Rhabdomyosarcoma in children: Retrospective analysis from a single tertiary care center in Saudi Arabia.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children occurring most commonly in the head and neck region. The treatment involves using a multimodality approach including chemotherapy, surgery, and radiation therapy. Survival for patients with localized disease has improved markedly, but the treatment of advanced disease remains a challenge. We report the clinical characteristics and outcome for patients treated at a tertiary care center in Saudi Arabia. METHODS: Patients aged 0-14 years diagnosed with RMS between 2005 and 2018 were included. Statistical analysis was performed using SPSS software. Kaplan-Meier method was used to calculate overall and event free survival. Cox proportional hazards model was used for multivariate analysis. RESULTS: One hundred and twenty-four patients were analyzed. The median age was 5.7 years with male predominance (2.4:1). The most common primary sites were head/neck (30%) and the genitourinary tract (25%). Embryonal RMS was present in 81%; alveolar in 19%. Most patients had intermediate risk disease (60%). The 5-year overall and event free survivals were 64.3% and 53.3%, respectively. Survival was influenced by primary tumor site, histology, and clinical risk group. Unfavorable primary site, high risk stratification, and poor initial response to therapy predicted a poor outcome. CONCLUSION: This study provides an insight on the current management outcomes for our patients with RMS. Cytogenetics and molecular diagnostics need to be incorporated as standard of care in the therapeutic approach of our patients. In addition, there is a need for national collaborative efforts to improve the outcome of RMS in children and adolescents.

Pediatric high risk neuroblastoma with autologous stem cell transplant - 20 years of experience.

BACKGROUND AND OBJECTIVE: Neuroblastoma is the most common extracranial solid tumor found in pediatric patients. High-risk neuroblastoma (HR-NBL) can be characterized by metastasis, age, and other tumor characteristics that result in an adverse outlook for this patient cohort. The standard of care includes induction chemotherapy, surgery, followed by stem cell autologous transplant (ASCT), and later, antidisialoganglioside (anti-GD2) antibodies. In this study, we provide the survival and toxicity data of our HR-NBL patients treated with a single ASCT. METHODS: We retrospectively analyzed pediatric HR-NBL patients treated with single ASCT after a carboplatin, etoposide, and melphalan (CEM) regimen in our institution between January 1993 and December 2014. RESULTS: There were 99 evaluable patients with male predominance. The median age at diagnosis was 3 years. Most of our HR-NBL patients were stage 4 (88%). All patients received ASCT. Peripheral blood was the graft source in 58% of the patients. Time for hematological count recovery with bone marrow as a graft source was prolonged but not statistically significant when compared with PBSCs. Of all the patients, 58% received radiation therapy to residual disease. Overt secondary leukemia was not seen in any of these patients. Three-year overall survival (OS) was 68.5% ± 5.2% and the 3-year event-free survival (EFS) was (48.3% ± 5.2%). CONCLUSION: Our HR-NBL patients tolerated high-dose chemotherapy well followed by single autologous stem cell transplant. Tandem transplant is a feasible option in our patient cohort. Apart from secondary solid tumors, there were no long-term complications seen.

Experience of treating pediatric hepatoblastoma at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia - Timely surgical intervention playing a key role.

BACKGROUND: Many studies have demonstrated that outcome in patients with hepatoblastoma is determined by tumor resectability and the presence or absence of metastatic disease. PURPOSE: To evaluate and disseminate information on diagnosis, treatment, and outcome of hepatoblastoma patients at a tertiary care hospital in Saudi Arabia. PATIENTS AND METHODS: Twenty-four pediatric patients with hepatoblastoma were treated at our institution between January 2005 and December 2012. The majority of our patients were stage III and above, while one-third of them presented with metastatic disease. Four (16.7%) had vascular invasion. Two-thirds of our patients (n = 16, 66.7%) had alpha-fetoprotein (AFP) level above 100,000 ng/mL. Twenty-one patients underwent surgery; two had upfront surgery before getting any chemotherapy, and 15 had surgery on schedule after pre-operative chemotherapy. Four patients had delayed surgery as the tumor was not resectable and received extra cycles of chemotherapy. Chemotherapy regimens used were based on SIOPEL study protocols until 2011 and Children's Oncology Group (COG) protocol from 2012 onwards. Relapse, progressive disease, or death from any cause were defined as events. RESULTS: Five-year overall survival (OS) of the cohort over a median follow-up time of 56.1 months was 70.6% ± 9.4% with seven (29.2%) events of mortality. No significant difference was found for age at diagnosis (less than 2 years vs. more), stage of disease, AFP levels (less than 100,000 vs. more), vascular invasion, or presence of metastatic disease at presentation in terms of OS. However, children receiving upfront or scheduled as-per-protocol surgery fared better than those who had delayed surgery (as the tumor was not resectable and they received extra cycles of chemotherapy) or did not undergo any surgery (P-Value .001). CONCLUSION: Favorable survival outcome could be achieved with complete tumor excision and adjuvant chemotherapy. Inability to perform surgical excision was the single most important predictor of mortality in our patients.

Empirical Monetary Valuation of a Quality-Adjusted Life-Year in the Kingdom of Saudi Arabia: A Willingness-to-Pay Analysis.

