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Objective: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. Methods: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). Results: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). Conclusions: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone. [ABSTRACT FROM AUTHOR]

Background: The data of the prognostic role of V‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early‐stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. Methods: We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan–Meier method and compared by log‐rank test. Cox proportional hazard models, propensity‐score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence‐free survival (RFS). Results: The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E‐mutant patients were detected to have concurrent EGFR mutations, one for 19‐del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild‐type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). Conclusions: In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The 9th edition of tumour–node–metastasis (TNM) staging for lung cancer was announced by Prof Hisao Asamura at the 2023 World Conference on Lung Cancer in Singapore. The purpose of this study was to externally validate and compare the latest staging of lung cancer. METHODS We collected 19 193 patients with stage IA–IIIA non-small cell lung cancer (NSCLC) who underwent lobectomy from the Surveillance, Epidemiology and End Results database. Survival analysis by TNM stages was compared using the Kaplan–Meier method and further analysed using univariable and multivariable Cox regression analyses. Receiver operating characteristic curves were used to assess model accuracy, Akaike information criterion, Bayesian information criterion and consistency index were used to compare the prognostic, predictive ability between the current 8th and 9th edition TNM classification. RESULTS The 9th edition of the TNM staging system can better distinguish between IB and IIA patients on the survival curve (P  < 0.0001). In both univariable and multivariable regression analysis, the 9th edition of the TNM staging system can differentiate any 2 adjacent staging patients more evenly than the 8th edition. The 9th and the 8th edition TNM staging have similar predictive power and accuracy for the overall survival of patients with NSCLC [TNM 9th vs 8th, area under the curve: 62.4 vs 62.3; Akaike information criterion: 166 182.1 vs 166 131.6; Bayesian information criterion: 166 324.3 vs 166 273.8 and consistency index: 0.650 (0.003) vs 0.651(0.003)]. CONCLUSIONS Our external validation demonstrates that the 9th edition of TNM staging for NSCLC is reasonable and valid. The 9th edition of TNM staging for NSCLC has near-identical prognostic accuracy to the 8th edition. [ABSTRACT FROM AUTHOR]

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+–CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization. The role of the tumor microenvironment in immunotherapy response in intrahepatic cholangiocarcinoma remains unclear. Here, single cell RNA and TCR sequencing of samples before and after immunotherapy highlights the role of CD8 T-cell status conversion and exhaustion induced by Macro CD5L+ in treatment response. [ABSTRACT FROM AUTHOR]

Background This study aimed to construct an effective nomogram based on the clinical and laboratory characteristics to predict the prognosis of stage I lung adenocarcinoma with EGFR alteration. Methods A retrospective study was performed of 913 eligible patients with EGFR alteration after surgery at Shanghai Pulmonary Hospital. The peripheral blood indicators were included in the nomogram. Calibration plots, concordance index, decision curve analysis, and X-tile software were used in this study. Recurrence-free survival (RFS) and overall survival were estimated by the Kaplan-Meier method and compared using the log-rank test. Results Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were independent risk factors for RFS. The calibration curves for RFS probabilities showed good agreement between the nomogram prediction and actual observation. Furthermore, the nomogram, including neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had a higher concordance index (0.732, 95% confidence interval = 0.706 to 0.758) than that without neutrophil to lymphocyte ratio or platelet to lymphocyte ratio (0.713, 95% confidence interval = 0.686 to 0.740), and decision curve analysis plots showed that the nomogram with neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had better clinical practicability. Additionally, the patients were divided into 2 groups according to cutoff values of risk points, and statistically significant differences in RFS and overall survival were observed between the high-risk and low-risk groups (P  <  .001). Conclusions High pretreatment levels of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were strongly associated with a worse prognosis in stage I EGFR -altered lung adenocarcinomas. Besides, the proposed nomogram with neutrophil to lymphocyte ratio and platelet to lymphocyte ratio presented a better prediction ability for the survival of those patients. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I–IIA ADC. METHODS We included 1585 patients with pathologically diagnosed stage I–IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan–Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717–0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P  <   0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I–IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I–IIA ADC patients. [ABSTRACT FROM AUTHOR]

