A FOCUS ON METASTATIC DISEASE Astract ID 17 … aua... · A FOCUS ON METASTATIC DISEASE. Astract ID...
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Outcomes in over 4,000 Patients with Renal Cell Carcinoma from the Latin American Renal Cancer Group (LARCG) A FOCUS ON METASTATIC DISEASE Astract ID 17-5670 / MP16 Diego Abreu 1 , Guillermo Gueglio 2 , Patricio Garcia 2 , Walter da Costa 3 , Daniel Beltrame 3 , Alvaro Zuñiga 4 , Luis Meza 5 , Rubén Bengió 6 , Carlos Scorticati 7 , Ricardo Castillejos 8 , Francisco Rodriguez 8 , Ana Maria Autran 9 , Carmen González 9 , Miguel Sánchez 10 , Jose Gadu 11 , Alejandro Nolazco 12 , Pablo Martínez 12 , Carlos Ameri 13 , Hamilton Zampolli 14 , Raul Langenhin 15 , Diego Muguruza 16 , Marcos Tobías Machado 17 , Antonio Lima Pompeo 17 , Pablo Mingote 18 , Nicolás Ginéstar 18 , Matías López 19 , Boris Camacho 20 , Juan Yandian 16 , Jorge Clavijo 16 , Roberto Puente 16 , Sergio de Miceu 21 , Lucas Nogueira 22 , Carlos Corradi 22 , Marcelo Torrico 23 , Martín Varela 24 , Omar Clark 24 , Luis Montes de Oca 25 , Sebastián Savignano 25 , Ricardo Decia 1 , Fernando Secin 26 , Agustín Rovegno 26 , Gustavo Guimarães 3 , Sidney Glina 27 , Joan Palau 28 , Gustavo Carvalhal 29 , Philippe Spiess 30 , Stenio Zequi 3 , Marston Linehan 31 Over the past several years, a major international study collaboration has occurred among centers of excellence caring for kidney cancer termed the Latin American Renal Cancer Group (LARCG). INTRODUCTION Clinical and Pathological Characteristics Kaplan-Meier Survival (mRCC n=530) OBJECTIVE METHODS The aim of the present study is to assess the impact of clinical and pathologic variables on cancer specific survival (CSS) and overall survival (OS). Analysis of data from 28 centers from 8 countries, revealed 4,060 patients with renal cell carcinoma (RCC) who underwent nephrectomy from 1990 to 2015, 530 of which (14.5%) had metastasis at clinical presentation. These are the focus of the present study. Median follow-up was six months (0-162). Of 455 patients with survival data, 203 died (44.6%), 184 (90.6%) of RCC. RESULTS CONCLUSIONS The median age of patients with metastatic RCC (mRCC) was 61 (23-71) years, 68% of patients were male and 32% female (2:1 ratio). The organs most frequently affected with metastasis were lungs (45.5%), bone (21.5%), lymph nodes (10.6%), liver (8.7%), adrenal (4%) and brain (2.2%). On univariate analysis, there were associations between 5-year OS and CSS and presence of ECOG-PS ≥ 1 (p=0.005 and p=0.007, respectively), ASA 3 classification (p<0.0001 for both), pT 3-4 (p=0.019 and p=0.009, respectively), pN1 (p=0.001 and p<0.0001), Fuhrman grades ≥3 (p=0.010 and p=0.008, respectively), Necrosis (p=0.024 and p=0.016), perirenal fat invasion (p<0.0001), Hemoglobin <11 (p=0.001 and p=0.002), multiple metastases (p=0.002 