Primary Metastatic Osteosarcoma: Presentation and Outcome of Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

Purpose: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. Patients and Methods: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. Results: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. Conclusion: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.

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Serum matrilysin (MMP7) levels are associated with progression, in curatively resected colorectal cancer (CRC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4124 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4124-4124 ◽

Cited By ~ 1

Author(s):

A. Martinez-Fernandez ◽

E. Pineda ◽

L. Visa ◽

X. Garcia-Albeniz ◽

J. Auge ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastases ◽

Primary Tumor ◽

Cox Regression ◽

Univariate Analysis ◽

Disease Free Survival ◽

Early Stage Disease ◽

Cox Regression Analysis ◽

Node Metastases

4124 Background: Matrilysin (MMP7) has been shown to be over-expressed in CRC, specially in liver metastases. Additionally MMP7 over-expression in primary tumor, predict metastatic potential in early-stage disease (Gut 12:1751;2005). As the activated pro-domain, could be detected in serum by ELISA method, we search if it could also identify a subgroup of non-metastatic CRC patients with a higher risk of relapse. Methods: Serum MMP7 (S-MMP7) was measured by commercially available ELISA, in 92 healthy controls and 175 consecutive patients before undergoing laparoscopy-assisted or open curative resection for CRC, between July 2003 to December 2004. Clinic- pathologic variables were tested for their effect on disease-free survival (DFS) in univariate and multivariate Cox regression analysis. Results: S-MMP7 levels were significantly higher in CRC patients than in controls (p=0.02). Mean age in CRC patients was 71 years (range 31–90). Median nodal retrieval was 14 (range 0–47). The median S-MMP7 (4.9 ng/ml) was chosen for cut-off value. After a median follow- up of 26 months, the rate of DFS was 72%. Univariate analysis identified high S-MMP7 levels, CEA concentration, age, extent of primary tumor and lymph-node metastases as variables associated with DFS. Multivariate analysis identified lymph-node metastases (OR.1,88, p=0.046) and S-MMP7 (OR.1,103, p=0.039) as independent prognostics factors. Conclusions: With a short follow-up, S-MMP7 levels predict recurrence in curatively resected CRC. As a subset of these patients could be managed with secondary liver resection, S-MMP7 determination would be particularly warranted for more intensive surveillance strategies. No significant financial relationships to disclose.

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Impact of next-generation sequencing (NGS) in patients with high grade glioma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13541 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13541-e13541

Author(s):

Tariq Zuheir Kewan ◽

Fahrettin Covut ◽

Bicky Thapa ◽

Timothy Peter Spiro ◽

Abdo S. Haddad ◽

...

Keyword(s):

Surgical Resection ◽

Cox Regression ◽

Multivariable Analysis ◽

Cleveland Clinic ◽

High Grade Glioma ◽

Rank Test ◽

High Grade ◽

Cox Regression Analysis ◽

Off Label ◽

Grade Iii

e13541 Background: Clinical utility of NGS in high grade glioma patients remain debatable. Methods: We reviewed patients who underwent Foundation One NGS between 7/2013 and 10/2018 after high-grade glioma diagnosis at Cleveland Clinic. Overall survival (OS) and progression free survival (PFS) were estimated by the Kaplan-Meier method and compared by log-rank test. Cox regression analysis was performed to identify predictors of OS. Results: We identified 153 patients, 130 (85%) had glioblastoma multiforme (GBM) and 23 (15%) had grade III glioma, 51 (33%) were female, and median age at diagnosis was 58 (range: 18 – 92). Sixteen (10%) patients had secondary glioma and 34 (22%) had multilobar involvement. ECOG performance score at diagnosis was 0 or 1, 2, and ≥ 3 for 79 (52%), 54 (35%), and 13 (9%) patients, respectively. Glioma was surgically resected for 112 (73%) patients, 85 (56%) had total and 27 (18%) had subtotal resection, whereas other 41 (27%) patients underwent biopsy only. Radiotherapy, temozolomide, and bevacizumab were given to 132 (86%), 129 (84%), and 67 (44%) patients, respectively. NGS revealed median of 5 mutated genes (range: 0 – 19), commonly mutated genes were TERT (63%), CDKN2AB (60%), EGFR (42%), TP53 (42%), PTEN (38%), and IDH1/2 (20%). Two patients received bevacizumab for KDR amplification, 1 received off-label lapatinib for EGFR amplification, and 3 received off-label everolimus for multiple mutations. Median follow-up was 18 months. Three-year OS and PFS for patients with GBM vs grade III glioma were 29% (95% CI: 22 – 39) vs 78% (95% CI: 63 – 97) and 17% (95% CI: 11 – 25) vs 74% (95% CI: 58 – 94), respectively (p < 0.0001 for both). On univariable analysis, each 10 increase in age, ECOG ≥3 vs < 3, grade IV vs III glioma, surgical resection vs biopsy, radiotherapy, temozolomide, bevacizumab, and IDH / TP53 / EGFR / TERT / PTEN / CDKN2AB / ATRX mutations predicted OS (p < 0.01 for all). On multivariable analysis, ECOG ≥3 vs < 3, grade IV vs III glioma, surgical resection vs biopsy, temozolomide, bevacizumab, PTEN and CDKN2AB mutations have remained to predict OS (p < 0.01 for all). Conclusions: In our cohort, NGS results provided additional prognostic value, however led to change in the management for only 4% of patients with high-grade glioma.

