P-346 A systematic review of the gonadotoxicity of osteoscarcoma and Ewinǵs sarcoma chemotherapies in postpubertal females and males
Authors: Weidlinger S , Graber S , Bratschi I , Pape J , Kollár A , Von Wolff M 
Published: July 2024

Abstract

Study question
What is the postpubertal gonadotoxicity of osteosarcoma (OS) and Ewing’s sarcoma (ES) chemotherapies to better counsel females and males about the risk of infertility?

Summary answer
Limited data indicate a risk of infertility in OS in 5.1% of females and 52.2% of males and in ES in 13.0% and 89.5% respectively.

What is known already
Data on the gonadotoxicity of different chemotherapies are essential to better advise young women and men about the risk of treatment-related infertility and to better assess the need for fertility preservation measures prior to cancer treatment. Such data specific to bone-cancer have not yet been systematically reviewed.
This review is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation.

Study design, size, duration
A systematic review was conducted to address the issue of gonadotoxicity of bone-cancer specific chemotherapies. Combined search topics included 1) bone-cancer, 2) cancer therapies and 3) fertility parameters after cancer therapy. All relevant documents published between 09/2000 and 08/2022 from the information sources MEDLINE, Embase, and Cochrane Library were included.

Participants/materials, setting, methods
Only post-pubertal women and men aged &lt; 40 years without recurrent or metastatic disease were included. Due to the inconsistent description of post-treatment fertility parameters, the parameter “suspected infertility” was introduced to summarise and interpret the results. “Suspected infertility” was defined as follows: in women, any menstrual cycle disorder, gonadotropin or anti-mullerian hormone outside the reference range and a diagnosis of premature ovarian failure; in men, the presence of azoospermia or oligozoospermia.

Main results and the role of chance
A total of 11 out of 831 trials were included in the review. All studies were registry or observational studies. The rate of suspected infertility varied considerably in both OS and ES. Suspected infertility was found in 10/190 (5.1%, range 0-66%) female patients with OS (6 studies), 24/46 (52.2%, range 46-100%) male patients with OS (3 studies), 18/138 (13.0%, range 3-18%) female patients with ES (3 studies) and 34/38 (89.5%) male patients with ES (1 study). It was not possible to calculate the risk associated with specific chemotherapies. The risk of suspected infertility tended to be higher in ES, where all (100%) patients received alkylating chemotherapy, compared with 40% of women and 90% of men in OS. In both OS and ES, the overall rate of suspected infertility appeared to be higher in men than in women.

Limitations, reasons for caution
The limited data and heterogeneity of fertility-related outcomes in most trials made it necessary to define the rather vague outcome “suspected infertility”.

Wider implications of the findings
Our data suggest a moderate to high risk of infertility due to chemotherapies in bone cancer. This appears to be more pronounced in males than in females, although precise information cannot be given due to limited data. However, even though the study emphasizes the importance to consider fertility preservation measures.

Trial registration number
not applicable