Abstract 2853: Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for metastatic colorectal cancer
Jeroen GoosAnnemieke C. HiemstraVeerle M.H. CoupéBegoña DiosdadoWendy KooijmanPien M. Delis‐van DiemenCemile KargaJeroen A.M. BeliënC. Willemien Menke‐van der Houven van OordtAlbert A. GeldofGerrit A. MeijerOtto S. HoekstraRemond J.A. Fijneman
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Abstract Background: Resection of colorectal cancer liver metastasis (CRCLM) with curative intent is beneficial in approximately 30% of cases, indicating the need for prognostic biomarkers to improve clinical management of CRCLM patients. Protein expression levels of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2 or COX2) have been associated with carcinogenesis, metastases and survival. EGFR and PTGS2 are targets for molecular drugs and exhibit complex molecular interactions. Aim: We aimed to determine the prognostic value of EGFR and PTGS2 expression in CRCLM of patients who underwent liver resection. Patients and methods: Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumor specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry and a hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival (OS) was calculated. Results were validated by 500-fold cross-validation. Results: EGFR expression could be evaluated in 323 patients and PTGS2 expression in 351 patients. EGFR expression in CRCLM was associated with poor prognosis in both univariate analysis (average HRR 1.47; P=0.03) and multivariate analysis with standard clinicopathological prognostic variables (average HRR 1.54; P=0.02). PTGS2 expression was also associated with poor prognosis in both univariate (average HRR 1.63; P<0.01) and multivariate analysis (average HRR 1.59; P=0.01). Stratification for systemic therapy demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated (HRR 1.78; P<.01 and HRR 1.64; P=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08; P<.01). CRCLM expression of PTGS2 was concordant in 69.2% of matched primary tumors (P=0.02), while there was no such correlation for EGFR expression (P=0.51). Conclusion: EGFR and PTGS2 expression are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with CRCLM. Citation Format: Jeroen A.C.M. Goos, Annemieke C. Hiemstra, Veerle M.H. Coupé, Begoña Diosdado, Wendy Kooijman, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Beliën, C. Willemien Menke-van der Houven van Oordt, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J.A. Fijneman. Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for metastatic colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2853. doi:10.1158/1538-7445.AM2014-2853Keywords:
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The limited supply of organ donors has led some groups to reconsider the role of retransplantation. Historically, except for children with malignancies, extrahepatic sources of sepsis, or severe irreversible neurologic injuries, our institution has offered all children with failing liver grafts the option of retransplantation regardless of their current severity of illness. The purpose of this study was to examine the outcome of hepatic retransplantation in children in an attempt to identify factors predictive of outcome and to assess the results of our approach to retransplantation.Between October 1984 and December 1995, 314 children less than 15 years of age underwent a total of 441 liver transplants. Data were obtained retrospectively by review of hospital records.With a mean follow-up period of 5.3+/-2.7 years, the overall patient survival rates at 1 and 5 years were 77.1% and 67.1%, respectively. Primary allograft survival rates were 65.6% and 56.5%, respectively. Of the 137 patients who developed failure of their primary allograft, 92 underwent retransplantation (29.3% of all primary transplants). Both patient and allograft survival rates were significantly decreased after retransplantation (P<0.0001 versus primary transplants). Univariate and multivariate analysis of retransplanted patients revealed only two factors that were statistically related to patient and graft survival: age at the time of retransplantation (P<0.02 univariate and P<0.05 multivariate) and retransplantation with a reduced-size allograft (P<0.005 univariate and P<0.05 multivariate). In this series, the effect on patient survival of differences in medical condition as reflected by United Network for Organ Sharing (UNOS) status approached, but did not achieve, significance (P=0.08 for UNOS 1 versus UNOS 2 and 3). UNOS status did not affect graft survival. Neither the cause of primary allograft loss or the timing of retransplantation relative to the first transplant were related to outcome.These data demonstrate that the failure of primary hepatic allografts remains a major problem in pediatric liver transplantation and that the overall results of retransplantation were significantly worse than those associated with primary transplants. We have identified a group of children who experienced a significantly worse outcome after retransplantation. This group consisted of children less than 3 years of age retransplanted using reduced-size grafts. Based on this finding, we now attempt to avoid retransplanting young children with reduced-size grafts. By using this approach, we hope to be able to offer children the option of retransplantation with improved results and simultaneously minimize the negative impact on patients awaiting primary transplants.
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Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, and factors associated with the recurrence of PTs are poorly understood. This study sought to identify clinicopathological factors associated with the recurrence of PTs.From January 2009 to December 2019, we identified 100 patients who underwent definitive surgery for PT. Clinicopathological risk factors associated with the recurrence of PT were assessed.The median age of the patients was 44 y (range, 19-62 y), and the median tumor size was 4 cm (0.8-30 cm). At a median follow-up of 26.7 mo (0-103 mo), 22 of the 100 patients experienced local recurrence. In the univariate and multivariate analyses, body mass index ≥ 23 kg/m2 (P = 0.042 in the univariate analysis; P = 0.039 in the multivariate analysis), tumor size ≥ 5 cm (P = 0.006 in the univariate analysis; P = 0.036 in the multivariate analysis), and the presence of stromal overgrowth (P = 0.032 in the univariate analysis; P = 0.040 in the multivariate analysis) were associated with an increased risk of local recurrence. Resection margins and grade were not associated with local recurrence.Normal- or underweight patients and those with larger tumor sizes were more prone to local recurrence. Further larger, multicenter studies with a long-term follow-up are required.
