scholarly journals Prognostic Parameters of Metastatic Adrenocortical Carcinoma

2007 ◽  
Vol 92 (1) ◽  
pp. 148-154 ◽  
Author(s):  
Guillaume Assié ◽  
Guillemette Antoni ◽  
Frédérique Tissier ◽  
Bernard Caillou ◽  
Gwenaelle Abiven ◽  
...  

Abstract Context: Prognostic parameters of metastatic adrenocortical carcinoma (ACC) are poorly characterized. Objective: The objective of the study was to describe the clinical presentation of metastatic ACC and determine prognostic factors for survival. Design: This was a retrospective cohort study (1988–2004). Setting: The study was conducted in an institutional practice. Patients: Participants included 124 consecutive patients with metastatic ACC, 70 from Gustave-Roussy Institute (main cohort) and 54 patients from the Cochin Hospital (validation cohort). Clinical data concerning all patients, histopathologic slides of primary tumors (44 in the main cohort and 40 in the validation cohort), and molecular biology data on 15 primary tumors (main cohort) were analyzed. Intervention: There was no intervention. Main Outcome: The main outcome was the specific survival after discovery of the first metastasis (Kaplan-Meier method). This included univariate analysis on the main cohort, confirmed on the validation cohort and then analyzed in a multivariate analysis. Results: In the main cohort, overall median survival was 20 months. In univariate analysis, the presence of hepatic and bone metastases, the number of metastatic lesions and the number of tumoral organs at the time of the first metastasis, a high mitotic rate (>20 per 50 high-power field), and atypical mitoses in the primary tumor predicted survival (P = 0.05, 0.003, 0.046, 0.001, 0.01, and < 0.001, respectively). The number of tumoral organs and a high mitotic rate were confirmed on the validation cohort (P = 0.009 and 0.03, respectively). These two parameters were confirmed in multivariate analysis (P = 0.0058 and 0.049). Conclusion: Metastatic ACC is a heterogeneous disease with poor outcome. The combination of the number of tumoral organs at the time of the first metastasis and the mitotic rate can predict different outcomes.

2020 ◽  
Author(s):  
Maxime Barat ◽  
Philippe Soyer ◽  
Fatima Al Sharhan ◽  
Benoit Terris ◽  
Ammar Oudjit ◽  
...  

Objectives: To discriminate hepatic metastases from pancreatic neuroendocrine tumors (pNET) and hepatic metastases from midgut neuroendocrine tumors (mNET) with magnetic resonance imaging (MRI). Methods: MRI examinations of 24 patients with hepatic metastases from pNET were quantitatively and qualitatively assessed by two blinded readers and compared to those obtained in 23 patients with hepatic metastases from mNET. Inter-reader agreement was calculated with kappa and intraclass correlation coefficient (ICC). Sensitivity, specificity and accuracy of each variable for the diagnosis of hepatic metastasis from pNET were calculated. Associations between variables and primary tumor (i.e., pNET vs. mNET) were assessed at univariate and multivariate analysis. A nomogram was developed and validated using an external cohort of 20 patients with pNET and 20 patients with mNET. Results: Interobserver agreement was strong to perfect (k=0.893-1) for qualitative criteria and excellent for quantitative variables (ICC: 0.9817-0.9996). At univariate analysis, homogeneity on T1-weighted images was the most discriminating variable for the diagnosis of pNET (OR, 6.417; P=0.013) with greatest sensitivity (88%; 21/24; 95% CI: 68-97%). At multivariate analysis, tumor homogeneity on T1-weighted images (P=0.007; OR, 17.607; 95%CI: 2.179–142.295) and target sign on DW images (P=0.007; OR, 19.869; 95%CI: 2.305–171.276) were independently associated with pNET. Nomogram yielded a corrected AUC of 0.894 (95%CI: 0.796–0.992) for the diagnosis of pNET in the training cohort and 0.805 (95%CI: 0.662–0.948) in the validation cohort. Conclusions: MRI provides qualitative features that can help discriminate between hepatic metastases from pNET and those from mNET.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3502-3502
Author(s):  
T. D. Yan ◽  
J. King ◽  
D. Glenn ◽  
K. Steinke ◽  
D. L. Morris

