Patterns and Outcomes of Acute Central Nervous System Complications During Treatment of Childhood Acute Lymphoblastic Leukemia: A Single-center Experience.

Central nervous system (CNS) complications are considered adverse events during the treatment of pediatric acute lymphoblastic leukemia (ALL). This study aimed to assess the incidence, types, clinical and radiologic patterns, risk factors, and the fate of different CNS complications during the treatment of pediatric ALL. A retrospective study included 390 patients with pediatric ALL, treated according to St. Jude total XV protocol at the National Cancer Institute, Cairo University, from January 2012 to December 2017. Thirty-nine (10%) patients developed different types of CNS complications. Nineteen (4.9%) patients had cerebrovascular complications, 12 (3.1%) patients had posterior reversible encephalopathy syndrome (PRES), and 6 (1.5%) patients had leukoencephalopathy; both CNS infections and leukemic infiltrates were diagnosed in one patient each. CNS complications were significantly higher in patients older than 10 years old, patients with high-risk disease, and patients who were classified as CNS III status with a statistically significant P value of 0.040, 0.020, and 0.002, respectively. There were 31 (79.5%) cases that achieved complete recovery, 6 (15.4%) patients who died, and 2 (5.1%) patients who developed residual neurological deficits. In conclusion, pediatric patients with ALL, who presented with older age, high-risk disease initially, and had initial CNS III status, were at higher risk of developing acute CNS complications during their treatment period. Patients who developed visual disturbances were associated with unfavorable outcomes. Despite that, around 80% of patients showed complete recovery, but still, 15% of them died from these complications.

The Brain Tumor Segmentation (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI.

Clinical monitoring of metastatic disease to the brain can be a laborious and timeconsuming process, especially in cases involving multiple metastases when the assessment is performed manually. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) guideline, which utilizes the unidimensional longest diameter, is commonly used in clinical and research settings to evaluate response to therapy in patients with brain metastases. However, accurate volumetric assessment of the lesion and surrounding peri-lesional edema holds significant importance in clinical decision-making and can greatly enhance outcome prediction. The unique challenge in performing segmentations of brain metastases lies in their common occurrence as small lesions. Detection and segmentation of lesions that are smaller than 10 mm in size has not demonstrated high accuracy in prior publications. The brain metastases challenge sets itself apart from previously conducted MICCAI challenges on glioma segmentation due to the significant variability in lesion size. Unlike gliomas, which tend to be larger on presentation scans, brain metastases exhibit a wide range of sizes and tend to include small lesions. We hope that the BraTS-METS dataset and challenge will advance the field of automated brain metastasis detection and segmentation.

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020-2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the "2020 ECMM/ISHAM consensus criteria"; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

Value of diffusion MRI versus [18F]FDG PET/CT in detection of cervical nodal metastases in differentiated thyroid cancer patients.

BACKGROUND: In differentiated thyroid cancer (DTC) patients, cervical nodal metastasis is a negative prognostic factor. Preoperative imaging plays an important role in treatment planning for nodal metastasis and recurrence. The aim of the study is to compare the diagnostic performance of the diffusion-weighted magnetic resonance imaging (DW-MRI) and the F-18 flurodeoxyglucose positron emission computed tomography ([18F]FDG PET/CT) in detection of cervical nodal deposits in DTC patients. MATERAL AND METHODS: The study was conducted on 30 patients, each performed both modalities just before the surgery. The gold standard was the pathological specimens with post-operative clinico-radiological follow-up, to assess the diagnostic performance of each modality. RESULTS: Based on pathological and post-operative clinico-radiological follow up data. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were 84%, 80%, 50%, 95% and 83% for PET/CT compared to 84%, 60%, 42.8%, 91.3% and 80% for DW-MRI. On comparing the diagnostic performance of combined DW-MRI and PET/CT to each modality alone, the sensitivity and NPV were improved to 96% and 80% respectively. CONCLUSIONS: [18F]FDG PET/CT study is a valuable diagnostic modality for the assessment of cervical nodal deposits in DTC patients, surpassing DW-MRI. Combined PET/CT and DW-MRI techniques seemed to have synergistic performance, mainly in terms of sensitivity and NPV, for detection of nodal metastases.

