Negative Predictor Of Overall Survival Research Articles

Colorectal Leiomyosarcoma: Demographics Patterns, Treatment Characteristics, and Survival Analysis in the U.S. Population.

Colorectal leiomyosarcoma (CR-LMS) is a rare neoplasm arising from smooth muscle cells. It accounts for less than 0.1% of all colorectal malignancies. In this population-based study, we aim to understand the demographics, treatment characteristics, and pathologic factors associated with survival in CR-LMS. Data from the SEER Program (2000-2018) were analyzed using SEER*Stat and SPSS. Statistical methods included descriptive analysis, Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazards regression to assess the impact of various factors on disease-specific and overall survival. A total of 191 cases of CR-LMS were identified. Most patients were 60-69years of age (median: 64years) and Caucasian (78%). There was nearly the same distribution in sex (M:F ratio; 1:1.2). The overall 5-year observed survival was 50.3% (95% C.I., 46.3-54.2). The 5-year disease-specific survival (DSS) was 66.1% (95% C.I., 62.0-70.1). The 5-year overall survival after resection was 60.8% (95% C.I., 56.3-65.3). Multivariable analysis identified grades III and IV (p = 0.028) as negative predictors of overall survival. Regional spread and distant stage are negative predictors of overall survival (p < 0.01). Our data reveals that colorectal leiomyosarcoma (CR-LMS) often presents in patients around 64years old with advanced stages and poor differentiation. Key adverse prognostic factors include older age, high tumor grade, large tumor size, and distant metastases, with surgical resection showing the best survival outcomes. To improve outcomes, further research and consolidation of data are essential for developing targeted therapies and comprehensive guidelines.

TP53 and EGFR amplification are negative predictors of overall survival in patients diagnosed with non-small cell lung cancer with brain metastases

BackgroundThe discovery of driver genes such as EGFR, KRAS, and ALK, has dramatically shifted treatment patterns in patients harboring these oncogenes. However, dissemination into the central nervous system (CNS) is a severe complication. In addition, the particular anatomical structure of the CNS has made it difficult to obtain tissue specimens from brain metastases (BM) to generate a gene map, as such, potential predictive markers for survival in patients with non-small cell lung cancer (NSCLC) and BM (NSCLC-BM) remain unclear. MethodsData from 28 patients diagnosed with NSCLC-BM between June 2019 and May 2021 at Guangdong Sanjiu Brain Hospital (Guangzhou, China), were reviewed. Targeted next-generation sequencing (NGS) of a 168 cancer-related gene panel was available for surgically resected brain tissues from all patients. In addition, molecular characteristics and overall survival (OS) were analyzed to determine potential predictive markers. ResultsAmong patients with NSCLC-BM, NGS revealed that TP53 was the most frequent mutation (61 %), with a detection rate of 39 %, closely by EGFR amplification. Additionally, CDKN2A, MYC, LRP1B, and RNF43 were frequently observed (18 %). The median OS was significantly shorter in the TP53 mutation group than in the wildtype group (14 versus undefined months, p = 0.014). Similar results were also found in the genetic alteration of EGFR amplification, suggesting that EGFR amplification was associated with worse OS (14 vs. 24 months, p = 0.039). Interestingly, NGS revealed that gene alternations such as TP53, EGFR amplification, and CDKN2A, tended to coexist and such a co-alteration panel indicated worse clinical outcomes (median OS, 5 months). In addition, the detection rate of negative survival genes, including TP53 or EGFR amplification, was much higher in tumor tissues than in plasma samples, indicating the limited predictive value of matched PLA samples. ConclusionsGene signatures, such as TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.

Sarcopenia is a prognostic factor in lymphoma patients: a systematic review and meta-analysis

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47–2.41; p < 0.001). The heterogeneity was high (I2=80%). However, the result of the Egger test indicated a significant publication bias (p < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant (p > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37–2.29; p < 0.001; I2=70%). There was no significant publication bias (p > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR = 1.61;95% CI: 1.19–2.18; I2=30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24–4.24; p = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04–4.65; p = 0.039; I2=68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL.

Patterns and Prognosis of Local Recurrence of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy.

