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.

Clinical outcomes and quality of life in children and adolescents with primary brain tumors treated with pencil beam scanning proton therapy.

BACKGROUND: Long-term treatment-related toxicity may substantially impact well-being, quality of life (QoL), and health of children/adolescents with brain tumors (CBTs). Strategies to reduce toxicity include pencil beam scanning (PBS) proton therapy (PT). This study aims to report clinical outcomes and QoL in PBS-treated CBTs. PROCEDURE: We retrospectively reviewed 221 PBS-treated CBTs aged <18 years. Overall-free (OS), disease-free (DFS), and late-toxicity-free survivals (TFS), local control (LC) and distant (DC) brain/spinal control were calculated using Kaplan-Meier estimates. Prospective QoL reports from 206 patients (proxies only ≤4 years old [yo], proxies and patients ≥5 yo) were descriptively analyzed. Median follow-up was 51 months (range, 4-222). RESULTS: Median age at diagnosis was 3.1 years (range, 0.3-17.7). The main histologies were ependymoma (n = 88; 39.8%), glioma (n = 37; 16.7%), craniopharyngioma (n = 22; 10.0%), atypical teratoid/rhabdoid tumor (ATRT) (n = 21; 9.5%) and medulloblastoma (n = 15; 6.8%). One hundred sixty (72.4%) patients received chemotherapy. Median PT dose was 54 Gy(relative biological effectiveness) (range, 18.0-64.8). The 5-year OS, DFS, LC, and DC (95% CI) were 79.9% (74-85.8), 65.2% (59.8-70.6), 72.1% (65.4-78.8), and 81.8% (76.3-87.3), respectively. Late PT-related ≥G3 toxicity occurred in 19 (8.6%) patients. The 5-year ≥G3 TFS was 91.0% (86.3-95.7). Three (1.4%) secondary malignancies were observed. Patients aged ≤3 years at PT (P = .044) or receiving chemotherapy (P = .043) experienced more ≥G3 toxicity. ATRT histology independently predicted distant brain failure (P = .046) and death (P = .01). Patients aged ≥5 years self-rated QoL higher than their parents (proxy assessment). Both reported lower social functioning and cognition after PT than at baseline, but near-normal long-term global well-being. QoL was well below normal before and after PT in children ≤4 years. CONCLUSIONS: The outcome of CBTs was excellent after PBS. Few patients had late ≥G3 toxicity. Patients aged <5 years showed worse QoL and toxicity outcomes.

Quality of Life of Patients With Osteosarcoma in the European American Osteosarcoma Study-1 (EURAMOS-1): Development and Implementation of a Questionnaire Substudy.

BACKGROUND: The quality of life (QoL) of patients with osteosarcoma (OS) may be adversely affected by the disease or its treatment. Therefore, it is important to understand the QoL of patients undergoing treatment for OS to improve the QoL. We report on the first prospective international QoL study that was embedded within a large randomized clinical trial from 4 national study groups. OBJECTIVE: This paper aimed to describe the QoL study development, methodology, accrual details, and characteristics of the QoL cohort. METHODS: A total of 2260 patients registered in the EURopean AMerican Osteosarcoma Study-1 (EURAMOS-1), of whom 97.92% (2213/2260) were eligible for the optional QoL assessment and could participate in terms of questionnaire availability. Overall, 61.86% (1369/2213) of patients and/or proxies completed the QoL evaluation at the first assessment time point (E1) after the start of preoperative treatment. The QoL measures used (self- and/or proxy reports) depending on the patient's age and national study group. Participants and nonparticipants in the ancillary QoL study were compared regarding relevant demographic and disease-related characteristics at registration in the trial. RESULTS: The participation rate at time point E1 did not differ with regard to age, gender, the occurrence of pathological fracture, or the presence of any metastases at diagnosis. No differences were found regarding the primary tumor site. Only the national study group affiliation had an influence on participation. Participation decreased linearly with trial progress up to 20% at the final time point of QoL assessment. CONCLUSIONS: This study demonstrates the feasibility of international cooperation for the purpose of assessing and understanding the QoL of pediatric and adolescent/young adult patients with cancer. Future outcomes of this QoL substudy will help to adapt interventions to improve QoL.

Health status, health-related quality of life, and socioeconomic outcome in childhood brain tumor survivors: a German cohort study.

