ParkinSong Online: Feasibility of Telehealth Delivery and Remote Data Collection for a Therapeutic Group Singing Study in Parkinson's.

BACKGROUND: Parkinson's disease can negatively affect vocal functioning and social wellbeing, particularly in the latter stages of disease progression. Face-to-face group singing interventions can improve communication and wellbeing outcomes, yet not all people can access in-person sessions. To help overcome barriers to participation, exploration of the feasibility and utility of online therapeutic singing programs is needed. OBJECTIVES: To evaluate the feasibility, acceptability, and preliminary efficacy of a 12-week ParkinSong Online intervention on speech and wellbeing for people with Parkinson's disease. METHODS: A total of 28 participants with idiopathic Parkinson's disease were recruited to a single-arm feasibility study. Weekly 90-minute online sessions were co-facilitated by a music therapist and speech pathologist. Speech and wellbeing assessments were conducted pre and post intervention. Participant and facilitator surveys were administered after each session, with focus group interviews at the end of the program. RESULTS: The recruitment rate was high (90%) with no attrition, adverse events, or safety issues. There was good intervention fidelity, attendance (average 89%), and positive participant experience. Feasibility was good, with technology reported as the main challenge (connecting and navigating Zoom). No improvements were seen in voice measures or wellbeing outcomes in this small trial. The online format used in this study did not provide the same benefits as in-person ParkinSong sessions. CONCLUSIONS: ParkinSong Online is feasible for recreational purposes and social engagement provided that people have adequate technological knowledge or support. The optimal online delivery format to achieve communication improvements in Parkinson's awaits confirmation.

Critical elements of pediatric liver cancer surgery.

The appropriate management of pediatric liver malignancies, primarily hepatoblastoma and hepatocellular carcinoma, requires an in depth understanding of contemporary preoperative risk stratification, experience with advanced hepatobiliary surgery, and a good relationship with one's local or regional liver transplant center. While chemotherapy regimens have become more effective, operative indications more well-defined, and overall survival improved, the complexity of liver surgery in small children provides ample opportunity for protocol violation, inadequate resection, and iatrogenic morbidity. These guidelines represent the distillation of contemporary literature and expert opinion as a means to provide a framework for preoperative planning and intraoperative decision-making for the pediatric surgeon.

The Wolfson Prize: designing the hospital of the future.

Background: The 2021 Wolfson Economics Prize asked how new hospitals should be designed to radically improve patient experiences, clinical outcomes, staff wellbeing and integration with wider health and social care. With a major programme to rebuild and renew hospitals in England underway, the Prize offered an opportunity to understand current thinking about hospitals and their future place. Methods: The 41 submissions that were identified as 'most promising' were reviewed and subjected to framework analysis. Emerging themes were identified and discussed iteratively. Results: Five dominant themes were identified: a calming environment; systems of care; distribution of services; use of technology; and going green. Several tensions and trade-offs were evident across the submissions and a number of gaps were identified in the knowledge base that need to be remedied to ensure that new hospitals are safe and efficient. Conclusion: The previous approach to building new hospitals, with its over-riding drive to reduce costs, has not served the UK well. New ways of thinking about hospital building and design are urgently needed, especially the funding of research and the creation of a national repository devoted to design solutions and post-build evaluations of new hospitals.

Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee.

BACKGROUND: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. PROCEDURES: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. RESULTS: Thirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). CONCLUSION: VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: Report from Children's Oncology Group Trial, AHEP0731.

BACKGROUND: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone. PATIENTS AND METHODS: Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology. RESULTS: A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8-84 months) and the median AFP at enrollment was 714 ng/ml (range: 18-77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6-9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%. CONCLUSION: This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation. LEVEL OF EVIDENCE: Prognosis study, Level I evidence.

Doxorubicin in combination with cisplatin, 5-flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma: A Children's Oncology Group study.

BACKGROUND: The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. METHODS: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. RESULTS: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. CONCLUSIONS: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.

Small Cell Undifferentiated Histology Does Not Adversely Affect Outcome in Hepatoblastoma: A Report From the Children's Oncology Group (COG) AHEP0731 Study Committee.

