Late effects care for childhood brain Tumor Survivors: A Quality-Improvement Initiative.

Childhood and adolescent brain tumor survivors are at risk for long-term consequences of therapy. We reviewed adherence to long-term follow-up (LTFU) guidelines, assessed provider perspectives, and studied the needs, experience and quality of life (QOL) of pediatric malignant brain tumor survivors in the McMaster Children's Hospital Neuro-Oncology clinic. LTFU areas for improvement were evaluated using an anonymous health provider needs assessment questionnaire. The Cancer Care Experience Questionnaire (CCEQ), Cancer Worry Scale (CWS), Self-Management Skills Scale (SMSS), and PedsQL measured parents/patients' needs and QOL. Individual care plans were based on the Children's Oncology Group (COG) LTFU guidelines. Based on 17 responses, staff perceived areas for improvement included: increased multi-disciplinary participation, improved patient education and increased surveillance for therapy-related late effects. Thirty-two families participated, most felt they received high-quality care. Mean cancer worry scores were low (71.8 (± 28.4)). Survivors reported limited self-management skills (58.5 (±18.2)), requiring support with medical needs and activities of daily living. Overall median QOL scores were 'good' (parental report 72.3 (±17.7), survivor 68.2 (±16.6)). Utilizing survivorship guidelines and assessments from patients, caregivers and health providers, we implemented improvements in our provision of neuro-oncology survivorship care. Lessons learned may assist other LTFU programs.

Salvage Therapy for Childhood Medulloblastoma: A Single Center Experience.

INTRODUCTION: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. METHODS: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. RESULTS: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. CONCLUSION: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Traitement de sauvetage dans le cas du médulloblastome chez l'enfant : une expérience menée au sein d'un établissement hospitalier. Introduction: Les enfants chez qui l'on a diagnostiqué un médulloblastome réfractaire à un traitement initial ou qui sont victimes d'une récidive présentent d'habitude des pronostics de guérison vraiment défavorables. Bien qu'il existe des traitements basés sur des essais cliniques de phases I et II, ces traitements ont tendance à produire des taux notables de morbidité et de mortalité. Méthodes: Nous avons ainsi mené à l'Université McMaster une analyse rétrospective des dossiers d'enfants chez qui l'on avait diagnostiqué entre 2002 et 2015 une récidive de médulloblastome. Résultats: La réapparition de cette maladie chez 10 patients a provoqué un phénomène de diffusion leptoméningée, trois d'entre eux étant victimes d'une récidive locale. Sur ces 10 jeunes patients, la maladie a progressé de façon importante : ces enfants ont alors été transférés aux soins palliatifs. Quant aux autres 10 enfants, ils ont subi un certain type de traitement de sauvetage (des résections chirurgicales, de la radiothérapie, de la chimiothérapie), que ce soit de façon exclusive ou en variant les combinaisons possibles. Sur les 13 enfants réfractaires à un traitement initial ou victimes d'une récidive, 4 sont toujours en vie, leur suivi médian ayant été de 38,5 mois (75,5 mois). Sur les 8 patients pour qui on a pu obtenir des données moléculaires, aucun de ceux qui étaient atteints d'un médulloblastome du sous-type Wnt n'a connu de récidive. Conclusion: Les médulloblastomes qui réapparaissent après une période de guérison complète présentent un pronostic de guérison défavorable. Leur taux de survie globale est en effet de 18,2 % au cours d'une période de 5 ans, et ce, même après avoir bénéficié d'un traitement de sauvetage. Ajoutons aussi que le type de traitement initial reçu, la disponibilité des traitements ainsi que la tolérance à l'égard des traitements de sauvetage proposés a entraîné une grande hétérogénéité dans le traitement de ces jeunes patients victimes d'une récidive.

Analysis of surgical and MRI factors associated with cerebellar mutism.

The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. Therefore, we aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with individuals who did not acquire CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). A total of 22 patients (11 with and 11 without CM) were included. Medulloblastoma was the most common pathology among CM patients (91%); the remaining 9% were diagnosed with a pilocytic astrocytoma. Tumor attachment to the floor of the fourth ventricle (OR 6; 95% CI 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR 5; 95% CI 0.5-236.5) were found to have the highest measures of association with CM. Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia have a relatively higher prevalence in patients with CM. Collectively, our work calls for a larger multi-institutional cohort study of CM patients to encourage further investigation of the determinants and management of CM in order to potentially minimize its development and predict onset.