BACKGROUND: No willingness-to-pay (WTP) per quality-adjusted life-year (QALY) value exists for the Kingdom of Saudi Arabia (KSA). OBJECTIVE: The primary objective of this study was to determine the WTP for a QALY in the KSA. METHODS: Adult citizens of the KSA, patients with cancer, or members of the general public (MGP) were recruited to participate in a time trade-off survey to elicit health utilities. Cancer was chosen as the disease of interest for patients and the MGP, with a scenario describing stage 3 colorectal cancer, because it is a disease condition that impacts on both quality of life and survival time. In a second step, respondents were asked about their WTP to move from the estimated health state to a state of perfect health for 1 year (QALY). Finally, that amount was processed to generate the WTP for a full QALY. The second step was repeated with a 5-year horizon. Sensitivity analyses were performed without outliers. RESULTS: From 400 participants, data from 378 subjects were obtained and usable: 177 patients, 201 MGP; 278 male, 100 female subjects; 231 aged 26-65 years. Demographic distribution varied widely between the two subgroups for age, education level, and employment status, but with less variation in sex and income. Elicited health utilities were 0.413 (0.472 after adjustment) for the overall group, 0.316 (0.416) for patients, and 0.499 (0.508) for MGP. Overall WTP for a QALY was $US25,600 (adjusted $US32,000) for the 1-year horizon and $US19,200 (adjusted $US22,720) for the 5-year horizon. CONCLUSION: This was the first empirical attempt to estimate the WTP per QALY for the KSA. Results are comparable to those in some other countries and to gross domestic product figures for the KSA. Further research in a country-wide sample is warranted.

Incidence, clinical distribution, and patient characteristics of childhood cancer in Saudi Arabia: A population-based analysis.

PURPOSE: Information regarding the incidence and patterns of childhood malignancies is disproportionately overrepresented by high-income countries, representing mainly the Caucasian population. There is a need to evaluate and disseminate information for other ethnicities, particularly from the Middle East. METHODS: Data from the National Cancer Registry, Saudi Arabia (SA-NCR), for pediatric patients (age 0-14 years) diagnosed between 2005 and 2009 and for similar patients at our institution during the same period were analyzed. Population numbers reported in the 2007 national census were used to calculate the annual incidence of childhood cancer. RESULTS: Data from SA-NCR on 3885 patients were included in this analysis. The median age was 5.58 years, and 57.3% were males. The annual age-specific cancer incidence rate (ASR) for children in SA is 99.83 per million population; ASR per million for lymphoid leukemia is 25.75, 12.05 for brain tumors, and 9.82 for Hodgkin lymphoma. Of all childhood cancers in SA, 35% were treated at our institution. The five-year overall survival for these 1350 patients is 74.6% (median follow-up 7.52 years [95% confidence interval: 7.36-7.68]). Significant differences in the distribution of childhood malignancy subtypes were evident compared with other countries. CONCLUSION: We have reported differences in the cancer ASR and cancer subtype distribution for children in SA as compared with the worldwide incidence and with other populations. This paper provides a comprehensive epidemiological overview of childhood cancer in SA, which could be extrapolated to other regional Arab populations.

Iridogoniodysgenesis: A Challenging Case.

Iridogoniodysgenesis is a rare autosomal dominant disorder affecting anterior segment of the eye. Fifty percent cases of iridogoniodysgenesis have glaucoma, which is particularly difficult to manage. We report here a case of 40 years old man with this rare disorder, presenting to our glaucoma department. It was characterised by iris hypoplasia and juvenile glaucoma. To stop fluctuation in his intraocular pressure (IOP) and to save his vision from glaucomatous damage, our team had to do three different surgical procedures, i.e. trabeculectomy with F5U, diode laser cycloablation and aqueous shunt procedure, over a period of 10 months. This case report discusses management of glaucoma in this particular patient and challenges faced during the treatment. Regular follow-up and timely intervention can save such patients from complete blindness. To authors' knowledge, this is the first reported case of iridogoniodysgenesis in Pakistan.

Wilms tumor: an update.

Wilms tumor (WT) is the most common neoplasm of the kidney in children. It is an embryologic tumor that histologically mimics renal embryogenesis and is composed of a variable mixture of stromal, blastemal, and epithelial elements. Nephrogenic rests, generally considered to be precursor lesions of the WT, are foci of the embryonic metanephric tissue that persist after the completion of renal embryogenesis. These are classified as perilobar and intralobar based on their location and maybe present as single or multiple foci. Intralobar and perilobar rests and the tumors arising from these rests differ morphologically and are characterized by 2 different sets of genetic abnormalities involving 2 adjacent foci, WT1 and WT2, on the short arm of chromosome 11. WTs arising in the intralobar rests tend to be stromal predominant and have a mutation or deletion of WT1. Germline mutation in WT1 may be associated with syndromic conditions such as WAGR and Denys-Drash syndromes. Perilobar rests and their corresponding tumors usually have loss of imprinting/loss of heterozygosity involving WT2, which contains several parentally imprinted genes. Loss of function of these genes, if present constitutionally, may be associated with Beckwith-Wiedemann syndrome or may result in isolated hypertrophy. Abnormalities in several other genes may also be seen in WT. These include WTX, (on chromosome X), CTNNB1 (chromosome 3), and TP53 (chromosome 17) among others. WT with loss of heterozygosity at 1p and 16q may have poor prognosis, requiring aggressive therapy. Treatment modalities for WT have evolved over many decades, primarily through the efforts of Dr J Bruce Beckwith at National WT study. This work is now being carried out by Children Oncology Group in North America and International Society of Pediatric Oncology in Europe. Although their therapeutic approaches are somewhat different, both have reported excellent results with equally high cure rates.