Independent Predictor Of Poor Overall Survival Research Articles

Diabetes and PKM2 affect prognosis in patients with intrahepatic cholangiocarcinoma.

Diabetes mellitus (DM) is a common disease, but its effect on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) has not been reported. The aim of the present study was to explore the prognostic significance of diabetes in patients with ICC treated with hepatectomy and to clarify the role of pyruvate kinase M2 (PKM2). A consecutive retrospective cohort of 110 patients with ICC (28 with DM and 82 without DM) who underwent therapeutic hepatectomy was evaluated between January 2006 and January 2011. The clinicopathological characteristics of the two groups and the differences between overall survival (OS) and recurrence-free survival (RFS) were analyzed. The Cox proportional hazards model was further used to identify independent prognostic predictors. PKM2 expression was measured using immunohistochemical staining in tissues collected, after obtaining informed consent. Patients with ICC with DM exhibited significantly lower OS and RFS rates at 1, 3 and 5 years compared with patients with ICC without DM. Cox multivariate analysis revealed that DM was an independent predictor of poor OS and RFS. Additionally, high PKM2 expression was significantly higher in patients with ICC with DM compared with that in patients without DM. Overall, DM was associated with significantly lower OS and RFS rates in patients with ICC. The underlying biological rationale may be attributed to the higher PKM2 expression rate.

Effect of allogeneic HCT from unrelated donors in AML patients with intermediate- or poor-risk cytogenetics: a retrospective study from the Japanese Society for HCT.

This study aimed to analyze the factors associated with outcomes of bone marrow transplantation (UR-BMT) or cord blood stem cell transplantation from unrelated donors (UR-CBT). We assessed the time from diagnosis to transplantation among acute myeloid leukemia (AML) patients with intermediate- or poor-risk cytogenetics to identify the potential clinical efficacy of transplantation. We retrospectively analyzed 5331 patients who received UR-BMT or UR-CBT between 2008 and 2017. Patients were divided into four groups according to time from diagnosis to transplantation: (1) UR-BMT and > 5months (n = 2353), (2) UR-BMT and ≤ 5months (n = 379), (3) UR-CBT and > 5months (n = 1494), and (4) UR-CBT and ≤ 5months (n = 1106). There was no difference in overall survival (OS) for transplantation at ≤5months and > 5months in patients with first complete remission for both UR-BMT and UR-CBT, but OS in patients with primary induction failure (PIF) and transplantation at ≤ 5months was significantly higher in the UR-CBT group compared with that at >5months (P < 0.001). Multivariate Cox regression analysis also showed that transplantation at >5months in patients with PIF was an independent predictor of poorer OS. Therefore, UR-CBT at ≤ 5months after diagnosis is an alternative option for AML patients with PIF.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma.

BACKGROUNDGallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase–to–platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases.AIMTo assess the prognostic value of GPR and to design a prognostic nomogram for GBC.METHODSThe analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan–Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index.RESULTSPatients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor–node–metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging.CONCLUSIONGPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

Histopathologic prognostic indices in tongue squamous cell carcinoma.

Consistent prognosticators are needed to guide adjuvant treatment in tongue squamous cell carcinoma (SCC). We validate the prognostic significance of histopathologic parameters in surgically treated tongue SCC. Archival specimens of 88 consecutive patients who were treated surgically for tongue SCC from 2003 to 2016 were re-analyzed by one pathologist. Patient records were retrospectively reviewed. Prognosticators of recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were identified using multivariate analysis. Tumor depth of invasion (DOI) > 6mm (OR 4.76; 95%CI 1.22-18.5; p = 0.024) and lymphovascular invasion (OR 5.61; 95%CI 1.00-31.5; p = 0.05) were independent predictors of nodal metastases. The overall 5-year RFS, OS and DSS were 70%, 82% and 84% respectively. Positive margins predicted poor RFS (HR 3.91; 95%CI 1.58-9.65; p = 0.003) and local recurrence-free survival (HR 4.96; 95%CI 1.36-18; p = 0.015). Presence of nodal metastases (HR 5.03; 95%CI 1.73-14.6; p = 0.003), tumor DOI > 6mm (HR 9.91; 95%CI 1.26-78.0; p = 0.029) and positive margins (HR 8.26; 95%CI 2.75-24.8; p < 0.001) were independent predictors of poor OS. Presence of nodal metastases (HR 3.87; 95%CI 1.17-12.8; p = 0.027) and positive margins (HR 12.3; 95%CI 3.54-42.9; p < 0.001) also independently predicted poor DSS. Margins' status was the only independent predictor of local recurrence. Tumor DOI, nodal and margin status were key prognosticators of survival and may determine the necessity for adjuvant therapy.