PURPOSE: Small cell undifferentiated (SCU) histology in hepatoblastoma (HB) tumors has historically been associated with a poor prognosis. Tumors from patients enrolled on Children's Oncology Group (COG) study AHEP0731 underwent institutional and central pathologic review for identification of SCU histology. PATIENTS AND METHODS: Patients with SCU histology identified at the local treating institution who had otherwise low-risk tumors were upstaged to the intermediate-risk treatment stratum, whereas those only identified by retrospective central review were treated per the local institution as low-risk. Patients with otherwise intermediate- or high-risk tumors remained in that treatment stratum, respectively. Central review was to be performed for all tissue samples obtained at any time point. Treatment was per local review, whereas analysis of outcome was based on central review. RESULTS: Thirty-five patients had some elements (1%-25%) of SCU identified on central review of diagnostic specimens. All but two patient tissue sample retained nuclear INI1 expression. The presence of SCU histology did not correlate with age, alpha-fetoprotein level at diagnosis, or sex. The presence of SCU did not affect event-free survival (EFS). EFS at 5 years for patients with low-risk, intermediate-risk, and high-risk with SCU HB was 86% (95% CI, 33 to 98), 81% (95% CI, 57 to 92), and 29% (95% CI, 4 to 61), respectively, compared with EFS at 5 years for patients without SCU enrolled with low-risk, intermediate-risk, and high-risk of 87% (95% CI, 72 to 95), 88% (95% CI, 79 to 94), and 55% (95% CI, 32 to 74; P = .17), respectively. CONCLUSION: The presence of SCU histology in HB does not appear to adversely affect outcome. Future studies should be able to treat patients with SCU HB according to risk stratification without regard to the presence of SCU histology.

Employment search, initial employment experience, and career preferences of recent pediatric surgical fellowship graduates: An APSA survey, part of the right child/right surgeon initiative.

BACKGROUND: APSA's Right Child/Right Surgeon Initiative addresses issues concerning patient access to appropriate pediatric surgical care and workforce distribution. The APSA Workforce Committee sought to understand the experiences and motivations of recent graduates of Pediatric Surgery Training Programs entering the workforce. METHODS: Using APSA membership databases, we identified members who completed fellowship training from 2010 to 2019. An online survey was created using Survey Monkey, and invitations to participate were sent via email. RESULTS: 144 of 447 invited participants responded (32% response rate). 91% of respondents participated in dedicated research prior to fellowship, but only 64% perform research during their employment. 23% completed an additional clinical fellowship, but only 54% currently practice within the second field. When asked to identify the top three factors used to choose a position, the most common responses were "location or geography" (71%), "available mentorship" (53%), and "compensation and benefits" (37%). Describing their first position, 77% reported working in an academic institution, 78% reported working in a metropolitan/urban area, and 55% reported working in a free-standing children's hospital. 94% participate in General Surgery resident education, and 49% are faculty within a Pediatric Surgery fellowship. Overall, 92% of respondents were able to find the type of employment position that they had wanted. CONCLUSION: In our survey the overwhelming majority of young pediatric surgeons found the type of job they desired. Most report beginning their practice in more populated, urban areas within academic institutions. Geographic location and work environment played heavily into their employment decisions. These preferences could contribute to continued disparity in access to pediatric surgeons between urban and rural America and to dilution of experience for urban surgeons. Possible solutions include alternative incentive programs for employment in less populated areas or new training models for general surgeons in rural areas to train in fundamentals of Pediatric Surgery.

ParkinSong Online: protocol for a telehealth feasibility study of therapeutic group singing for people with Parkinson's disease.

INTRODUCTION: Parkinson's disease can be associated with speech deterioration and low communication confidence which in turn compromises social interaction. Therapeutic singing is an engaging method for combatting speech decline; however, face-to-face delivery can limit access to group singing. The aim of this study is to test the feasibility and acceptability of an online mode of delivery for a Parkinson's singing intervention (ParkinSong) as well as remote data collection procedures. METHODS AND ANALYSIS: This ParkinSong Online feasibility trial is a single-arm, pre-post study of online singing delivery and remote data collection for 30 people living with Parkinson's. The primary outcome measure is feasibility: recruitment, retention, attendance, safety, intervention fidelity, acceptability and associated costs. Secondary outcomes are speech (loudness, intelligibility, quality, communication-related quality of life) and wellbeing (apathy, depression, anxiety, stress, health-related quality of life). This mode of delivery aims to increase the accessibility of singing interventions. ETHICS AND DISSEMINATION: Ethics approval was obtained from The University of Melbourne Human Research Ethics Committee (2021-14465-16053-3) and the trial has been prospectively registered. Results will be presented at national and international conferences, published in a peer-reviewed journal, and disseminated to the Parkinson's community, researchers and policymakers. TRIAL REGISTRATION NUMBER: ACTRN12621000940875.

