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1.
Radiat Oncol ; 16(1): 41, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622352

RESUMO

BACKGROUND: The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT. PATIENTS AND METHODS: We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses. RESULTS: Of the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07-13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP. CONCLUSIONS: Grade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.

2.
BMC Psychol ; 9(1): 26, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557956

RESUMO

BACKGROUND: Breast cancer is a common tumor in China and has become a public health problem in modern society. Stress plays an important role in the occurrence and progression of cancer. At present, the current situation of stress on breast cancer survivors (BCSs) in China has not been fully understood. This study aims to explore the stress and coping strategies of Chinese BCSs, which provide suggestions to help BCSs reduce stress. METHODS: Sixty-three BCSs from the Shanghai Cancer Rehabilitation Club in China were included in this study and were divided into eight focus groups. These were transcribed verbatim, coded using thematic analysis and analyzed using NVivo 11. RESULTS: Three themes were extracted from the data to address our research objectives: stress, coping strategies and expectations. The stress of BCSs included psychological stress, stress caused by physical pain, economic stress, stress caused by the change of life status, and stress caused by information overload; the coping strategies included self-strategies and help from others; from the perspective of the survivors, they put forward their expectations for both the society and themselves. CONCLUSIONS: This study shows that BCSs face a variety of stress. In the face of stress, BCSs need comprehensive support, including social and family support to cope with stressors. The findings from this study provide evidence for improving the quality of life among BCSs.


Assuntos
Adaptação Psicológica , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Neoplasias da Mama/etnologia , China/epidemiologia , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Motivação , Pesquisa Qualitativa
3.
Artigo em Inglês | MEDLINE | ID: mdl-33573245

RESUMO

This study aimed at investigating the sleep status and its associated factors in Shaanxi province, China. We conducted a cross-sectional study among 11,399 subjects in Shaanxi Province, China. Data were collected via spot field questionnaire surveys. The contents included demographic characteristics, sleep status, lifestyles, disease history and other associated factors. Logistic regression analysis was used to estimate the effect of associated factors on sleep quality. A total of 11,036 subjects were included in the final analysis. In total, 12.8% of the participants had bad or very bad sleep. In the last month, 8.4% of the participants had difficulty in initiating sleep, 7.6% of the participants had difficulty in maintaining sleep, 8.8% of the participants suffered from awakening earlier and 10.3% of the participants had the problem of feeling sleepy during the day ≥3 times per week. Poorer sleep quality was associated with being female, being unmarried or without cohabiting with a boyfriend/girlfriend, being divorced or widowed, heart diseases, musculoskeletal diseases, concerns about their own health, drinking alcohol, taking hypnotics, and a longer daily screen time. Better sleep quality was associated with medium education level, high family monthly income, good self-reported health status, and having breakfast regularly. In conclusion, more than one in ten people did not sleep well and suffered from different sleep problems in Shaanxi, China. Sleep quality was associated with sex, marital status, educational level, family monthly income, heart disease, musculoskeletal diseases, degree of concerning about their own health, self-reported health status, drinking alcohol, having breakfast, taking hypnotics and daily screen time.

4.
Neuroreport ; 32(3): 206-213, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33470766

RESUMO

BACKGROUND: The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics. METHODS: Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis. RESULTS: We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems. CONCLUSIONS: Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration.

5.
Cancer Lett ; 502: 166-179, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33450361

RESUMO

The brain is one of the most common metastatic sites in non-small cell lung cancer (NSCLC), which is associated with an extremely poor prognosis. Despite the availability of several therapeutic options, the treatment efficacy remains unsatisfactory for NSCLC brain metastases. Anti-programmed cell death-1 (PD-1) and its ligand (PD-L1) monoclonal antibodies have reshaped therapeutic strategies in advanced NSCLC. Preliminary evidence has shown that anti-PD-(L)1 monotherapy is also effective in NSCLC patients with brain metastases. However, the traditional view asserted that these therapeutic antibodies were incapable of crossing the blood-brain barrier (BBB) with large molecular size, thus most patients with brain metastases were excluded from most studies on anti-PD-(L)1 immunotherapy. Therefore, the efficacy and its mechanisms of action of anti-PD-(L)1 immunotherapy against brain metastases in NSCLC have not been clarified. In this review, we will survey the underlying mechanisms and current clinical advances of anti-PD-(L)1 immunotherapy in the treatment of brain metastases in NSCLC. The trafficking of activated cytotoxic T cells that are mainly derived from the primary tumor and deep cervical lymph nodes is critical for the intracranial response to anti-PD-(L)1 immunotherapy, which is driven by interferon-γ (IFN-γ). Additionally, promising combined strategies with the rationale in the treatment of brain metastases will be presented to provide future directions for clinical study design. Several significant challenges in the preclinical and clinical studies of brain metastases, as well as potential solutions, will also be discussed.

