Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study

BackgroundCheckpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.MethodsMGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB–IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR.ResultsPretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p<0.0001), in the confirmation cohort (HR 3.62, 95% CI 2.19 to 5.98, p<0.0001) and in the independent validation cohort (HR 2.57, 95% CI 1.56 to 4.25, p=0.00023). Prior lines of systemic treatment did not influence the significance of MGR. Importantly, the prognostic impact of MGR was independent of total tumor burden, diameter of the largest metastasis, number of prior lines of systemic treatment, LDH, as well as liver and brain metastasis (discovery and confirmation cohorts: both p<0.0001). Superiority of MGR compared with these variables was confirmed in the independent multicenter validation cohort (HR 2.92, 95% CI 1.62 to 5.26, p=0.00036).ConclusionsHigh pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens.

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PET Evaluation Before Autografting Has a Strong Prognostic Impact in High-Risk, Relapsed Follicular Lymphoma Patients

Blood ◽

10.1182/blood.v118.21.1612.1612 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1612-1612

Author(s):

Loic Ysebaert ◽

Jehan Dupuis ◽

Michel Meignan ◽

Anne Julian ◽

Christian Recher ◽

...

Keyword(s):

Stem Cell ◽

Follicular Lymphoma ◽

Conditioning Regimen ◽

Tumor Burden ◽

Prognostic Impact ◽

High Tumor Burden ◽

Richter Syndrome ◽

The Impact ◽

Cell Harvest

Abstract Abstract 1612 INTRODUCTION: in follicular lymphoma (FL) patients with high tumor burden (as defined by GELF criteria), R-CHOP is the standard upfront immunochemotherapy. Results from the PRIMA study suggest that a positive PET after induction therapy predicts for earlier relapses, even despite maintenance with rituximab (RTX) for two years [Trotman J, 2011]. For patients under 65y, who relapse after R-CHOP+/−RTX maintenance with high tumor burden, R-chemo+autografting is a recommended option. In a retrospective cohort of 43 relapsed FL pts in two French University Hospitals, we explored the role of such a strategy on outcome - in the era of new RTX based modalities - and also evaluated the impact of PET results before autografting. PATIENTS AND METHODS: Patients with relapsed FL after R-CHOP, with at least 1 GELF criteria at relapse (high tumor burden), and who received R-chemo before autografting were eligible. IWC+PETresponse criteria (Cheson 2007) were used, after R-CHOP frontline, and after salvage (before autografting). Patients with Richter transformation at relapse were excluded from this study. OS was calculated from date of salvage to date of death or last follow-up; progression-free survival (PFS) and time to next treatment (TTNT) were calculated from completion of salvage to date of FL relapse or next chemotherapy, respectively. RESULTS: 43 pts (60% males) younger than 65y were identified: they received either FCR-based (2 cycles of FCR, 1 cycle of R-DHAP then stem cell harvest, 2 last cycles of FCR, n=25) or R-DHAP-based (4 cycles of R-DHAP or DHAOx (oxaliplatin replacing cisplatin), and stem cell harvest, n=18). Characteristics at salvage: median age was 54 (range 28–62), with median GELF score of 1 (1–4). Thirty % had progression within 6 mo of R-CHOP (refractory);median PFS was 12mo (range 1–40mo) andmedian TTNT was 15mo. RTX maintenance in 12/43 pts did not significantly increased PFS (15 vs 9 mo, p=0.1). FLIPI1 was low in 39%, Int 36%, high 25% of pts, and FLIPI2 was low in 22%, Int 62.5%, high 15.5% of pts. 1/43 pt had CD20- relapse (who received RTX maintenance), and received FC without RTX. Results: response to FCR/R-DHAP included CR+CRu 68/72%, PR 24/28% respectively, PET evaluation was found negative in 23.5/36% respectively (p=ns). Median stem cell harvest (median 2 leukaphereses) was 4.37 vs 7.8.106 CD34+/kg in FCR vs R-DHAP pts (Mann-Whitney p=0.09), without failure (only one patient required plerixafor). Four patients did not receive the planned autologous transplant (2 failures after FCR (including one Richter transformation), 1 hepatitis before conditioning regimen, 1 withdrawal of consent). Conditioning regimen for the remaining 39 pts was BEAM in 16 (4 FCR+12 R-DHAP), Zevalin-BEAM in 23 pts (9 FCR+14 R-DHAP), including 9 pts who further received RTX maintenance post-autografting. At a median follow up of living pts of 18mo, 9 pts had relapsed, of which 8 needed additional therapy. At time of analysis (June 2011), 37 pts were alive. Causes for death included 1 pancytopenia and infection, 1 Richter syndrome, 1second cancer, 2 complications of allografting (received later on). Late complications were common: pancytopenia or prolonged grade III-IV neutropenia (>3mo) after procedure occurred in 5/43 pts (3 FCR, 2 R-DHAP, without evidence of MDS/AML in these cases), Richter syndrome occurred in 2 patients (1 death), second cancer in 3 pts (1 Hodgkin, 1 womb sarcoma, 1 lung cancer). On an intend-to-treat basis, 41 pts are evaluable. For FCR/R-DHAP pts, 2y PFS was 68/68%, 2y TTNT 80/70%, and 2y OS 73/100%, respectively (logrank p=ns). Two years TTNT tended to be higher in pts receiving Z-BEAM (55 vs 83%), or with PET negativity before autografting (70 vs 85%), both without reaching significance (logrank p=0.1). PET negativity before autografting was the only variable statistically associated with superior OS in our series (logrank p=0.0003). CONCLUSIONS: Our data suggest that PET negativity before consolidative autografting is an achievable and desirable goal in FL salvaged after R-CHOP. Disclosures: Ysebaert: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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The demand for psycho-oncological support in 820 melanoma patients: What are the determinants for the development of distress?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9514 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9514-9514

