Independent Risk Factor For Overall Survival Research Articles

Comparison of Postoperative Outcome and Prognosis Among Laparoscopic Left Colectomy and Laparoscopic Sigmoidectomy in Sigmoid Colon Cancer Patients: A Propensity Score Matching Study.

The purpose of this study was to investigate the effect of laparoscopic left colectomy (LLC) and laparoscopic sigmoidectomy (LSD) on short-term outcomes and prognosis of sigmoid colon cancer (SCC) patients using propensity score matching (PSM). In this retrospective study, the SCC patients who underwent LLC or LSD surgery were collected from a single clinical center from Jan 2011 to Dec 2019. Short-term outcomes and prognosis were compared between patients who received LSD surgery and LLC surgery. A total of 356 patients were included in this study. After 1:1 PSM analysis, there were 50 patients who underwent LLC surgery and 50 patients who underwent LSD surgery left in this study. No significant difference was found in baseline characteristics after PSM (P > .05). In comparison with the LLC surgery group, the LSD surgery group had shorter operation time (P = .003) after PSM. Moreover, the surgical procedure was not an independent predictor for overall survival (OS) (P = .918, 95% CI = .333-2.688) and disease-free survival DFS (P = .730, 95% CI = .335-2.150), but age (OS: P = .009, 95% CI = 1.010-1.075; DFS: P = .014, 95% CI = 1.007-1.061) and tumor stage (OS: P = .004, 95% CI = 1.302-3.844; DFS: P < .01, 95% CI = 1.572-4.171) were the independent risk factors for OS and DFS in SCC patients. There was no significant difference between the two surgical procedures for prognosis of SCC patients. However, the possible reasons for changing the surgical procedures should be cautious by surgeons.

High MICAL1 expression correlates with cancer progression and immune infiltration in renal clear cell carcinoma

BackgroundMolecule interacting with CasL 1 (MICAL1), a multidomain flavoprotein monooxygenase, is strongly involved in the biological processes related to cancer cell proliferation and metastasis. However, there were few reports on the clinical significance of MICAL1 in renal clear cell carcinoma.MethodsThe expression and prognostic value of MICAL1 in renal clear cell carcinoma were explored using immunohistochemical assays, public TCGA-KIRC databases and multiple analysis methods, including survival analysis, univariate and multivariate analyses, KEGG and GSEA. Wound healing and Transwell assays were performed to check the 786-O cell and Caki-1 cell migration abilities after knockdown of MICAL1. Western blotting was used to assess the regulatory effect of MICAL1 on the Rac1 activation. Additionally, the function of MICAL1 and the correlations between MICAL1 and immune infiltration levels in KIRC were investigated using TIMER and TISIDB.ResultsMICAL1 expression was significantly higher in carcinoma tissue compared with non-cancerous tissue. A survival analysis revealed that patients with high MICAL1 expression had shorter overall survival (OS) and disease-specific survival (DSS) compared with patients with low MICAL1 expression. ROC analysis also confirmed that MICAL1 has a high diagnostic value in KIRC. Importantly, the univariate and multivariate Cox analysis further confirmed that high MICAL1 expression was an independent risk factor for OS in patients with KIRC. In accordance with this, knockdown of MICAL1 expression decreased Rac1 activation and cell migration. KEGG and GSEA analysis revealed that the immune infiltration and Ras signaling pathways were significantly upregulated in the high MICAL1 expression group. In terms of immune infiltrating levels, MICAL1 expression was positively associated with CD8+/Treg cell infiltration levels. Specifically, bioinformatic analysis showed that MICAL1 expression had strong relationships with various T cell exhaustion markers.ConclusionsMICAL1 expression may act as a prognostic biomarker for determining the prognosis in renal clear cell carcinoma and plays an important role in regulating tumor immune microenvironment and cell migratory capacity.

Prognostic value of semi-quantitative parameters of 18F-FDG PET/CT in newly diagnosed multiple myeloma patients