Objective: To investigate the patterns of local failure and prognosis in patients with locally recurrent nasopharyngeal carcinoma (rNPC) after primary intensity-modulated radiotherapy (IMRT). Methods: The data of 298 patients with locally rNPC after IMRT were retrospectively analyzed. Magnetic resonance images of the initial and recurrent tumors were reviewed and, for patients with extra-nasopharyngeal local recurrence, the gross tumor volume of local recurrence was transferred to the original IMRT plan for dosimetry analysis. Significant prognostic factors for overall survival (OS) were selected by multivariate Cox regression analysis. Results: The commonest recurrence sites were the nasopharynx (93%, 277/298) and skull base (53.7%, 160/298). Of the 21 patients with extra-nasopharyngeal recurrence (19 cases valid), 12 had in-field failures, 4 had marginal failures, and 3 had out-field failures. The ethmoid sinus (57.1%, 4/7) and nasal cavity (28.6%, 2/7) were the most frequent sites of marginal and out-field failures. After median follow-up of 37 months, the 3-year and estimated 5-year OS rates were 57.3% and 41.7%, respectively. Multivariate analysis showed that age, recurrence interval, plasma Epstein-Barr virus (EBV) DNA level, and recurrent T stage were independent prognostic factors for OS. Conclusions: Local failure after IMRT occurs most commonly in the nasopharynx and skull base. In patients with extra-nasopharyngeal recurrence, in-field failure remains the main failure pattern, and marginal and out-field failures mainly occur in the ethmoid sinus and nasal cavity. Elder age, shorter recurrence interval, detectable plasma EBV DNA, and advanced recurrent T stage are negative predictors of OS in patients with rNPC.

Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: a systematic review and meta-analysis of 1471 patients with solid tumors

BackgroundThe clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.MethodsWe conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.ResultsA total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74–3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49–2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58–4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50–4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.ConclusionsCTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.

Linking GATA2 to myeloid dysplasia and complex cytogenetics in adult myelodysplastic neoplasm and acute myeloid leukemia

AbstractGATA binding protein 2 (GATA2) is a conserved zinc finger transcription factor that regulates the emergence and maintenance of complex genetic programs driving development and function of hematopoietic stem and progenitor cells (HSPCs). Patients born with monoallelic GATA2 mutations develop myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML), whereas acquired GATA2 mutations are reported in 3% to 5% of sporadic AML cases. The mechanisms by which aberrant GATA2 activity promotes MDS and AML are incompletely understood. Efforts to understand GATA2 in basic biology and disease will be facilitated by the development of broadly efficacious antibodies recognizing physiologic levels of GATA2 in diverse tissue types and assays. Here, we purified a polyclonal anti-GATA2 antibody and generated multiple highly specific anti-GATA2 monoclonal antibodies, optimized them for immunohistochemistry on patient bone marrow bioosy samples, and analyzed GATA2 expression in adults with healthy bone marrow, MDS, and acute leukemia. In healthy bone marrow, GATA2 was detected in mast cells, subsets of CD34+ HSPCs, E-cadherin–positive erythroid progenitors, and megakaryocytes. In MDS, GATA2 expression correlates with bone marrow blast percentage, positively correlates with myeloid dysplasia and complex cytogenetics, and is a nonindependent negative predictor of overall survival. In acute leukemia, the percent of GATA2+ blasts closely associates with myeloid lineage, whereas a subset of lymphoblastic and undifferentiated leukemias with myeloid features also express GATA2. However, the percent of GATA2+ blasts in AML is highly variable. Elevated GATA2 expression in AML blasts correlates with peripheral neutropenia and complex AML cytogenetics but, unlike in MDS, does not predict survival.

Yttrium-90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver

PurposeTo assess whether yttrium-90 transarterial radioembolization (TARE) is safe and effective in the treatment of primary lung cancer metastases to the liver (LCML). Methods and MethodsThis retrospective study included 57 patients with LCML who were treated with 79 TARE treatments. Histology included non–small cell lung cancer (NSCLC) (n = 27), small cell lung cancer (SCLC) (n = 17), and lung carcinoid (LC) (n = 13). Survival was calculated using Kaplan–Meier method; differences between groups were estimated using log rank test. Cox proportional hazards model was used to determine factors influencing survival. Adverse events were graded using the Society of Interventional Radiology Adverse Events Classification. ResultsMedian overall survival (OS) was as follows: NSCLC, 8.3 months (95% confidence interval [CI], 6.3–16.4 months); SCLC, 4.1 months (95% CI, 1.9–6.6 months); and LC, 43.5 months (95% CI, 7.8–61.4 months). For NSCLC, presence of bilobar vs unilobar disease (hazard ratio [HR], 5.24; 95% CI, 1.64–16.79; P = .002); more tumors, 2–5 vs 1 (HR, 4.88; 95% CI, 1.17–20.37; P = .003) and >5 vs 1 (HR, 3.75; 95% CI, 0.95–6.92; P = .05); and lobar vs segmental treatment (HR, 2.56; 95% CI, 0–NA; P = .002) were negative predictors of OS. For SCLC, receipt of >2 lines of chemotherapy vs ≤2 lines (HR, 3.16; 95% CI, 0.95–10.47; P = .05) was a negative predictor of OS. For LC, tumor involvement of >50% was a negative predictor of OS (HR, 3.77 × 1015; 95% CI, 0–NA; P = .002). There were 11 of 79 severe or life-threatening adverse events within 30 days (abdominal pain, altered mental status, nausea/vomiting, acalculous/aseptic cholecystitis, hyponatremia, pancreatitis, renal failure, and death from pneumonia). ConclusionsTARE has an acceptable safety profile for the treatment of LCML, with survival benefits best seen in LC tumors.

