Risk Factor For Disease-free Survival Research Articles

MRI-based radiomics for stratifying recurrence risk of early-onset rectal cancer: a multicenter study

Early-onset rectal cancer (EORC) is characterized by a unique disease process with different clinicopathological features compared with late-onset rectal cancer (LORC). Research on the risk of recurrence in EORC patients, however, is limited. We aim to develop a predictive model to accurately predict EORC recurrence risk. Rectal cancer patients who underwent radical surgery and T2-weighted imaging and diffusion-weighted imaging magnetic resonance imaging (MRI) were retrospectively enrolled from three medical institutions from November 2012 to November 2018. Differences in clinicopathological characteristics between EORC and LORC were compared. Five prediction models for disease-free survival were constructed based on clinicopathological variables and five radiomic features from pretreatment MRI of the EORC. A fixed cut-off value calculated in the training set was used to stratify EORC patients into high-risk and low-risk groups of post-operative recurrence. Model performance was evaluated by concordance index (C-index) and receiver operating characteristic curve. A total of 264 EORC patients (median age, 43 years, 163 males) and 778 LORC patients (median age, 62 years, 520 males) were enrolled. Pretreatment positive carcinoembryonic antigen [hazard ratio (HR)= 2.84, P= 0.006], pathological positive lymph node status (pN positive) [HR= 2.86, P= 0.011] and MRI-based radiomics score [HR= 2.72, P < 0.001] are independent risk factors for disease-free survival in EORC patients. The EORC-ClinPathRadiom model, constructed by integrating the clinicopathological characteristics and MRI-based radiomics features of EORC, showed C-index of 0.82, 0.82, and 0.81 in the training, internal, and external test sets, respectively. This model effectively stratified EORC patients into high risk and low risk of recurrence (HRs for the training, internal, and external test sets were 8.96, 6.81, and 7.46, respectively). The EORC-ClinPathRadiom model can effectively predict and stratify the risk of post-operative recurrence in EORC patients.

The impact of family cancer history on tumor metabolism and prognosis in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, and the role of family cancer history in disease progression and treatment response remains underexplored. This study aims to investigate the influence of family tumor history on disease-free survival, tumor metabolism, and treatment response in NSCLC patients. A retrospective, single-center study of 414 NSCLC patients was conducted, with 101 patients having a family history of cancer (FHC). Disease-free survival (DFS), tumor glucose metabolism assessed by 18F-FDG PET/CT, and treatment response to chemoradiotherapy, targeted therapy, and immunotherapy were analyzed. Multivariate modeling was performed to improve prognostic prediction. Patients with FHC exhibited higher TNM staging, increased susceptibility to lymph node invasion, and elevated tumor glucose metabolism levels. Family history of cancer, particularly colorectal and lung cancer, was a significant risk factor for disease-free survival. Targeted therapy and immunotherapy significantly improved patient prognosis, while family history of cancer affected the efficacy of chemoradiotherapy but not targeted therapy or immunotherapy. Multivariate modeling combining FHC, treatment, and tumor metabolism levels yielded improved predictive performance. Our study highlights the importance of considering a patient's family history when assessing risk profiles and formulating treatment decisions for NSCLC patients. Further research is needed to understand the molecular mechanisms underlying these observed associations and to develop more effective treatment strategies for NSCLC patients with a cancer family history.

Immediate and long-term outcomes of surgical treatment in patients with retroperitoneal and abdominal desmoid fibromatosis: A retrospective study

Background. The main method of treatment of desmoid fibromatosis is surgical, especially in patients with symptomatic disease or in cases of progression during the Look and Stay period. Due to the rarity of the disease, different localization, unpredictability of the clinical course, the lack of generally accepted clear criteria for choosing a treatment method and/or a sequence of treatment methods, the determination of prognostic criteria for the course of the disease is of great scientific and practical interest. Aim. To study the immediate and long-term outcomes of surgical treatment in patients with retroperitoneal and abdominal desmoid fibromatosis. Materials and methods. The study analyzed the data of 121 patients with histologically verified retroperitoneal and abdominal desmoid fibromatosis who underwent surgical treatment at the Blokhin National Medical Research Center of Oncology from 1999 to 2022. Results. In 89% of cases, desmoid tumors are resectable; however, resections of adjacent organs are often required to remove the tumor mass completely. The frequency of combined interventions in the abdominal and retroperitoneal groups was 7.0 and 60.4%, respectively. Tumor cells along the edge of the incision are identified in 15.8% of patients, including 10% of patients with macroscopically detectable residual tumors. Surgical treatment of patients with desmoid tumors is associated with an acceptable complication rate and provides high rates of overall and relapse-free survival. Risk factors for disease-free survival of operated patients are retroperitoneal localization, multicentric tumor growth, and R2 category. Conclusion. The treatment of patients with retroperitoneal and abdominal desmoid tumors should be carried out in specialized clinics with sufficient experience in performing surgical interventions, including combined ones. The treatment approach in patients with desmoid tumors should be selected by a multidisciplinary team based on personalized oncological and functional prognoses in accordance with the prognostic risk groups.

