The Impact of Tumor Laterality (Unilateral vs. Bilateral) on Presentation and Management Outcome in Patients with Retinoblastoma.

Background: This study compares the outcomes of managing retinoblastoma between patients with unilateral and bilateral presentations. Methods: The study, conducted at the King Hussein Cancer Center in Amman, Jordan, retrospectively analyzed cases of retinoblastoma treated between March 2003 and December 2019. Evaluation criteria included clinical features, disease stage, treatment methods, and overall management outcomes. Results: The study comprised 697 eyes from 478 patients with retinoblastoma, with 52% being males. Bilateral disease was observed in 70% of patients, and a family history of retinoblastoma was more prevalent in cases with bilateral disease (20%) compared to those with unilateral disease (4%). Unilateral cases had a median age at diagnosis of 28 months, whereas bilateral cases were diagnosed at a median age of 6 months. Extra-ocular retinoblastoma was detected in 1% of eyes. According to the International Intraocular Retinoblastoma Classification (IIRC), 88% of unilateral cases presented with advanced disease (IIRC group D/E), compared to 46% in bilateral cases. Primary enucleation was performed in 29% of unilateral cases and 16% of bilateral cases (p-value 0.0007). Eye salvage rates were 31% in unilateral cases and 68% in bilateral cases (p-value < 0.0001). At 120 months of follow-up, 5% of patients died from secondary neoplasms or metastases, 81% were alive, and 14% were lost to follow-up. There was no significant difference in metastasis, secondary neoplasms, or mortality between patients with unilateral and bilateral retinoblastoma. Conclusions: This study highlights the nuanced differences in clinical characteristics and outcomes between unilateral and bilateral retinoblastoma, emphasizing the necessity of customized management and early detection strategies. It demonstrates that while bilateral retinoblastoma benefits from earlier detection and has a higher rate of eye salvage, there is no significant difference in metastasis or mortality rates when compared to unilateral cases. The critical roles of primary enucleation in advanced cases, along with effective communication and patient education, are also underscored to improve treatment adherence. Overall, these findings point to the importance of tailored approaches in optimizing outcomes for the diverse patient population affected by retinoblastoma.

Comparative Analysis of Skip Metastasis in Pediatric Osteosarcoma: Clinical Features and Outcomes.

BACKGROUND: Skip metastasis (SM) is a synchronous regional bone metastasis. Using new imaging modalities, the detection of SM is easier and possibly more common. We reviewed patients with SM and compared their characteristics and outcomes to other patients with osteosarcoma treated at our center. METHODS: We reviewed retrospectively children (<18 years) with newly diagnosed osteosarcoma who presented from June 2006 to March 2022. Patients' characteristics, treatment modalities, and outcomes were analyzed. All cases were discussed in a multidisciplinary clinic that included 2 experienced radiologists. RESULTS: We identified 155 patients with osteosarcoma, among which 13 (8.3%) patients had SM detected by MRI. Patients with SM had a median age at diagnosis of 11.2 years (range 7 to 17). Three patients had lung metastasis at diagnosis. Bone scan was positive for the SM in 8 patients (62%). All patients underwent primary tumor resection after neoadjuvant chemotherapy (amputation in 5, limb salvage surgery in 8). Five had postchemotherapy necrosis ≥90% in primary tumor. Seven patients relapsed/progressed (1 local and 6 in the lung), all relapsed patients died of disease. Compared to the rest of the patients, those with SM had similar clinical features to patients without SM; outcomes were similar with no significant differences in event-free survival and overall survival ( P =0.7 and 0.3, respectively). CONCLUSION: In this study, we observed a percentage of patients with SM comparable to previous reports. Patients with SM exhibited clinical features akin to the rest of our patients. Thorough evaluation of imaging studies and multidisciplinary care, coupled with meticulous surgical planning, are crucial for achieving a cure, which remained unjeopardized in our patients with SM.

Smoking-Related Disease Impact in the Eastern Mediterranean Region: A Comprehensive Assessment Using Global Burden of Disease Data.

