Influence of Body Mass Index, Cancer Type and Treatment on Long-Term Metabolic and Liver Outcomes in Childhood Cancer Survivors.

In the last decade, the survival of subjects affected by cancer in childhood has significantly improved. The increased lifespan of childhood cancer survivors (CCS) led to a greater risk for long-term, therapy-related morbidity. To identify the clinical predictors of metabolic adverse outcomes in CCS (average off-therapy period: 12 years), we recruited 126 survivors of different childhood cancers (86.5% hematological cancers) who received at least anticancer chemotherapy, consecutively approached during their annual oncohematological outpatient visit. At examination, anthropometric measures and cancer-related history were collected. Moreover, a fasting venous sample was carried out for measuring fasting plasma glucose and insulin, glycated hemoglobin, lipid panel, and transaminases. We calculated the indexes of insulin resistance (HOMA-IR, McAuley, and QUICKI) and secretion (HOMA-ß), liver steatosis (Hepatic Steatosis Index) and fibrosis (FIB-4 and NAFLD fibrosis score), and visceral fat dysfunction (Visceral Adiposity Index). More than one-third of the subjects (37.3%) did not have normal weight, with 11.1% of them affected by obesity. At recruitment, obese subjects were at significantly higher risk for impaired fasting glucose, metabolic syndrome, visceral adipose dysfunction, and liver steatosis/fibrosis. Subjects who received bone marrow transplantation were prone to insulin resistance, while survivors of lymphoma presented a visceral adipose dysfunction These results suggest a carefully metabolic monitoring of CCS, particularly in subgroups at higher risk, to early detect these conditions, promptly begin therapeutic interventions, and mitigate the dysmetabolic-related health burden.

Preserved Long-Term Lung Function in Young Adult Survivors of Common Childhood and Adolescence Malignancies.

Purpose: We aimed to evaluate long-term lung function and respiratory outcomes in young adults who survived common pediatric malignancies, treated in a single center. Methods: We enrolled young adults who had been treated during their childhood or adolescence for hematological or solid cancer at our Pediatric Oncology Unit, and performed pulmonary function tests (PFT) and clinical evaluation. PFT included spirometry and Diffusing Capacity of Lung for Carbon Monoxide (DLCO). Results: We included 121 survivors, mean age 23 years at follow-up, median 15 years from diagnosis. The most common diagnoses were hematological malignancies, mainly acute lymphoblastic leukemia, whereas 31% of the patients were treated for nonhematological cancer, mainly neuroblastoma. Treatments consisted of chemotherapy alone or in combination with radiotherapy and/or hematopoietic stem cell transplantation. Most of the patients denied respiratory symptoms throughout the years. In the whole group only eight patients (6%) had abnormal PFT, consisting mainly in a restrictive pattern and reduced DLCO. PFT abnormalities were of mild degree in most of the cases. Overall, the mean values of forced vital capacity, forced expiratory volume in 1 second, and DLCO were normal, but lower in females, in those who received radiotherapy and in those treated for lymphoma. Conclusion: In a group of young adults, surviving the most common childhood malignancies, we found a preserved lung function after a median follow-up of 15 years. The constantly increasing survival in childhood cancer is now associated with a trend toward an improvement in long-term respiratory outcomes.

Risk of Benign and Malignant Thyroid Disorders in Subjects Treated for Paediatric/Adolescent Neoplasia: Role of Morphological and Functional Screening.

BACKGROUND: Patients treated for paediatric/adolescent (P/A) neoplasia have a high incidence of both benign and malignant thyroid diseases. Given the high incidence of sequelae, literature data show a clinical benefit of morpho-functional thyroid screening in paediatric/adolescent cancer survivors and a careful lifetime follow-up. PATIENTS AND METHODS: The incidence of thyroid alterations was evaluated in a consecutive series of 343 patients treated with chemotherapy (CHE) and radiotherapy (RTE) or only with CHE for P/A tumours between 1976 and 2018 (mean age at time of primary paediatric malignancy 7.8 ± 4.7 years). All patients underwent thyroidal morpho-functional evaluation between 2000 and 2019. RESULTS: 178 patients (51.9%) were treated only with CHE and 165 (48.1%) with CHE+RTE. A functional and/or structural thyroid disease was diagnosed in 147 (42.5%; 24.2% in CHE and 62.4% in CHE+RTE group; p = 0.0001). Of note, 71 (20.7%) patients with no evidence of disease at first evaluation developed a thyroid alteration during the follow-up. Primitive hypothyroidism was diagnosed in 54 patients (15.7%; 11.2% in CHE vs. 20.6% in CHE+RTE group; p = 0.01) and hyperthyroidism in 4. Sixty-three patients developed thyroid nodules (18.4%; 4.0% in CHE and 14.1% in CHE+RTE group; p < 0.001); thyroid cancer was diagnosed in 30 patients (8.7%; 4.5% in CHE and 12.4% in CHE + RTE group; p = 0.007). CONCLUSIONS: In patients treated with CHE+RTE, the prevalence of hypothyroidism and nodular pathology, both malignant and benign, were significantly greater than in patients treated with CHE. However, also in the CHE group, the frequency of thyroid disease is not negligible and the pathogenetic mechanisms remain to be clarified. Our data suggest the clinical benefit of morpho-functional thyroid screening in P/A cancer survivors.

