Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Mass Measurement of Upper fp-Shell N=Z-2 and N=Z-1 Nuclei and the Importance of Three-Nucleon Force along the N=Z Line.

Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.

[Influencing factors of mild cognitive impairment among the Chinese elderly: a meta-analysis].

Objective: To conduct a meta-analysis on the influencing factors of mild cognitive impairment (MCI) in the Chinese elderly. Methods: The literature related to the influencing factors of MCI in Chinese elderly population was retrieved through CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases up to March 13, 2022. Stata17.0 software was used to calculate the combined risk ratio (RR) with the 95% confidence interval (CI), test the heterogeneity, and assess the publication bias. Results: A total of 2 450 articles were retrieved, and 49 articles met the inclusion criteria, including 5 cohort studies and 44 case-control studies. Meta-analysis results showed that male (RR=0.778, 95%CI: 0.696-0.870, I2=73.1), education>6years (RR=0.428, 95%CI: 0.374-0.490, I2=86.9) and regular exercise (RR=0.496, 95%CI: 0.421-0.585, I2=81.5) were protective factors for MCI, while age≥70 years (RR=2.431, 95%CI: 2.086-2.833, I2=79.3), family history of dementia (RR=3.228, 95%CI: 2.140-4.867, I2=0.0), smoking (RR=1.214, 95%CI: 1.098-1.342, I2=78.8), alcohol consumption (RR=1.165, 95%CI: 1.047-1.297, I2=68.2), solitary living (RR=2.816, 95%CI: 2.123-3.736, I2=42.0), insomnia (RR=1.402, 95%CI: 1.093-1.799, I2=41.3), overweight/obesity (RR=1.431, 95%CI: 1.207-1.696, I2=75.9), hypertension (RR=1.731, 95%CI: 1.589-1.886, I2=67.1), hyperlipidemia (RR=1.722, 95%CI: 1.541-1.924, I2=63.9), diabetes mellitus (RR=1.495, 95%CI: 1.341-1.666, I2=71.6), cardiovascular diseases (RR=1.671, 95%CI: 1.446-1.932, I2=74.6) and cerebrovascular diseases (RR=2.309, 95%CI: 2.040-2.613, I2=76.3) were risk factors of MCI. Conclusion: The present study indicates that male, junior high school education or above and regular exercise are protective factors of MCI, while age≥70 years, family history of dementia, smoking, alcohol consumption, living alone, insomnia, overweight/obesity, hypertension, hyperlipidemia, diabetes, cardiovascular diseases and cerebrovascular diseases are risk factors of MCI.

ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer.

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Evaluation of safety and clinical efficacy of bilateral percutaneous kyphoplasty in treatment of osteoporotic thoraco-lumbar burst fractures].

Objective: To evaluate the safety and clinical efficacy of bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral burst fractures. Methods: It was a prospective study, 28 patients with osteoporotic thoraco-lumbar burst fractures who were treated in Beijing Chao-Yang Hospital from January 2021 to July 2021 were included, including 10 males and 18 females, with a median age of 73.6 years (range: 56.0-87.0 years). The X-ray radiographs, bone mineral density (BMD), CT three-dimensional reconstruction scan and MRI were taken and measured before operation to observe the fracture location and the posterior wall of the vertebral body, and further to determine the diagnosis. The X-ray radiographs and CT three-dimensional reconstruction scans were taken on the first day after operation and the last follow-up to observe whether there were bone cement leakage or not. The changes of kyphosis angle (KA), the height of anterior wall (HAW) and the height of posterior wall (HPW) before the operation, on the 1st day post operation and at the last follow-up were recorded. The visual analogue scale (VAS) of back pain and Oswestry dysfunction index (ODI) before the operation, 1 day post operation and at the last follow-up were used to evaluate the clinical effect of the operation. Results: All the patients were followed up for (12.2±6.0) months. The HAW on the 1st day post operation [(22.5±2.0) mm] was significantly increased as compared with that before the operation [(21.2±2.4) mm] (P<0.05). The HAW at the last follow-up [(18.9±1.6) mm] decreased signficantly as compared with that on the 1st day post opertion [(22.5±2.0) mm] (P<0.05). The HPW was also significantly corrected after surgery (P<0.05). At the end of the follow-up, the HPW [(27.2±1.3) mm] was comparable with that on the 1st day after surgery [(27.5±1.6) mm] (P>0.05). The KA on the 1st day after the operation (14.2°±1.5°) decreased significantly when compared with that before the operation (18.8°±1.3°) (P<0.05), but it was increased to 17.6°±1.4° at the last follow-up and was higher than that on the 1st day after the operation (P<0.05). There were bone cement leakage in 5 cases and adjacent vertebral fracture in 1 case. The VAS and ODI scores were all significantly lower on the 1st day and at last follow-up than that before the operation (all P<0.05). Conclusions: Bilateral PKP is effective, safe and reliable in the treatment of osteoporotic vertebral burst fracture. Careful evaluation of preoperative imaging data, accurate puncture and timing of bone cement injection are the key factors to ensure the success of the operation.

