Quality-of-life evaluations in children and adolescents with Ewing sarcoma treated with pencil-beam-scanning proton therapy.

BACKGROUND With improved survival rates for children with cancer, quality-of-life (QoL) issues have increasingly become the focus of attention. We report the QoL of children with Ewing sarcoma (EWS) treated with pencil-beam-scanning proton therapy (PT). METHODS A PEDQOL (QoL questionnaire for children 4-18 years) self/proxy questionnaire was used to prospectively assess the QoL of 23 children <18 years with EWS treated with PT. This questionnaire evaluates eight different domains. Children (self-rating) and parents (proxy-rating) filled out the questionnaire at the start of PT (E1), 2 months after treatment (E2), and thereafter once yearly (E≥3). RESULTS Compared with healthy controls, parents rated the QoL of their children at E1 significantly worse in all but two (cognition and social functioning-family) domains. At E4, significant differences between the two groups only remained in three of eight domains. At E1, children self-rated their QoL significantly worse in the domain Physical functioning (p = .004) and significantly better in the domain Body image (p = .044) compared to healthy controls, whereas no significant differences were observed at E4. For the longitudinal comparison E1 versus E4, according to parents, Emotional functioning, Cognition and Social functioning-peers were slightly decreased 2 years after PT. The children rated Emotional functioning and Body image poorly 2 years after PT. CONCLUSIONS Children with EWS usually recovered seemingly well to normal QoL levels 2 years after the end of PT. They tended to rate their QoL substantially higher than their parents. However, in the longitudinal analysis at 2 years, children rated their Emotional functioning and Body image scores poorly

Posterior hypothalamus-sparing surgery improves outcome after childhood craniopharyngioma

Objective: Quality of life (QoL) is frequently impaired in childhood-onset craniopharyngioma (CP) by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or surgical hypothalamic lesions (HL) determine outcome, is controversial. Design: Survival and outcome of CPs recruited between 2007 and 2014 in KRANIOPHARYNGEOM 2007 were analyzed with regard to reference-confirmed presurgical HI and surgical HL. Methods: Radiological findings, BMI and QoL were assessed at diagnosis and during follow-up. QoL was assessed using Pediatric Quality of Life (PEDQOL) questionnaire. Results: One hundred sixty-nine CPs were included presenting with no HI (n = 11), anterior (n = 49) and anterior + posterior (a + p) HI (n = 109) prior to surgery. The latter 109 were analyzed for postoperative HL (no lesion: n = 23, anterior HL: n = 29, a + pHL: n = 57). Progression-free survival (PFS) was higher after complete resection. The highest PFS was observed in CP with a + pHL, especially when compared between non-irradiated subgroups (P = 0.006). Overall survival (OS) rates were 1.0 in all subgroups. CP with a + pHL developed higher BMI (P ≤ 0.001) during follow-up compared between subgroups. 55/109 pts with a + pHI completed PEDQOL at diagnosis (48/109 at 3 years follow-up). QoL was worse for a + pHL patients in terms of physical, social and emotional functionality when compared with the anterior HL and no HL subgroup. BMI development and QoL during follow-up were similar for patients with anterior HL and without HL. Conclusions: Posterior hypothalamus-sparing surgical strategies are associated with higher QoL, decreased development of obesity and lower PFS in CP

Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy

The aim of this analysis was to assess the early clinical results of pencil beam scanning proton therapy (PT) in the treatment of young children with non-metastatic atypical teratoid/rhabdoid tumor (ATRT) of the CNS. Fifteen children (male, n = 8, 53 %) were treated with PT between May 2008 and January 2013. Mean age at diagnosis was 17.4 ± 7.0 months. The localization was infratentorial in 9 (60 %) patients. Gross total resection of the primary tumors was achieved in 7 (47 %) patients. The dose administered focally under sedation was 54 Gy (RBE). After a median follow-up of 33.4 months (range 9.7-69.2), 3 (20 %), 4 (27 %) and 2 (13 %) patients presented with local failure (LF), distant brain failure (DBF) and spinal failure (SF), respectively. Six patients died, all of tumor progression. The 2-year overall- and progression-free survival was 64.6 and 66.0 %. Tumor location (supratentorial) and the extent of surgical resection (non-gross total resection) were negative prognostic factors for both OS and PFS. PT was well tolerated. No grade >2 acute toxicity was observed. The estimated 2-year toxicity-free survival was 90 %. As assessed by the PedsQoL proxy, no decrease in QoL was observed after PT. We conclude that PBS PT is an effective treatment for young children with ATRT. After PT, with or without concomitant chemotherapy, two third of the patients survived >2 years. Acute toxicity was manageable. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and treatment-induced toxicity

Epidemiology and Characteristics of Gastric Carcinoma in Childhood : An Analysis of Data from Population-Based and Clinical Cancer Registries

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz–Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments

Health outcomes in offspring born to survivors of childhood cancers following assisted reproductive technologies

Purpose: An increasing number of childhood cancer survivors are using assisted reproductive technologies (ART) to overcome treatment-related fertility impairment. We report perinatal and health outcomes of offspring born to survivors following ART. Methods: The FeCt Multicenter Offspring Study surveyed the health of offspring of childhood cancer survivors. Health outcomes in offspring born to survivors following ART (n = 57, 4.6%) or after spontaneous conception (n = 1182) were assessed in the German cohort (n = 1239) using bivariate analysis. Findings were put into the context of the general German population by health outcome assessment in 1:1 matched-pair analysis (n = 2478). Results: Nearly twice the survivors used ART compared with numbers reported for the German general population (4.6% vs. 2.6%). Successful pregnancies were achieved after a median of two cycles, mainly using non-cryopreserved oocytes/sperm. Multiple sibling births (p < 0.001, 28.1% vs. 3.0%) and low birth weight (p = 0.008; OR = 2.659, 95% CI = 1.258-5.621) occurred significantly more often in offspring born to survivors who utilized ART than spontaneously conceived children, whereas similar percentages were born preterm or too small for their gestational age. ART did not increase the prevalence of childhood cancer or congenital malformations in offspring born to survivors. Conclusion: ART use by childhood cancer survivors was successful with both fresh and cryopreserved oocytes/sperm, and did not influence perinatal health or health outcomes when known confounders were taken into account. Implications for cancer survivors: Oncofertility is an important component of patient care. Our study implicates that the utilization of ART by adult survivors of childhood cancer does not put offspring at additional risk for adverse perinatal or health outcomes

Auditory complications among childhood cancer survivors and health-related quality of life: a PanCareLIFE study.

