High risk Langerhans cell histiocytosis in children: the role of salvage in improving the outcome. A single center experience.

BACKGROUND: In pediatric multi-system high risk organs (RO +) Langerhans cell histiocytosis (LCH), failing 1st line treatment has the highest mortality. We aim to present the outcome of failure of 1st line whether due to disease progression (DP) at end of induction or reactivation (REA) after initial better status response. PATIENTS AND METHODS: Sixty-seven RO + LCH patients with hemopoietic, hepatic or splenic involvement, treated between 2007 and 2019 were retrospectively analyzed. The median follow-up (IQR) is 6 years (4-8.8 y).They were subjected to 2 eras of treatment; one with salvage by 2-Cda based regimen (2-CdABR) and another without. RESULTS: Of 67 patients, M/F 40/27, median age 1.74 y (0.2-10 y), 42 failed 1st line (62.7%). Of them DP n = 22 (52%) and REA n = 20 (48%). Of those with DP, 9/22 patients received 2-CdABR, where 5 survived in better status. While the remaining 13 did not receive 2-CdABR and all of them died. Otherwise, of those with REA, 12/20 reactivated on RO + mode. Of them, 8/12 received 2-CdABR, where only one survived in better status and the remaining 4 received vinblastine-based regimen,where 2 died and 2 were rescued. RO + 5-year overall survival (OS) was 65% (CI 95% 54 -78) while the event free survival (EFS) 36% (26.3-50.1). The OS of DP 27% (14-54) versus REA 67% (49-93) p 0.004. OS of DP with 2-CdABR 56% (31-97.7) versus 8% without (2-51), p < 0.001. While OS of REA with 2-CdABR 38% (13-100) versus 74% without (53-100) p 0.7. CONCLUSION: Survival of RO + remains limited. Failure of 1st line in RO + due to DP carries worse prognosis in relation to REA. In DP those who were not salvaged by 2-CdABR, showed dismal outcome. This could not be shown when applied in REA.

Serum MicroRNA-146b Expression for Malignancy Prediction in Euthyroid Patients with Indeterminate Thyroid Nodules.

Thyroid nodules are frequently found, but the vast majority of them are benign. The difficulty in managing thyroid nodules is correctly diagnosing the minority of those who have malignancy. Thyroid fine-needle aspiration cytology (FNAC) with indeterminate cytology continues to raise doubts about the presence of thyroid cancer, leading to an unnecessary thyroidectomy. Circulating miRNAs may be useful as diagnostic and prognostic markers for a variety of cancers, including thyroid cancer. The goal of the present study was to determine the predictive value of serum miRNA-146b expression level for thyroid cancer by estimating its level in a group of euthyroid patients with thyroid nodules with indeterminate FNAC results. This cross-sectional study included 45 euthyroid patients with indeterminate thyroid nodules who visited the Endocrine Outpatient Clinic and Endocrine Surgical Ward at Ain Shams University Hospitals. For all patient thyroid profiles, ultrasound of the thyroid gland and FNAC of the thyroid nodule were performed. In addition, preoperative assessment of serum microRNA-146b expression by real-time PCR was achieved and the results correlated with post-operative thyroid histopathology. There was no difference in serum miRNA-146b expression between patients with benign thyroid nodules versus patients with malignant nodules (p= 0.789). The risk of malignancy increased with the increase in size of the dominant thyroid nodules, as larger nodules had a higher risk of malignancy (p= 0.027). In conclusion, in euthyroid patients with indeterminate thyroid nodules, serum miRNA-146b is a poor predictor of thyroid malignancy, however, the larger the nodule size, the higher the risk of cancer.

Pediatric pulmonary multisystem langerhans cell histiocytosis: does lung lesion severity affect the outcome?

