Prognostic Analysis of Lung Cancer With Brain Metastases in Elderly Patients: A Multicenter Retrospective Study

Elderly patients with early stage T pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis for distant metastasis (DM). In this study, we aimed to construct and validate a novel nomogram for predicting distant metastasis and prognosis in elderly patients with T1-T2 PDAC. In this study, patients diagnosed with pancreatic ductal adenocarcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2017. Univariate and multivariate logistic regression analyses were used to determine independent risk factors for distant metastasis in elderly patients with T1-T2 PDAC. Univariate and stepwise multivariate Cox regression analyses were used to determine independent prognostic factors in elderly patients with T1-T2 PDAC. two novel nomograms were developed, and the results were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Multivariate logistic regression analysis demonstrated that the independent risk factors for DM in elderly patients with T1-T2 PDAC included primary site, grade, N stage, T stage and sex. Stepwise multivariate Cox regression analysis indicated that age, grade, primary site, tumour size, liver metastasis, surgery and chemotherapy were independent prognostic factors. The performance of the two prediction models was further validated by the analysis of the ROC curves of the training and validation sets, calibration, DCA and Kaplan-Meier (K-M) survival curves, which confirmed their capacity to accurately predict the risk and prognosis of DM in elderly patients with T1-T2 PDAC. The two nomograms are expected to serve as effective tools for predicting the risk of DM in elderly patients with T1-T2 PDAC and for providing personalized prognosis prediction in elderly T1-T2 PDAC patients with DM, which may significantly improve clinical decision-making and patient management.

Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut-off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan-Meier method, and significant differences were evaluated by the log-rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early-stage disease (stage 0-II) for sensitivity analysis. Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19-9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p < 0.05). These prognostic factors were used to establish and verify the OS nomogram. Poorer OS was linked to higher RDW (HR = 1.52; 95% CI, 1.11-2.08; p < 0.01) and ΔRDW (HR = 1.65; 95% CI, 1.19-2.28; p < 0.01) in all-stage patients, and was only linked to higher RDW in early-stage patients. In competing risk model, H-RDW and H-ΔRDW were confirmed to be independent risk factors for CSS in CRC patients. High preoperative RDW and ΔRDW are both risk factors for OS and CSS in CRC.

Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

It remains controversial whether elderly patients with transverse colon cancer present worse prognoses. Our study utilized evidence from multi-center databases to evaluate the perioperative and oncology outcomes of radical resection of colon cancer in elderly and nonelderly patients. In this study, we analyzed 416 patients with transverse colon cancer who underwent radical surgery from January 2004 to May 2017, including 151 elderly (aged ≥ 65 years) and 265 nonelderly (aged < 65 years) patients. We retrospectively compared the perioperative and oncological outcomes between these 2 groups. The median follow-up in the elderly and nonelderly groups was 52 and 64 months, respectively. There were no significant differences in the overall survival (OS) (P = .300) and disease-free survival (DFS) (P = .380) between the elderly and nonelderly groups. However, the elderly group had longer hospital stays (P < .001), a higher complication rate (P = .027), and fewer lymph nodes harvested (P = .002). The N classification and differentiation were significantly associated with OS based on univariate analysis, and the N classification was an independent prognostic factor for OS based on multivariate analysis (P < .05). Similarly, the N classification and differentiation were significantly correlated with the DFS based on univariate analysis. However, multivariate analysis indicated that the N classification was an independent prognostic factor for DFS (P < .05). In conclusion, the survival and surgical outcomes in elderly patients were similar to nonelderly patients. The N classification was an independent factor for OS and DFS. Even though elderly patients with transverse colon cancer present a higher surgical risk than nonelderly patients, performing radical resection in elderly patients can be an appropriate choice for treatment.

The Immunohistochemical Profile and Other Prognostic Factors In Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Pineoblastoma: prognostic factors and survival outcomes in young children.