Self- and Parent-Reported Psychological Symptoms in Young Cancer Survivors and Control Peers: Results from a Clinical Center.

Pediatric cancer survivors are at increased risk for psychological distress. We sought to understand the severity and symptoms' co-occurrence among pediatric survivors compared to controls by rating both self- and parent-reported symptomatology. Forty survivors (22 males; mean age at study time: 12.9 years) participated in the study. Most survivors (85%) had a diagnosis of acute lymphoblastic leukemia. Seventy-nine healthy controls with the same age and gender distribution as the patients were included. A standardized assessment of psychological functioning was conducted by self- and parent-reported symptoms evaluations. The self-reported anxious symptom severity was significantly higher in survivors. A significantly higher proportion of survivors compared to controls had clinically significant anxiety, depression, and combined anxiety symptoms (i.e., social anxiety, separation anxiety, or physical symptoms). In both study groups, the self-reported emotional and somatic symptoms were significantly associated. The multi-informant assessments of the psychological symptoms revealed distinct associations between the child- and parent-reported symptoms in the survivors' group: the survivors' self-reports of depressive symptoms, somatic symptoms, and functional impairment were significantly correlated with the parent reports of child behavioral concerns, somatic complaints, and functional impairment, respectively. Conclusion: Self-reported symptoms showed similar comorbidity profiles in survivors and control peers. The multi-informant assessments detected differences in the association of self- and parent-reported symptoms between the survivor and control groups. The present study showed that multi-informant assessment is critical to understanding symptom profiles and to informing intervention with particular regard to parental participation and support.

Lung clearance index: A new measure of late lung complications of cancer therapy in children.

INTRODUCTION: Childhood cancer survivors (CSs) might face an increased lifelong risk of lung function impairment. The lung clearance index (LCI) has been described as being more sensitive than spirometry in the early stages of some lung diseases. The aim of this study was to evaluate this index in a cohort of patients with a history of childhood cancer for the first time. MATERIALS AND METHODS: We evaluated 57 off-treatment CSs aged 0-18 years old and 50 healthy controls (HCs). We used the multiple-breath washout method to study LCI and spirometry. RESULTS: CSs did not show any differences from the controls in ventilation homogeneity (LCI 6.78 ± 1.35 vs. 6.32 ± 0.44; p: not significant [ns]) or lung function (FEV1 99.9 ± 11.3% vs. 103.0 ± 5.9% of predicted; p: ns; FVC 98.2 ± 10.3% vs. 101.1 ± 3.3% of predicted). LCI significantly correlated with the number of years since the last chemotherapy (r = .35, p < .05). CONCLUSIONS: Our study describes the trend of LCI in a cohort of CSs and compares it with the results obtained from HCs. The results show that patients maintain both good values of respiratory function and good homogeneity of ventilation during childhood. Moreover, as LCI increases and worsens as the years pass after the end of the treatment could identify the tendency toward pulmonary fibrosis, which is typical of adult CSs, at an earlier time than spirometry.

Testicular Function of Childhood Cancer Survivors: Who Is Worse?

BACKGROUND: A multi-disciplinary approach has led to an improvement in prognosis of childhood cancers. However, in parallel with the increase in survival rate, there is a greater occurrence of long-term toxicity related to antineoplastic treatment. Hypogonadism and infertility are among the most frequent endocrinological sequelae in young adult childhood cancer survivors. The aim of this study was to identify which category of patients, grouped according to diagnosis, therapy, and age at treatment, shows the worst reproductive function in adulthood. METHODS: We evaluated morpho-volumetric development of the testis, endocrine function of the hypothalamic-pituitary-gonadal axis, and sperm parameters in 102 young adult childhood cancer survivors. RESULTS: Overall, about one-third of patients showed low total testicular volume, total testosterone (TT) <3.5 ng/mL, and altered sperm count. Hodgkin's disease, hematopoietic stem cell transplantation, and non-cranial irradiation associated to chemotherapy were risk factors for poor gonadal function. Patients treated in pubertal age showed lower total testicular volume; however, the difference was due to more gonadotoxic treatment performed in older age. Testicular volume was more predictive of spermatogenesis than follicle-stimulating hormone (FSH), while anti-Müllerian hormone (AMH) was not useful in the evaluation of testicular function of male childhood cancer survivors. CONCLUSIONS: Pre-pubertal subjects at high risk of future infertility should be candidates for testicular tissue cryopreservation.

