Sites of metastasis and survival in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 642-642
Author(s):  
Shaan Dudani ◽  
Guillermo de Velasco ◽  
Connor Wells ◽  
Chun Loo Gan ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Cox Regression ◽  
Underlying Disease ◽  
Patient Counseling ◽  
Metastatic Site ◽  
Disease Biology ◽  
Endocrine Organs ◽  
Metastatic Involvement ◽  
Metastatic Sites ◽  
Genetic Profiles ◽  
Sites Of Metastases

642 Background: Across a variety of malignancies, sites of metastatic involvement are known to be associated with differences in survival. We sought to characterize the frequency and survival of patients with different sites of metastases in mRCC. Methods: Patients with mRCC starting treatment between 2002-2019 were identified and sites of metastatic involvement at time of systemic therapy initiation were documented. The primary outcomes of interest were prevalence of metastatic site involvement and overall survival (OS). Multivariable Cox regression models were performed to adjust for imbalances in IMDC risk factors. Results: A total of 10,320 patients were included. Median age at diagnosis was 60, 73% were male, 87% had clear-cell histology and 80% underwent nephrectomy. The most common sites of metastases were: lung (71%), lymph nodes (49%), bone (36%), liver (21%), adrenal (9%), brain (9%), pancreas (5%), pleura (4%) and thyroid (0.6%). Survival by metastatic site and adjusted hazard ratios are presented in Table. Conclusions: Metastases to endocrine organs (pancreas, thyroid, adrenal) are infrequent but are associated with the longest median OS, whereas bone, liver, pleura and brain metastases are associated with median OS < 18 months. These benchmark values are useful for patient counseling and study design. Sites of metastatic involvement may reflect differences in underlying disease biology, and further work to investigate differences in immune, molecular and genetic profiles between metastatic sites is encouraged.[Table: see text]

Association between sites of metastases (mets) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 445-445
Author(s):  
Dimitrios Makrakis ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Vadim S Koshkin ◽  
Ajjai Shivaram Alva ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Factor Model ◽  
Poor Response ◽  
Specific Tumor ◽  
Research Sponsor ◽  
Prognostic Implications ◽  
Advanced Urothelial Carcinoma ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Sites Of Metastases

445 Background: Different metastatic sites have variable prognostic implications in aUC. However, details on response and outcomes with ICI for particular mets is still unknown. We hypothesized that bone and liver mets would have poor response and outcomes with ICIs. Methods: We performed a retrospective cohort study in patients (pts) with aUC who received ICI. We compared overall response rate (ORR) and overall survival (OS) between pts with different mets at ICI initiation. We developed 4 different models: 1) lymph node (LN) only vs other; 2) visceral mets (bone, lung, liver) vs other; 3) bone + liver mets vs bone without liver vs liver without bone vs neither and 4) 6 factor model: a. LN +/- soft tissue/locoregional recurrence b. lung +/- (a) c. bone +/- (b) d. liver +/- (c) e. central nervous system (CNS) +/- (d) and f. other. ORR and OS were compared among groups using multivariable (adjusting for ECOG PS and hemoglobin<10g/dl) logistic regression and cox regression, respectively. Results: We identified 984 pts (24 institutions); 703 and 696 were included in OS and ORR analyses, respectively. Median age at ICI start was 71 (range 32-93), 77% white race, 74% men, 67% ever smokers, 72% pure UC, 18% upper tract UC, 55% extirpative surgery. Prevalence of LN, lung, bone and liver mets at ICI start was 74%, 32%, 27% and 21%, respectively. LN-only mets had significantly higher ORR (44% vs 22%, OR 2.6, p<0.05) and longer mOS (22 vs 8 months, HR 0.5, p<0.05) vs other mets. Visceral mets had significantly lower ORR (21% vs 35%, OR 0.5, p<0.05) and shorter mOS (7 vs 17 months, HR 1.8, p<0.05) vs non-visceral mets. Pts with bone and liver mets had significantly lower ORR and shorter OS vs those with bone or liver mets, which both had significantly lower ORR and shorter OS vs those with neither and with LN +/- local recurrence (Table). Conclusions: In the context of ICI treatment, bone, liver, lung or CNS mets were associated with lower ORR and/or shorter OS, and bone and liver mets were particularly associated with low ORR and short OS. LN-only mets were associated with higher ORR and longer OS. Further work is needed to interrogate site-specific tumor-host immune interactions and identify biomarkers. Research Sponsor: None[Table: see text]