PURPOSE Auditory complications are potential side effects from childhood cancer treatment. Yet, limited evidence exists about the impact of auditory complications-particularly tinnitus-on health-related quality of life (HRQoL) among childhood cancer survivors (CCS). We determined the prevalence of hearing loss and tinnitus in the European PanCareLIFE cohort of CCS and examined its effect on HRQoL. METHODS We included CCS from four European countries who were diagnosed at age ≤ 18 years; survived ≥ 5 years; and aged 25-44 years at study. We assessed HRQoL (Short Form 36), hearing loss, and tinnitus using questionnaires. We used multivariable linear regression to examine associations between these two auditory complications and HRQoL adjusting for socio-demographic and clinical factors. RESULTS Our study population consisted of 6,318 CCS (53% female; median age at cancer diagnosis 9 years interquartile range [IQR] 5-13 years) with median age at survey of 31 years (IQR 28-35 years). Prevalence was 7.5% (476/6,318; confidence interval [CI]: 6.9-8.2) for hearing loss and 7.6% (127/1,668; CI: 6.4-9.0) for tinnitus. CCS with hearing loss had impaired physical (coefficient [coef.] -4.3, CI: -7.0 to -1.6) and mental (coef. -3.2, CI: -5.5 to -0.8) HRQoL when compared with CCS with normal hearing. Tinnitus was associated with impaired physical (coef. -8.2, CI: -11.8 to -4.7) and mental (coef. -5.9, CI: -8.8 to -3.1) HRQoL. CONCLUSION We observed reduced HRQoL among CCS with hearing loss and tinnitus. Our findings indicate timely treatment of hearing loss and tinnitus may contribute to quality of life of survivors. IMPLICATIONS FOR CANCER SURVIVORS CCS who experience auditory complications should be counseled about possible therapeutic and supportive measures during follow-up care

Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol

Background: The clinical management of ependymoma in childhood and adolescence is complex and the clinicobiopathological correlates of outcome remain poorly understood. This international SIOP Ependymoma II (SIOP EPII) trial aims to improve the outcome of patients with ependymoma. Methods: SIOP EPII includes any patient <22 years at diagnosis with ependymoma, stratified by age, tumor location, and outcome of the initial surgery. Centralized pathology and imaging is required for diagnosis confirmation. SIOP EPII included three randomized studies according to age, postoperative residue, and suitability to receive radiotherapy. Patients ineligible for interventional strata are followed-up in an observational study. The staging phase aims to determine if central neurosurgical and radiological postoperative MRI reviews increase the resection rate. Patients ≥12 months with (i) no residual disease are randomly assigned in a phase III trial to evaluate the efficacy of post-radiation 16-week chemotherapy (VEC + CDDP) on PFS (stratum I); (ii) centrally confirmed measurable inoperable residual disease are allocated to randomized frontline chemotherapy phase II study (VEC vs. VEC + high-dose methotrexate) and considered for a second-look surgery (stratum II). If second-look surgery is not feasible or tumor residuum remains, patients receive 8 Gy-boost radiotherapy after conformal radiotherapy (phase I). (iii) Patients < 12 months (18 months in the UK) or not eligible to receive radiotherapy are randomized in a phase II study to receive chemotherapy (alternated myelosuppressive and nonmyelosuppressive chemotherapy), with or without valproate (stratum III). To overcome the limitations encountered in the preliminary conclusions of the ACNS-0831 study, a SIOP EPII dedicated on-study amendment has been planned to definitively conclude the relevance of maintenance chemotherapy in stratum I. Secondary outcomes include overall survival, quality of life, neuropsychological and neuroendocrine outcomes, safety, and identification of key prognostic biomarkers (BIOMECA). Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02265770

Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma

PURPOSE: The available questionnaires for quality-of-life (QoL) assessments are age-group specific, limiting comparability and impeding longitudinal analyses. The comparability of measurements, however, is a necessary condition for gaining scientific evidence. To overcome this problem, we assessed the viability of harmonising data from paediatric and adult patient-reported outcome (PRO) measures. METHOD: To this end, we linked physical functioning scores from the Paediatric Quality of Life Inventory (PedsQL) and the Paediatric Quality of Life Questionnaire (PEDQOL) to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) for adults. Samples from the EURAMOS-1 QoL sub-study of 75 (PedsQL) and 112 (PEDQOL) adolescent osteosarcoma patients were concurrently administered both paediatric and adult questionnaires on 98 (PedsQL) and 156 (PEDQOL) occasions. We identified corresponding scores using the single-group equipercentile linking method. RESULTS: Linked physical functioning scores showed sufficient concordance to the EORTC QLQ-C30: Lin's ρ = 0.74 (PedsQL) and Lin's ρ = 0.64 (PEDQOL). CONCLUSION: Score linking provides clinicians and researchers with a common metric for assessing QoL with PRO measures across the entire lifespan of patients

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up

Background: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. Methods: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. Results: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. Discussion: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown