Chemotherapy alone vs. chemotherapy plus radiotherapy in female adolescent and young adults with Hodgkin’s lymphoma: reproductive health outcomes

Purpose To examine the effects of Hodgkin’s lymphoma and its treatment on reproductive health in female adolescent and young adults (AYA). Methods We conducted a retrospective, population-based, matched-cohort study of female patients with Hodgkin’s lymphoma diagnosed at 15–39 years of age from 1995 to 2014 in Ontario, Canada. Three female individuals with no history of cancer (unexposed) were matched by birth year and census subdivision to each patient with cancer (exposed). In a subset of the cohort (2005 onwards), the Hodgkin’s lymphoma patients were further classified into two groups for analysis based on treatment exposure: (1) chemotherapy alone or (2) combined chemotherapy and radiation. Reproductive health outcomes were infertility, childbirth, and premature ovarian insufficiency (POI). Relative risks (RR) were calculated using modified Poisson regression adjusted for income quintile, immigration status, and parity. Results A total of 1443 exposed and 4329 unexposed individuals formed our cohort. Hodgkin’s lymphoma patients were at an increased risk of infertility (aRR 1.86; 95% CI 1.57 to 2.20) and POI (aRR 2.81; 95% CI 2.16 to 3.65). While the risk of infertility persisted in both treatment groups (chemotherapy alone, combined chemotherapy plus radiotherapy), the increased risk of POI was only statistically significant in the chemotherapy plus radiotherapy group. No differences in childbirth rates were observed, overall or by treatment exposure compared with unexposed individuals. Conclusions Female AYA survivors of Hodgkin’s lymphoma face an increased risk of infertility, independent of exposure to chemotherapy alone, or chemotherapy plus radiotherapy. The risk of POI is higher in those requiring radiotherapy vs. chemotherapy alone. Implications for cancer survivors These results emphasize the importance of pre-treatment fertility counseling and reproductive health surveillance for AYAs diagnosed with Hodgkin’s lymphoma. Supplementary Information The online version contains supplementary material available at 10.1007/s11764-023-01388-z.

The DAD is compiled by the Canadian Institute for Health Information and contains administrative, clinical (diagnoses and procedures/interventions), demographic, and administrative information for all admissions to acute care hospitals, rehab, chronic, and day surgery institutions in Ontario.At ICES, consecutive DAD records are linked together to form 'episodes of care' among the hospitals to which patients have been transferred after their initial admission.National Ambulatory Care Reporting System (NACRS) The NACRS is compiled by the Canadian Institute for Health Information and contains administrative, clinical (diagnoses and procedures), demographic, and administrative information for all patient visits made to hospital-and community-based ambulatory care centres (emergency departments, day surgery units, hemodialysis units, and cancer care clinics).At ICES, NACRS records are linked with other data sources (DAD, OMHRS) to identify transitions to other care settings, such as inpatient acute care or psychiatric care.Ontario Health Insurance Plan Claims Database (OHIP) The OHIP claims database contains information on inpatient and outpatient services provided to Ontario residents eligible for the province's publicly funded health insurance system by fee-for-service health care practitioners (primarily physicians) and "shadow billings" for those paid through non-fee-for-service payment plans.The main data elements include patient and physician identifiers (encrypted), code for service provided, date of service, associated diagnosis, and fee paid.

Same-Day Surgery (CIHI SDS)
The SDS is compiled by the Canadian Institute for Health Information and contains administrative, clinical (diagnoses and procedures), demographic, and administrative information for all patient visits made to day surgery institutions in Ontario.The main data elements include patient demographics, clinical data (diagnoses, procedures, physician), administrative data (institution/hospital number etc.), financial data, service-specific data elements for day surgery and emergency.

Population and Demographics Registered Persons Database (RPDB)
The RPDB provides basic demographic information (age, sex, location of residence, date of birth, and date of death for deceased individuals) for those issued an Ontario health insurance number.The RPDB also indicates the time periods for which an individual was eligible to receive publicly funded health insurance benefits and the best known postal code for each registrant on July 1st of each year.

Postal Code Conversion File (PCCF)
The PCCF database will link to postal codes within a given cohort and determine other census geographic identifiers such as, dissemination/enumeration area, census division, longitude/latitude, urban/rural flag and neighbourhood income quintile.Patient Contact and Eligibility Yearly Files (CONTACT) Once a person becomes eligible for OHIP an initial record is created with a start date and an infinite end date.When eligibility ends a second record is created with the same start date but a finite end date.

Immigration Refugees and Citizenship Canada Permanent Resident (IRCC-PR) Database
The Ontario portion of the IRCC-PR Database includes immigration application records for people who initially applied to land in Ontario since 1985.The dataset contains permanent residents' demographic information such as country of citizenship, level of education, mother tongue, and landing date.New immigrants who are currently residing in Ontario but originally landed in another province are not captured in this dataset.

ICES Derived Cohorts Linked Delivering Mothers and Newborns (MOMBABY)
The ICES MOMBABY Database is an ICES-derived cohort that links the DAD inpatient admission records of delivering mothers and their newborns.From 2002 onward, this linkage is performed deterministically using a maternal-newborn chart matching number.Prior to 2002, mothers were linked to their children by matching on the institutions they were admitted, their postal codes, and their admission/discharge dates.

Table A1 .
Data sources accessed at ICES

Table A3 .
Codes and descriptions for group classifications