Prognostic and predictive factors for overall survival (OS) in metastatic esophagogastric cancer (EGC): A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4048-4048 ◽  
Author(s):  
Emil ter Veer ◽  
Jessy Joy van Kleef ◽  
Sandor Schokker ◽  
Stephanie Van Der Woude ◽  
Marety Laarman ◽  
...  

4048 Background: Prognostic and predictive factors for metastatic EGC are important to estimate prognosis, inform clinical decision-making and design future trials. We performed a systematic review with meta-analysis to identify these factors. Methods: We searched Medline, EMBASE and CENTRAL for phase 2/3 randomized controlled trials (RCTs) until January 2016 on palliative chemotherapy and targeted therapy for metastatic EGC. Prognostic and predictive factors were identified from respectively multivariate cox regressions and stratified treatment comparisons. Hazard Ratio’s (HR) for OS were extracted and pooled with meta-analysis if possible. Prognostic factors were considered independent if the multivariate HR was significant (P≤0.05). Predictive factors were clinically relevant if P for subgroup interaction was ≤0.20 and the HR in one of the subgroups was significant (P≤0.05). Results: We identified 47 RCTs (14,853 patients), wherein 54 potential prognostic and 40 predictive factors were reported. Eight independent prognostic factors for poor OS reported in ≥2 RCTs based on ≥300 patients were: performance status of ≥1 vs 0 (pooled HR, 95% confidence interval: 1.47, 1.25-1.73) or 2 vs 0-1 (1.52, 1.32-1.76); metastatic vs locally advanced disease (1.55, 1.39-1.72); diffuse vs intestinal/other histology (1.38, 1.12-1.71); ≥3 vs < 2 metastatic sites (1.35, 1.07-1.70); presence of metastases in peritoneum (1.24, 1.01-1.51) or liver (1.45 (1.28-1.64); measurable vs non-measurable disease (1.31, 1.04-1.66); and no prior vs prior surgery (1.33, 1.16-1.53). Predictive factors for specific treatment comparisons based on ≥300 patients were: age (≥65 vs < 65); performance status; tumor location (GEJ vs stomach); disease stage; number of metastatic sites; peritoneal metastasis; measurable disease; histology; HER2; KRAS; VEGF A; and Neuropilin-1 for first line treatments; and time to progression on first line therapy ( < 3, 3-6 or ≥6 months) for second-line treatments. Conclusions: Eight independent prognostic factors for OS and thirteen clinically relevant predictive factors for treatment efficacy of EGC were found.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15169-15169
Author(s):  
V. Catalano ◽  
F. Graziano ◽  
D. Santini ◽  
A. M. Baldelli ◽  
P. Giordani ◽  
...  

15169 Background: Currently, there is no established second-line chemotherapy for pts with advanced gastric cancer who failed to respond or progressed after a first-line chemotherapy. Many of these pts still have a good performance status or have symptoms to be palliated at the time of first-line failure and are candidates for second-line chemotherapy. However, phase II trials demonstrate divergent results about pts more likely to benefit from second-line chemotherapy. We retrospectively analyzed the influence of various clinicopathologic factors on the survival of pts treated with second-line chemotherapy. Methods: Analysis is based on the data of 169 pts consecutively treated at 3 oncology department with a second-line chemotherapy. Univariate and multivariate analyses were performed to determine prognostic factors of survival. The variable used for analysis were: sex, age, ECOG performance status, a weight loss > 5 Kg in the last month; site of primary tumor, histopathology; hemoglobin, serum albumin, and CEA levels, number and site of metastatic disease, response to and time-to-progression (TTP) with the first- line chemotherapy. Results: The variables predictive of better survival were: ECOG PS 0–1 (p<0.001), no weight loss (p=0.001), hemoglobin level > 10 g/dl (p=0.01), CEA level <50 U/ml (p<0.02), number of metastatic sites = 2 (p=0.002), TTP of the first-line chemotherapy > 4 months (p=0.008). Peritoneal carcinomatosis was predictive of poor survival only when associated with one or more signs or symptoms as vomiting, anorexia, abdominal pain, ascites(p=0.03). Four factors were independently associated with better overall survival: ECOG PS 0–1 (p=0.002; HR 0.46; CI 95%, 0.29–0.75), CEA level <50 U/ml (p=0.008; HR 0.54; CI 95%, 0.35–0.85), one or two metastatic sites of disease (p=0.01; HR 0.58; CI 95%, 0.39–0.88), and TTP of the first-line chemotherapy > 4 months (p=0.02; HR 0.66; CI 95%, 0.45–0.95). Conclusions: In the absence of data deriving from randomized, controlled, clinical trials, this analysis suggests that some clinical factors may help clinicians to better select groups of pts with gastric cancer more likely to benefit from a second-line chemotherapy. No significant financial relationships to disclose.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 690-690
Author(s):  
Pilar Garcia Alfonso ◽  
Gonzalo Garcia ◽  
Iria Gallego ◽  
Isabel Peligros ◽  
Ana Corcuera ◽  
...  