and p=0.001), two or more involved organs (p=0.002 and p=0.005, respectively), bone vs pulmonary metastasis (p=0.017 and p=0.024), vertebral metastasis (p=0.035, for both), and more than five lungs metastases (p=0.003, for both). On multivariate analysis, the independent prognostic factor of 5-year OS was the ASA (p=0.020). Both OS and CSS were influenced by perirenal fat invasion (p=0.001 for both), and two or more metastatic organ sites (p<0.0001 and p=0.003 respectively). This study of the impact of clinical and pathologic variables on survival in mRCC in Latin America was possible thanks to the collaborative work done by the LARCG. The presence of two or more sites of metastasis and the presence of perirenal fat invasion within the primary tumor predict shorter OS and CSS. ASA Classification was an independent predictor of OS. 1 Hospital Pasteur, Montevideo, Uruguay 2 Hospital Italiano, Buenos Aires, Argentina 3 A C Camargo Cancer Center, Sao Paulo, Brazil 4 Universidad Católica, Santiago de Chile, Chile 5 INEN, Lima, Peru 6 Clinica Profesor Bengio, Cordoba, Argentina 7 Hospital de Clinicas, Buenos Aires, Argentina 8 INCNSZ, Ciudad de México, México 9 Fundación Jiménez Díaz, Madrid, España 10 Hospital Rey Juan Carlos, Madrid, España 11 Hospital Militar, Ciudad de México, México 12 Hospital Británico, Buenos Aires, Argentina 13 Hospital Aleman, Buenos Aires, Argentina 14 IAVC, Sao Paulo, Brazil 15 COMEPA, Paysandu, Uruguay 16 Hospital de Clinicas, Montevideo, Uruguay 17 EMABC, Sao Paulo, Brazil 18 Policlinico Neuquén, Neuquén, Argentina 19 SEDU, Buenos Aires, Argentina 20 Hospital Obrero, La Paz, Bolivia 21 Hospital Ramos Mejía, Buenos Aires, Argentina 22 UMG, Belo Horizonte, Brazil 23 Clinica Los Olivos, Cochabamba, Bolivia 24 Hospital Militar, Montevideo, Uruguay 25 CDU, Buenos Aires, Argentina 26 CEMIC, Buenos Aires, Argentina 27 Hospital Ipiranga, Sao Paulo, Brazil 28 Fundación Puigvert, Barcelona, Spain 29 PUC-RS, Porto Alegre, Brazil 30 Moffitt Cancer Center, Tampa, USA 31 NIH/NCI, Bethesda, USA Variable Evaluated Patients (n=530) N° % Age Median Range Sex Male 528 359 68.0 Female 169 32.0 ECOG PS 0 373 76 20.4 ≥ 1 297 79.6 ASA 1-2 513 232 45.2 3-4 281 54.8 Symptoms at presentation No 489 114 23.3 Yes 375 76.7 Subtype Histological Clear cell 347 285 82.0 Papillary 9 2.6 Chromophobe 4 1.2 Unclassified 15 4.3 Sarcomatoid differentiation 34 9.8 Nephrectomy Radical 511 483 94.5 Partial 28 5.5 Treatment of Metastasis Surgery 177 5 2.8 Radioterapy 16 9.0 Others 31 17.5 Immunotherapy IFN 177 17 9.6 IL-2 8 4.5 IFN + IL-2 1 0.6 Second line after Immunotherapy (anti-VEGF) 177 3 1.7 anti-VEGF 2 1.1 Systemic Therapy Sunitinib 177 63 35.6 Pazopanib 12 6.8 Sorafenib 6 3.4 Bevacizumab 5 2.8 Temsirolimus 2 1.1 anti-VEGF + Others 5 2.8 Metastases Single 451 111 24.6 Multiple 340 75.4 Metastases 1 organ 