"Feasible and effective administration of Bortezomib with Rituximab in children with relapsed/resistant B-cell precursor acute lymphoblastic leukemia (BCP-ALL): A step toward the first line".

Despite a high cure rate in childhood BCP-ALL, 20% of children still presents with relapse, mostly due to a persistent leukemic clone during the first-line treatment. In this context, obtaining a molecular remission is crucial for reaching a successful allogeneic hematopoietic stem cell transplantation. Bortezomib was effectively administered to children with resistant/relapsed (r/r) BCP-ALL. Moreover, high risk ALL is characterized by the increasing expression of CD20. For the first time we reported two children with r/r BCP-ALL who received a treatment schema including Bortezomib and Rituximab, achieving morphological and molecular remission. Children with high risk features, such as persistent minimal residual disease during induction, will benefit from this combination. Is it time to move toward the first line?

General anesthesia, conscious sedation, or nothing: Decision-making by children during painful procedures.

BACKGROUND: Following diagnosis, children with cancer suddenly find themselves in an unknown world where unfamiliar adults make all the important decisions. Children typically experience increasing levels of anxiety with repeated invasive procedures and do not adapt to the discomfort. The aim of the present study is to explore the possibility of asking children directly about their medical support preferences during invasive procedures. PROCEDURE: Each patient was offered a choice of medical support on the day of the procedure, specifically general anesthesia (GA), conscious sedation (CS), or nothing. An ad hoc assessment tool was prepared in order to measure child discomfort before, during, and after each procedure, and caregiver adequacy was measured. Both instruments were completed at each procedure by the attending psychologist. RESULTS: We monitored 247 consecutive invasive procedures in 85 children and found that children in the 4 to 7 year age group showed significantly higher distress levels. GA was chosen 66 times (26.7%), CS was chosen 97 times (39.3%), and nothing was chosen 5 times and exclusively by adolescents. The child did not choose in 79 procedures (32%). The selection of medical support differed between age groups and distress level was reduced at succeeding procedures. CONCLUSIONS: Offering children the choice of medical support during invasive procedures allows for tailored support based on individual needs and is an effective modality to return active control to young patients, limiting the emotional trauma of cancer and treatment.

Triptorelin for Fertility Preservation in Adolescents Treated With Chemotherapy for Cancer.

BACKGROUND: Triptorelin, a gonadotropin releasing hormone analogue, can be administered to postpubertal female individuals with cancer who receive chemotherapy to obtain menstrual suppression and decrease the risk of hemorrhage caused by thrombocytopenia. Our goal was to assess whether triptorelin also has a protective role against the gonadotoxicity of chemotherapy. PATIENTS AND METHODS: This retrospective observational study includes all postmenarchal female patients who presented to our Unit from 2000 to 2015 and received chemotherapy for cancer. They were administered depot triptorelin. We evaluated long-term ovarian function in order to detect clinical signs of ovarian damage, miscarriages, and pregnancies. Laboratory follow-up consisted in dosing serum follicle stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone. Ultrasound of the ovaries was performed as well. RESULTS: Of 36 evaluable patients, 9 received hematopoietic stem cell transplantation (HSCT). The remaining 27 patients maintained normal ovarian function at clinical, laboratory, and ultrasound assessment. Five of them achieved spontaneous physiological pregnancy. Four of the 9 patients who underwent HSCT developed premature ovarian failure. CONCLUSION: Our study suggests that gonadotropin releasing hormone-a administered during chemotherapy can prevent premature ovarian failure in patients treated without HSCT and that it is not enough to preserve the ovarian function during HSCT. Hence, a prospective randomized trial with a larger population would be recommended.

Successful Treatment of a Very Late Isolated Relapse in an Adolescent With a PICALM-MLLT10 Positive T-lineage Acute Lymphoblastic Leukemia.

T-lineage ALL is an aggressive disease that needs to be treated with intensive treatment schedules. A late relapse rarely occurs and a clear choice for second-line treatment is on debate. We report on a young adult with a very late isolated extramedullary relapse of PICALM-MLLT10 positive T-ALL, successfully treated with a chemotherapy-based and radiotherapy-based pediatric protocol. We demonstrate that relapse can occur in T-ALL although a SR-MRD behavior treated with a high-risk protocol; specific molecular diagnostic aberrations, as PICALM-MLLT10, are still conserved at very late relapse; a second-line treatment based on pediatric protocol can be effective.