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer.

BACKGROUND: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. PATIENTS AND METHODS: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25-75 mg p.o. twice a day; continuous or intermittent), savolitinib (600-800 mg p.o. once a day), or durvalumab (3-10 mg/kg intravenous every 2 weeks). RESULTS: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm-diarrhea (75%), rash (58%), nausea (47%); savolitinib arm-nausea (67%), rash (56%), vomiting (50%); durvalumab arm-rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. CONCLUSION: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. CLINICAL TRIALS NUMBER: NCT02143466.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.

[Accuracy of Xpert® MTB/RIF for the detection of tuberculosis and rifampicin-resistance tuberculosis in China: A systematic review and meta-analysis].

OBJECTIVE: To systematically review the diagnostic accuracy of Xpert® Mycobacterium tuberculosis/rifampicin (Xpert® MTB/RIF) for the detection of active tuberculosis (TB) and rifampicin-resistance TB in Chinese patients. METHODS: Four Chinese databases (SinoMed, CNKI, WanFang database, and VIP) and three English databases (PubMed, Embase, and The Cochrane Library) were searched from January 1, 2000 to September 15, 2017, to identify diagnostic tests about the accuracy of Xpert® MTB/RIF in Chinese patients. Two investigators screened the articles and extracted the information independently, and then the quality of each included study was evaluated by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. Bivariate random-effects meta-analysis was conducted to pool the sensitivity and specificity. In addition, subgroup analyses were performed based on patient type (TB patient and TB suspected patient), sample type (sputum, bronchoalveolar lavage fluid and others). All statistical analyses were conducted with Stata version 13.0. RESULTS: A total of 47 articles were included in this systematic review. Most of them (38 articles) were in Chinese and only 9 articles were in English. All the articles were published during 2014 to 2017, and the sample size ranged from 31 to 3 151. Forty articles including 42 comparisons about TB were finally included with the pooled sensitivity of 0.94 (95%CI: 0.92, 0.95) and the pooled specificity of 0.87 (95%CI: 0.84, 0.91). Subgroup analysis showed that different patient and specimen types had no significant differences on sensitivity, but the specificity of sputum group was higher than that of bronchoalveolar lavage fluid. As for the detection of rifampicin-resistant TB, 33 articles (38 comparisons) were analyzed, the pooled sensitivity and specificity were 0.92 (95%CI: 0.89, 0.94) and 0.98 (95%CI: 0.97, 0.99) respectively. There were no significant differences between the patient and specimen in the subgroup analyses. The Deeks funnel plot showed a possible publication bias for detecting active tuberculosis (P=0.08) and no publication bias for rifampicin-resistant TB (P=0.24). The likelihood ratio scatter gram showed that in clinical applications, Xpert® MTB/RIF had a good diagnostic ability for detecting active tuberculosis, and it had good clinical diagnostic value in detecting rifampicin-resistant TB. CONCLUSION: Xpert® MTB/RIF has good sensitivity and specificity in detecting TB and rifampicin-resistant TB in Chinese people. In particular, it has good clinical value in diagnosing rifampicin-resistance TB.

Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.

[Quality assessment of global guidelines on colorectal cancer screening].