BACKGROUND: With rising numbers of childhood cancer survivors, somatic and socioeconomic outcome as well as health-related quality of life (QoL) gain increasing relevance. Based on the first nationwide German Survey on Life Situation, State of Health, and Quality of Life of Childhood Cancer Survivors, the VIVE survey, we report the outcome of survivors of childhood brain tumors localized in the posterior fossa. METHODS: Two hundred seventy participants with a median follow-up period of 21.9 years completed a questionnaire on socioeconomic and somatic late effects as well as a standardized QoL questionnaire (European Organisation for Research and Treatment of Cancer QLQ-C30). Comparisons were performed between World Health Organization (WHO) grades I-II, WHO grades III-IV brain tumor survivors (BTS), and the general population adjusting for potential confounders. RESULTS: The socioeconomic and QoL results of WHO grades I-II BTS were largely comparable to the general population, while grades III-IV BTS were at higher risk for significantly worse outcomes. Of WHO grades III-IV BTS, 36.8% were still living with their parents or in assisted living facilities compared with 16.1% of grades I-II BTS and 7.8% of the age-adjusted general population. Of grades III-IV BTS, 60.8% achieved at least an intermediate school degree in comparison to 80.5% of grades I-II BTS and 75.6% of the general population. Grades III-IV BTS developed up to 2 times more somatic late effects than survivors of grades I-II tumors. CONCLUSION: Derived from a large and homogeneous cohort, these results stress the importance of an appropriate follow-up period focusing not only on physical aspects but encompassing the entire living situation to allow patient-tailored support.

Quality of life in long-term survivors following treatment for Hodgkin's disease during childhood and adolescence in the German multicentre studies between 1978 and 2002.

PURPOSE: The purpose of this study was to cross-sectionally assess quality of life (QoL) in survivors of childhood Hodgkin's disease (HD) in a cohort treated for HD in the successive German-Austrian therapy studies HD-78, HD-82, HD-85, HD-87, HD-90, HD-95, respectively, in accordance with the HD-Interval-Treatment recommendation between 1978 and 2002. PATIENTS AND METHODS: Data from QoL questionnaires were provided by 1,202 (66 %) of 1,819 invited survivors. These included the EORTC QLQ-C30 and socio-demographic variables. Data of a homogenous sub-sample (n = 725) defined by age (21-41 years) and event- free-survival (no progress, relapse or secondary malignancies) were compared to an age-adjusted German reference sample (n = 659). RESULTS: While the global and physical QoL scores were comparable to those of the general population, survivors' mean scores were more than 10 points lower on the EORTC QLQ-C30 scales "Emotional" and "Social Functioning". On the symptom scales, higher mean scores, exceeding 10 points, were obtained for the scales "Fatigue" and "Sleep". In general, there was a gender effect showing lower functioning and higher symptom levels in women, most prominently in the group of young women (21-25 years). The results within the group of HD survivors could not be associated with the time since treatment, the age of HD survivors at diagnosis or the extent of therapy burden. CONCLUSION: Clinicians engaged in follow-up care should be sensitive to aspects of fatigue and related (emotional) symptoms in HD childhood cancer survivors and encourage their patients to seek further support if needed.

Brain metastases during follow-up of children and adolescents with extracranial malignant germ cell tumors: risk adapted management decision tree analysis based on data of the MAHO/MAKEI-registry.

BACKGROUND: The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important. PROCEDURE: We analyzed 900/2,160 patients from the German MAHO/MAKEI registry on children and adolescents with malignant extracranial GCT (pure teratomas (grade 0-3) were not included). For follow-up evaluation, patients with brain metastases at diagnosis and those with a follow-up shorter than 32 months after diagnosis (longest interval to brain metastases in our cohort) were excluded. Patients were censored at detection of brain metastases or death due to other causes. A decision tree analysis considering age, gender, site of primary tumor, and presence of other metastases at diagnosis as risk factors for brain metastases was performed. RESULTS: Among 838 eligible patients, 9 acquired brain metastases during follow-up, accounting for death in 5. There were no brain metastases in absence of extracranial metastases at diagnosis. If extracranial metastases were detected in absence of mediastinal mGCT the risk for brain metastases was 1.2% (95% CI: 0.2-3.5.%). In contrast, risk was increased to 37.5 (95% CI 15.2-64.6%) in patients with mediastinal GCTs and extracranial metastases. CONCLUSION: A high-risk subgroup is detected with a decision tree analysis approach. These patients may benefit from an intensified chemotherapy. Close surveillance for CNS-metastases is warranted in this high-risk group while less close monitoring in low-risk patients is justified. Pediatr Blood Cancer 2013;60:217-223. © 2012 Wiley Periodicals, Inc.

Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up.

