Preliminary findings of German-sourced ONC201 treatment in H3K27 altered pediatric pontine diffuse midline gliomas.

PURPOSE: H3K27 altered pediatric pontine diffuse midline gliomas (pDMG) have a poor prognosis, and conventional treatments offer limited benefits. However, recent advancements in molecular evaluations and targeted therapies have shown promise. The aim of this retrospective analysis was to evaluate the effectiveness of German-sourced ONC201, a selective antagonist of dopamine receptor DRD2, for the treatment of pediatric H3K27 altered pDMGs. METHODS: Pediatric patients with H3K27 altered pDMG treated between January 2016 and July 2022 were included in this retrospective analysis. Tissue samples were acquired from all patients via stereotactic biopsy for immunohistochemistry and molecular profiling. All patients received radiation treatment with concurrent temozolomide, and those who could acquire GsONC201 received it as a single agent until progression. Patients who could not obtain GsONC201 received other chemotherapy protocols. RESULTS: Among 27 patients with a median age of 5.6 years old (range 3.4-17.9), 18 received GsONC201. During the follow-up period, 16 patients (59.3%) had progression, although not statistically significant, the incidence of progression tended to be lower in the GsONC201 group. The median overall survival (OS) of the GsONC201 group was considerably longer than of the non-GsONC201 group (19.9 vs. 10.9 months). Only two patients receiving GsONC201 experienced fatigue as a side effect. 4 out of 18 patients in the GsONC201 group underwent reirradiation after progression. CONCLUSION: In conclusion, this study suggests that GsONC201 may improve OS in pediatric H3K27-altered pDMG patients without significant side effects. However, caution is warranted due to retrospective design and biases, highlighting the need for further randomized clinical studies to validate these findings.

A Rare Case of BRAF-mutated Metastatic Pleomorphic Xanthoastrocytoma Patient who Developed Radiodermatitis After Receiving Anti-BRAF Treatment.

Pleomorphic xanthoastrocytoma (PXA) is a rare type of grade 2 or 3 brain tumor that usually occurs in children and young adults. The standard treatment for PXA is maximally safe resection, usually with adjuvant radiation therapy, for high-grade tumors. BRAF V600E mutation is one of the most common molecular alterations in these tumors, with nearly 70% of cases carrying this mutation. Although BRAF inhibitors have shown promise in treating progressive or refractory disease, their use has been associated with various adverse effects, including radiodermatitis, which is a relatively common complication. This paper presents a case of a 16-year-old male patient with BRAF-mutated metastatic PXA, who developed mild radiodermatitis after receiving BRAF inhibitors with concurrent radiation therapy.

EWSR1(22q12) Translocation Positive Pediatric Adrenal Tumor with Loss of 1p, 11q, and Unbalanced Gain of 17q: Neuroblastoma or Ewing Sarcoma?

Background Although neuroblastoma and Ewing sarcoma/Primitive neuroectodermal tumor are different clinical entities, they are both a member of small round blue cell tumors and can mimic each other's behavior in clinical and molecular aspects. Case report: A 3 year-old girl with an abdominal mass was found to have a small round blue cell tumor originating from the right adrenal gland. High level of neuron specific enolase, initial genetic test results (N-Myc amplification: negative, loss of 1p, 11q, and unbalanced gain of 17q) and characteristic radiological appearance of the tumor suggested a preliminary diagnosis of neuroblastoma but further analysis showed CD99 expression and presence of EWSR1 rearrangement, which are mostly observed in Ewing sarcoma. Conclusion: Adrenal gland tumors of childhood with complex immunophenotypic features requires distinguishing two discrete tumors in the small round blue cell tumor group, neuroblastoma and Ewing sarcoma. Although no exact diagnosis of the tumor was made, we reached a good response with neuroblastoma treatment protocol.

Evaluation of Clinical Properties and Treatment Responses of Infantile Hemangioma.