Prognostic impact of abutment to the branches of the superior mesenteric artery in borderline resectable pancreatic cancer.

The clinical impact of abutment to an artery and its branch on resectability and prognosis in patients with borderline resectable pancreatic cancer is unclear. Patients diagnosed with borderline resectable pancreatic cancer due to artery abutment between April 2012 and December 2018 were enrolled. Contact between arteries and the tumour was assessed by computed tomography (CT). A primary lesion was resected in 63 patients (R group) and unresected in 19 patients (UR group). Overall survival (OS) was worse in the UR group than in the R group (P < 0.001). Multivariate analysis showed that abutment to the superior mesenteric artery (SMA) branches (P = 0.001) was an independent predictor of poor OS after surgery. Regarding the initial recurrence pattern, abutment to the SMA branches was significantly associated with high incidence of distant metastasis (P < 0.001). According to the most distal SMA branch attached on CT, significant differences in RFS were found between absent-J1A (P = 0.017), J2A-J3A (P = 0.0313) and J3A-middle colic artery (MCA, P = 0.0476) but not between J1A-J2A (P = 0.8207). Significant prognostic differences in OS after initiation of the treatment were found between absent-J1A/J2A (P = 0.006) and J1A/J2A-J3A/MCA (P = 0.033) but not between J3A/MCA-UR (P = 0.494). Abutment to the SMA branches was associated with high incidence of distant metastasis after resection and a poor survival. Especially, abutment to the J3A or MCA was associated with poor prognosis comparable with that of the UR group.

Prognostic factors in patients with locally advanced or borderline resectable pancreatic ductal adenocarcinoma: chemotherapy vs. chemoradiotherapy.

To identify common and unique pre-treatment prognostic factors in patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), treated with chemotherapy (CTx) or concurrent chemoradiotherapy (CRT). We enrolled 215 patients with BR/LA PDAC, who were treated with either CTx (n = 82) or CRT (n = 133) as a first-line treatment between 2013 and 2016. Clinical data and CT imaging findings for predicting overall survival (OS) and progression-free survival (PFS) were analyzed using Cox regression analysis. Carbohydrate antigen (CA) 19-9 > 1000 U/mL (hazard ratio [HR] 1.91; p = 0.001) and non-homogeneous enhancement (HR 1.95; p < 0.001) were associated with shorter OS in all study populations. There was no significant difference in median OS (15.3 vs 16.8months, p = 0.297) and PFS (10.0 vs 11.7months, p = 0.321) between the CTx and CRT groups. Non-homogeneous enhancement (HR 2.04; p = 0.006) and presence of positive lymph node on CT (HR 2.38; p = 0.036) were associated with poor OS in the CTx group, while CA 19-9 > 1000 U/mL (HR 2.38; p = 0.001) and non-homogeneous enhancement (HR 1.73; p = 0.006) were independent predictors for poor OS in the CRT group. Enhancement pattern on CT was a common prognostic factor for patients with PDAC treated with either CTx or CRT. Presence of positive lymph nodes on CT was a poor prognostic factor for the CTx group only, whereas CA 19-9 > 1000 U/mL was a poor prognostic factor for the CRT group only.

SMYD3 overexpression indicates poor prognosis and promotes cell proliferation, migration and invasion in non‑small cell lung cancer.

SET and MYND domain-containing protein 3 (SMYD3) is a lysine methyltransferase, and its aberrant expression has been implicated in several malignancies. However, its clinical and biological roles in non-small cell lung cancer (NSCLC) remain unclear. In the present study, it was revealed that SMYD3 was significantly upregulated in NSCLC tissues, as compared with paired adjacent normal tissues. A high SMYD3 expression was associated with aggressive clinicopathological characteristics, as well as poor disease-free survival and overall survival (OS) in NSCLC patients. Multivariate analysis revealed that SMYD3 overexpression was an independent predictor of poor OS in NSCLC patients. In addition, SMYD3 knockdown inhibited cell proliferation, triggered apoptosis, and blocked migration and invasion in NSCLC cells in vitro, whereas stable SMYD3 overexpression promoted NSCLC cell proliferation. Furthermore, the SMYD3-silenced NSCLC cells became more sensitive, whereas the SMYD3-overexpressed NSCLC cells became more resistant to the apoptosis induced by cisplatin. Mechanistic analysis revealed that SMYD3 knockdown led to the upregulation of Bim, Bak and Bax, and the downregulation of Bcl-2, Bcl-xl, MMP-2 and MMP-9 in NSCLC cells. In combination, the present findings indicated that SMYD3 has oncogenic potential in the context of NSCLC, providing evidence that may be exploited for both prognostic and therapeutic purposes in the future.