6.
Lung Cancer ; 151: 39-43, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33296806

RESUMO

INTRODUCTION: B-cell lymphoma 2-like 11 (BCL-2-like 11, BCL2L11, also known as BIM) deletion polymorphism (BIM-del) has been associated with resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and is a poor prognostic factor for EGFR-mutant non-small-cell lung cancer (NSCLC) patients. Nevertheless, the impact of BIM-del in advanced NSCLC patients treated with the third-generation EGFR-TKI osimertinib remains undetermined. This study aims to evaluate the relationship between BIM-del and therapeutic efficacy of osimertinib in pretreated NSCLC patients. METHODS: Patients subjected to EGFR T790 M detection and prior osimertinib treatment between December 2015 and December 2019 in our hospital were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del. RESULTS: In total, 152 Chinese Han NSCLC patients-including 143 T790M-positive and nine T790M-negative patients-were enrolled. BIM-del was detected in only 17.5 % of T790M-positive patients (25/143). The majority of patients were aged <65 years (81.8 %, 117/143), were female (58.7 %, 84/143), were non-smokers (82.5 %, 118/143), had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (88.8 %, 129/143), and exhibited metastases in the central nervous system (CNS) (54.5 %, 78/143). There were no associations between the BIM-del and clinical characteristics (including age, sex, histology, smoking status, stage, ECOG PS score, and CNS metastases). Patients with BIM-del had a poorer objective response rate than those without (28.0 % versus 52.5 %, p = 0.026). Besides, BIM-del was associated with a significantly shorter progression-free survival (PFS) and a moderately shorter overall survival (OS) (8.3 versus 10.5 months, p = 0.031 and 15.9 versus 25.2 months, p = 0.1, respectively). Multivariate analysis indicated that BIM-del was an independent prognostic factor for PFS but not for OS in EGFR T790 M NSCLC patients. CONCLUSIONS: BIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment.

7.
Cancer Cell Int ; 20(1): 580, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33292253

RESUMO

BACKGROUND: Despite an enormous research effort, patients diagnosed with advanced colorectal cancer (CRC) still have low prognosis after surgical resection and chemotherapy. The major obstacle for CRC treatment is chemoresistance to front line anti-cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin. However, the mechanism of chemoresistance to these drugs remains unclear. METHODS: Cell viability to 5-FU and oxaliplatin was measured by the CellTiter-Glo® 2.0 Cell Viability Assay. The endogenous REV7 protein in CRC cells was detected by western blotting. The translesion synthesis (TLS) events were measured by plasmid-based TLS efficiency assay. Cell apoptosis was evaluated by caspase3/7 activity assay. The in vivo tumor progression was analyzed by HT29 xenograft mice model. RESULTS: In this study, we found that expression of REV7, which is a key component of translesion synthesis (TLS) polymerase ζ (POL ζ), is significantly increased in both 5-FU and oxaliplatin resistant CRC cells. TLS efficiency analysis revealed that upregulated REV7 protein level results in enhanced TLS in response to 5-FU and oxaliplatin. Importantly, inhibition of REV7 by CRISPR/Cas9 knockout exhibited significant synergy with 5-FU and oxaliplatin in cell culture and murine xenograft model. CONCLUSION: These results suggest that combination of REV7 deficiency and 5-FU or oxaliplatin has strong inhibitory effects on CRC cells and identified REV7 as a promising target for chemoresistant CRC treatment.

8.
Bioeng Transl Med ; : e10202, 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33349797

RESUMO

The S1 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein contains an immunogenic receptor-binding domain (RBD), which is a promising candidate for the development of a potential vaccine. This study demonstrated that intradermal delivery of an S-RBD vaccine using a dissolvable microneedle skin patch can induce both significant B-cell and significant T-cell responses against S-RBD. Importantly, the outcomes were comparable to that of conventional bolus injection.

