Effects of treatments on gonadal function in long-term survivors of pediatric hematologic malignancies: A cohort study.

BACKGROUND: Potentially gonadotoxic protocols are currently used for the treatment of childhood hematologic malignancies. This study aims to evaluate the prevalence of gonadal dysfunction and the most important associated risk factors in a cohort of hematologic malignancy survivors. PROCEDURE: We considered all patients referred to our long-term follow-up clinic for childhood cancer survivors, between November 2001 and December 2017. Inclusion criteria were: (a) previous diagnosis of hematologic malignancy; (b) age at hematologic malignancy diagnosis < 18 years; (c) at least five years after the end of anticancer treatments; (d) at least one evaluation of gonadal function after the 18th birthday. Patients diagnosed before January 1, 1990, were excluded. RESULTS: Three hundred twenty-seven survivors (males = 196) were included. Isolated spermatogenesis damage was found in 58/196 (29.6%) of males, whereas 18/196 (9.2%) had Leydig cell failure. In females, 35/131 (26.7%) experienced premature ovarian insufficiency. In both sexes, abdominopelvic irradiation and hematopoietic stem cell transplantation were strongly associated with the risk of gonadal dysfunction. For every 1000 mg/m2 increase in cyclophosphamide-equivalent dose exposure, the risk of spermatogenesis damage increased 1.52-fold and that of Leydig cell failure increased 1.34-fold, whereas the risk of premature ovarian insufficiency increased 1.80-fold. About 30% of those males who developed Leydig cell failure did so more than five years after the end of treatments. CONCLUSIONS: Gonadal dysfunction is still a significant late effect of therapies for pediatric hematologic malignancies. In males, the reevaluation of Leydig cell function may be useful even several years after the exposure to gonadotoxic treatments.

No Child Should Be Left Behind by COVID-19: A Report about the COVID-19 Pandemic Experience in Children and Adolescents with Acute or Chronic Disease Treated at a Pediatric Referral Hospital in Italy.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) was undoubtedly a stressful experience for everyone. General opinion believed that children with acute or chronic illness could experience additional burden, but this is not confirmed. The aim of this study is to understand how children and adolescents already suffering from acute or chronic illness (e.g., cancer, cystic fibrosis, neuropsychiatric disorders) feel about the COVID-19 pandemic, and if the experience is significantly different between these children and children without illness. METHODS: Children and adolescents affected by acute or chronic illness (named the "fragile group") treated at the Regina Margherita Children Hospital in Italy, were enrolled in the study by filling a questionnaire about their pandemic experiences. Also, a group of children and adolescents without acute or chronic illness (named the "low-risk group") recruited in the emergency department of the hospital, participated in the study in order to compare experiences. RESULTS: The study group was composed of 166 children and adolescents (Median age = 12 yrs; 78% fragile group, 22% low-risk group). Participants experienced a general state of fear of the virus and of a potential infection for both themselves and their families, while feelings and thoughts that interfere with daily functioning were less frequent. The fragile group seems to be more resilient towards the pandemic situation than low-risk group and some differences on the basis of the type of illness were found in the fragile group. CONCLUSIONS: Dedicated psychosocial intervention must be proposed in order to support fragile children and adolescents' well-being during the pandemic, also on the basis of their clinical and mental history.

Emotional Distress, Self-Management Skills, and Expectations Among Adolescents and Young Adult Childhood Cancer Survivors in Transition from Pediatric to Adult Care: A Brief Report.

The transition from pediatric to adult care poses several emotional and personal challenges to adolescents and young adult (AYA) childhood cancer survivors (CCSs), which need attention to avoid the risk of nonadherence and medical dropout. This brief report describes the condition of AYA-CCSs at the moment of transition in terms of emotional state, personal autonomy, and expectations regarding future care. The results provide insights for clinicians dealing with survivorship care, to enhance AYA-CCSs emotional resilience and to support them in being in charge of their health, thus facilitating their transition to adulthood.

The Creation of a Transition Protocol Survey for Childhood, Adolescent, and Young Adult Cancer Survivors in Transition from Pediatric to Adult Health Care in Italy.

Purpose: The purpose of the study was to create in Italian a transition protocol survey to monitor the readiness of childhood, adolescent, and young adult (CAYA) cancer survivors who are undergoing transition from pediatric to adult health care. A protocol could support clinical practice through the proposal of individualized transition care pathways for CAYA survivors and inform future scientific studies that focus on barriers to successful transition. Methods: Three international questionnaires that investigate the biopsychosocial issues and needs of survivors were subjected to the Forward and Backward Translation process. Following this, CAYA survivors were recruited from September 2019 to August 2020 in the pediatric oncology centers of the Interregional Pediatric Oncology Network of Piedmont and the Aosta in Italy to participate in cognitive interviews as part of the validation and cultural adaptation process of the questionnaires, which will form the transition protocol survey. Results: Revisions and cognitive interviews with 40 CAYA survivors identified any inadequate expressions and resolved any concepts of misunderstanding or cultural unsuitability for the Italian translation. Overall, they found the scales to be easily understandable, and an Italian version of the scales was produced to create the final transition protocol survey. Conclusion: The transition protocol survey might be used as a valid tool to highlight critical issues to support sustainable transition processes between Italian oncology centers. The protocol can be implemented into clinical practice thus offering CAYA the possibility of resolving some needs, receiving personalized support, and surveillance before the transition.