Age-dependent survival impact of body mass index in patients with oesophageal squamous cell carcinoma

BackgroundPatients with oesophageal squamous cell carcinoma (ESCC) generally have distinctive body compositions; being underweight is highly prevalent and sarcopenic obesity is rare. We investigated the survival impacts of body mass index (BMI) in elderly (≥65 years) and non-elderly patients undergoing surgery for ESCC. MethodsIn total, 379 ESCC patients were retrospectively reviewed. Patients were divided into 3 groups according to BMI; low (<20), medium (20–25) and high (≥25). The skeletal muscle index (SMI) was calculated and its relationship with BMI was analysed. Univariate and multivariate Cox hazards models were applied to determine independent predictors of poor overall survival (OS) and cancer-specific survival (CSS). ResultsThe low-, medium- and high-BMI groups included 102 (26.9%), 231 (60.9%) and 46 (12.1%) patients, respectively. High BMI with low SMI was rare (n = 6, 1.6%). Patients with low BMI had significantly poorer OS and CSS than those with high and medium BMI (OS; P < 0.001, CSS; P = 0.003). Notably, OS and CSS curves were well-demarcated by BMI (both P < 0.001) in elderly patients, while not being stratified according to BMI in non-elderly patients (OS; P = 0.08, CSS; P = 0.54). Multivariable analysis revealed low BMI, as well as pStage III disease and non-curative resection, to be independent predictors of poor OS (HR 2.73, P < 0.001) and poor CSS (HR 2.88, P < 0.001) in the elderly group. ConclusionsThe survival and oncological impacts of low BMI were evident only in elderly patients with ESCC. Our findings highlight the age-dependent significance of BMI in patients with this tumour entity.

Retrospective study on the potential of albumin/globulin ratio as a prognostic biomarker for oral cavity cancer patients.

Although the serum albumin/globulin ratio (AGR) is recognized as a valuable prognostic biomarker in various cancers, its clinical value in oral cavity squamous cell carcinoma (OSCC) is still unclear. We aimed to probe the prognostic value of AGR in patients with OSCC undergoing curative surgery. This retrospective study analyzed 306 patients who were newly diagnosed as having OSCC and receiving curative surgery between 2008 and 2017. The correlation of AGR with survival outcomes was estimated using Cox proportional hazards models and Kaplan-Meier analysis. A nomogram based on AGR was established, and its accuracy was assessed according to the concordance index. The log rank test and Kaplan-Meier analysis indicated that patients who had low AGR had significantly shorter disease-free survival (DFS) as well as 5-year overall survival (OS) than those with high AGR. The multivariate Cox analysis revealed that low AGR was an independent predictor of poor OS and DFS (adjusted hazard ratio [aHR] = 2.812; 95% CI 1.729-4.573; p < 0.001, and aHR = 1.743; 95% CI 1.201-2.530; p = 0.003, respectively). The concordance index of the nomogram model based on TNM staging alone was 0.656 and could increase to 0.783 with the inclusion of AGR and other prognostic variables in the calculation. Preoperative AGR may represent an accessible, valuable prognostic biomarker in patients with OSCC. The nomogram model incorporating AGR and clinicopathological prognostic variables may improve the accuracy of prognostic predictions in these patients.