The Right Child/Right Surgeon initiative: A position statement on pediatric surgical training, sub-specialization, and continuous certification from the American Pediatric Surgical Association.

The past 50 years have witnessed profound changes in the specialty of pediatric surgery in North America. There has been a marked increase in the number of both pediatric surgical training programs and practicing pediatric general and thoracic surgeons. Despite this trend, the population of children in the United States and the birth rate have recently remained relatively flat. Some pediatric surgeons have become "super specialists", concentrating their practices in oncology or colorectal surgery. This has the potential to result in a dilution of experience for both pediatric surgical trainees and practicing pediatric surgeons, thus limiting their ability to acquire and maintain expertise, respectively. Coincident with this, there has been a relative paradigm shift in recognition that "quality of life" is based more on maintaining a creative balance in lifestyle and is not "all about work". There has been a parallel growth in the number of practicing pediatric general and thoracic surgeons in urban settings, but we have not appreciated as much growth in rural and underserved areas, where access to pediatric surgical care remains limited and fewer pediatric general and thoracic surgeons practice. This is a complex issue, as some underserved areas are economically depressed and geographically sparse, but others are just underserved with adult providers taking care of children in settings that are often under resourced for pediatric surgical care. This problem may extend beyond the boundaries of pediatric general and thoracic surgery to other specialties. As the premier association representing all pediatric surgeons in the United States, the American Pediatric Surgical Association (APSA) has concluded that the quality of pediatric surgical care will likely decline should the status quo be allowed to continue. Therefore, APSA has initiated a Right Child/Right Surgeon initiative to consider these issues and propose some potential solutions. What follows is a brief statement of intent.

Successful use of transarterial radioembolization with yttrium-90 (TARE-Y90) in two children with hepatoblastoma.

Primary malignant liver tumors are rare but all require surgical resection as part of therapy with curative intent. A minority of patients have resectable tumors at diagnosis. Chemotherapy has a therapeutic role in hepatoblastoma but only one-third of patients have resectable disease at diagnosis. Two children with hepatoblastoma and suboptimal responses to initial chemotherapy received therapy with transarterial radioembolization utilizing yttrium-90 (TARE-Y90) and had significant response leading to resection and remission. The role of TARE-Y90 needs to be studied further to define its use in primary pediatric liver neoplasms.

Evaluation of the diagnostic biopsy approach for children with hepatoblastoma: A report from the children's oncology group AHEP 0731 liver tumor committee.

BACKGROUND: The histopathological assessment of pediatric liver tumors at presentation is critical to establish a diagnosis, guide treatment, and collect appropriate research samples. The purpose of this study was to evaluate complications associated with different approaches to liver biopsy for newly diagnosed hepatoblastoma. METHODS: Children with hepatoblastoma were enrolled on Children's Oncology Group study AHEP0731 (September 2009-March 2012). This analysis evaluated the study cohort of initially unresectable patients who therefore underwent a biopsy procedure at diagnosis. The primary endpoint was clinically significant postbiopsy hemorrhage, defined as requiring red blood cell transfusion. RESULTS: We identified 121 children who underwent open (n = 76, 63%), laparoscopic (n = 17, 14%), or percutaneous (n = 28, 23%) liver biopsies. All biopsy procedures yielded adequate tissue for diagnosis. Postbiopsy hemorrhage requiring transfusion occurred after 26% (n = 31) of biopsies. Need for blood product transfusion most frequently occurred following open (n = 27/76, 36%) and laparoscopic (n = 4/17, 24%) biopsies, compared with percutaneous (n = 0/28, 0%) biopsies (p < 0.01). CONCLUSIONS: Pretreatment biopsy of pediatric liver tumors via a percutaneous approach yielded the lowest frequency of clinically significant hemorrhage requiring transfusion, without evidence of sacrificing diagnostic accuracy. LEVEL OF EVIDENCE: Level I.

Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial.

