Patients under the age of 40 constitute less than 10% of all gastrointestinal stromal tumor (GIST) cases. Lower the cutoff to 21 years old and the percentage falls to under 1%.
It is fair to say that GIST is primarily a disease of the elderly. The median age of diagnosis for this disease is in the 60-65 years age bracket. One study reported that only 2.3% of patients with GIST are in the pediatric/young adult category.
It is no surprise, therefore, that medical literature has heavily focused on the treatment of GIST in adult patients, since they are overwhelmingly more likely to be diagnosed with this disease than younger patients. However, clinical findings gleaned from trials with adult participants are often extrapolated to children, which can be problematic because many physiological functions differ between children and adults.
“With advances in genetic sequencing, there is accumulating data now suggesting that pediatric GIST is very different from its adult disease counterpart,” Raitio and colleagues wrote in Pediatric Surgery International.
Different Responses Seen in Children
Raitio and colleagues conducted a systematic review of published studies focused on the outcomes of pediatric GIST. They imposed no time limit on the studies they examined and even included non-English articles.
The research team reported surgery is the mainstay of treatment for primary tumors, which is also the case in adult patients. Patients who had unresectable tumors received chemotherapy or tyrosine receptor kinase inhibitors such as imatinib.
Read more about GIST etiology
The results also demonstrated that 3 potential prognostic indicators—age at diagnosis, gender, and tumor location—were not significantly associated with disparities in survival; neither did KIT or PDGFRA mutations make a difference.
The longest latent GIST recurrence identified in the review was 26 years. Complete remission was reported in 52% of patients. Factors that raised the risk of death included spindle morphology, tumors that were larger than 5 cm, and a high mitotic index.
The overall conclusion favors patients who were diagnosed and treated during the pediatric stage of their life, compared to older patients. However, given that late recurrences can occur, regularly scheduled follow-ups are needed to monitor remission.
Pregnancy Presents Other Issues
For teenage female patients of reproductive age, another issue looms large: fertility and pregnancy. In fact, the best practice when it comes to seeing females of reproductive age is to ask about sexual history openly, as some drugs might be contraindicated in pregnancy. Needless to say, cultural impediments do prevent physicians from openly doing so in more conservative countries, but seeing that the consultation room is a private, safe space, physicians should be able to have these conversations openly with the consent of their patients.
How do anticancer GIST treatments affect fertility, pregnancy, and lactation? Simply put, data is limited, and hence speculation is futile. In rat studies, imatinib produced significant changes in fetal growth.
“[Scientists] found changes in the epigenetic markers of essential genes imprinted in the placenta and a reduction in the labyrinthine zone and blood vessels in the placenta,” Dudzisz-Śledź and colleagues wrote in Cancers, describing rat studies. “Moreover, an effect on placental growth was observed in case of treatment discontinuation before pregnancy.”
Read more about GIST complications
These studies suggest imatinib may affect pregnancy in the long term. Hence, physicians would be wise to consider drug withdrawal prior to pregnancy, coupled with closer monitoring for possible placental failure.
Studies involving women who became pregnant while taking imatinib demonstrated that 28% resulted in termination, 15% resulted in spontaneous abortion, and 9.6% of newborns had fetal abnormalities. However, it should be noted that a direct link between these unfavorable statistics and the drug has not been explored fully. Tyrosine kinase inhibitors are still routinely prescribed during pregnancy.
However, the possible negative effects of GIST drugs on pregnancy should not be discounted altogether. And this highlights the challenge of treating pediatric patients: often there is a need to distinguish between pediatric patients of reproductive age and those who are not. As mentioned, the scarcity of clinical data on children does not help.
A Changing Landscape
However, the landscape of pediatric care is changing, as researchers invest more time and money into studying diseases according to various age categories, not just in the age category in which the incidence of the disease is at the highest. And this does not involve just the biological testing of pediatric patients, but also encouraging patients to talk about their own disease experiences. The idea is to ensure that both the physical and psychological aspects of a disease are explored more fully.
“Participatory research is a positive experience for both children and researchers,” Haijes and van Thiel wrote in Pediatric Research. “Benefits for the children are their increased empowerment, self-confidence, and self-esteem.”
Raitio A, Salim A, Mullassery D, Losty PD. Current treatment and outcomes of pediatric gastrointestinal stromal tumors (GIST): a systematic review of published studies. Pediatr Surg Int. 2021;37(9):1161-1165. doi:10.1007/s00383-021-04931-0
Haijes HA, van Thiel GJ. Participatory methods in pediatric participatory research: a systematic review. Pediatr Res. 2016;79(5):676-683. doi:10.1038/pr.2015.279
Dudzisz-Śledź M, Bylina E, Teterycz P, Rutkowski P. Treatment of metastatic gastrointestinal stromal tumors (GIST): a focus on older patients. Drugs Aging. 2021;38(5):375-396. doi:10.1007/s40266-021-00841-x