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.

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.

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.

The Predictive Value of the Eighth Edition of the Clinical TNM Staging System for the Likelihood of Eye Salvage for Intraocular Retinoblastoma by Systemic Chemotherapy and Focal Therapy.

BACKGROUND: The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) cTNM staging is emerging as a universal staging for all cancers, including retinoblastoma. METHODS: Here we evaluated the predictive value of the eighth edition AJCC/UICC cTNM staging in comparison with the International Intraocular Retinoblastoma Classification for eye globe salvage by primary systemic chemotherapy and focal therapy (CRD) using logistic regression model for the probability of treatment failure. RESULTS: The eye salvage rate for 565 treated eyes was 95% (n=139/147) for T1 tumors (98% for T1a and 93% for T1b), 56% (n=230/410) for T2 (81% for T2a and 53% for T2b), and 0% for T3 tumors, and was 98%, 93%, 76%, and 44% for group A, B, C, and D tumors, respectively. As estimated by odds ratios, T2 were 13.6-fold more likely to fail treatment than T1, and T1b, T2a, and T2b were 2.8-, 9.4-, and 35.1-fold more likely to fail treatment than T1a, respectively. Group B, C, and D tumors were 2.8-, 12.7-, and 50.1-fold more likely to fail treatment than group A tumors, respectively. Eye salvage rate was 62% for eyes with focal seeds (3 mm close to the tumor), and 42% for eyes with diffuse seeds (clouds more than 3 mm from tumor edge) (P<0.0001). CONCLUSION: Both, the eighth edition cTNM classification and the International Intraocular Retinoblastoma Classification systems, can effectively predict eye salvage rates for retinoblastoma by CRD. Eyes with higher cT stages are more likely to experience treatment failure. Because the cT2b group is very heterogeneous, our findings suggest further division of this group based on the severity of vitreous/subretinal seeds, this should be revised in the next edition of cTNM system.

Clinical impact of post-induction resolution of pulmonary lesions in metastatic Ewing sarcoma.

BACKGROUND: Patients with metastatic Ewing sarcoma experience poor outcomes despite intensive systemic and local therapy. Early chemotherapy response of pulmonary metastases has been associated with prognosis in other pediatric malignancies. We reviewed the outcomes of patients with Ewing sarcoma and pulmonary metastases treated at our institution based on therapy received and early pulmonary response. MATERIALS AND METHODS: We retrospectively reviewed patients with newly diagnosed Ewing sarcoma and pulmonary metastases at St. Jude Children's Research Hospital between 1979 and 2015. Data obtained included demographic and treatment characteristics including chemotherapy, local control measures, whole lung irradiation (WLI) administration, autologous stem cell transplantation, and outcomes. Patients were evaluated for radiographic post-induction pulmonary complete response (CR). We estimated event-free survival (EFS) and overall survival (OS) and used Cox proportional hazards regression to examine the effects of clinical and treatment factors on outcomes. RESULTS: Fifty-four patients (median age, 12.9 years) were evaluated. Post-induction pulmonary CR was observed in 33 (61%) patients. WLI was delivered to 16 patients (4/33 with pulmonary CR and 12/21 with non-CR). At median 3.6 years follow-up, five-year EFS and OS were 30.8% ± 6.4% and 49.6% ± 7.1%, respectively. Post-induction pulmonary CR was associated with prolonged EFS (P < 0.001) but not improved OS (P = 0.065). Post-induction pulmonary CR was associated with a lower incidence of lung failure (P = 0.031). CONCLUSIONS: Post-induction pulmonary CR is associated with improved EFS in patients with Ewing sarcoma who present with pulmonary metastases.

The impact of local control timing in Ewing sarcoma.

AIM: To assess the impact of delay in local control on survival outcomes of Ewing sarcoma (ES) patients. BACKGROUND: The cornerstone of therapy of localized ES includes chemotherapy and local control with surgery or radiotherapy. We sought to assess the impact of delay (>15 weeks) in timing of local control on survival outcomes of ES patients. METHODS: Data of consecutive patients with primary non-metastatic ES of the extremities, treated at a single institution were collected. The impact of delay of timing for local control, demographics, and disease characteristics on overall survival (OS) was analyzed. RESULTS: A total of 43 patients with ES of the extremity were included. All patients received neoadjuvant chemotherapy. Local control was by surgery in 36 patients and definitive radiation in 7. A total of 16 patients had delay in local control. At a median follow of up of 48 months, patients with delay in local control had significantly inferior OS compared to those with optimal local control timing (5-year OS 56% vs. 80%, respectively, p = 0.044). Other factors that predicted inferior OS included definitive radiation as opposed to definitive surgery (5-year OS 25% vs. 79%, respectively, p = 0.041) and tumor necrosis <90% as opposed to ≥90% (5-year OS 55% vs. 90%, respectively, p = 0.01). CONCLUSION: Delay in definitive therapy, local control with radiation as opposed to surgery and poor post-chemotherapy tumor necrosis predict inferior OS in ES. Adopting strategies to minimize delay in local control could improve survival outcomes.