Employment among Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

To date, there are heterogeneous studies related to childhood cancer survivors' (CCS) employment rates. Given the importance of this topic, we aimed to perform a systematic review and meta-analysis to investigate the prevalence of employment among CCS and to examine its association with socio-demographic and clinical factors. We followed the PRISMA guidelines to search for pertinent articles in relevant electronic databases. Eighty-nine articles comprising 93 cohorts were included. The overall prevalence of employment was 66% (CI: 95% 0.63-0.69). Subgroup meta-analyses showed that lower rates were found for central nervous system tumor survivors (51%, CI: 95% 0.43-0.59), and for CCS treated with cranial-radiotherapy (53%, CI: 95% 0.42-0.64) or haematopoietic stem-cell transplantation (56%, CI: 95% 0.46-0.65). The studies conducted in Asia highlighted employment rates of 47% (CI: 95%, 0.34-0.60). Univariate meta-regressions identified the following socio-demographic factors associated with higher rates of employment: a female gender (p = 0.046), a higher mean age at the time of investigation (p = 0.00), a longer time since diagnosis (p = 0.00), a higher educational level (p = 0.03), and a married status (p = 0.00). In conclusion, this systematic review and meta-analysis provides evidence that two-thirds of CCS are employed worldwide. Identifying vulnerable groups of CCS may allow for the design of multidisciplinary support strategies and interventions to promote employment in this population.

Work Placement and Job Satisfaction in Long-Term Childhood Cancer Survivors: The Impact of Late Effects.

Late effects of cancer and its treatments during childhood or adolescence can impact work placement and increase the risk of unemployment. The aim of this study is to describe the work placement and the perceived job and economic satisfaction of long-term childhood cancer survivors (CCS). Jobs have been categorized according to the International Standard Classification of Occupations version 08 (ISCO-08), and satisfaction has been evaluated through the Satisfaction Profile (SAT-P). Out of 240 CCS (female = 98) included: 53 were students, 46 were unemployed and 141 were employed. Within unemployed survivors, 89.13% were affected by late effects (n = 41). The presence of at least one severe late effect was significantly associated with the probability of unemployment (OR 3.21; 95% CI 1.13−9.12, p < 0.050), and having any late effect was inversely related to the level of satisfaction of the financial situation of unemployed CCS (b −35.47; 95% CI −59.19, −11.74, p = 0.004). Our results showed that being a survivor with severe comorbidities has a significantly negative impact on occupation and worsens the perception of satisfaction of economic situations. Routinary follow-up care of CCS should include the surveillance of socioeconomic development and provide interventions, helping them to reach jobs suitable for their health.

Distress, anxiety, depression and unmet needs in thyroid cancer survivors: a longitudinal study.

PURPOSE: Despite a good prognosis, thyroid cancer (TC) survivors often report psychological distress and decreased quality of life. This longitudinal study aims to evaluate TC survivors' levels of distress, anxiety, depression and unmet needs, checking potential life events. METHODS: Distress Thermometer, Hospital Anxiety Depression Scale, Supportive Care Need Survey (short form) and Interview for Recent Life Events were administered to 73 TC survivors (T0) and 44 of them were re-tested one year later (T1). Participants were at 0-5, 5-10 or >10 years from the end of their cancer-related treatments. RESULTS: At T0, distress, anxiety and depression mean scores were 6.4, 6.8 and 5.3, while at T1 they were 5.5, 4.8 and 5.1. Only anxiety scores decreased significantly between T0 and T1. 50.7% of patients had unmet psychological needs at T0 and 50.0% at T1. Most participants were satisfied in the communicative/ informative (T0:79.5%; T1: 77.3%) and social/health care areas (T0:74.0%; T1:75.0%). The most experienced stressful events detected concerned their working areas. CONCLUSIONS: Results confirmed that patients reported distress, anxiety and depression concerns even many years after the end of treatments. Both medical and psychological surveillance are relevant to improving TC survivors' wellbeing.

Impact of Allogeneic Stem Cell Transplantation on Testicular and Sexual Function.

High-dose chemotherapy and radiotherapy, administered as a conditioning regimen before stem cell transplantation, are known to negatively impact testicular function and sexuality. However, to date, only a few studies have simultaneously analyzed the real prevalence of these complications in this clinical setting. Therefore, this study aimed to assess the prevalence of testicular dysfunction and sexual impairment in a cohort of males who underwent allogeneic stem cell transplantation in adulthood. This observational, cross-sectional, single-center study consecutively enrolled 105 subjects on outpatient follow-up. Testicular function and sexuality were evaluated through a hormonal profile (testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B) and the IIEF-15 questionnaire, respectively. We found a higher prevalence of hypogonadism (21%), impaired spermatogenesis (87%), and erectile dysfunction (72%) compared with the general population. Chronic graft-versus-host disease, especially of moderate/severe grade, was associated with an increased risk of developing erectile dysfunction (odds ratio, 6.338). Moreover, a high proportion of patients presented with alterations in all domains of sexual function, even after complete clinical remission of hematologic disease. Our data confirm both testicular function and sexuality alterations as frequent complications after allogeneic stem cell transplantation. A multidisciplinary approach is advisable for early diagnosis and adequate treatment.

Optimal Delivery of Follow-Up Care After Allogeneic Hematopoietic Stem-Cell Transplant: Improving Patient Outcomes with a Multidisciplinary Approach.

The increasing indications for allogeneic stem-cell transplant in patients with hematologic malignancies and non-malignant diseases combined with improved clinical outcomes have contributed to increase the number of long-term survivors. However, survivors are at increased risk of developing a unique set of complications and late effects, besides graft-versus-host disease and disease relapse. In this setting, the management capacity of a single health-care provider can easily be overwhelmed. Thus, to provide appropriate survivorship care, a multidisciplinary approach for the long-term follow-up is essential. This review aims at summarizing the most relevant information that a health-care provider should know to establish a follow-up care plan, in the light of individual exposures and risk factors, that includes all organ systems and considers the psychological burden of these patients.