Independent Risk Factor For Overall Survival Research Articles

Prognostic analysis of patients with stage IIIC1p cervical cancer treated by surgery

BackgroundCervical cancer (CC) is one of the most common gynaecologic malignancies. The prognosis of stage IIIC1p cervical cancer patients treated by surgery is heterogeneous. Therefore, the aim of this study was to analyse the factors influencing the prognosis in such patients.MethodsFrom January 2012 to December 2017, 102 patients with cervical cancer who underwent surgical treatment in the Department of Gynaecology and Tumours, Changzhou Maternal and Child Health Hospital, and had pelvic lymph node metastasis confirmed by pathology were analysed retrospectively. All patients underwent radical hysterectomy with/without oophorectomy with pelvic lymphadenectomy with/without para-aortic lymphadenectomy. Clinical data was collected including age, surgical method, ovarian status, intraoperative blood loss, perioperative complications, tumour size, pathological type, depth of stromal invasion (DSI), whether the lymphatic vascular space was infiltrated, number of pelvic lymph node metastases, location of pelvic lymph node metastases, total number of lymph nodes resected, lymph node ratio (LNR), nature of vaginal margin, whether parametrium was involved, postoperative adjuvant therapy, preoperative neutrophil–lymphocyte ratio (NLR) and prognostic information of patients. Survival curves for overall survival (OS) and disease-free survival (DFS) were plotted using the Kaplan–Meier method, and the difference between the survival curves was tested using the log-rank test. Univariate and multivariate COX regression models were used to assess the factors associated with overall survival and disease-free survival in patients with stage IIIC1p cervical cancer. Nomogram plots were constructed to predict OS and DFS, and the predictive accuracy of the nomograms was measured by Harrell’s C-index and calibration curves.ResultsA total of 102 patients with stage IIIC1p cervical cancer were included in the study, and the median follow-up time was 63 months (range from 6 to 130 months). The 5-year OS was 64.7%, and the 5-year DFS was 62.7%. Multivariate analysis showed that no postoperative adjuvant therapy, LNR > 0.3 and NLR > 3.8 were independent risk factors for OS and DFS in patients with stage IIIC1p cervical cancer.ConclusionsPatients with stage IIIC1p cervical cancer have a poor prognosis. Lower OS and DFS were associated with no postoperative adjuvant therapy, LNR > 0.3 and NLR > 3.8.

Chemotherapy combined with radiotherapy can benefit more unresectable HCC patients with portal and/or hepatic vein invasion: a retrospective analysis of the SEER database.

The purpose of this study is to evaluate the effects of chemotherapy and radiotherapy on the prognosis of unresectable HCC patients with portal and/or hepatic vein invasion. A retrospective analysis of unresectable HCC patients with portal and/or hepatic vein invasion registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. The propensity score-matching (PSM) method was used to balance differences between groups. Overall survival (OS) and cancer-specific survival (CSS) were the interesting endpoints. OS was calculated from the date of diagnosis to the date of death caused by any cause or the last follow-up. CSS was defined as the interval between the date of diagnosis and date of death due only to HCC or last follow-up. OS and CSS were analyzed by using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model. A total of 2,614 patients were included. 50.2% patients received chemotherapy or radiotherapy and 7.5% patients received both chemotherapy and radiotherapy. Compared to the untreated group, chemotherapy or radiotherapy (COR) (HR = 0.538, 95% CI 0.495-0.585, p < 0.001) and chemotherapy and radiotherapy (CAR) (HR = 0.371, 95% CI 0.316-0.436, p < 0.001) showed better OS. In the COR group, Cox analysis results showed AFP, tumor size, N stage and M stage were independent risk factor of OS. Competing-risk analysis results showed AFP, tumor size and M stage were independent risk factor of CSS. In the CAR group, AFP and M stage were independent risk factors of OS. Competing-risk analysis results showed M stage were independent risk factor of CSS. Kaplan Meier analysis showed chemotherapy combined with radiotherapy significantly improves OS (10.0 vs. 5.0 months, p < 0.001) and CSS (10.0 vs. 6.0 months, p = 0.006) than monotherapy. AFP positive and distant metastasis are the main risk factors affecting OS and CSS of unresectable HCC patients with portal and/or hepatic vein invasion. Chemotherapy combined with radiotherapy significantly improves OS and CSS of unresectable HCC patients with portal and/or hepatic vein invasion.

Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis.

The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In current study, we aim to compare the long-term oncological outcomes of pelvic organ preserving-radical cystectomy (POPRC) versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort. Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and recurrence-free survival (RFS). To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching (PSM) was performed. Among 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After PSM, each cohort included 99 matched patients. The OS (P=0.940), CSS (P=0.957), and RFS (P=0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (HR 0.874, 95% CI 0.592-1.290; P=0.498). The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.

Combination of alpha-fetoprotein and neutrophil-to-lymphocyte ratio to predict treatment response and survival outcomes of patients with unresectable hepatocellular carcinoma treated with immune checkpoint inhibitors

BackgroundImmune-checkpoint inhibitors (ICIs) have revolutionized the treatment of hepatocellular carcinoma (HCC). However, long-term survival outcomes and treatment response of HCC patients undergoing immunotherapy is unpredictable. The study aimed to evaluate the role of alpha-fetoprotein (AFP) combined with neutrophil-to-lymphocyte ratio (NLR) to predict the prognosis and treatment response of HCC patients receiving ICIs.MethodsPatients with unresectable HCC who received ICI treatment were included. The HCC immunotherapy score was developed from a retrospective cohort at the Eastern Hepatobiliary Surgery Hospital to form the training cohort. The clinical variables independently associated with overall survival (OS) were identified using univariate and multivariate Cox regression analysis. Based on multivariate analysis of OS, a predictive score based on AFP and NLR was constructed, and patients were stratified into three risk groups according to this score. The clinical utility of this score to predict progression-free survival (PFS) and differentiate objective response rate (ORR) and disease control rate (DCR) was also performed. This score was validated in an independent external validation cohort at the First Affiliated Hospital of Wenzhou Medical University.ResultsBaseline AFP ≤ 400 ng/ml (hazard ratio [HR] 0.48; 95% CI, 0.24–0.97; P = 0.039) and NLR ≤ 2.77 (HR 0.11; 95% CI, 0.03–0.37; P<0.001) were found to be independent risk factors of OS. The two labolatory values were used to develop the score to predict survival outcomes and treatment response in HCC patients receiving immunotherapy, which assigned 1 point for AFP > 400 ng/ml and 3 points for NLR > 2.77. Patients with 0 point were classified as the low-risk group. Patients with 1–3 points were categorized as the intermediate-risk group. Patients with 4 points were classified as the high-risk group. In the training cohort, the median OS of the low-risk group was not reached. The median OS of the intermediate-risk group and high-risk group were 29.0 (95% CI 20.8–37.3) months and 16.0 (95% CI 10.8–21.2) months, respectively (P < 0.001). The median PFS of the low-risk group was not reached. The median PFS of the intermediate-risk group and high-risk group were 14.6 (95% CI 11.3–17.8) months and 7.6 (95% CI 3.6–11.7) months, respectively (P < 0.001). The ORR and DCR were highest in the low-risk group, followed by the intermediate-risk group and the high-risk group (P < 0.001, P = 0.007, respectively). This score also had good predictive power using the validation cohort.ConclusionThe HCC immunotherapy score based on AFP and NLR can predict survival outcomes and treatment response in patients receiving ICI treatments, suggesting that this score could serve as a useful tool for identification of HCC patients likely to benefit from immunotherapy.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Local resection versus radical resection after neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer: a propensity-score matched cohort analysis

BackgroundWe aimed to address the shortage of evidence regarding the safety of the local resection approach by comparing long-term oncological outcomes between patients managed by local resection and those who underwent radical resection.MethodsThis was a propensity-score matched cohort analysis study that included patients of all ages diagnosed with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) at the Fujian Medical University Union Hospital and Fujian Medical University Affiliated Zhangzhou Hospital, China, between Jan 10, 2011, to Dec 28, 2021. Partial patients with a significant downstage of the tumor were offered management with the local resection approach, and most of the rest were offered radical resection if eligible.FindingsOne thousand six hundred ninety-three patients underwent radical resection after nCRT, and another 60 patients performed local resection. The median follow-up times were 44.0 months (interquartile range = 4–107 months). After propensity-core matching (PSM), in the Kaplan–Meier curves, local resection (n = 56) or radical resection (n = 211) was not significantly associated with 1-, 3-, and 5-year cumulative incidence of overall survival (OS) (HR = 1.103, 95% CI: 0.372 ~ 3.266), disease-free survival (DFS) ((HR = 0.972, 95% CI: 0.401 ~ 2.359), local recurrence (HR = 1.044, 95% CI: 0.225 ~ 4.847), and distant metastasis (HR = 0.818, 95% CI: 0.280 ~ 2.387) (all log-rank P > 0.05). Similarly, multivariate Cox regression analysis indicates that local excision still was not an independent risk factor for OS (HR = 0.863, 95% CI: 0.267 ~ 2.785, P = 0.805) and DFS (HR = 0.885, 95% CI: 0.353 ~ 2.215, p = 0.794).ConclusionLocal resection can be a management option in selected patients with middle-low rectal cancer after nCRT for LARC and without loss of oncological safety at five years.

