using the Meta-Disc l.4, RevMan 5.3. Seven studies involving 2,216 cases were finally included. Regarding the diagnosis of lung cancer, the sensitivity, specificity, and diagnostic odds ratio of combined CEA and CA125 detection were higher than those of CEA detection alone. The area under the curve (AUC) of combined detection was 0.90, whereas the independently detected AUC was 0.73. Combined CEA and CA125 detection has higher diagnostic efficiency for lung cancer than CEA detection alone. The significance of combined serum CEA and CA125 detection in lung cancer is confirmed.

Response and acquired resistance to MET inhibitors in de novo MET fusion-positive advanced non-small cell lung cancer.

OBJECTIVES: De novo mesenchymal-to-epithelial transition (MET) gene fusions in non-small cell lung cancer (NSCLC) are a promising target for MET tyrosine kinase inhibitors (TKIs). We aimed to examine the response to targeted therapy with MET TKIs and resistance mechanisms in de novo MET fusion-positive NSCLC as these have not been comprehensively explored. MATERIALS AND METHODS: We examined the MET fusions in 4,429 patients with advanced-stage NSCLC using targeted next-generation sequencing and validated the results using RT-PCR. We analyzed cellular models harboring MET fusions and established a patient-derived organoid (PDO) model. RESULTS: We identified 13 (0.29 %, 13/4429) patients with de novo MET fusions and found EPHB4, THAP5, TNPO3, and DST as novel MET fusion partners. The most common concomitant gene with MET fusions was TP53 mutations. Among 12 patients receiving MET TKI treatment, two achieved stable disease, six achieved partial response, and four underwent progressive disease. An in vitro study showed that EPHB4-MET is a functional driver gene. MET inhibitors significantly inhibited the proliferation and phosphorylation of downstream STAT3, AKT, and ERK1/2 in EPHB4-MET overexpressing cells. Acquired MET D1228H/N or D1246N mutations were found in patients harboring MET fusions after acquiring resistance to MET TKIs. Tivantinib showed optimal suppression efficacy in a PDO model with an acquired MET D1228N mutation. CONCLUSION: MET fusions occur in a rare subset of patients with NSCLC and represent a promising therapeutic target. MET secondary mutations D1228H/N or D1246N present the potential resistance mechanisms of MET inhibitors in patients with de novo MET fusions.

Evaluation of the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Administering corticosteroid is an effective therapeutic strategy for treating most inflammatory conditions. However, there is a chance for corticosteroid treatment to adversely affect bones, resulting in corticosteroid-induced osteoporosis, which is a highly prevalent type of secondary osteoporosis. Elevated bone resorption and reduced formation of bone are pathogenesis indicators of corticosteroid-induced osteoporosis. Preventative therapy is recommended for patients initiating steroids. This study aims to evaluate the efficiency of calcium and vitamin D in treating adults diagnosed with osteoporosis caused by corticosteroid therapy. METHODS: Electronic databases will be searched systematically to source studies that have evaluated the efficiency of calcium and vitamin D as a treatment method for adult patients with osteoporosis from corticosteroid therapy. The databases include, PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science. The timeline of the search will be limited from inception to November 2020. This study will utilize the Cochrane risk of bias tool to assess the quality of the studies reviewed. Moreover, appropriate methods will be chosen to analyze the data. The RevMan 5.3 software is utilized to perform statistical analysis. RESULTS: This study will provide additional practical and targeted results of evaluating the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis. CONCLUSION: The results of this study will provide further evidence about calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis, clinicians and policymakers can make practical use of the results. ETHICS AND DISSEMINATION: Since this systematic review does not involve any human or animal participants, an ethics approval is not required. SYSTEMATIC REVIEW REGISTRATION: Aug 19, 2021. osf.io/zvb38. (https://osf.io/zvb38/).

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 real-world study in advanced non-small cell lung cancer with de novo brain metastasis.

Brain metastases are the major cause of life-expectancy shortened for patients with lung cancer. The prognostic value of EGFR mutation subtypes and survival benefit of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) patients with de novo brain metastasis is still not clear. Here, we present a real-world study nation-wide focusing on the prognostic value of genomic and therapeutic factors in overall survival (OS) of those patients. We enrolled a total of 233 patients diagnosed with advanced NSCLC and de novo BM from multi-medical centers across China. The enrolled patients were divided into 4 groups, including EGFR 19del, EGFR L858R, EGFR wild-type, and EGFR unknown groups. The median OS of patients with EGFR mutations and all patients were 29.0 and 25.0 months, respectively. There was significant difference in OS of patients among EGFR 19del (n=76), EGFR L858R (n=94), EGFR wild-type (n=46) and EGFR unknown (n=17) groups (30.5 vs 27.5 vs 16.0 vs 25.0, P=0.025). Patients treated by icotinib showed better OS than gefitinib and erlotinib (31.0 vs 25.5 vs 26.5, P=0.02). There was a difference in OS of patients received the whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or WBRT+SRS (20.0 vs 31.0 vs 30.0 months, P<0.001), respectively. In multivariate analysis, patients treated with icotinib had superior iPFS benefit than gefitinib and erlotinib (HR=0.86[95%CI (0.74-1.0)], P=0.04). Besides, the histology of non-adenocarcinomas, the number of BM (>3), and extracranial metastases status could have an independent negative impact on the OS of all patients (P<0.001). EGFR mutant NSCLC patients with de novo BM had a better OS than patients with EGFR wild type. Patients treated with icotinib had longer iPFS than gefitinib and erlotinib but not in OS. Non-adenocarcinomas, number of BM (>3) and extracranial metastases were independent negative prognostic factors in iPFS and OS of all patients. Prospective clinical trials are warranted to explore more effective multimodality in this population.