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Identification of prognostic alternative splicing events in sarcoma

Scientific Reports ◽

10.1038/s41598-021-94485-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hongshuai Li ◽

Jie Yang ◽

Guohui Yang ◽

Jia Ren ◽

Yu Meng ◽

...

Keyword(s):

Alternative Splicing ◽

Cox Regression ◽

Univariate Analysis ◽

Area Under The Curve ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Cox Regression Analysis ◽

Functional Roles ◽

Cancer Pathogenesis ◽

Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

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High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽

10.1186/s12885-020-07541-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Min Li ◽

Xue Cheng ◽

Rong Rong ◽

Yan Gao ◽

Xiuwu Tang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cox Regression ◽

Paraffin Section ◽

Progression Free Survival ◽

High Grade ◽

Serous Ovarian Cancer ◽

Systematic Analysis ◽

Cox Regression Analysis ◽

Genes Expression ◽

High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

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Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

Journal of Clinical Oncology ◽

10.1200/jco.2014.55.9070 ◽

2014 ◽

Vol 32 (27) ◽

pp. 2983-2990 ◽

Cited By ~ 120

Author(s):

Andrew R. Davies ◽

James A. Gossage ◽

Janine Zylstra ◽

Fredrik Mattsson ◽

Jesper Lagergren ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Surgical Resection ◽

Esophagogastric Junction ◽

Cox Regression ◽

Tumor Regression ◽

Clinical Stage ◽

Tumor Stage ◽

Response To Treatment ◽

Cox Regression Analysis ◽

Systemic Recurrence

Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. Conclusion The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

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Endobronchial Therapy With Gentamicin and Dexamethasone After Airway Clearance by Bronchoscopy in Exacerbation of Non-Cystic Fibrosis Bronchiectasis: A Real-World Observational Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.773241 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiuhong Li ◽

Beijie Huang ◽

Hongyan Gu ◽

Ying Zhou ◽

Xizheng Shan ◽

...

Keyword(s):

Cystic Fibrosis ◽

Cox Regression ◽

Univariate Analysis ◽

Intratracheal Instillation ◽

Drug Group ◽

Control Group ◽

Cox Regression Analysis ◽

Airway Clearance ◽

Significant Prolongation

Background: The exacerbation of non-cystic fibrosis bronchiectasis (NCFB) may lead to poor prognosis. The objective of this study was to retrospectively analyze the clinical efficacy and safety of endobronchial therapy with gentamicin and dexamethasone after airway clearance by bronchoscopy in the exacerbation of NCFB.Methods: We retrospectively reviewed 2,156 patients with NCFB between January 2015 and June 2016 and 367 consecutive patients with exacerbation of bronchiectasis who had complete data and underwent airway clearance (AC) by bronchoscopy. The final cohort included 181 cases of intratracheal instillation with gentamicin and dexamethasone after AC (a group with airway drugs named the drug group) and 186 cases of AC only (a group without airway drugs named the control group). The last follow-up was on June 30, 2017.Results: The total cough score and the total symptom score in the drug group were improved compared to those in the control group during 3 months after discharge (p < 0.001). Re-examination of chest HRCT within 4–6 months after discharge revealed that the improvements of peribronchial thickening, the extent of mucous plugging, and the Bhalla score were all significantly improved in the drug group. Moreover, the re-exacerbations in the drug group were significantly decreased within 1 year after discharge. Univariate analysis showed a highly significant prolongation of the time to first re-exacerbation in bronchiectasis due to treatment with airway drugs compared with that of the control group. Multivariate Cox regression analysis showed that the risk of first re-exacerbation in the drug group decreased by 29.7% compared with that of the control group.Conclusion: Endobronchial therapy with gentamicin and dexamethasone after AC by bronchoscopy is a safe and effective method for treating NCFB.