Preoperative systemic immune-inflammation index predicts prognosis of patients with non-metastatic renal cell carcinoma: a propensity score-matched analysis

BackgroundA novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes and platelet counts, is associated with the prognosis of several cancers. The present study evaluates the prognostic significance of SII in non-metastatic renal cell carcinoma (RCC).MethodThe present study retrospectively reviewed the medical record of patients with non-metastatic RCC who underwent nephrectomy between 2010 and 2013. Receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cut-off value. In addition, the propensity score matching (PSM) was performed with a matching ratio of 1:1. Univariate and multivariate Cox proportional hazards models were used to identify the prognostic factors. The results were reported by hazard ratio (HR) with 95% confidence interval (95% CI).ResultsA total of 646 patients were included in the final analysis. High SII group (> 529) was significantly associated with older age (P = 0.014), larger tumor (P < 0.001), higher pathological T stage (P < 0.001), higher tumor grade (P < 0.001) and more tumor necrosis (P < 0.001). Multivariate Cox regression analysis demonstrated that the higher preoperative SII was significantly associated with worse overall survival (OS) (HR = 2.26; 95% CI 1.44–3.54; P < 0.001) and cancer-specific survival (CSS) (HR = 2.17; 95% CI 1.33–3.55; P = 0.002). After PSM, elevated preoperative SII was an independent predictor of poor OS (HR = 1.78; 95% CI 1.1–2.87; P = 0.018) and CSS (HR = 1.8; 95% CI 1.07–3.03; P = 0.027).ConclusionIn conclusion, preoperative SII is associated with adverse factors for RCC. Furthermore, higher preoperative SII is an independent predictor of poor OS and CSS in surgically treated patients with non-metastatic RCC. More prospective and large scale studies are warranted to validate our findings.

Pain progression at initiation of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of PROSELICA.

5558 Background: PROSELICA phase III trial (NCT01308580) showed that cabazitaxel 20 mg/m2 (C20) is non-inferior to C25 in mCRPC patients (pts) post-docetaxel (DOC) (Eisenberger JCO 2017). Pts enrolled were symptomatic or not. This post-hoc analysis evaluates the influence of progression type at randomization on outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (Radio-p), no pain), Radio-p (± PSA-p, no pain) or pain progression (pain-p, ±PSA-p, ±Radio-p). The relationship between progression type and overall survival (OS), radiological progression-free survival (rPFS) and PSA response (confirmed PSA decrease ≥ 50%) was analyzed. Results: All patients randomized (n = 1200) had received prior DOC and 25.7% had received prior abiraterone or enzalutamide. Progression type was evaluable in 1065 pts (PSA-p = 24.5%, radio-p = 20.9%, pain-p = 54.6%). Pain progression was associated with clinical and biological features of aggressive disease and worse outcomes (decreased PSA response, rPFS and OS) vs PSA-p or radio-p (Table). The survival (rPFS and OS) on C25 was numerically higher than on C20 in pts with radio-p and pain-p. Conversely, C20 and C25 equally benefited pts with PSA-p only. In multivariate analysis (all arms combined), pain progression was an independent predictor of poor OS. Conclusions: This post-hoc analysis of PROSELICA shows that pain progression at initiation of cabazitaxel in mCRPC pts previously treated with DOC is prognostic. The activity of C25 was numerically higher than C20 in patients with radiological or pain progression. Clinical trial information: NCT01308580 . [Table: see text]

The Usefulness of the Pretreatment Neutrophil/Lymphocyte Ratio as a Predictor of the 5-Year Survival in Stage 1–3 Triple Negative Breast Cancer Patients

Background: We have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC). Methods: Patients with stage 1–3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Results: The average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3–5.9, p < 0.001) and DFS (HR 2.3, CI 1.2–4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2–13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3–11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low) and nodal status (positive vs. negative) resulted in four groups with significantly different OS and DFS (log rank p < 0.0001). Significant improvements in OS (p < 0.001) and DFS (p < 0.001) were observed for patients who received chemotherapy and had high NLR but not for patients with low NLR (p = 0.65 and p = 0.07, respectively). Conclusion: High pretreatment NLR is an independent predictor of poor OS and DFS among TNBC patients. Combining NLR and pN provides better risk stratification for TNBC patients. Chemotherapy appears to be beneficial only in patients with high NLR. Larger prospective studies are needed to validate these findings.

Predicting the treatment outcome of nivolumab in recurrent or metastatic head and neck squamous cell carcinoma: prognostic value of combined performance status and modified Glasgow prognostic score.