Background: Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no effective therapeutic target, intra- and intertumoral heterogeneity, inadequate effective drugs, and an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas and finding out the working mechanisms are urgent and necessary for glioma treatment. Identification of prognostic biomarkers and targeting the biomarker genes will be a promising therapy. Methods: From our RNA-sequencing data of the oxidative phosphorylation (OXPHOS)-inhibition sensitive and OXPHOS-resistant cell lines, we found that the scaffolding protein caveolin 1 (CAV1) is highly expressed in the resistant group but not in the sensitive group. By comprehensive analysis of our RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) data and public databases, we found that CAV1 is highly expressed in gliomas and its expression is positively related with pathological processes, higher CAV1 predicts shorter overall survival. Results: Further analysis indicated that (1) the differentiated genes in CAV1-high groups are enriched in immune infiltration and immune response; (2) CAV1 is positively correlated with tumor metastasis markers; (3) the methylation level of CAV1 promoters in glioma group is lower in higher stage than that in lower stage; (4) CAV1 is positively correlated with glioma stemness; (5) higher expression of CAV1 renders the glioma cells' resistant to oxidative phosphorylation inhibitors. Conclusion: Therefore, we identified a key gene CAV1 and deciphered its function in glioma progression and prognosis, proposing that CAV1 may be a therapeutic target for gliomas. [ABSTRACT FROM AUTHOR]

Background: The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort. Materials and methods: We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component. Results: The new pN classification had a satisfactory effect on survival curves (Log-rank P < 0.001). After adjusting for other confounders, the new pN classification could be an independent prognostic indicator. Besides, the new pN component had a much more accurate predictive ability in the prognostic assessment for SCLC patients of pathological classifications T1-2N0-2M0 compared with the current pN classification in the SEER database (AIC: 4705.544 vs. 4731.775; C-index: 0.654 vs. 0.617, P < 0.001). Those results were validated in the MCDB from China. Conclusions: The multicenter cohort developed and validated a modified nodal classification for SCLC patients with pathological category T1-2N0-2M0 after surgery. Besides, we propose that an adequate lymph node dissection is essential; surgeons should perform and consider the situation of ELNs and LNR when they evaluate postoperative prognoses of SCLC patients. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the second most commonly diagnosed cancer and ranks the first in mortality. Pathological lymph node status(pN) of lung cancer affects the treatment strategy after surgery while systematic lymph node dissection(SLND) is always unsatisfied. Methods: We reviewed the clinicopathological features of 2,696 patients with LUAD and one single lesion ≤ 5 cm who underwent SLND in addition to lung resection at the Sun Yat-Sen University Cancer Center. The relationship between the pN status and all other clinicopathological features was assessed. All participants were stochastically divided into development and validation cohorts; the former was used to establish a logistic regression model based on selected factors from stepwise backward algorithm to predict pN status. C-statistics, accuracy, sensitivity, and specificity were calculated for both cohorts to test the model performance. Results: Nerve tract infiltration (NTI), visceral pleural infiltration (PI), lymphovascular infiltration (LVI), right upper lobe (RUL), low differentiated component, tumor size, micropapillary component, lepidic component, and micropapillary predominance were included in the final model. Model performance in the development and validation cohorts was as follows: 0.861 (95% CI: 0.842–0.883) and 0.840 (95% CI: 0.804–0.876) for the C-statistics and 0.803 (95% CI: 0.784–0.821) and 0.785 (95% CI: 0.755–0.814) for accuracy, and 0.754 (95% CI: 0.706–0.798) and 0.686 (95% CI: 0.607–0.757) for sensitivity and 0.814 (95% CI: 0.794–0.833) and 0.811 (95% CI: 0.778–0.841) for specificity, respectively. Conclusion: Our study showed an easy and credible tool with good performance in predicting pN in patients with LUAD with a single tumor ≤ 5.0 cm without SLND and it is valuable to adjust the treatment strategy. [ABSTRACT FROM AUTHOR]

Introduction: At present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model. Methods: Stage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)—who had undergone esophagectomy in 1995–2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses. Results: The Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history − 0.012 × hemoglobin–0.042 × albumin − 0.032 × lymph nodes]. Patients were grouped into three classes—Class A (5.14–7.26, low risk), Class B (7.27–7.70, middle risk), and Class C (7.71–9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P < 0.001). Similar findings were observed in the validation group. Additionally, Cox regression analysis showed that Esorisk aggregate score remained significantly associated with CSS in the training cohort and validation cohort after adjusting for other confounders. Conclusions: We combined the data of two large clinical centers, and comprehensively considered their valuable clinical factors and hematological indicators, established and verified a new prognostic risk classification that can predict CSS of stage T1-3N0M0 ESCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: A retrospective study was performed on 955 eligible patients with stage I lung adenocarcinoma (LUAD) after surgery. The systematic oxidative stress score (SOS) was established based on three biochemical indicators, including serum creatinine (CRE), lactate dehydrogenase (LDH), and uric acid (UA). SOS is an independent prognostic indicator for stage I LUAD. In addition, the constructed nomogram based on SOS could accurately predict the survival of those patients. This study aimed to construct an effective nomogram based on the clinical and oxidative stress-related characteristics to predict the prognosis of stage I lung adenocarcinoma (LUAD). A retrospective study was performed on 955 eligible patients with stage I LUAD after surgery at our hospital. The relationship between systematic-oxidative-stress biomarkers and the prognosis was analyzed. The systematic oxidative stress score (SOS) was established based on three biochemical indicators, including serum creatinine (CRE), lactate dehydrogenase (LDH), and uric acid (UA). SOS was an independent prognostic factor for stage I LUADs, and the nomogram based on SOS and clinical characteristics could accurately predict the prognosis of these patients. The nomogram had a high concordance index (C-index) (0.684, 95% CI, 0.656–0.712), and the calibration curves for recurrence-free survival (RFS) probabilities showed a strong agreement between the nomogram prediction and actual observation. Additionally, the patients were divided into two groups according to the cut-off value of risk points based on the nomogram, and a significant difference in RFS was observed between the high-risk and low-risk groups (p < 0.0001). SOS is an independent prognostic indicator for stage I LUAD. These things considered, the constructed nomogram based on SOS could accurately predict the survival of those patients. [ABSTRACT FROM AUTHOR]

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. Methods: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan–Meier survival analysis were also used in this study. Results: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694–0.704). Moreover, the Cox proportional hazards analysis and Kaplan–Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. Conclusion: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

Background: The study on skip-N2 metastasis in small-cell lung cancer (SCLC) is lacking. Therefore, this study aimed to explore the prognostic significance of skip-N2 metastasis based on a multicenter cohort. Methods: We collected 176 SCLC patients with pathological categories T1-4N1-2M0 from four hospitals in China. Survival curves were drawn through the Kaplan–Meier method and compared by the log-rank test. The Cox regression method was used to calculate the hazard ratio (HR) and 95% confidence interval of the characteristics for cancer-specific survival (CSS). Two propensity-score methods were used to reduce the bias, including the inverse probability of treatment weighting (IPTW) and propensity-score matching (PSM). Results: This multicenter database included 64 pN1 patients, 63 non-skip-N2 cases, and 49 skip-N2 cases. Skip-N2 and the non-skip-N2 patients had gap CSS rates (skip-N2 no versus yes: 41.0% versus 62.0% for 1-year CSS, 32.0% versus 46.0% for 2-year CSS, and 20.0% versus 32.0% for 3-year CSS). After PSM, there were 32 pairs of patients to compare survival differences between N2 and skip-N2 diseases, and 34 pairs of patients to compare prognostic gaps between N1 and skip-N2 diseases, respectively. The results of IPTW and PSM both suggested that skip-N2 cases had better survival outcomes than the non-skip-N2 cases (IPTW-adjusted HR = 0.578; PSM-adjusted HR = 0.510; all log-rank p < 0.05). Besides, the above two analytic methods showed no difference in prognoses between pN1 and skip-N2 diseases (all log-rank p > 0.05). Conclusions: Skip-N2 patients were confirmed to have a better prognosis than non-skip-N2 patients. Besides, there was no survival difference between pN1 and skip-N2 cases. Therefore, we propose that the next tumor-node-metastasis staging system needs to consider the situation of skip metastasis with lymph nodes in SCLC. [ABSTRACT FROM AUTHOR]