BACKGROUND: Smoking remains a significant risk factor for numerous health issues, including lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, stroke, and respiratory infections. This study investigates the burden of tobacco-related diseases in the Middle East and North Africa (MENA) region. METHODS: Utilizing the GBD data, we examined the risk of smoking and second-hand smoke exposure and their related causes of death and disability in the 22 MENA countries. Smoking prevalence and disease burden data were analyzed with estimates reported as age-standardized rates. RESULTS: Tobacco abuse accounted for 14.5% of all deaths and 23.2% of deaths tied to known risk factors, with an age-standardized death rate of 110.8 per 100,000. Cardiovascular diseases were the primary cause of smoking-related deaths and DALYs, representing 53.4% of all deaths and 50.3% of all DALYs. This was followed by neoplasms (24.6% of all deaths and 20.3% of all DALYs), chronic respiratory diseases(12.4% of all deaths and 11.9% of all DALYs), and respiratory infections and tuberculosis(4% of all deaths and 3.4% of all DALYs). Second-hand smoking caused 20.5% of tobacco-related deaths and 21.5% of tobacco-related DALYs, disproportionately affecting younger individuals. An increasing disease burden was observed in Lebanon, Turkey, Syria, Tunisia, UAE, and Libya, and declining rates were most evident in Oman and Qatar. CONCLUSION: Our study emphasizes the impact of smoking on cardiovascular disease, the primary cause of smoking-related mortality and morbidity in the MENA region. Our findings highlight the urgent need for effective tobacco control policies and interventions.

Survival Trends in Pediatric Differentiated Thyroid Cancer: A Middle Eastern Perspective.

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan-Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12-15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans.

Health-related quality of life of pediatric brain tumor survivors after treatment in Jordan.

Background: The number of cancer survivors and survivorship are increasing. Health-related quality of life (HRQOL) has not been widely studied in low-and-middle-income countries (LMICs). The aim of this study is to explore HRQOL of childhood brain tumor survivors and its determinants in Jordan. Methods: Health-related quality of life information was collected from 80 patients treated at the King Hussein Cancer Center and their parents using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales questionnaire in Arabic. Multivariable linear OLS regression models were used to analyze correlates of HRQOL and compare differences between child- and parent-reported responses. Results: Health-related quality of life scores reported by survivors and by parents were positively correlated on all subscales and total PedsQL scores (r = 0.59, P = .001). Survivors reported better HRQOL in cognitive subscale (ß = 0.56, P = .03) and worse HRQOL in work subscale (ß = 0.43, P = .04), but no significant differences in the physical, emotional, and social subscales and total PedsQL scores. Significant predictors of HRQOL reported by parents and by children were different. Supratentorial tumor location was associated with a 10.97-unit lower physical HRQOL score, and recurrence of tumors predicted a 17.5-unit lower total HRQOL score, indicating worse quality of life. Male gender (ß = 14.9, P = .002) and diagnosis of hypopituitarism (ß = 16.1, P = .03) were associated with better HRQOL. Furthermore, patients that only had radiotherapy treatment had better emotional HRQOL (ß = 32.9, P = .006) compared to patients that had combined radiotherapy and chemotherapy. Conclusion: This study provides evidence on determinants of HRQOL of pediatric brain tumor patients in Jordan. Future studies need to capitalize on the findings of this study to institute a system for regular assessment of quality of life of pediatric cancer patients in Jordan and other countries with similar health care systems and sociocultural backgrounds.

Doxorubicin Dose Deintensification in Pediatric Osteosarcoma, Is Less Better?

Hadeel HalalshehIntroduction We implemented new clinical practice guidelines (CPG) for patients with osteosarcoma starting in January 2009. These guidelines were based on standard European and American Osteosarcoma Study regimen, which includes six cycles of doxorubicin with a cumulative dose of 450 mg/m 2 . Aiming to reduce cardiac toxicity at our center, we opted to reduce the cumulative dose of doxorubicin to 375 mg/m 2 . Materials and Methods This is a retrospective cohort of osteosarcoma patients aged <18 years, treated at our center between 2009 and 2018. Patients were treated with unified CPG and were prospectively followed. Disease and treatment characteristics were depicted, and survival rates were calculated. When needed, comparison of survival of different groups were conducted using log-rank test. Results After a median follow-up of 43.3 months (range, 2-153 months), 79 patients were diagnosed with osteosarcoma and treated with dose-reduced doxorubicin. Median age at diagnosis was 12.8 years. At diagnosis, 58 patients (73%) had localized disease. The 5-year event-free survival (EFS) for the whole group was 50 ± 5.9%, and overall survival (OS) was 64 ± 5.7%. For patients with extremity nonmetastatic tumors ( N = 56), 5-year EFS and OS were 60 ± 6.9% and 70 ± 6.8%, respectively, and for this group of patients, response to chemotherapy was associated with better EFS ( p = 0.0048) and OS ( p = 0.013). Only two patients suffered transient cardiac dysfunction, which was resolved after treatment. Conclusion Our findings suggest that deintensification of doxorubicin may provide adequate control for pediatric osteosarcoma. In the absence of large randomized clinical trials addressing this issue, developing countries with less resources to treat patients with heart failure may consider using the lower dose.

Using ChatGPT to Predict Cancer Predisposition Genes: A Promising Tool for Pediatric Oncologists.

BACKGROUND: Determining genetic susceptibility for cancer predisposition syndromes (CPS) through cancer predisposition genes (CPGs) testing is critical in facilitating appropriate prevention and surveillance strategies. This study investigates the use of ChatGPT, a large language model, in predicting CPGs using clinical notes. METHODS: Our study involved 53 patients with pathogenic CPG mutations. Two kinds of clinical notes were used: the first visit note, containing a thorough history and physical exam, and the genetic clinic note, summarizing the patient's diagnosis and family history. We asked ChatGPT to recommend CPS genes based on these notes and compared these predictions with previously identified mutations. RESULTS: Rb1 was the most frequently mutated gene in our cohort (34%), followed by NF1 (9.4%), TP53 (5.7%), and VHL (5.7%). Out of 53 patients, 30 had genetic clinic notes of a median length of 54 words. ChatGPT correctly predicted the gene in 93% of these cases. However, it failed to predict EPCAM and VHL genes in specific patients. For the first visit notes (median length: 461 words), ChatGPT correctly predicted the gene in 64% of these cases. CONCLUSION: ChatGPT shows promise in predicting CPGs from clinical notes, particularly genetic clinic notes. This approach may be useful in enhancing CPG testing, especially in areas lacking genetic testing resources. With further training, there is a possibility for ChatGPT to improve its predictive potential and expand its clinical applicability. However, additional research is needed to explore the full potential and applicability of ChatGPT.

Early T-Cell Precursor Leukemia: A High-Risk Subtype of Acute Lymphoblastic Leukemia, Single Center Experience in Jordan.

BACKGROUND AND OBJECTIVES: Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied. PATIENTS AND METHODS: We compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens. RESULTS: Sixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups. CONCLUSION: ETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population.

Long-Term Survival Analysis and Prognostic Factors of Arabic Patients with Differentiated Thyroid Carcinoma: A 20-Year Observational Study at the King Hussein Cancer Center (KHCC) Involving 528 Patients.

DTC accounts for the majority of endocrine tumors. While the incidence of thyroid cancer has been increasing globally over the past few decades, papillary thyroid carcinoma (PTC) generally shows an excellent prognosis, except in cases with aggressive clinicopathological features. This study aimed to assess the 5- and 10-year overall survival (OS) and progression-free survival (PFS) of 528 Arabic patients diagnosed with primary DTC from 1998 to 2021. Additionally, the study aimed to analyze the impact of various factors on both OS and PFS. An univariable survival analysis was conducted using Kaplan-Meier curves. The 5- and 10-year OS for patients with DTC have exceeded 95%. Additionally, PFS showed very good rates (ranging between 96.5 and 85% at 5 and 10 years, respectively). Age, male gender, risk of recurrence, and distant metastasis were identified as the main negative prognostic factors for both OS and PFS, while RAI treatment was found to be a significant factor in improving OS. Moreover, adherence to the King Hussein Cancer Center's (KHCC) CPG demonstrated significant improvement in PFS. These findings highlight common prognostic factors and favorable outcomes in Arabic patients with DTC treated at a tertiary cancer center using standard of care approaches.