9569 Background: Mucosal melanoma is rare and associated with extremely poor prognosis. Little is known about its outcome and prognostic analysis. In this study, we evaluated prognostic factors among mucosal melanomas. Methods: The survival rates, Relapse Free Survival (RFS), Overall Survival (OS) and prognostic factors were compared for 706 mucosal melanomas at different anatomical sites. Results: Mucosal melanoma from nasal pharyngeal and oral (268 pts), upper and lower gastrointestinal (GI) (221 pts), gynecological and urological (196 pts) had a similar survival with a 1-y survival rate (88%, 83%, 86%), 2-y survival rate (66%, 57%, 61%), 5-y survival rate (27%, 16%, 20%), respectively. Multivariate analysis revealed that Depth of Invasion (p &lt; 0.001), Lymph node metastases (p &lt; 0.001), Distant metastases (p &lt; 0.001) were three independent prognostic factors for OS among 706 pts. Anatomical site (p = 0.031), Depth of Invasion (p &lt; 0.001), Lymph node metastases (p &lt; 0.001) were three independent prognostic factors for RFS among 543 pts. KPS status, Depth of Invasion, Lymph node metastases, Distant metastases were independent factors for OS among nasal pharyngeal and oral pts. Depth of Invasion, Lymph node metastases, CKIT Mutation were independent factors for RFS among nasal pharyngeal and oral pts. Gender, Lymph node metastases, Distant metastases were independent factors for OS among GI pts. Gender, Depth of Invasion, Lymph node metastases were independent factors for RFS among GI pts. Lymph node metastases, Distant metastases were independent factors for OS among Gynecological and Urological pts. Depth of Invasion, Lymph node metastases were independent factors for RFS among Gynecological and Urological pts. Conclusions: This is the first prognostic analysis for mucosal melanoma with the largest sample size for the first time. with few exceptions, It revealed that Depth of Invasion, Lymph node metastases, Distant metastases were independent prognostic factors for OS, Depth of Invasion and Lymph node metastases were independent prognostic factors for RFS. These results should be incorporated into the establishment of stage system and design of future clinical trials involving patients with mucosal melanoma.

Immune checkpoint inhibitors (ICIs) are widely used to treat local or metastatic lung cancer. However, the efficacy of ICI in patients with brain metastases (BM) from lung cancer is unknown. This study aimed to evaluate the efficacy of PD-1/PD-L1 ICIs compared with chemotherapy for patients with lung cancer with BM. Electronic databases (PubMed, Embase, The Cochrane Library, and Web of Science) were searched. The meta-analysis assessed overall survival (OS) and progression-free survival (PFS) of the PD-1/PD-L1 inhibitors axis and its relationship with pathological type, drug modality, and the treatment line number in patients with BM from lung cancer. We included 694 patients with BM from lung cancer from 11 randomized controlled trials. Statistical analysis showed that compared with chemotherapy, PD-1/PD-L1 inhibitors could significantly prolong OS (hazard ratio (HR) = 0.75, 95%confidence interval (95%CI) = 0.51–0.99) and PFS (HR = 0.65, 95%CI = 0.51–0.80). In the subgroup analysis, ICIs plus chemotherapy improved PFS (HR = 0.60, 95%CI = 0.40–0.80), but not OS (HR = 0.75, 95%CI = 0.30–1.19). The efficacy of ICI monotherapy in patients with BM was significantly different between OS and PFS: OS pooled HR = 0.81 (95%CI = 0.57–1.05) and PFS = 0.78 (95%CI = 0.62–0.94). Among different pathological types, the OS pooled HR was 0.67 (95%CI = 0.39–0.95) for non-small cell lung cancer (NSCLC) and 0.94 (95%CI = 0.56–1.33) for small cell lung cancer (SCLC); the PFS pooled HR was 0.58 (95%CI = 0.39–0.76) for NSCLC and 0.79 (95%CI = 0.65–0.93) for SCLC. Subgroups analysis of treatment line showed that no advantage for OS with ICIs as first-line or subsequent-line therapy, whereas ICIs as first-line (HR = 0.63, 95%CI = 0.53–0.74) and second-line (HR = 0.62, 95%CI = 0.62–0.96) benefitted PFS. This meta-analysis implied that compared with chemotherapy, PD-1/PD-L1 inhibitors significantly improved efficacy treatment of patients with BM from lung cancer. Further studies are needed to confirm the role of ICIs in different pathological types and drug treatment modalities.

BackgroundMethyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).MethodsSpecimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson’s or Spearman’s chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.ResultsWe found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR− MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II–IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).ConclusionOur findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

BackgroundThe prolonged survival of individuals diagnosed with cancer has led to an increase in the number of secondary primary malignancies. We undertook to perform a definitive study to characterize and predict prognosis of multiple primary malignancies (MPM) involving hepatocellular carcinoma (HCC), due to the scarcity of such reports.MethodsClinicopathological data were analyzed for 68 MPM patients involving HCC, with 35 (target group) underwent curative liver resection. Additional 140 HCC-alone patients with hepatectomy were selected randomly during the same period as the control group.ResultsOf the 68 patients with extrahepatic primary malignancies (EHPM), 22 were diagnosed synchronously with HCC, and 46 metachronously. The most frequent EHPM was nasophargeal carcinoma, followed by colorectal and lung cancer. Univariate analysis demonstrated that synchronous (P = 0.008) and non-radical treatment for EHPM (P < 0.001) were significant risk factors associated with poorer overall survival (OS). While, Cox modeling revealed that the treatment modality for EHPM, but not the synchronous/metachronous determinant, was an independent factor for OS, and that therapeutic option for HCC was an independent factor for HCC-specific OS. Moreover, no HCC-specific overall and recurrence-free survival benefit were observed in the control group when compared with that of the target group (P = 0.607, P = 0.131, respectively).ConclusionsCurative treatment is an independent predictive factor for OS and HCC-specific OS, and should been taken into account both for synchronous and metachronous patients. MPM patients involving HCC should not be excluded from radical resection for HCC.

BackgroundBrain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice.MethodsA total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan–Meier method and Cox proportional hazards models.ResultsThe median time from diagnosis of EC to BM was 11.8 months (0–249.2 months). The median overall survival (OS) was 4.8 months (1.13–23.3 months), with 20% of patients achieving the 1‐year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score<70 (8.4 vs. 3.9 months, p = 0.033). Compared to patients without brain radiotherapy, patients with brain radiotherapy showed better outcomes in both median OS (8.4 vs. 2.9 months) and 1‐year survival rate (23.1% vs. 14.3%, p = 0.043). The median OS of patients with radiotherapy combined with chemotherapy and/or targeted therapy and radiotherapy alone was 9.7 months (3.4–23.3 months) and 7.2 months (1.7–18.4 months), respectively, with no significant difference between the two groups (p = 0.215).ConclusionsBrain radiotherapy provided clinically meaningful survival benefit for elderly patients with BM from EC. Thus, active treatments for those patients might be required.

Objective To determine long-term survival of 214 patients of lung cancer with brain metastases and to detect the potential prognostic factors.Methods A retrospective review was pedormed evaluating patients diagnosed as lung cancer with brain metastasis from Jan 1992 to Dec 2001 at Zhejiang Cancer Hospital.Two hundred and fourteen cases were enrolled.All hospital records were thoroughly reviewed in a retrospective manner.The management of the brain metastases were as follows: 8 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT); 2 cases received resection and chemotherapy; 10 had resection alone; 10 underwent WBRT alone,36 had chemotherapy alone; 15 received the combination of resection,chemotherapy and WBRT; 104 were performed with chemotherapy combined with WBRT; 29 had only supportive care.Survival time was measured from the date of the first treatment for malignancy to the date of death or the last follow-up.Seven further potential prognostic factors were investigated for survival including age,gender,T or N status,number of extra cranial metastases,pathological type and treatment modality.Statistical analysis was performed using the Kaplan-Meier method and Cox-regression analysis.Results The overall median survival time was 10 months (95% CI9.06--10.94) and the 1,3,5 year survival rates were 7.46%,1.14% and 0,respectively.In the univariate model,none of the following variables had effect on survival: age,gender,T stage of the tumor,nodal status,number of extra cranial metastases and histological type.Univariate analysis showed a better survival for the combination of surgical resection,chemotherapy and radiation (P=0.00).Based on Cox-regression analysis,treatment modality was the only independent predictor of survival Conclusions Aggressive combined therapy of brain metastases may achieve a survival advantage.Excellent overall survival of lung cancer with brain metastases has been achieved with a combination of WBRT with surgical resection and chemotherapy. Key words: Lung neoplasms; Brain neoplasms; Neoplasm metastasis; Prognosis