9.
Front Immunol ; 11: 580335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224142

RESUMO

Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.

10.
Cancer Med ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33230935

RESUMO

Immune checkpoint blockades (ICBs) have changed the standard of care of squamous and adenocarcinoma non-small cell lung cancer (NSCLC). Whereas detailed researches regarding ICBs in the two major histological subtypes are rare. In order to uncover the clinical efficacy differences between squamous and adenocarcinoma NSCLC and better understand the underlying immune-regulatory mechanisms, we compared the survival benefits of ICBs between the two subtypes by revealing phase 3 randomized trials and attempted to uncover the immune-regulatory discrepancy. Generally, compared with nonsquamous NSCLC, squamous NSCLC benefited more from ICBs in Keynote 024, CheckMate 026, CheckMate 227 and CheckMate 017 and similar in OAK, but less in Keynote 010 and PACIFIC. We revealed that the tumor mutation burden (TMB) level, the programmed cell death ligand 1 (PD-L1) expression, tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME), chemokines, and oncogenic driver alterations within the two subtypes may contributed to the clinical outcomes of ICBs. We prospected that the combinations of ICBs with chemotherapy, radiation therapy, and antiangiogenic therapy could be promising strategies to re-immunize the less immunogenic tumors and further enhance the efficacy of ICBs.

11.
Front Oncol ; 10: 576700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194690

RESUMO

Background: Owing to improved systemic therapies, the survival of patients with non-small cell lung cancer (NSCLC) was prolonged, and the risk of brain metastases was consequently increased. This study aims to compare different radiotherapy for brain metastases in patients with NSCLC. Materials and methods: The patients with NSCLC who were treated with whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for brain metastases at three medical centers between January 2012 and December 2017 were retrospectively analyzed. Results: Of the 684 eligible patients, 217 received WBRT plus focal radiation boost (WBRT+boost), 324 received WBRT, and 143 received SRS. Patients with WBRT+boost lived longer than those with WBRT (median overall survival (OS), 22.2 vs 13.7 months, P < 0.001) or SRS (22.2 vs 17.3 months, P = 0.011). In subgroup analyses, the survival advantage of WBRT+boost was more obvious among patients with 1 to 3 brain metastases or who received targeted therapy than did SRS. From pair-wise comparisons of intracranial progression-free survival (iPFS), WBRT+boost was also superior to WBRT (12.9 vs 10.6 months, P = 0.028) and SRS (12.9 vs 9.1 months, P = 0.001). Conclusions: Patients who were treated with WBRT+boost experienced significantly longer OS and iPFS than those with WBRT or SRS alone. WBRT+boost should be a preferred strategy for brain metastases in NSCLC patients.

12.
Int Immunopharmacol ; : 107178, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33218939

RESUMO

OBJECTIVE: We initially aimed to investigate pre/post-treatment inflammatory biomarkers (pre/post-IBs) and their dynamic changes (delta-IBs) on the short-term outcome (STO) of radiotherapy or chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). Furthermore, a nomogram was built to provide an accurate prediction of STO. METHODS: The STO using the treatment response evaluation was assessed according to RECIST 1.1 at 1 month after radiotherapy or chemoradiotherapy. The IBs (absolute lymphocyte counts (ALC), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and lymphocyte/monocyte (LMR)) and clinical variables were collected and analyzed from 398 ESCC patients at Shandong Cancer Hospital between 2015 and 2019. The nomogram was then established for predicting STO. RESULTS: Pre-ALC and pre-LMR significantly increased, pre-NLR and pre-PLR significantly decreased during radiotherapy or chemoradiotherapy (all P < 0.001). Meanwhile, there was a positive correlation between delta-NLR as well as delta-PLR (r = 0.621) and delta-LMR (r = 0.613), whereas a negatively correlated between delta-LMR and delta-PLR (r = -0.573). Multivariate analysis indicated that gender [OR, 0.473; 95%CI, 0.274-0.816; P = 0.007], pre-ALC [OR, 0.554; 95%CI, 0.335-0.915; P = 0.021], pre-NLR [OR, 3.176; 95%CI, 1.733-5.823; P < 0.001], post-NLR [OR, 2.418; 95%CI, 1.271-4.600; P = 0.007] and delta-NLR [OR, 1.929; 95%CI, 1.035-3.595; P = 0.039] were statistically significant with STO. And c-index of the nomogram established by combining all independent predictors for STO was 0.770 [95%CI, 0.719-0.820]. CONCLUSION: Pre-NLR, pre-ALC, post-NLR, and delta-NLR were significant with STO in ESCC patients treated with radiotherapy or chemoradiotherapy. Further, pre-NLR had the best predictive value, and the developed nomogram with superior prediction ability for STO could assist in patients counseling and guide to make individual treatments.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33220395