Feasibility of high-dose chemotherapy protocols to treat infants with malignant central nervous system tumors: Experience from a middle-income country.

BACKGROUND: Results of high-dose chemotherapy (HDCT) protocols for the management of malignant central nervous system (CNS) tumors in infants are mostly reported in high-income countries. We evaluated the feasibility and results of such protocols in a middle-income country (Jordan). METHODS: A retrospective study of infants' charts with CNS tumors between 2006 and 2015 who were treated according to HeadStart (HS) protocols. Data included patients' demographics, chemotherapy complications, and cost. RESULTS: We identified 18 patients with median age 29 months (range, 9-62 months) at diagnosis (12 HS-I and six HS-II). Distribution according to pathology was: atypical teratoid rhabdoid tumors (ATRT) (nine), primitive neuoroectodermal tumors (PNET)/pineoblastoma (five), and medulloblastoma (four). Six patients (33%) had metastatic disease, and 14 (78%) had an incomplete resection. Eleven patients achieved partial or complete remission, two stabilized, and five progressed. Ten patients did not proceed to HDCT due to progression (five), financial reasons (two), failure to collect stem cells (one), and undocumented reasons (two). Seventy-eight chemotherapy cycles were administered (median interval 26 days). Main complications during induction and consolidation were febrile neutropenia (73% and 100%), documented infections (8% and 13%), and mucositis (12% and 88%), respectively. Three patients developed moderate hearing loss. No protocol-related mortality was reported. At the last follow-up, five patients were alive: three with medulloblastoma (19, 29, and 89 months) and two with ATRT (18 and 42 months). Three survivors received focal/craniospinal radiation. The median cost of a complete HS protocol, excluding surgery/radiotherapy, was $103 500 per patient; 39% of the median cost was related to pharmacy expenses. CONCLUSIONS: These protocols were manageable in our context of limited health care resources. However, considering the significant costs and the modest survival rate, better selection criteria need to be used to identify patients likely to benefit from this approach.

Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma.

Mesoblastic nephroma is the most frequent renal tumor in newborns and young infants, and the cellular type is characterized by an ETV6-NTRK fusion, which constitutively activates the tropomyosin-related kinase (TRK) signaling pathway. Larotrectinib is a highly selective TRK inhibitor with activity in adult and pediatric patients who have TRK fusions. We present a rare case of a patient with mesoblastic nephroma metastatic to bone who had a dramatic response to larotrectinib.

The role of routine imaging in pediatric cutaneous melanoma.

BACKGROUND: Optimal imaging for children with pediatric malignant melanoma (MM) is unknown. METHODS: We reviewed clinical and imaging findings of patients with American Joint Commission on Cancer (AJCC) stage IIC-IV MM treated on our institutional MEL06 trial. All patients had baseline brain magnetic resonance imaging/computed tomography (MRI/CT), positron emission tomography/computed tomography (PET/CT), CT chest, abdomen, and pelvis (CTCAP). Patients on stratum A (PEG-interferon, where PEG is pegylated; AJCC IIC, IIIA, IIIB; n = 16) had imaging every 6 months; stratum B1 (PEG-interferon and temozolomide; unresectable measurable disease, metastatic, or recurrent; n = 2) had PET/CT scans every 2 months and brain imaging studies every 4 months; stratum B2 patients (PEG-interferon and temozolomide; unresectable nonmeasurable, metastatic, or recurrent, n = 3) had imaging every 4 months. Off-therapy imaging was done every 6 months for 3 years. RESULTS: There were 21 patients (11 females, 11 spitzoid, median age 14 years, head/neck [6], trunk [7], extremities [8]). Patients with spitzoid melanoma underwent 236 imaging studies in total (86 PET/CT, 81 CTCAP, 11 CT chest, 10 CT brain, 48 MRI brain) at a median cost per patient of $32,718. Thirteen studies (5.8%) had findings that led to two biopsies (one positive). For conventional MM, 162 studies (61 PET/CT, 57 CTCAP, 8 CT chest, 7 CT brain, and 29 MRI brain) were performed with a median cost per patient of $23,420. Twenty (14%) had findings leading to six biopsies (four positive). At 6.3 years (range 0.4-9.2), 17 patients remain disease-free. CONCLUSION: Children with spitzoid melanoma require minimal imaging at diagnosis and follow-up. Patients with conventional MM should be imaged according to adult guidelines.