3502 Background: This current study was an open, prospective and nonrandomized phase II study, which critically evaluated the prognostic parameters for local disease-free survival (DFS) and overall survival (OS) in patients who underwent percutaneous radiofrequency ablation (RFA) for inoperable colorectal pulmonary metastases (CRPM). Methods: The inclusion criteria were patients who had inoperable CRPM, due to number, distribution, poor performance status or patients’ refusal to accept surgery. The exclusion criteria were lesions > 6 per hemithorax; diameter of metastases > 5 cm; bleeding diathesis; and/or significantly compromised lung function. All patients underwent percutaneous RFA with a radiological clear margin of at least 2 cm. The end-points of this study were local DFS and OS, determined from the time of RFA intervention. Ten clinical and six treatment-related prognostic parameters were assessed in univariate and multivariate analyses. All patients were reviewed at one week, one month and every three months thereafter with chest CT. Fifty-five patients entered into the study. The follow-up was complete and the median follow-up was 24 months (6 to 40). Results: The median local DFS was not reached and 2-year local DFS was 57%. Univariate analysis demonstrated that largest size of lung metastasis, location of lung metastases, post-RFA CEA at 1 month and 3 months were significant for local DFS. In multivariate analysis, largest size of lung metastasis of ≤ 3 cm and post-RFA CEA of ≤ 5 ng/ml at 1 month were independently associated with an improved local DFS. The median OS was 33 months (4 to 40), with 1-, 2-, and 3-year survival of 85%, 64% and 46%, respectively. Univariate analysis demonstrated that interval between the diagnoses of colorectal cancer and pulmonary metastasis; largest size of lung metastasis and location of lung metastases were significant for OS. In multivariate analysis, only size of lung metastasis of ≤ 3 cm was independently associated with an improved OS. Conclusions: Percutaneous RFA of inoperable CRPM may have a useful role in patients with a lesion of ≤ 3 cm. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9545-9545
Author(s):  
C. S. McGuire ◽  
K. L. Cobb ◽  
P. G. Fisher

9545 Background: Supratentorial (SUP) ependymoma in childhood has been reported in studies with limited samples to carry improved overall survival (OS) compared to infratentorial (INF) tumors, with spinal (SPI) ependymoma having the best outcome. Moreover, radiation therapy (XRT) for INF tumors has been considered standard of care, though there have been case reports of children treated successfully without XRT. Thus, we aimed to examine how age, gender, location, XRT and race influence OS in childhood ependymoma by rigorous analysis of a large registry. Methods: We queried the Surveillance Epidemiology End Results (SEER) registry from 1973 to 2003, strictly defining ependymomas by histology (ICD-O-3: 9391–9394). ICD-0–2 site codes, when available, were used to distinguish SUP, INF, and SPI tumors. OS was compared by age, gender, race, location, and XRT, using Kaplan-Meier analysis with logrank tests in SPSS 12.0 (Chicago, IL). Cox regression incorporated all significant covariates from univariate analysis. A similar analysis was conducted to determine whether findings differed in adults. Results: 635 children <18 years at diagnosis were identified (265 females; 510 whites, 77 blacks; 106 SUP, 193 INF, 55 SPI) with 5-year OS 57.1% ± standard error 2.3%. With univariate analysis, OS did not differ by gender or race. For location, 5-year OS did not differ between SUP 59.5% ± 5.4% and INF 57.1% ± 4.1%, but was significantly better for SPI 86.7% ± 5.2%. With multivariate analysis, location and age remained significant predictors for OS, with younger children having worse outcome. A similar multivariate analysis in 1388 adults again showed age and location to be significant. Adults fared better than children (logrank p <0.0001). XRT of INF tumors was associated with significantly improved OS in children (logrank p <0.018), but did not lead to an OS difference among adults. Conclusions: Age and location directly influence OS in childhood ependymoma. SPI tumors are associated with a significantly better prognosis than other ependymomas. This study could not show a difference in OS between SUP and INF tumors, proposed recently to have different stem cell origins. SPI tumors may represent a distinct biological entity. Curiously, XRT is associated with improved OS in pediatric, but not adult, INF ependymomas. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Takeru Wakatsuki ◽  
Eiji Shinozaki ◽  
Mitsukuni Suenaga ◽  
Izuma Nakayama ◽  
Tomohiro Matsushima ◽  
...  

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.


2020 ◽  
Author(s):  
Gloria Mittica ◽  
Margherita Goia ◽  
Angela Gambino ◽  
Giulia Scotto ◽  
Mattia Fonte ◽  
...  

Abstract Background Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival. Results We collected other 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous ( p <0.001) and as discrete variable (10% cut-off: p <0.003; Immunoreactive score: p <0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the whole dataset showed that AR<10% significantly correlates with worse outcomes (p=0.005 for PFS and p=0.002 for brain PFS (bPFS) respectively). Comparison of AR expression between primary tissue and paired brain metastases in the whole dataset did not show any statistically significant difference. Conclusions AR’s deficiency confirms its predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients’ prognosis.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
David Waldron ◽  
Eoin Condon ◽  
...  