Treatment and prognosis of primary malignant melanoma of the esophagus.

BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is rare with high malignancy and poor prognosis. The aim of this study was to investigate the relationship between prognosis and clinicopathological characteristics of this disease. METHODS: A total of 9 patients with PMME were treated in Zhejiang Cancer Hospital between 2009 and 2019 retrospectively. According to 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction, none of the patients were in stage I. However, 5 patients were in stage II, 2 patients were in stage III, and 2 patients were in stage IV at diagnosis. Five patients received surgery, while one of them received palliative resection. Three patients received postoperative chemotherapy; two of them (2/5) were diagnosed with recurrence. One patient in stage II received targeted therapy. One patient in stage III received first line chemotherapy and efficacy evaluation was stable disease (SD). Another one in stage III received biotherapy. One patient in stage IV received Chinese Medicine treatment and another received chemotherapy and palliative surgery. RESULTS: The 1-year disease-free survival (DFS) and overall survival (OS) rates of stage II who received surgery were 50% (2/4) and 100% (4/4) respectively. The 2-year DFS and OS rates were 50% (2/4) and 75% (3/4), respectively. However, patients with stage III-IV have a very poor prognosis. The 1-year OS is 0%. CONCLUSIONS: Due to the small sample size, the statistic efficacy is low, but it can provide a certain theoretical basis for future research.

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.

Association between BRAF mutant classification and the efficacy of pemetrexed-based chemotherapy in Chinese advanced non-small cell lung cancer patients: a multicenter retrospective study.

BACKGROUND: BRAF mutation plays a rare but aggressive oncogenic role in non-small cell lung cancer (NSCLC) patients. The controversy of first-line chemotherapy in patients with different BRAF mutations exists. Here, we identified 41 stage IIIB/IV NSCLC patients with BRAF mutation from 3,669 NSCLC patients by next-generation sequencing (NGS) testing of ctDNA in plasma or tumor tissues. METHODS: Kaplan-Meier survival curves were used to compare the prognostic difference of progression-free survival (PFS) and overall survival (OS) in different classes of BRAF mutations. Multivariate Cox proportional-hazards regression was used to determine the hazard ratio (HR) of different prognostic factors in survival. RESULTS: A total of 40 stage IIIB/IV NSCLC patients with BRAF mutation were further divided into four groups according to the updated functional classification of BRAF mutations, 56.1% (23/41) of class 1, 12.2% (5/41) of class 2, 12.2% (5/41) of class 3 and 19.5% (8/41) of others. The median PFS of patients after first-line pemetrexed-based chemotherapy was longer than other regimens of chemotherapy (7.0 vs. 4.0 months, P<0.001). The patients with class 1 BRAF mutation treated with pemetrexed-based first-line chemotherapy had a better OS than other regimens of chemotherapy (30 vs. 22 months, P<0.001). A significant improvement of OS was observed in patients with class 1 BRAF mutation than other groups (25 vs. 12, 15 and 14 months, P<0.0001). Multivariate analysis showed that first-line pemetrexed-based chemotherapy was associated with better PFS and OS (HR =0.16 and 0.31, respectively; P<0.001 and 0.02, respectively), as well as improved OS in patients with class 1 BRAF mutation than other classes (HR =2.15, P<0.001). CONCLUSIONS: Pemetrexed-based regimen could be considered as first-line chemotherapy in advanced NSCLC patients with BRAF mutants when target therapy is unavailable, especially in patients harboring class 1 mutations compared with other classes.

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 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.

Molecular Characteristics and Clinical Outcomes of EGFR Exon 19 C-Helix Deletion in Non-Small Cell Lung Cancer and Response to EGFR TKIs.

Epidermal growth factor receptor (EGFR) exon 19 deletion (E19del) is the most common activating mutation in advanced non-small cell lung cancer (NSCLC) and associates with the sensitivity of EGFR tyrosine kinase inhibitors (TKIs) treatment. However, not all mutant patterns of E19del have been well studied for the limited coverage of regular EGFR mutation testing. Here, we performed a retrospective cohort study of the C-helix E19del in advanced NSCLC patients based on the screening data by the next-generation sequencing (NGS) platform. From May 2012 to December 2019, clinical information and specimen from 7544 consecutive advanced (IIIB/IV) NSCLC patients were collected and screened for EGFR gene mutations by NGS from multicenters in China. The molecular characteristics and responsiveness to first-line EGFR TKIs therapy in NSCLC patients with C-helix E19del were analyzed. The clinical characteristics were also compared between patients with classical E19del and C-helix E19del. Thirty-eight (2.6%) patients with C-helix E19del and 1400 (97.4%) patients with classical E19dels were identified from 1438 patients with E19del. No significant difference in clinical characteristics was observed between the C-helix E19del and classical E19del groups (P > .05), except for histology (P < .001). All 22 patients with C-helix E19del as p.S752_I759del, p.A750_E758del, p.A750_E758delinsP, p.T751_A755delinsNY, p.T751_I759delinsG, p.T751_I759delinsLD, p.T751_I759delinsN, p.T751_L760delinsNL, and p.T751_D761delinsLY reached the best response as partial response rate (72.7%), and the progression-free survival (PFS) was 12.0 months. The PFS after EGFR TKIs in patients with C-helix E19del tended to be longer than patients with classical E19del but has no statistical significance (12.0 months vs 8.5 months, P = .06). The C-helix E19del could be a positive biomarker for predicting response to EGFR TKIs in advanced NSCLC patients. NGS should be the appropriate platform to identify this rare population, especially when patients harbor no actionable driver mutation initially and are reluctant to accept chemotherapy as first-line therapy.