Comparison of breast-conserving surgery without radiotherapy and mastectomy in the treatment of elderly patients with early breast cancer: A PSM and SEER database study.

At present, there is no research on which surgical method can lead to a better prognosis in elderly patients with early breast cancer. The purpose of this study was to establish a nomogram to predict the survival outcome of elderly patients with early breast cancer and to compare the prognosis of the breast-conserving surgery (BCS) group who did not receive postoperative radiotherapy and the mastectomy group through risk stratification. This study included patients with early breast cancer aged ≥70 years from the Surveillance, Epidemiology, and End Results database (n = 20,520). The group was randomly divided into a development cohort (n = 14,363) and a validation cohort (n = 6157) according to a ratio of 7:3. Risk factors affecting overall survival (OS) and breast-cancer-specific survival (BCSS) were analyzed using univariate and multivariate Cox regression. Present results were obtained by constructing nomograms and risk stratifications. Nomograms were evaluated by the concordance index and calibration curve. Kaplan-Meier curves were established based on BCSS and analyzed using the log-rank test. Multivariate Cox regression results showed that age, race, pathological grade, T and N stages, and progesterone receptor (PR) status were independent risk factors for OS and BCSS in the BCS group and mastectomy group. Subsequently, they were incorporated into nomograms to predict 3- and 5-year OS and BCSS in patients after BCS and mastectomy. The concordance index was between 0.704 and 0.832, and the nomograms also showed good calibration. The results of risk stratification showed that there was no survival difference between the BCS group and the mastectomy group in the low-risk and high-risk groups. In the middle-risk group, BCS improved the BCSS of patients to a certain extent. This study constructed a well-performing nomogram and risk stratification model to assess the survival benefit of BCS without postoperative radiotherapy in elderly patients with early breast cancer. The results of the study can help clinicians analyze the prognosis of patients and the benefits of surgical methods individually.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: A retrospective study.

e15562 Background: There had been no phase III trial to compare the efficacy between trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) with TAS-102 monotherapy in refractory metastatic colorectal cancer (mCRC). Our study sought to investigate the efficacy and safety of TAS-102 plus BEV versus TAS-102 monotherapy in these patients. Methods: We retrospectively analyzed the patients with refractory mCRC who received TAS-102 (35 mg/m2 twice daily; day 1–5 and 8–12; every 28 days) with or without BEV (5 mg/kg; day 1,15; every 28 days) between November 2020 and October 2022 in Hunan Cancer Hospital. All patients had previously received at least second-line treatment. The primary endpoint was overall survival (OS). Results: A total of 58 patients received TAS-102 plus BEV, and another 32 patients received TAS-102 monotherapy. With a median follow-up of 4.60 months (range, 0.20–22.80), the median overall survival (mOS) was 10.83 months [95% confidence interval (CI), 10.10–NA] for TAS-102 plus BEV, 7.43months (95% CI, 5.17–NA) for TAS-102 monotherapy. The hazard ratio (HR) was 0.90 (95% CI, 0.42–1.92), P= 0.78. Median progression-free survival (mPFS) was 4.67 months (95% CI, 3.57–7.37) for TAS-102 plus BEV, and 4.30 months (95% CI, 3.03–NA) for TAS-102 monotherapy. The HR was 1.04 (95% CI, 0.54–1.99), P= 0.91. The Cox multivariate regression analysis demonstrated that the patients who received treatment after TAS-102 with or without BEV(HR:0.25;95% CI, 0.09-0.71) and previously undergone Irinotecan (HR:0.23;95% CI, 0.06-0.95) were independent risk factors for OS and the patients who previously received Cetuximab was confirmed to have a significant better PFS(HR:0.17;95% CI, 0.03-0.91). Of the 70 patients who were evaluated, the TAS-102 plus BEV showed higher ORR and DCR than TAS-102 monotherapy, but the difference was not significant (ORR: 12.2% versus 0%; p= 0.16; and DCR: 77.5% versus 61.9%; p= 0.29). The incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group than the TAS-102 monotherapy group (3.00% vs. 0.00%, p = 0.03), whereas other adverse events were comparable between the two groups. Conclusions: Compared with TAS-102 monotherapy, TAS-102 plus BEV seemed to have comparable safety but improved disease control and prognosis in patients with refractory mCRC, although the difference was not significant. Further prospective studies are still needed to confirm our conclusions. [Table: see text]