ObjectiveTo investigate the prognostic value of fluroine-18 fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameter in newly diagnosed multiple myeloma (NDMM) and to design a new staging system including 18F-FDG PET/CT semi-quantitative parameters for NDMM.MethodsA total of 38 NDMM patients who underwent 18F-FDG PET/CT examination in Yichang Central People’s Hospital from February 2014 to April 2021 were collected. The relationship between the characteristics of 18F-FDG PET/CT (metabolic tumor volume of all lesions (aMTV), total lesion glycolysis of all lesions (aTLG), maximum standardized uptake values (SUVmax) of the lesion with largest MTV (mSUVmax), extramedullary disease (EMD), focal lesions (FLs)), the laboratory parameters, and prognostic parameters (progression-free survival (PFS) and overall survival (OS)) were analyzed retrospectively. SPSS 25.0 statistical software was used for statistical processing, Kaplan–Meier method was used for survival analysis, Log-rank method was used for univariate analysis, and Cox proportional risk model was used for multivariate analysis.ResultsUnivariate analysis showed that aMTV ≥ 90.97cm3, aTLG ≥ 283.31 g, hemoglobin (Hb) < 100 g/L, focal lesions (FLs) ≥ 10, (percentage of circulating plasma cells (CPC%) ≥ 30%, creatinine (Cr) ≥ 177umol/L, lactic dehydrogenase (LDH) ≥ 250 g/L might be the adverse prognostic factors of PFS in patients with NDMM, all p < 0.05; aMTV ≥ 90.97 cm3, aTLG ≥ 283.31 g, Hb < 100 g/L, FLs ≥ 10, mSUVmax ≥ 5.8, the presence of extramedullary disease (EMD) and PCPs ≥ 30% may be adverse prognostic factors for OS in patients with NDMM, all p < 0.05. Multivariate regression analysis showed that aMTV ≥ 90.97 cm3 was an independent risk factor for PFS in NDMM patients, p < 0.05; aMTV ≥ 90.97 cm3, mSUVmax ≥ 5.8, and the presence of EMD were independent risk factors for OS in the NDMM patients, all p < 0.05. According to the multivariate analysis results of OS, the New stage (NS) was performed. The 3-year OS rates of stage I, stage II, and stage III in NDMM patients were 100.0, 53.5, and 32.1%, respectively, p = 0.000.ConclusionaMTV can predict PFS and OS of NDMM patients better than other parameters. NS which combined with aMTV can predict OS of NDMM patients better and can provide an accurate and simple method for risk stratification of NDMM patients.

Impact of type 2 diabetes mellitus on the prognosis of patients with hepatocellular carcinoma after laparoscopic liver resection: A multicenter retrospective study.

The effect of type 2 diabetes mellitus (T2DM) on survival of patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) has not been reported. This study aimed to explore the relationship between preoperative T2DM and long-term prognosis in HCC patients undergoing LLR. HCC patients receiving LLR as initial treatment at four cancer centers were retrospectively included in this study. Clinicopathological factors associated with the prognosis of HCC patients were identified using univariate and multivariate Cox regression analysis. Recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. Of 402 HCC patients included, 62 patients had T2DM and 340 patients did not have T2DM. The OS and RFS of patients with T2DM were significantly worse compared to those without T2DM (P = 0.001 and 0.032, respectively). In Cox multivariate analysis, T2DM was identified as an independent risk factors for OS (HR = 2.31, 95% CI = 1.38-3.85, P = 0.001) and RFS (HR = 1.66, 95% CI = 1.08-2.55, P = 0.020). Following laparoscopic surgical approach, HCC patients with T2DM had poorer prognoses than those without T2DM. Preoperative T2DM was an independent risk factor for HCC patients. Thus, patients with concurrent HCC and T2DM should be closely monitored after LLR.

Efficacy and safety analyses of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy in the treatment of advanced non–small-cell lung cancer with an EGFR/TP53 co-mutation

PurposeEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non–small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation.MethodsNinety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS).ResultsThere were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025).ConclusionOur study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.

Prospective Investigation of 18FDG-PET/MRI with Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Survival in Patients with Oropharyngeal or Hypopharyngeal Carcinoma.

To prospectively investigate the prognostic value of 18F-FDG PET/MRI in patients with oropharyngeal or hypopharyngeal squamous cell carcinomas (OHSCC) treated by chemoradiotherapy. The study cohort consisted of patients with OHSCC who had undergone integrated PET/MRI prior to chemoradiotherapy or radiotherapy. Imaging parameters derived from intravoxel incoherent motion (IVIM), dynamic contrast-enhanced MRI (DCE-MRI), and 18F-FDG PET were analyzed in relation to overall survival (OS) and recurrence-free survival (RFS). In multivariable analysis, T classification (p &lt; 0.001), metabolic tumor volume (p = 0.013), and pseudo-diffusion coefficient (p = 0.008) were identified as independent risk factors for OS. The volume transfer rate constant (p = 0.015), initial area under the curve (p = 0.043), T classification (p = 0.018), and N classification (p = 0.018) were significant predictors for RFS. The Harrell's c-indices of OS and RFS obtained from prognostic models incorporating clinical and PET/MRI predictors were significantly higher than those derived from the traditional TNM staging system (p = 0.001). The combination of clinical risk factors with functional parameters derived from IVIM and DCE-MRI plus metabolic PET parameters derived from 18F-FDG PET in integrated PET/MRI outperformed the information provided by traditional TNM staging in predicting the survival of patients with OHSCC.