Prediction of prognosis and immunotherapy response in lung adenocarcinoma based on CD79A, DKK1 and VEGFC

BackgroundTumor immune microenvironment (TIME) is crucial for tumor initiation, progression, and metastasis; however, its relationship with lung adenocarcinoma (LUAD) is unknown. Traditional predictive models screen for biomarkers that are too general and infrequently associated with immune genes. MethodsRNA sequencing data of LUAD patients and immune-related gene sets were retrieved from public databases. Using the common genes shared by The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), differential gene expression analysis, survival analysis, Lasso regression analysis, and univariate and multivariate Cox regression analyses were performed to generate a novel risk score model. LUAD cohort in International Cancer Genome Consortium (ICGC), GSE68465 cohort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes constructed risk score. The LUAD-related prognosis, clinical indicators, immune infiltrate characteristics, response to immunotherapy, and response to chemotherapeutic agents in different risk groups were evaluated by CIBERSORT, ImmuCellAI, pRRophetic and other tools. ResultsThe risk score model was constructed using CD79a molecule (CD79A), Dickkopf WNT signaling pathway inhibitor 1 (DKK1), and vascular endothelial growth factor C (VEGFC). High risk score was identified as a negative predictor for overall survival (OS) in subgroup analyses with tumor stage, TNM classification, therapy outcome, and ESTIMATE scores (P < 0.05). Low risk score was positively associated with plasma cells, memory B cells, CD8 T cells, regulatory T cells and γδT cells (P < 0.05). In low-risk group, programmed cell death 1 receptor (PD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3) and indoleamine 2,3-dioxygenase (IDO) were more robustly expressed (P < 0.05). The treatment responses of immune checkpoint blockade (ICB) therapy and chemotherapy were likewise superior in low-risk group (P < 0.05). In immunohistochemical analysis, the tumor group had significantly higher levels of CD79A, DKK1, and VEGFC than the adjacent normal group (P < 0.01). ConclusionsCD79A, DKK1 and VEGFC are important differential genes related to LUAD, risk score could reliably predict prognosis, composition of TIME and immunotherapy responses in LUAD patients. The excellent performance of the risk model shows its strong and broad application potential.

How reliable is the high-volume definition in prostate cancer patients: the potential game-changing role of PSMA.

To evaluate whether metabolic and volumetric data from 68Ga-PSMA PET/CT performed during staging of de-novo high-volume mCSPC patients who received docetaxel could be used to predict survival. Forty-two de-novo high-volume mCSPC patients, who received ADT + Docetaxel and underwent 68Ga-PSMA PET/CT for staging, were included in the study. The association between patients' pathological data, all PSA measurements, treatments they received, the data obtained from 68Ga-PSMA PET/CT and progression-free and overall survival were examined. In the multivariate analysis, PSMA-TV (primary) and PSMA-TV (WB) variables were shown to be independent negative predictors of overall survival. For the threshold value of 19.91 cm3 obtained for PSMA-TV (primary), HR was calculated as 6.31, the 95% confidence interval (CI): 1.01-39.18, P = 0.048. For the threshold value of 1226.5 cm3 obtained for PSMA-TV (WB) variable, HR was calculated as 58.62, the 95% CI: 2.55-1344.43, P = 0.011. In our study, SUVmax (WB) variable was found to be an independent and negative predictor of progression-free survival. For the determined threshold value of 17.74, HR was calculated as 16.24, 95% CI: 1.18-22.76, P = 0.037. Metabolic and volumetric data obtained from 68Ga-PSMA PET/CT can be used to predict survival in de-novo high-volume mCSPC. Our results show that in ADT + Docetaxel receiving patients, a subgroup with higher PSMA-TV (WB) values have a significantly worse prognosis. This situation suggests that the high-volume disease definition in the literature may be insufficient for this group, and that 68Ga-PSMA PET/CT can play an essential role in demonstrating the heterogeneity within the group.

