Molecular and Clinical Studies of Bone and Soft Tissue Tumors
ConditionBone and Soft Tissue Tumors
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorKarolinska Institutet
About this trial
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 deoxyribonucleic acid (DNA) and ribonucleic acid (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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
No retrievable diagnostic material or diagnostic report
Documented objection by the participant to the research use of their material or data
Trial population
People of any age with a tumor or tumor-like lesion of bone or soft tissue, benign, intermediate or malignant, diagnosed or reviewed at the Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden. The retrospective cohort is identified from the pathology archive by a predefined search based on the Systematized Nomenclature of Medicine (SNOMED) covering bone and soft tissue tumor codes, with an addendum capturing non-mesenchymal tumors that enter the differential diagnosis, such as melanoma, sarcomatoid carcinoma and lymphoma. The prospective cohort comprises people evaluated at the center during the study period. The center is a national referral center for sarcoma, so the population includes both locally diagnosed and referred cases.
Trial design
Design model
Cohort
Time perspective
Other
Treatments tested in this trial
Not listed
Trial groups
50,000 Participants
are grouped into 2 trial groupsGroup A: Group/Cohort 1 - Retrospective archival cohort
Group B: Group/Cohort 2 - Prospective cohort
Trial outcomes
Primary outcomes
1
Discordance between molecularly defined class and the original histopathological diagnosis
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 diagnosis based on the World Health Organization (WHO) classification 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.
Time frame
Through completion of the primary analysis of the molecular cohort, up to [5] years after study start.Secondary outcomes
1
Number of stable molecular classes identified
Number of classes recovered by consensus clustering of the integrated data that meet pre-specified stability criteria, reported with the stability metrics used (consensus matrix concordance, proportion of ambiguous clustering, cophenetic correlation) across the tested range of cluster numbers.
Time frame
Through completion of the primary analysis, up to [5] years.2
Proportion of tumors in residual diagnostic categories that receive a defined molecular class
Among tumors originally reported as undifferentiated pleomorphic sarcoma, spindle cell sarcoma not otherwise specified, or an equivalent unclassified bone lesion, the proportion assigned above the confidence threshold to a molecular class that has a defined biological identity.
Time frame
Through completion of the primary analysis, up to [5] years.3
Accuracy of molecular class prediction from digitized slides
Performance of machine learning models predicting molecular class membership from whole slide images, evaluated in held-out data split at the level of individual participants. Reported as balanced accuracy and macro-averaged area under the receiver operating characteristic curve, with 95 percent confidence intervals, plus per-class sensitivity and specificity.
Time frame
Through completion of model development and evaluation, up to [5] years.4
Frequency of clinically actionable somatic alterations
Proportion of tumors carrying at least one somatic alteration classified as clinically actionable according to a pre-specified evidence framework, reported by molecular class and by original World Health Organization (WHO) diagnosis.
Time frame
Through completion of the primary analysis, up to [5] years.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Karolinska Institutet
Lead sponsor
Region Stockholm
Collaborator
Lund University
Collaborator
KTH Royal Institute of Technology
Collaborator
Uppsala University
Collaborator
Source ClinicalTrials.gov