Late Effects of Childhood Cancer and Its Treatment

Recommendations from the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer emphasize the importance of reproductive health care, yet little is known regarding adherence to these recommendations and non-fertility-related sexual and reproductive health (SRH) outcomes.

Follow-up of outcomes on the basis of the COG-LTFU guidelines was assessed in female patients who underwent fertility preservation consultation before gonadotoxic therapy between 2016 and 2022 at a single institution and were at least 6 months from treatment completion.

We included 140 patients, with a mean time of 2.7 years from treatment completion. Eighty-six patients were 12 years old or older, of whom sexual activity was recorded in 59 (68.7%), and 12 of 31 (38.7%) sexually active patients underwent sexual function assessment. The 57 (66.3%) patients at high risk of premature ovarian insufficiency (POI) at diagnosis were more likely than minimal-risk counterparts (29, 33.7%) to have abnormal uterine bleeding (42.1% vs 17.2%, P = .03), to be diagnosed with POI (29.8% vs 0%, P = .01), and to have sexual activity recorded (77.2% vs 51.7%, P = .03). Of 17 patients with POI, 82.4% were on hormone replacement therapy, and 58.8% had undergone bone mineral density testing.

This study adds to the limited literature regarding non-fertility-related SRH outcomes after gonadotoxic therapy and illustrates opportunities to improve adherence to the COG-LTFU guidelines. Increased attention to SRH guidelines may increase detection and treatment of SRH conditions, improving the health and quality of life of female cancer survivors.

Although the physiological late effects of childhood cancer survivors are more obvious, appropriate assessment of psychosocial effects is needed. Therefore, it was aimed to develop a scale to evaluate psychosocial late effects in cancer survivors and to test its validity and reliability.

This methodological study was conducted with 100 children and adolescents who survived were collected at the oncology center in the south of Türkiye in 2022. Data were collected with the “Personal Information Form” and “Pediatric Cancer Survivors Psychosocial Late Effects Scale (PCSLES)” IBM SPSS 24.0 and IBM AMOS 24.0 software programs were used for data analysis, and descriptive statistics were used to analyze numeric variables. Exploration and confirmatory factor analyses were performed to determine the scale's factorial structure.

The factorial analysis was used to test the structural validity of the scale. A four-factor structure consisting of 17 items was developed. The Cronbach's alpha coefficient for “1” was 0.89, “2” was 0.87, “3” was 0.80, “4” was 0.82 and the total score was 0.92. Fit indices resulting from the study were χ2/SD: 1.497, root mean square error of approximation (RMSEA): 0.071, goodnessof-fit index (GFI): 0.85, comparative-of-fit index (CFI): 0.94, and normed fit index (NFI): 0.85.

The scale is a valid and reliable scale that can be used to determine psychosocial late effects in pediatric cancer patients.

Utilizing the PCSLES can assist in identifying the psychosocial symptoms of child survivors/adolescents and facilitate the planning of appropriate interventions.

Therapeutic advancements have improved pediatric cancer prognosis, shifting the interest towards the management of psychosocial burden and treatment-related morbidity. To critically appraise the available evidence, we conducted an umbrella review of meta-analyses of randomized controlled trials on supportive interventions for childhood cancer. Thirty-four publications (92 meta-analyses, 1 network, 14,521 participants) were included. The most concrete data showed a reduction in procedure-related pain and distress through hypnosis. Moreover, exercise improved the functional mobility of the patients. Regarding pharmacological interventions, most of the meta-analyses pertained to the treatment of nausea/vomiting (ondansetron was effective) and infections/febrile neutropenia [granulocyte-(macrophage) colony-stimulating factors showed benefits]. Substantial heterogeneity was detected in 31 associations. Conclusively, supportive interventions for pediatric cancer are being thoroughly evaluated. However, most of the studies are small and of moderate quality, highlighting the need for more randomized evidence in order to increase precision in improving the quality of life of patients, survivors and their families.

The effects of anticancer drugs used in childhood on brain function in adulthood are unclear. Here, we report the long-term changes in the proliferation of neuronal stem/progenitor cells (NPCs) in the hippocampal dentate gyrus after treatment with cyclophosphamide (CYP), which is often used as a therapeutic medicine in childhood cancer. A systemic injection of CYP into 3-week-old mice decreased 5-bromo-2′-deoxyuridine (BrdU)-incorporated cells in the hippocampal subgranular zone 2 and 55 days after the injection in a dose-dependent manner. Restraint stress induced increase in corticosterone level, which was enhanced by CYP at day 35 after injection. These findings suggest that CYP injection into post-weaning mice causes prolonged alteration in NPC proliferation in the hippocampus and the stress response.

Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.

We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.

We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to “pediatric,” “cancer,” and “TCM.”

We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.

The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.

The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as “moderate.” In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49–4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13–0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08–0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.

There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.