BACKGROUND: Hepatoblastoma treatment with curative intent requires surgical resection, but only about a third of newly diagnosed patients with hepatoblastoma have resectable disease at diagnosis. Patients who have upfront resection typically receive a total of 4-6 cycles of adjuvant chemotherapy post-surgery, with the combination of cisplatin, fluorouracil, and vincristine. We aimed to investigate whether event-free survival in children with hepatoblastoma who had complete resection at diagnosis could be maintained with two cycles of adjuvant chemotherapy. METHODS: In this Children's Oncology Group, multicentre, phase 3 trial, patients were enrolled in four risk groups on the basis of Evans surgical stage, tumour histology, and levels of α-fetoprotein at diagnosis to receive risk-adapted therapy. Here, we report on the low-risk stratum of the trial. Eligible patients were younger than 21 years and had histologically confirmed, stage I or II hepatoblastoma without 100% pure fetal stage I or small-cell undifferentiated histology; elevated serum α-fetoprotein level (>100 ng/mL); a complete resection at diagnosis; at least 50% Karnofsky (patients >16 years) or Lansky (patients ≤16 years) performance status; and had received no previous chemotherapy or other hepatoblastoma-directed therapy. Patients received two 21-day cycles of cisplatin, fluorouracil, and vincristine within 42 days of resection, consisting of cisplatin (100 mg/m2 per dose or 3·3 mg/kg per dose for children <10 kg) intravenously over 6 h on day 1; fluorouracil (600 mg/m2 per dose or 20 mg/kg per dose for children <10 kg) intravenous push on day 2; and vincristine (1·5 mg/m2 per day to a maximum dose of 2 mg, or 0·05 mg/kg per day for children <10 kg) intravenous push on days 2, 9, and 16. The primary outcome was investigator-assessed event-free survival. As prespecified by protocol, we analysed the primary endpoint 6 years after enrolment (cutoff date June 30, 2017). This trial is registered with ClinicalTrials.gov, number NCT00980460, and is now permanently closed to accrual. FINDINGS: Between May 18, 2010, and May 28, 2014, 51 patients in 32 centres in two countries were enrolled into the low-risk stratum of this trial, of whom 49 received c hemotherapy treatment after surgery and were evaluable for activity and safety. Median follow-up time for all evaluable patients was 42 months (IQR 36-62). 4-year event-free survival was 92% (95% CI 79-97) and 5-year event-free survival was 88% (72-95). Two (4%) of 49 patients had surgical complications (bile leaks). The most common grade 3-4 adverse events were febrile neutropenia in seven (14%) patients, decreased neutrophil count in three (6%) patients, infections in four (8%) patients, and diarrhoea in four (8%) patients. Ototoxicity occurred in one (2%) patient. One (2%) patient of the three who relapsed in this cohort died from disease. Two (4%) patients died in clinical remission after therapy discontinuation. One patient died of pneumonia and bacterial sepsis 1 year after therapy discontinuation and another patient died of unrelated causes 57 months after therapy completion. There were no treatment-related deaths. INTERPRETATION: Minimal postoperative chemotherapy with two cycles of cisplatin, fluorouracil, and vincristine can ensure disease control in patients with hepatoblastoma resected at diagnosis. Our results show that dose reduction of ototoxic agents is a safe, effective treatment for these children. FUNDING: National Institutes of Health.

Post-transplant lymphoproliferative disease of the larynx.

Laryngeal post-transplant lymphoproliferative disease (PTLD) is rare. Here, we describe two pediatric cases. The first, a 15-month-old who underwent liver transplantation at 5 weeks, presented with airway distress. Airway evaluation identified epiglottic and arytenoid infiltrate, and biopsy was consistent with polymorphic PTLD. The second, a 23-month-old who underwent liver transplantation at 13 months, presented with progressive stridor. Airway evaluation revealed sub-mucosal infiltrate of the epiglottis, arytenoids, post-cricoid region, and uvula. Biopsy was consistent with monomorphic PTLD. Airway findings and symptoms resolved for both after immunosuppression reduction. PTLD diagnosis requires a high index of suspicion in post-transplant patients with airway obstruction.

Extracorporeal Membrane Oxygenation in a Pediatric Patient with Hepatopulmonary Syndrome and Interrupted Inferior Vena Cava After Living Related Liver Donation.

