Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer.

BACKGROUND AND OBJECTIVES: Colorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature. METHODS: CRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature. RESULTS: From the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients. CONCLUSION: MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

Neoadjuvant sintilimab combined with chemotherapy in resectable locally advanced non-small cell lung cancer: case series and literature review.

BACKGROUND: In recent years, neoadjuvant immunotherapy with chemotherapy has shown increasing promise for locally advanced non-small cell lung cancer (NSCLC). However, to establish its clinical efficacy and safety, it is imperative to amass more real-world clinical data. This retrospective study aims to assess the safety and effectiveness of combing sintilimab, a PD-1 inhibitor, with chemotherapy as a neoadjuvant treatment modality in patients diagnosed with potentially resectable NSCLC. METHODS: We retrospectively reviewed patients with stage II-III NSCLC receiving neoadjuvant chemoimmunotherapy in Sichuan Cancer Hospital between February 2021 and February 2023. Sintilimab injection (intravenously,200 mg, iv, d1, q3w) and platinum-based chemotherapy were administered intravenously every 3 weeks, with radical lung cancer resection planned approximately 4-11 weeks after the last dose. The primary endpoint of the study was pathologic complete response (pCR). The secondary endpoints were objective response rate (ORR), and safety. RESULT: Thirteen patients were enrolled, they were mostly diagnosed with stage III NSCLC (IIB 15.4% IIIA 38.5%; IIIB 46.2%). Most of them had pathologically confirmed squamous cell carcinoma (69.2%). All patients received sintilimab combined with platinum-based chemotherapy for 2 to 4 cycles. Notably, none of the patients necessitated a reduction in initial dosages or treatment postponement due to intolerable adverse events. Then, all of them underwent surgical operation. Impressively, nine patients (69.2%) achieved a pathologic complete response. The objective response rate (ORR) stood at 46.15%. Nine patients experienced neoadjuvant treatment-related adverse events (TRAEs), with only one patient (7.6%) encountering a grade 4 neoadjuvant TRAE. CONCLUSION: Therefore, the current study suggested that neoadjuvant sintilimab plus platinum-based chemotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.

A Scoring System to Select the Candidates for Adjuvant Chemotherapy Alone in High-Risk Early-Stage Cervical Cancer Patients With Pelvic Lymph Node Metastases After Surgery.

BACKGROUND: The aim was to build a risk scoring system to guide the adjuvant treatment for early-stage cervical cancer patients with pelvic lymph node (LN) metastases after surgery. METHODS: A cohort of 1213 early-stage cervical cancer patients with pelvic LN metastases (T1-2aN1M0) were selected from the NCI SEER database, of which 1040 patients received adjuvant external beam radiotherapy concurrent with chemotherapy (EBRT+Chemo) and 173 patients received adjuvant chemotherapy alone. The Cox regression analysis was applied to identify the risk factors associated with worse survival. The exp (ß) of each independent risk factors from multivariate analysis was assigned to develop the risk scoring system. The total cohort was divided into different risk subgroups accordingly and the efficacy of different adjuvant modalities in each risk subgroups was compared. RESULTS: The patients were divided into 3 risk subgroups (Low-risk: total score <7.20, Middle-risk:7.20≤ total score≤ 8.40, High-risk: total score<8.40) based on the scoring system incorporating 5 independent risk factors. The survival analysis suggested that low-risk (hazard ratio [HR]=1.046, 95% CI: 0.586-1.867; P= 0.879) and middle-risk patients (HR=0.709, 95% CI: 0.459-1.096; P =0.122) could not benefit more from EBRT+Chemo than Chemo alone. However, EBRT+Chemo remained the superiority to Chemo alone in the high-risk subgroup (HR=0.482, 95% CI: 0.294-0.791; P =0.003). CONCLUSION: A risk scoring system has been built to direct the adjuvant treatment for early-stage cervical cancer patients with pelvic LN metastases after surgery, where Chemo alone was totally enough for low-risk and middle-risk patients stratified by the model while EBRT+Chemo was still recommended for patients in the high-risk subgroup.

A population-based risk scoring system to individualize adjuvant treatment for stage IIIC endometrial cancer patients after surgery.

BACKGROUND: To develop a risk scoring system to tailor the adjuvant treatment for stage IIIC EC patients after surgery. METHODS: Data source was from the Surveillance, Epidemiology, and End Results (SEER) registry, where 3251 post-operative stage IIIC EC patients with different adjuvant treatment were included. Cox regression analysis was used to identify risk factors. The exp (ß) of each independent risk factors generating from the cox analysis was used to construct the risk scoring system, which was further utilized to divide the patients into different risk subgroups and the efficacy of different adjuvant modalities in each risk subgroups would be compared accordingly. RESULTS: Six independent risk factors were identified to develop the scoring system, which further divided the patients into three risk subgroups based on the total risk score (Low-risk≤8.46, 8.47 ≤ Middle-risk≤9.94, High-risk≥9.95). This study revealed that CRT was not superior to RT alone (HR:1.208, 95%CI: 0.852-1.741; P = 0.289) or CT alone (HR:1.260, 95%CI: 0.750-2.116; P = 0.382) in Low-risk subgroup. We also observed that CRT had a survival advantage over other treatment modalities in the Middle-risk subgroup (All P < 0.001), but CRT and CT alone to be superimposable in the High-risk subgroup (HR: 1.395, 95%CI: 0.878-2.216; P = 0.159). CONCLUSION: A risk scoring system has been developed to tailor the adjuvant treatment for stage IIIC EC patients after surgery, where RT or CT alone could be a substitute for CRT in Low-risk patients and CT alone was a potential alternative for High-risk patients while CRT remained to be the optimal choice for the Middle-risk patients.

Prognostic model for the exemption of adjuvant chemotherapy in stage IIIC endometrial cancer patients.

Background: This study aimed to develop a nomogram to predict the survival for stage IIIC endometrial cancer (EC) patients with adjuvant radiotherapy (ART) alone and personalize recommendations for the following adjuvant chemotherapy (ACT). Methods: In total, 746 stage IIIC EC patients with ART alone were selected from the Surveillance, Epidemiology, and End Results (SEER) registry. Cox regression analysis was performed to identify independent risk factors. A nomogram was developed accordingly, and the area under the receiver operating characteristic curve (AUC) and C-index were implemented to assess the predictive power. The patients were divided into different risk strata based on the total points derived from the nomogram, and survival probability was compared between each risk stratus and another SEER-based cohort of stage IIIC EC patients receiving ART+ACT (cohort ART+ACT). Results: Five independent predictors were included in the model, which had favorable discriminative power both in the training (C-index: 0.732; 95% CI: 0.704-0.760) and validation cohorts (C-index: 0.731; 95% CI: 0.709-0.753). The patients were divided into three risk strata (low risk <135, 135 ≤ middle risk ≤205, and high risk >205), where low-risk patients had survival advantages over patients from cohort ART+ACT (HR: 0.45, 95% CI: 0.33-0.61, P < 0.001). However, the middle- and high-risk patients were inferior to patients from cohort ART+ACT in survival (P < 0.001). Conclusion: A nomogram was developed to exclusively predict the survival for stage IIIC EC patients with ART alone, based on which the low-risk patients might be perfect candidates to omit the following ACT. However, the middle- and high-risk patients would benefit from the following ACT.

Role of adjuvant chemotherapy after concurrent chemoradiotherapy in patients with locally advanced cervical cancer.

Aims: With the use of concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC), survival outcomes are still not optimal. This study was designed to evaluate the efficacy and safety of adjuvant chemotherapy (ACT) for patients with LACC after treatment with CCRT. Methods: Patients diagnosed with stage IIA-IIIB LACC, were retrospectively analyzed. All patients received cisplatin-based CCRT and were divided into two groups: ACT after CCRT (CCRT + ACT group) and observation after CCRT (CCRT group). Overall survival (OS), progression-free survival (PFS) and adverse effects were recorded and analyzed. Results: In total, 375 patients were included; 262 patients accepted ACT after CCRT while the remaining 113 patients chose observation. With a median follow-up of 40 months, no significant differences were found in the OS rates for patients in the CCRT + ACT and CCRT groups at 1 year, 3 years and the end of follow-up. There was also no significant discrepancy in PFS between groups. Subgroup analysis showed the International Federation of Gynecology and Obstetrics (FIGO) stage and age had negligible influence on both OS and PFS. Acute adverse events (grades 3-4) happened more frequently in CCRT + ACT group than in the CCRT group, with significant differences in neutropenia, anemia and creatinine. Conclusion: ACT after CCRT did not show benefit in survival but did induce some adverse effects. Therefore, this regimen is not recommended unless further large-scale randomized controlled trials are executed.

Construction and validation of a prognostic model for stage IIIC endometrial cancer patients after surgery.

BACKGROUND: To explore the most predictive lymph node (LN) scheme for stage IIIC endometrial cancer (EC) patients after hysterectomy and develop a scheme-based nomogram. METHODS: Data from 2626 stage IIIC EC patients, diagnosed between 2010 and 2014, were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. The predictive ability of four LN schemes was assessed using C-index and Akaike information criterion (AIC). A nomogram based on the most predictive LN scheme was constructed and validated. The comparison of the predictive ability between nomogram and FIGO stage was conducted using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: FIGO stage (stage IIIC1/stage IIIC2) was not an independent risk factor for OS in stage IIIC EC patients (P = 0.672) and log odds of positive lymph nodes (LODDS) had the best predictive ability (C-index: 0.742; AIC: 8228.95). A nomogram based on LODDS was constructed and validated, which had a decent C-index of 0.742 (0.723-0.762). The nomogram showed a better predictive ability than that of the FIGO staging system. CONCLUSION: FIGO IIIC1/FIGO IIIC2 could not differentiate the prognosis for stage IIIC EC patients. We developed and validated a nomogram based on LODDS to predict OS for post-operative patients with stage IIIC EC.