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Background
Hospital Acquired Pneumonia (HAP) is defined as lung infection in a non-intubated patient with new infiltrates on chest X-ray, >48 hours after hospital admission. Prediction scores exist for Community Acquired Pneumonia (CAP); no such scores exist in HAP. We aimed to identify features which are predictive of mortality in HAP.Methods
All cases coded as HAP in Heart of England Foundation NHS trust in 2013 trust were identified (293 cases). For each of these cases the chest X-ray (including radiologists report) was reviewed; if X-ray did not show infiltrates consistent with pneumonia, cases were excluded leaving 153 cases for whom case notes were reviewed. Cases were excluded if diagnosis of HAP was made <48 hours after admission leaving 136 cases. Data was collected regarding demographics, co-morbidities, investigations, observations, mortality during admission and within 12 months. Univariate analysis was conducted to identify features associated with mortality. Multivariate analysis was completed using identified associated features.Results
Sixty-four cases (47.0%) died during admission; and a further 32 within 12 months (70.5%). Demographics: Mean age was 81.6 years (range 52–98); mean number of co-morbidities was 5 (range 0–11). Mean haemoglobin was 110.9 g/dL. The mean white cell count (WCC) was 13.68 × 109/L (range 1.87–51.7 × 109/L). Mean urea was 10.5 mmol/L (range 1.9–6.1 mmol/L) Univariate analysis: Table 1 shows the results of the univariate analysis. Multivariate analysis: Only combination of raised urea and raised or low WCC were significantly associated with mortality (p = 0.024). Adding features of age, observations and co-morbidities did not improve prediction of mortality.Conclusion
Prediction of mortality in HAP is more complex than in CAP. On multivariate analysis, raised urea and raised or low WCC were predictive of mortality. Other features including age, number of comorbidities and observations at the time of diagnosis were not associated with mortality. This perhaps reflects our elderly cohort, with the majority having multiple co-morbidities, with very small numbers aged <65 years or with few co-morbidities. Further work with a larger dataset is ongoing.Univariate analysis
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In 221 patients with FIGO stage I and II endometrial carcinoma, the impact on survival of age at diagnosis, menopausal status, FIGO stage, myometrial invasion, tumor grade and histology was evaluated by univariate and multivariate analysis. At a median follow-up of 50 months (range 45-210), 42 patients had died, and therefore overall survival was 81% (179/221). Univariate analysis showed that age, menopausal status and histology did not influence survival, whereas FIGO stage, myometrial invasion and tumor grade were important prognostic factors. Multivariate analysis showed that tumor grade had a significant and independent impact on survival and confirmed that FIGO stage is the most important parameter influencing survival.
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Objective To evaluate and analyse the prognostic factors of cerebral glioma treated with radiotherapy. Methods Records of 162 patients with cerebral glioma. Cox model was used for univariate and multivariate analysis. Results Mean follow- up time was 30 months, 14 patients relapsed, and 45 patients died. Univariate analysis showed that histologic grade, histologic type, Karnofsky performance state before radiotherapy, extent of resection, and age were significant predictors in association with overall survival rate of patients with glioma. Multivariate analysis showed that histologic grade, histologic type, age, Kamofsky before radiotherapy, extent of resection,and radiotherapy technology were independent prognostic factors of glioma. Conclusion Low grade, AC and OD, age≤40 years, Kamofsky >80 before radiotherapy, and total resection axe independent factors for predicting better survival of glioma patients.
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Brain neoplasms; Glioma; Radiotherapy, computer-assisted; Prognosis
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To determine the prognostic factors from the view of clinic and pathology.A retrospective analysis was performed on a data set of 78 patients with Ewing's sarcoma treated at Peking University People's Hospital Musculoskeletal tumor center between July 1998 and July 2007. Five-year overall survival (OS), recurrence rate and prognostic factors were analyzed in this study. Univariate and multivariate analysis were performed to determine the prognostic factors for OS.Fifty-three cases were followed up, follow-up time ranged from 8.0 to 101.0 months (median 37.6 months). The 5-year overall survival rate and local recurrence rate were 33.7% and 20.8% respectively. Univariate showed age < 20 years, metastases free at diagnosis, tumor located at extremities, tumor size < 10 cm, adequate surgical margin had better survival rate (all P < 0.05). Multivariate analysis demonstrated that metastases at diagnosis, primary site and tumor size were independent prognostic factors for OS.The independent prognostic factors Ewing's sarcoma are metastases at diagnosis, primary site, tumor size.
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