Health-related Quality of Life in Long-term Survivors of Brain Tumors in Childhood and Adolescence: A Serial Study Spanning a Decade.

Survivors of brain tumors in childhood experience adverse sequelae that are greater in prevalence and severity than those encountered by survivors of all other forms of cancer in early life, reflected in a burden of morbidity by instruments measuring health-related quality of life (HRQL). However, there are few studies of the change in HRQL over time in such populations. Patients who were above 5 years of age, at least 2 years from completion of therapy, and able to communicate in English were eligible for study of HRQL by the Health Utilities Index HUI2 and HUI3 at study entry, and again 5 and 10 years later. An initial cohort of 40 patients was reduced to 37 and 25 at the second and third time points, respectively, although only 1 death occurred during the study. HRQL showed a progressive decline over the decade, reaching conventional levels of clinical significance for the sizes of the changes. Median scores for HUI2 were 0.93, 0.90, and 0.88; and for HUI3 were 0.88, 0.85, and 0.77 at baseline, 5, and 10 years, respectively. The serial decline in HRQL demands further examination and an exploration of potential targets for therapeutic intervention.

Exploration of Morbidity in a Serial Study of Long-Term Brain Tumor Survivors: A Focus on Pain.

PURPOSE: Children surviving brain tumors are frequently identified as having substantially decreased health-related quality of life (HRQL) in cross-sectional studies. This study explored the HRQL of a cohort of such survivors, who were recruited as adolescents and followed for a decade, in order to determine the trajectory of their morbidities. METHOD: Children diagnosed between January 1, 1985, and December 31, 1998, more than 2 years from diagnosis (N = 40), were recruited in 2000/2001 (T1) aged 16.74 ± 4.23 years. Health Utilities Index questionnaires (HUI2/3) were completed in 2000/2001 and again at 5 years (T2) and 10 years (T3), with 37 and 25 participants then aged 21.54 ± 4.29 and 27.97 ± 4.07 years, respectively. In addition to study subjects, parental proxies completed questionnaires at T1 and T2, while study subjects selected proxies at T3. Single attributes (domains/dimensions) of HRQL and details of pain were analyzed. RESULTS: Cognition was the attribute compromised most often (T1 = 66.7% of participants, T2 = 62.2%, T3 = 60.0%). Pain was also reported frequently (T1 = 35%, T2 = 25%, T3 = 52%), and at T3 correlated moderately with HUI2 sensation (0.77) and HUI3 vision (0.44), speech (0.51), and ambulation (0.50). The lower median utility score for pain at T3 than at T1/T2 was a clinically important difference. Severe pain was identified in the lower extremities, back, upper extremities, and abdomen. Morbidity was observed also in emotion (worry HUI2 and unhappiness HUI3), sensation, and vision. CONCLUSION: Decreased HRQL in survivors of brain tumors in childhood is multifaceted. Pain is a prominent burden, along with morbidity in cognition, emotion, sensation, and vision. Further studies should explore pain and neurologic deficits, and potential opportunities for therapeutic intervention.

Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies.

PURPOSE: Therapy for central nervous system (CNS) atypical teratoid rhabdoid tumor (ATRT) is controversial. We describe 4 children treated with sarcoma-like therapy and review the literature to evaluate outcome in relation to treatment modalities. PROCEDURE: Reports from 1995 to 2007, describing clinical features of children (< or =18 years) were reviewed for details of demography, therapy, and outcome. Kaplan-Meier survival analyses were used to study the impact of clinical features, demography, and therapy on overall survival (OS). RESULTS: The median OS for patients treated with multiagent chemotherapy (n=79) was 17.3 months (range, 1.5-93 mo); unrelated to age at diagnosis, sex, tumor site, and extent of resection. Overall mortality was 67%. Disease progression (craniospinal spread in 58%) was the major cause of death. Patients (n=30) treated with intrathecal (IT) chemotherapy had significantly higher 2-year OS [64% (95% confidence interval, 46.5-82.0) vs. 17.3% (95% confidence interval, 5.4-29.3); P<0.0001] and lower prevalence of distant CNS metastasis compared with those without IT therapy (n=49) (20% vs. 59.2%; P=0.001). CONCLUSIONS: Despite dismal OS, multimodal therapy can induce remission even in metastatic CNS ATRT with partial resection. IT chemotherapy results in higher OS and, because of an overall high rate of distant relapse, should be considered in future trials.