OBJECTIVE: To systematically review and assess the quality of guidelines on colorectal cancer screening worldwide to provide guidance for the development of high-quality colorectal cancer screening guidelines in mainland China. METHODS: CNKI, WanFang Data, VIP, SinoMed, PubMed, Embase, and Web of Science were systematically searched to identify guidelines on colorectal cancer screening from inception to Jun. 20th, 2018, and so were some websites and major search engines about the development of the guidelines from the existing literature (search date: Aug. 3rd, 2018). Two experienced reviewers independently examined these abstracts and then extracted information, and the Appraisal of Guidelines for Research and Evaluation II (AGREE II) were used to evaluate the methodological quality of these guidelines by four well trained reviewers. RESULTS: In this study, 46 guidelines published from 1994 to 2018 were finally included in our analysis from 10 countries and 5 regions, among which 5 were from mainland China. The quality of these guidelines was relatively high in domain 1 (scope and purpose) and domain 4 (clarity of presentation), and medium in domain 2 (stakeholder involvement). While in the other three domains (domain 3: rigour of development; domain 5: applicability; domain 6: editorial independence), the results were quite different among these guidelines. The quality of evidence-based guidelines (defined by the criteria based on World Health Organization guideline development handbook) was generally higher than that of the common guidelines. Existing guidelines from mainland China were not evidence-based guidelines, which were of low quality. CONCLUSION: The colorectal cancer screening guidelines all over the world are generally large in number, low in quality, different in statements, and so are the guidelines in China. There are no evidence-based guidelines in mainland China, which cannot provide effective guidance for colorectal cancer screening, so we need to pay more attention to the establishment of guidelines with high quality and high credibility for colorectal cancer screening as well as for cancer screening based on the national condition, in order to provide reasonable guidance for practice in public health and improve the health conditions in our society.

[Surgical results and sagittal alignment analysis of different fusion levels for degenerative scoliosis].

Objective: To retrospectively investigate the effects of long segment fusion and short segment fusion on lumbar sagittal alignment and quality of life in patients with degenerative scoliosis. Methods: From January 2011 to December 2014, 75 patients with degenerative scoliosis were treated with pedicle screw fixation. Total of 56 females and 19 males were included in this study. Fifty-four patients underwent short-segment fusion (≤3 segments) and 21 patients underwent long-segment fusion (>3 segments). The average age of the patients was (63±8) years. The patients were followed-up for a mean time of (2.9±1.3) years. The postoperative follow-up included Cobb angle, pelvic tilt, sacral slope, lumbar lordosis, visual analogue scale of pain on lumbar and lower extremities and Oswestry disability index. Fusion levels, blood loss, surgery length and postoperative hospital stay were recorded. All above parameters were evaluated statistically with Student's t test. Results: The short segment fusion group averaged (1.8±0.7) segments, and the long segment fusion group averaged (5.2±1.6) segments. Coronal Cobb angle changed from (21.3±7.8) degrees preoperatively to (15.3±5.6) degrees at final follow-up in short-segment fusion group (t=2.315, P=0.024) and from (44.5±11.2) degrees preoperatively to (11.4±5.8) degrees at the final follow-up in long-segment fusion group (t=8.214, P<0.01). In the short segment fixation group, the preoperative lumbar lordosis changed from (44.3±9.7) degrees to (48.9±8.2) degrees at final follow-up (t=2.123, P=0.038), and it changed from (25.3±9.5) degrees to (52.1±11.2) degrees in the long segment fusion group (t=5.982, P<0.01). The sacral slope in the short segment fusion group increased from (22.6±6.8) degrees preoperatively to (34.1±7.5) degrees at the final follow-up (t=2.872, P=0.006), and it increased from (12.1±9.5) degrees to (37.8±8.4) degrees in long segment fusion group (t=7.314, P<0.01). The pelvic tilt in the short segment fusion group changed from (23.5±5.5) degrees preoperatively to (19.5±4.7) degrees at final follow-up (t=2.217, P=0.031), and it decreased from (27.1±6.1) degrees to (22.9±4.3) degrees in the long segment fusion group(t=2.131, P=0.045). The visual analogue scale of pain on lumbar and lower extremities and Oswestry disability index were all improved after the operation in both groups. Conclusions: Both short segment fusion and long segment fusion can achieve satisfactory surgical results and improves the spinal-pelvic parameters. Short segment fusion can reduce surgery trauma and shorten hospital stay relative to long segment fixation.