BACKGROUND: The pediatric pulmonary multisystem Langerhans cell histiocytosis (PPM LCH) is associated with either low risk or high risk organ(s). The nodulo-cystic lung lesions although pathognomonic, yet are very variable in severity and remain a source of controversy in certifying pulmonary LCH diagnosis. The study aimed to examine the prognostic value of clinical respiratory manifestations and radiological lung lesions severity. This is through associating a CT chest triad of bilateral, extensive and diffuse lesions. It is a retrospective study of 350 LCH patients who received systemic treatment at Children's Cancer Hospital Egypt during the period from 2007 to 2020. RESULTS: Sixty-seven patients (67/350-19.1%) had PPM LCH at presentation. Severe lung lesions were present in 24 of them. The median follow-up period was 61 months (IQR: 3.4-8.3). The 5-year overall survival (OS) and event free survival (EFS) was 89% and 56.6% respectively. The EFS, for severe radiological lesions triad was 38% ± 20.7 versus 66% ± 16.2 for non-severe lesions triad p 0.002, while for presence of chest X-ray changes 27% ± 22.344 versus absence of chest X ray changes 66% ± 14.7 p 0.001, for clinical respiratory manifestations 13% ± 13.9 versus none 62% ± 22.9 p < 0.001, for RO- with severe lung lesions 47% ± 30.4 versus RO- without severe lung lesions 69% ± 5.9 p 0.04. There was a tendency for the independent prognostic impact of severe lung involvement; aHR = 1.7 (95% CI 0.92-3.13, p = 0.09). CONCLUSION: Although the lung is a low -risk organ per se in LCH, our study demonstrates a non negligeable prognostic impact of severe lung involvement in the risk stratification of pediatric LCH. This warrants further study and external validation.

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes.

Osteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.

Prognostic Factors and Treatment Outcome of Relapsing and Refractory Pediatric Mature B-cell Non-Hodgkin Lymphoma, Children's Cancer Hospital Egypt Experience.

BACKGROUND: Relapsed non-Hodgkin lymphoma treated by chemotherapy and hematopoietic stem cell transplantation (HSCT) has a dismal prognosis. PATIENTS: It is a retrospective study, including pediatric patients diagnosed as mature B-cell non-Hodgkin lymphoma who were primarily refractory or relapsed over 8 years at CCHE. The aim of the study was to analyze the prognostic factors and outcomes of this group of patients. Our result is, 53 of 750 (7%) patients were included. Thirty-four (64.2%) patients had Burkitt lymphoma. Forty-eight (90.6%) patients received LMB 96 protocol initially. The median delay of duration between chemotherapy cycles in first-line treatment was 37 days. Thirty-five (66%) patients relapsed, 23 (65.7%) of them relapsed early, whereas 18 (34%) had tumor progression. Thirty-one (58.5%) patients presented with stage IV at the time of relapse. rituximab, ifosfamide, carboplatin, etoposide was the second line of treatment in 42 (79.24%) patients, and complete second remission was achieved only in 13 (24.3%) patients. Allogeneic HSCT was done for 4 (7.5%) patients, and auto HSCT was done for 3 (5.7%) patients. Three years of overall survival for relapsed and progressed patients were 35.3% and 11.1%, respectively, with a P-value of 0.009. Three years overall survival for patients who underwent HSCT was 85.7% compared with 18.1% for no HSCT with a P-value of 0.007. CONCLUSIONS: The relapse rate is higher than literatures because of the delay of duration between chemotherapy cycles in first-line treatment and more advanced stage at time of relapse. Progression of the disease had a worse outcome than relapse. HSCT in patients with the second remission markedly improved the outcome.

Parotid gland masses: outcomes in the pediatric age group.

BACKGROUND: Childhood parotid neoplasms appear to have different characteristics from adults. This point, in addition to the rarity of these tumors, reflects the challenges faced in diagnosing and treating parotid neoplasms in children. PATIENTS AND METHODS: This retrospective study included all children who presented to the Children's Cancer Hospital Egypt (CCHE, 57357) with parotid masses from January 2008 to December 2020. RESULTS: Twenty-one patients were included. Malignant neoplasms were found in 12 (57.1%) of which mucoepidermoid carcinoma was the most common. Benign neoplasms were found in 6 (28.6%) all of them were pleomorphic adenoma, and non-neoplastic lesions were found in 3 (14.3%). Superficial, deep, or total parotidectomy was performed according to the involved lobes. The facial nerve was sacrificed in three cases because of frank invasion by the tumor. Neck dissection was considered in clinically positive lymph nodes and/or T3/4 masses. Complications occurred in 7 (33.3%) all were of the malignant cases. Adjuvant radiotherapy was restricted to high-risk cases (7 cases). Recurrence occurred in two cases, and one patient died of distant metastasis. Fine needle aspiration cytology (FNAC) showed 88.9% sensitivity and 100% specificity for diagnosing malignant neoplasms. The correlation of radiological and pathological staging was fair (66.74% for overall staging). CONCLUSIONS: Parotidectomy is the backbone treatment for benign and malignant pediatric parotid tumors. Neck nodal dissection should be considered after preoperative FNAC of suspicious nodes. Adjuvant radiotherapy is considered only in high-risk tumors. Preoperative FNAC of parotid masses and clinically suspicious lymph nodes is highly recommended.

Prognostic significance of the ratio of surgically resected to radiologically detected lung nodules in patients with metastatic osteosarcoma.

The factors that affect the prognosis of patients' metastatic osteosarcoma are still poorly understood. In this study, we investigated a new prognostic factor, the ratio of surgically resected to radiologically detected osteosarcoma lung nodules (SR/RD), which may have predictive value. PATIENTS AND METHODS: Data from patients with metastatic osteosarcoma who underwent metastasectomy between January 2009 and December 2020, in a single center, were reviewed. The relationships between survival and the SR/RD ratio, timing of lung metastases, number of nodules, laterality, and presence of tumor necrosis at first metastasectomy were investigated. RESULTS: Among the 125 metastatic osteosarcoma patients, 80 patients had an SR/RD ratio ≤1. The median duration of follow-up was 72 months, ranging from 6 to 118 months. The five-year overall survival (OS) and postmetastasectomy event-free survival (EFS) for all patients were 36.5% and 18.1%, respectively. The five-year OS of patients with a low SR/RD ratio was 49.6% and that of patients with a high SR/RD ratio was 11.8 (P = 0.001). The two-year postmetastasectomy EFS rates of the high and low ratio groups were 24.1% and 9.4%, respectively (P = 0.001). The SR/RD ratio, number of nodules, and tumor necrosis had significant effects on OS and postmetastasectomy EFS in univariate analysis. A Cox proportional hazard model demonstrated that tumor necrosis and an SR/RD ratio >1 were associated with OS (HR = 1.8 and 2.01) and postmetastasectomy EFS (HR = 1,69 and 1.97). CONCLUSIONS: A high SR/RD ratio of greater than 1 and poor tumor necrosis were significantly associated with poor survival among patients with metastatic osteosarcoma who had lung metastasectomy. The high SR/RD ratio may be a surrogate outcome for incomplete metastatic tumor resection.

Prognostic value of detection of CD99+ , CD45- cells in peripheral blood by flow cytometry in children with Ewing sarcoma.

