AbstractPurpose Severe radiation pneumonitis (grade≥3 RP) remains an important dose-limiting toxicity after thoracic radiotherapy (RT). This study aimed to investigate risk factors for severe RP in patients with locally-advanced non-small cell lung cancer (NSCLC) after thoracic RT, develop a prediction model to identify high-risk groups and investigate impact of severe RP on overall survival (OS). Methods We retrospectively collected clinical, hematological and dosimetric factors from 351 stage-Ⅲ NSCLC patients after thoracic RT between 2018 and 2022. The primary endpoint was development of severe RP. The secondary endpoint was OS. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression analysis were used to identify risk factors of severe RP. Nomogram was generated based on multivariate regression coefficients. Area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were conducted to validate the model. After a long-term follow-up, OS of patients with RP vs. non-RP and mild RP vs. severe RP groups was analyzed by Kaplan‒Meier method. Results ILD (p<0.001), percentage of contralateral lung volume receiving≥5Gy (contraV5) (P=0.013), percentage of ipsilateral lung volume receiving≥20Gy (ipsiV20)(P=0.039), pre-RT derived neutrophil lymphocyte ratio (dNLR) (P=0.015) and post-RT systemic inflammation response index (SIRI) (p=0.001) were showed to be independent predictors of severe RP and were included in the nomogram. ROC curves revealed the AUC of the nomogram was 0.782. Calibration curves showed favorable consistency, and DCA showed satisfactory positive net benefits of the model. Median follow-up time was 19.8 months (1.4-52.9 months), and cases who developed severe RP showed shorter OS than those developed mild RP (P=0.027). Conclusion We identified that ILD, contraV5(>11%), ipsiV20(>45%), pre-RT dNLR (>1.9) and post-RT SIRI (>3.4) could predict severe RP among patients with locally-advanced NSCLC receiving thoracic RT. Combining these indicators, a nomogram was first built and validated, showing its potential value in clinical practice.
Abstract Background: To investigate comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients who had stage I non-small cell lung cancer (NSCLC) and a high risk for lobectomy. Methods: From January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection biases in SBRT and SLR patients. Results: 86 SBRT and 79 SLR patients were collected. Median follow-up periods of SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significant increased age, larger tumor diameter, lower FEV1, poorer PS and higher rates of male comparing with SLR. There were no significant differences in terms of 3-year overall survival (OS) (80.3% and 82.3%, P = 0.405), cause-specific survival (CSS) (81.3% and 83.4%, P = 0.383) and local control (LC) (89.7% and 86.0%, P = 0.501) were found in SBRT and SLR patients. 49 patients were identified from each group after performing PSM. The differences of matching factors were balanced based on age, gender, performance status, tumor characteristics and pulmonary function, as no significant differences in terms of 3-year OS (85.4% and 73.3%, P = 0.649), CSS (87.2% and 74.9%, P = 0.637) and LC (95.6% and 82.1%, P = 0.055) in matched SBRT and SLR patients were observed. The rate of grade 3 or the occurrence of worse adverse events was 0 and 10.2% in the matched SBRT and SLR groups (P = 0.056), respectively. Conclusion: These results suggest that disease control and survival achieved by SBRT were equivalent to SLR in patients who had clinical stage I NSCLC and were at high risk for lobectomy. SBRT can be an alternative option to SLR in treating patients with a high operative risk.
Accurately predicting the risk level for a lymph node metastasis is critical in the treatment of non-small cell lung cancer (NSCLC). This study aimed to construct a novel nomogram to identify patients with a risk of lymph node metastasis in T1-2 NSCLC based on positron emission tomography/computed tomography (PET/CT) and clinical characteristics.From January 2011 to November 2017, the records of 318 consecutive patients who had undergone PET/CT examination within 30 days before surgical resection for clinical T1-2 NSCLC were retrospectively reviewed. A nomogram to predict the risk of lymph node metastasis was constructed. The model was confirmed using bootstrap resampling, and an independent validation cohort contained 156 patients from June 2017 to February 2020 at another institution.Six factors [age, tumor location, histology, the lymph node maximum standardized uptake value (SUVmax), the tumor SUVmax and the carcinoembryonic antigen (CEA) value] were identified and entered into the nomogram. The nomogram developed based on the analysis showed robust discrimination, with an area under the receiver operating characteristic curve of 0.858 in the primary cohort and 0.749 in the validation cohort. The calibration curve for the probability of lymph node metastasis showed excellent concordance between the predicted and actual results. Decision curve analysis suggested that the nomogram was clinically useful.We set up and validated a novel and effective nomogram that can predict the risk of lymph node metastasis for individual patients with T1-2 NSCLC. This model may help clinicians to make treatment recommendations for individuals.
Telomerase Cajal body protein 1 (TCAB1) is a telomerase holoenzyme, which is markedly enriched in Cajal bodies (CBs) and facilitates the recruitment of telomerase to CBs in the S phase of the cell cycle. This recruitment is dependent on TCAB1 binding to a telomerase RNA component. The majority of cancer cells are able to grow indefinitely due to telomerase and its mechanism of trafficking to telomeres. In the present study, a certain level of TCAB1 expression in A549 human lung cells was identified and TCAB1 knockdown exhibited a potent antiproliferative effect on these cells, which was coupled with a decrease in the cell density and activity of the cellular enzymes. In addition, TCAB1-depletion was demonstrated to inhibit telomerase trafficking to telomeres in the A549 cells, leading to subsequent G1 cell cycle arrest without inducing apoptotic cell death. Overall, these observations indicated that TCAB1 may be essential for A549 cell proliferation and cell cycle regulation, and may be a potential candidate for the development of a therapeutic target for lung adenocarcinomas.