Colonization with multidrug-resistant organisms is associated with impaired survival of patients with surgically resected cholangiocarcinoma.

Colonization with multidrug-resistant organisms (MDRO) has been shown to impair survival in patients with various malignancies. Despite the increasing spread of MDRO, its impact on patients with cholangiocarcinoma (CCA) is unclear. Aim of this study was to analyse the impact of MDRO-colonization on overall prognosis in CCA patients. All patients with surgically resected CCA diagnosed between August 2005 and November 2021 at the University Hospital Frankfurt were screened for MDRO. CCA patients with a positive MDRO screening before or within the first 90 days after diagnosis of CCA were defined as colonized. Patients with a negative MDRO screening were defined as non-colonized. Hundred and sixty nine patients were included. 32% (n= 54) were screened MDRO positive, while 68% (115) were non-colonized. Median overall survival (OS) for colonized patients was 17.1 months (95% CI=9-25.2 months) compared to 50 months (95% CI=37.1-62.8) for MDRO-negative patients (p≤ .001). Non-cancer-related mortality (p≤ .001) and infectious-related death (p≤ .001) was significantly higher in the MDRO-colonized group. In multivariate analysis, MDRO colonization (HR=2.1, 95% CI=1.4-3.3, p= .001), ECOG 1 (HR=2.5, 95% CI=1.6-4, p≤ .001) and N1 status (HR=1.7, 95% CI=1.1-2.6, p= .017) were independent risk factors for OS. MDRO-colonization contributes to poor survival in patients with surgically resected CCA. MDRO surveillance is necessary to optimize clinical management of infections and to potentially reduce mortality in this critical population.

Prognostic risk factors for pT4 colon cancer: A retrospective cohort study.

The present study aimed to clarify the prognostic risk factors for pathological T4 (pT4) colon cancer and provide a basis for improved treatment in affected patients. The current retrospective cohort study included 83 consecutively enrolled patients who underwent curative surgery for primary pT4 colon cancer between January 2014 and December 2021 at Tokyo Medical Women's University (Tokyo, Japan). Oncological outcomes, including recurrence pattern, were compared between patients with pT4a and pT4b colon cancer. Independent risk factors associated with overall survival (OS) and relapse-free survival (RFS) were analyzed using a multivariate Cox regression model. The 3-year OS rates were 85.1 and 95.0% in the pT4a and pT4b groups (P=0.089) and 3-year RFS rates were 64.1 and 60.5% (P=0.589), respectively. Moreover, the 3-year peritoneal recurrence-free survival was 71.0 and 90.2% (P=0.085) in these groups, respectively. Independent risk factors for OS were histology (mucinous or poorly differentiated adenocarcinoma), tumor location (right-sided) and pN status (positive). The risk factors for RFS were histology and pN status. Patients with pT4b colon cancer and R0 resection may not have a poorer prognosis compared with those with pT4a colon cancer. However, patients with pT4a colon cancer tended to have more peritoneal recurrence patterns. Histology and pN status were associated with OS and RFS, and right-sided colon cancer was also a risk factor for OS.

Treatment options for unresectable hepatocellular carcinoma with hepatitis virus infection following sorafenib failure

BackgroundCurrently, there are a few treatment options for unresectable hepatocellular carcinoma (HCC) after progression following sorafenib (SOR) therapy, but with limited benefit. The purpose of this study was to investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) as second-line treatment.MethodsFrom May 2018 to May 2021, a total of 93 HCCs who failed SOR treatment were included in this study and divided into TKI group (n = 37) and TKI-ICI group (n = 56). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety were estimated among the two groups. In addition, univariate and multivariate Cox regression analyses were performed for OS and PFS to identify possible prognostic factors.ResultsWith a median follow-up time of 13.7 months, the median age of patients was 56 (range, 50–64) years and most were male. All of the patients were hepatitis virus-related HCC. Both median OS (7.63 months vs 19.23 months, P < 0.001) and median PFS (2.97 months vs 8.63 months, P < 0.001) were significantly improved in the TKI-ICI group compared to the TKI group. A significant increase in DCR was demonstrated in the TKI-ICI group compared to the TKI group (83.9% vs 45.9%, P = 0.0003), although no significant difference in ORR was reported (21.4% vs 8.1%, P = 0.1552). Multivariate Cox regression analysis of OS and PFS revealed that second-line regimen was an independent protective factor affecting death and progression in HCCs after SOR failure. In addition, Child–Pugh B7 was an independent risk factor of OS. Finally, there was no significant difference in the incidence of any grade or grade 3/4 adverse events (AEs) between the two groups, and no treatment-related deaths were observed.ConclusionThis real-world study suggests that the combination of TKIs and ICIs benefits more than mono-TKIs and is well tolerated in HCCs with hepatitis virus infection after SOR failure.

Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers.

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan-Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38-90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8-82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient's condition. The median follow-up of surviving patients was 63 months (range, 1-126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.

Synaptophysin-like 2 expression correlates with lymph node metastasis and poor prognosis in colorectal cancer patients.

Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. Synaptophysin-like 2 (SYPL2) is a neuroendocrine-related protein highly expressed in skeletal muscle and the tongue. The involvement of SYPL2 in CRC, including its level of expression and function, has not been evaluated. To evaluate the correlations of SYPL2 expression with lymph node metastasis (LNM) and prognosis in patients with CRC. The levels of expression of SYPL2 in CRC and normal colorectal tissues were analyzed in multiple public and online databases. The associations between clinical variables and SYPL2 expression were evaluated statistically, and the associations between SYPL2 expression and prognosis in patients with CRC were analyzed using the Kaplan-Meier method and univariate/multivariate Cox regression analyses. SYPL2 expression was assessed in 20 paired CRC tissue and adjacent normal colorectal tissue samples obtained from Fuyang People's Hospital, and the associations between SYPL2 expression and the clinical characteristics of these patients were investigated. Correlations between the levels of expression of SYPL2 and key targeted genes were determined by Pearson's correlation analysis. The distribution of immune cells in these samples was calculated using the CIBERSORT algorithm. Gene set enrichment analysis (GSEA) was performed to evaluate the biofunction and pathways of SYPL2 in CRC. SYPL2 expression was significantly lower in CRC tissue samples than in normal colorectal tissue samples (P < 0.05). High SYPL2 levels in CRC tissues correlated significantly with LNM (P < 0.05) and a poorer patient prognosis, including significantly shorter overall survival (OS) [hazard ratio (HR) = 1.9, P < 0.05] and disease-free survival (HR = 1.6, P < 0.05). High SYPL2 expression was an independent risk factor for OS in both univariate (HR = 2.078, P = 0.014) and multivariate (HR = 1.754, P = 0.018) Cox regression analyses. In addition, SYPL2 expression correlated significantly with the expression of KDR (P < 0.0001, r = 0.47) and the BRAF V600E mutation (P < 0.05). Higher SYPL2 expression was associated with the enrichment of CD8 T-cells and M0 macrophages in the tumor microenvironment. GSEA revealed that SYPL2 was associated with the regulation of epithelial cell migration, vasculature development, pathways in cancer, and several vital tumor-related pathways. SYPL2 expression was lower in CRC tissue than in normal colorectal tissue. Higher SYPL2 expression in CRC was significantly associated with LNM and poorer survival.

Therapy-Related AML: Clinical/Biological Features and Long-Term Outcome in a Cohort of 1133 Adult AML Patients