A real-world, population-based study of the trends for incidence and prognosis in high-grade neuroendocrine tumor of cervix.

To explore the incidence and prognosis trends for high-grade cervical neuroendocrine tumor (HGCNET) and construct a nomogram to predict prognosis for HGCNET. Annual age-adjusted incidence of HGCNET from 1975 to 2015 was retrieved from the Surveillance, Epidemiology, and End Results program, the linear regression, poisson regression and annual percentage changes were used to assess the incidence trend. Also, trends for relative survival (RS) and overall survival (OS) in HGCNET patients from 1975 to 2015 were evaluated. From 1988 to 1975, 514 HGCNET patients were selected and divided into two cohorts with a ratio of 7:3. Nomogram to predict OS for these patients was constructed and validated. The incidence trend for HGCNET was unchanged in the past four decades (P = 0.734), but the proportion of HGCNET in diagnosed cervical cancer slightly increased from 0.9% in 1975 to 1.9% in 2015 (P < 0.001). The 5-year RS and OS for HGCNET in the study periods decreased steadily (RS: P = 0.009; OS: P = 0.008). Nomogram incorporating age, T stage, lymph-node positive, distant metastasis and surgery was constructed. The C-index of the nomogram was 0.716 (0.680-0.752), which was higher than the FIGO staging system. The incidence of HGCNET remained unchanged in the past four decades but the proportion of HGCNET has slightly increased. Besides, a steadily decreasing survival for HGCNET was observed in the study periods. A nomogram was constructed to better predict prognosis for HGCNET.

Low level of complement factor H increases the risk of cancer-related death in patients with small-cell lung cancer.

INTRODUCTION: Pulmonary cancer is a kind of deeply invasive tumour which is difficult to treat, and its mortality rate is high. Previous research has shown that activation of complement could contribute to the progression of non-small-cell lung cancer (SCLC). However, little research has been done on SCLC. METHODS: Complement factor H (CFH), complements C3 as well as C4 were measured in patients, and the prognostic impact of different parameters was assessed by log-rank function analysis and Cox multifactor models. Besides, we constructed a predictive model based on complement fractions and validated the accuracy of the model. RESULTS: Among these 242 patients, 200 (82.6%) died. The median survival time was 18.3 months. We found by multifactorial analysis that high levels of CFH decreased the risk of death (HR 0.23, 95% CI 0.10 to 0.57, p<0.001), while elevated complement C4 displayed poor prognosis (HR 2.28, 95% CI 1.66 to 3.13, p<0.001). We screened variables by Cox models and constructed CFH-based prediction models to plot a nomogram by internal validation. The nomogram showed excellent accuracy in assessing the probability of death, yielding an adjusted C-statistics of 0.905. CONCLUSIONS: CFH can be recognised as a biomarker to predict the risk of death in SCLC. The prediction model established based on CFH, C3 and C4 levels has good accuracy in patients' prognostic assessment.

Patterns of Treatment Failure after Concurrent Chemoradiotherapy or Adjuvant Radiotherapy in Patients with Locally Advanced Cervical Cancer.

OBJECTIVE: To identify patterns of therapy failure after radiotherapy in Chinese patients with locally advanced cervical cancer (LACC). METHODS: A retrospective study was conducted at a Chinese hospital from June 2012 to July 2018. All analyses were done using SPSS 26. RESULTS: 105 patients with treatment failure were included. After a median follow-up of 27 months (range 10-82), the 3-year survival rate after therapy failure was 19.4%. In multivariate analysis, squamous cell carcinoma antigen (SCC-Ag) <4 ng/mL (p < 0.001) and disease-free interval >12 months (p = 0.013) showed significant survival benefits. We identified 3 types of failure: distant lymph node metastasis (n = 50), hematogenous metastasis (n = 53) and pelvic failure (n = 48). Most metastatic para-aortic lymph nodes (PALN) were inferior to the level of left renal hilum (84.8%, n = 28). A total of 80% of patients with supraclavicular lymph nodes (SCLN) metastasis ignored imaging on supraclavicular region. For solitary SCLN or lung metastasis, the prognosis was better than that combined with other sites failure, respectively (p = 0.005; p = 0.001). Many patients with central sites recurrence received insufficient doses of intracavitary brachytherapy (IBT) for low tolerance to pain. CONCLUSION: The distribution of metastatic PALN is asymmetrical and optimizing clinical target volume to minimize toxicity of para-aortic radiation is necessary. The effect of ultrasonography as preliminary screening and follow-up means on SCLN metastasis can be expected. Pain management and psychological interventions are essential for patients receiving IBT.