BACKGROUND: Infantile hemangiomas are the most common vascular tumors in childhood. Although spontaneous regression is common; several infantile hemangioma patients need treatment due to possible morbidities. The aim of this study was to investigate the medical methods used in the treatment of infantile hemangiomas and to evaluate the factors affecting treatment response. METHODS: Clinical and demographic characteristics, risk factors, treatment indications, modalities, duration, and responses of 100 patients between January 2007 and January 2017 were evaluated. RESULTS: The most common form of hemangiomas was superficial lesions. Sixty three per cent of the patients were female. Ulceration and hemorrhage were found in 26% of the cases and ocular problems were detected in 3% of the cases. Among the indications for treatment were cosmetic reasons with 56%, ulcer and bleeding with 25% and risk of vision problems with 13%. Propranolol with/without steroid was used as first line treatment and response rates were: 84 patients with more than 50% response, 9 patients with less than 50% response and 7 patients with treatment refractory. The most important factor affecting the treatment response was age at the beginning of the treatment. Duration of treatment, presence of ulceration, location, and size of hemangioma were also found to have significant effects on responses. CONCLUSIONS: This study demonstrated the importance of the kind and initiation time of infantile hemangioma treatment. A strong positive effect can be reached by starting treatment before the end of the proliferation phase. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5009.

Cross-sectional study: long term follow-up care for pediatric cancer survivors in a developing country, Turkey: current status, challenges, and future perspectives

Aim: The main purpose of this study is to determine the current status of long-term follow-up (LTFU) for childhood cancer survivors and the challenges of LTFU for pediatric cancer survivors at pediatric oncology institutions in Turkey. Material and methods: A questionnaire was e-mailed to the directors of 33 pediatric oncology centers (POCs) registered in the Turkish Pediatric Oncology Group (TPOG). Of these 33 active TPOG institutions, 21 participated in the study and returned their completed questionnaires. Results: Only 1 of the 21 participating centers had a separate LTFU clinic. The remaining centers provided LTFU care for childhood cancer survivors at the pediatric oncology outpatient clinic. Of these centers, 17 (80.9%) reported difficulty in transition from the pediatric clinic to the adult clinic, 14 (66.6%) reported insufficient care providers, and 12 (57.1%) reported insufficient time and transportation problems. As neglected late effects, 16 (76.1%) centers reported psychosocial and getty job problems and 11 (52.3%) reported sexual and cognitive problems. None of the centers had their own LTFU guidelines for their daily LTFU practice Conclusion: This study was the first to gain an overview of the needs of POCs and the gaps in survivorship services in Turkey. The results from this study will help to develop a national health care system and national guidelines for pediatric cancer survivors.

Subclinical anthracycline-induced cardiotoxicity in long-term follow-up of asymptomatic childhood cancer survivors: Assessment by speckle tracking echocardiography.

OBJECTIVE: Survivors of childhood cancer treated with anthracyclines carry the risk for developing late-onset cardiotoxicity. The purpose of this study was to evaluate left ventricular (LV) function in this patient group and compare it with healthy controls by means of conventional and speckle tracking echocardiography (STE) after exposure to chemotherapy. MATERIAL AND METHODS: Conventional and STE were performed in 45 childhood cancer survivors (mean age 11 ± 4.6; 26 male) treated with anthracyclines (median cumulative dosage 240 mg/m2 ; range, 100-460) and compared with age, gender and body surface area matched healthy controls. Follow-up period after chemotherapy was 21.9 ± 17.8 months. Blood samples were taken from survivors and controls to determine brain natriuretic peptide (BNP). RESULTS: Following anthracycline exposure, pediatric cancer survivors had lower longitudinal, radial anteroseptal, and radial anterior strain values compared to controls (P < .05). The calculated global longitudinal and global radial strain values were lower compared to the control group (P < .05). Both groups had normal ejection fraction (EF) and fractional shortening (FS). Brain natriuretic peptide (BNP) levels of both groups were in the normal range. CONCLUSION: Despite normal EF and FS, children exposed to anthracycline therapy may have late-onset subtle changes of LV strain values measured by STE. Whether these changes of strain can predict future risk of developing heart failure needs to be explored in further studies.

Malignant triton tumor of trigeminal nerve-case report.