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Subdivision of metastatic colorectal cancer for identifying patients who benefit more from primary tumor resection

10.21203/rs.3.rs-62901/v2 ◽

2021 ◽

Author(s):

Dakui Luo ◽

Zezhi Shan ◽

Zhiqiang Li ◽

Simin Chen ◽

Sanjun Cai ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Primary Tumor ◽

Cox Regression ◽

Tumor Resection ◽

Signet Ring Cell ◽

Normal Serum ◽

Primary Tumor Resection ◽

Cox Regression Analysis ◽

Serum Cea

Abstract Background Stage IV colorectal cancer (CRC) patients are heterogeneous with distinctive clinicopathologic features and prognosis. Radical resection of primary tumor and distant metastases is associated with improved survival outcomes in metastatic CRC. The value of palliative primary tumor resection is controversial. The present study explored which subgroups benefited more from primary tumor resection in metastatic CRC. Methods Between 2004 and 2015, patients with metastatic CRC were identified using the surveillance, epidemiology, and end results (SEER) database. Uni- and multivariable Cox regression analysis were performed to identify factors associated with decreased cancer-specific mortality. The subgroups were divided based on the independent prognostic factors. Results Age, marital status, race, serum CEA, histologic type, differentiation, tumor location, surgery of primary or metastatic lesion, site of metastases, number of metastatic sites, chemotherapy and radiotherapy were identified as independent prognostic factors. Patients with non-white race, normal serum CEA, non-signet ring cell carcinoma, well or moderate differentiation, surgery of metastases, isolated liver metastasis, single metastasis, receiving chemotherapy or radiotherapy presented more survival benefit from primary tumor resection. Conclusion Subgroup of metastatic CRC optimizes decision-making and selected patients will benefit more from primary tumor resection.

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Surgical Resection Significantly Promotes the Overall Survival of Patients with Hepatocellular Carcinoma: A Propensity Score Matching Analysis

10.21203/rs.3.rs-148506/v1 ◽

2021 ◽

Author(s):

Pei-Min Hsieh ◽

Hung-Yu Lin ◽

Chao-Ming Hung ◽

Gin-Ho Lo ◽

I-Cheng Lu ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Overall Survival ◽

Propensity Score ◽

Propensity Score Matching ◽

Surgical Resection ◽

Cox Regression ◽

Survival Rates ◽

Hbv Infection ◽

Cox Regression Analysis

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

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Construction and Validation of a Prognostic Risk Model Based on Autophagy-Related Genes in Hepatocellular Carcinoma Cells

10.21203/rs.3.rs-714025/v1 ◽

2021 ◽

Author(s):

Rui Feng ◽

Jian Li ◽

Weiling Xuan ◽

Hanbo Liu ◽

Dexin Cheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Differential Expression ◽

Prognostic Model ◽

Risk Model ◽

Cox Regression ◽

Univariate Analysis ◽

Differential Expression Analysis ◽

Cox Regression Analysis ◽

Dismal Prognosis

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

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Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia

Journal of International Medical Research ◽

10.1177/03000605211058872 ◽

2021 ◽

Vol 49 (11) ◽

pp. 030006052110588

Author(s):

Tomonori Aratani ◽

Hitoshi Tsukamoto ◽

Takashi Higashi ◽

Takaaki Kodawara ◽

Ryoichi Yano ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Regression Analysis ◽

Cox Regression ◽

Methicillin Resistance ◽

Univariate Analysis ◽

Cox Regression Analysis ◽

Staphylococcus Aureus Bacteremia ◽

Mortality Outcome ◽

Delayed Initiation ◽

Hospital Acquired

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

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