Author(s):

Andrea Forschner ◽

Petra Riedel ◽

Maximilian Gassenmaier ◽

Alexander Scheu ◽

Lukas Kofler ◽

...

Keyword(s):

Lower Risk ◽

Systemic Treatment ◽

Female Gender ◽

Advanced Melanoma ◽

Stage Iii ◽

Patient Specific ◽

Psychological Burden ◽

Younger Age ◽

Melanoma Patients ◽

The Impact

9514 Background: There is limited data about the impact of melanoma on the psychological burden of patients. Despite some known predictors for distress like female gender or younger age, melanoma stages have not been found being related to distress in melanoma patients and there is no data concerning distress in melanoma patients under systemic treatment for metastases. Methods: Between July and September 2016, 820 melanoma patients at the outpatient clinic at the Department of Dermatology at the University of Tuebingen underwent psycho-oncological screening. The patients routinely completed the distress thermometer (DT), supplemented by a problem list, before consulting the physician. DT scores ≥ 5 are above-threshold, indicating the need for psycho-oncological support. We matched psycho-oncological data with tumor and patient specific data to examine tumor or patient specific influence on distress using logistic regression. Results: 406 (49.5%) men and 414 (50.5%) women were included, mean age was 62.35 years (IQR 52-75), mean time since primary diagnosis of melanoma was 54.84 months (IQR 15-76). 359 (44%) of the patients suffered from advanced melanoma (stage III n = 182, stage IV n = 177). 120 patients (14.6%) received systemic treatment for metastases: 90/120 (75%) checkpoint inhibitors, 27/120 (22.5%) targeted therapy and 3/120 (2.5%) chemotherapy. 338/820 (41.2%) of the patients met the cut-off score for distress. Significant influencing factors (p < 0.05) for DT values of ≥ 5 were: female gender, younger age, melanoma stage III and IV. Interestingly we found a lower risk for values above-threshold for patients under systemic treatment, although this was not significant (p = 0.252). Conclusions: This is the first analysis to demonstrate the impact of advanced melanoma stages on DT scores above-threshold. Our study is also the first to indicate a lower risk for distress in patients under systemic treatment. This might be due to the closer contact between these patients and their physicians. Nevertheless, more than 40% of our patients needed psycho-oncological support. Departments that care for melanoma patients should therefore be fitted by a sufficient number of psycho-oncologists.