339 173 51.0 ≥ 2 organs 166 49.0 Metastatic site Lung 321 146 45.5 Bone 69 21.5 Liver 28 8.7 Brain 7 2.2 Adrenal gland 13 4.0 Lymph node 34 10.6 Others 24 7.5 Status Survival Alive 455 252 55.4 Dead 203 44.6 Dead by Cancer 184 90.6 491 61 23 - 94 Patients Metastases Characteristics Cox regression analysis for Overall Survival (OS) and Cancer-Specific Survival (CSS) Kaplan-Meier Survival (mRCC) BMI: Body Mass Index ECOG-PS: Eastern Cooperative Oncology Group-Performance Status ASA: American Society of Anesthesiologists CC: Clear Cell M+: Metastasis Vert.: Vertebral Org.: Organs Hb: Hemoglobin Variable HR 95% CI p HR 95% CI p HR 95% CI p HR 95% CI p Age (≥65 vs <65 years) 1.08 0.79 -1.49 0.605 1.10 0.79 - 1.53 0.562 Sex (F/M) 1.35 0.97 - 1.86 0.067 1.41 1.01 - 1.97 0.039 BMI (<25 vs ≥25) 1.43 0.93 - 2.20 0.103 1.52 0.97 - 2.39 0.066 ECOG-PS (≥ 1 vs 0) 2.28 1.28 - 4.08 0.005 2.21 1.24 - 3.95 0.007 ASA (3-4 vs 1-2) 1.88 1.37 - 2.57 <0.0001 1.64 1.08 - 2.49 0.02 1.81 1.31 - 2.50 <0.0001 1.4 0.89 - 2.21 0.138 Symptomatic (yes/no) 0.91 0.64 -1.29 0.602 0.94 0.66 - 1.36 0.778 Size pT (>7 vs ≤7 cm) 1.61 1.08 - 2.41 0.019 1.17 0.481 1.77 1.15 - 2.73 0.009 1.25 0.76 - 2.07 0.367 Nodes (pN1 vs pN0) 2.14 1.35 - 3.39 0.001 2.31 1.44 - 3.70 <0.0001 Fuhrman (3-4 vs 1-2) 1.80 1.15 - 2.82 0.010 1.86 1.17 - 2.97 0.008 Necrosis 1.50 1.05 - 2.14 0.024 1.57 1.08 - 2.27 0.016 Perirenal Fat Invasion 1.87 1.31 - 2.67 <0.0001 2.02 1.32 - 3.09 <0.0001 2.06 1.42 - 2.99 <0.0001 2.21 1.40 - 3.47 0.001 Renal Vein Invasion 1.28 0.87 - 1.88 0.209 1.09 0.72 - 1.66 0.669 No-CC vs CC 1.42 0.93 - 2.17 0.099 1.40 0.90 - 2.19 0.130 Sarcomatoid features 1.10 0.63 - 1.91 0.726 1.11 0.62 - 1.96 0.720 Hb (< 11 vs ≥ 11 gr/dl) 1.79 1.25 - 2.56 0.001 1.80 1.24 - 2.59 0.002 M+ (Multiple vs Single) 1.94 1.28 - 2.95 0.002 2.07 1.33 - 3.23 0.001 M+ (≥ 2 Org. vs 1 Org.) 1.67 1.21 - 2.32 0.002 2.19 1.43 - 3.34 <0.0001 1.62 1.15 - 2.27 0.005 2.01 1.27 - 3.19 0.003 M+ (Bone vs Lung) 2.10 1.14 - 3.88 0.017 2.03 1.10 - 3.76 0.024 M+ (Vert. vs non-Vert.) 3.61 1.00 - 12.98 0.035 3.61 1.00 - 12.98 0.035 M+ Lung (> 5 vs ≤ 5) 3.21 1.47 - 7.00 0.003 3.21 1.47 - 7.00 0.003 5-year OS 5-year CSS Univariate Multivariate Univariate Multivariate Organs N° % 1 organ 173 51.0 2 organs 128 37.8 3 organs 36 10.6 4 organs 2 0.6 Total 339 Organ Sites N° % Lung 146 45.5 Bone 69 21.5 Lymph Node 34 10.6 Liver 28 8.7 Adrenal 13 4.0 Brain 7 2.2 Other 24 7.5 Total 321 Metasteses N° % 2 to 5 31 47.0 > 5 and ≤ 10 12 18.2 > 10 23 34.8 Total 66 Metastases N° % N° % N° % 1 40 30.3 30 43.5 11 42.3 >1 92 69.7 33 47.8 15 57.7 Total 132 63 26 Single vs Multiple Metastases (M+) Number of Involved Organs Groups (N°) of Pulmonary Metastases Metastatic Sites Lung Bone Liver
Transcript of A FOCUS ON METASTATIC DISEASE Astract ID 17 … aua... · A FOCUS ON METASTATIC DISEASE. Astract ID...
