Displaced children with cancer in Lebanon: A sustained response to an unprecedented crisis.

BACKGROUND: The unrest in Syria has resulted in an escalating refugee crisis. The postwar lack of health care infrastructure in Iraq has also resulted in Iraqis seeking health care in neighboring countries. Pediatric cancer is largely curable, although its treatment is expensive and complex. Strategies to implement pediatric cancer care with curative intent in these vulnerable populations are lacking. METHODS: To assess the feasibility of a collaborative approach for the provision of care to displaced children with cancer, this study reviewed the experience of the authors over the past 6 years in Lebanon, the country with the highest number of refugees per capita in the world. RESULTS: The American University of Beirut Medical Center and the Children's Cancer Center of Lebanon Foundation, in partnership with St. Jude Children's Research Hospital and the American Lebanese Syrian Associated Charities, established 3 successive funding programs to treat displaced children with cancer along with a continuous assessment of resource utilization. Between 2011 and 2017, 575 non-Lebanese children suspected to have cancer were evaluated. Of those, 311 received direct medical support, with 107 receiving full-treatment coverage and 204 receiving limited-workup/specialty services; the remaining 264 patients received medical consultations. CONCLUSIONS: In addition to providing lifesaving humanitarian support, the coordination of care delivery, including the establishment of guidelines for prioritization, can help direct future efforts. Many patients continue to be in dire need of support, and this should be addressed via collaboration among governmental, nongovernmental, and health care organizations. Cancer 2018;124:1464-72. © 2018 American Cancer Society.

Pediatric cancer pathology review from a single institution: Neuropathology expert opinion is essential for accurate diagnosis of pediatric brain tumors.

BACKGROUND AND OBJECTIVES: Second pathology review has been reported to improve accuracy in oncologic diagnoses, including pediatric malignancies. We assessed the impact of second review on the diagnosis of pediatric malignancies at a tertiary care referral center in Beirut, Lebanon. METHODS: Pathology reports of patients treated at the Children's Cancer Institute in Lebanon were retrospectively reviewed for the period 2008-2016 and compared with same samples' diagnoses at St. Jude Children's Research Hospital. Diagnostic disagreements were divided into major, minor, and none based on their effect on diagnosis and/or patient management. RESULTS: Second review was requested for 171 cases, accounting for 19% of all cases during that period. Second opinion was mostly requested for brain tumors (62% of all brain tumor cases) and neuroblastoma for NMYC testing (65% of all neuroblastoma), while hematologic malignancies had the fewest referrals (3% of all hematologic cases). Major disagreements in second review occurred in 20 cases (12% of total), and minor disagreements in 21 cases (12% of total). The largest proportion of major disagreements (71%) occurred in pediatric brain tumors, and novel molecular tests contributed to the diagnosis in 55% of these cases. CONCLUSIONS: The availability of a specialized pediatric neuropathologist and a basic panel of relevant molecular testing are essential for appropriate diagnosis of pediatric brain tumors. Centers that do not have the available infrastructure in place can benefit greatly from second review referrals for this challenging subset of tumors.

Approach to Non-Neutropenic Fever in Pediatric Oncology Patients-A Single Institution Study.

BACKGROUND: Pediatric oncology patients with fever, even when not neutropenic, are known to be at an increased risk of bloodstream infections. However, there are no standard guidelines for management of fever in non-neutropenic patients, resulting in variability in practice across institutions. PROCEDURE: We retrospectively analyzed the clinical characteristics, management, and outcome of all febrile non-neutropenic episodes in pediatric oncology patients at a single institution over the two-year period 2011-2012, to identify predictors of bloodstream infections. We assessed the efficacy of a uniform approach to outpatient management of a defined subset of patients at low risk of invasive infections. RESULTS: A total of 254 episodes in 83 patients were identified. All patients had implanted central venous catheters (port). Sixty-two episodes (24%) were triaged as high-risk and admitted for inpatient management; five (8%) had positive blood cultures. The remaining 192 episodes were triaged as low risk and managed with once daily outpatient intravenous ceftriaxone; three (1.6%) were associated with bacteremia, and 10% required eventual inpatient management. Of all the factors analyzed, only signs of sepsis (lethargy, chills, hypotension) were associated with positive bloodstream infection. CONCLUSIONS: Treatment of a defined subset of patients with outpatient intravenous ceftriaxone was safe and effective. Signs of sepsis were the only factor significantly associated with bloodstream infection. This study provides a baseline for future prospective studies assessing the safety of withholding antibiotics in this subset of patients.

The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The alveolar subtype (ARMS) is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 that drives oncogenic cellular properties. Exosomes are small, secreted vesicles that affect paracrine signaling. We show that PAX3-FOXO1 transcript alters exosome content of C2C12 myoblasts, leading to pro-tumorigenic paracrine effects in recipient cells. Microarray analysis revealed alteration in miRNA content of exosomes, affecting cellular networks involved in cell metabolism, growth signaling, and cellular invasion. Overexpression and knockdown studies showed that miR-486-5p is an effector of PAX3-FOXO1, and mediates its paracrine effects in exosomes, including promoting recipient cell migration, invasion, and colony formation. Analysis of human RMS cells showed miR-486-5p is enriched in both cells and exosomes, and to a higher extent in ARMS subtypes. Analysis of human serum samples showed that miR-486-5p is enriched in exosomes of patients with RMS, and follow-up after chemotherapy showed decrease to control values. Our findings identify a novel role of both PAX3-FOXO1 and its downstream effector miR-486-5p in exosome-mediated oncogenic paracrine effects of RMS, and suggest its possible use as a biomarker.

Collaborative Pediatric Bone Tumor Program to Improve Access to Specialized Care: An Initiative by the Lebanese Children's Oncology Group.

BACKGROUND: Children with malignant bone tumors have average 5-year survival rates of 60% to 70% with current multimodality therapy. Local control modalities aimed at preserving function greatly influence the quality of life of long-term survivors. In developing countries, the limited availability of multidisciplinary care and limited expertise in specialized surgery and pediatric radiation therapy, as well as financial cost, all form barriers to achieving optimal outcomes in this population. METHODS: We describe the establishment of a collaborative pediatric bone tumor program among a group of pediatric oncologists in Lebanon and Syria. This program provides access to specialized local control at a tertiary children's cancer center to pediatric patients with newly diagnosed bone tumors at participating sites. Central review of pathology, staging, and treatment planning is performed in a multidisciplinary tumor board setting. Patients receive chemotherapy at their respective centers on a unified treatment plan. Surgery and/or radiation therapy are performed centrally by specialized staff at the children's cancer center. Cost barriers were resolved through a program development initiative led by St Jude Children's Research Hospital. Once program feasibility was achieved, the Children's Cancer Center of Lebanon Foundation, via fundraising efforts, provided continuation of program-directed funding. RESULTS: Findings over a 3-year period showed the feasibility of this project, with timely local control and protocol adherence at eight collaborating centers. We report success in providing standard-of-care multidisciplinary therapy to this patient population with complex needs and financially challenging surgical procedures. CONCLUSION: This initiative can serve as a model, noting that facilitating access to specialized multidisciplinary care, resolution of financial barriers, and close administrative coordination all greatly contributed to the success of the program.