Hypofractionated Radiation Therapy For Diffuse Intrinsic Pontine Glioma: A Noninferiority Randomized Study Including 253 Children.

PURPOSE: Pediatric diffuse intrinsic pontine glioma is an orphen disease. This study aimed to confirm the noninferiority of hypofractionated (HF) radiation therapy. Identification of the prognostic factors that determine the overall survival (OS) and progression-free survival (PFS) was the secondary objective. METHODS AND MATERIALS: We randomized 253 patients into 3 arms of radiation therapy regimens: HF1, receiving 39 Gy in 13 fractions; HF2, receiving 45 Gy in 15 fractions; and conventional fractionation (CF), receiving 54 Gy in 30 fractions. The OS and PFS were calculated using Kaplan-Meier methods, and the noninferiority was estimated against the CF arm. RESULTS: The median OS for the HF1, HF2, and CF were 9.6, 8.2, and 8.7 months, respectively. The 1-, 1.5-, and 2-year OS were 34.6%, 17.9%, and 10.7% for HF1; 26.2%, 13.1%, and 4.8% for HF2; and 25.3%, 12.1%, and 8.4% for CF, respectively (P = .3). The hazard ratio was 0.776 and 1.124 for HF1 and HF2, respectively. Considering the noninferiority margin (Δ) of 15% and a power of 90%, the lower inferiority confidence interval for HF1 was -14.34% and for HF2 it was 11.37% (both below Δ), confirming its noninferiority at 18-months OS. Younger patients (2-5 years of age) had better median OS in the whole cohort (11.6 months), HF1 (13.5), and CF (12.1) but not HF2 (6.2) (P = .003). Furthermore, the OS rates at 1, 1.5, and 2 years for children 2 to 5 years of age in the HF2 arm were lower than those in the HF1 and CF arms. However, similar acute and late side effects were reported in the 3 arms. CONCLUSIONS: Two hypofractionated radiation therapy proved to be noninferior to conventional fractionation. Young age (2-5 years) is the only prognostic factor determining both OS and PFS. The young age superiority was lost with a higher hypofractionated radiation therapy dose, necessitating more caution in applying 45 Gy in 15 fractions in younger children (2-5 years of age).

Swallowing sparing intensity modulated radiotherapy versus standard parotid sparing intensity-modulated radiotherapy for treatment of head and neck cancer: a randomized clinical trial.

BACKGROUND: Dysphagia is a distressing symptom during and after radiotherapy treatment in head and neck cancer (HNC) patients. The objective of this prospective study was to investigate whether swallowing sparing intensity modulated radiotherapy (SW-IMRT) reduces the occurrence of swallowing dysfunction compared to the standard IMRT (ST-IMRT). METHODS: We randomized, planned, and treated patients with HNC who needed whole neck irradiation using the simultaneous integrated boost (SIB) IMRT technique. Doses of 70, 60, and 54 Gy (over 33 daily fractions) were prescribed to the primary tumor, high-risk and low-risk regions, respectively. The postoperative cases received 60 and 54 Gy (over 30 daily fractions) to the high-risk planning target volume (PTV) and low-risk PTV. We contoured organs at risk related to swallowing dysfunction (SWOARs) in all cases. In the ST-IMRT group, parotids only were spared. In the SW-IMRT group, parotids and SWOARs outside the high-risk PTV were spared. Assessment of dysphagia included clinical and instrumental evaluation. RESULTS: One hundred forty-six patients ended their radiotherapy treatment. Dose distribution showed comparable PTV coverage and no difference in parotid glands sparing between the two groups. SWOARs dose reduction with SW-IMRT differs according to tumor location and its overlap with SWOARs. Using different assessment methods, SW-IMRT was associated with a lower occurrence of dysphagia up to one year after treatment. There was no difference between the two groups regarding acute dysphagia (p = 0.262), overall survival (p = 0.811), and disease-free survival (p = 0.876). CONCLUSION: SW-IMRT is significantly better than ST-IMRT regarding a physician-rated and objective assessment of swallowing dysfunction at short- and long-term post-treatment follow-up.

Aggresomes predict poor outcomes and implicate proteostasis in the pathogenesis of pediatric choroid plexus tumors.

PURPOSE: Protein misfolding and aggregation result in proteotoxic stress and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated proteins in different inclusion bodies. The aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Choroid plexus tumors (CPTs) are rare neoplasms comprised of three pathological subgroups. The underlying mechanisms of their pathogenesis remain unclear. This study aims to elucidate the prognostic role and the biological effects of aggresomes in pediatric CPTs. METHODS: We examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients' outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs. RESULTS: Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients' outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications. CONCLUSIONS: These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients' outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control.

Patterns, risk factors and outcome predictors of posterior reversible encephalopathy syndrome in pediatric cancer patients.

The purpose of this study was to assess the clinical and radiological patterns and outcome predictors of posterior reversible encephalopathy syndrome (PRES) in pediatric cancer patients. A retrospective study included patients who developed PRES during their treatment at the Children's Cancer Hospital Egypt. A total of 50 patients developed PRES. Leukemia and lymphoma were the commonest diagnoses (64%). Regarding the MRI findings, occipital affection was the most common (92%), followed by frontal and temporal lobes involvement in 32% and 22% respectively and advanced PRES was described in 8 patients. Of the whole patients, 80% had complete clinical resolution and 60% showed complete radiological resolution at 2 weeks' evaluation and 2 patients died out of PRES. Unfavorable outcome was associated with those who had motor dysfunction, status epilepticus at presentation, frontal lobe and thalamic affection and atypical PRES. PRES might present in atypical sites with poor outcome including death.

Accuracy of combined quantitative diffusion-weighted MRI and routine contrast-enhanced MRI in discrimination of benign and malignant salivary gland tumors.

BACKGROUND: Preoperative imaging of salivary gland tumors is important for predicting and differentiating benign from malignant tumors, and for aiding management planning. We aimed to investigate the accuracy of combined quantitative diffusion-weighted magnetic resonance imaging (MRI) and routine contrast-enhanced MRI in the evaluation of salivary gland tumors and the differentiation of benign from malignant tumors. RESULTS: This study included 51 patients with a total of 16 benign and 35 malignant lesions that were detected by histopathological analysis. There was a statistically significant difference between the apparent diffusion coefficient values (ADC) of malignant and benign lesions (0.69 ± 0.22 × 10-3 mm2/s and 1.39 ± 0.52 × 10-3 mm2/s respectively). The optimal cut-off ADC value was 1.08 with 75% specificity and 97% sensitivity. The routine contrast-enhanced MRI had predicted benign and malignant tumors with 65% sensitivity and 44% specificity. The sensitivity and specificity were greatly increased when quantitative diffusion-weighted MRI was combined with routine contrast-enhanced MRI: 100%, and 88% respectively. A receiver operating curve was generated. The area under curve was 0.88 (p < 0.001, 95% CI: 0.76-0.99). CONCLUSION: Combined quantitative diffusion-weighted MRI with ADC measurements and routine contrast-enhanced magnetic resonance imaging are helpful tools for the evaluation of salivary gland tumors and help differentiate benign from malignant lesions.

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.

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Role of FDG-PET scan in the management of pediatric mature B cell non-Hodgkin's lymphoma. CCHE experience.

AIM OF WORK: To evaluate the sensitivity (Se), specificity (Sp), and predictive values (PV) of PET scan during management of pediatric mature B cell non-Hodgkin's lymphoma (NHL) in comparison with conventional computed tomography (CT) scan. PATIENTS AND METHODS: A retrospective study enrolled on pediatric NHL patients at Children Cancer Hospital Egypt (CCHE) during the period from July 2007 to the end of June 2013. RESULTS: For 115 pediatric patients diagnosed with mature B cell NHL, 152 PET and 152 CT scans were done simultaneously. Median age was 5.7years. They were 85 males (74%) and 30 females (26%). One hundred twenty six scans (82.9%) were done for 100 (87%) Burkitt lymphoma (BL) patients, while 26 scans (17.1%) were done for 15 (13.0%) patients with diffuse large B cell NHL (DLBC). Nineteen examination (12.5%) were done before starting chemotherapy (group 1), 107 (70.3%) at time of evaluation (group 2), and 26 (17.1%) during follow up (group C). Overall sensitivity was 91.6% for PET and 70.0% for conventional CT (p=0.02). Specificity was 84.1% for PET and 58.9% for CT (p<0.001). Positive predictive value (PPV) for PET was 50%, while was 22% for CT scan (p<0.001). Negative predictive value (NPV) for PET was 98%, and 92% for CT (p=0.01). CONCLUSION: PET scan is significantly more sensitive than conventional CT in the management of aggressive pediatric mature B cell NHL. PET negativity is an excellent indicator of tumor response.