Objective: This study explored the safety and of feasibility of video-assisted thoracoscopy (VATS) in re-operations for post-operative hemothorax. Methods: The clinical data of patients underwent re-operations due to post-operative hemothorax after pulmonary resection in Shanghai Pulmonary Hospital from 2006 to 2018 were retrospectively analysed. The incidence of re-operations were analyzed. The mortality and morbidity were compared between thoracotomy and thoracoscopic procedure for re-exploration. Results: A total of 114 patients were included. The annual incidence rate ranged from 0.21 to 0.54%; the perioperative mortality was 2.6%; there were 114 cases of re-operations for hemothorax after 2012, including 62 cases in thoracoscopy group and 52 cases in open group. The durations of chest-tube drainage (7.2 ± 3.9 days vs 10.9 ± 12.0 days, P = 0.001) and length of stay in hospital (13.7 ± 6.7 days vs 18.9 ± 10.6 days, P = 0.002) in the thoracoscopic group were shorter than those in the open group. The thoracoscopic group had fewer post-operative complications as well (P = 0.023). Meanwhile, post-operative complications in the delayed group were significantly higher than those in the non-delayed group, with a longer length of hospital stay and higher hospitalization costs. Conclusion: Complete VATS is safe and feasible for re-operation due to post-operative hemothorax and can be an alternative to thoracotomy. Delayed re-operations are associated with more post-operative complications and higher costs. [ABSTRACT FROM AUTHOR]

Simple Summary: According to reports from more than a decade ago, the proportion of primary salivary gland-type carcinoma (SGC) among all lung cancers is only 0.1–1.0% and the 5-year overall survival rate is more than 60%. However, previous reported studies mostly had small sample sizes due to the low proportion of primary SGC in lung cancer. The characteristics of SGC proportion and prognosis have not yet been elucidated. The aim of this study was to elucidate the clinical and prognostic characteristics of primary SGC. This study found that lung SGC has the best prognosis among adenocarcinoma, squamous cell carcinoma, and SGC. In addition, lobectomy can further improve the prognosis of SGCs. This study aimed to explore the clinical and prognostic characteristics of primary salivary gland-type carcinoma (SGC). The entire cohort from the Surveillance, Epidemiology, and End Results database was used to calculate the SGC proportion. In total, 253,096 eligible patients, including 165,715 adenocarcinomas (ADCs), 87,062 squamous cell carcinomas (SCCs), and 319 SGCs, were selected to perform survival analyses. The data of 42 SGC patients from our hospital showed postoperative survival. Overall survival (OS) curves for different histological and surgical types were presented. The proportion of primary SGCs was 0.8 per 1000 patients. Patients with age ≤ 64 years old had a much higher proportion of SGC than those patients with age >64 years old. After adjusting for other confounders, among ADCs, SCCs, and SGC, SGCs had the best prognosis (HR 0.361, p < 0.001). Moreover, the 5-year OS rates of SGC patients were 55% and 7% in the group with surgery or without surgery, respectively (p < 0.001). The data of 42 patients from our hospital also showed a good survival of SGCs. Lobectomy improved the survival of SGCs significantly (adjusted HR 0.439, p = 0.016). In conclusion, pulmonary SGCs had the best prognosis among ADCs, SCCs, and SGCs. In addition, lobectomy could further improve the prognostic outcomes of SGCs. [ABSTRACT FROM AUTHOR]