BACKGROUND: Hypothalamic obesity has major impact on prognosis and quality of life (QoL) in childhood craniopharyngioma. PATIENTS AND METHODS: For this study, 120 patients were prospectively recruited during 2001 and 2007 and evaluated after 3 years of follow-up (KRANIOPHARYNGEOM 2000). Body mass index (BMI) and QoL at diagnosis and 36 months after diagnosis were analysed based on the reference assessment of tumour localisation and post-surgical hypothalamic lesions. Treatment was analysed based on the neurosurgical strategy of 50 participating neurosurgical centres, the centre size based on the patient load. RESULTS: BMI SDS at diagnosis was similar in patients with or without hypothalamic involvement. Surgical lesions of anterior and posterior hypothalamic areas were associated with higher increase in BMI SDS during 36 months post-diagnosis compared with patients without or only anterior lesion (+1.8 BMISD, P=0.033, +2.1 BMISD; P=0.011), negative impact on QoL in patients with posterior hypothalamic lesions. Surgical strategies varied among the 50 neurosurgical centres (three large-sized, 24 middle-sized and 23 small-sized centres). Patients treated in small-sized centres presented with a higher rate of hypothalamic involvement compared with those treated in the middle- and large-sized centres. Treatment in large-sized centres was less radical, and the rates of complete resection and hypothalamic surgical lesions were lower in large-sized centres than those of the middle- and small-sized centres. However, a multivariable analysis showed that pre-operative hypothalamic involvement was the only independent risk factor for severe obesity (P=0.002). CONCLUSIONS: Radical neurosurgical strategies leading to posterior hypothalamic lesions are not recommended due to the potential to exacerbate hypothalamic obesity and impaired QoL. Treatment should be confined to experienced multidisciplinary teams.

Germ cell tumors of the head and neck: report from the MAKEI Study Group.

BACKGROUND: Germ cell tumors (GCTs) of the head and neck region are rare but may pose significant problems for perinatal management as well as surgical and adjuvant therapy. PROCEDURE: Thirty-two prospectively reported patients from the German MAKEI studies (Maligne Keimzelltumoren) were analyzed with regard to perinatal management and long-term survival. RESULTS: Twenty-three tumors were diagnosed around birth and four during the first 3 months of life. All were primarily diagnosed as teratomas, but in two tumors, yolk sac tumor (YST) foci were identified. Another pure teratoma was diagnosed at 12 months. Four tumors were diagnosed after the first year of life and showed YST as leading histology. Most neonates presented with huge tumors causing external airway obstruction. All tumors were resected (complete resection, 16/26 patients with complete surgical information; incomplete resection, 10/26 patients). Eight tumors including five of six YSTs were treated with chemotherapy. In total, six patients relapsed. Relapse rate was higher after incomplete (5/10 patients) than after complete resection (1/16 patients). Accordingly, more relapses were observed in pharyngeal than in neck tumors due to incomplete resection. Nevertheless, half of the patients with incomplete resection remained in remission. One patient with YST died after multiple relapses. CONCLUSIONS: GCTs of the head and neck region require a multidisciplinary approach in specialized centers. Most patients with antenatal tumor growth are identified by ultrasound and delivered preterm by cesarian section. After delivery, immediate intubation and ventilation aim for respiratory stabilization, followed by elective resection. With this approach, outcome was favorable.

Epidemiologic analysis of 1,442 children and adolescents registered in the German germ cell tumor protocols.

BACKGROUND: Germ cell tumors (GCTs) constitute a heterogeneous group of tumors that significantly vary with respect to their clinical presentation and biology. The objective of this analysis was to analyze a large population-based pediatric cohort of GCTs and to evaluate the parameters age, sex, site of the tumor, histology, and potential correlations between these parameters. PROCEDURE: Between 1981 and 2000, 1,442 patients were prospectively enrolled onto the German protocols for testicular and non-testicular GCTs. Tumors were histologically classified according to the WHO. RESULTS: We observed a bimodal age distribution with a first peak during infancy and a second after the onset of puberty. At birth, almost all tumors were teratomas, sometimes with microfoci of yolk sac tumor, which on the other hand, was the predominant histology during childhood. After the onset of puberty, germinomatous GCTs represented the most frequent histological subtype, and malignant non-germinomatous GCTs often presented as mixed tumors with choriocarcinoma and embryonal carcinoma components. During infancy, non-gonadal GCTs accounted for the majority of GCTs, while after the onset of puberty, gonadal GCTs predominated. Notably, among non-gonadal GCTs, there was a female predominance during childhood and a strong male predominance during adolescence. CONCLUSIONS: Two separate groups of GCTs with distinct clinical features relevant for differential diagnosis and the diagnostic assessment can be distinguished. This observation correlates with genetic studies that reveal different genetic changes in childhood and adolescence GCTs. Further studies are needed to elucidate the molecular mechanisms of germ cell and GCT development that account for the age- and sex-dependent clinical manifestation.