Integrated machine learning algorithms reveal a bone metastasis-related signature of circulating tumor cells in prostate cancer

Bone metastasis is an essential factor affecting the prognosis of prostate cancer (PCa), and circulating tumor cells (CTCs) are closely related to distant tumor metastasis. Here, the protein-protein interaction (PPI) networks and Cytoscape application were used to identify diagnostic markers for metastatic events in PCa. We screened ten hub genes, eight of which had area under the ROC curve (AUC) values > 0.85. Subsequently, we aim to develop a bone metastasis-related model relying on differentially expressed genes in CTCs for accurate risk stratification. We developed an integrative program based on machine learning algorithm combinations to construct reliable bone metastasis-related genes prognostic index (BMGPI). On the basis of BMGPI, we carefully evaluated the prognostic outcomes, functional status, tumor immune microenvironment, somatic mutation, copy number variation (CNV), response to immunotherapy and drug sensitivity in different subgroups. BMGPI was an independent risk factor for disease-free survival in PCa. The high risk group demonstrated poor survival as well as higher immune scores, higher tumor mutation burden (TMB), more frequent co-occurrence mutation, and worse efficacy of immunotherapy. This study highlights a new prognostic signature, the BMGPI. BMGPI is an independent predictor of prognosis in PCa patients and is closely associated with the immune microenvironment and the efficacy of immunotherapy.

ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p

Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.

Prognostic Analysis of Stage I Non-Small Cell Lung Cancer Abutting Adjacent Structures on Preoperative Computed Tomography.

Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection. We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared. The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS. NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.

Margin to depth of invasion ratio as an indicator for stratifying close margins in early-stage oral squamous cell carcinoma

ObjectivesIn early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear. MethodsPatients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5. ResultsWe analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001). ConclusionFor early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment.

Prognostic factors in gastric cancer patients: a 10-year mono-institutional experience.

Gastric cancer (GC) is one of the main causes of death from cancer globally. Long-term survival, especially in Western countries, remains dismal, with no significant improvements in recent years. Therefore, precise identification of clinical and pathological risk factors is crucial for prognosis, as it allows a better selection of patients suitable for oncologically radical treatments and contributes to longer survivals. We devised a retrospective observational longitudinal study over 10 years of experience with GC patients operated with curative intent. Several factors were thoroughly investigated in a multivariate analysis to look for significance as independent risk factors for disease-free survival. Our results showed that only BMI, pTNM, and lymph node ratio expressed hazard ratios with implications for survival in our series of patients. Although limited by the retrospective nature of the study, this is one of the few cancer reports from Northern Italy showing results over 10 years, which may in our view, have an impact on decision-making processes for multidisciplinary teams dedicated to the care of gastric cancer patients.

Prognostic value of preoperative white blood cell to hemoglobin ratio and fibrinogen to albumin ratio in patients with colorectal cancer.

The prognostic value of preoperative white blood cell to hemoglobin ratio (WHR) and fibrinogen to albumin ratio (FAR) in colorectal cancer (CRC) is unknown. The purpose of this study was to analyze the correlation between preoperative WHR and FAR and the prognosis of CRC patients. The retrospective study analyzed the medical records of 207 patients with colorectal cancer who were admitted to Linyi People's Hospital between June 1, 2017 and June 1, 2021. The receiver operator curve was used to determine the cutoff value of 4.604 for WHR and 0.086 for FAR, and the patients were divided into high and low groups for comparative analysis of clinical data. Cox proportional hazards regression models were used to assess independent risk factors for disease-free survival (DFS) and overall survival (OS) in univariate and multifactorial analyses. Kaplan-Meier methods were used for survival analysis and logrank tests were used to assess survival differences. Multifactorial Cox analysis showed that tumor pathological stage (HR = 6.224, 95% CI:3.063-12.647, P < .001), and WHR (HR = 3.681, 95% CI:1.768-7.401, P < .001) were the independent risk factors for DFS in CRC patients. Tumor pathological stage (HR = 4.080, 95% CI:1.992-8.360, P < .001), and WHR (HR = 3.397, 95% CI:1.662-6.940, P = .001) were independent risk factors for OS. High levels of WHR and high levels of FAR were associated with lower DFS (P < .001) and OS (P < .001).CRC patients with both higher WHR and FAR had significantly lower DFS (P < .001) and OS (P < .001). DFS and OS may be shorter in CRC patients with high WHR and high FAR, perhaps associated with poor prognosis in CRC patients, and WHR and FAR may be potential CRC prognostic markers.

