Metastatic tropism of molecularly defined clear-cell renal cell carcinoma clusters
Gaelle Haddad, Junyu Guo, Yin Xi, Emin Albayrak, Mahrukh Huseni, Habib Hamidi, Romain Banchereau, Edward Kadel, Sarita Dubey, Corey Carter, Payal Kapur, James Brugarolas, Ivan Pedrosa
Gaelle Haddad, Junyu Guo, Yin Xi, Emin Albayrak, Mahrukh Huseni, Habib Hamidi, Romain Banchereau, Edward Kadel, Sarita Dubey, Corey Carter, Payal Kapur, James Brugarolas, Ivan Pedrosa
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Clinical Research and Public Health Clinical Research Oncology Public Health

Metastatic tropism of molecularly defined clear-cell renal cell carcinoma clusters

Abstract

BACKGROUND The relationship between molecular subgroups in clear-cell renal cell carcinoma (ccRCC) and metastatic tropism is poorly understood.METHODS We analyzed over 5,000 metastatic sites from 305 treatment-naive ccRCC patients in the IMmotion150 phase II clinical trial, where patients were randomized to atezolizumab, atezolizumab/bevacizumab, or sunitinib.RESULTS Angiogenic tumors (clusters 1 and 2) had a higher rate of pancreatic (21% vs. 6.9%; P = 0.002) and lower absolute number of lymph node (2.5 vs. 4.2; P = 0.006) metastases. In contrast, proliferative tumors (clusters 4 and 5) exhibited a higher absolute number of lymph node metastases (5.5 vs. 3.5; P = 0.019). Patients with pancreatic metastases receiving sunitinib had higher odds of overall response (OR, 7.13; 95% CI, 1.81–28.07; P = 0.0049) and longer progression-free survival than those without pancreatic metastases (P = 0.02).CONCLUSION ccRCC metastatic tropism relates to molecular clusters that predict response to therapy for tumors that metastasize to the pancreas.TRIAL REGISTRATION ClinicalTrials.gov NCT01984242FUNDING NIH grants R01CA154475 and P50CA196516.

Authors

Gaelle Haddad, Junyu Guo, Yin Xi, Emin Albayrak, Mahrukh Huseni, Habib Hamidi, Romain Banchereau, Edward Kadel, Sarita Dubey, Corey Carter, Payal Kapur, James Brugarolas, Ivan Pedrosa

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Figure 1

Prevalence of metastases by anatomic location at baseline and follow-up for each molecular cluster.

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Prevalence of metastases by anatomic location at baseline and follow-up ...
Radar plots showing the frequency of metastases by anatomic site. Spokes correspond to a specific anatomic locations. Each graph displays the percentage of patients with metastasis in each anatomic location, where the inner circle represents no metastasis (0%) and the 4 concentric circles increasing in size represent 25%, 50%, 75%, and 100% of patients with metastases, respectively. The solid area with different colors indicates the distribution of metastases at baseline for each cluster. The light pink area indicates the distribution of metastases at follow-up imaging. At baseline imaging, the lungs and lymph nodes were the most common locations for metastases in all clusters. The lung was the most common site in clusters 1 and 4, whereas lymph nodes were the most common site in clusters 3 and 5. The frequency of metastases in lung and lymph nodes in clusters 2, 6, and 7 were almost identical, whereas lung metastases were less common in cluster 5. At follow-up imaging, the frequency of metastasis did not change for most anatomic sites, resulting in complete overlap between the colored and light pink areas, except for the increased metastases in the brain (clusters 1–4 and 6). Cluster 6 also exhibited increase metastases in bone, lung, and lymph nodes. Cluster 5 exhibited increased metastases predominantly in lung, liver, and adrenal glands. Neuro, CNS; snoRNA, small nucleolar RNA.