BACKGROUND: Early detection of metastasis and recurrence of Ewing sarcoma (ES) is important for early management. This work aimed to detect CD99+ , CD45- cells in peripheral blood by flow cytometry (FC) before and during chemotherapy and evaluate their prognostic significance. PROCEDURE: This prospective cohort study was carried out on 60 children newly diagnosed with ES at Children Cancer Hospital-Egypt 57357 and 40 healthy children control group. Detection of CD99+ , CD45- cells in peripheral blood was accomplished by FC at baseline before treatment and after five cycles of chemotherapy. Samples were classified as positive if they had more than the upper limit of cells observed in the control cases. Correlation between FC results and relapse and overall survival (OS) after one year was performed. RESULTS: Median percentage of CD99+ , CD45- cells was significantly increased in patients compared with controls (0.002% vs 0%, respectively, P < 0.001). Post-cycle 5 CD99+ , CD45- cells were increased in 12 patients, of them 11 patients' disease had either relapsed or progressed. Post-cycle 5 CD99+ ; CD45- cells had a 73.3% sensitivity and 97.8% specificity for predicting relapse or progression, whereas baseline only had 6.7% sensitivity and 77.8% specificity. The hazard ratio for mortality in the post-cycle 5 positive group was 18.4 [95% confidence interval (1.86 to 181.46)] times that of the negative group. One year OS was 91.67%. CONCLUSION: Post-cycle 5 CD99+ , CD45- cells in peripheral blood by FC is a strong predictor for relapse, progression, and mortality whereas baseline is a poor predictor in newly diagnosed patients with ES.

Can FDG-PET replace biopsy for the evaluation of residual tumor in pediatric mature B-cell non-Hodgkin lymphoma?

INTRODUCTION: The aim of our study is to evaluate the role of 18 F-labeled fluorodeoxy glucose positron emission tomography (18 FDG-PET) scan for the detection of viable residual mass in pediatric mature B-cell non-Hodgkin lymphoma (NHL). This study also aims to detect the negative predictive value, positive predictive value (PPV), sensitivity, and specificity of 18 FDG-PET. PATIENTS AND METHODS: A retrospective, cross-sectional nonrandomized study was carried out. We included all patients with newly diagnosed mature B-cell NHL treated at the Children Cancer Hospital Egypt during the period between July 2007 and the end of May 2018. Patients were included in the study if they (a) had a residual tumor mass, (b) underwent an 18 FDG-PET scan, and (c) had a pathologic documentation of this residual tumor. Patients were followed up till June 2019. RESULTS: Thirty-six patients were included, for whom 39 biopsies were performed. Mean age was 7.7 years. Median follow-up period was 52.8, range 6.1 to 117 months.18 FDG-PET scan was positive (Deauville score 3, 4, or 5) in 24 of 39 patients (61.5%), while it was negative (Deauville score 1 or 2) in 15 patients (38.5%). Positive 18 FDG-PET scan and biopsy were performed in 15 of 39 samples (38.4%; true positive, TP), while they were both negative in 13 samples (33.3%; true negative). Nine patients (23%) had positive scan and a negative biopsy (false positive), while 2 patients had negative uptake and a positive biopsy (false negative, FN)). Sensitivity of the 18 FDG-PET scan was 88.2% and specificity was 59.1%. PPV was 62.5% and NPPV was 86.6%. CONCLUSION: Changing therapy on the basis of a positive finding alone at the time of evaluation is not recommended. FN results exist, so biopsy confirmation is required to avoid the missing refractory disease. If negative, 18 FDG- PET can replace a biopsy if the latter is inaccessible or carries an unnecessary risk.

Whole lung irradiation for completely responding pulmonary metastases in pediatric Ewing sarcoma.

Aim: Scarce data assessing the real value of whole lung irradiation (WLI) in Ewing's sarcoma (ES) with lung-only metastasis, with published conflicting results. We studied the impact of WLI in a homogenous pediatric population. Materials & methods: Retrospective study evaluating the survival outcomes of WLI in these patients. Results: Out of 163 metastatic ES; 41 patients were eligible for WLI. 30 patients (73.1%) received WLI (+ve) while 11 patients (26.8%) did not receive WLI (-ve). Five-year event-free survival was statistically significant in WLI (+ve). Five-year pulmonary relapse-free survival showed trend for improvement with WLI (+ve), while 5-year overall survival was not statistically significant between the two arms. Conclusion: WLI added significantly to the long term clinical outcome of metastatic ES patients, with no irreversible toxicity.

"Comparative study between the efficacy of fractional CO2 laser, Q-switched Nd:YAG laser (1064 nm), and both types in treatment of keratosis pilaris".