Prognostic Significance of Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Hepatocellular Carcinoma.

HALP score consisting of hemoglobin content, albumin content, lymphocyte count, and platelet count can comprehensively evaluate the inflammatory response and nutritional status. Many researchers have indicated that the HALP score is an effective predictor of the overall prognosis of various tumors. However, there is no relevant research to suggest whether the HALP score can predict the prognosis of patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 273 HCC patients who underwent surgical resection. Hemoglobin content, albumin content, lymphocyte count, and platelet count in peripheral blood were measured for each patient. The relationship between the HALP score and overall survival (OS) was investigated. With a mean of 56.69 ± 1.25 months follow-up, the 1-, 3-, and 5-year OS was 98.9%, 76.9%, and 55.3% for all patients, respectively. HALP scores (HR=1.708, 95% CI=1.192-2.448, P=0.004) were significant independent risk factors of OS. The 1-, 3-, and 5-year OS were 99.3%, 84.3%, and 63.4% for patients with high HALP scores; and 98.6%, 69.8%, and 47.5% for patients with low HALP scores, respectively (P=0.018). In TNM I-II stage patients, compared with high HALP scores, low HALP scores have worse OS (P=0.039). In AFP positive patients, compared with high HALP scores, low HALP scores have worse OS (P=0.042). Our research showed the preoperative HALP score is an independent predictive factor of overall prognosis, and a low HALP score indicates a worse prognosis in HCC patients who underwent surgical resection.

Effect of Different Liver Resection Modalities on the Prognosis of Patients with Hepatocellular Carcinoma on the Left Lateral Lobe.

To investigate the effect of different liver resection modalities on the prognosis of left lateral lobe hepatocellular carcinoma (HCC) patients. 315 patients with HCC on left lateral lobe were divided into open left lateral lobectomy (LLL) group (n=249) and open left hepatectomy (LH) group (n=66). The differences in long-term prognosis between two groups were compared. The results showed that narrow resection margin (Hazard Ratio (HR):1.457, 95% Confidential Interval (CI): 1.038-2.047; HR:1.415, 95% CI: 1.061-1.887), tumor diameter > 5 cm (1.645, 1.161-2.330; 1.488, 1.123-1.971), multiple tumors (2.021, 1.330-3.073; 1.987, 1.380-2.861), and microvascular invasion (MVI) (1.753, 1.253-2.452; 1.438, 1.087-1.902) are independent risk factors for overall survival (OS) and tumor recurrence (TR), while liver resection modality is not. After propensity score matching, liver resection modality is not an independent risk factor for OS and TR. Further analysis revealed that wide resection margins were achieved in all patients in the LH group but only 59.0% patients in the LLL group. The OS and TR rates were not significantly different between wide patients with resection margins in LLL group and LH group (P=0.766 and 0.919, respectively), but significantly different between patients with narrow resection margins in LLL group and LH group (P=0.012 and 0.017, respectively). Liver resection modality is not an independent risk factor for the prognosis of patients with HCC on the left lateral lobe as long as wide margins are obtained. Nevertheless, with narrow margins, patients who underwent LH rather than LLL did better.

Preoperative EUS vs. PET-CT Evaluation of Response to Neoadjuvant Therapy for Esophagogastric Cancer and Its Correlation with Survival.

The objective of our study was to investigate whether Endoscopic Ultrasonography (EUS) and Positron Emission Tomography-Computed Tomography (PET-CT) restaging can predict survival in upper gastrointestinal tract adenocarcinomas and to assess their accuracy when compared to pathology. We conducted a retrospective study on all patients who underwent EUS for staging of gastric or esophago-gastric junction adenocarcinoma between 2010 and 2021. EUS and PET-CT were performed, and preoperative TNM restaging was conducted using both procedures within 21 days prior to surgery. Disease-free survival (DFS) and overall survival (OS) were evaluated. A total of 185 patients (74.7% male) were included in the study. The accuracy of EUS for distinguishing between T1-T2 and T3-T4 tumors after neoadjuvant therapy was 66.7% (95% CI: 50.3-77.8%), and for N staging, the accuracy was 70.8% (95% CI: 51.8-81.8%). Regarding PET-CT, the accuracy for N positivity was 60.4% (95% CI: 46.3-73%). Kaplan-Meier analysis revealed a significant correlation between positive lymph nodes on restaging EUS and PET-CT with DFS. Multivariate COX regression analysis identified N restaging with EUS and PET-CT, as well as the Charlson comorbidity index, as correlated factors with DFS. Positive lymph nodes on EUS and PET-CT were predictors of OS. In multivariate Cox regression analysis, the independent risk factors for OS were found to be the Charlson comorbidity index, T response by EUS, and male sex. Both EUS and PET-CT are valuable tools for determining the preoperative stage of esophago-gastric cancer. Both techniques can predict survival, with preoperative N staging and response to neoadjuvant therapy assessed by EUS being the main predictors.

Do patients with metastatic renal cell carcinoma obtain survival benefits from cytoreductive nephrectomy? A population-based study.

This study aimed to explore the value of cytoreductive nephrectomy (CN) and develop nomograms to predict the prognosis of metastatic renal cell carcinoma (mRCC) patients with receiving radiology therapy or/and chemotherapy (RT/&CT). Clinical data of patients with mRCC between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic nomograms were constructed to predict the overall survival (OS) and cancer-specific survival (CSS) probability for 1-, 3-, and 5- years in patients with mRCC. A series of validation methods were used to validate the accuracy and reliability of the model, including area under the receiver operating curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA). 1394 patients were enrolled in this study. All patients were randomly divided into the training cohort (n = 976) and the validation cohort (n = 418). In the training cohort, multivariate Cox regression analysis suggested that pathology grade, histology type, T stage, N stage, surgery, and distant metastasis were independent risk factors for OS and CSS. The AUC and C-index were both over 0.65 in both cohorts, indicating that the nomograms for OS and CSS had satisfactory discriminative power. The calibration curves revealed that the predictive nomograms had a good consistency between the observed and the predicted survival. This study provided evidence that mRCC patients underwent RT/&CT could gain survival benefits from CN. The prognostic nomogram constructed in our study is reliable and practical, may help guide clinical strategies in the treatment of mRCC.

A nomogram for individually predicting the overall survival in colonic adenocarcinoma patients presenting with perineural invasion: a population study based on SEER database.

Colonic adenocarcinoma, representing the predominant histological subtype of neoplasms in the colon, is commonly denoted as colon cancer. This study endeavors to develop and validate a nomogram model designed for predicting overall survival (OS) in patients with colon cancer, specifically those presenting with perineural invasion (PNI). The Surveillance, Epidemiology, and End Results (SEER) database supplied pertinent data spanning from 2010 to 2015, which facilitated the randomization of patients into distinct training and validation cohorts at a 7:3 ratio. Both univariate and multivariate analyses were employed to construct a prognostic nomogram based on the training cohort. Subsequently, the nomogram's accuracy and efficacy were rigorously evaluated through the application of a concordance index (C-index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic (ROC) curves. In the training cohorts, multivariable analysis identified age, grade, T-stage, N-stage, M-stage, chemotherapy, tumor size, carcinoembryonic antigen (CEA), marital status, and insurance as independent risk factors for OS, all with P-values less than 0.05. Subsequently, a new nomogram was constructed. The C-index of this nomogram was 0.765 (95% CI: 0.755-0.775), outperforming the American Joint Committee on Cancer (AJCC) TNM staging system's C-index of 0.686 (95% CI: 0.674-0.698). Calibration plots for 3- and 5-year OS demonstrated good consistency, while DCA for 3- and 5-year OS revealed excellent clinical utility in the training cohorts. Comparable outcomes were observed in the validation cohorts. Furthermore, we developed a risk stratification system, which facilitated better differentiation among three risk groups (low, intermediate, and high) in terms of OS for all patients. In this study, we have devised a robust nomogram and risk stratification system to accurately predict OS in colon cancer patients exhibiting PNI. This innovative tool offers valuable guidance for informed clinical decision-making, thereby enhancing patient care and management in oncology practice.

Effects of preoperative bicarbonate and lactate levels on short-term outcomes and prognosis in elderly patients with colorectal cancer

PurposeThe aim of this study was to analyze the effect of preoperative bicarbonate and lactate levels (LL) on the short-term outcomes and prognosis in elderly (≥ 65 years) patients with colorectal cancer (CRC).MethodsWe collected the information of CRC patients from Jan 2011 to Jan 2020 in a single clinical center. According to the results of preoperative blood gas analysis, we divided patients into the higher/lower bicarbonate group and the higher/lower lactate group, and compared their baseline information, surgery-related information, overall survival (OS) and disease-free survival (DFS).ResultsA total of 1473 patients were included in this study. Comparing the clinical data of the higher/lower bicarbonate group and the higher/lower lactate group, the lower group were older (p < 0.01), had higher rates of coronary heart disease (CHD) (p = 0.025), a higher proportion of colon tumors (p < 0.01), larger tumor size (p < 0.01), higher rates of open surgery (p < 0.01), more intraoperative blood loss (p < 0.01), higher overall complications (p < 0.01) and 30-day deaths (p < 0.01). The higher LL patients had more male patients (p < 0.01), higher body mass index (BMI) (p < 0.01) and drinking rates (p = 0.049), higher rates of type 2 diabetes mellitus (T2DM) (p < 0.01) and lower rates of open surgery (p < 0.01). In multivariate analysis, age (p < 0.01), BMI (p = 0.036), T2DM (p = 0.023), and surgical methods (p < 0.01) were independent risk factors of overall complications. The independent risk factors for OS included age (p < 0.01), tumor site (p = 0.014), tumor stage (p < 0.01), tumor size (p = 0.036), LL (p < 0.01), and overall complications (p < 0.01). The independent risk factors of DFS included age (p = 0.012), tumor site (p = 0.019), tumor stage (p < 0.01), LL (p < 0.01), and overall complications (p < 0.01).ConclusionPreoperative LL significantly affected postoperative OS and DFS of CRC patients, but bicarbonate might not affect the prognosis of CRC patients. Therefore, surgeons should actively focus on and adjust the LL of patients before surgery.

Clinicopathological characteristics and survival outcomes in patients with angiosarcoma of breast.

Angiosarcoma of the breast is a rare malignancy. There are little data evaluating the survival and estimating the prognostic factors. The best surgical management and the role of systemic adjuvant therapy remain ill-defined. This study aimed to investigate the clinicopathological features, survival, and prognostic factors of breast angiosarcoma. The data on patients diagnosed with breast angiosarcoma were extracted from the Surveillance, Epidemiology, and End Results database (1975-2016). Univariate and multivariate Cox regression analyses were used to estimate the influential prognostic factors. The overall survival (OS) and disease-specific survival (DSS) of patients with breast angiosarcoma were evaluated. This study included 656 patients diagnosed with breast angiosarcoma between 1975 and 2016. The 5-year OS rate of all patients was 44.9% (95% CI 40.8-49.0). In both OS and DSS, Kaplan-Meier survival analyses revealed significant differences for both OS and DSS according to age, year at diagnosis, laterality, grade, and stage (all log-rank p < 0.05). Multivariate analysis suggested that lesions of the right breast, poor differentiation, and advanced stage were independent risk factors for OS or DSS (all p < 0.05). Older age was a risk factor in OS, but was protective in DSS. In primary breast angiosarcoma, age, laterality, grade, and stage were independent prognostic factors in OS and DSS (all p < 0.05). Mastectomy was also a risk factor in DSS (p = 0.034). The proportion of patients with grade III and regional disease was larger in the mastectomy group. Angiosarcoma of the breast had a poor prognosis. In our study, age, laterality, histologic grade, and stage were identified as significant prognostic factors. Why patients with angiosarcoma of the right breast had a worse prognosis remains equivocal. Mastectomy was adopted more often by surgeons in this cohort study for patients with advanced primary breast angiosarcoma.

Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

BackgroundNeuroblastoma (NB) places a substantial health burden on families worldwide. This study aimed to develop an immune checkpoint-based signature (ICS) based on the expression of immune checkpoints to better assess...