Outcomes in over 4,000 Patients with Renal Cell Carcinoma from the Latin American Renal Cancer Group (LARCG)
A FOCUS ON METASTATIC DISEASE Astract ID 17-5670 / MP16Diego Abreu1, Guillermo Gueglio2, Patricio Garcia2, Walter da Costa3, Daniel Beltrame3, Alvaro Zuñiga4, Luis Meza5, Rubén Bengió6, Carlos Scorticati7, Ricardo Castillejos8,
Francisco Rodriguez8, Ana Maria Autran9, Carmen González9, Miguel Sánchez10, Jose Gadu11, Alejandro Nolazco12, Pablo Martínez12, Carlos Ameri13, Hamilton Zampolli14, Raul Langenhin15, Diego Muguruza16, Marcos Tobías Machado17, Antonio Lima Pompeo17, Pablo Mingote18, Nicolás Ginéstar18, Matías López19, Boris Camacho20, Juan Yandian16, Jorge Clavijo16,
Roberto Puente16, Sergio de Miceu21, Lucas Nogueira22, Carlos Corradi22, Marcelo Torrico23, Martín Varela24, Omar Clark24, Luis Montes de Oca25, Sebastián Savignano25, Ricardo Decia1, Fernando Secin26, Agustín Rovegno26, Gustavo Guimarães3, Sidney Glina27, Joan Palau28, Gustavo Carvalhal29 , Philippe Spiess30, Stenio Zequi3, Marston Linehan31
Over the past several years, a major international study collaboration has occurred among centers of excellence caring for kidney cancer termed the Latin American Renal Cancer Group (LARCG).
INTRODUCTION Clinical and Pathological Characteristics Kaplan-Meier Survival (mRCC n=530)
OBJECTIVE
METHODS
The aim of the present study is to assess the impact of clinical and pathologic variables on cancer specific survival (CSS) and overall survival (OS).
Analysis of data from 28 centers from 8 countries, revealed 4,060 patients with renal cell carcinoma (RCC) who underwent nephrectomy from 1990 to 2015, 530 of which (14.5%) had metastasis at clinical presentation. These are the focus of the present study. Median follow-up was six months (0-162). Of 455 patients with survival data, 203 died (44.6%), 184 (90.6%) of RCC.
RESULTS
CONCLUSIONS
The median age of patients with metastatic RCC (mRCC) was 61 (23-71) years, 68% of patients were male and 32% female (2:1 ratio). The organs most frequently affected with metastasis were lungs (45.5%), bone (21.5%), lymph nodes (10.6%), liver (8.7%), adrenal (4%) and brain (2.2%). On univariate analysis, there were associations between 5-year OS and CSS and presence of ECOG-PS ≥ 1 (p=0.005 and p=0.007, respectively), ASA 3 classification (p<0.0001 for both), pT 3-4 (p=0.019 and p=0.009, respectively), pN1 (p=0.001 and p<0.0001), Fuhrman grades ≥3 (p=0.010 and p=0.008, respectively), Necrosis (p=0.024 and p=0.016), perirenal fat invasion (p<0.0001), Hemoglobin <11 (p=0.001 and p=0.002), multiple metastases (p=0.002 and p=0.001), two or more involved organs (p=0.002 and p=0.005, respectively), bone vs pulmonary metastasis (p=0.017 and p=0.024), vertebral metastasis (p=0.035, for both), and more than five lungs metastases (p=0.003, for both). On multivariate analysis, the independent prognostic factor of 5-year OS was the ASA (p=0.020). Both OS and CSS were influenced by perirenal fat invasion (p=0.001 for both), and two or more metastatic organ sites (p<0.0001 and p=0.003 respectively).