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A digital pathology demonstration of an "immune hot" ICOS+/CD45RO+ immunephenotype and the impact on survival in patients with esophageal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4062 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4062-4062

Author(s):

Matthew Philip Humphries ◽

Natalie Fisher ◽

Rafal Kacprzyk ◽

Stephanie G Craig ◽

Victoria Bingham ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Adenocarcinoma ◽

Immune Checkpoint ◽

Validation Cohort ◽

Survival Advantage ◽

Immune Checkpoints ◽

Discovery Cohort ◽

Therapeutic Implications ◽

Immune Biomarkers ◽

The Impact

4062 Background: Therapies targeting immune checkpoints are changing our understanding of the biology and treatment of cancer. Analysing the immune landscape in esophageal adenocarcinoma (EA) may help future prognostication and therapeutic decision-making. Methods: We assembled 310 EA cases in a tissue microarray format with associated clinicopathological information, including a discovery cohort of 156 EA from Northern Ireland and a 154 EA validation cohort from Aberdeen. We carried out validated immunohistochemistry (IHC), stained for range of adaptive immune (CD3, CD4, CD8 and CD45RO) and immune checkpoint biomarkers (ICOS and IDO-1). Slides were digitised and assessed using QuPath image analysis software program to quantify their expression and correlate them with outcome. Results: In the discovery cohort we identified a group of patients highly expressing several immune biomarkers, conferring a significant positive survival advantage (p = 0.022). CD3, CD4, CD8, CD45RO, and ICOS were individually prognostic for better overall survival (Log rank p = 0.0003; p = 0.0292; p = 0.0015; p = 0.0008; p = 0.0051 and p = 0.0264 respectively). Multivariate and correlation analysis identified a subgroup of CD45RO+/ICOS+ patients with significantly improved overall survival (p = 0.0002). The co-expression of CD45RO+/ICOS+ immunophenotype was investigated in the validation cohort and a confirmed survival advantage was seen (p = 0.042). Additionally, the Opal Multiplex IHC technology revealed the much higher frequency of single-cell, dual labelling of CD45RO+/ICOS+ in immune hot cases. Conclusions: These data demonstrate the advantage of immune markers other than the traditional CD3/CD4/CD8 in EA prognostication. The fact that one of these biomarkers is an immune checkpoint inhibitor may have therapeutic implications.

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Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment

Haematologica ◽

10.3324/haematol.2019.237990 ◽

2020 ◽

Vol 105 (11) ◽

pp. 2592-2597 ◽

Cited By ~ 1

Author(s):

Annarita Conconi ◽

Catherine Thieblemont ◽

Luciano Cascione ◽

Valter Torri ◽

Barbara Kiesewetter ◽

...

Keyword(s):

Systemic Treatment ◽

Reference Group ◽

B Cell Lymphoma ◽

Prognostic Impact ◽

Poor Overall Survival ◽

Early Progression ◽

Progression Of Disease ◽

Validation Set ◽

Lost To Follow Up ◽

The Impact

Early progression of disease (POD) within two years from diagnosis is linked with poor overall survival (OS) in follicular lymphoma but its prognostic role is less clear in extranodal marginal zone B-cell lymphoma (EMZL). We sought to identify prognostic factors associated with early POD and to determine whether is associated with inferior OS. We analyzed the impact of early POD in the IELSG19 clinical trial dataset (training set of 401 patients randomly assigned to chlorambucil or rituximab or chlorambucil plus rituximab). Reproducibility was examined in a validation set of 287 patients who received systemic treatment. In both sets, we excluded from the analysis the patients who, within 24 months from treatment start, died without progression or were lost to follow-up without prior progression. OS was calculated from progression in patients with early POD and from 24 months after start of treatment in those without (reference group). Early POD was observed in 69 of the 384 (18%) evaluable patients of the IELSG19 study. Patients with high-risk MALT-IPI were more likely to have early POD (p=0.006). The 10-year OS rate was 64% in the early POD group and 85% in the reference group (HR= 2.42, 95%CI, 1.35-4.34; log-rank P=0.002). This prognostic impact was confirmed in the validation set, in which early POD was observed in 64 out of 224 (29%) evaluable patients with 10-year OS rate of 48% in the early POD group and 71% in the reference group (HR= 2.15, 95%CI, 1.19-3.90; log-rank P=0.009). In patients with EMZL who received front-line systemic treatment, early POD is associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.

