Clinical trial NCT06391879: Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma
Official title: Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma Based on Accurate Genotyping: a Population-based Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: VHL Syndrome
Renal Cell Carcinoma
Keywords: VHL
VHL syndrome
Renal cell carcinoma
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Based on the previous establishment of the largest biobank of VHL syndrome in Asia, as well as the unique characteristics and genotype-phenotypic relationship of patients in Chinese population, this cohort-study aims to retrospectively and prospectively incorporated patients with VHL-related RCC.

Brief summary: VHL syndrome is a rare hereditary tumor syndrome caused by mutation of tumor suppressor gene VHL. One of the most important clinical manifestations and main cause of death is VHL-related renal cell carcinoma (RCC). Facing the challenges of multilesion of both kidneys, slow progress and life-long repeated surgeries in VHL-related RCC, individualized prediction of the best surgical treatment time and reduction of times of surgeries are very important to improve the prognosis of patients with VHL syndrome. Therefore, there is an urgent need to establish a more effective and accurate prediction model for the natural course of VHL syndrome. This cohort-study aims to retrospectively and prospectively analyze the factors related to the natural course of VHL-related RCC. At the same time, some patients were selected for prospectively continuous molecular evolution dynamic monitoring after comprehensively considering the results of single cell sequencing, whole genome and metabonomic sequencing. This study will provide scientific basis for accurate diagnosis and treatment of natural course of VHL-related RCC.

Detailed description: VHL syndrome is a rare hereditary tumor syndrome caused by mutation of tumor suppressor gene VHL. One of the most important clinical manifestations and main cause of death is VHL-related renal cell carcinoma (RCC). Previous small sample studies have confirmed that the natural course of VHL-related RCC is different from that of sporadic RCC. Facing the challenges of multilesion of both kidneys, slow progress and life-long repeated surgeries in VHL-related RCC, individualized prediction of the best surgical treatment time and reduction of times of surgeries are very important to improve the prognosis of patients with VHL-related RCC. Therefore, there is an urgent need to establish a more effective and accurate prediction model for the natural course of VHL syndrome. Based on the previous establishment of the largest biobank of VHL syndrome in Asia, as well as the unique characteristics and genotype-phenotypic relationship of patients in Chinese population, this cohort-study aims to retrospectively and prospectively analyze the factors related to the natural course of VHL-related RCC. At the same time, some patients were selected for prospectively continuous molecular evolution dynamic monitoring after comprehensively considering the results of single cell sequencing, whole genome and metabonomic sequencing. This study will systematically analyze the specific molecular characteristic and evolution of VHL-related different from sporadic RCC, reveal new specific driving genes and their molecular regulatory mechanisms, and establish a multi-dimensional prediction model of natural course of VHL-related RCC based on accurate genotyping. It will provide scientific basis for accurate diagnosis and treatment of natural course of VHL-related RCC.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of VHL syndrome based on clinical diagnostic criteria or genetic test results of syndrome
* Upon enrollment, multiple organ assessments for VHL syndrome should be completed, including fundus examination, CT/MR examination of the brain, spinal cord, and abdominal and pelvic organs.
* If subjects have undergone surgery for renal tumors, the follow-up observation time in each branch center before surgery should be more than 12 months, and imaging examinations should be performed at least once every 6 months.

Exclusion Criteria:

* Do not meet the clinical diagnostic criteria for VHL disease or the genetic test is negative
* Other hereditary RCC syndromes

Primary outcomes:
measure: Tumor growth rate
timeFrame: From date of diagnosis of the VHL-related RCC until the date of surgical treatment, death from any cause or the date of last follow-up, whichever came first, assessed up to 60 years.
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From date of diagnosis of the VHL-related RCC until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 20 years.
measure: Cancer-specific survival (CSS)
timeFrame: From date of diagnosis of the VHL-related RCC until the date of death from the same disease or the date of last follow-up, whichever came first, assessed up to 20 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Kan Gong
role: PRINCIPAL_INVESTIGATOR
References: