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Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy
BACKGROUND: Selecting the appropriate patients to receive immunotherapy (IO) remains a challenge due to the lack of optimal biomarkers. The presence of liver metastases has been implicated as a poor prognostic factor in patients with metastatic cancer. We investigated the association between sites o...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716879/ https://www.ncbi.nlm.nih.gov/pubmed/31464611 http://dx.doi.org/10.1186/s12885-019-6073-7 |
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author | Bilen, Mehmet Asim Shabto, Julie M. Martini, Dylan J. Liu, Yuan Lewis, Colleen Collins, Hannah Akce, Mehmet Kissick, Haydn Carthon, Bradley C. Shaib, Walid L. Alese, Olatunji B. Steuer, Conor E. Wu, Christina Lawson, David H. Kudchadkar, Ragini Master, Viraj A. El-Rayes, Bassel Ramalingam, Suresh S. Owonikoko, Taofeek K. Harvey, R. Donald |
author_facet | Bilen, Mehmet Asim Shabto, Julie M. Martini, Dylan J. Liu, Yuan Lewis, Colleen Collins, Hannah Akce, Mehmet Kissick, Haydn Carthon, Bradley C. Shaib, Walid L. Alese, Olatunji B. Steuer, Conor E. Wu, Christina Lawson, David H. Kudchadkar, Ragini Master, Viraj A. El-Rayes, Bassel Ramalingam, Suresh S. Owonikoko, Taofeek K. Harvey, R. Donald |
author_sort | Bilen, Mehmet Asim |
collection | PubMed |
description | BACKGROUND: Selecting the appropriate patients to receive immunotherapy (IO) remains a challenge due to the lack of optimal biomarkers. The presence of liver metastases has been implicated as a poor prognostic factor in patients with metastatic cancer. We investigated the association between sites of metastatic disease and clinical outcomes in patients receiving IO. METHODS: We conducted a retrospective review of 90 patients treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University between 2009 and 2017. Overall survival (OS) and progression-free survival (PFS) were measured from the first dose of IO to date of death or hospice referral and clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a best response of complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and Multivariate analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Covariates included age, whether IO is indicated for the patient’s histology, ECOG performance status, Royal Marsden Hospital (RMH) risk group, number of metastatic sites, and histology. RESULTS: The median age was 63 years and 53% of patients were men. The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). Most patients (73.3%) had more than one site of distant metastasis. Sites of metastasis collected were lymph node (n = 58), liver (n = 40), lung (n = 37), bone (n = 24), and brain (n = 8). Most patients (80.7%) were RMH good risk. Most patients (n = 62) had received 2+ prior lines of systemic treatment before receiving IO on trial; 27 patients (30.0%) received prior ICB. Liver metastases were associated with significantly shorter OS (HR: 0.38, CI: 0.17–0.84, p = 0.017). Patients with liver metastasis also trended towards having shorter PFS (HR: 0.70, CI: 0.41–1.19, p = 0.188). The median OS was substantially longer for patients without liver metastases (21.9 vs. 8.1 months, p = 0.0048). CONCLUSIONS: Liver metastases may be a poor prognostic factor in patients receiving IO on phase 1 clinical trials. The presence of liver metastases may warrant consideration in updated prognostic models if these findings are validated in a larger prospective cohort. |
format | Online Article Text |
id | pubmed-6716879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67168792019-09-04 Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy Bilen, Mehmet Asim Shabto, Julie M. Martini, Dylan J. Liu, Yuan Lewis, Colleen Collins, Hannah Akce, Mehmet Kissick, Haydn Carthon, Bradley C. Shaib, Walid L. Alese, Olatunji B. Steuer, Conor E. Wu, Christina Lawson, David H. Kudchadkar, Ragini Master, Viraj A. El-Rayes, Bassel Ramalingam, Suresh S. Owonikoko, Taofeek K. Harvey, R. Donald BMC Cancer Research Article BACKGROUND: Selecting the appropriate patients to receive immunotherapy (IO) remains a challenge due to the lack of optimal biomarkers. The presence of liver metastases has been implicated as a poor prognostic factor in patients with metastatic cancer. We investigated the association between sites of metastatic disease and clinical outcomes in patients receiving IO. METHODS: We conducted a retrospective review of 90 patients treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University between 2009 and 2017. Overall survival (OS) and progression-free survival (PFS) were measured from the first dose of IO to date of death or hospice referral and clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a best response of complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and Multivariate analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Covariates included age, whether IO is indicated for the patient’s histology, ECOG performance status, Royal Marsden Hospital (RMH) risk group, number of metastatic sites, and histology. RESULTS: The median age was 63 years and 53% of patients were men. The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). Most patients (73.3%) had more than one site of distant metastasis. Sites of metastasis collected were lymph node (n = 58), liver (n = 40), lung (n = 37), bone (n = 24), and brain (n = 8). Most patients (80.7%) were RMH good risk. Most patients (n = 62) had received 2+ prior lines of systemic treatment before receiving IO on trial; 27 patients (30.0%) received prior ICB. Liver metastases were associated with significantly shorter OS (HR: 0.38, CI: 0.17–0.84, p = 0.017). Patients with liver metastasis also trended towards having shorter PFS (HR: 0.70, CI: 0.41–1.19, p = 0.188). The median OS was substantially longer for patients without liver metastases (21.9 vs. 8.1 months, p = 0.0048). CONCLUSIONS: Liver metastases may be a poor prognostic factor in patients receiving IO on phase 1 clinical trials. The presence of liver metastases may warrant consideration in updated prognostic models if these findings are validated in a larger prospective cohort. BioMed Central 2019-08-29 /pmc/articles/PMC6716879/ /pubmed/31464611 http://dx.doi.org/10.1186/s12885-019-6073-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Bilen, Mehmet Asim Shabto, Julie M. Martini, Dylan J. Liu, Yuan Lewis, Colleen Collins, Hannah Akce, Mehmet Kissick, Haydn Carthon, Bradley C. Shaib, Walid L. Alese, Olatunji B. Steuer, Conor E. Wu, Christina Lawson, David H. Kudchadkar, Ragini Master, Viraj A. El-Rayes, Bassel Ramalingam, Suresh S. Owonikoko, Taofeek K. Harvey, R. Donald Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
title | Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
title_full | Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
title_fullStr | Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
title_full_unstemmed | Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
title_short | Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
title_sort | sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716879/ https://www.ncbi.nlm.nih.gov/pubmed/31464611 http://dx.doi.org/10.1186/s12885-019-6073-7 |
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