Preoperative IL-8 levels as prognostic indicators of overall survival: an extended follow-up in a prospective cohort with colorectal liver metastases

IntroductionCRC with liver metastases is a major contributor to cancer-related mortality. Despite advancements in liver resection techniques, patient survival remains a concern due to high recurrence rates. This study seeks to uncover prognostic biomarkers that predict overall survival in patients undergoing curative hepatic resection for CRC liver metastases.MethodsProspectively collected serum samples from a cohort of 49 patients who received curative hepatic resection for CRC liver metastases were studied. The patients are part of a cohort, previously analyzed for perioperative complications (see methods). Various preoperative serum markers, clinical characteristics, and factors were analyzed. Univariate and multivariate Cox regression analyses were conducted to determine associations between these variables and disease-free survival as well as overall survival.ResultsFor disease-free survival, univariate analysis highlighted the correlation between poor outcomes and advanced primary tumor stage, high ASA score, and synchronous liver metastases. Multivariate analysis identified nodal-positive primary tumors and synchronous metastases as independent risk factors for disease-free survival. Regarding overall survival, univariate analysis demonstrated significant links between poor survival and high preoperative IL-8 levels, elevated neutrophil–lymphocyte ratio (NLR), and presence of metastases in other organs. Multivariate analysis confirmed preoperative IL-8 and having three or more liver metastases as independent risk factors for overall survival. The impact of IL-8 on survival was particularly noteworthy, surpassing the influence of established clinical factors.ConclusionThis study establishes preoperative IL-8 levels as a potential prognostic biomarker for overall survival in patients undergoing curative liver resection for CRC liver metastases. This study underscores the importance of incorporating IL-8 and other biomarkers into clinical decision-making, facilitating improved patient stratification and tailored treatment approaches. Further research and validation studies are needed to solidify the clinical utility of IL-8 as a prognostic marker.

Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study.

Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection. A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis. Multivariate COX regression showed that HBV DNA ≥10,000 IU/mL (P < 0.001), HALP score ≤38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III-IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001). We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.

Prognostic Implications of LRP1B and Its Relationship with the Tumor-Infiltrating Immune Cells in Gastric Cancer.

Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II-III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28-5.14, p = 0.008). The Kaplan-Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10-0.93, p = 0.042). LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits.

Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world.

Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable-risk by European Leukemia Net (ELN), CBF-AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF-AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. Retrospective analysis of 149 AML patients (75 CBF-AML, 74 non-CBF) at Peking University First Hospital (March 2012-March 2022). CBF-AML patients have significantly lower disease-free survival (DFS) (p = 0.005) and higher non-relapse mortality (NRM) (p = 0.028) compared to non-CBF AML. inv (16) and t(8;21) show distinct co-occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves prognosis in low-risk t(8;21). Prognosis of CBF-AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo-HSCT may benefit low-risk t(8;21), but further research is needed for conclusive evidence.

Nucleolus Scoring May Increase the Objectivity of Pathological Evaluation of Endometrial Cancers

Aim: Nucleolus has been shown as a prognostic parameter in many cancer types. In this study, we showed that the nucleolus score may provide more objective FIGO grading in endometrial cancers (ECs). We examined the role of nucleolus score in predicting treatment and prognosis in ECs.&#x0D; Material and Methods: The presence of nucleoli were scored as 1, 2 and 3 in curettage materials. The relationship between this value and clinicopathological parameters was examined. &#x0D; Results: Nucleolus score was associated with FIGO grade, myometrial invasion and lymphovascular invasion. The nucleolus score, which has the potential for objective evaluation,was found as an independent risk factor for disease-free survival (DFS) as well as there was an association between nucleolus score and DFS. &#x0D; Conclusion: Nucleolus score was associated with better prognosis in ECs. It can be evaluated objectively with no need of requiring extra cost and time. Thus, adding nucleolus score in FIGO grading can provide more reliable prediction in prognosis and choice of the treatment method.