Introduction: Therapy-related acute myeloid leukemia (t-AML) affects approximately 7% of AML patients and exhibits adverse genetic features that are assumably caused by increased DNA damage after antecedent radiation/chemotherapy. There is an ongoing medical need for a better understanding of differences between patients with t-AML and de novo AML. Here, we assess clinical and biological characteristics of patients with t-AML and compare long-term survival with de novo AML in a large cohort of AML patients. Methods: 225 t-AML patients who were newly diagnosed between 1995-2018 were retrospectively analyzed and compared to a cohort of 908 patients with de novo AML. Mann-Whitney U- and Chi square test were used to assess differences in baseline characteristics between subgroups. Kaplan Meier procedure was applied to calculate overall survival (OS). Cox regression was used to identify hazard ratios (HR) of independent prognostic risk factors. Non-relapse mortality (NRM) and risk of relapse (RR) were calculated by the cause-specific hazard method. Results: As compared to de novo AML, t-AML patients were older (61 vs. 55 years, p<0.001), had increased comorbidity and a higher frequency of adverse genetic alterations (e.g. monosomal or complex karyotypes, -5/-5q, -7, t(v;11)(v;23)). Prior to t-AML, solid cancer was diagnosed in 61% of patients (138/225), whereas 31% had hematologic malignancies (69/225) and 8% had autoimmune diseases (18/225). Previous malignancies had been treated with combined radiochemotherapy in 33% (75/225), chemotherapy in 27% (60/225), radiation therapy in 22% (50/225), immunosuppressive therapy (Cyclophosphamide, Mitoxantrone, Methotrexate, Azathioprine) in 7% (16/225), radio-iodine therapy in 4% (9/225) or multiple preceding cytotoxic therapies in 7% (15/225). Median latency period between cytotoxic therapy and t-AML was 5.8 years. In intensively treated t-AML patients (172/225), median OS was 13.7 months as compared to 39.4 months in de novo AML (823/908, p<0.001). The substantial difference in median OS particularly applied to patients <60 years with a 5-year OS of 31% in t-AML (96/225) as compared to 51% in de novo AML (562/908, p<0.001). In patients ≥60 years, there was a tendency towards better OS in de novo AML, however, this did not reach statistical significance (p=0.066). Interestingly, OS in patients receiving intensive therapy for t-AML was comparable with de novo AML within the favorable genetic risk groups (APL p=0.927, ELN-favorable p=0.714). In contrast, a significant difference in favor of de novo AML was observed within the ELN-intermediate (p=0.009) and ELN-adverse (p=0.016) risk groups, which was most likely caused by age differences between these groups. However, there was no age difference within the favorable ELN risk group (p=0.878). Considering only patients who received non-intensive therapy, OS (p=0.394), age (p=0.087), ECOG status (p=0.123) and ELN risk group (p=0.098) did not differ significantly between t-AML (53/225) and de novo AML (85/908). Multivariate analysis (including several covariates such as age, ELN risk, ECOG and CCI) did not confirm t-AML per se as an independent risk factor for OS (p=0.081), RR (p=0.982) or NRM (p=0.320) in intensively treated patients. Interestingly, OS was particularly favorable after radio-iodine therapy as compared to other treatment modalities (p=0.042) and highly unfavorable after pretreatment with multiple cytotoxic therapies (p=0.009). Multivariate analysis revealed ECOG score >1 (HR 2.3, p=0.002), adverse ELN risk (HR 1.7, p=0.003), BMI <18,5 kg/m2 (HR 2.7, p=0.029), diabetes (HR 2.0, p=0.029) and intensive treatment (HR 0.3, p<0.001) as independent prognostic factors in t-AML. Conclusion: Our data indicate that inferior OS in t-AML as compared to de novo AML rather results from an accumulation of adverse genetic alterations and patient-associated risk factors than from t-AML itself. Thus, our study strongly supports the current view that risk stratification in t-AML (including indication for allo-HSCT) should align with strategies used in de novo AML patients (based on genetic features), both in the case of intensive and non-intensive therapy. Regarding the new International Consensus Classification of AML, our data are in accordance with the classification of t-AML as a "diagnostic qualifier" within the different AML subgroups rather than a separate subcategory.

Comparison of ATG-Based Immunosuppressive Treatment and Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Transfusion-Dependent Non-Severe Aplastic Anemia: A Single Center, Retrospective Analysis

Transfusion-dependent non-severe aplastic anemia (TD-NSAA) refers to aplastic anemia (AA) that is dependent on blood transfusion but does not fulfilling the criteria for severe AA (SAA). It has been clear that allogeneic hematopoietic stem cell transplantation (HSCT) and anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) is the front line for the treatment of SAA, but there is no consensus on the treatment timing and strategy for TD-NSAA. The natural history observation reported that the progress-free survival (PFS) of TD-NSAA at 60 months after diagnosis is around 62%, but decreased significantly to 22% at 120 months. In China, the practical guideline recommends cyclosporine-based IST with or without hematopoietic stimulating regimes (such as androgens) as initial treatment, and further treated as SAA if no response was observed after 6 months management. As reported, the hematopoietic response of ATG-based IST was much better than CsA-based IST (75% Vs. 55.8%, 6-month) for TD-NSAA, however, the relapse and clonal expansion are still the unavoidable events. For HSCT, the long-term PFS is much better than IST for SAA, but the complications (including graft versus host disease, various infection, etc.), transplantation related mortality, as well as donor availability still limited its application. At present, there is limited data compared the efficiency of HSCT and IST for TD-NSAA. With the development of haplo-identical transplantation in China, most TD-NSAA own a donor, and we also performed HSCT for those young patients after informed consent. Herein, we respectively compared the efficiency of ATG-based IST and HSCT for TD-NSAA, and also analyzed the risk factors that contribute to the overall survival (OS) as well as event free survival (EFS). During Jul 2011 to Dec 2019, 97 TD-NSAA patients were diagnosed in our cohort, among them, 5 only received supportive treatment, 30 received CsA-based IST with or without androgen, and the other 62 patients received HSCT or ATG-based IST therapy. We further analyzed the efficiency and prognosis of 55 patients aged 16-60 years old who received HSCT or ATG-based IST therapy. Among them, 27 (49.09%) patients received ATG-based IST, and the others performed HSCT (including 14 from sibling donor, 7 from haplo-identical donor and 7 from unrelated donor) (the baseline information showed in Table1). Results showed that the 12-month overall response rate (ORR) of ATG-based IST and HSCT were 48.1% (with 18.52% CR) and 78.57% (with 60.71% CR), respectively (P=0.04, Fig A). The median time of achieving transfusion-free was 94(35-205) and 24(11-139) days, respectively in ATG-based IST and HSCT group (P<0.001, Fig B). The 5-year OS and EFS rates were 54.9±13.3% and 34.5±12.1% in ATG-based IST group respectively, and 70.0±9.0% and 62.6±9.6% in HSCT group, while no statistically differences was observed (Fig C and D). To explore the possible influencing factors of 5-year OS and EFS, we performed COX regression analysis based on age, disease duration, baseline absolute neutrophil count (ANC), hemoglobin (HB), platelet count (PLT), serum ferritin (SF), lymphocyte percentage, and CD4/CD8 ratio. Univariate analysis showed that disease duration, baseline HB, SF, and ANC may affect OS and EFS of patients in ATG-based IST group (Table 2), and multivariate analysis showed that SF≧1000ng/ml was an independent risk factor for OS in ATG-based IST group. While in the HSCT group, patients with disease duration≧20 months had a higher risk of events (Table 3). The subgroup analysis showed that in HSCT group, patients with disease duration of 6 to 20 months had a lower risk of events (HR=0.196, 95%CI: 0.046-0.832); the HR of the group <6 months and ≥20 months were not statistically significant (Fig E). TD-NSAA patients with disease duration between 6 months and 20 months had a higher EFS rate in HSCT group than that in ATG-based IST group (Fig F). The subgroup analysis of mortality was not statistically significant (Fig G). To conclusion, TD-NSAA patients should be actively treated, patients with shorter disease duration and no iron overload may achieve a better response. The 12-month ORR in the HSCT group was higher than that in the IST group, but there was no significant difference in OS rate and EFS rate, even there is a great difference tendency. For TD-NSAA patients with a disease duration between 6 to 20 months, HSCT has a higher EFS rate than IST, which may be a better choice. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Role of postoperative chemoradiotherapy in head and neck cancer without positive margins or extracapsular extension: a propensity score-matching analysis