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.


2010 ◽  
Vol 17 (3) ◽  
pp. 797-807 ◽  
Author(s):  
Pasqualino Malandrino ◽  
Abir Al Ghuzlan ◽  
Marine Castaing ◽  
Jacques Young ◽  
Bernard Caillou ◽  
...  

To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level ≥14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.


2020 ◽  
Vol 37 (4) ◽  
pp. 349-358
Author(s):  
Miljana Džunić ◽  
Ivan Petković ◽  
Ana Cvetanović ◽  
Ivica Pejčić ◽  
Svetislav Vrbić ◽  
...  

The aim of the research was to investigate prognostic factors in patients with resected colorectal liver metastases (CLMs) after biological and chemotherapy, which made initially unresectable disease suitable for resection. Sixty-six patients with resected CLMs, operated after induction bio-chemotherapy with bevacizumab + FOLFOX4, treated at the Clinic of Oncology, Clinical Center Niš from 2010 - 2017 were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test according to demographic characteristics, characteristics of the disease and the treatment. A univariate COX regression analysis was performed. In patients with up to 4 CLMs, DFS was significantly longer than in patients with five or more metastases (18,384 v.s. 6,85 months; p < 0,001). Significantly longer OS was present in patients with up to four CLMs than in those with five or more CLMs (44,687 v.s. 29,723 months; p=0,006) and in patients without extrahepatic disease (41,71 v.s. 23,283 months; p=0,012). In the univariate analysis, five or more CLMs were predictors of poorer DFS (HR 3,989; 95% CI 1,055 - 15,087; p = 0,042), whereas the absence of extrahepatic disease was a predictor of better OS (HR 0,122; 95% CI 0,017 - 0,869; p = 0,036). Results of this research are in concordance with previous larger studies in patients with resected CLMs. The number of hepatic and the presence of extrahepatic metastases are prognostic parameters in patients with resected CLM after conversion bio-chemotherapy.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1542-1542
Author(s):  
Silvia M Rojas ◽  
María Díez-Campelo ◽  
Elisa Luño ◽  
Teresa Bernal ◽  
Monica Cabrero ◽  
...  

Abstract Myelodysplastic syndrome with 5q- (MDS 5q-) is the only cytogenetically defined MDS category recognized by the world Health Organization (WHO) in 2001 and 2008 and is defined as a MDS with isolated deletion on the long arm of chromosome 5 and less than 5% of blast cells in bone marrow (BM). It is well known that for patients with MDS 5q- and transfusion dependence (TD), Lenalidomide is the first choice treatment. However, as far as we know there are no data regarding factors that may impact on the development of TD in these patients or the disease evolution in patients diagnosed without TD. In the present study a retrospective multicenter analysis on patients with low-int 1 MDS 5q- without TD at diagnosis has been performed in order to answer these questions. Patients and methods Data from eighty-four low-Int 1 risk MDS 5q- patients diagnosed between 1980 and 2012 were retrospectively analyzed. Ninety percent of patients had a single 5q deletion and according to IPSS-R 99% were in low and very low risk. Statistical analysis The event of TD was defined as the development of TD according to the IWG criteria (2006) and/or the beginning of a treatment which could modify disease course (Lenalidomide or ESA). Patients follow up was updated on March 30, 2013, and all follow up data were censored at that point. Transfusion free survival (TFS), Overall survival (OS) and AML were analyzed using the Kaplan – Meier method. TFS, OS, and Leukemia free survival (LFS) were measured from diagnosis to TD or to last follow up if transfusion free (TFS), death from any cause or last follow up (OS) and evolution to AML or last follow up (LFS). Multivariate analysis was performed using Cox’s proportional hazards regression model. Incidence of progression to AML was analyzed with cumulative incidence competing risk method. For comparison of Kaplan Meier curves the long rank test was used, with statistical significance with p<0.05 statistical analysis was performed using SPSS 15.0 and NCSS V.8, 2010. Results During the study 61 (73%) became TD at a median of 1.7 years from diagnosis. The unique factor associated with poorer TFS was Hb level <9 g/dl (p=0.007) and this impact retained statistical significance in the multivariate analysis (table.1) Among the 61 TD patients, 49 received treatment: 19 lenalidomide, 24 ESA and 6 other treatments. Fifteen patients were treated (7 with lenalidomide and 8 with ESA) previous to TD development. In order to know the evolution of this very good prognostic subgroup of patients, OS and LFS analysis were performed. Median follow up was 48 months, 46% of patients are alive at the time of the last follow up and 31% developed secondary AML (sAML). Estimated OS at 2 and 5 y was 92% and 50% respectively. Regarding Univariate analysis, platelet <100.000 x109/L, and IPSS-R intermediate risk group were associated with poorer OS (p=0.001 and 0.019 respectively). On the contrary, patients who had received treatment showed better OS. This benefit is more evident among patients receiving Lenalidomide (p=0.015). In the multivariate analysis platelets <100.000 x109/L and Lenalidomide treatment retained the statistical significant impact on OS (table1). When LFS was analyzed the cumulative incidence of progression into AML was 4,4% after 2 y. and 12,7% after 5 y from diagnosis with median time to sAML of 8.16 years (CI 95%: 6.05-10.27). LFS at 2 and 5 y was 86% and 73% respectively. When univariate analysis was performed variables with impact on sAML were platelet <100.000 x109/L (p=<0,001), and to have received treatment (p=0,02). In the multivariate analysis only thrombocytopenia retained statistical significance (table1).In summary, the present analysis shows that Hb is the only parameter that conditions the TD development in MDS-5q- patients. In this very good prognostic subgroup beginning treatment with lenalidomide improves survival. Disclosures: Díez-Campelo: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen-Cilag: Research Funding. Off Label Use: In the present study we describe Lenalidomide treatment among patients with MDS and del(5q-) receiving this drug, not approval for this use in Europe, patients with anemia and transfusional requirements. Solé:Celgene: Consultancy, Honoraria; Celgene: Consultancy. Consuelo:Celgene Jansen-Cilag Arry Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 251-251
Author(s):  
J. Wang ◽  
C. C. Hsu ◽  
C. D. Fuller ◽  
T. M. Pawlik ◽  
R. C. Miller ◽  
...  