Simple Summary: The therapeutic effect of postoperative radiotherapy for small-cell lung cancer (SCLC) patients with limited stage remained unclear. The aim of this retrospective study was to construct and validate a nomogram to assess the prognosis of small-cell lung cancer patients followed surgery in a large cohort (882 patients) which involved patients from Shanghai Pulmonary Hospital and the Surveillance, Epidemiology and End Results database. The nomogram derived from the training cohort achieved good predictive ability and could discriminate low- and high-risk subgroups in four cohorts. Postoperative radiotherapy promoted survival for high-risk patients but had little effect on low-risk patients. Moreover, by subgroup analysis based on the N stage, we suggested that N2 patients in the high-risk subgroup could benefit more from postoperative radiotherapy. Therefore, our nomogram might help with clinical decisions on the strategy of postoperative radiotherapy for SCLC patients. This study constructed and validated a prognostic model to evaluate the survival of small-cell lung cancer (SCLC) patients following surgery, and shed light on the strategy of postoperative radiotherapy. A total of 882 patients from Shanghai Pulmonary Hospital and the Surveillance, Epidemiology and End Results database after lung resection were selected. Multivariable Cox analysis was used to identify the indicators affecting long-term survival in patients. A nomogram was constructed to predict the prognosis of eligible patients. Indices of concordance (C-index) was used to access the predictive ability of cancer-specific survival (CSS) for the prognostic model. CSS discrimination in the prognostic model was comparable in the training and validation cohorts (C-index = 0.637[NORAD-T], 0.660[NORAD-V], 0.656[RAD] and 0.627[our hospital], respectively. Stratification based on the cutoff value of the nomogram yielded low- and high-risk subgroups in four cohorts. For patients in the high-risk group, postoperative radiotherapy was considered a survival-promoting strategy (unadjusted HR 0.641, 95% CI 0.469–0.876, p = 0.0046). In the low-risk group, however, the implementation of radiotherapy barely had an influence on CSS. In conclusion, the nomogram we constructed and validated could predict the prognosis of SCLC patients followed surgery and identify high-risk patients who were likely to benefit from postoperative radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: This study was to explore the difference and significance of parietal pleura invasion and rib invasion in pathological T classification with non-small cell lung cancer. Methods: A total of 8681 patients after lung resection were selected to perform analyses. Multivariable Cox analysis was used to identify the mortality differences in patients between parietal pleura invasion and rib invasion. Eligible patients with chest wall invasion were re-categorized according to the prognosis. Cancer-specific survival curves for different pathological T (pT) classifications were presented. Results: There were 466 patients considered parietal pleura invasion, and 237 patients served as rib invasion. Cases with rib invasion had poorer survival than those with the invasion of parietal pleura (adjusted hazard ratio [HR]= 1.627, P =0.004). In the cohort for parietal pleura invasion, patients with tumor size ≤5cm reached more satisfactory survival outcomes than patients with tumor size >5cm (unadjusted HR =1.598, P =0.006). However, there was no predictive difference in the cohort of rib invasion. The results of the multivariable analysis revealed that the mortality with parietal pleura invasion plus tumor size ≤5cm were similar to patients with classification pT3 (P =0.761), and patients for parietal pleura invasion plus tumor size >5cm and pT4 had no stratified survival outcome (P =0.809). Patients identified as rib invasion had a poorer prognosis than patients for pT4 (P =0.037). Conclusions: Rib invasion has a poorer prognosis than pT4. Patients with parietal pleura invasion and tumor size with 5.1-7.0cm could be appropriately up-classified from pT3 to pT4. [ABSTRACT FROM AUTHOR]

Background: The postoperative survival effect of the number of examined lymph nodes on patients of R0-resected esophageal squamous cell carcinoma with pathological stage T1-3N0M0 is still unclear.Methods: Patients diagnosed with pathological stage T1-3N0M0 esophageal squamous cell carcinoma from two cancer databases-our cancer center (N = 707), and Surveillance Epidemiology and End Results (N = 151). The primary clinical endpoint was overall survival. The X-tile software was used to determine the optimal cutoff value of the number of examined lymph nodes, and propensity score matching was conducted to reduce selection bias according to the results of X-tile software. The cohort of 151 patients from another database was used for validation.Results: X-tile software provided an optimal cutoff value of 15 examined lymph nodes based on 707 patients, and 231 pairs of matched patients were included. In the unmatched cohort, Cox proportional hazard regression analysis revealed better overall survival in patients with more than 15 examined lymph nodes (adjusted hazard ratio, 0.566, 95% confidence interval, 0.445-0.720; p < 0.001) compared with patients with 15 or fewer examined lymph nodes. In the validation cohort, patients with more than 15 examined lymph nodes also had better overall survival (adjusted hazard ratio 0.665, p = 0.047).Conclusions: The number of examined lymph nodes is a significant prognostic factor in esophageal squamous cell carcinoma patients with pathological stage T1-3N0M0, and more than 15 examined lymph nodes are associated with better overall survival. Although the difference is not significant, the survival curve of patients with examined lymph nodes > 30 is better than those with examined lymph nodes 15-30. We believe that the number of examined lymph nodes can provide prognostic guidance for those patients, and the more examined lymph nodes cause lesser occult lymph nodes metastasis and lead to a better prognosis. Therefore, surgeons and pathologists should try to examine as many lymph nodes as possible to evaluate the pathological stage precisely. However, we need more validation from other studies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the incidence and long-term survival outcomes of occult lung cancer between 2004 and 2015.Methods: A total of 2958 patients were diagnosed with occult lung cancer in the 305,054 patients with lung cancer. The entire cohort was used to calculate the crude incidence rate. Eligible 52,472 patients (T1-xN0M0, including 2353 occult lung cancers) were selected from the entire cohort to perform survival analyses after translating T classification according to the 8th TNM staging system. Cancer-specific survival curves for different T classifications were presented.Results: The crude incidence rate of occult lung cancer was 1.00 per 100 patients, and it was reduced between 2004 and 2015 [1.4 per 100 persons in 2004; 0.6 per 100 persons in 2015; adjusted risk ratio = 0.437, 95% confidence interval (CI) 0.363-0.527]. In the survival analysis, there were 2206 death events in the 2353 occult lung cancers. The results of the multivariable analysis revealed that the prognoses with occult lung cancer were similar to patients with stage T3N0M0 (adjusted hazard ratio = 1.054, 95% CI 0.986-1.127, p = 0.121). Adjusted survival curves presented the same results. In addition, adjusted for other confounders, female, age ≤ 72 years, surgical treatment, radiotherapy, adenocarcinoma, and non-squamous and non-adenocarcinoma non-small cell carcinoma were independent protective prognostic factors (all p < 0.05).Conclusions: Occult lung cancer was uncommon. However, the cancer-specific survival of occult lung cancer was poor, therefore, we should put the assessment of its prognoses on the agenda. Timely surgical treatment and radiotherapy could improve survival outcomes for those patients. Besides, we still need more research to confirm those findings. [ABSTRACT FROM AUTHOR]