Association between length of stay and postoperative survival in patients with lung cancer: a propensity score matching analysis based on National Cancer Database.

Postoperative complications tend to result in prolonged hospitalization. The aim of this study was to investigate whether prolonged postoperative length of stay (LOS) can predict patient survival, particularly long-term survival. All patients undergoing lung cancer surgery between 2004 and 2015 were identified in the National Cancer Database (NCDB). The highest quintile of LOS (more than 8 days) was defined as prolonged length of stay (PLOS). We performed 1:1 propensity score matching (PSM) between the groups with and without PLOS (Non-PLOS). Excluding confounding factors, postoperative LOS was used as a surrogate for postoperative complications. Kaplan-Meier and Cox proportional hazards survival analyses were performed to analyze survival. A total of 88,007 patients were identified. After matching, 18,585 patients were enrolled in the PLOS and Non-PLOS groups, respectively. Before and after matching, 30-day rehospitalization rate and 90-day mortality in the PLOS group were significantly higher than they were in the Non-PLOS group (P<0.001), indicating a potential worse short-term postoperative survival. After matching, the median survival of the PLOS group was significantly lower than that of the Non-PLOS group (53.2 vs. 63.5 months, P<0.0001). Multivariable analysis revealed that PLOS is independent negative predictor of overall survival [OS; hazard ratio (HR) =1.263, 95% confidence interval (CI): 1.227 to 1.301, P<0.001]. In addition, age (<70 or ≥70), gender, race, income, year of diagnosis, surgery type, pathological stage, and neoadjuvant therapy also were independent prognostic factors of postoperative survival for patients with lung cancer (all P<0.001). Postoperative LOS could be taken as the quantitative indicator of postoperative complications of lung cancer in NCDB. In this study, PLOS predicted worse short-term and long-term survival independent of other factors. Avoiding PLOS could be considered to benefit patient survival after lung cancer surgery.

The Japanese 5-5-500 Rule Predicts Prognosis of Hepatocellular Carcinoma After Hepatic Resection.

The 5-5-500 rule has been proposed to increase the candidates of liver transplantation for patients with hepatocellular carcinoma with reasonable recurrence rates. However, the clinical significance of the 5-5-500 rule in patients who underwent hepatic resection for hepatocellular carcinoma has not been fully investigated. The study comprised 206 patients who had undergone primary hepatic resection for hepatocellular carcinoma between 2008 and 2018. We retrospectively investigated prognostic significance of the 5-5-500 rule and disease-free, as well as overall, survival and further prognostic stratification using inflammatory-based biomarkers. 132 patients (64%) were classified within the 5-5-500 rule, while 74 patients (36%) were classified outside the 5-5-500 rule. Among the patients outside the 5-5-500 rule, 62 patients had tumors greater than 5 cm, and 23 patients showed serum AFP levels greater than 500 ng/ml. In the multivariate analysis, being female (p<0.01), HBs-Ag positive (p<0.01), having an ICGR15 ≥15% (p=0.03), and being outside the 5-5-500 rule (p=0.01) were independent and significant predictors of disease-free survival, while being HBs-Ag positive (p=0.04), having poor tumor differentiation (p=0.03), and residing outside the 5-5-500 rule (p=0.01) were independent and negative predictors of overall survival. Elevated CRP-to-albumin ratio was associated with poor overall survival in the patients outside the 5-5-500 rule, but not in patients within the 5-5-500 rule (p=0.17). The 5-5-500 rule can be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection. CRP-to-albumin ratio might be useful to stratify the outcomes in patients outside the 5-5-500 rule.