Prognostic value of prior malignancy history in stage I differentiated thyroid cancer: a SEER-based study.

Thyroid cancer is the most common endocrine cancer today. Differentiated thyroid cancer (DTC) comprises more than 95% of all thyroid cancers. With the increasing incidence of tumors and development of screening, more patients suffer from multiple cancers. The purpose of this study was to explore the prognostic value of a history of prior malignancy for stage I DTC. Stage I DTC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and Cox proportional hazards regression method were used to determine the risk factors for overall survival (OS) and disease-specific survival (DSS). A competing risk model was also used to determine the risk factors for DTC-related death after considering the competitive risks. In addition, conditional survival analysis in patients with stage I DTC was performed. A total of 49,723 patients with stage I DTC were enrolled in the study, and 4,982 (10.0%) had prior malignancy history. Prior malignancy history was a factor affecting OS (P<0.001) and DSS (P<0.001) in the Kaplan-Meier analysis and an independent risk factor for OS [hazard ratio (HR) =3.6, 95% confidence interval (CI): 3.17-4.088, P<0.001] and DSS (HR =4.521, 95% CI: 2.224-9.192, P<0.001) in the multivariate Cox proportional hazards regression analysis. In the competing risk model, in the multivariate analysis, prior malignancy history was a risk factor for the DTC-related deaths [subdistribution HR (SHR) =4.32, 95% CI: 2.233-8.3593, P<0.001] after considering the competitive risks. Conditional survival showed that the probability of achieving 5-year DSS was not changed in either the two groups with or without prior malignancy history. For the patients with prior malignancy history, the probability of achieving 5-year OS increased with each additional year survived, but for the patients without prior malignancy history, the improvement of conditional OS only appeared with 2 years already prior survived. Prior malignancy history has an adverse impact on the survival of patients with stage I DTC. The probability of achieving 5-year OS for stage I DTC patients with prior malignancy history increases with each additional year survived. The inconsistent survival effects of prior malignancy history should be considered in clinical trial design and recruitment.

Expression and Prognostic Value of Lgr5 in Patients with Recurrent Nasopharyngeal Carcinoma.

As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous. We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis. Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively). Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Establishment and validation of lncRNA-related prognostic signatures in cholangiocarcinoma

BackgroundThe prognosis of CCA is extremely poor, making it one of the most lethal cancers. Therefore, there is a need to elucidate the pathogenic mechanisms of CCA. In this study, we aimed at identifying lncRNA-related prognostic signatures for CCA through bioinformatics analysis and further validated their functions in CCA tumorigenesis and progression. MethodsThe RNA-seq data of CCA were downloaded from public databases. Differentially expressed lncRNAs (DElncRNAs) were screened. Then, candidate OS- and DFS-related DElncRNAs were selected through Kaplan–Meier survival analysis. Furthermore, LASSO regression was performed to establish the OS and DFS signatures, respectively. Multivariate COX models and nomograms for overall survival (OS) and disease-free survival (DFS) were established based on OS/DFS signature and clinical data. Hub lncRNAs were identified and enrichment analyses were performed to explore their potential functions. Finally, in vitro and in vivo models were used to validate the effects of the hub lncRNAs in CCA tumorigenesis and progression. ResultsA total of 925 DElncRNAs were selected, of which six candidate OS-related lncRNAs and 15 candidate DFS-related lncRNAs were identified. The OS and DFS signatures were then established using four lncRNAs, respectively. We found that the OS signature and vascular invasion were independent risk factors for the OS of CCA, while the DFS signature, vascular invasion, and CA19–9 were independent risk factors for the DFS of CCA. Then, nomograms were established to achieve personalized CCA recurrence and death prediction. Furthermore, our study uncovered that MIR4435-2HG and GAPLINC might play crucial roles in CCA progression and be selected as hub lncRNAs. GO and KEGG enrichment analyses revealed that the two hub lncRNAs were closely related to CCA tumorigenesis. Finally, we demonstrated that MIR4435-2HG and GAPLINC can stimulate CCA proliferation and migration in vitro and in vivo. ConclusionsThe established OS and DFS signatures are independent risk factors for OS and DFS of CCA patients, respectively. MIR4435-2HG and GAPLINC were identified as hub lncRNAs. In vitro and in vivo models revealed that MIR4435-2HG and GAPLINC can prompt CCA progression, which might be novel prognostic biomarkers and therapeutic targets for CCA.