The aim of this study was to assess and compare the efficacy of fractional CO2 laser, Q-switched Nd:YAG laser (1064 nm), and their combined use in treatment of keratosis pilaris. The study included twenty female patients. For each patient, three areas were randomly assigned to treatment by either fractional CO2 laser (area A) or Q-switched laser (1064 nm) (area C), or both types of laser (area B). All patients were assessed by digital photography at baseline and 1 month after the last session. Assessment was done by two non-blinded and two blinded investigators (blinded investigators do not know which area is treated with which machine and non-blinded knows). Patients reported the degree of satisfaction or any adverse effects also after 1 month from the last session. The three treatment modalities led to overall improvement in the KP lesions. According to patients' score and investigator two, area B showed statistically significant improvement compared to areas A and C (p=0.001 and p=0.039, respectively). The first blinded investigators' assessment revealed that there was statistically significant improvement in area C compared to A and B (p = 0.023). The assessment of both investigator one and the second blinded investigator revealed that there was improvement in the three areas with no statistically significant difference between them. Both fractional CO2 and Q-switched Nd:YAG laser (1064 nm) proved to be safe and effective in the treatment of keratosis pilaris regarding not only pigmentation but also follicular prominence; their combination may have an additive effect.

Characterization of pediatric head and neck masses with quantitative analysis of diffusion-weighted imaging and measurement of apparent diffusion coefficients.

PURPOSE: Our objective was to investigate the accuracy of quantitative diffusion-weighted imaging (DWI) to determine the histopathologic diagnosis of pediatric head and neck lesions. MATERIALS AND METHODS: This retrospective study included 100 pediatric patients recently diagnosed with head and neck tumors. All patients underwent preoperative conventional magnetic resonance imaging (MRI) and DWI. Each lesion was evaluated according to signal characteristics, enhancement pattern, and diffusivity. The average apparent diffusion coefficient (ADC) obtained from each tumor was compared to the histological diagnosis of benign, locally malignant, or malignant categories. RESULTS: Our retrospective study showed a significant negative correlation between average ADC and tumor histopathologic diagnosis (P < 0.001, r = -0.54). The mean ADC values of benign, locally malignant lesions, and malignant tumors were 1.65 ± 0.58 × 10-3, 1.43 ± 0.17 × 10-3, and 0.83 ± 0.23 × 10-3 mm2 s-1, respectively. The ADC values of benign and locally malignant lesions were overlapped. We found a cut-off value of ≥1.19 × 10-3 mm2s-1 to differentiate benign from malignant pediatric head and neck masses with a sensitivity of 97.3%, specificity of 80.0%, positive predictive value of 94.7%, and negative predictive value of 88.9%. CONCLUSION: Diffusion-weighted MRI study is an accurate, fast, noninvasive, and nonenhanced technique that can be used to characterize head and neck lesions. DWI helps to differentiate malignant from benign lesions based on calculated ADC values. Additionally, DWI is helpful to guide biopsy target sites and decrease the rate of unnecessary invasive procedures.

Outcome of High-risk Langerhans Cell Histiocytosis (LCH) in Egyptian Children, Does Intermediate-dose Methotrexate Improve the Outcome?

