Molekylära Och Kliniska Studier av Ben Och mjukdelstumörer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50,000
- 试验地点
- 1
- 主要终点
- Discordance between molecularly defined class and the original histopathological diagnosis
研究概览
简要总结
The goal of this observational study is to learn whether tumors of bone and soft tissue can be sorted into groups by their genes. Today these tumors are named mainly by how they look under a microscope. There are more than 150 names in use. The same tumor can be given different names by different doctors.
The study includes people of any age with a bone or soft tissue tumor. All of them had tissue sampled at Karolinska University Hospital in Stockholm, Sweden.
The main questions it aims to answer are:
Can tests of a tumor's genes sort these tumors into clearer groups than the names used today? How often does a tumor's gene group differ from the name it was given at diagnosis? Can a computer program tell these groups apart from scanned pictures of the tissue?
Researchers will compare the groups found by the gene tests with the diagnoses given at the time. They will also look at how each group did over the years that followed. This shows which way of sorting tumors better matches what happened to participants.
Participants will not have extra visits, tests, or treatment for this study. The study does not change anyone's care.
Researchers will:
Use tumor tissue that was already taken as part of regular care Read the DNA and RNA in the tumor, which carry its genetic instructions Read the chemical marks on the tumor's DNA that switch genes on and off Scan the glass slides of the tissue into digital pictures Collect facts about treatment and health from medical records
Participants who are newly diagnosed will also be asked for a blood sample. Blood shows which gene changes a person was born with and which ones started in the tumor.
If the study finds a gene change that matters for a participant's care, the study team tells the treating doctors through normal hospital routines.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologically diagnosed tumor or tumor-like lesion of bone or soft tissue, including benign, intermediate and malignant lesions
- •Tissue sampled, resected or reviewed at the study center
- •Archived diagnostic material available and adequate for the analyses of the relevant cohort: formalin-fixed paraffin-embedded tissue, fresh-frozen tissue, or diagnostic glass slides
- •For the prospective cohort, documented informed consent
排除标准
- •No retrievable diagnostic material or diagnostic report
- •Documented objection by the participant to the research use of their material or data
研究组 & 干预措施
Group/Cohort 1 - Retrospective archival cohort
People of any age with a bone or soft tissue tumor sampled or resected at the study center before the start of the study, identified from the pathology archive using a predefined SNOMED-based search. Diagnostic glass slides are scanned for the full archival cohort. A nested subset with tissue of sufficient quality also undergoes whole genome sequencing, RNA sequencing and DNA methylation profiling. Clinical and outcome data are taken from pathology reports and medical records. No study procedure is performed on participants.
Assigned Interventions:
Diagnostic Test: Digital pathology and computational image analysis Genetic: Whole genome and whole transcriptome sequencing (nested subset) Genetic: Genome-wide DNA methylation profiling (nested subset)
Group/Cohort 2 - Prospective cohort
People of any age newly diagnosed with, or referred for evaluation of, a bone or soft tissue tumor at the study center during the study period, who consent to the use of their tissue and data. Diagnostic tissue undergoes whole genome and transcriptome sequencing with a matched germline reference sample, DNA methylation profiling and slide digitization. Diagnosis and treatment follow routine practice and are not altered by the study.
Assigned Interventions:
Diagnostic Test: Digital pathology and computational image analysis Genetic: Whole genome and whole transcriptome sequencing Genetic: Genome-wide DNA methylation profiling
结局指标
主要结局
Discordance between molecularly defined class and the original histopathological diagnosis
时间窗: Through completion of the primary analysis of the molecular cohort, up to [5] years after study start.
Proportion of tumors in the molecularly profiled cohort whose class assignment from integrated genomic, transcriptomic and methylation data, made without reference to the diagnostic label, differs from the WHO-based diagnosis in the original pathology report. Reported with a 95 percent confidence interval and accompanied by the adjusted Rand index for the full cross-classification. Only assignments above a pre-specified confidence threshold are counted as discordant; low-confidence assignments are reported separately. Discordant cases undergo blinded review by two sarcoma pathologists to separate reclassification from diagnostic error.
次要结局
- Number of stable molecular classes identified(Through completion of the primary analysis, up to [5] years.)
- Proportion of tumors in residual diagnostic categories that receive a defined molecular class(Through completion of the primary analysis, up to [5] years.)
- Accuracy of molecular class prediction from digitized slides(Through completion of model development and evaluation, up to [5] years.)
- Frequency of clinically actionable somatic alterations(Through completion of the primary analysis, up to [5] years.)
- Frequency of pathogenic germline variants in cancer predisposition genes(Through completion of the primary analysis, up to [5] years.)
- Overall survival by molecular class(From date of diagnosis to death from any cause, assessed up to [30] years.)
- Prognostic information added by molecular class beyond current diagnosis and grade(From date of diagnosis to death from any cause, assessed up to [30] years.)
研究者
Felix Haglund de Flon
Associate Professor, Research group leader
Karolinska Institutet