This study of the impact of clinical and pathologic variables on survival in mRCC in Latin America was possible thanks to the collaborative work done by the LARCG. The presence of two or more sites of metastasis and the presence of perirenal fat invasion within the primary tumor predict shorter OS and CSS. ASA Classification was an independent predictor of OS.
1Hospital Pasteur, Montevideo, Uruguay 2Hospital Italiano, Buenos Aires, Argentina 3A C Camargo Cancer Center, Sao Paulo, Brazil 4Universidad Católica, Santiago de Chile, Chile 5INEN, Lima, Peru 6Clinica Profesor Bengio, Cordoba, Argentina 7Hospital de Clinicas, Buenos Aires, Argentina 8INCNSZ, Ciudad de México, México 9Fundación Jiménez Díaz, Madrid, España 10Hospital Rey Juan Carlos, Madrid, España 11Hospital Militar, Ciudad de México, México 12Hospital Británico, Buenos Aires, Argentina 13Hospital Aleman, Buenos Aires, Argentina 14IAVC, Sao Paulo, Brazil 15COMEPA, Paysandu, Uruguay 16Hospital de Clinicas, Montevideo, Uruguay 17EMABC, Sao Paulo, Brazil 18Policlinico Neuquén, Neuquén, Argentina
19SEDU, Buenos Aires, Argentina 20Hospital Obrero, La Paz, Bolivia 21Hospital Ramos Mejía, Buenos Aires, Argentina 22UMG, Belo Horizonte, Brazil 23Clinica Los Olivos, Cochabamba, Bolivia 24Hospital Militar, Montevideo, Uruguay 25CDU, Buenos Aires, Argentina 26CEMIC, Buenos Aires, Argentina 27Hospital Ipiranga, Sao Paulo, Brazil 28Fundación Puigvert, Barcelona, Spain 29PUC-RS, Porto Alegre, Brazil 30Moffitt Cancer Center, Tampa, USA 31NIH/NCI, Bethesda, USA
VariableEvaluated Patients(n=530) N° %
Age Median RangeSex Male 528 359 68.0 Female 169 32.0 ECOG PS 0 373 76 20.4 ≥ 1 297 79.6 ASA 1-2 513 232 45.2 3-4 281 54.8 Symptoms at presentation No 489 114 23.3 Yes 375 76.7 Subtype Histological Clear cell 347 285 82.0 Papillary 9 2.6 Chromophobe 4 1.2 Unclassified 15 4.3 Sarcomatoid differentiation 34 9.8 Nephrectomy Radical 511 483 94.5 Partial 28 5.5 Treatment of Metastasis Surgery 177 5 2.8 Radioterapy 16 9.0 Others 31 17.5 Immunotherapy IFN 177 17 9.6 IL-2 8 4.5 IFN + IL-2 1 0.6 Second line after Immunotherapy (anti-VEGF) 177 3 1.7 anti-VEGF 2 1.1 Systemic Therapy Sunitinib 177 63 35.6 Pazopanib 12 6.8 Sorafenib 6 3.4 Bevacizumab 5 2.8 Temsirolimus 2 1.1 anti-VEGF + Others 5 2.8 Metastases Single 451 111 24.6 Multiple 340 75.4 Metastases 1 organ 339 173 51.0 ≥ 2 organs 166 49.0 Metastatic site Lung 321 146 45.5 Bone 69 21.5 Liver 28 8.7 Brain 7 2.2 Adrenal gland 13 4.0 Lymph node 34 10.6 Others 24 7.5 Status Survival Alive 455 252 55.4 Dead 203 44.6 Dead by Cancer 184 90.6