High-risk multisystem organ (RO+) Langerhans cell histiocytosis (LCH) has the least survival. We present the outcome of RO+ LCH in a pediatric single center. Fifty RO+ LCH patients, treated between 07/2007 and 07/2015, were retrospectively analyzed. Induction vinblastine (VBL) and prednisone (PRED) with intermediate-dose methotrexate (idMTX) was adopted until 2012 (n=20) wherein idMTX was omitted (n=30). The 3-year overall survival (OS) of MTX and non-MTX groups was 75% and 63%, respectively, P=0.537, while the event-free survival (EFS) was 36.9% and 13.2%, respectively, P=0.005. At week 12 of induction, "better status" was obtained in 80% of those receiving MTX, and 55% of those who were not. The statistically significant factors associated with both poor OS and EFS were trihemopoietic cytopenias, hepatic dysfunction, tri RO+ combination, and single induction. The factors associated with disease progression (DP) on induction were trihemopoietic cytopenias, hepatic dysfunction, and lack of idMTX, while those for disease reactivations (REA), the season of autumn/winter, lung disease, male sex, and idMTX were the associated factors. The 1-year OS was remarkably affected with the occurrence of DP versus REA versus none, wherein it was 47%, 93%, and 95%, respectively, P=0.001. In conclusion, idMTX is associated with better EFS. DP on induction remains of dismal prognosis in relation to disease REA afterwards. Risk stratification should highlight the role of trihemopoietic cytopenias, hepatic dysfunction, tri RO+, central nervous system risk site, and lung association.

Osteonecrosis in children with acute lymphoblastic leukemia: A report from Children's Cancer Hospital Egypt (CCHE).

BACKGROUND: As survival rates for children with acute lymphoblastic leukemia (ALL) improve, awareness of treatment complications becomes important. Osteonecrosis (ON) is a serious disabling complication in treated ALL patients. The aim of the study was to define the frequency of ON identified by magnetic resonance imaging (MRI) and to study the risk factors for ON. PATIENTS AND METHODS: The frequency of ON was evaluated retrospectively in 858 patients with ALL who were diagnosed at Children's Cancer Hospital of Egypt from January 2009 to December 2012. Patients were treated with St Jude Total Therapy Study XV. RESULTS: Of 858 patients evaluated, 665 were eligible for the study and 65 (9.7%) developed ON. The cumulative 5-year incidence of ON was 11.96% (SE, 0.131%). Of 154 patients aged 10 years and older, 40 (26%) developed ON. The mean age of patients with ON was 10.7 years. The prognostic factors with a significant relationship with ON were age 10 years and older (P = 0.0001) and intermediate-/high-risk group (P = 0.0001). However, gender did not have a significant relationship. At the onset of ON, the mean cumulative dexamethasone dose was 796 mg/m2 , and the mean total corticosteroid dose, calculated as prednisolone equivalence, was 6,431 mg/m2 . Out of 43 patients who developed ON while on corticosteroid therapy, 36 (84%) required dexamethasone dose modification and/or discontinuation. CONCLUSION: The frequency of ON among the studied patients was 9.7%. Risk factors with a significant association with ON were older age and more intensive corticosteroid therapy.

A Pharmacogenetic Study of VDR fok1 and TYMS Polymorphisms and Their Association With Glucocorticoid-Induced Osteonecrosis in Egyptian Children With Acute Lymphoblastic Leukemia.

Purpose: Osteonecrosis is a significant toxicity resulting from the treatment of pediatric Acute Lymphoblastic Leukemia (ALL). This study aimed to investigate the relationship between vitamin D receptor fok1 (VDR fok1) and thymidylate synthase (TYMS) gene polymorphisms with the glucocorticoid (GC) induced osteonecrosis (ON) in Egyptian pediatric ALL patients. In addition, to identify the possible association of genetic polymorphisms with other factors such as gender and ALL subtypes. Patients and Methods: A retrospective case-control study was conducted on 102 pediatric ALL patients under the age of 18 who were treated at Children Cancer Hospital Egypt according to St Jude SR/HR total XV protocol. The recruited patients were composed of 51 cases who developed GC-induced osteonecrosis and 51 age- and gender-matched patients who received glucocorticoids but remained osteonecrosis-free (controls). Genotyping of the VDR fok1 and TYMS genes was performed using restriction fragment length polymorphism (RFLP) and conventional PCR, respectively. Results: For the total 102 studied patients, the VDR fok1 single nucleotide polymorphisms (SNPs) frequency distribution were TT (8.8%), CT (34.3%), and CC (56.9%), while the TYMS tandem repeat gene variations were reported as 2R2R (20.6%), 2R3R (45.1%), and 3R3R (34.3%). VDR fok1 and TYMS polymorphic variants showed no association neither with gender; P-values 0.3808 and 0.1503, respectively, nor with ALL subtypes; P-values 0.9396 and 0.6596, respectively. The VDR fok1 polymorphisms showed a significant association with the development of ON; P-value = 0.003, on the other hand, TYMS tandem repeats did not show significant impact on osteonecrosis development; P-value = 0.411. Conclusion: This study showed a significant association between the VDR fok1 polymorphism and osteonecrosis. Such clinical pharmacogenetics results would be promising to discuss the possibility of dose adjustments aiming a regimen with the highest efficacy and least toxicity.