Sustained Response to Targeted Therapy in a Patient With Disseminated Anaplastic Pleomorphic Xanthoastrocytoma.

Pleomorphic xanthoastrocytoma is a rare brain tumor with unique high frequency of BRAF V600E mutation which is plausible for targeted therapy. The anaplastic variant has generally worse prognosis. We present an adolescent patient with a disseminated relapse of anaplastic pleomorphic xanthoastrocytoma following surgery, radiotherapy, and chemotherapy. She had a dramatic and prolonged response to a BRAF inhibitor (Dabrafinib) and later to addition of a MEK inhibitor (Trametinib) on tumor progression. With minimal side effects and a good quality of life, the patient is alive more than 2 years after initiation of targeted therapy. This experience confirms the potential role of targeted treatments in high-grade BRAF-mutated brain tumors.

Review of management and morbidity of pediatric craniopharyngioma patients in a low-middle-income country: a 12-year experience.

BACKGROUND: Management of craniopharyngioma in children is challenging, and their quality of life can be significantly affected. Series describing this from low-middle income countries (LMIC) are few. PATIENTS AND METHODS: The study provides a retrospective chart review of pediatric patients <18 years old, diagnosed with craniopharyngioma between 2003 and 2014, and treated at King Hussein Cancer Center, Jordan. RESULTS: Twenty-four patients (12 males) were identified. Median age at diagnosis was 7.4 years (0.9-16.4 years). Commonest symptoms were visual impairment and headache (71%). Review of seventeen preoperative MRIs showed hypothalamic involvement in 88% and hydrocephalus in 76%. Thirteen patients (54%) had multiple surgical interventions. Five patients (21%) had initial gross total resection. Eleven patients (46%) received radiotherapy and six (25%) intra-cystic interferon. Five years' survival was 87 ± 7% with a median follow-up of 4.5 years (0.3-12.3 years). Four patients (17%) died; one after post-operative cerebral infarction and three secondary to hypothalamic damage. At their last evaluation, all but one patient required multiple hormonal supplements. Ten patients (42%) had best eye visual acuity (VA) >20/40, and four (16%) were legally blind. Eleven patients (46%) were overweight/obese; one had gastric bypass surgery. Seven patients had hyperlipidemia, and eight developed fatty liver infiltration. Eleven patients (65%) were attending schools and one at college. Nine of the living patients (53%) expressed difficulty to engage in the community. CONCLUSIONS: Management of pediatric craniopharyngioma is particularly complex and demanding in LMIC. Multidisciplinary care is integral to optimize the care and minimize the morbidities. A management outline for LMIC is proposed.

Optimizing Surgical Management for Rhegmatogenous Retinal Detachment in Eyes with Active Retinoblastoma: A Safety-Driven Approach.

Introduction: Intraocular surgeries are conventionally contraindicated for patients with active retinoblastoma (Rb) due to the potential risk of tumor dissemination. However, surgery is occasionally necessary to preserve vision in patients with a single eye when the eye is complicated by rhegmatogenous retinal detachment (RRD). Objective: This study aims to evaluate the outcomes of surgical repair for RRD in pediatric patients with active Rb utilizing a non-drainage scleral buckling approach. Results: This cohort included six eyes from six patients who harbored active Rb and presented with RRD; one had a concurrent tractional component. All eyes (100%) had active intraocular Rb and were undergoing active therapy (systemic chemotherapy, cryotherapy, and thermal laser therapy) when RRD developed. RRD consistently manifested at the site of recent cryotherapy in all cases. RRD repair in the affected eyes was performed by scleral buckling without subretinal fluid drainage. Five of the six eyes (83%) achieved complete retinal reattachment. One eye (17%) with a tractional component exhibited partial reattachment and was eventually enucleated due to persistent active disease. At a median follow-up of 15 months (range 12-180 months) after scleral buckling, all five eyes had persistent retinal attachment, and no case developed orbital or distant metastasis. Conclusions: Our study demonstrates that nondrainage scleral buckling is an effective and safe method for the surgical repair of RRD in eyes harboring active Rb, as most cases achieved persistent complete retinal reattachment without the risk of tumor spread.

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.

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.

Stigma in Pediatric Cancer: An Exploratory Study of Osteosarcoma and Retinoblastoma in Guatemala, Jordan, and Zimbabwe.