Comparison of Supraclavicular Surgery plus Radiotherapy vs. Radiotherapy Alone in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis: A Multicenter Retrospective Study

To evaluate and compare the outcomes of supraclavicular lymph node dissection (SLND) plus radiotherapy (RT) and RT alone for patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM). In all, 293 patients with sISLM across three centers were included. Of these, 85 (29.0%) received SLND plus RT and 208 (71.0%) received RT alone. All patients received preoperative systemic therapy followed by mastectomy or lumpectomy and axillary dissection. Supraclavicular recurrence-free survival (SCRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated by using the Kaplan-Meier method and multivariate Cox models. Multiple imputation was used for missing data. The median follow-up duration of the RT and SLND+RT groups were 53.7 and 63.5 months, respectively. For the RT and SLND+RT groups, the 5-year SCRFS rates were 91.7% vs. 85.5% (P = 0.522), LRRFS rates were 79.1% vs. 73.1% (P = 0.412), DMFS rates were 60.4 vs. 58.8% (P = 0.708), DFS rates were 57.6% vs. 49.7% (P = 0.291), and OS rates were 71.9% vs. 62.2% (P = 0.272), respectively. There was no significant effect on any outcome when comparing SLND+RT versus RT alone in the multivariate analysis. Based on four risk factors of DFS, patients were classified into three risk groups: the intermediate- and high-risk groups had significantly lower survival outcomes than the low-risk group. SLND+RT did not improve outcomes of any risk group compared with RT alone. Patients with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study

BackgroundWe aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy.MethodsThis study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect.ResultsA total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54–72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282–3.660, P = 0.004; HR 1.583, 95% CI 0.985–2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725).ConclusionsPerineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study.Trial registrationThis study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Estimating disease-free survival of thyroid cancer based on novel cuprotosis-related gene model.

Cuprotosis is a newly discovered form of cell death that differs from other types of cell death. The aim of this study was to investigate the functional role and a possible prognostic model for thyroid cancer. TCGA and GEO were used to investigate the differential expression of CRGs in THCA. KEGG and GO enrichment analyses were applied to investigate the possible molecular functions. The features of CRGs were selected by LASSO regression. 20 pairs of samples were randomly collected from the hospital to compare expression between tumor and normal. Among the 19 CRGs related to thyroid cancer recurrence, 16 genes were differentially expressed in thyroid cancer. KEGG analysis showed that the 19 CRGs were mainly enriched in cell death, cell cycle and ribosomal pathways. K-M survival analysis and subsequent multiple logistic regression revealed that the expression of BUB1 and GINS2 were potential risk factors for disease-free survival (DFS) of thyroid cancer. In addition, further LASSO-regression selected the following three DFS-related CRGs: FDX1, BUB1 and RPL3. A novel prognostic prediction model was constructed by nomogram, and the prediction probability for 1-, 3- and 5-year survival approached the actual time. As for the possible mechanisms, FDX1, BUB1 and RPL3 were associated with immune infiltration. The cell model experiment illustrated that the ATM signaling pathway might be involved in thyroid cancer cell death. Three CRG models (FDX1, BUB1, RPL3) could better predict the prognosis of thyroid cancer. Immune cell infiltration and the ATM pathway were the possible mechanisms.

Risk factors affecting oncological outcomes of surgical resections for middle and lower rectal cancer.