The importance of nivolumab for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rapidly increasing. However, prognostic factors have not been determined for predicting treatment outcome. We aimed to investigate the prognostic factors in R/M HNSCC patients treated with nivolumab. This retrospective study included 42 patients with R/M HNSCC who received nivolumab therapy. Correlations of overall survival (OS) with various patient characteristics including age, recurrent/metastatic site, performance status (PS), programmed death-ligand 1 positivity, body mass index, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score (mGPS), previous cetuximab administration, and immune-related adverse events were investigated. The overall response rate and disease control rate were 16.7% and 45.2%, respectively. Estimated 1-year OS and progression-free survival (PFS) were 56.4% and 24.5%, respectively. Multivariate analysis revealed that PS = 2 (hazard ratio 0.147; 95% CI 0.041-0.527; p = 0.003) and mGPS = 2 (hazard ratio 0.188; 95% CI, 0.057-0.620; p = 0.006) were independent predictors of poor OS. Given that the PS and mGPS were independent prognostic factors, we classified patients into three groups according to PS and mGPS: Group 1, both PS and mGPS were 0 or 1 (n = 30); Group 2, either PS or mGPS was 2 (n = 9); Group 3, both PS and mGPS were 2 (n = 3). The OS curves were significantly stratified among the three groups. The combination of PS and mGPS accurately predicted OS after nivolumab therapy. Preventive intervention to maintain general condition without simultaneously exceeding level 2 of PS and mGPS might be important for improving treatment outcomes of nivolumab.

Hepatic resection for breast cancer liver metastases: Impact of intrinsic subtypes

IntroductionThe role of surgery for breast cancer liver metastases (BCLM) remains controversial. This study aimed to analyze survival in patients treated with hepatectomy plus systemic therapy or systemic therapy alone for BCLM and to determine selection factors to guide surgical therapy. Materials and methodsPatients who underwent hepatectomy plus systemic therapy (n = 136) and systemic therapy alone for isolated BCLM (n = 763) were compared. Overall survival (OS) was analyzed after propensity score matching. Intrinsic subtypes were defined as: luminal A (estrogen receptor [ER]+ and/or progesterone receptor positive [PR]+, human epidermal growth factor receptor 2 [HER2]–), luminal B (ER and/or PR+, HER2+), HER2-enriched (ER and PR–, HER2+), and basal-like (ER, PR, HER2–). ResultsAfter hepatectomy, independent predictors of poor OS were number and size of liver metastases, and intrinsic subtype (hazard ratios, 1.11, 1.16, and 4.28, respectively). Median OS was 75 and 81 months among patients with luminal B and HER2-enriched subtypes, compared with 17 and 53 months among patients with basal-like and luminal A subtypes (P < .001). Median progression-free survival (PFS) was 60 months with the HER2-enriched subtype, compared with 17, 16, and 5 months with luminal A, luminal B, and basal-like subtypes, respectively (P < .001). After propensity score matching, 5-year OS rates were 56% vs. 40% in the surgery vs. systemic therapy alone groups (P = .018). ConclusionSurgical resection of BCLM yielded higher OS compared with systemic therapy alone and prolonged PFS among patients with the HER2-enriched subtype. These findings support the use of surgical therapy in appropriately selected patients, based on intrinsic subtypes.

The survival impact of postoperative complications after curative resection in patients with esophageal squamous cell carcinoma: propensity score-matching analysis.

The relationship between postoperative complications and long-term survival after surgery for esophageal squamous cell carcinoma (ESCC) is controversial. A total of 210 patients with ESCC who underwent subtotal esophagectomy with a reconstructed gastric tube were investigated according to the development of postoperative complications. The associations of age, gender, T and N factors, and pStage with grade 0-2 complications (NSC) and grade 3 and higher complications (SC) were compared by propensity score-matching analysis. Fifty-one pairs of NSC and SC groups were selected for the final analysis. We divided 102 patients between the NSC and SC groups or between the no pulmonary complication (NPC) and the pulmonary complication (PC) groups. The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method and were compared by log-rank tests. Possible predictors of OS and DFS were subjected to univariate analysis and multivariate Cox proportional hazard regression analysis. The propensity score matching revealed that the 5-year OS and DFS of the NSC group were not different from those of the SC group. However, the 5-year OS of the PC group was significantly worse than that of the NPC group, while no significant differences were observed in the DFS between the PC and NPC groups. In the multivariate analysis, UICC pStage, pulmonary complication, and American Heart Association (AHA) classification for OS and UICC pStage for DFS were significant prognostic factors. The OS and DFS did not differ in patients with or without severe postoperative complications. However, postoperative pulmonary complications were independent predictors of poorer OS, but not DFS, in patients who underwent R0 resection for ESCC.

Outcomes and Prognostic Factors for Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia Who Underwent Allogeneic Hematopoietic Cell Transplantation: A KSGCT Multicenter Analysis.