Epithelial tumors of the thymus with pleural dissemination: the potential role of surgery

Background. Pleural metastases of thymic epithelial tumors are detected in 5–7 % of patients at initial diagnosis and in 10 % of patients during a follow-up after radical surgery for the primary tumor. Partial pleuroectomy is the cornerstone of treatment strategy in this group of patients.The aim of the study was to assess the role of surgery in the treatment of patients with thymic epithelial tumors with pleural dissemination.Material and Methods. From January1, 2010 to June 30, 2021, 21 patients with thymic epithelial tumors (thymoma – 13, thymic cancer – 8) and pleural implants (stage IVA – 11, isolated pleural metastases as tumor progression after radical surgery – 10) underwent partial pleuroectomy with resection of the diaphragm and lung if necessary. Four patients underwent inthraoperative photodynamic therapy and another 4 patients received intrapleural hyperthermic chemotherapy.Results. R0 resection was performed on 12 (57.2 %) patients. Postoperative complications were observed in 6 (28.6 %) patients. The mortality rate was 7.5 %. The overall 1-, 3- and 5-year survival rates were 78 % (95 % CI 61–95), 49 % (95 % CI 23–75), and 41 % (95 % CI 15–67), respectively. The median overall survival time was 29 months (95 % CI 0–60.6). Recurrence occurred in 10 (47.6 %) cases. One-year recurrence-free survival was 60 % (95 % CI 30–90). Independent negative predictors for overall survival were: thymic cancer, incomplete resection, presence of postoperative complications and local recurrence.Conclusion. Surgery is the mainstay of treatment for patients with pleural metastases (stage IVA thymomas and recurrent thymomas). Metastasectomy of pleural implants will be suffcient to achieve a complete resection.

Improved Survival of Patients with Primary Plasma Cell Leukemia with VRD or Daratumumab-Based Quadruplets: A Multicenter Study By the Greek Myeloma Study Group

Primary plasma cell leukemia (pPCL) is a rare plasma cell disorder with poor outcome. Recently, the International Myeloma Working Group revised its definition proposing cPCS of ≥5% as the new cut-off value. There is still limited information regarding the impact of novel effective anti-myeloma combinations, i.e., bortezomib-lenalidomide triplet (VRd) or daratumumab-based quadruplets (DBQ) on pPCL outcome. Therefore, considering the lack of prospective trials, our aim was to compare retrospectively treatment approaches, and to evaluate prognostic factors of overall survival (OS) in an extended cohort of pPCL patients including those fulfilling the new criteria, in the real-world setting. We analyzed the medical records of 110 pPCL patients (M/F: 51/59; median age 65 years, range: 44-86; IgG: 47, IgA: 17, light-chain: 32, IgD: 3, IgM: 2, non-secretory: 9; ISS1: 9, ISS2: 32, ISS3: 69) out of 3324 myeloma patients (3%), registered in our database, between 2001-2021; 51% of patients were ≤65 years; Eastern Cooperative Group (ECOG) was ≥2 in 46%; 65% had advanced bone disease and 15% had bone/soft tissue plasmacytomas; 72% had Bence-Jones proteinuria, 45% had abnormal LDH, 27% had hypercalcemia, 72% had hemoglobin <10 g/dL and 24% had estimated glomerular filtration rate <30ml/min/1.73m2. High-risk molecular abnormalities i.e., del17p, t(4;14), t(14;16) and 1q21+ tested by FISH hybridization were detected in 56%; 30% had t(11;14). Revised ISS (RISS) was distributed as follows: RISS1: 4%, RISS2: 58%, RISS3: 38%. Median cPCs % was 11% (range: 5-71%), in line with multiparameter flowcytometry findings (10%; range: 4,5-71%). Immunophenotype of PCs was similar in bone marrow and peripheral blood in 92% of patients; CD56(-) and CD27(+) cPCs was found in 52% and 35%, respectively. 37% had cPCS 5-20%; Patients' characteristics did not correlate with cPCs %, except from platelets (PLT) that were significantly lower in patients with >20% cPCs; 89% of patients received novel therapies; DBQ: 21%, VRd: 16%, bortezomib standard combinations (BSC): 52%, conventional chemotherapy (CT): 11%; 35% underwent autologous stem cell transplantation (ASCT). Regarding response to treatment 83% achieved objective response (≥PR); 24% had very good partial response (vgPR), and 26% had complete response (CR). Median time to response was one month (range 1-5). Treatment with VRd/DBQ or ASCT strongly correlated with higher CR rates (45% vs. 19%; p=0.007; 52% vs. 11%; p<0.001, respectively). After a median follow up of 51 months (95% CI: 45-56), 67 patients died (progression: 42, infection: 20, other: 5) and 43 patients remain alive. Early mortality (≤1 month) occurred in 4/67 deceased patients; 51/110 (46%) patients received 2nd line therapy (lenalidomide-based: 17, proteasome inhibitor-based: 12, daratumumab-based: 9, pomalidomide-based: 4, CT: 9). Median number of treatment lines was 1 (range: 1-5). Progression-free survival was 16 months (95% CI: 12-19.8), significantly longer in patients treated with VRd/DBQ vs. BSC/CT (25 months 95% CI: 13.5-36.5, vs. 13 months 95% CI: 9-16.8; p=0.03). Median OS was 29 months (95% CI: 19.6-38.3), significantly longer in patients treated with VRd/DBQ vs. BSC/CT (not reached vs. 20 months, 95% CI: 14-26; 3-year OS: 70% vs. 32%, respectively; p<0.001; HR: 3.88). Median survival after pPCL progression was 8 months (95% CI: 3.5-13.5). In the univariate analysis, ECOG ≥2, PLT <100.000/μL, cPCs (5-20% vs >20%), del17p(+), upfront treatment with VRd/DBQ, ASCT and CR were independent prognostic factors for OS; treatment with VRd/DBQ, del17p(+) and PLT <100.000/μL, significantly predicted for OS in the multivariate analysis (p<0.05). Median OS for patients with del17p(+) vs. del17p(-) was 17 months (95% CI: 11.7-22) vs. 48 months, respectively (95% CI: 27.8-68) (p=0.01, HR: 3.1). Median OS for patients with PLT <100.000/μL vs. ≥100.000/μL was 16 months (95% CI: 9-23) vs. 46 months (95% CI: 28-64) respectively (p=0.01; HzR: 0.34). These real-world data, based on the largest reported national multicenter series of pPCL incorporating the new criteria, has shown that treatment with VRd or antiCD38-based quadruplets induces deep and durable responses and is one of the strongest prognostic factors for OS representing currently the best therapeutic approach for pPCL; ASCT maintained its therapeutic value. Del17p (+) and thrombocytopenia were negative predictors for OS.