Extracorporeal membrane oxygenation (ECMO) is used for cardiopulmonary dysfunction. Hepatopulmonary syndrome (HPS) occurs in the setting of liver failure and may cause hypoxemia. Previous reports have described the use of ECMO for HPS after liver transplant. Our patient is a 19-month-old female with biliary atresia, an interrupted inferior vena cava, and HPS on 8 liters per minute of high-flow oxygen. Following liver transplantation, her postoperative course was complicated by severe hypoxemia requiring ECMO. Due to her interrupted inferior vena cava, our standard bi-caval cannula could not be used. Hence, a 16-French double lumen venovenous right internal jugular to right atrial cannula was used to provide extracorporeal life support. She was decannulated after 17 days, remained intubated for 2 days, and weaned to room air over the next 3 weeks. This is the third pediatric liver transplant patient supported with ECMO identified in the literature, and the youngest and smallest of those reported. This approach to cannulation is unique because of the use of a double lumen venovenous cannula for HPS in a child, selected due to complex anatomy. Posttransplant ECMO may provide pediatric patients with HPS and posttransplant hypoxemia a period of support for their pulmonary remodeling and recovery from HPS.

Polymer coating on a micropillar chip for robust attachment of PuraMatrix peptide hydrogel for 3D hepatic cell culture.

For better mimicking tissues in vivo and developing predictive cell models for high-throughput screening (HTS) of potential drug candidates, three-dimensional (3D) cell cultures have been performed in various hydrogels. In this study, we have investigated several polymer coating materials to robustly attach PuraMatrix peptide hydrogel on a micropillar chip for 3D culture of Hep3B human hepatic cells, which can be used as a tool for high-throughput assessment of compound hepatotoxicity. Among several amphiphilic polymers with maleic anhydride groups tested, 0.01% (w/v) poly(maleic anhydride-alt-1-octadecene) (PMA-OD) provided superior coating properties with no PuraMatrix spot detachment from the micropillar chip and no air bubble entrapment in a complementary microwell chip. To maintain Hep3B cell viability in PuraMatrix gel on the chip, gelation conditions were optimized in the presence of additional salts, at different seeding densities, and for growth medium washes. As a result, salts in growth media were sufficient for gelation, and relatively high cell seeding at 6 million cells/mL and two media washes for pH neutralization were required. With optimized 3D cell culture conditions, controlled gene expression and compound toxicity assessment were successfully demonstrated by using recombinant adenoviruses carrying genes for green and red fluorescent proteins as well as six model compounds. Overall, PuraMatrix hydrogel on the chip was suitable for 3D cell encapsulation, gene expression, and rapid toxicity assessment.

Acute and chronic rapamycin use in patients with Fibrodysplasia Ossificans Progressiva: A report of two cases.

Fibrodysplasia Ossificans Progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification for which there is presently no definitive treatment. Several recent studies in genetic mouse models of FOP support involvement of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the pathophysiology of FOP and propose the repurposed use of rapamycin, an inhibitor of mTORC1 signaling in clinical trials for the management of FOP. Here we report two patients with the classic FOP mutation who received rapamycin-one for four months on a compassionate basis for treatment of acute flare-ups of the neck and back that were refractory to corticosteroid therapy-and the other for 18years for chronic immunosuppression following liver transplantation for intercurrent cytomegalovirus infection. In both patients, FOP progressed despite the use of rapamycin. This report highlights the real-world use of rapamycin in two FOP patients and provides insight into the use of rapamycin in clinical trials for the management of FOP.

Characterization of Pulmonary Metastases in Children With Hepatoblastoma Treated on Children's Oncology Group Protocol AHEP0731 (The Treatment of Children With All Stages of Hepatoblastoma): A Report From the Children's Oncology Group.

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children's Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and pulmonary surgery. Results Among the 29 evaluable patients, only 31% met Response Evaluation Criteria in Solid Tumors (RECIST) for measurable metastatic disease. The presence of measurable disease by RECIST, the sum of nodule diameters greater than or equal to the cumulative cohort median size, bilateral disease, and ≥ 10 nodules were each associated with an increased risk for an event-free survival event ( P = .48, P = .08, P = .065, P = .03, respectively), with nodule number meeting statistical significance. Ten patients underwent pulmonary resection/metastasectomy at various time points, the benefit of which could not be determined because of small patient numbers. Conclusion Children with metastatic HB have a poor prognosis. Overall tumor burden may be an important prognostic factor for these patients. Lesions that fail to meet RECIST size criteria (ie, those < 10 mm) at diagnosis may contain viable tumor, whereas residual lesions at the end of therapy may constitute eradicated tumor/scar tissue. Patients may benefit from risk stratification on the basis of the burden of lung metastatic disease at diagnosis.