Objectives: To construct a simplified prognostic risk model to predict overall survival after adjuvant radiotherapy for parotid gland carcinoma patients with stage T1-4aN1-3M0. Materials and Methods: We evaluated 879 patients who were pathological diagnosed as stage T1-4aN1-3M0 parotid gland cancer. Those eligible patients treated with parotidectomy and neck lymph node dissection between 2004 and 2015 in the Surveillance Epidemiology and End Results database. All cases received adjuvant radiotherapy. Independent prognostic factors included in the original model were identified by Cox regression analysis. The primary endpoint was overall survival. The model's prediction power was evaluated by the concordance index. The entire cohort was categorized into new low- and high-risk groups using X-tile software according to the results of prognostic model. Kaplan-Meier method was used to depict the survival curves. And the statistical significance was determined by log-rank test. Besides, a heat map was visually described the association between the survival time and 2 most significant prognostic factors. Results: In the univariable and multivariate analyses, 4 independent factors for overall survival were age, tumor size, pTNM stage, and the number of positive lymph nodes, which were all selected in the parsimonious prognostic model. The concordance indices of the prognostic model and pTNM stage were 0.652 and 0.565, respectively. Patients in the low-risk group had better overall survival over patients in the high-risk group [unadjusted hazard ratio = 2.578, 95% confidence interval 2.095-3.172, P < 0.001]. The results of the heat map revealed that patients with smaller tumor size and fewer positive lymph nodes had much longer survival time. Conclusions: This parsimonious prognostic model could estimate the long-term survival after adjuvant radiotherapy for parotid gland carcinoma with stage T1-4aN1-3N0M0. The tools may be valuable to guide multidisciplinary team in making treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Hematological indicators and clinical characteristics play an important role in the evaluation of the progression and prognosis of thymic epithelial tumors. Therefore, we aimed to combine these potential indicators to establish a prognostic nomogram to determine the relapse-free survival (RFS) of patients with thymic epithelial tumors undergoing thymectomy.Methods: This retrospective study was conducted on 156 patients who underwent thymectomy between May 2004 and August 2015. Cox regression analysis were performed to determine the potential indicators related to prognosis and combine these indicators to create a nomogram for visual prediction. The prognostic predictive ability of the nomogram was evaluated using the consistency index (C-index), receiver operating characteristic (ROC) curve, and risk stratification. Decision curve analysis was used to evaluate the net benefits of the model.Results: Preoperative albumin levels, neutrophil-to-lymphocyte ratio (NLR), T stage, and WHO histologic types were included in the nomogram. In the training cohort, the nomogram showed well prognostic ability (C index: 0.902). Calibration curves for the relapse-free survival (RFS) were in good agreement with the standard lines in training and validation cohorts.Conclusions: Combining clinical and hematologic factors, the nomogram performed well in predicting the prognosis and the relapse-free survival of this patient population. And it has potential to identify high-risk patients at an early stage. This is a relatively novel approach for the prediction of RFS in this patient population. [ABSTRACT FROM AUTHOR]

