Early Ageing During Therapy in AYA Cancer Patients

Longitudinal Assessment of Therapy-related Early Ageing in Adolescent and Young Adult (AYA) Cancer Patients

Longitudinal cohort study; measurements before start of systemic therapy and one year later.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Leukemia; Cancer; Breast Cancer; Hodgkin Lymphoma; Osteosarcoma; Ewing Sarcoma; Testicular Cancer
• Intervention / Treatment: Procedure: Blood sampling

Detailed Description

Rationale:

Compared with survivors of childhood cancer, there is sparse knowledge about the long-term morbidity and mortality of adolescent and young adult (AYA) cancer patients, who are diagnosed at age 18-39 and have an 80% chance to survive. Following cancer treatment, many cancer survivors, including those at AYA age, have an increased risk of cardiovascular disease. Early ageing has been described in paediatric and certain adult cancer survivor populations. One of the responsible mechanisms behind biological ageing is cellular senescence, characterized by a stable arrest of the cell cycle which occurs in response to stress and damage. In all organisms the number of senescent cells increases with age and senescence has been associated with age-related diseases, like atherosclerosis and Alzheimer. Early ageing as a result of intensive cancer treatment with systemic therapy and radiation may result in early cardiovascular disease. However, information about senescence, early vascular ageing and related patient and tumour characteristics is missing for AYAs.

Objective:

to determine markers related to early ageing and senescence in AYA cancer patients before and after systemic therapy, in order to assess treatment-related early vascular ageing and associated tumour and patient characteristics.

Study design:

Longitudinal cohort study; measurements before start of systemic therapy and one year later.

Study population:

Patients aged 18-39 years, with a first histological and/or cytological diagnosis of a haematological or solid malignancy, scheduled to start systemic therapy with curative intent.

Main study parameters/endpoints:

Primary endpoint is change in senescence marker P16 between start of systemic therapy and one year later. Secondary endpoints are: changes in senescence-associated secretory phenotype (SASP) and vascular markers; prevalence of classical cardiovascular risk factors (smoking, lipids, body mass index (BMI), glucose); tumour (treatment) and patient (age, sex, pre-existent cardiometabolic status) factors related to the changes in senescence, SASP and cardiovascular risk factors.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Study measurements will be performed twice and consist of blood withdrawal and physical examination (weight, height, waist-hip ratio, and blood pressure).

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: J. Nuver, MD, PhD; Phone Number: +31 50 361 2821; Email: j.nuver@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: J. Nuver, MD, PhD; Phone Number: +31 50 361 2821; Email: j.nuver@umcg.nl
    • Principal Investigator: J. Nuver, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

AYA patients who will start systemic treatment at the Department of Medical Oncology or Haematology of the University Medical Center Groningen are potential study participants. Patients will be informed about the study during a regular visit to the outpatient clinic or during their admission to the nursing ward. From the moment the study starts, the investigators aim to include all consecutive patients during a period of 2 years.

Description

Inclusion Criteria:

• Aged 18-39 years at cancer diagnosis
• Having a histologically and/or cytologically confirmed cancer diagnosis, including leukemia, (non-)Hodgkin lymphoma, testicular cancer, osteosarcoma, Ewing sarcoma, breast cancer, and cervical cancer.
• Scheduled to start systemic therapy with curative intent. Allowed treatments (concurrent or sequential) are: surgery, radiotherapy, chemotherapy, antibodies.

Exclusion Criteria:

• patients who are not able to understand the patient information letter and informed consent form
• patients who will be treated with immune checkpoint inhibitors or targeted therapy with inhibitors of angiogenesis
• patients who have been treated with systemic therapy or radiotherapy for a previous malignancy (exceptions: in situ carcinoma of the cervix or uterus and adequately treated basal and squamous cell carcinoma of the skin).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AYA cancer patients; Patients aged 18-39 years, with a first histological and/or cytological diagnosis of a haematological or solid malignancy, scheduled to start systemic therapy with curative intent.	Procedure: Blood sampling; Study measurements will be performed twice and consist of blood withdrawal and physical examination (weight, height, waist-hip ratio, and blood pressure).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in senescence marker P16	determine change in senescence marker P16 between start of systemic therapy and one year later.	at baseline and 1 year after start systemic therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in SASPs and vascular markers	Determine changes in SASPs and vascular markers	at baseline and 1 year after start systemic therapy
Prevalence of classical cardiovascular risk factors (smoking, lipids, BMI, glucose)	Determine prevalence of classical cardiovascular risk factors (lipids, BMI, glucose)	at baseline and 1 year after start systemic therapy
Association between treatment type and change in senescence marker P16	Determine association between treatment type and change in senescence marker P16	at baseline and 1 year after start systemic therapy
Association between age and change in senescence marker P16	Determine association between age and change in senescence marker P16	at baseline and 1 year after start systemic therapy
Associations between senescence, inflammation, and cardiovascular risk factors	Determine associations between senescence, inflammation, and cardiovascular risk factors	at baseline and 1 year after start systemic therapy

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: UMCG Kanker Researchfonds
• Investigators: Principal Investigator: J. Nuver, MD, PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: September 21, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): September 30, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Male Urogenital Diseases; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Gonadal Disorders; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Testicular Diseases; Sarcoma, Ewing; Osteosarcoma; Testicular Neoplasms
• Other Study ID Numbers: 202100484

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No