[Clinical characteristics of human adenovirus type 7 pneumonia and genetic characteristics of human adenovirus type 7].

Objective: To better understand the clinical features of human adenovirus type 7 (hAdV7) pneumonia and to identify whether there is a variation in the genome of the strain (CHN/BeiJing/2018) isolated during the small-scale epidemic. Method: Forty-two patients were diagnosed with hAdV7 pneumonia between October 27th, 2017 and February 28th, 2018. They were all males with an average age of (21±2) years. Demographic and clinical data were reviewed and analyzed in detail. The nucleic acid of the epidemic strain was extracted from a bronchoalveolar lavage fluid sample. Whole genome sequencing (WGS) was then performed and sequences were compared with other hAdV7 strains distributed globally. Phylogenetic tree analysis was conducted based on whole genome sequences of the epidemic strain. Results: Thirty-eight cases with hAdV7 pneumonia presented with influenza-like symptoms (90.5%) at the onset and 36 cases developed fever (85.7%), followed by cough (97.6%), expectoration (90.5%) and chest pain (28.6%). Five cases presented with tonsillitis(11.9%) and 4 had transient hemoptysis (9.5%), while 3 patients reported dyspnea (7.1%). Moist rales were only heard in 3 patients (7.1%). Notably elevated creatine kinase (CK) concentrations were observed in 8 patients (19.1%), but all returned to normal after treatment. Four cases developed hypoxemia (9.5%), but none of them progressed to respiratory failure or acute respiratory distress syndrome (ARDS). Chest CT imaging showed bilateral patchy parenchymal opacities with a random distribution with or without consolidation. Ten patients were co-infected with influenza virus (23.8%), while 32 patients developed atypical pneumonia (76.2%). Genomic analysis revealed that the strain isolated during this epidemic was 99% similar to the known hAdV7 strains (19BOVLB/Volgograd/Rus/2014 and 0901HZ/ShX/CHN/2009). Phylogenetic tree analysis suggested that the strain was closely related to the hAdV7 strain isolated in Jingmen China in 2012. Conclusions: Cases with hAdV7 pneumonia were generally mild. Symptomatic treatment was sufficient for a favorable prognosis. A good genome stability of the hAdV7 strain was observed, indicating that hAdV7 could remain stable for a long period and cause continuing sporadic cases and clusters.

Overview of current systemic management of EGFR-mutant NSCLC.

Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.

CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials.

Background: Central nervous system (CNS) metastases are common in patients with non-small-cell lung cancer (NSCLC). Osimertinib has shown systemic efficacy in patients with CNS metastases, and early clinical evidence shows efficacy in the CNS. To evaluate osimertinib activity further, we present a pre-specified subgroup analysis of CNS response using pooled data from two phase II studies: AURA extension (NCT01802632) and AURA2 (NCT02094261). Patients and methods: Patients with T790M-positive advanced NSCLC, who had progressed following prior epidermal growth factor receptor-tyrosine kinase inhibitor treatment, received osimertinib 80 mg od (n = 411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment; prior CNS treatment was allowed. Patients with ≥1 measurable CNS lesion (per RECIST 1.1) on baseline brain scan by blinded independent central neuroradiology review (BICR) were included in the evaluable for CNS response set (cEFR). The primary outcome for this CNS analysis was CNS objective response rate (ORR) by BICR; secondary outcomes included CNS duration of response, disease control rate (DCR) and progression-free survival (PFS). Results: Of 128 patients with CNS metastases on baseline brain scans, 50 were included in the cEFR. Confirmed CNS ORR and DCR were 54% [27/50; 95% confidence interval (CI) 39-68] and 92% (46/50; 95% CI 81-98), respectively. CNS response was observed regardless of prior radiotherapy to the brain. Median CNS duration of response (22% maturity) was not reached (range, 1-15 months); at 9 months, 75% (95% CI 53-88) of patients were estimated to remain in response. Median follow-up for CNS PFS was 11 months; median CNS PFS was not reached (95% CI, 7, not calculable). The safety profile observed in the cEFR was consistent with the overall patient population. Conclusions: Osimertinib demonstrated clinically meaningful efficacy against CNS metastases, with a high DCR, encouraging ORR, and safety profile consistent with that reported previously. ClinicalTrials.gov number: NCT01802632; NCT02094261.