BackgroundThe aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT).MethodsPatients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method.ResultsAfter matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p < 0.001), DFS (p < 0.001), LRFS (p < 0.001) and DMFS (p = 0.002), while pT3-4 was a poor prognostic factor for DMFS (p = 0.005). Overall, patients receiving POCRT had no significant differences from those receiving PORT in OS (p = 0.062), DFS (p = 0.288), LRFS (p = 0.076) or DMFS (p = 0.692). But notably, patients with pN2-3 achieved better outcomes from POCRT than PORT in 3-year OS (p = 0.050, 63.9% vs. 47.9%) and LRFS (p = 0.019, 74.6% vs. 54.9%). And patients with pT3-4 also had higher 3-year LRFS (p = 0.014, 88.5% vs. 69.1%) if receiving POCRT.ConclusionsAmong all intermediate-risk pathological features, pN2-3 and pT3-4 were independent unfavorable prognostic factors for patients with HNSCC without PMs or ECE. POCRT can improve the survival outcomes of patients with pN2-3 or pT3-4.

Effects of radiotherapy on the survival of patients with malignant spermatic cord tumors: A retrospective cohort study.

Malignant spermatic cord tumors (SCT) are rare and currently, there is no consensus regarding the role of radiotherapy in their treatment. This study evaluated the effect of radiotherapy on the overall survival (OS) of patients with malignant SCT based on the large-sample advantage of the Surveillance, Epidemiology, and End Results (SEER) database. Patients with malignant SCT recorded in the SEER database from 1975 to 2016 were included. All patients were divided into non-radiation and radiation groups, and propensity score matching (PSM) (1:1) was performed for baseline covariates between the two groups. The overall survival rate between the two groups of patients was analyzed using the Kaplan-Meier curve. The effects of radiotherapy on patient prognosis were analyzed using univariate and multivariate COX regression analyses. In total, 389 patients with malignant SCT were included. There were 285 (73.26%) and 104 (26.74%) patients who either did or did not receive radiotherapy, respectively. Kaplan-Meier curves before and after PSM showed no significant differences in OS between the two groups. Similarly, multivariate COX regression models before and after PSM showed that radiotherapy was not an independent risk factor for OS in patients with malignant SCT. Radiotherapy has no obvious advantage in improving the survival time of patients with malignant SCT.

Transarterial Chemoembolization Combined with Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors versus Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Advanced Hepatocellular Carcinoma.