Currently, the incidence of esophageal squamous cell carcinoma (ESCC) in China is high and its prognosis is poor. To evaluate the prognosis of patients with ESCC, we performed computerized quantitative analyses on diagnostic computed tomography (CT) and digital histopathological slices. A retrospective study was conducted to assess the prognosis of ESCC in 153 patients who underwent esophagectomy, and the cohort was selected based on strict clinical criteria. Each patient had an enhanced CT image, and there were two imaging protocols for CT images of all patients. Each patient in the cohort also had a histopathological tissue slide after hematoxylin–eosin staining. Under an electron microscope, the tissue slide was scanned as an image of large size. We then performed quantitative analyses to identify factors related to the prognosis of ESCC on digital histological images and diagnostic CT images. For CT images, we used the radiomics method. For histological images, we designed a set of quantitative features based on machine learning algorithms, such as K-means and principal component analysis. These features describe the patterns of different cell types in histopathological images. Subsequently, we used the survival analysis model established using only CT image features as the baseline. We also compared multiple machine learning models and adopted a five-fold cross-validation method to establish a robust survival model. In establishing survival models, we first used CT image features to establish survival models, and the C-index from the Weibull Cox model on the test set reached 0.624. Then we used histopathlogical features to establish survival models, and the C-index from the Weibull Cox model on the test set reached 0.664, which was obviously better than CT's. Lastly, we combined CT image features and histopathological image features to establish survival models. The performance was better than that in the models built using only CT image features or histopathological image features, and the C-index from the regularized Cox model on the test set reached 0.694. We also proved the effectiveness of the quantified histopathological image features in terms of prognosis using the log-rank test. Histopathological image features are more relevant to prognosis than features extracted from CT images using radiomics. The results of this study provide clinicians with a reference to improve the survival rate of patients with ESCC after surgery. These results have implications for advancing the process of explaining the poor prognosis of esophageal cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients. Methods: We retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy. Results: Five PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all p<0.05). Using Model D, we stratified patients into low- and high-risk groups. The 3-year overall survival rates of low- and high-risk patients were 38.0% and 25.0%, respectively (p<0.001). Conclusion: Quantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups. [ABSTRACT FROM AUTHOR]

Background: To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS).Methods: Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion.Results: Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort).Conclusion: Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: For patients with stage IA non-small cell lung cancer (NSCLC) with tumor size ≤ 2 cm, the prognostic significance of the number of removed lymph nodes (NLNs) through different surgical methods remains unclear. To determine the association of NLNs with cancer-specific survival (CSS) and overall survival (OS) in patients with stage IA NSCLC with tumor size ≤ 2 cm who underwent different lung surgeries. Methods: We retrospectively enrolled 7293 patients from the Surveillance, Epidemiology and End Results database. Median NLNs was used to classify the patients into two groups: group A with NLNs ≤ 5 and group B with NLNs > 5. Propensity score matching (PSM) was performed to decrease selection bias. Kaplan–Meier analysis and Cox regression analysis were performed to identify the association between NLNs and survival outcomes. Results: Group B had better survival than group A in the unmatched cohort and matched cohort (all P < 0.05). Multivariable analyses revealed that the NLNs significantly affected CSS and OS of eligible cases in the unmatched cohort and matched cohort. Additionally, we found that the NLNs was a protective prognostic predictor of OS for patients who underwent wedge resection, segmental resection, or lobectomy. Conclusion: The NLNs was a protective prognostic factor in NSCLC patients with tumor size ≤ 2 cm. We demonstrated that patients with > 5 NLNs in the cohort of wedge resection, segmental resection, or lobectomy exhibited a significantly better OS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the significance of preoperative levels of squamous cell carcinoma antigen (SCC-Ag) and albumin on the cancer-specific survival (CSS) of patients with stage T1-3N0M0 in esophageal squamous cell cancer (ESCC).Methods: The data of 308 patients who underwent esophagectomy between 1996 and 2011 were analyzed. SCC-Ag and albumin levels were measure 1 week before surgery. The optimal cutoff levels of SCC-Ag and albumin were determined using the X-Tile software, which were 1.0 μg/L and 39.8 g/L, respectively. The associations between SCC-Ag and albumin levels and clinicopathological characteristics were assessed using the χ2 test, Student's t-test and Fisher's exact test. Cox univariable and multivariable analyses were computed to identify SCC-Ag and albumin levels as independent prognostic factors related to the CSS of patients with ESCC. We used the Kaplan-Meier survival curve to determine the significance of SCC-Ag and albumin level on ESCC in the long-term follow-up.Results: The 5-year CSS rate for the entire cohort was 65.0%. There was a significant difference in CSS between the low and high SCC-Ag level groups (hazard ratio [HR], 1.828, 95% confidence interval [CI], 1.203-2.778; P = 0.005). Patients with ESCC with low albumin level had a worse CSS than those with high albumin level (HR, 0.540; 95% CI, 0.348-0.838; P = 0.006). Patients with both high SCC-Ag and low albumin levels had worse 5-year CSS than patients with low SCC-Ag and high albumin levels (P < 0.05).Conclusions: Preoperative serum SCC-Ag and albumin levels can predict survival in patients ESCC with stage T1-3N0M0. Patients with ESCC with high SCC-Ag and low albumin levels may have a poor survival outcome. [ABSTRACT FROM AUTHOR]