Validation of the Score Index for Radiosurgery (SIR) in Predicting Survival of Patients With Brain Metastases Submitted to Radiosurgery

BackgroundSeveral studies investigated the utility of inflammation and nutritional markers in predicting the prognosis in patients with gastric cancer; however, the markers with the best predictive ability remain unclear. This retrospective study aimed to determine inflammation and nutritional markers that predicted prognosis in elderly patients over 75 years of age undergoing curative gastrectomy for gastric cancer.MethodsBetween January 2005 and December 2015, 497 consecutive elderly gastric cancer patients aged over 75 years underwent curative gastrectomy in 12 institutions. The geriatric nutritional risk index (GNRI), prognostic nutritional index, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and C-reactive protein/albumin ratio were examined as prognostic markers for overall survival (OS) and disease-specific survival (DSS) using area under the curve (AUC) using receiver operating characteristic (ROC) curve analysis.ResultsThe GNRI had the highest AUC and predictive value for both OS (0.637, p < 0.001) and DSS (AUC 0.645, p < 0.001). The study cohort was categorized into the high and low GNRI groups based on the optimal GNRI cut-off values for OS (97.0) and DSS (95.8) determined with the ROC analysis. For both OS and DSS, there was a significant correlation between the GNRI and several clinicopathological factors including age, body mass index, albumin, American Society of Anesthesiologists physical status score, depth of tumor invasion, lymph node metastasis, lymphatic invasion, pathological stage, operation duration, bleeding, procedure, approach, death due to primary disease, and death due to other disease. The GNRI remained a crucial independent prognostic factor for both OS (Hazard ratio [HR] = 1.905, p < 0.001) and DSS in multivariate analysis (HR = 1.780, p = 0.043).ConclusionsAmong a panel of inflammation and nutritional markers, the GNRI exhibited the best performance as a prognostic factor after curative gastrectomy in elderly patients with gastric cancer, indicating its utility as a simple and promising index for predicting OS and DSS in these patients.

Non-small-cell lung cancer (NSCLC) is associated with a high incidence of brain metastasis (BM), and the prognosis of patients with NSCLC and BM is poor. This study aimed to identify the prognostic factors and elucidate the survival rates of Japanese patients with NSCLC and BM at initial diagnosis. HOT 1701 is a retrospective multicenter study of patients with NSCLC and BM at initial diagnosis. The medical records of all consecutive patients diagnosed with advanced or recurrent NSCLC and BM at 14 institutions of the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) in Japan were reviewed. The participants were categorized based on the presence or absence of driver mutations. The Kaplan-Meier method was used to estimate median overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors in these patients. Among 566 patients with NSCLC and BM, the median OS was 11.8 months. Patients with driver mutations survived longer than those without driver mutations. The univariate and multivariate analyses revealed 6 independent prognostic factors: age ≥65 years, poor performance status, T factor, absence of driver gene mutations, presence of extracranial metastases, and number of BM. According to the prognostic score based on these 6 factors, the patients were stratified into 3 risk groups: low-, intermediate-, and high-risk, with median OS of 27.8, 12.2, and 2.8 months, respectively. We developed a new prognostic model for patients with NSCLC and BM, which may help determine prognosis at diagnosis.