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Genotype of CDC73 germline mutation determines risk of parathyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-20-0149 ◽

2020 ◽

Vol 27 (9) ◽

pp. 483-494 ◽

Cited By ~ 1

Author(s):

Yulong Li ◽

Jianhua Zhang ◽

Poorni R Adikaram ◽

James Welch ◽

Bin Guan ◽

...

Keyword(s):

Parathyroid Carcinoma ◽

Validation Cohort ◽

High Impact ◽

National Institutes Of Health ◽

Parathyroid Cancer ◽

Discovery Cohort ◽

Kaplan Meier ◽

Increased Risk ◽

Increase Risk ◽

The Impact

Mutation of the CDC73 gene, which encodes parafibromin, has been linked with parathyroid cancer. However, no correlation between genotypes of germline CDC73 mutations and the risk of parathyroid cancer has been known. In this study, subjects with germline CDC73 mutations were identified from the participants of two clinical protocols at National Institutes of Health (Discovery Cohort) and from the literature (Validation Cohort). The relative risk of developing parathyroid cancer was analyzed as a function of CDC73 genotype, and the impact of representative mutations on structure of parafibromin was compared between genotype groups. A total of 419 subjects, 68 in Discovery Cohort and 351 in Validation Cohort, were included. In both cohorts, percentages of CDC73 germline mutations that predicted significant conformational disruption or loss of expression of parafibromin (referred as ‘high-impact mutations’) were significantly higher among the subjects with parathyroid cancers compared to all other subjects. The Kaplan–Meier analysis showed that high-impact mutations were associated with a 6.6-fold higher risk of parathyroid carcinoma compared to low-impact mutations, despite a similar risk of developing primary hyperparathyroidism between two groups. Disruption of the C-terminal domain (CTD) of parafibromin is directly involved in predisposition to parathyroid carcinoma, since only the mutations impacting this domain were associated with an increased risk of parathyroid carcinoma. Structural analysis revealed that a conserved surface structure in the CTD is universally disrupted by the mutations affecting this domain. In conclusion, high-impact germline CDC73 mutations were found to increase risk of parathyroid carcinoma by disrupting the CTD of parafibromin.

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Prognostic Impact of ABCA3 Expression in Pediatric Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v128.22.1694.1694 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1694-1694

Author(s):

Antony Ceraulo ◽

Aminetou Mint-Mohamed ◽

Delphine Maucort-Boulch ◽

Helene Lapillone ◽

Guy Leverger ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Validation Cohort ◽

Multivariate Analyses ◽

Prognostic Impact ◽

Discovery Cohort ◽

Pediatric Acute Myeloid Leukemia ◽

Primer Sets ◽

Pediatric Aml ◽

Acute Myeloid

Abstract Background. Despite progress in the molecular and genetic classification of pediatric acute myeloid leukemia (AML), the prognosis remains heterogeneous. The ATP-binding cassette transporter A3 (ABCA3) seems specifically involved in the resistance of pediatric AML to intensive chemotherapy. However, studies having investigated the prognostic impact of ABCA3 expression have yielded conflicting results with respect to patient outcomes while the small sample size of these studies precluded the use of multivariate analysis. Here we investigated the prognostic impact of ABCA3 expression in a representative series of homogeneously treated pediatric AML. Methods. Samples derived from 233 patients with available high-quality RNA and enrolled in the ELAM2 protocol (NCT00149162). qRTPCR amplification of 2 conserved ABCA3 mRNA sequences was performed with GUS and ABL as reference genes. Primer sets were complementary to exons 6-7 and exons 19-20 junctions. Patients were classified according to their standardized cytogenetic and molecular (NPM1 mutations, FLT3-ITD, CEBPA double mutations) risk subgroups (Rubnitz JE, Blood 2012;119:5980-5988, Creutzig U, Blood 2012;120:3187-3205). Treatment consisted of 1 induction course (AraC and mitoxantrone) and 3 consolidation courses (course 1 and 3 with high dose AraC); all children with either intermediate or high-risk disease were candidates for hematopoietic stem cell transplant (HSCT) in complete remission (CR) after 1 to 2 consolidation courses. Results. The discovery cohort included 120 patients. Median age, median WBC, CR rate, relapse rate, median follow-up, 5-years EFS, DFS, and OS were 9.4 years, 19.3 G/L, 95%, 29%, 60 months, 58±6%, 61±6%, and 71±5 months, respectively. The two primer sets yielded consistent results (R=0.9, p<10-4, Spearman Rank Correlation). Lower ABCA3 expression was positively associated with CBFB-MYH11 AML (p=0.002) and thereby with favorable cytogenetics (p=0.036) and low-risk AML (p=0.027). Higher ABCA3 expression was associated with higher relapse rate (p=0.006), shorter EFS (5-years, 34±9 vs 61±6 % p=0.0005), DFS (36±9 vs 62±6% p=0.0028), and OS (49±12 vs 79.5±5% p=0.0007). Multivariate analyses identified age, WBC, risk group, and ABCA3 expression as independent prognostic factors for EFS, DFS, and OS (Table 1). The validation cohort included 113 patients in whom the proportions of AML1-ETO- and MLL-positive AML were significantly higher than in the discovery cohort: 26,5% vs 6,7% (p<10-4) and 24.8 vs 14.2% (p=0.03). There was no significant difference in patients' outcome between the 2 cohorts. Using the same cutoff value in the validation cohort, higher ABCA3 expression remained significantly associated with shorter 5-years EFS: 63±7% vs 43±9% (p=0.025) with a trend for shorter DFS: 45±9 vs 53±11% (p=0.065). Multivariate analyses identified ABCA3 expression as an independent negative prognostic factor for EFS and DFS (Table 1). In the entire patients population, ABCA3 expression independently predicted EFS, DFS, and OS (not shown). In the low- (n=74) and adverse-risk (n=59) groups, higher ABCA3 expression remained associated with shorter 5-years EFS (low: 46±12 vs 75±7%, p=0.006; adverse: 12±10 vs 44±16%, p=0.018), DFS (low: 49±13 vs 75±7%; high: 12±11 vs 45±16%, p=0.016), and OS (low: 76±10 vs 94±4%; adverse: 32±14 vs 57±18%, p=0.046). Conclusion. ABCA3 expression represents an independent prognostic factor in pediatric AML. As they indicate that the level of ABCA3 expression is significantly associated with survival for currently accepted cytogenetic and molecular prognostic categories, our findings suggest that assessing ABCA3 expression will permit a better assessment of disease risk. Finally our results suggest that inhibiting ABCA3 expression, such as with indomethacin, could be beneficial in order to overcome drug resistance in pediatric AML. Disclosures No relevant conflicts of interest to declare.

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The Role Of Sentinel Node Tumor Burden In Modeling The Prognosis Of Melanoma Patients With Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup Study (N=2,086)

10.21203/rs.3.rs-959141/v1 ◽

2021 ◽

Author(s):

Saveria Tropea ◽

Paolo Del Fiore ◽

Andrea Maurichi ◽

Roberto Patuzzo ◽

Mario Santinami ◽

...

Keyword(s):

Sentinel Node ◽

Cox Regression ◽

Univariate Analysis ◽

Primary Melanoma ◽

Tumor Burden ◽

Breslow Thickness ◽

Practical Implementation ◽

Cox Regression Analysis ◽

Melanoma Patients ◽

The Impact

Abstract Background: The management of melanoma patients with metastatic sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. Methods: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. Results: The 3-year, 5-year and 10-year OS rates were 79 %, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P< 0.0001), male gender (P= 0.04), increasing Breslow thickness (P <0.0001), presence of ulceration (P =0.004), SNTB size (P <0.0001) and metastatic NSN (P <0.0001) were independent negative predictors of OS. Conclusion: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.