In our study, it was aimed to evaluate the factors affecting oncological outcomes in resections for rectal cancer. Between January 2010 and December 2014, patients with rectal tumors were analyzed retrospectively. Demographic and pathological data and oncological outcomes were analyzed as disease-free survival, overall survival, and local recurrence. A total of 158 patients' data were obtained. Median age was 60 (22-83). Fifty-three patients were older than 65 years of age (138). Ninety-five (60%) patients were males, and 63 (40%) were females. Eighty patients (50.4%) had middle rectal, and 78 (49.6) patients had lower rectal cancer. There was no effect of tumor localization on oncological outcomes. Univariate analyses revealed the effects of age (p= 0.003), operation type (p <0.001), nodal status (p <0.001), malignant lymph node ratio (p <0.001), stage of the disease (p <0.001), distal resection margin (p= 0.047), perineural invasion (p <0.001), lymphatic invasion (p <0.001), venous-vascular invasion (p= 0.025), local recurrence (p <0.001) and distant metastasis (p <0.001) on overall survival rates. Univariate analyses revealed the effects of nodal status (p= 0.007), malignant lymph node ratio (p= 0.005), stage of the disease (p= 0.008), perineural invasion (p= 0.004) and venous-vascular invasion (p <0.001) on disease-free survival rates. Univariate analyses revealed the effects of anastomotic leak (p= 0.015) and venous-vascular invasion (p= 0.001) on local recurrence rates. Older age, advanced nodal status, and distant metastasis were detected as independent risk factors for overall survival. Perineural and venous-vascular invasion were detected as independent risk factors for disease-free survival. Lastly, anastomotic leak and venous-vascular invasion were detected as independent risk factors for local recurrence.

The effect of haploidentical hematopoietic stem cell transplantation on comutations based on next-generation sequencing in adult acute myeloid leukemia patients with the FLT3-ITD mutation.

According to the 2022 European LeukemiaNet, all acute myeloid leukemia (AML) cases with FLT3-ITD mutations are now categorized as intermediate risk irrespective of the FLT3-ITD allelic ratio or concurrent presence of NPM1 mutation. However, whether other next-generation sequencing (NGS) comutation genes can add layers to FLT3-ITD and whether the poor outcomes of FLT3-ITD comutations can be overcome by haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are unclear. This study aimed to investigate which comutations based on NGS at diagnosis affect the clinical prognosis of de novo AML patients with FLT3-ITD mutations and the effect of haplo-HSCT on comutations. We analyzed 95 de novo AML patients with FLT3-ITD mutations from January 2018 to August 2021 based on the NGS 99-gene platform. Forty-one other types of molecular mutations were detected. The most common cooccurring mutations were NPM1 (n=43, 45.3%) and DNMT3A (n=21, 22.1%). NPM1 mutation did not affect the clinical outcomes. Acute myeloid leukemia patients with FLT3-ITD and DNMT3A comutations had significantly worse 3-year Disease-free survival (DFS) (49.5% vs. 69.3%, P=0.01) and Overall survival (OS) rates (61.1% vs. 69.8%, P=0.54) than those without DNMT3A mutations, and survival was significantly more favorable after haplo-HSCT than that after chemotherapy (3-year DFS, 85.7% vs. 30.8%, P=0.006; 3-year OS, 85.7% vs. 43.1%, p=0.08). In multivariate analysis, DNMT3A mutation was a risk factor for DFS, while haplo-HSCT was a protective factor. In conclusion, DNMT3A mutation might be a poor prognostic factor in adult AML patients with FLT3-ITD mutations, and haplo-HSCT could overcome the poor prognosis of DNMT3A comutation.

Laparoscopic posterior pelvic exenteration is safe and feasible for locally advanced primary rectal cancer in female patients: a comparative study from China PelvEx collaborative.

Posterior pelvic exenteration (PPE) for locally advanced rectal cancer is a technical and challenging procedure. The safety and feasibility of laparoscopic PPE remain to be determined. This study aims to compare short-term and survival outcomes of laparoscopic PPE (LPPE) with open PPE (OPPE) in female patients. From January 2015 to December 2020, data from 105 female patients who underwent PPE at three institutions were retrospectively analyzed. The short-term and oncological outcomes between LPPE and OPPE were compared. A total of 54 cases with LPPE and 51 cases with OPPE were enrolled. The operative time (240 vs. 295min, p = 0.009), blood loss (100 vs. 300ml, p < 0.001), surgical site infection (SSI) rate (20.4% vs. 58.8%, p = 0.003), urinary retention rate (3.7% vs. 17.6%, p = 0.020), and postoperative hospital stay (10 vs. 13days, p = 0.009) were significantly lower in the LPPE group. The two groups showed no significant differences in the local recurrence rate (p = 0.296), 3-year overall survival (p = 0.129), or 3-year disease-free survival (p = 0.082). A higher CEA level (HR1.02, p = 0.002), poor tumor differentiation (HR3.05, p = 0.004), and (y)pT4b stage (HR2.35, p = 0.035) were independent risk factors for disease-free survival. LPPE is safe and feasible for locally advanced rectal cancers and shows lower operative time and blood loss, fewer SSI complications, and better preservation of bladder function without compromising oncological outcomes.