Using plain language skills to create an educational brochure about sperm banking for adolescent and young adult males with cancer.

Writing in plain language makes it easier for patients to read, understand, and make informed decisions about sperm banking. Greater attention to the issue and properly designed educational brochures for use by nurses in oncology and reproductive health is of evident importance but of unknown impact. A multidisciplinary clinical team followed an evidence-based, patient-centered approach to develop "plain language" patient education materials about sperm banking for adolescent and young adult (AYA) males with cancer. A patient education booklet was produced and implemented as part of the planned patient education for AYA male oncology patients at McMaster Children's Hospital, Hamilton Health Sciences, in Hamilton, Ontario, Canada. The patient education booklet for use by health professionals as a teaching tool to facilitate discussion with AYA males has been produced with the hope that it will contribute to better informed decision making regarding sperm banking and increased use of this technology for fertility preservation.

Effectiveness of sperm banking in adolescents and young adults with cancer: a regional experience.

BACKGROUND: Improving success in the treatment of cancer has resulted in an increasing number of survivors. An important quality of life issue among younger survivors is the ability to have a family. Current gonadotoxic treatments for cancer pose a challenge to future fertility. Preservation of fertility after gonadotoxic therapy is an important consideration for these patients. In a regional center, the authors evaluated efficacy and utilization of sperm banking for preservation of male fertility in adolescents and young adults (AYA) with cancer. METHODS: A retrospective chart review was conducted to obtain data on clinical features, andrology, and fertility from patients (ages < 30 years) who cryopreserved samples of semen from 1995-2005. RESULTS: Of 821 newly diagnosed male AYA cancer patients, aged 14-30 years, only 146 (17.8%) used sperm cryopreservation technology. Patients who used their cryopreserved semen for attempted conception had a 36.4% success rate with intrauterine insemination (IUI) and a 50.0% clinical pregnancy rate with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). CONCLUSIONS: Sperm cryopreservation by AYA males with cancer is an efficacious method for preserving future fertility. Awareness and employment of assisted reproductive technologies needs to be implemented by an interdisciplinary team of experts caring for these patients and can result in successful paternity in males after treatment for cancer.

Osteopenia, physical activity and health-related quality of life in survivors of brain tumors treated in childhood.

BACKGROUND: Osteopenia has been reported in children surviving acute lymphoblastic leukemia and brain tumors, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a role in the development of this complication. In order to explore that possibility, we examined survivors of brain tumors treated with and without radiation in childhood to investigate associations between radiation, osteopenia, physical activity, health status and overall health-related quality of life (HRQL). PROCEDURE: Subjects were survivors of posterior fossa tumors (astrocytoma or medulloblastoma) or optic glioma, < 18 years of age at diagnosis and > 1 year off treatment. Measurements of growth velocity, body composition, bone densitometry, physical activity and HRQL were undertaken. RESULTS: Twenty-five (62.5%) of the 40 eligible patients participated in the study. Of the 25 patients, 12 (48%) received radiation therapy (R group) while 13 received no radiation (NR group). Growth hormone (GH) deficiency had been detected in three subjects, one had completed GH therapy while two were still on hormone replacement. The prevalence of osteopenia was 44% in the entire group, and 67% versus 27% in the R and NR groups. Florid osteoporosis was present in 20% of the entire group, more than 40% of the R group but none of the NR group. A significant correlation (P < 0.01) was observed between overall HRQL and Z scores of bone mineral density (BMD) of the lumbar spine. Pain and ambulation/mobility utility scores correlated significantly (P < 0.05) with BMD, while levels of physical activity correlated (P < 0.05) with overall HRQL utility scores. CONCLUSIONS: This pilot study demonstrates that in survivors of brain tumors treated in childhood, radiation therapy is associated with significant loss of bone mineral. Among these survivors, HRQL is less, pain is more severe and ambulation is more restricted in those with low BMD scores. The reduction in HRQL is reflected in diminished physical activity. A larger multi-center study is needed to confirm these results.