Impact of preoperative anemia, iron-deficiency and inflammation on survival after colorectal surgery-A retrospective cohort study.

BackgroundAnemia is present in up to two-thirds of patients undergoing colorectal surgery mainly caused by iron deficiency and inflammation. As anemia is associated with increased risk of perioperative death, diagnosis and treatment of preoperative anemia according to etiology have been recommended.ObjectiveThe aim of the present study was to assess if the association between anemia and survival in patients undergoing colorectal surgery was determined by the severity of anemia alone or also by anemia etiology.MethodsTo determine the prevalence of anemia and etiology, preoperative hematological parameters, C-reactive protein, ferritin and transferrin saturation were retrospectively assessed and correlated with outcome in a cohort of patients undergoing colorectal surgery between 2005 and 2019 at the University Hospital of Innsbruck. Anemia was defined as hemoglobin <120 g/L in females and <130 g/L in males. The etiology of anemia was classified on the basis of serum iron parameters, as iron deficiency anemia, anemia of inflammation or other anemia etiologies.ResultsPreoperative anemia was present in 54% (1316/2458) of all patients. Anemia was associated with iron deficiency in 45% (134/299) and classified as anemia of inflammation in 32% (97/299) of patients with available serum iron parameters. The etiology of anemia was a strong and independent predictor of survival, where iron deficiency and anemia of inflammation were associated with better postoperative survival than other anemia etiologies. One year survival rates were 84.3%, 77.3% and 69.1% for patients with iron deficiency anemia, anemia of inflammation and other anemia types. Inflammation indicated by high C-reactive protein is a strong negative predictor of overall survival.ConclusionsAnemia has a high prevalence among patients undergoing colorectal surgery and rational treatment requires early assessment of serum iron parameters and C-reactive protein.

High Red Cell Distribution Width Is Associated with Worse Prognosis in Early Colorectal Cancer after Curative Resection: A Propensity-Matched Analysis.

Simple SummaryThe association between red blood cell distribution width (RDW) and the prognosis of certain cancers has been established. However, RDW is also related to age, nutrition status, and many systemic disorders. Therefore, it is still unclear whether the association is contributed by these confounders. Here, we present a propensity-score match study demonstrating that RDW is an independently negative predictor for overall survival, disease-free survival, and cancer-specific survival in patients with stage I-II colorectal cancer.The red blood cell distribution width (RDW) is a simple and widely available parameter obtained from a complete blood cell count test and is usually used in the analysis of anemia. Recently, studies have discovered the association between RDW and the host inflammatory response of cancer patients. We aimed to determine the prognostic value of RDW in colorectal cancer (CRC) patients. 5315 total patients with stage I-II CRC from the Chang Gung Memorial Hospital between 2001 and 2018 were enrolled. The study cohort was divided into two groups using RDW = 13.8 as the cutoff value as determined by receiver operating curve. High RDW had worse overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS), and was also independently related to older age, more advanced tumor stage, lower albumin level, lower hemoglobin level, and more co-morbidities including diabetes, hypertension, and chronic kidney disease. We performed a propensity-score matched analysis to balance the heterogeneity between the two groups and to reduce the influence of confounding factors that may have compromised the prognosis. High RDW remained a negative predictor of OS (HR = 1.49, 95% CI: 1.25–1.78), as well as DFS and CSS. In conclusion, this is the first report using propensity matching to demonstrate the relationship between RDW and the prognosis of early-stage CRC patients.

P-181: Treatment outcome and prognostic factors of newly diagnosed Multiple Myeloma receiving Bortezomib-based induction in Hong Kong: an analysis of 448 patients

<h3>Background</h3> Autologous stem cell transplant (ASCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM). In Hong Kong, NDMM received bortezomib-based triplet induction. NDMM ≤65 years of age were considered transplant-eligible (TE), and >65 years transplant-ineligible (TIE). Therefore, upfront ASCT is offered to all TE patients ≤65 years, unless considered medically unfit (TE-unfit) or ASCT refused (TE-refused). The outcome and risk factors were analysed herein. Data was retrieved from the HKSOM database from 2006 to Jan 2021 for 448 NDMM patients treated with bortezomib-based induction therapy, with bortezomib-based triplet in the majority (n=425; 94.9% were triplets). For the entire cohort, apart from being TIE, additional adverse factors for both event free survival (EFS) and overall survival (OS) male gender, advance ISS, R-ISS stage 3, high LDH, failure of post- induction CR, and high-risk FISH. Multivariate analysis excluding high-risk cytogenetics (incomplete data in many) showed that male gender (p=0.026), advance ISS (p=0.000357), high LDH (p=0.000129), CR induction (p=0.003) and ASCT (p=0.001) were negative predictors for OS. In the TE group, upfront ASCT were conducted in 252 (76.1%). Among the TE patients, ASCT was not performed in 63, due to being medically unfit (TE-unfit) (N=41; 12.4%) or patient refusal (TE-refusal) (N=22; 6.6%). Compared with transplanted MM, failure to undergo ASCT rendered a much inferior OS in TE-unfit and TE-refusal (p=1.03×10-8) and EFS (p=0.000043), with survivals comparable to that of TIE patients (median OS 48 months p=0.576, median EFS 31 months p=0.614). Among TE patients who had undergone ASCT, adverse risk factors for OS and EFS included advance ISS (p=0.000293), RISS stage 3 (p=8.5×10-9) and high LDH (p=0.000019). Multivariate analysis excluding high-risk cytogenetics (incomplete data in many) showed age (p=0.012), ISS (p=0.000353) and high LDH (p=0.002) were adverse predictors OS. Post-induction CR predicted superior EFS (median 83 months vs 45 months p=0.006) but not OS. The presence of high-risk FISH (median OS 131 months vs 86 months p=0.022) negatively impacted on OS despite ASCT. Our data reaffirmed the favourable impact of ASCT <h3>Conclustion</h3> Among transplanted patients, adverse risk factors for both OS and EFS included ISS, LDH, HR FISH and post-induction CR status. Moreover, while ASCT was offered to those MM patients ≤65 years, advanced age remained an adverse risk factor. Importantly, among TE patients, refusal of ASCT rendered an inferior EFS and OS comparable to TIE MM that requires due consideration when providing counselling on ASCT in TE MM.

Association Between Regorafenib Dose and Efficacy Against Metastatic Colorectal Cancer in a Real-World Setting.

