Prognostic Cancer Model
Conditions
Keywords
Hodgkin lymphoma, circulating tumor DNA, next generation sequencing
Brief summary
Specific somatic mutations using ctDNA will be analyzed in predefined subgroups of cHL (e.g., age \<60 and ≥ 60 years, EBV). These mutations will be correlated with response to the treatment in the first line, in the relapse, during brentuximab vedotin and/or nivolumab treatment. Circulating tumor DNA will be correlated with the extent of tumor mass and chemo/radiotherapy.
Detailed description
Samples of plasma from peripheral blood will be taken for investigational ctDNA examination during the specific timepoints: at diagnosis, after 2 cycles of initial chemotherapy, at the end of chemotherapy, 3 months after radiotherapy, at the diagnosis of the first relapse, after salvage chemotherapy before ASCT, 3 months after ASCT, at the diagnosis of second relapse and every 3 months during brentuximab vedotin treatment or during nivolumab treatment until progression. The buccal swab for germline DNA extraction will be performed at the time of enrollment into the study. Samples of peripheral blood for EBV-DNA analysis will be obtained from the EBV-positive cHL patients to measure EBV load at the same time-points as ctDNA. Microdissected HRS cells from fresh frozen biopsies at the diagnosis and at the relapse will be used for tumor cells next generation sequencing.
Interventions
None listed
Sponsors
Charles University, Czech Republic
General University Hospital, Prague
University Hospital Olomouc
University Hospital Hradec Kralove
University Hospital, Motol
Interni hematologicka klinika FNKV
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
* Patients ≥ 18 years with newly histologically confirmed classical Hodgkin lymphoma (cHL) will be enrolled * signing the informed consent
Exclusion criteria
* Pacients without signing the informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of tumor specific mutation profiles at dg. of HL based on ctDNA | 4 years | Identification of tumor specific mutation profiles at diagnosis of classical Hodgkin: 1. age at diagnosis \< 60 years in comparison to patients with age at diagnosis 60 years and more 2. EBV negative versus EBV positive cases 3. correlation with the first line treatment outcome lymphoma based on ctDNA analysis with correlation to clinical and pathological characteristics |
| Quantitative analysis of ctDNA level during the first-line chemotherapy | 4 years | Quantitative analysis of ctDNA level during the first-line chemotherapy: 1. analysis in relation to the type of chemotherapy: BEACOPP escalated vs ABVD 2. dynamics of ctDNA decline in correlation with treatment response |
| Identification of tumor specific mutation profiles at relapse of classical HL | 4 years | Identification of tumor specific mutation profiles at relapse of classical Hodgkin lymphoma: 1. detection of newly developed mutations in comparison to the initial diagnosis 2. characteristics of mutations in HL tumors refractory to brentuximab vedotin 3. characteristics of mutations in HL tumors refractory to nivolumab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In vitro functional characterization of identified DNA variants and/or mutations | 4 years | In vitro functional characterization of identified DNA variants and/or mutations: 1. variants with unknown impact on classical HL development 2. variants identified as associated with features analyzed in above mentioned goals |
Countries
Czechia
Contacts
Primary ContactHeidi Mocikova, M.D., Ph.D.
Backup ContactOndrej Havranek, assoc. prof.
Outcome results
None listed