RESUMO

PURPOSE: This study aimed to compare erlotinib (E) and etoposide/cisplatin (EP) with concurrent radiotherapy (RT) for patients with stage IIIA/B unresectable advanced non-small-cell lung cancer (NSCLC) with activating epidermal growth factor receptor mutation (EGFRm+). METHODS: and patients: This was a multicenter, randomized, open-label, phase 2 trial conducted across 19 institutions in China (December 2012 to January 2016). Enrolled patients were randomized (1:1) to E+RT (oral erlotinib 150 mg/day for 2 years or until disease progression or intolerable toxicity and RT 200 cGy/day, 5 days/week for 6 weeks from the first day of erlotinib) or EP+RT (etoposide 50 mg/m2 intravenously on days 1-5 and 29-33; cisplatin 50 mg/m2 intravenously on days 1, 8, 29 and 36; and RT as above). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and safety. RESULTS: A total of 252 patients were screened and 20 patients with EGFRm+ in each group received the allocated E+RT or EP+RT treatment. Patient characteristics were well-balanced between groups. Compared with EP+RT, median PFS with E+RT was significantly longer (24.5 vs 9.0 months [hazard ratio, 0.104; 95% confidence interval, 0.028-0.389; P < 0.001]). ORR in the E+RT and EP+RT groups was 70% and 61.9%, respectively (P = 0.744). The incidence of adverse events (any grade) was similar between E+RT and EP+RT groups (88.9% and 84.2%). CONCLUSIONS: The primary endpoint of PFS was met, and the data showed that E+RT might provide PFS improvement compared with EP+RT, with similar tolerability. However, definitive statements regarding the efficacy of concurrent E+RT in patients with unresectable stage III NSCLC with activating EGFRm+ cannot be made, and slow patient accrual will likely make it infeasible to conduct a phase 3 study.

14.
Cancer Manag Res ; 12: 10573-10585, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149667

RESUMO

Introduction: Postoperative adjuvant radiation therapy (RT) and chemotherapy (aCRT) have been supposed to improve prognosis and outcomes in patients with node-positive thoracic esophageal squamous cell carcinoma (TESCC). Our aim was to analyze the impacts of interval between surgery and aCRT on prognosis, determining the optimal time interval. Methods: We retrospectively reviewed 520 patients with TESCC between 2007 and 2015 treated with aCRT following radical esophagectomy without neoadjuvant chemotherapy and RT. These patients underwent RT (50-60 Gy) combined with 2-6 cycles chemotherapy after surgery. The time intervals were from 17 days to 145 days and divided into three groups: short interval group (≤28 days, S-Int group), medial interval group (≥29 and ≤ 56 days, M-Int group) and long interval group (≥57 days, L-Int group). Results: Median follow-up was 35.6 months and the 3-, 5-year survival rates and median survival were 49.5%, 36.6% and 35.9 months. The duration of postoperative interval was a predictor of survival outcomes. The median survival and 5-year survival rates in S-Int, M-Int and L-Int groups were 23.6 (32.1%), 44.2 (43.3%) and 32.0 (31.5%) months (P=0.007). The difference was statistically significant between the M-Int and S-Int or L-Int group but was not between the S-Int and L-Int group. Besides, toxic reactions including early, late and adverse events (grade ≥3) in M-Int group were significantly less than S-Int and show no significant differences with L-Int group. Conclusion: The optimal time interval was from 29 days to 56 days (5-8 weeks) both in terms of survival outcomes and toxic reactions.