The association between regorafenib dosage in the treatment of metastatic colorectal cancer (mCRC) and efficacy is currently not well established. It was previously reported that the regorafenib dose as prescribed is associated with efficacy, but doses in actual clinical settings have not been analyzed. We retrospectively analyzed patients with mCRC who had received regorafenib as third-line or later chemotherapy between May 2013 and June 2018. Patients who were not treated in the Pharmaceutical Outpatient Clinic for compliance assessment were excluded. Overall survival was calculated using the Kaplan–Meier method. Prognostic factors, including baseline demographics and adverse events, were evaluated using Cox proportional hazard models. A total of 176 patients were enrolled. By multivariate analysis, total dose until the second cycle < 3180 mg (HR = 1.71, 95% CI, 1.20–2.44, P = .003) was one of independent negative predictors of overall survival. Median survival times of the lower-dose group (< 3180 mg) and higher-dose group (≥ 3180 mg) were 5.8 and 7.6 months, respectively (P = .045). The cumulative dose of regorafenib until the second cycle in patients with mCRC was associated with survival. It is important to individualize regorafenib dose in mCRC patients.

Impact of age on the outcomes of extracorporeal cardiopulmonary resuscitation: analysis using inverse probability of treatment weighting.

Patient selection is crucial to improving the outcomes of extracorporeal cardiopulmonary resuscitation (ECPR). However, ECPR's efficacy with older patients remains unknown. We reviewed patients who underwent extracorporeal membrane oxygenation (ECMO) for refractory cardiac arrest from January 2006 to December 2018. Exclusion criteria were age <18 years, cannulation failure and ECMO applied at another hospital. We divided patients into 2 groups with an age cut-off of 66 years, using the Contal and O'Quigley method for overall survival. We performed inverse probability of treatment weighting (IPTW) between the 2 groups and set the primary outcome as overall survival. We included 318 patients in our study (≤66 years, n = 199; >66 years, n = 119). Before IPTW, we observed that the older group had a higher frequency of diabetes, hypertension, and myocardial infarction. In the young group, more patients had out-of-hospital cardiac arrest as compared with the older group. The hospital mortality rate was 55% (48.7% in the young group, 65.5% in the older group; P = 0.004). In the multivariable analysis after IPTW, the older group showed worse outcomes in overall survival [hazard ratio (HR) = 2.02; 95% confidence interval (CI), 1.50-2.70; P < 0.001] and neurological outcomes at discharge (odds ratio = 2.95; 95% CI, 1.69-5.14; P = <0.001). ECMO insertion during catheterization (HR = 0.57; 95% CI, 0.36-0.90; P = 0.015) and recovery of spontaneous circulation before pump-on (HR = 0.67; 95% CI, 0.50-0.89; P = 0.007) were positive predictors, but initial asystole rhythm, non-cardiac cause (HR = 2.39; 95% CI, 1.59-3.61; P < 0.001), out-of-hospital cardiac arrest (HR = 1.86; 95% CI, 1.24-2.79; P = 0.003) and prolonged cardiopulmonary resuscitation to pump-on time (HR = 1.01; 95% CI, 1.01-1.02; P < 0.001) were negative predictors for overall survival. Older patients who had ECPR had significantly worse survival and neurological outcomes. For patients older than age 66 years, more careful patient selection is critically important for improving the efficacy of ECPR.

Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients.

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

A population-based analysis of clinical features and lymph node dissection in head and neck malignant neurogenic tumors

BackgroundThe influence of lymph node dissection (LND) on survival in patients with head and neck neurogenic tumors remains unclear. We aimed to determine the effect of LND on the outcomes of patients with head and neck neurogenic tumors.MethodsData of patients with surgically treated head and neck neurogenic tumors were identified from the Surveillance, Epidemiology, and End Results (SEER) database (1975–2016) to investigate the relationship between LND and clinical outcomes by survival analysis. Subgroup analysis was performed in IVa and IVb group.ResultsIn total, 662 head and neck neurogenic tumor patients (median age: 49.0 [0–91.0] years) met the inclusion criteria, of whom 13.1% were in the IVa group and 86.9% were in the IVb group. The median follow-up time was 76.0 months (range: 6.0–336.0 months), and the 5-year and 10-year overall survival was 82.4% (95% CI, 0.79–0.85) and 69.0% (95% CI, 0.64–0.73). Cox regression analysis revealed older age (P < .001), advanced stage (P = .037), African American race (P = .002), diagnosis before 2004 (P < .001), and chemotherapy administration (P < .001) to be independent negative predictors of overall survival. Kaplan-Meier analysis demonstrated that LND was not a predictor of clinical nodal negativity (cN0) in either IVa or IVb patients.ConclusionsIn head and neck neurogenic patients, LND may not impact the outcome of cN0 in either IVa or IVb group. These data can be recommended in guiding surgical plan and future studies.