Objective: To assess the postoperative prognosis of patients with stage IB non-small cell lung cancer (NSCLC), using a prognostic model (PM). Methods: Patients with stage IB of NSCLC from the two academic databases {the Surveillance, Epidemiology, and End Results [SEER-A, N = 1,746 (training cohort)], Sun Yat-sen University Cancer Center [SYSUCC, N = 247 (validation cohort)], and SEER-B (N = 1,745)} who had undergone lung surgery from 2001 to 2015 were enrolled. The primary clinical endpoint was cancer-specific survival (CSS). Covariate inclusion of prognostic indicators was carried out using a multivariable two-sided P < 0.05. We identified and integrated significant prognostic factors for survival in the training cohort to build a model that could be validated in the validation cohort. We used univariate analysis to evaluate the utilized ability of PM in the different races/ethnicities. Results: CSS discrimination in the PM was comparable in both the training and validation cohorts [C index = 0.66(SEER-A), 0.67(SYSUCC), and 0.61(SEER-B), respectively]. Discretization with a fixed PM cutoff of 291.5 determined from the training dataset yielded low- and high-risk subgroups with disparate CSS in the validation cohort (training cohort: hazard ratio [HR] 2.724, 95% confidence intervals [CI], 2.074–3.577; validation cohort: SEER-B HR 1.679, 95% CI, 1.310–2.151, SYSUCC HR 3.649, 95% CI 2.203–6.043, all P < 0.05). Our five-factor PM was able to predict CSS; 48-month CSS was 87% in the low-risk subgroup vs. 69% in the high-risk subgroup for the training cohort, while in the validation cohort, they were 80 vs. 73%(SEER-B) and 84 vs. 60% (SYSUCC), respectively. In addition, the results showed that PM with all unadjusted HR > 1 was a significant risk prognostic indictor in white men (P < 0.001), Chinese people (P < 0.001), and other races (P = 0.012). Conclusion: We established and validated a PM that may predict CSS for patients with IB NSCLC in different races/ethnicities, and thus, help clinicians screen subgroups with poor prognosis. In addition, further prospective studies and more cases from different regions are necessary to confirm our findings. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC. Patients and Methods: MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients' tissues and serum were detected by qRT-PCR, and their correlation with patients' pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report. Results: The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ≥ 3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and β-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level. Conclusion: Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC. [ABSTRACT FROM AUTHOR]

The stems of Dendrobium officinale Kimura et Migo (Dendrobii Officinalis Caulis) have a high medicinal value as a traditional Chinese medicine (TCM). Because of the limited supply, D. officinale is a high priced TCM, and therefore adulterants are commonly found in the herbal market. The dried stems of a closely related Dendrobium species, Dendrobium devonianum Paxt., are commonly used as the substitute; however, there is no effective method to distinguish the two Dendrobium species. Here, a high performance liquid chromatography (HPLC) method was successfully developed and applied to differentiate D. officinale and D. devonianum by comparing the chromatograms according to the characteristic peaks. A HPLC coupled with electrospray ionization multistage mass spectrometry (HPLC-ESI-MS) method was further applied for structural elucidation of 15 flavonoids, 5 phenolic acids, and 1 lignan in D. officinale. Among these flavonoids, 4 flavonoid C-glycosides were firstly reported in D. officinale, and violanthin and isoviolanthin were identified to be specific for D. officinale compared with D. devonianum. Then, two representative components were used as chemical markers. A rapid and reliable high performance thin layer chromatography (HPTLC) method was applied in distinguishing D. officinale from D. devonianum. The results of this work have demonstrated that these developed analytical methods can be used to discriminate D. officinale and D. devonianum effectively and conveniently. [ABSTRACT FROM AUTHOR]