251 Background: To assess the effect of adjuvant therapy in gallbladder adenocarcinoma (GBC). Methods: Retrospective review was conducted at five institutions to identify pts who had surgery for confirmed dx of GBC from 1985-2008 (N = 189). Pts were excluded if they had chemo alone (N = 8), path other than adenoca (N= 7), carcinoma in situ (N=1), < 30 days of follow-up (N = 2), or missing data (N=14). Of the remaining 156 pts, 58 received surgery only and 98 received adj RT ± chemo. Kaplan-Meier was used for overall survival (OS) and Cox proportional hazards to compare risk factors. Results: Median age of dx was 64.4, 68.0% were female, 37.9% had ≥ stage 2b, 37.2% had + nodes, and 32.1% had + margins. Overall, 35.9% of the patients had simple cholecystectomy (SC) only and 64.1% had radical resection (ER). mOS for pts treated with surgery alone was 49.7 months (95% CI: 24.8 to Inf). On univariate analysis, + margins (HR 2.72, p<0.001) was associated with worse OS, whereas ER compared to SC improved survival in both univariate (HR 0.46, p<0.001) and multivariate (HR 0.53, p=0.033) analyses after adjusting for node/margins, T-stage, adj RT, age, gender, and institution. mOS for the entire cohort vs. adj RT (median 50.4 Gy) ± chemo was 30.7 months (95% CI: 19.2 to 46.9) vs. 26.9 months (95% CI: 15.5 to 39.1). But, compared to surgery alone, the adj group was more likely to have had node +, margin +, or T-stage 3+ (all p<0.001). The adj RT group was also less likely than surgery alone pts to have undergone ER (p = 0.007). On multivariate analysis, decreased OS was also found for node + (HR 2.09, p=0.004), margin + (HR 1.84, p=0.043), and T3/T4 disease (HR 2.37, p=0.002). After adjusting for surgical extent, node, margin, T stage, age, gender, and institution, there was improved OS with adj therapy (HR: 0.43, p = 0.020). When stratified by surgical extent, the risk estimate for adj RT improved OS among those with SC (n=56; HR 0.20, p=0.135) and ER (n=100; HR 0.46, p=0.067), but was not statistically significant. Conclusions: ER was associated with improved OS, whereas node/margin+ and T-stage 3+ were associated with worse survival. In multivariate analysis, adj RT improved OS after surgery. Given the poor prognosis of GBC patients with advanced disease, consideration of adj therapy is appropriate. No significant financial relationships to disclose.


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