15.
Transl Lung Cancer Res ; 9(5): 2137-2144, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209632

RESUMO

The standard treatment of unresectable locally advanced non-small cell lung cancer (LA NSCLC) is concurrent chemoradiotherapy. With the addition of immunotherapy, patients with LA NSCLC received a significantly prolonged outcome, while patients with harboring epidermal growth factor receptor (EGFR) mutation benefited less. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of stage IV with harboring EGFR mutation and anaplastic lymphoma kinase rearrangement, but there are few recommendations indicating whether TKI treatment is effective in unresectable NSCLC. Preclinical studies have shown that TKIs could have a radiosensitizing effect, which provided a rationale to consider the application TKI with radiotherapy. In this review, we summarize the clinical studies that have used TKIs in LA-NSCLC as well as ongoing trials, and discuss recent progress in research related to the efficacy of TKI for unresectable LA NSCLC patients. Recent results of small studies evaluating TKI therapy for LA NSCLC patients in combination with radiation or chemoradiation demonstrated promising efficacy, improved outcomes with a tolerable toxicity profile. However, there is a lack of strong evidence for TKI treatment in unresectable LA NSCLC, because of unpowered statistics, lack of molecular selection, or lack of large randomized arms. We prospect the combination of TKI and radiation or chemoradiation therapy might eventually replace the current standard treatment for patients with LA NSCLC harboring oncogene-driven mutation.

16.
Children (Basel) ; 7(11)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202785

RESUMO

BACKGROUND: To save assessment time and improve the efficiency, it is necessary to find sensitive indicators from the test items of gross motor development in the C-LAP system for children aged 24~36 months and analyze the influencing factors of the passing rate of these indicators. METHODS: This retrospective study was conducted among 1354 toddlers (3058 person-times) aged 24 to 36 months in Beijing, Shanghai, Guangdong between January 2013 and December 2019. A linear regression model and Cox regression model were performed to screen sensitive indicators and explore their influencing factors, respectively. RESULTS: "Walk backwards", "Stand from supine position" and "Hop with one foot at least twice" are the three sensitive indicators for evaluating the development of gross motor function in 24~36 month old children. The child's physiological age at first measurement and region are the two common independent factors influencing the passing rate of the three items, while paternal age and education may influence one or two of them. CONCLUSIONS: "Walk backwards", "Stand from supine position" and "Hop with one foot at least twice" are sensitive indicators for the effective evaluation of the development of gross motor function in 24~36 month old children, and their passing rates are influenced by some demographic variables.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33245275

RESUMO

BACKGROUND: Diagnosis of Leptomeningeal Metastases (LM) from Non-Small Cell Lung Cancer (NSCLC) is usually based on clinical symptoms, cerebral-spinal fluid (CSF) cytology, and neuro-imaging. However, early diagnosis of LM in NSCLC is challenging due to the low sensitivity of these approaches. The Next-Generation Sequencing (NGS) using CSF could help improve the diagnosis of LM and guide its treatment options. METHODS: We report a 39-year-old male NSCLC patient with negative molecular testing results in lung cancer tissue sample. The patient developed symptoms of LM with the negative CSF cytology and MRI, however the NGS analysis of CSF revealed a EGFR exon 19 del mutation. The patient attained 6 months of Progression-Free Survival (PFS) by treating with erlotinib and anlotinib before the neurological symptoms appeared again. EGFR Thr790Met was positive in the CSF but negative in his plasma. The patient was then treated with osimertinib therapy and the response was maintained for more than 1 year. RESULTS & DISCUSSION: This case is the first study reporting the clinical benefit of using the combination of erlotinib and anlotinib for the treatment of LM with the EGFR 19 del, osimertinib with EGFR T790M mutation in CSF, but negative gene mutation in the blood or lung tumor biopsy specimens. Our results support that genetic analysis should be performed on CSF samples in all cases of suspected LM when the results of testing for EGFR/ALK/ROS1 mutation in blood samples or tumor biopsy specimens are negative, as these patients could benefit from treatment of TKIs in a poor prognostic setting. CONCLUSION: In parallel to current patents, NGS could be applied as a novel strategy in the managing of NSCLC patients with LM.