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Body mass index and survival of patients with metastastic renal cell carcinoma: Data from the German prospective RCC registry.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.454 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 454-454

Author(s):

Lothar Mueller ◽

Peter J. Goebell ◽

Ulla Von Verschuer ◽

Hans-Juergen Hurtz ◽

Melanie Franzem ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Systemic Treatment ◽

Prognostic Score ◽

Supporting Evidence ◽

Prognostic Impact ◽

Prospective Longitudinal ◽

The Impact

454 Background: Being overweight is a known risk factor for developing renal cell carcinoma (RCC). On the other hand, overweight patients may harbor a less aggressive type of disease. A recent meta-analysis was able to demonstrate that a high preoperative BMI was an independent prognostic indicator for better overall survival in patients with RCC. We present data on the prognostic impact of the postoperative BMI, at the start of systemic treatment in patients with advanced or metastatic RCC (mRCC). Methods: The German RCC registry is a prospective, longitudinal, multicenter study conducted by a network of 133 office-based medical oncologists in Germany to document treatment of unselected patients with mRCC. Based on the inclusion criteria for this analyses we identified 475 prospectively documented patients who received 1st-line systemic treatment. Patients were grouped by their BMI and overall survival was estimated by Kaplan-Meier analysis. A multivariate cox proportional hazards model was used to determine the impact of potentially prognostic variables at the start of systemic treatment (sex, age, BMI, comorbidity, Motzer’s score, tumor stage [TNMRG], and number of metastatic sites) on overall survival. Results: The mean age of patients at the start of systemic treatment was 68 years and the median follow-up was 23.8 months. 118 (25%) presented with a BMI < 24, 195 (41%) with a BMI 24 - 28 and 162 (34%) with a BMI > 28. Patient characteristics did not differ between groups, except more patients in the low BMI group had a higher prognostic risk according to Motzer-score (11% vs. 5 % vs. 6 %). Median overall survival was 10.0 month, 16.7 month and 23.4 month in the low, medium and high BMI group, respectively. In a multivariate analysis, BMI (HR 0.94, 95% CI 0.91-0.98, p < .001) and Motzer-Score (HR 1.83, 95% CI 1.59-2.12, p < .001) had a significant impact on overall survival. Conclusions: In addition to Motzer’s prognostic score, the BMI at the start of palliative treatment may be used to discriminate mRCC patients with good and poor prognosis. Patients with a higher BMI tend to live longer than patients with low or normal BMI supporting evidence from previous meta-analyses on preoperative BMI and outcome.

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International trade: Research of the reasons for the fall

Voprosy Ekonomiki ◽

10.32609/0042-8736-2019-1-79-91 ◽

2019 ◽

pp. 79-91 ◽

Cited By ~ 2

Author(s):

V. S. Nazarov ◽

S. S. Lazaryan ◽

I. V. Nikonov ◽

A. I. Votinov

Keyword(s):

Growth Rate ◽

International Trade ◽

Exchange Rate ◽

Global Economy ◽

Structural Changes ◽

Global Value Chains ◽

Value Chains ◽

Negative Contribution ◽

Basic Commodity ◽

The Impact

The article assesses the impact of various factors on the growth rate of international trade. Many experts interpreted the cross-border flows of goods decline against the backdrop of a growing global economy as an alarming sign that indicates a slowdown in the processes of globalization. To determine the reasons for the dynamics of international trade, the decompositions of its growth rate were carried out and allowed to single out the effect of the dollar exchange rate, the commodities prices and global value chains on the change in the volume of trade. As a result, it was discovered that the most part of the dynamics of international trade is due to fluctuations in the exchange rate of the dollar and prices for basic commodity groups. The negative contribution of trade within global value chains in 2014 was also revealed. During the investigated period (2000—2014), such a picture was observed only in the crisis periods, which may indicate the beginning of structural changes in the world trade.

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