Posterior reversible encephalopathy syndrome in cancer patients: a single institution retrospective study.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiologic entity. Its management and outcome in the oncology population is limited because it is still difficult to identify despite an increasingly recognized occurrence. This is the largest retrospective study of PRES in cancer patients reported from a single institution. We explore the clinical manifestations and radiologic features to comprehensively assess PRES in order to prevent permanent neurologic deficits and mortality. We retrospectively identified 69 patients with cancer who developed PRES at MDACC between 01/2006 to 06/2012. Clinical and radiographic data were abstracted from their records and reviewed for our analysis. Mean age at PRES onset was 52 ± 17.8 years. Fifty-two (75 %; p < 0.001) patients were women. Most common diagnoses were leukemia (30 %) and lymphoma (12 %). Forty-eight (70 %) patients were treated with chemotherapy, 21 (30 %) bone marrow transplant and 14 (20 %) tacrolimus. Most common clinical presentation was seizures (67 %). PRES was associated with hypertension in 62 (90 %) patients. On brain MRI, 33 (44 %) patients had some evidence of hemorrhage, 22 (73 %) of these were thrombocytopenic. Thirty-five (51 %) patients fully recovered and 19 (28 %) had permanent neurological deficits. Morbidity and mortality were associated with continuation with offending agent, thrombocytopenia, variations in mean arterial pressure ≥20 mmHg, electrographic seizures at onset, atypical MRI pattern and delay in diagnostic imaging (7.4 ± 4.8 days vs. 1.9 ± 1.8 days; p = 0.031) as half of them did not receive a prompt intervention. Special attention should be given to patients who present with high-risk factors in order to prevent development of PRES or decrease patient morbidity and mortality. Management of PRES should be guided by the radiographic findings. Overall, early recognition, discontinuation of the offending agents, correction of thrombocytopenia and blood pressure control are still the main strategies to manage PRES.

Echinococcal Cyst of the Pancreas with Cystopancreatic Duct Fistula Successfully Treated by Partial Cystectomy and Cystogastrostomy.

The primary pancreatic hydatid (echinococcal) cyst is extremely rare with a reported incidence of <1%. Owing to its rareness and a considerable overlap of imaging features, a preoperative diagnosis is usually difficult. The dilemma in confirming this benign diagnosis has often questioned the extent of radical pancreatic resection. The involvement of pancreatic duct (cystopancreatic duct fistula) further complicates the management of such cystic lesions. In this report, we present a case of isolated hydatid cyst of the pancreatic body and tail communicating with the pancreatic duct. Cystogastrostomy preceded by partial cystectomy in the same setting has never been reported to date. The patient had an uneventful postoperative course and follow-up showed no evidence of cyst recurrence or dissemination. We consider this a safe surgical option in longstanding large cysts, especially if a cystopancreatic fistula is detected beforehand. The success of such a procedure however may rely on the size and thickness of the cyst wall to support this anastomosis.

Hematopoietic tumors of the female genital system: imaging features with pathologic correlation.

Various hematopoietic neoplasms can involve the female genital system. The most common hematological malignancy that involves the female genital system is lymphoma and secondary involvement is more common than primary genital lymphoma. Rarely, leukemic infiltration and extramedullary plasmacytomas of the female genital tract may also occur. Being infrequent, these lesions are commonly misdiagnosed radiologically. Therefore, understanding these malignancies of the female genital system and recognizing their imaging features are of utmost clinical importance. Although definitive diagnosis can be made only by histological analysis, imaging of these tumors plays an important role in detecting lesion extensions, guiding biopsies, staging disease, planning therapy, and detecting recurrence.