Bone metastases as predictors of treatment response and rapidly progressive disease in NSCLC patients on PD-1/PD-L1 immune checkpoint inhibitors (ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20667-e20667
Author(s):  
Sally CM Lau ◽  
Lisa W Le ◽  
Elliot Charles Smith ◽  
Sze Wah Samuel Chan ◽  
Malcolm Ryan ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Bone Metastases ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Smoking Status ◽  
Clinicopathologic Characteristics ◽  
Metastatic Site ◽  
Overall Response ◽  
Nsclc Patients ◽  
Sites Of Metastases

e20667 Background: The tissue microenvironment associated with specific organ metastases potentially influences the efficacy of checkpoint inhibitors. The presence of liver metastases is a predictor of poor response and survival in melanoma and is correlated with reduced CD8+ T cell infiltration. Our study examined clinicopathologic characteristics, focusing on sites of metastatic disease, that are associated with poor outcomes. Methods: Advanced NSCLC patients treated with ≥1 cycle of ICI were reviewed. Baseline age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and sites of metastases were recorded. Best overall response (BOR) was determined by clinical imaging response and categorized ordinally as shrinkage, stable, or progression, adapted from RECIST for CR/PR, SD, PD. A rapidly progressive phenotype (RPP) was defined as BOR of progression and ICI use of ≤2 months. The association between sites of metastases and clinical outcomes were investigated using logistic and cox regression models. Results: Among 219 eligible patients, bone was the most common metastatic site (34.7%), followed by brain (21.5%), adrenals (14.2%), and liver (13.7%). Bone metastases (OR 0.45, p = 0.004) were associated with a worse BOR, while only a trend was observed for liver metastases (OR 0.47, p = 0.06). Adrenal metastases were associated with a better BOR (OR 2.08, p = 0.04). But thorax limited disease did not associate with BOR (OR 1.08, p = 0.76). In a multivariate model, bone was the only metastatic site associated with a worse BOR (OR 0.50, p = 0.01). Further, bone metastases were associated with RPP (adjusted OR 1.91, p = 0.04). Both bone (adjusted hazard ratio/aHR 1.61, p = 0.01) and liver metastases (aHR 1.80, p = 0.02) were associated with a shorter time-to-treatment-failure. The presence of liver (aHR 2.63, p < 0.001) but not bone (aHR 1.04, p = 0.86) metastases was a significant predictor of poor OS. Conclusions: We report a novel finding that the presence of bone metastases was associated with a worse clinical overall response on ICI and a rapidly progressive phenotype. Further investigations into the mechanisms of RPP in the presence of bone metastases are needed.

New perspectives on metastatic patterns in lung cancer: The M. D. Anderson thoracic medical oncology database

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7630-7630
Author(s):  
Y. Oh ◽  
J. J. Lee ◽  
J. M. Hanneken ◽  
S. Liu ◽  
M. C. Camarillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Medical Oncology ◽  
Performance Status ◽  
Rank Test ◽  
Metastatic Site ◽  
Unit Increase ◽  
Metastatic Patterns ◽  
Metastatic Sites

