Dataset Information

Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing.

ABSTRACT: BACKGROUND:Investigating genome evolution in response to therapy is difficult in human tissue samples. To address this challenge, we develop an unbiased whole-genome plasma DNA sequencing approach that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach is applied to study longitudinal blood plasma samples from prostate cancer patients, where longitudinal tissue biopsies from the bone and other metastatic sites have been challenging to collect. RESULTS:A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identifies clinical correlations of aneuploid plasma DNA profiles with poor survival, increased plasma DNA concentrations, and lower plasma DNA size distributions. Deep-exome sequencing and genomic copy number profiling are performed on 23 patients, including 9 patients with matched metastatic tissues and 12 patients with serial plasma samples. These data show a high concordance in genomic alterations between the plasma DNA and metastatic tissue samples, suggesting the plasma DNA is highly representative of the tissue alterations. Longitudinal sequencing of 12 patients with 2-5 serial plasma samples reveals clonal dynamics and genome evolution in response to hormonal and chemotherapy. By performing an integrated evolutionary analysis, minor subclones are identified in 9 patients that expanded in response to therapy and harbored mutations associated with resistance. CONCLUSIONS:This study provides an unbiased evolutionary approach to non-invasively delineate clonal dynamics and identify clones with mutations associated with resistance in prostate cancer.

SUBMITTER: Ramesh N

PROVIDER: S-EPMC7336456 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing.

Ramesh Naveen N Sei Emi E Tsai Pei Ching PC Bai Shanshan S Zhao Yuehui Y Troncoso Patricia P Corn Paul G PG Logothetis Christopher C Zurita Amado J AJ Navin Nicholas E NE

Genome biology 20200706 1

<h4>Background</h4>Investigating genome evolution in response to therapy is difficult in human tissue samples. To address this challenge, we develop an unbiased whole-genome plasma DNA sequencing approach that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach is applied to study longitudinal blood plasma samples from prostate cancer patients, where longitudinal tissue biopsies from the bone and other metastatic sites have been ch ...[more]

PMID: 32631448

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Project description:Purpose:During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions. Methods and Materials:Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches. Results:Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation. Conclusions:Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.

Project description:PurposeDuring a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.Methods and materialsRadiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches.ResultsRecommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation.ConclusionsResources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.

Dataset Information

Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing.

Publications

Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing.

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