690 Background: In recent years, prognostic and predictive factors in mCRC are becoming more important, outstanding the tumor and metastasic location, the primary tumor and/or metastasis resections as well as molecular biomarkers (KRAS, NRAS, BRAF and PIK3CA). Methods: We conducted a retrospective study of 334 patients with mCRC diagnosticated between January 2010 and June 2015 in the Oncology Service from HGUGM. The objective of our study was to evaluate the overall survival (OS) relating to each of these settings. We also evaluated OS considering the biological treatment received in first line. Multivariant analysis was performed with independence of tumor and metastasic location, metastasectomies, no primary tumor resection, biological treatment used in first line, age, sex and moleculars biomarkers. Results: Median OS was 24,34m. The advantageous prognostic factors which statistically significant impact on the median OS have been triple (RAS and BRAF) (n = 86) and quadruple (RAS, BRAF and PIK3CA) (n = 76) wild-type (wt 36,6m vs mut 23m, p = 0,02; wt 37,6m vs mut 23,38m, p = 0.02, respectively), left tumor location with rectum (left 25,55m vs right 19,44m, p = 0,001) and isolated hepatic and pulmonary metastasic location (30,32 vs 23 m, p = 0,03; 45,32m vs 23,38 m, p = 0,004, respectively). The main disadvantageous prognostic factor has been the no primary tumor resection (13,75m vs 31,61m, p = 0,00001) with independence of synchronous presentation of the disease as well as biomarkers mutational status. Median OS in first line was 30.13 m with bevacizumab (n = 54) vs 16,18m with antiEGFR (n = 28) (p = 0.02) in extended RAS wild-type patients (n = 101). Considering the multivariate analysis, the independent prognostic factors have been the isolated pulmonary metastasis (HR = 0,46; CI 95% 0,30-0,73;p = 0,001), quadruple wild-type (HR = 0,69;CI 95% 0,49-0,97; p = 0,031), metastasectomies (HR = 0,29; CI 95% 0,21-0,4; p = 0,000), right location (HR = 1,43; CI 95% 1,08-1,9;p = 0,014) and no primary tumor resection (HR = 2,06; CI 95% 1,49-2,86; p = 0,000). Conclusions: Isolated pulmonary metastasis, quadruple wild-type, metastasectomies, left location and primary tumor resection have independent positive prognostic value, according to our retrospective study.


Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 530 ◽  
Author(s):  
van den Ende ◽  
ter Veer ◽  
Mali ◽  
van Berge Henegouwen ◽  
Hulshof ◽  
...  

Background: An overview of promising prognostic variables and predictive subgroups concerning the curative treatment of esophageal and gastric cancer from randomized controlled trials (RCTs) is lacking. Therefore, we conducted a systematic review and meta-analysis. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to March 2019 for RCTs on the curative treatment of esophageal or gastric cancer with data on prognostic and/or predictive factors for overall survival. Prognostic factors were deemed potentially clinically relevant according to the following criteria; (1) statistically significant (p < 0.05) in a multivariate analysis, (2) reported in at least 250 patients, and (3) p < 0.05, in ≥ 33% of the total number of patients in RCTs reporting this factor. Predictive factors were potentially clinically-relevant if (1) the p-value for interaction between subgroups was <0.20 and (2) the hazard ratio in one of the subgroups was significant (p < 0.05). Results: For gastric cancer, 39 RCTs were identified (n = 13,530 patients) and, for esophageal cancer, 33 RCTs were identified (n = 8618 patients). In total, we identified 23 potentially clinically relevant prognostic factors for gastric cancer and 16 for esophageal cancer. There were 15 potentially clinically relevant predictive factors for gastric cancer and 10 for esophageal cancer. Conclusion: The identified prognostic and predictive factors can be included and analyzed in future RCTs and be of guidance for nomograms. Further validation should be performed in large patient cohorts.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7138-7138
Author(s):  
G. L. Pappagallo ◽  
O. Belvedere ◽  
O. Vinante ◽  
F. Grossi

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18048-18048
Author(s):  
S. Altug ◽  
C. Li ◽  
M. Marek ◽  
S. Guclu ◽  
Y. Kim ◽  
...  