7630 Background: We previously reported a retrospective study suggesting that sites of metastatic disease characterize distinct prognostic groups with non-small cell lung cancer (NSCLC) (ASCO 2005 Abstract No: 7197). To confirm these observations, we prospectively evaluated pts with newly diagnosed NSCLC to correlate extent of disease with survival. Methods: We developed a prospective comprehensive database of 2,487 pts registered in the Thoracic Medical Oncology Department from 9/1/2004 - 8/31/2006, with up to 845 days follow-up. 694 were untreated stage IV NSCLC pts with data for ECOG performance status (PS), TNM staging, histology, identification of all metastatic sites, and survival. Results: Bone was the most common metastatic site, affecting 280 pts, 114 having bone only metastases (280/114). Similarly, the following results were found for lung (261/137), brain (143/46), adrenal (112/36), and liver (98/31). PS = 0 (101), PS = 1 (329), PS = 2 (103), PS = 3 (74), PS = 4 (10), PS = unknown (77). As of January 2007, median survival for the group was 8 months. By the Cox regression model, statistically significant effects on overall survival were seen for gender, smoking status, age, performance status, and number of metastases. The following hazard ratios [with 95% CI] of death were seen for males vs. females 1.41 ([1.13, 1.75], p = 0.0025), former smokers vs. non-smokers 1.66 ([1.18, 2.31], p = 0.0032), active smokers vs. non-smokers 1.79 ([1.21, 2.64], p = 0.0036), for one year increase in age 1.02 ([1.00, 1.03], p = 0.0046), for one unit increase in performance status 1.63 ([1.45, 1.82], p < 0.0001) and for one unit increase in number of metastases 1.48 ([1.32, 1.66], p < 0.0001). Pts with one metastatic site had superior survival over pts with more sites. Six of 10 metastatic sites were found to have significant independent effects on overall survival, based on log-rank test. Conclusions: Number and sites of metastases were strong independent determinants of survival in NSCLC. Furthermore, our work suggests marked heterogeneity of metastatic patterns at presentation. Pts with fewer metastatic sites demonstrate better survival. Future targeted therapy protocols should stratify according to metastatic sites to better analyze patterns of failure and outcomes. No significant financial relationships to disclose.

Characterizing sites of metastatic involvement in metastatic clear-cell, papillary, and chromophobe renal cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5071-5071 ◽  
Author(s):  
Shaan Dudani ◽  
Guillermo de Velasco ◽  
Connor Wells ◽  
Chun Loo Gan ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Clear Cell ◽  
Lymph Node Involvement ◽  
Metastatic Site ◽  
Metastatic Involvement ◽  
Sites Of Metastases ◽  
Histologic Subtypes

5071 Background: There exists considerable biological and clinical variability between histologic variants of metastatic renal-cell carcinoma (mRCC). Data reporting on sites of metastatic involvement in less common histologies of mRCC are sparse. We sought to characterize the frequency of metastatic site involvement across the three most common histologies of mRCC: clear-cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Methods: Using the International mRCC Database Consortium (IMDC) database, patients with mRCC starting systemic therapy between 2002-2019 were identified and sites of metastases at the time of systemic therapy initiation were documented. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. The primary outcomes were prevalence of metastatic site involvement and overall survival (OS). Patients with mixed histology were excluded. Results: 10,105 patients were eligible for analysis. Median age at diagnosis was 60, 72% were male and 79% underwent nephrectomy. 92%, 7% and 2% of patients had ccRCC, pRCC, and chrRCC, respectively. Frequency of metastatic site involvement across the histologic subtypes is shown in Table. Lung, adrenal, brain and pancreatic metastases were more frequent in ccRCC, lymph node involvement was most frequent in pRCC, and liver metastases were most frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (brain/pleura) and 50 months (pancreas). OS by site of metastatic involvement was compared between histologies for the four most common sites of metastases (lung, lymph nodes, bone, liver). As compared to patients with ccRCC, patients with pRCC had lower OS regardless of site of metastasis (p < 0.05). Power was limited and thus differences in OS between ccRCC and chrRCC were not detectable. Conclusions: Sites of metastatic involvement differ based on histology in mRCC. These data highlight the clinical and biologic variability between histologic subtypes of mRCC and constitute the largest cohorts of patients with metastatic pRCC and chrRCC to report on sites of metastases. Sites of Metastatic Involvement by Histology. [Table: see text]

scholarly journals Tau and TDP-43 synergy: a novel therapeutic target for sporadic late-onset Alzheimer’s disease