Progression before local control in osteosarcoma: Outcome and prognosis-predictive factors.

BACKGROUND: The prognosis and impact of early disease progression in patients with osteosarcoma prior to local control (LC), and the potential therapeutic benefits of ifosfamide/etoposide (IE) remain underexplored in the medical literature. METHODS: A retrospective study was conducted on pediatric patients (≤18 years) with osteosarcoma who presented to King Hussein Cancer Center between June 2006 and March 2022. We studied patients with disease progression before LC. RESULTS: Among 195 patients, 31 (17males) exhibited disease progression before LC. The median age at diagnosis was 14.1 years, and patients were followed for a median of 23.1 months (range: 5.8-94.7). The majority of tumors were located in the extremities (n = 28). Ten patients (48%) had lung-only metastasis. Twenty-five patients showed progression at the local site only, and six showed progression both at local/metastatic sites. For the 25 patients with local-site-only progression, the decision for 24 was immediate LC via LSS (n = 9), amputation (n = 10), hemimandibulectomy (n = 1), and radiation therapy (n = 1). Three families refused amputation. Among the six patients with combined local/metastatic site progression, the decision was for two to intensify chemotherapy by adding IE, while the other four were recommended immediate LC. However, two of them refused surgery. In total, five patients received IE as intensification for progression, all of whom subsequently progressed. The 5-year event-free survival and overall survival were 27.2% and 31.3%, respectively. CONCLUSION: Our findings suggest that early disease progression before LC in patients with osteosarcoma is associated with poor prognosis. However, patients initially diagnosed with localized disease and who later exhibited local-disease-only progression appeared to have better outcomes. The potential role of IE in the treatment of patients exhibiting early progression merits further investigation in a larger study cohort.

The burden and scope of childhood cancer in displaced patients in Jordan: The King Hussein Cancer Center and Foundation Experience.

Introduction: Jordan hosts one of the highest numbers of refugees per capita in the world, with the Syrian crisis leading to an influx of displaced persons to the already vulnerable population. However, limited resources and a lack of cancer-care strategies have made it difficult for refugees in Jordan to access quality cancer care. The King Hussein Cancer Center (KHCC) and Foundation (KHCF) have played a pivotal role in providing financial and medical support for displaced children with cancer, treating 968 non-Jordanian children with cancer between 2011-2022, with a median age of 6 years. Of these, 84% were fully funded by KHCF, and nationalities included Syrians (29%), Palestinians (26%), Iraqis (23%), and Yemenis (17%). Cancer diagnoses included solid tumors (44%), leukemia (23%), lymphoma (13%), bone sarcomas (9.5%), and retinoblastoma (9.1%). The median cost of treatment was JOD 18,000 (USD 25,352), with a total estimated cost of JOD 23.8 million (USD 33.5 million). More recently, in partnership with St. Jude Children's Research Hospital (SJCRH), two successive humanitarian funds (HF) were established to optimize cancer care for displaced children in Jordan. Results: Between February 2018 and September 2022, 51 children were fully treated on KHCC-SJCRH-HF, with a median age of 6 years and nationalities including Syrians (80%), Iraqis (6%), and Yemenis (8%). The most common cancer diagnoses were leukemia (41%), lymphoma (25%), solid tumors (24%), retinoblastoma (6%), and brain tumors (4%). Of these, 94% are alive and 51% are still receiving coverage. The median coverage for patients was JOD 21,808 (USD 30,715), and the total cost of treatment on KHCC/KHCF-SJCRH/American Lebanese Syrian-Associated Charities HF1 and HF2 was JOD 1.44 million (USD 1.97 million) and JOD 1.18 million (USD 1.67 million), respectively. Conclusion: This experience highlights the high burden of displaced children with cancer in Jordan, and the importance of local foundations like KHCC/KHCF and partnerships with international partners like SJCRH in providing lifesaving humanitarian initiatives and quality cancer care. Innovative cancer-care delivery models and sustainable financing are essential to ensure continuous coverage and access to cancer care for displaced persons in Jordan.