491 6123 - 94
Patients
Metastases Characteristics Cox regression analysis for Overall Survival (OS) and Cancer-Specific Survival (CSS)
Kaplan-Meier Survival (mRCC)
BMI: Body Mass IndexECOG-PS: Eastern Cooperative Oncology Group-Performance Status
ASA: American Society of AnesthesiologistsCC: Clear Cell
M+: MetastasisVert.: Vertebral
Org.: OrgansHb: Hemoglobin
Variable HR 95% CI p HR 95% CI p HR 95% CI p HR 95% CI pAge (≥65 vs <65 years) 1.08 0.79 -1.49 0.605 1.10 0.79 - 1.53 0.562Sex (F/M) 1.35 0.97 - 1.86 0.067 1.41 1.01 - 1.97 0.039 BMI (<25 vs ≥25) 1.43 0.93 - 2.20 0.103 1.52 0.97 - 2.39 0.066ECOG-PS (≥ 1 vs 0) 2.28 1.28 - 4.08 0.005 2.21 1.24 - 3.95 0.007ASA (3-4 vs 1-2) 1.88 1.37 - 2.57 <0.0001 1.64 1.08 - 2.49 0.02 1.81 1.31 - 2.50 <0.0001 1.4 0.89 - 2.21 0.138Symptomatic (yes/no) 0.91 0.64 -1.29 0.602 0.94 0.66 - 1.36 0.778Size pT (>7 vs ≤7 cm) 1.61 1.08 - 2.41 0.019 1.17 0.481 1.77 1.15 - 2.73 0.009 1.25 0.76 - 2.07 0.367Nodes (pN1 vs pN0) 2.14 1.35 - 3.39 0.001 2.31 1.44 - 3.70 <0.0001Fuhrman (3-4 vs 1-2) 1.80 1.15 - 2.82 0.010 1.86 1.17 - 2.97 0.008Necrosis 1.50 1.05 - 2.14 0.024 1.57 1.08 - 2.27 0.016Perirenal Fat Invasion 1.87 1.31 - 2.67 <0.0001 2.02 1.32 - 3.09 <0.0001 2.06 1.42 - 2.99 <0.0001 2.21 1.40 - 3.47 0.001Renal Vein Invasion 1.28 0.87 - 1.88 0.209 1.09 0.72 - 1.66 0.669No-CC vs CC 1.42 0.93 - 2.17 0.099 1.40 0.90 - 2.19 0.130Sarcomatoid features 1.10 0.63 - 1.91 0.726 1.11 0.62 - 1.96 0.720Hb (< 11 vs ≥ 11 gr/dl) 1.79 1.25 - 2.56 0.001 1.80 1.24 - 2.59 0.002M+ (Multiple vs Single) 1.94 1.28 - 2.95 0.002 2.07 1.33 - 3.23 0.001M+ (≥ 2 Org. vs 1 Org.) 1.67 1.21 - 2.32 0.002 2.19 1.43 - 3.34 <0.0001 1.62 1.15 - 2.27 0.005 2.01 1.27 - 3.19 0.003M+ (Bone vs Lung) 2.10 1.14 - 3.88 0.017 2.03 1.10 - 3.76 0.024M+ (Vert. vs non-Vert.) 3.61 1.00 - 12.98 0.035 3.61 1.00 - 12.98 0.035M+ Lung (> 5 vs ≤ 5) 3.21 1.47 - 7.00 0.003 3.21 1.47 - 7.00 0.003
5-year OS 5-year CSSUnivariate Multivariate Univariate MultivariateOrgans N° %
1 organ 173 51.0 2 organs 128 37.8 3 organs 36 10.6 4 organs 2 0.6Total 339
Organ Sites N° % Lung 146 45.5 Bone 69 21.5 Lymph Node 34 10.6 Liver 28 8.7 Adrenal 13 4.0 Brain 7 2.2 Other 24 7.5Total 321
Metasteses N° % 2 to 5 31 47.0> 5 and ≤ 10 12 18.2> 10 23 34.8Total 66
Metastases N° % N° % N° % 1 40 30.3 30 43.5 11 42.3 >1 92 69.7 33 47.8 15 57.7Total 132 63 26
Single vs Multiple Metastases (M+)
Number of Involved Organs
Groups (N°) of Pulmonary Metastases
Metastatic Sites
Lung Bone Liver