GeroScience ◽  
2021 ◽  
Author(s):  
Caitlin S. Latimer ◽  
Nicole F. Liachko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Hippocampal Sclerosis ◽  
Model Organism ◽  
Amyloid Β ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Biology ◽  
Rapid Cognitive Decline

AbstractAlzheimer’s disease (AD) is traditionally defined by the presence of two types of protein aggregates in the brain: amyloid plaques comprised of the protein amyloid-β (Aβ) and neurofibrillary tangles containing the protein tau. However, a large proportion (up to 57%) of AD patients also have TDP-43 aggregates present as an additional comorbid pathology. The presence of TDP-43 aggregates in AD correlates with hippocampal sclerosis, worse brain atrophy, more severe cognitive impairment, and more rapid cognitive decline. In patients with mixed Aβ, tau, and TDP-43 pathology, TDP-43 may interact with neurodegenerative processes in AD, worsening outcomes. While considerable progress has been made to characterize TDP-43 pathology in AD and late-onset dementia, there remains a critical need for mechanistic studies to understand underlying disease biology and develop therapeutic interventions. This perspectives article reviews the current understanding of these processes from autopsy cohort studies and model organism-based research, and proposes targeting neurotoxic synergies between tau and TDP-43 as a new therapeutic strategy for AD with comorbid TDP-43 pathology.

scholarly journals Impact of sarcopenia in advanced and metastatic soft tissue sarcoma

2021 ◽  
Author(s):  
Dennis Strassmann ◽  
Bennet Hensen ◽  
Viktor Grünwald ◽  
Katharina Stange ◽  
Hendrik Eggers ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cox Regression ◽  
Therapy Response ◽  
Prognostic Impact ◽  
Patient Counseling ◽  
Skeletal Muscle Index ◽  
Prognostic Parameter ◽  
Dismal Prognosis ◽  
Metastatic Soft Tissue Sarcoma

Abstract Introduction Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. Methods 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. Results 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9–6.0] vs. 16 months [95%CI 8.8–23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4–4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). Conclusion This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

scholarly journals Survival predictors of metastatic angiosarcomas: a surveillance, epidemiology, and end results program population-based retrospective study

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shihong Ren ◽  
Yucheng Wang ◽  
Zhan Wang ◽  
Jinxiang Shao ◽  
Zhaoming Ye
Keyword(s):  
Tumor Size ◽  
Cox Regression ◽  
Radiation Treatment ◽  
Tumor Grade ◽  
Population Based ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Metastatic Sites ◽  
Survival Predictors ◽  
End Results

Abstract Background Angiosarcomas (AS) have poor prognosis and often metastasize to distant sites. The potential predictors of metastatic angiosarcomas (MAS) have not been extensively investigated. The main objective of this study was to identify survival predictors of MAS. Methods Surveillance, Epidemiology, and End Results (SEER) datasets were used to identify patients with MAS from 2010 to 2016. Risk predictors were determined with the aid of Kaplan-Meier and Cox regression model analyses. Results A total of 284 MAS patients met the study entry criteria. Among these, 121 patients (42.6%) were diagnosed with metastasis in bone, 26 in brain (9.2%), 86 in liver (30.3%) and 171 in lung (60.2%). Overall, 96 patients (33.8%) had two or more metastatic sites. The 1- and 3-year overall survival (OS) rates were 20.8 and 3.8% while 1- and 3-year cancer-specific survival (CSS) rates were 22.0 and 5.2%, respectively. Cox regression analysis revealed chemotherapy, radiation treatment (RT) and tumor size ≤10 cm as independent favorable predictors of OS. In terms of CSS, tumor grade IV, tumor size > 10 cm and absence of chemotherapy were independent adverse predictors. Surgery did not prolong survival outcomes (both OS and CSS) in the current cohort. Conclusion MAS is associated with extremely poor survival. Chemotherapy, RT, and tumor size are independent predictors of OS. Chemotherapy and tumor size are independent prognostic factors of CSS. Chemotherapy is therefore recommended as the preferred treatment option for MAS patients.