The Impact of Graft CD3+ T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.

Background: Data on whether the graft CD3-positive (CD3+) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. Methods: Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3+ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3+ T-cell dose (n = 34) and cohort 2 with high CD3+ T-cell dose (n = 18). Correlative analyses were performed between CD3+ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. Results: Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3+ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3+ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3+ T-cell cohort compared with high CD3+ T-cell cohort. Graft CD3+ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). Conclusions: Our data suggest that high graft CD3+ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.

Outcome of Primary Mediastinal Large B Cell Lymphoma Treated with RCHOP.

Purpose: Primary mediastinal large B-cell Lymphoma (PMLBCL) is a rare aggressive lymphoma with unique clinical, pathological, and molecular features. The optimal frontline therapy is subject of ongoing debate. Our study aims to evaluate the outcomes of PMLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) at King Hussein Cancer Center. Patients and Methods: Adult patients >18 years of age with PMLBCL treated with RCHOP from January 2011 to July 2020 were identified. All demographics, disease and treatment related variables were retrospectively collected. Correlations of clinical and laboratory variables with progression-free survival (PFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. The PFS and OS were plotted using Kaplan‒Meier curves. Results: 49 patients were included with a median age of 29 years. 14 (28.6%) had stage III or IV, 31 (63.3%) had mediastinal bulky disease. International prognostic index (IPI) was 0-1 in 35 (71.4%). Radiotherapy was given to 32 (65.3%) patients. End of treatment (EOT) response was complete (CR) in 32 (65.3%), partial response (PR) in 8 (16.3%) and progressive disease (PD) in 9 (18.4%). Patients who achieved CR at EOT, compared favorably with those who did not in regard to 4-year OS (92.5% vs 26.9%, p=<0.001). Overall objective response to salvage chemotherapies was 26.7%. At a median follow-up of 46 months, 4-year PFS and OS were 60% and 71% respectively. In multivariate analysis, IPI > one correlated with the EOT response (p=0.009), PFS (p=0.004) and OS (p= 0.019). Conclusion: In PMLBCL, RCHOP chemotherapy backbone in the frontline therapy is suboptimal but can be used in patients with low IPI. Adapting more intensive chemoimmunotherapy regimens may be considered for patients with high IPI. Salvage chemotherapy has limited activity in patients with relapsed or refractory disease.

Early post-induction augmented therapy improves outcome in children and adolescents with T-cell acute lymphoblastic leukemia.

INTRODUCTION: T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre-B ALL. We aimed to decrease T-ALL relapses by intensifying our regimen. METHODS: Patients with T-ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Reintensification. Cranial radiation was limited to patients with WBC ≥ 100 k/µl at diagnosis and/or patients with CNS2/CNS3 status. RESULTS: Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed up for a median of 70 months (range 14-181). Median age at diagnosis was 9 years (range 0.5-17.8). Forty-eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range 14-74). The 5-year-EFS estimates for patients who received the augmented regimen versus standard regimen were 87% ± 4.9% versus 67% ± 6.8% (p = .03); and the 5-year-OS estimates were 87% ± 5.1% versus 71% ± 6.3% (p = .06), respectively. Treatment related mortality (TRM) was reported in two patients treated per standard regimen but none for patients who received the augmented regimen. CONCLUSIONS: We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total-XV regimen for patients with T-ALL that resulted in improved outcome with no treatment related mortality.

Addressing the Gap in Research Methodologies Education in Pediatric Oncology in the Eastern Mediterranean Region.