Objective
To investigate the value of tracing thyroglobulin(Tg)in predicting metastasis of post-operative patients with differentiated thyroid carcinoma(DTC)before its first pre-ablation with 131I.
Methods
106 cases with DTC, undergoing total thyroidectomy and lymphadenectomy, were assigned to 2 groups as M0 group(without metastasis)and M1 group(with metastasis). Clinical data including pre-ablation stimulated thyroglobulin(sTg)and pre-operative Tg were determined. sTg, pre-operative Tg, Tg variation(ΔTg), and Tg variation rate (ΔTg/pre-operative Tg)between 2 groups were compared. The ROC curve and the diagnostic critical point(DCP)were analyzed.
Results
sTg, Pre-operative Tg, Tg variation, and Tg variation rate were significantly higher than those of M0(all P<0.01). The corresponding areas under the ROC curve(AUC)to differentiate the two groups were 0.913, 0.702, 0.773, and 0.943, respectively. The best diagnostic value points(DCP)were 40.60 ng/ml and -72.5%. The sensitivity and specificity were 70.21%, 100.00%, and 89.36%, 88.13%, respectively.
Conclusion
The pre-ablation sTg seems to be a useful diagnostic marker for predicting metastasis before the first 131I ablation. The sTg value can be effectively corrected by the Tg variation rate, and the sensitivity and accuracy of sTg for metastasis in DTC patients can be improved, finally providing evidence for pre-ablative assessment as well as strategies of 131I therapy. (Chin J Endocrinol Metab, 2018, 34: 102-105)
Key words:
Differentiated thyroid carcinoma; Thyroglobulin; Radioiodine therapy; Iodine radioisotopes
To explore the mechanisms of HSPA2 downregulation in inhibiting the proliferation of lung adenocarcinoma.We obtained 85 specimens of human lung adenocarcinoma and specimens of adjacent nontumor tissues from the First Affiliated Hospital, School of Medicine, Zhejiang University. We then analyzed the expression of HSPA2 in these tissues and in lung adenocarcinoma and normal lung cell lines. Human lung adenocarcinoma cell lines were transfected with siRNA silencing HSPA2 and subjected to colony forming, Thiazolyl blue tetrazolium bromide (MTT), propidium iodide flow cytometry, immunofluorescence assay and western blotting to explore the causes of the reduction in the proliferation of lung adenocarcinoma cells and the endoplasmic reticulum stress induced by HSPA2 downregulation. Finally, we confirmed these mechanisms via rescue assay.Greater HSPA2 expression was found in the lung adenocarcinoma specimens than in the specimens of adjacent nontumor tissues, and greater expression was found in lung adenocarcinoma cell lines than in normal cell lines. HSPA2 knockdown via siRNA reduced proliferation and led to G1/S phase cell cycle arrest in the lung adenocarcinoma cell lines. G1/S phase cell cycle arrest triggered by HSPA2 downregulation could be attributed, at least in part, to phosphorylation and activation of the Erk1/2 pathway and probably to activation of IRE1α/PERK-mediated endoplasmic reticulum stress.HSPA2 plays an important role in the origin and development of lung adenocarcinoma. It is thus deserving of further study as a promising clinical therapeutic target.
Traditional Chinese medicine (TCM) makes a synergistic and attenuative effect when combined with chemoradiotherapy. However, strong evidence-based studies are lacking. The study sought to investigate whether Zengxiao Jiandu decoction as an adjunctive therapy is superior to definitive concurrent chemoradiotherapy (DCCRT) alone in unresectable, locally advanced (LA), stage III non-small cell lung cancer (NSCLC).Patients with unresectable LA-NSCLC were randomly assigned to receive DCCRT either combined with Zengxiao Jiandu decoction (TCM arm) or placebo therapy (Control arm), by computer-generated random assignment lists using a central randomization system. The patients were routinely followed-up every 3 months for the first 2 years after the therapy, and every 6 months for the subsequent 3 years, or earlier if clinically indicated. The primary endpoint was grade ≥3 chemoradiotherapy-related toxicities, while secondary endpoints included the completion rate of chemoradiotherapy, the clinical objective response rate (ORR), and survival. The placebo achieved full consistency in color, aroma, taste and appearance with the Zengxiao Jiandu decoction.From February 2019 to December 2020, 163 patients were randomly allocated to TCM arm (n=82) or Control arm (n=81). Fifty-nine (72.0%) patients in TCM arm finished chemoradiotherapy per protocol and 79 (96.3%) received protocol-specified Zengxiao Jiandu decoction. Forty-two patients in Control arm finished chemoradiotherapy per protocol. The incidence of grade ≥3 chemoradiotherapy-related toxicities was higher in Control arm than TCM arm (44.4% vs. 31.7%, P=0.094). Grade ≥3 radiation pneumonitis occurred more frequently in Control arm than TCM arm (13.6% vs. 3.7%, P=0.024). The completion rate of the protocol-specified chemotherapy was significantly higher in TCM arm than Control arm (79.3% vs. 64.2%, P=0.033), but the completion rates of the definitive-dose radiotherapy were similar. There were no significant differences in ORR between the 2 arms. The progression-free survival (PFS) of TCM arm was significantly better than Control arm (median PFS, 12.0 vs. 9.0 months, P=0.035). However, Zengxiao Jiandu decoction was not found to produce any significant benefit in overall survival.The Zengxiao Jiandu decoction adjunctive therapy, as compared to DCCRT alone, reduced grade ≥3 radiation pneumonitis, improved the completion rate of DCCRT, and prolonged PFS for unresectable LA-NSCLC.Chinese Clinical Trial Registry ChiCTR2000031667.
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