scholarly journals Hemodialysis Adequacy and Its Impact on Long-Term Patient Survival in Demographically, Socially, and Culturally Homogeneous Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Reza Hekmat
Keyword(s):  
Cox Regression ◽  
Patient Survival ◽  
Underlying Disease ◽  
Chronic Hemodialysis ◽  
Historical Cohort ◽  
Cox Regression Analysis ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Iranian Patients

Background. Impact of hemodialysis adequacy on patient survival is extensively studied. The current study compares the survival of chronic hemodialyzed, undocumented, uninsured, Afghan immigrant patients with that of a group of insured Iranian patients matched for underlying disease, age, weight, level of education, marital status, income, and number of comorbid conditions. Methods. Eighty chronic hemodialysis patients (mean age 42.8 ± 10.5 years) entered this historical cohort study in Mashhad, Iran, between January 2012 and January 2015. Half of the patients were undocumented, uninsured, Afghan immigrants (Group A) matched with forty insured Iranian patients (Group B). To compare the survival rate of the two patient groups, Kaplan–Meir survival analysis test was used. Results. Group A patients were underdialyzed with a weekly Kt/V which was significantly less in comparison with that of Group B (1.63 ± 0.63 versus 2.54 ± 0.12, p value = 0.01). While Group A’s number of hemodialysis sessions per week was fewer than that of Group B (1.45 ± 0.56 versus 2.8 ± 0.41, p value = 0.04), the mean of Kt/V in each hemodialysis session was higher in them, in comparison with Group B (1.43 ± 0.25 versus 1.3 ± 0.07, p value = 0.045). In Group B and Group A patients, one-year survival was 70% versus 50%, two-year survival was 55% versus 30%, and three-year survival was 40% versus 20%, respectively (p values = 0.04, 0.02 and 0.04, respectively). In Cox regression analysis, hemodialysis adequacy and uninsurance were factors impacting patients’ survival (OR = 1.193 and 0.333, respectively). Conclusions. Undocumented, uninsured, inadequately hemodialyzed, Afghan patients had a significantly lower one-, two-, and three-year survival as opposed to their Iranian counterparts, probably due to lack of insurance.

HER2/neu status in primary breast cancer and in metastatic site as detected using FNA.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11502-e11502
Author(s):  
Francesco Giotta ◽  
Maria Consilia Asselti ◽  
Stella Petroni ◽  
Onsina Popescu ◽  
Vincenza Rubini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proliferative Activity ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Significant Loss ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Metastatic Site ◽  
Her 2 ◽  
Metastatic Sites

e11502 Background: As for hormonal receptor (ER, PgR), also human epidermal growth factor receptor-2 (HER-2) expression in breast cancer primitive tumor (PT) could be different from that of metastatic site (MS). These differences arise some questions about clinically useful information given and accuracy of methods to detect biological features. Fine Needle Aspiration (FNA) of metastatic sites could be an available tool to characterize biologic pattern of lesions, using immunocytochemical and/or molecular assay. The aim of the study is to compare prognostic and predictive factors obtained from PT and corresponding MS. Methods: Thirty-eight consecutive metastatic breast cancer patients underwent FNA on metastatic sites in order to re-evaluate receptor status, proliferative activity and HER-2/Neu amplification. In MS the material was achieved using FNA with a 21-23 G needle and obtaining monolayer and the corresponding cito-inclusion. MS were localized in liver (21), lung (8) and distant lymph-nodes (9). ERs, PgRs and Ki-67 were detected in both PT and MS, in 38 cases by immunochemistry, whereas HER-2/Neu amplification was detected on citoinclusion in 35 evaluable cases by FISH. Results: ERs, PgRs and Ki-67 were detected in both PT and in MS, in 36, 34, 25 out of 38 cases respectively, showing a significant loss of hormonal receptors and a decreased proliferative activity in MS versus PT (t-test p: 0.0195, <0.0001 and 0.0120 respectively). Regarding to HER-2/Neu amplification, 28 out of 35 evaluable cases were not amplified while 6 were amplified both in PT and in MS (Pearson Test: r=0.9 p: <0.0001). Another case, HER/Neu amplified in TP, after therapy with trastuzumab resulted not amplified in MS. Conclusions: According to other authors, our data demonstrated that the lost of HER/Neu amplification in MS is a possible event and that FNA samples of MS are available for HER/Neu detection.