[Percutaneous endoscopic transforaminal lumbar interbody fusion for lumbar spinal stenosis].

Objective: To evaluate the clinical effects of percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) for L(4/5) single-segment lumbar spinal stenosis. Methods: From September 2016 to March 2018, 7 patients with L(4/5) single-segment lumbar spinal stenosis were treated by PE-TLIF in the Department of Orthopedics, Beijing Chaoyang Hospital. There were 1 male and 6 females, with a mean age of (57±13) years(43-77 years). The operation time, intraoperative blood lose, blood transfusion and complications were recorded, and the pain relief effects were evaluated by visual analog scale (VAS) score and Oswestry dability index (ODI). The indexes before and after the operation were compared with t test. Results: The average of follow-up time was 13.3 months (6-21 months), and the clinical symptoms relieved significantly. The VAS scores of low back pain and leg pain at 3-day postoperatively and at the last follow-up were (2.28±0.48), (1.57±0.53) and (0.42±0.53), (0.14±0.37), respectively; and the VAS scores were significantly improved when compared with those before the operation[(7.42±0.78), (6.14±1.77)](t=19.718, 6.672, 18.520, 7.937, all P<0.05). At the last follow-up, the ODI score was also significantly lower than that before surgery (54%±10% and 15%±9%, t=12.551, P<0.05). During the follow-up period, one patient had transient hyperreflexia after surgery, and the other 6 patients had no significant complications. None nerve root injury or lower extremity paralysis occurred. Conclusion: PE-TLIF can obtain satisfactory short-term results in the treatment of single-segment lumbar spinal stenosis, with a lower incidence of complications and rapid recovery after surgery.

A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer.

BACKGROUND: Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician's choice (TPC). PATIENTS AND METHODS: Patients with advanced NSCLC who had received ≥2 prior therapies, including platinum-based doublet and epidermal growth factor receptor tyrosine kinase inhibitor, were randomly assigned to receive eribulin or TPC (gemcitabine, pemetrexed, vinorelbine, docetaxel). The primary endpoint was OS. Secondary endpoints were progression-free survival and objective response rate. RESULTS: Five hundred and forty patients were randomized to either eribulin (n = 270) or TPC (n = 270). Median OS for eribulin and TPC was the same: 9.5 months [hazard ratio (HR): 1.16; 95% confidence interval: 0.95-1.41; P = 0.13]. Progression-free survival for eribulin and TPC was 3.0 and 2.8 months, respectively (HR: 1.09; 95% confidence interval: 0.90-1.32; P = 0.39). The objective response rate was 12% for eribulin and 15% for TPC. Clinical benefit rate (eribulin, 57%; TPC, 55%) and disease control rate (eribulin, 63%; TPC, 58%) were similar between treatment arms. The most common adverse event was neutropenia, which occurred in 57% of eribulin patients and 49% of TPC patients at all grades. Other non-hematologic side-effects were manageable and similar in both groups except for peripheral sensory neuropathy (all grades; eribulin, 16%; TPC, 9%). CONCLUSION: This phase 3 study did not demonstrate superiority of eribulin over TPC with regard to overall survival. However, eribulin does show activity in the third-line setting for NSCLC. TRIAL REGISTRATION ID: www.ClinicalTrials.gov; NCT01454934.

Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer).

BACKGROUND: Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60 mg/m2 in Japan, 75 mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80-120 mg/day, depending on body surface area; days 1-28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2. RESULTS: A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms, respectively [HR 0.945; 95% confidence interval (CI) 0.833-1.073; P = 0.3818]. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913-1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm. CONCLUSION: S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC. CLINICAL TRIAL NUMBER: Japan Pharmaceutical Information Center, JapicCTI-101155.