This study aimed to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (TACE+IT) versus ICIs plus TKIs (IT) for advanced hepatocellular carcinoma (HCC). Data of consecutive advanced HCC patients receiving TACE+IT or IT between January 2019 and December 2021 were included and were retrospectively analyzed. Propensity score matching (PSM) was performed to reduce bias due to confounding variables. The primary outcome of the study was overall survival (OS). The secondary outcomes were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs), respectively. Sixty-four patients were enrolled in the study, among which 24 and 40 received TACE+IT and IT, respectively. The PSM cohort included 24 patients receiving TACE+IT (TACE+IT group) and 24 patients receiving IT (IT group) alone. During a median follow-up of 23 months, patients in TACE+IT group had significantly longer OS (median, 17.3 vs 11.8 months, P = 0.023), better ORR (41.7% vs 12.5%, P = 0.023) and DCR (79.2% vs 50.0%, P = 0.035) than those in the IT group, whereas a non-significant trend in PFS (median, 7.4 vs 6.7 months, P = 0.23) was observed. According to multivariable cox regression analysis, it was found that treatment modality was the only independent risk factor for OS (HR = 0.404, 95% CI = 0.179-0.911, P < 0.05). There were no remarkable differences in AEs associated with ICIs and TKIs between the two groups, with the exception of gastrointestinal reaction. TACE combined with ICIs plus TKIs significantly improved OS, ORR, and DCR and showed a relatively longer PFS trend over ICIs combined with TKIs for advanced HCC.

Evaluation of prognostic factors and oncological outcomes in patients with limb-localized myxoid liposarcoma

This study aims to evaluate the prognostic factors and treatment outcomes of patients with extremity-localized myxoid liposarcoma (MLS). Between January 2001 and October 2019, a total of 43 patients (29 males, 14 females; mean age: 56.3±11.4 years; range, 34 to 76 years) who were histopathologically diagnosed with MLS in our clinic were retrospectively analyzed. Data including demographic characteristics, tumor localization, tumor volume and length, histopathological characteristics, the surgery and chemotherapy (CT)/radiotherapy (RT) applied, survival rates, and complications such as local recurrence and metastasis were recorded. The treatment results and potential prognostic factors were identified. The overall survival (OS) and cancer-specific survival (CSS) rates were evaluated. The mean follow-up was 106.8±54.1 (range, 29 to 204) months. The mean tumor size was 11.4±6.5 (range, 4.7 to 36) cm. Tumor localization was determined as lower extremity in 76.7% of cases and upper extremity in 23.2%. The patients were divided into two groups according to the type of RT they received as follows: the patients who underwent neoadjuvant RT + wide surgical resection (n=14, 32.5%) and patients who underwent extensive surgical resection + adjuvant RT (n=29, 67.4%). To four patients who developed distant metastasis and to two who developed local recurrence, adjuvant CT was applied. In the whole cohort, the OS rate was 87.1% at five years and 73.2% at 10 years. The five and 10-year CSS rates were 83.5% and 66.4%, respectively. Local recurrence developed in 12 (27.9%) and distant metastasis in four (9%) patients. In the multivariate analysis, high tumor grade, R2 margins, and metastasis were found to be independent risk factors for OS. Although wide resection provided significantly good local control, neoadjuvant RT and adjuvant CT were not found to be prognostic factors for OS or CSS (p>0.05). High tumor grade, R2 margins, and metastasis are independent risk factors for increased OS and OSS. Surgery with CT and neo/adjuvant RT is not an independent risk factor for OS or CSS. Despite patients with a larger tumor size and neurovascular proximity, similar disease-free survival rates can be achieved in the patients receiving neoadjuvant RT. Neoadjuvant RT can be considered in lesions close to neurovascular structures or in large lesions, with a high risk of wound complications.

Anatomical Resection Improved the Outcome of Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis of a Retrospective Cohort.

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy after hepatocellular carcinoma (HCC), with a dismal prognosis and high heterogeneity. The oncological advantages of anatomical resection (AR) and nonanatomical resection (NAR) in HCC have been studied, but surgical strategies for ICC remain controversial with insufficient investigations. From Jan 2013 to Dec 2016, 3880 consecutive patients were retrospectively reviewed from a single center. Patients with ICC undergoing AR or NAR have been enrolled according to inclusion and exclusion criteria. Propensity score matching (PSM) analysis was performed between two groups with a 1 : 1 ratio. The primary endpoint was overall survival (OS), and the secondary endpoints included disease-free survival (DFS), intraoperative patterns, postoperative morbidity, mortality, complications and recurrence. A prognostic nomogram was developed by a multivariate Cox proportion hazard model. After PSM, 99 paired cases were selected from 276 patients enrolled in this study. Patients in the AR group achieved better 1-, 3-, and 5-year OS (70%, 46%, and 34%, respectively) and DFS (61%, 21%, and 10%, respectively) than patients in the NAR group with statistical significance after PSM analysis. The postoperative complications and recurrence patterns were comparable between the two groups. Multivariate analysis identified NAR, tumor size >5 cm, multiple tumors, and poor differentiation as independent risk factors for OS (p < 0.05). Selected patients can benefit most from AR, according to subgroup analysis. A prognostic nomogram based on six independent risk factors for OS and factors with clinical significance was constructed to predict OS in ICC patients. AR improved the long-term survival of ICC with comparable postoperative complications and similar recurrence patterns. AR is suggested in ICC patients with sufficient remnant liver volume. In addition to surgery strategy, malignant characteristics of tumors are risk factors for ICC prognosis.