Cytoreductive nephrectomy (CN) in metastatic renal cancer (mRCC): Update on Carmena trial with focus on intermediate IMDC-risk population.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4508-4508 ◽  
Author(s):  
Arnaud Mejean ◽  
Simon Thezenas ◽  
Christine Chevreau ◽  
Karim Bensalah ◽  
Lionnel Geoffrois ◽  
...  
Keyword(s):  
Risk Factor ◽  
Risk Group ◽  
Risk Groups ◽  
Phase Iii ◽  
Intermediate Risk ◽  
Metastatic Renal Cancer ◽  
Phase Iii Trial ◽  
Metastatic Site ◽  
Trial Testing ◽  
Metastatic Sites

4508 Background: Carmena was a randomized phase III trial, testing the benefit of CN followed by sunitinib (arm A) vs sunitinib alone (arm B), with stratification by MSKCC risk groups in 450 mRCC patients. Based on this trial, CN is not anymore recommended in mRCC (NEJM, Mejean et al, 2018). However there are questions about which patients could still benefit from CN, especially in intermediate risk group. In the present study, we investigated different subgroups from the Carmena trial to answer these questions. Methods: Carmena trial was initially stratified according to MSKCC risk groups. For the purpose of this analysis, we reclassified the patients based on IMDC risk groups. We also analyzed patients with one metastatic site vs more than one, as well as patients with secondary nephrectomy in arm B. Overall survival (OS) was the primary endpoint. Results: With a updated median FU of 61.5 months (mo), the median OS by ITT analysis was 15.6 vs 19.8 mo in arm A and B respectively stratified on MSKCC (HR 0.933 ; 95% CI [0.76- 1.15]) / stratified on IMDC (HR 0.957 ; 95% CI [0.78- 1.18]). Using IMDC risk group factors, 58.6% patients were intermediate and 41.4 % were poor risk. When looking at intermediate risk group only, 48.1% had only one risk factor (interval between diagnosis and treatment < 1y), with a median OS of 30.5 and 25.2 mo in arm A and B respectively (HR 1.24 [0.81 – 1.90]). By contrast, 51.9 % had two risk factors (mostly low hemoglobin, high corrected calcium or neutrophils), with a median OS of 16.6 and 31.2 mo in arm A and B respectively (HR 0.61 [0.41 – 0.91] p = 0.015). Regarding number of metastatic sites, 33% had only one metastatic site. Median OS was 23.6 and 22.7 mo in arm A and B respectively (HR 1.08 [0.75 – 1.57]. Finally, 40 patients had a secondary nephrectomy in arm B, with median OS of 48.5 mo [CI 95%: 27.9-64.4] vs 15.7 mo [CI 95%: 13.3-20.5] in patients who never had surgery. Conclusions: With longer FU, Carmena trial confirms that CN is not superior to sunitinib alone in ITT population, both with MSKCC and IMDC risk groups. However for patients with only one IMDC risk factor, CN might be beneficial. Number of metastatic site is not helpful to define good candidates for surgery. Finally, patients with secondary nephrectomy have very long OS, supporting this strategy. Clinical trial information: NCT00930033.

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