Reconstruction of the Scapula in Pediatric and Adolescent Patients After Total Scapulectomy. A Report of 10 Patients Treated by Extracorporeal Irradiation and Reimplantation of the Scapula.

BACKGROUND: Ewing sarcoma of the scapula is uncommon. Restoration of shoulder function after total scapulectomy is challenging. Extracorporeal irradiation and reimplantation is a well-known method of biological reconstruction in orthopaedic oncology; yet very few reports in the literature describe its specific use in tumors of the scapula. PATIENTS AND METHODS: Ten patients with the diagnosis of Ewing sarcoma of the scapula were surgically treated by total scapulectomy and extracorporeal irradiation and reimplantation of the scapula. The mean age at presentation was 10 years (3 to 15 y). Six patients were male individuals and 4 were female individuals. An extracorporeal single dose of 5000 cGy was applied to each graft. At reimplantation, internal fixation was used in the first 2 cases, whereas, in the following 8 patients, stabilization was carried out by resuturing of the glenohumeral and acromioclavicular joint capsules without internal fixation. An ipsilateral Latissimus Dorsi muscle flap was used in all patients to cover the irradiated scapula. RESULTS: The mean follow-up duration was 29.2 months (13 to 50 m). At the latest follow-up, 8 patients were continuously disease free and 2 patients had systemic relapse. No patient had local recurrence. The mean musculoskeletal tumor society functional score was 87% (66.6% to 100%). Eight of the 10 patients (80%) could actively elevate the upper limb up to and beyond 90 degrees in both the forward and scapular planes. Complications included wound gaping in 2 patients (20%), dislocation of the acromioclavicular joint in 3 patients (30%), and partial resorption of the scapular graft in 5 patients (50%). No patient showed any progressive deterioration of his or her shoulder function throughout the follow-up period. CONCLUSIONS: The irradiated scapular graft provides a stable biological fulcrum for the reattached muscles of the shoulder joint after total scapulectomy, thereby providing an adequate postoperative range of shoulder elevation. A longer follow-up study is needed to evaluate the progression and effect of graft resorption on the functional outcome. LEVEL OF EVIDENCE: Level IV.

Outcome of resectable pediatric Ewing sarcoma of the ribs.

PURPOSE: Was to evaluate the outcome of multimodality treatment in resectable primary Ewing sarcoma/primitive neuroectodermal tumor ES/PNET of the ribs and role of thoracoscopy in facilitating resection of these tumors. PATIENTS AND METHODS: This was a retrospective study including 22 patients with primary ES/PNET of the ribs surgically treated at Children's Cancer Hospital Egypt (CCHE) between January 2008 until the end of December 2014. RESULTS: Median age was 8.5years (range 5months to 16years.). All patients received neoadjuvant chemotherapy. Thoracoscopic exploration was performed in 15 (68%) patients. Resection included 1,2,3 and 4 ribs in (7,4,8 and 3 patients) respectively, parts of the diaphragm (3 patients), wedge resection of the lung (10 patients) and pleural nodules (2 patients). Primary closure was feasible in 11 patients and rib transposition was done in one patient. Reconstruction by proline mesh covered by muscle flap was done in 10 patients. Margins were microscopically positive in 3 patients and close in 2 patients. Postoperative radiotherapy was given in 8 patients. With a median follow-up of 38.5months, the 3-year event -free survival (EFS) and overall survival(OS) rates were 31.6% and 55.6%, respectively. CONCLUSION: Multimodality treatment is essential in the management of ES-PNET of the ribs. Neoadjuvant chemotherapy facilitates adequate resection. The role of thoracoscopy and the indications of postoperative radiotherapy need further evaluation.

Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): a randomized controlled trial.

BACKGROUND: The pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains dismal despite multiple therapeutic attempts. PURPOSE: To compare the results of treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using hypofractionated versus conventional radiotherapy. PATIENTS AND METHODS: Seventy-one newly diagnosed DIPG children were randomized into hypofractionated (HF) (39Gy/13 fractions in 2.6weeks) and conventional (CF) arm (54Gy/30 fractions in 6weeks). RESULTS: The median and one-year overall survival (OS) was 7.8months and 36.4±8.2% for the hypofractionated arm, and 9.5 and 26.2±7.4% for the conventional arm respectively. The 18-month OS difference was 2.2%. The OS hazard ratio (HR) was 1.14 (95% CI: 0.70-1.89) (p=0.59). The hypofractionated arm had a median and one-year progression-free survival (PFS) of 6.6months and 22.5±7.1%, compared to 7.3 and 17.9±7.1% for the conventional arm. The PFS HR was 1.10 (95% CI: 0.67-1.90) (p=0.71). The 18-month PFS difference was 1.1%. These differences exceed the non-inferiority margin. The immediate and delayed side effects were not different in the 2 arms. CONCLUSIONS: Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption.

Role of PET/CT in malignant pediatric lymphoma.

INTRODUCTION: Malignant pediatric lymphoma accounts for 10-15% of all pediatric cancers, (representing 2-3% of all malignancies), with a peak incidence between 5-9 years. Chemotherapy is usually the first and most common mode of treatment. The choice of treatment and prediction of prognosis depend on the histological type of tumor, initial staging, evaluating treatment response, and detection of early recurrence. Conventional imaging modalities have many limitations. PET/CT is more accurate, however so far the literature lacks the results of a large group of patients. AIM OF STUDY: To report the role of PET/CT in the above-mentioned objectives at the newly established Children's Cancer Hospital in Cairo, Egypt, which is one of the busiest dedicated pediatric oncology centers of such purposes in the world. All findings were proven by histopathology, clinically, and by clinical follow-up. PATIENT POPULATION: A total of 152 patients (35 girls and 117 boys) with histologically proven malignant lymphoma (117 HD, 35 NHL) were included in this study. They were divided into four groups. Group I: 41 patients for initial staging. Group II: 51 patients for evaluating early treatment response after two to three cycles of chemotherapy. Group III: 42 patients for evaluating treatment response 4-8 weeks after the end of their treatment. Group IV: 18 patients evaluated for long-term follow-up. Results of PET/CT were compared with the other conventional imaging modalities (CIM). RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values of PET/CT and CIM were as follows: In Group I: PET/CT modified staging and treatment in 11 out of 41 cases (26.8%), upstaged 5(12.2%) patients and down-staged six (14.6%) patients. Group II: 100%, 97.7%, 98%, 85.7%, 100%, respectively, for PET/CT and 83%, 66.6%, 68.6%, 25%, 96.7% for CIM respectively Group III: At the end of chemotherapy 100%, 90.9%, 92.8%, 75%, 100%, respectively, for PET/CT and 55.5%, 57.5%, 57.1%, 26.3%, 82.6% for CIM, respectively. Group IV: For long-term follow-up, all the parameters scored 100% for PET/CT, 100%, 38.4%, 72.2%, 50%, 100% for CIM, respectively. CONCLUSION: PET/CT in pediatric lymphoma is more accurate than CIM. We recommend that it should be the first modality for all purposes in initial staging, evaluating treatment response and follow-up.