Context Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective To determine whether 8 weeks of intranasal OXT (vs. 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Design Randomized, double-blind, placebo-controlled, cross-over pilot trial (NCT02849743). Setting Outpatient academic medical center. Participants Aged 10y to 35y, hypothalamic obesity from hypothalamic/pituitary tumors. Intervention Intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs. excipient-matched placebo, 16-24 IU three times daily at mealtimes. Main outcome measure(s) Weight loss attributable to OXT vs. placebo, safety (adverse events). Results Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3y, IQR 13.3-20.6), 10 completed the entire study. We observed a non-significant within-subject weight change of -0.6 kg (95% CI: -2.7, 1.5) attributable to OXT vs. placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography (ECG) prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusions In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, as well as potential psychosocial benefits.
ContextIndividuals treated for pediatric craniopharyngioma, a rare, grade 1 brain tumor, frequently develop hypothalamic obesity, a complication often recalcitrant to intervention. Although hypothalamic obesity is known to adversely impact quality of life, less is known about how caregivers and patients experience this condition.ObjectiveOur goal was to examine the approaches that families take towards weight management and the impact on social function in individuals with craniopharyngioma and obesity. Individuals with craniopharyngioma without obesity were included as a comparison.Subjects and MethodsAdult caregivers of children <18y with craniopharyngioma completed a web-based survey posted by a patient advocacy organization between February and July 2020. Questions related to the child’s diagnosis, medications, lifestyle modifications, and social function along with research priorities. Descriptive statistics were generated. Linear regression was used to assess the independent effects of obesity and other covariates on social function.ResultsOf 106 respondents, 60 (57%) reported their child had obesity at the time of survey completion. In contrast, only 6 (5.7%) had obesity prior to craniopharyngioma diagnosis. A majority (92%) of those with obesity had tried limiting calories or carbohydrates; 31% and 69% found these helpful, respectively. Thirty-eight percent had tried weight loss medications (stimulants, metformin, GLP1R-agonists, and topiramate) and 48% found at least one helpful. Both stimulant and anti-depressant use were reported more frequently with obesity. An index (T-score) reflecting social function was lower in the cohort than a population reference, 41 (SD 11) vs. 50 (SD 10), p<0.001. In a linear model, both older age and obesity were independently associated with greater social impairment. Ninety-four percent of respondents caring for a child with obesity (and 79% of all respondents) identified “improving treatments and prevention for hypothalamic obesity” as a key research priority.ConclusionsOnly a minority of individuals with hypothalamic obesity had trialed medication, even though many reported that lifestyle modification was inadequate. Furthermore, social function was significantly impaired overall in survivors compared to a reference cohort, and even more so in individuals with obesity. These findings highlight the opportunity to improve social functioning as an additional potential benefit of improved treatments for hypothalamic obesity.
Craniopharyngiomas are rare, histologically benign, sellar/parasellar tumors with significant tumor and therapy related morbidity and impairment in quality of life (QOL). We report survey results from patients/families affected by childhood-onset craniopharyngioma to identify opportunities for improvement in management. An anonymous REDCap survey was distributed via social media and clinic visits to patients/families of craniopharyngioma survivors. Survey questions investigated perspectives on clinical management and functional and survival outcomes at initial diagnosis and recurrence. A total of 159 patients/families completed the survey, 40% (n=64) reported craniopharyngioma recurrence. For primary craniopharyngioma, maximal safe resection was the most frequent treatment reported (n=84), followed by partial resection (n=40), radiation (n=8), biopsy (n=5), and chemotherapy (n=3). Most patients (n=120) decided on a treatment plan within one week, 63 (40%) decided in one day. For recurrent craniopharyngioma, maximal safe resection and radiation were the most frequent interventions (n=33 each), followed by partial resection (n=13), chemotherapy (n=4) and biopsy (n=2). Multiple treatment options and/or participation in a clinical trial were offered to similar numbers of patients across primary and recurrent diagnoses (~21% for each). Most recurrent craniopharyngioma patients decided on management within one week (n=43). Long term effects related to tumor and treatment were identified as the primary concern in all respondents. The most common deficits for all patients were neuro-endocrine followed by vision and neurocognition problems. Neuro-endocrine complications were self-reported as the biggest impact on QOL. Families reported that they would prefer treatment options with the potential for improved QOL, even if these options also carried an increased risk of recurrence. Craniopharyngioma continues to be predominantly treated with surgery and radiation initially and with recurrence. Survivors have multiple comorbidities, with an interest in targeted therapies that preserve QOL. Novel therapies to prevent co-morbidities and provide long term benefits are necessary and upcoming.
BACKGROUND: Pediatric craniopharyngioma is associated with long-term survival, but tumor- and therapy-related complications often negatively impact quality of life (QoL). Standard treatments include resection and radiation, but institutional practices vary and recurrence rates remain high. In this review, we utilized a cohort from the Children’s Brain Tumor Network (CBTN) to evaluate outcomes for craniopharyngioma. METHODS: CBTN provides clinical and genomic data for pediatric patients diagnosed with primary central nervous system tumors across 25+ institutions. We collected data for 124 patients, ages 0-21, diagnosed with craniopharyngioma between 2012-2020. Variables collected included treatment, recurrence/progression, and comorbidities. RESULTS: Excluding patients without confirmed pathologic diagnosis (n=10) or follow-up data (n=39), 75 patients remained. For initial treatment, most (n=46, 61%) received surgery alone (9 partial, 33 near-total resection). Twenty-six (35%) underwent both surgery and radiation, with 9 receiving both therapies upfront and 17 receiving radiation at progression/recurrence. Four (5%) patients received chemotherapy. Over half of the cohort (n=39, 52%) had at least one progression/recurrence, and four died (5%). Significantly higher rates of progression/recurrence (84% vs. 32%, p=4.0e-5) were identified in patients that had surgery and radiation, compared to surgery alone. Time to recurrence, progression, or death was shorter for the surgery and radiation group (HR=4.1, p<1.0e-4), and for those that underwent partial versus near-total resection (HR=2.7, p=0.1.2e-2). Comorbidities were likely underreported, based on low rates of visual (32%), neuroendocrine (27%), and neurologic (28%) deficits at diagnosis, and 29 patients (39%) with unspecified medical history. CONCLUSIONS: CBTN provides a robust repository of information on treatment and survival of craniopharyngioma patients. However, we found a paucity of data on associated comorbidities and QoL outcomes. We advocate that future datasets and clinical trials routinely collect functional outcomes alongside therapy and survival data, particularly in craniopharyngioma where long-term survival is balanced with future QoL.
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