PURPOSE: Stigma is an understudied barrier to health care acceptance in pediatric oncology. We sought to explore the stigma experience, including its impact on cancer treatment decision making, and identify strategies to mitigate stigma for patients with osteosarcoma and retinoblastoma in Guatemala, Jordan, and Zimbabwe. METHODS: Participants included caregivers, adolescent patients (age 12-19 years), and health care clinicians. A semistructured interview guide based on The Health Stigma and Discrimination Framework (HSDF) was adapted for use at each site. Interviews were conducted in English, Spanish, Arabic, or Shona, audio-recorded, translated, and transcribed. Thematic analysis focused on stigma practices, experiences, outcomes, drivers, mitigators, and interventions. RESULTS: We conducted 56 interviews (28 caregivers, 19 health care clinicians, nine patients; 20 in Guatemala, 21 in Jordan, 15 in Zimbabwe). Major themes were organized into categories used to adapt the HSDF to global pediatric cancer care. Themes were described similarly across all sites, ages, and diagnoses, with specific cultural nuances noted. Pediatric cancer stigma was depicted as an isolating and emotional experience beginning at diagnosis and including internalized and associative stigma. Stigma affected decision making and contributed to negative outcomes including delayed diagnosis, treatment abandonment, regret, and psychosocial fragility. Overcoming stigma led to positive outcomes including resilience, treatment adherence, pride, and advocacy. Identified stigma drivers and mitigators were linked to potential interventions. CONCLUSION: Participants describe a shared stigma experience that transcends geography, cultural context, age, and diagnosis. Stigma manifestations have the potential to impact medical decision making and affect long-term psychological outcomes. Stigma assessment tools and interventions aimed at stigma mitigation including educational initiatives and support groups specific to pediatric cancer should be the focus of future research.

6-Mercaptopurine-induced recurrent acute pancreatitis in children with acute lymphoblastic leukemia/lymphoma.

Two children with acute lymphoblastic leukemia/lymphoma developed recurrent acute pancreatitis during treatment; the etiology was presumed to be secondary to 6-mercaptopurine (6MP). Both had no further attacks after discontinuation of 6MP. Acute pancreatitis secondary to 6MP is extremely rare in acute leukemia/lymphoma although it has been reported in patients with other conditions like inflammatory bowel disease; the reason for this difference is not clearly understood.

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.

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.

Retinoblastoma and uveal melanoma in Jordan: incidence, demographics, and survival (2011-2020).

PURPOSE: We present an epidemiologic analysis of retinoblastoma (RB) and uveal melanoma (UM) in Jordan to aid national strategies for improved ocular cancer surveillance and control. METHODS: A retrospective cohort of all Jordanian patients with RB and UM diagnosed over 10 years (2011-2020). Outcome measures included incidence, demographics, and outcomes. RESULTS: Retinoblastoma (n = 124) was more common than UM (n = 82); there was no sex predilection for either group. The median age at diagnosis of RB was 15 months(Six and 28 months for bilateral and unilateral cases, respectively), and the mean age-adjusted incidence was 8.2 cases per-million-children per year for children aged five years or less(one per 15,620 newborn per year). Fifty-one(41%) had bilateral disease, and 18(15%) had familial disease. Ninety-six(55%) eyes were group D or E(78% were T3/T4), and the five-year survival rate was 96%.For UM, the median age at diagnosis was 45 years with an incidence of 1.39 new cases per year per one million population. All(100%) had nonfamilial unilateral disease. Seventy-three(89%) had the tumor in the choroid, and 48(58%) had an advanced tumor that had invaded the sclera or the orbit (T3/T4) tumor. Sixty-two(76%) were treated by I-125 radioactive plaque, with globe salvage in 59(95%); the five-year survival rate was 85%. CONCLUSION: In Jordan, RB is more common and has better survival than UM. RB in Jordan and Western countries is equal in terms of incidence, globe salvage, and survival. UM is less common, with lower age at diagnosis (that was associated with better survival) in Jordan than in Western countries.

Causes of death and survival analysis for patients with retinoblastoma in Jordan.

Purpose: To analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan. Methods: We reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death. Results: Twenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4-38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p < 0.0001), the presence of high-risk pathological features in the enucleated eyes (p = 0.013), parental refusal of the recommended primary treatment plan (p < 0.0001), and extraocular extension (p < 0.0001). Conclusion: The 5-year survival rates of Rb patients in Jordan are as high as those in high-income countries. However, 5% are still dying from metastatic disease, prompting the need for awareness campaigns to educate the public about the high cure rates and to prevent treatment abandonment.