The Clinical Characteristics and Treatments for Large Cell Carcinoma Patients Older than 65 Years Old: A Population-Based Study.

Pulmonary large cell carcinoma, a type of non-small cell lung cancer (NSCLC), is a rare neoplasm with poor prognosis. In this study, our aim was to investigate the impact of radiation sequences with surgery for stage III/IV LCC patients between different age groups, especially in the elderly patients. The patients with LCC and other types of NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015 were retrospectively analyzed. Then we divided the LCC patients into two age groups: &lt;65 years old group and ≥65 years old group. Propensity score method (PSM) was used to control potential differences between different groups. The overall survival (OS) of LCC patients and other types of NSCLC patients were evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression analysis were employed to explore the independent risk factors of OS. The forest plots of HRs for OS were generated to show the above outcomes more visually. In total, 11,349 LCC patients and 129,118 other types of NSCLC patients were enrolled in this study. We divided LCC patients into &lt;65 years old group (4300) and ≥65 years old group (7049). LCC patients was more common in whites (81.4%), males (58.3%), elderly (≥65 years old: 62.1%), east regions (52.7%), upper lobe (51.6%), right-origin of primary (55.4%), with advanced grade (54.2%) or stage (76.7%). After PSM, Kaplan-Meier analysis and multivariate Cox analysis showed significantly worse survival prognosis for LCC patients compared to other types of NSCLC, especially in the group ≥65 years old (HR: 1.230; 95% CI: 1.171-1.291; p &lt; 0.001). For LCC patients, there were some risk survival factors including whites, males, not upper lobe, advanced stage, elder age at diagnosis, bone metastasis, liver metastasis, singled status, no lymphadenectomy, no surgery, and no chemotherapy (p &lt; 0.05). In LCC patients ≥65 years old, radiation after surgery had significantly better impact on overall survival outcomes (HR: 0.863, 95% CI: 0.765-0.973, p = 0.016), whereas radiation prior to surgery (HR: 1.425, 95% CI: 1.059-1.916, p = 0.019) had significantly worse impact on prognosis of patients. In LCC patients &lt;65 years old, radiation sequences with surgery had no significant impact on the OS of patients (p = 0.580), but ≥4 LNRs had significantly survival benefits to prognosis (HR:0.707, 95% CI: 0.584-0.855). Elderly LCC patients had worse malignant tumors than young patients, of which the majority were diagnosed as stage III/IV tumors. Postoperative radiotherapy may achieve a better prognosis for stage III/IV LCC patients older than 65 years old compared to other radiation sequences with surgery.

Survival and risk factors among upper tract urothelial carcinoma patients after radical nephroureterectomy in Northeast China.

The study objective was to investigate the prognostic risk factors related to overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Patients were then divided into different risk groups (based on their number of prognostic risk factors), and specific postoperative treatment plans were formulated for patients in different risk groups. We retrospectively analyzed the data of 401 patients with UTUC who underwent RNU between 2010 and 2020. Univariate and multivariate Cox regression analyses were used to evaluate the associations of clinicopathological variables with prognosis among UTUC patients.Kaplan-Meier survival analysis of patients in different risk groups (based on their number of prognostic risk factors) was conducted. Multivariate Cox regression analysis showed that sex (being male), LVI, pT stage (>pT2), and lack of postoperative intravesicalinstillation were independent risk predictors of shorter OS, CSS, RFS, and MFS (all P<0.05).Laparoscopic RNU was also associated with shorter OS, CSS, and MFS, but not with shorter RFS (P=0.068). After risk stratification, the 5-year OS, CSS, RFS, and MFS in the high-risk group were 42.3%, 46.4%, 41%, and 46%, respectively. Sex (being male), LVI, pT stage (>pT2), and intravesical instillation were independent predictors of OS, CSS, RFS, and MFS for UTUC. All were risk factors, except for intravesicalinstillation, which was a protective factor. Additionally, laparoscopic RNU was an independent risk factor for OS, CSS, and MFS. Patients in the high-risk group may benefit greatly from adjuvant or neoadjuvant chemotherapy.