18048 Background: The aim of this prospective, multi-country, observational study (B9E-AA-B004) is to estimate the effect of prognostic factors, including continued smoking during therapy, on treatment outcomes in patients (pts) with advanced NSCLC receiving first- line chemotherapy with a gemcitabine (gem)-platinum combination as part of their routine care. Methods: Major eligibility criteria included: tissue diagnosis of advanced stage IIIB/IV NSCLC not amenable to curative surgery/radiotherapy; no prior chemotherapy; ECOG performance status (PS) 0 or 1; and written informed consent. A predictive model was constructed and validated by splitting the data at random by centre into two datasets in a ratio of 3:1 Construction:Validation. The primary and secondary endpoints are the effect of prognostic factors on survival and selected adverse events (AEs), respectively. The association of smoking with outcomes was tested in the Construction dataset. Results: This interim analysis to assess the effect of prognostic factors on AEs occurred when all pts had completed treatment. 1214 pts were enrolled: 75.1% male; mean age 60.5 yr, range 23–86 yr; 57.1% Stage IV; 66.2% PS 1; 69.4% received gem-cis, 30.5% gem-carb; 25.7% had never smoked, 70.8% had ever smoked and 11.2% continued smoking during therapy. 22.0% of pts had =1 AE. After variable selection in the Construction database (891 pts) the following factors were associated with an AE possibly related to therapy: disease stage (IV vs III, odds ratio (OR) =1.48, p=0.034), weight loss >10% (OR=0.60, p=0.017), age (<70 vs =70, OR=0.66, p=0.046), treatment (gem- carb vs gem-cis, OR=1.5, p=0.04), pain at baseline (present vs absent, OR=1.5, p=0.03), country (OR vs Taiwan ranged from 0.32 (Israel) to 4.2 (Egypt), p<0.0001). Sex (F vs M, OR=0.86) was then added to the model because of its clinical importance. There was a trend towards a higher probability of an AE with continued smoking during therapy (OR=1.4), but this was not statistically significant (p=0.28). Conclusions: This model can be used to improve the prediction of whether patients are likely to experience treatment-related AEs. While the trend was for a greater AE rate in pts who continued to smoke during therapy, this was not proven. [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6517-6517
Author(s):  
William G. Wierda ◽  
Susan Mary O'Brien ◽  
Stefan Faderl ◽  
Alessandra Ferrajoli ◽  
Jan Andreas Burger ◽  
...  

6517 Background: First-line chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) demonstrated improved outcomes, including survival, for fit patients (pts) with CLL. Modifications of this regimen, including intensified rituximab (FCR3), addition of mitoxantrone (FCMR) or addition of alemtuzumab fir high-risk CLL (CFAR), were evaluated but did not improve outcomes in historic comparisons. Methods: We correlated outcomes, including complete remission (CR), time-to-treatment failure (TTF) and overall survival (OS), with new and traditional pretreatment prognostic factors to identify high-risk pts. Results: All pts (N=473) had an NCI-WG indication for treatment and received a first-line FCR-based regimen on trial; the intended treatment was 6 courses. Patient characteristics correlated with outcomes are presented in the table. Factors not associated with outcomes included absolute lymphocyte count; platelet count; performance status; spleen size; liver size; and number of involved lymph node sites. Conclusions: We identified the following as high-risk pretreatment features for patients going on first-line FCR-based therapy: advanced age, presence of 17p del, high B2M (≥4mg/l), and unmutated IGHV gene. Pts with these features should be pursued with new treatment modalities and novel agents in order to improve outcomes. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21634-e21634
Author(s):  
Marios P. Decatris ◽  
Joy A Thomas ◽  
Mark Hayes ◽  
Philip Ryan ◽  
Aled Phillips ◽  
...  

e21634 Background: Hyperprogressive disease(HPD) is a recently recognized type of accelerated tumor progression with immune checkpoint inhibitor(ICI) therapy. A recent meta-analysis identified serum lactate dehydrogenase(LDH) above upper limit of normal(ULN), liver metastases and > 2 metastatic sites to be associated with increased likelihood of HPD. Methods: We performed a single-center retrospective analysis of NSCLC patients treated with ICI from 2/2017-1/2020. We defined HPD using combined criteria of failure to complete > 4 cycles of ICI and radiological progression with development of new lesions or marked clinical progression where restaging was not achievable because of rapid decline in performance status. Treatment discontinuation/interruption because of toxicity alone, was not designated as HPD. Results: HPD was seen in 9/41(22%) patients treated with at least 1 cycle of ICI. In 6/9 there was marked radiological progression (new lesions/significant progression of existing lesions); in the remaining 3 restaging was not possible because of rapid decline which mandated treatment cessation. Patients with HPD were more likely to have a raised LDH, liver metastases or > 2 metastatic sites but these differences were not statistically significant. 9/9 versus 5/32 patients in the HPD/non-HPD cohorts respectively progressed within 10 weeks of treatment (p < 0.001) and 7/9 versus 12/32 respectively did not survive beyond 6months (p = 0.057). Conclusions: This small study has shown a non-statistically significant trend for association between HPD, raised LDH, liver metastases and presence of > 2 metastatic sites. A better understanding of risk/predictive factors for HPD is essential for improved patient selection for treatment with ICI. [Table: see text]


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