PURPOSE: Formal training in clinical research methodologies is limited in limited-resource countries. Through collaboration among high- and middle-resource settings and in response to an identified need verbalized by regional pediatric oncology practitioners, Pediatric Oncology East & Mediterranean Group and St Jude Global developed a workshop focused on capacity building in research skills. Here, we describe its structure, implementation, and early results. METHODS: Leveraging virtual capabilities, the format included lectures and small group breakout exercise sessions, for 3 hours per day on 2 consecutive days per week for 2 consecutive weeks. Topics included basics of study design, introduction to health care statistics, research ethics, data registries, and scientific writing. Applicants were required to submit an abstract for a potential research project. Each breakout group selected one abstract for further development and presented the final version in a groupwide session. The participants' experience was evaluated through an online survey. RESULTS: Attendance included 29 registrants from 12 countries and six disciplines. Each breakout group was assigned a themed category: cohort studies, clinical trials, or registries. Critical feedback from the breakout sessions helped strengthen the selected projects, which included a retrospective study, a prospective observational study, a prospective interventional study, and a registry proposal. After the workshop, participants were invited to further develop their original abstracts, and three proposals received additional mentoring, one of which was a multi-institutional prospective study that was subsequently submitted through the Pediatric Oncology East & Mediterranean Group network for implementation. The postworkshop survey revealed an overall highly positive experience, and feedback provided potential themes for future workshops. CONCLUSION: This workshop demonstrated the potential for collaborative network partnerships in targeting research training gaps in pediatric oncology. Lessons learned will be applied to future workshops to strengthen research in limited-resource settings.

Long-Term Outcomes of Limb-Salvage Surgery for Malignant Bone Tumors at a Single Institution in a Developing Country.

INTRODUCTION: With the introduction of neoadjuvant chemotherapy, increased expertise in surgical oncology, and advanced skeletal imaging techniques, limb salvage surgery is becoming the standard of care for treating malignant bone tumors. However, few studies have examined the outcomes of limb salvage surgery with relatively large sample sizes in developing countries. MATERIALS AND METHODS: Therefore, we conducted a retrospective study of 210 patients who received limb salvage surgery at King Hussein Cancer Center in Amman, Jordan, over a follow-up period of 1 to 14.5 years (2006-2019). RESULTS: Negative resection margins occurred in 203 (96.7%) patients and local control occurred in 178 (84.8%) patients. The mean functionality outcome for all patients was 90%, and 153 (72.9%) patients did not experience any complications. The 10-year survival rate for all patients was 69.7%, and the rate of secondary amputations was 4%. CONCLUSION: Therefore, we conclude that the outcomes of limb salvage surgery in a developing country are comparable to those in developed countries when adequate resources and trained orthopedic oncology teams are available.

A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma.

AIM: To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. METHODS: A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis-to-enucleation, results of pathology, metastasis, and mortality were retrieved. RESULTS: Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). CONCLUSION: Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.

Outcomes of Pediatric Patients With Metastatic Ewing Sarcoma Treated With Interval Compression.

BACKGROUND: Interval compression (IC), a regimen of alternating vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide every 2 weeks, improves survival for localized Ewing sarcoma (ES), with uncertain effect on metastatic disease. MATERIALS AND METHODS: We reviewed the charts of pediatric patients with metastatic ES treated with IC at our center between January 2013 and March 2020. We calculated event-free survival and overall survival (OS) and used log-rank tests for univariate comparisons. RESULTS: We identified 34 patients 2.7 to 17.1 years of age (median: 11.6 y). Twenty-six patients (76%) had pulmonary metastases, and 14 (41%) had extrapulmonary metastases. All patients received local control therapy: surgery only (n=7, 21%), radiotherapy only (n=18, 53%), or both (n=9, 26%). The estimated 3-year OS and event-free survival were 62%±9% and 39%±9%, respectively. Patients with pulmonary-only and extrapulmonary metastasis had a 3-year OS of 88%±8% and 27%±13%, respectively ( P =0.0074). Age group (above vs. below 12 y), or primary tumor site did not affect survival, but local control therapy did (surgery only, 83%±15%; combined surgery and radiation, 30%±18%; radiation only, 15%±10%; P =0.048). CONCLUSION: IC yielded similar outcomes for patients with metastatic ES to other reported regimens. We suggest including this approach to other blocks of therapy.