PURPOSE 131I-metaiodobenzylguanidine (MIBG) is an active radiotherapeutic for neuroblastoma. The primary aim of this trial was to identify which of three MIBG regimens was likely associated with the highest true response rate. PATIENTS AND METHODS Patients 1-30 years were eligible if they had relapsed or refractory neuroblastoma, at least one MIBG-avid site, and adequate autologous stem cells. Patients received MIBG 18 mCi/kg on day 1 and autologous stem cell on day 15. Patients randomly assigned to arm A received only MIBG; patients randomly assigned to arm B received intravenous vincristine on day 0 and irinotecan daily on days 0-4; patients randomly assigned to arm C received vorinostat (180 mg/m2/dose) orally once daily on days 1 to 12. The primary end point was response after one course by New Approaches to Neuroblastoma Therapy criteria. The trial was designed with 105 patients to ensure an 80% chance that the arm with highest response rate was selected. RESULTS One hundred fourteen patients were enrolled, with three ineligible and six unevaluable, leaving 105 eligible and evaluable patients (36 in arm A, 35 in arm B, and 34 in arm C; 55 boys; and median age 6.5 years). After one course, the response rates (partial response or better) on arms A, B, and C were 14% (95% CI, 5 to 30), 14% (5 to 31), and 32% (18 to 51). An additional five, five, and four patients met New Approaches to Neuroblastoma Therapy Minor Response criteria on arms A, B, and C, respectively. On arms A, B, and C, rates of any grade 3+ nonhematologic toxicity after first course were 19%, 49%, and 35%. CONCLUSION Vorinostat and MIBG is likely the arm with the highest true response rate, with manageable toxicity. Vincristine and irinotecan do not appear to improve the response rate to MIBG and are associated with increased toxicity.

Objectives Meniscal tears caused by acute trauma or degenerative fraying affect a wide array of individuals. An effective, long‐lasting treatment has widely been sought after. Intra‐articular corticosteroid injections have been among the methods of controlling pain for more than 60 years. However, such injections tend to produce short‐lasting results, with profound effects lasting an average of up to 4 weeks. The purpose of this study was to determine the average duration and magnitude of pain relief after meniscal‐targeted injections. Methods The electronic medical records of 135 patients were accessed for this retrospective chart review. Patients who had meniscal tears or degenerative fraying and were treated with meniscal‐targeted injections were selected. Patients’ visual analog scale (VAS) pain scores (before and after treatment) were recorded, along with the percentage of pain relief and duration of pain relief. Results Ultrasound‐guided meniscus‐targeted corticosteroid injections for meniscal tears or degenerative fraying produced 5.68 (SD, 5.28) weeks of pain relief on average, with a decrease in pain from initial to follow‐up visits of 2.14 (P < .0001) as per the visual analog scale score, and an Integral of Pain Relief score of 3.98. Conclusions Our findings indicate a substantial benefit from 20‐ or 40‐mg meniscus‐targeted triamcinolone injections, granted the limitations of chart review research and no control group comparison. Results highlight the need for future prospective research comparing meniscus‐targeted injections with intra‐articular injections to identify a better modality for treating patients with chronic knee pain caused by meniscal tears or degenerative fraying.

10012 Background: Circulating tumor DNA (ctDNA) is detectable in children with neuroblastoma. Less is known about how levels change during treatment and the implications of these changes. We evaluated ctDNA pre- and post- 131I-metaiodobenzylguanidine (MIBG) therapy. Methods: We utilized plasma samples from NANT11-01 (NCT02035137), a multi-center, open label, randomized phase II clinical trial evaluating MIBG with or without radiation sensitizers for patients with relapsed or refractory neuroblastoma. Plasma was collected at Baseline prior to MIBG, 72 hours (Hr72), 96 hours (Hr96), 15 days after MIBG (D15), and prior to a second course among patients without progression who received a second course (C2). Samples were analyzed for percent ctDNA levels using ultra-low passage whole genome sequencing. We evaluated associations between ctDNA findings with baseline disease measures of percent involvement in bone marrow, Curie score, and RECIST disease sum of diameters as well as overall response by NANT Response Criteria v1.2 (complete response or partial response coded as responders). Results: Eighty-four patients had a baseline sample and were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32% (range 3.9-91%). Baseline ctDNA levels showed a significant positive correlation with percent involvement in bone marrow (r=0.37; p=0.0004) and Curie score (r=0.26; p = 0.018), but not RECIST sum of diameters for soft tissue sites (r=0.065; p=0.56). Following therapy, the proportions of patients with detectable ctDNA were: Hr72 47% (34/73; median level 28%); Hr96 50% (26/52; median 28%); D15 33% (7/21; median 4%); and C2 14% (3/21; median 50%). Rate of ctDNA detection was similar between responders and non-responders at baseline, Hr72, and Hr96, but lower among responders at D15 and C2 (Table). Among the 21 patients with C2 data, ctDNA levels were either undetectable (n=18) or lower than Cycle 1 Baseline (n=3). Among patients with detectable baseline ctDNA, the median relative ctDNA level at Hr72 (Hr72 ctDNA/baseline ctDNA) for non-responders was 0.87 (n=24) vs. 1.16 for responders (n=7). In contrast, the median relative ctDNA level at C2 for non-responders was 0.56 (n=4) vs. 0 for responders (n=4). Conclusions: ctDNA is detectable in a substantial proportion of patients with relapsed / refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints (Hr72 and Hr96) are less informative, whereas ctDNA becomes undetectable at D15 and C2 more commonly in patients with clinical response.[Table: see text]