18.
Theranostics ; 10(25): 11707-11718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052242

RESUMO

Prognostic biomarkers that can reliably predict early disease progression of non-small cell lung cancer (NSCLC) are needed for identifying those patients at high risk for progression, who may benefit from more intensive treatment. In this work, we aimed to identify an imaging signature for predicting progression-free survival (PFS) of locally advanced NSCLC. Methods: This retrospective study included 82 patients with stage III NSCLC treated with definitive chemoradiotherapy for whom both baseline and mid-treatment PET/CT scans were performed. They were randomly placed into two groups: training cohort (n=41) and testing cohort (n=41). All primary tumors and involved lymph nodes were delineated. Forty-five quantitative imaging features were extracted to characterize the tumors and involved nodes at baseline and mid-treatment as well as differences between two scans performed at these two points. An imaging signature was developed to predict PFS by fitting an L1-regularized Cox regression model. Results: The final imaging signature consisted of three imaging features: the baseline tumor volume, the baseline maximum distance between involved nodes, and the change in maximum distance between the primary tumor and involved nodes measured at two time points. According to multivariate analysis, the imaging model was an independent prognostic factor for PFS in both the training (hazard ratio [HR], 1.14, 95% confidence interval [CI], 1.04-1.24; P = 0.003), and testing (HR, 1.21, 95% CI, 1.10-1.33; P = 0.048) cohorts. The imaging signature stratified patients into low- and high-risk groups, with 2-year PFS rates of 61.9% and 33.2%, respectively (P = 0.004 [log-rank test]; HR, 4.13, 95% CI, 1.42-11.70) in the training cohort, as well as 43.8% and 22.6%, respectively (P = 0.006 [log-rank test]; HR, 3.45, 95% CI, 1.35-8.83) in the testing cohort. In both cohorts, the imaging signature significantly outperformed conventional imaging metrics, including tumor volume and SUVmax value (C-indices: 0.77-0.79 for imaging signature, and 0.53-0.73 for conventional metrics). Conclusions: Evaluation of early treatment response by combining primary tumor and nodal imaging characteristics may improve the prediction of PFS of locally advanced NSCLC patients.

19.
Oncol Rep ; 44(6): 2527-2536, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125501

RESUMO

Cognitive deficit is one of the most serious complications of cranial radiotherapy of head and neck cancers. However, the underlying mechanism of this cognitive impairment remains unclear. In the present study, the role of tropomyosin receptor kinase A (TrkA) and its ligand neurotrophin nerve growth factor (NGF) were investigated following whole­brain irradiation (WBI). Young male Sprague­Dawley rats underwent WBI at a single dose of 10 Gy. WBI was determined to result in notable memory decline and substantial neurogenesis impairment in the hippocampus 3 months post­irradiation. Compared with the control group, TrkA protein expression was greater in irradiated rats 1 week after WBI, which then decreased significantly by the 3­month time­point. However, no difference in NGF expression was observed from 1 day to 3 months post­WBI. Overexpression of hippocampal TrkA in rats using adeno­associated virus ameliorated memory decline induced by irradiation. Additionally, upregulating TrkA expression rescued irradiation­induced hippocampal precursor cell proliferation and promoted neurogenesis. PI3K, Akt and ERK1/2 phosphorylation were also revealed to be significantly inhibited by WBI, which was ameliorated by TrkA overexpression. Findings of the present study indicated that the TrkA­dependent signaling pathway may serve a critical role in radiotherapy­induced cognitive deficit and impairments in neurogenesis.

20.
Radiat Oncol ; 15(1): 243, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087143

RESUMO

INTRODUCTION: There is no standard treatment for locoregional recurrent (LR) esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) previously. This retrospective study aimed to examine the efficacy and toxicity of re-irradiation (re-RT) for ESCC patients with LR. PATIENTS AND METHODS: A total of 252 patients were enrolled. Gross tumor volumes for re-RT were defined using contrast enhanced computed tomography and/or positron emission tomography/computed tomography. Overall survival (OS), after recurrence survival (ARS) and toxicities were assessed. RESULTS: Through a median follow-up of 38 months, the median OS and ARS were 39.0 and 13.0 months, respectively. The 6-, 12-, and 24-month ARS rates were 81.9%, 50.5%, and 21.8%, respectively. Multivariate analyses showed that chemotherapy, esophageal stenosis and recurrence-free interval (RFI) may be independent prognostic factors for ARS. The incidence of esophageal fistula/perforation (EP), radiation-induced pneumonitis and esophagorrhagia was 21.4%, 12.8% and 9.1%, respectively. RFI ≤ 12 months, esophageal stenosis and fat space between tumor and adjacent tissue disappeared were independent risk factors for the development of EP after re-RT. CONCLUSIONS: Re-RT was feasible for LR ESCC patients after RT initially, the complication occurred in re-RT is acceptable. Patients with RFI ≤ 12 months, esophageal stenosis and fat space between tumor and adjacent tissue disappeared should be closely observed during and after re-RT.

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