A multicenter retrospective study was performed to evaluate the prognostic factors in 104 patients with relapsed or refractory acute lymphoblastic leukemia (ALL), who underwent allogeneic hematopoietic cell transplantation (HCT) between 2005 and 2015. The median age was 38 (range, 17 to 68), and the median blast fraction in peripheral blood and bone marrow was 1% (range, 0 to 99%) and 52% (range, 0 to 100%), respectively. With a median follow-up of 47 months (range, 8.3 to 105 months), overall survival (OS), nonrelapse mortality, and relapse mortality at 1 year were 25%, 44%, and 31%, respectively. Multivariate analysis demonstrated independent predictors for poor OS, including nuclear cell count in the bone marrow ≥10×104/μL (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.33 to 3.43; P=.002), elevated lactate dehydrogenase level (HR, 1.66; 95% CI, 1.05 to 2.62; P=.031), and no primary induction failure (HR, 2.05; 95% CI, 1.11 to 3.78; P=.022). A prognostic scoring index was designed based on these survival predictors. At 2 years, OS was 28%, 14%, and 0% for good (score 0 or 1; n=47), intermediate (score 2; n=40), and poor (score 3; n=17), respectively (P < .001). This scoring system may be useful in identifying the patient population for which allogeneic HCT is least beneficial in advanced stages of ALL.

Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer

Background:Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs).Methods:We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated.Results:Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC.Conclusions:These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.

Association between esophagogastric varices in hepatocellular carcinoma and poor prognosis after transarterial chemoembolization: A propensity score matching analysis

Whether esophagogastric varices (EGV) can determine the outcome of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) remains unknown. This study aimed to assess the impact of EGV on the prognosis of HCC patients after TACE. From 2007 to 2012, we retrospectively enrolled 251 treatment-naïve HCC patients who underwent TACE and received esophagogastroduodenoscopy when HCC was diagnosed. The prognostic factors were analyzed using a Cox proportional hazards model and propensity score-matching analysis. There were 120 (47.8%) patients with EGV. Compared to those without EGV, patients with EGV had worse liver functional reserve. After a median follow-up of 14.7 months (25th-75th percentiles, 6.4-35.6 months), 152 patients died. The cumulative 5-year overall survival (OS) rates were 11.2% and 38.8% in patients with and without EGV, respectively (p<0.001). Multivariate analysis showed that presence of EGV, presence of ascites, tumor size >5cm, serum alpha-fetoprotein >20ng/mL, progressive disease by modified Response Evaluation Criteria in Solid Tumors, Assessment for Retreatment with TACE score ≥2.5, and higher albumin-bilirubin grades were the independent predictors of poor OS. Subgroup analysis also demonstrated that EGV was associated with poor OS in most of the subgroups. After propensity score matching, the EGV group still had a lower OS rate than their counterparts (p=0.004). HCC patients with EGV had worse liver functional reserve compared to those without EGV. Moreover, EGV was an independent risk factor to predict poor prognosis in patients with HCC after TACE.

Is laparoscopic liver resection suitable for selected patients with BCLC stage B HCC? A propensity score-matched analysis

BackgroundThe optimal treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is controversial given the variability of tumour status within this group of patients. This aim of this study was to compare the outcomes of laparoscopic liver resection (LLR) to transarterial chemoembolization (TACE) in a subset of selected patients with BCLC stage B HCC. MethodsPatients with resectable BCLC stage B HCC who underwent treatment between April 2015 and October 2018 were identified for further analysis. Propensity score matching (PSM) was conducted to minimize effect of confounding factors. Perioperative and long-term outcomes were compared between the two groups and multivariate analysis was performed to identify risk factors related to the overall survival (OS). ResultsFrom a total of 224 patients 70 were included into each group after PSM. The overall and major morbidity were comparable between the LLR and TACE groups (P = 0.700 and P = 0.500 after PSM, respectively). The OS in LLR group was significantly better than that in the TACE group (P < 0.001). Tumor number ≥4, the diameter of the biggest tumor >5 cm, and patients who underwent TACE were independent predictors of poorer OS. ConclusionsLLR for selected patients with BCLC stage B HCC is safe and feasible and has improved survival as compared to TACE.

Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma.

To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV). We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test. High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62-6.34) and PFS (HR = 2.22, 95% CI = 1.33-3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208). High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status. • Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma. • APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma. • APT imaging may be valuable for preoperative screening and treatment guidance.