10500 Background: 131I-metaiodobenzylguanidine (MIBG) remains one of the most active agents for neuroblastoma. It is not clear if putative radiation sensitizers improve upon this activity. The primary aim of this trial was to identify the MIBG treatment regimen with highest response rate among: MIBG monotherapy (Arm A); MIBG/Vincristine/Irinotecan (Arm B); MIBG/Vorinostat (Arm C). The secondary aim was to compare toxicity across arms. Methods: We conducted a multicenter, randomized phase II trial. Patients 1-30 years with relapsed/refractory high-risk neuroblastoma were eligible with at least one MIBG-avid site and adequate autologous stem cells (ASCs). All patients received MIBG 18 mCi/kg on Day 1 and ASC on day 15. Patients on Arm A received only MIBG; patients on Arm B also received vincristine (2 mg/m2) IV on Day 0 and irinotecan (50 mg/m2) IV daily on Days 0-4; patients on Arm C also received vorinostat (180 mg/m2) orally once daily on days -1 to 12. The primary endpoint was response after one course according to NANT response criteria. The trial was designed as a pick-the-winner study with a maximum of 105 eligible and evaluable patients to ensure an 80% chance that the arm with highest response rate is selected, if that response rate is at least 15% higher than the other arms. Results: 114 patients enrolled. Three patients were ineligible and 6 eligible patients never received MIBG, leaving 105 eligible and evaluable patients (36 Arm A; 35 Arm B; and 34 Arm C; 55 boys; median age 6.5 years). 9 patients had received prior MIBG monotherapy, 65 prior irinotecan, and 7 prior vorinostat. After one course, the response rates (Partial Response or better) on Arms A, B, and C were 17% (95% CI 7-33%), 14% (5-31%), and 32% (18-51%). An additional 4, 4, and 7 patients met NANT Minor Response criteria [partial response in one disease category (e.g., bone marrow) and stable disease in other categories] on Arms A, B, and C, respectively. On Arms A, B, and C, rates of any grade 3+ non-hematologic toxicity were 19%, 49% and 32%; rates of grade 3+ diarrhea were 0%, 11%, 0%; and rates of grade 3+ febrile neutropenia were 6%, 11%, and 0%. Conclusions: The combination of vorinostat/MIBG had the highest response rate, with manageable toxicity. Vincristine and irinotecan do not improve the response rate to MIBG and are associated with increased toxicity. These data provide response rates for MIBG monotherapy in a contemporary patient population assessed with current response criteria. Clinical trial information: NCT02035137.

Background Congenital pulmonary airway malformations (CPAMs) are a heterogenous collection of congenital lung malformations, often diagnosed prenatally. The Stocker Type III CPAM is a rare CPAM sub-type, and, when large, may be associated with hydrops. Furthermore, reports of CPAM management which may include surgical resection in extreme preterm infants are limited. Case presentation We report a case of a female neonate born at 28 weeks of gestation with severe respiratory distress and diffuse pulmonary opacification on the right concerning for a large congenital lung lesion. This lesion was not detected on routine antenatal imaging, and she did not have clinical findings of associated hydrops. Her respiratory status improved dramatically after surgical resection of a mass at 12 day of age. The mass was consistent pathologically with a Stocker Type III CPAM. Lung expansion showed subsequent improvement at 16 months of age. Conclusions Our case describes a preterm neonate with severe respiratory distress that was found postnatally to have a large, unilateral congenital lung lesion despite a normal prenatal ultrasound. Additionally, this lesion required excision early in life due to severity of respiratory compromise. This case highlights that rare congenital lung lesions, like this rare sub-type of CPAM, should remain a diagnostic consideration in neonates with severe respiratory distress. Early lung resection for CPAM in preterm infants is not well described and the favorable outcomes of this case help expand perspectives on potential management strategies.