INTRODUCTION: Here we are presenting a unique case of malignant triton tumor of the trigeminal nerve in a 4-year-old boy who presented with diplopia and ptosis. INTERVENTION: Near total excision of the tumor was performed, and adjuvant chemotherapy and radiotherapy were administered. RESULTS: The patient is in good health and has no evidence of clinical and radiological tumor recurrence for 22  months.

Post-traumatic stress disorder in mothers of children who have undergone cancer surgery.

BACKGROUND: The aim of this study was to investigate the rate of post-traumatic stress disorder (PTSD) and associated risk factors among mothers of children who underwent cancer surgery. METHOD: This cross-sectional, multi-center study included a total of 60 mothers whose children underwent major thoraco-abdominal surgery and were under follow up in the outpatient setting between February 2016 and May 2016. Clinical Data Form, Hospital Anxiety and Depression Scale (HADS), and Clinician-Administered PTSD scale were used. RESULTS: Of all participants, 13 (21.7%) were diagnosed with PTSD. These mothers had shorter duration of marriage, longer duration of hospital stay after surgery, and higher HADS scores, compared with the others without PTSD. Thoughts of guilt such as "I am being punished or tested" were more frequent in mothers with PTSD. Insomnia, irritability, concentration problems, and psychological reactivity were the most common symptoms. CONCLUSION: Post-traumatic stress disorder is a severe disorder that may worsen the daily functioning of mothers and may also have an unfavorable effect on child. It is therefore of utmost importance for clinicians to recognize PTSD and the associated risk factors in order to guide these parents.

The effect of childhood cancer therapy on ovarian reserve and pubertal development.

The effects of childhood cancer therapy on ovarian reserve tests and on pubertal development within 5 years were compared with a control group. The study group was composed of 41 patients who underwent chemotherapy during pre-menarche (subgroup A; n = 15) and after menarche (subgroup B; n = 26); the control group was composed of 44 patients admitted with non-cancer related diseases (in total n = 85). Mean total ovarian volume and total antral follicle counts on ultrasound examination were significantly lower in the study group compared with the control group (3.5 ± 2.3 versus 5.2 ± 2.4 ml; P = 0.001; and 3.4 ± 3.3 versus 8.6 ± 3.5; P < 0.001, respectively). Mean FSH level was significantly higher in the study group (13.5 ± 16.2 versus 7.3 ± 2.7 mIU/ml; P = 0.017). Anti-Müllerian hormone levels in subgroup A were significantly higher than in subgroup B (1.8 ± 0.1 versus 1.5 ± 0.08 pg/dl; P = 0.034). In conclusion ovarian volume, antral follicle count and FSH can be used for evaluating the harmful effect of cancer chemotherapy on ovarian follicles. Post-menarche, Anti-Müllerian values reveal that ovarian follicles are more sensitive to the devastating effects of cytotoxic treatment.

Golden bullet-denosumab: early rapid response of metastatic giant cell tumor of the bone.

Giant cell tumor of the bone (GCTB) is usually a benign, locally aggressive tumor with metastatic potential. Histogenesis of GCTB is unknown and a correlation has not been found between histologic and clinical course. For this reason, many authors consider its prognosis unpredictable. Lung metastasis after GCTB treatment is well known and generally has unfavorable outcome, despite varied chemotherapy regimens. Denosumab, which inhibits RANK-RANKL interaction, is a new, promising actor among targeted therapeutic agents for GCTB. In this report, we emphasize on early rapid response to denosumab in metastatic GCTB.

Do proinflammatory cytokine levels predict serious complication risk of infection in pediatric cancer patients?

Determination of risk of severe bacterial infection complication in children with cancer is important to diminish the cost of hospitalization and therapy. In this study, children with cancer (leukemia excluded) were evaluated for risk of severe infection complication, success of therapy and the relation between clinical and inflammatory parameters during neutropenic fever attacks. Children who fulfilled the criteria of neutropenic fever with cancer were enrolled in the study. During admission, together with clinical and laboratory parameters; interleukin-6, interleukin-8, soluble tumor necrosis factor receptor II, and soluble interleukin 2 reseptor ve procalcitonin levels were detected. Empirical therapy was started with piperacillin/tazobactam and relation between the inflammatory cytokine levels and therapy response parameters were evaluated. The study population included 31 children and 50 neutropenic attacks were studied. In 48% of the attacks, absolute neutrophile count was >100/mm(3) and infectious agents were shown microbiologically in 12% of the attacks. In the study group with piperacillin/tazobactam monotherapy, the success rate without modification was 58%. In the therapy modified group mean duration of fever, antibiotherapy and hospitalization were significantly longer than the group without modification. Inflammatory cytokines' levels during admission (interleukin-6, interleukin-8, soluble tumor necrosis factor reseptor II) were higher in patients with fever >3 days and in multiple regression analysis, it has been shown that they have a determinative role on fever control time. Other cytokines did not show any significant relationship with risk of severe bacterial infection complication and success of therapy.

Are cardiac magnetic resonance imaging and radionuclide ventriculography good options against echocardiography for evaluation of anthracycline induced chronic cardiotoxicity in childhood cancer survivors?

Anthracyclines are widely used for the treatment of solid tumors in pediatric oncology. However, their uses may be limited by progressive chronic cardiotoxicity related to the cumulative dosage. The aims of this study are to compare diagnostic techniques and prepare an algorithm for diagnosis of anthracycline induced chronic cardiotoxicity. The patients were evaluated according to age, sex, time elapsed since the last dose of anthracycline treatment, presence of cardiovascular symptoms, follow-up duration, type of anthracycline, cumulative anthracycline dose, and concomitant mediastinal radiation therapy. Late subclinical cardiotoxicity was detected by history, physical examination, electrocardiography (ECG), Holter monitor, echocardiography (ECHO), radionuclide ventriculography (MUGA), and cardiac magnetic resonance imaging (MRI). Thirty-seven male and 19 female patients with a median age of 11.2 ± 4.6 (range, 3.5-22.0) years were included in the study. Patients were grouped according to cumulative anthracycline doses. Subclinical cardiac dysfunction was detected in 20 patients by at least one of ECHO, MRI or MUGA after anthracycline chemotherapy. We revealed that other than ECHO, MRI and MUGA have high clinical importance for evaluating subclinical late cardiac complications in children treated with anthracyclines.

Mediastinal Hodgkin lymphoma arising from cystic lymphangioma: case report in a child.

Mediastinal disease is a frequent clinical presentation in children with Hodgkin lymphoma. It is usually due to mediastinal lymphadenopathy or involvement of the thymus gland. Cystic lymphangiomas are benign tumors of the lymphatic system, and less than 1% present as a solitary mediastinal mass. To our knowledge, there has been no report in the literature describing Hodgkin lymphoma arising from cystic lymphangioma. In this report, we describe a patient with mediastinal cystic lymphangioma, from which Hodgkin lymphoma was determined to have arisen.

Psychosocial Impact of the War in Ukraine on Pediatric Cancer Patients and Their Families Receiving Oncological Care Outside Their Country at the Onset of Hostilities.

Psychosocial care of pediatric cancer patients and their families is as critical as the medical and surgical components of their therapies. Strains on family communication and structure and financial need are linked to poorer psychological outcomes for both patients and families. It is critical that children remain as connected as possible to their communities and extended families during therapy. For Ukrainian pediatric cancer patients receiving care outside of their nation's borders on February 24, 2022, the Russian invasion of Ukraine compounded these problems. Based on conversations with patients and parents, we evaluated the psychosocial impact of war on pediatric Ukrainian cancer patients and their families who had left their country before the onset of the conflict to undergo treatment of pediatric malignancies at our medical center. These families shared with us the problems they have experienced after the Russian invasion of Ukraine. Their concerns can be summarized in 4 categories: (1) emotional stress experienced by the patients, families and relatives related to the dangers of war; (2) difficulties in obtaining previous hospital records in Ukraine; (3) medical expenses; and (4) uncertainty regarding the patient's and their family's future and the ability of the children to ever return to their homes. Psychosocial distress relating to the violence of war will hopefully pass in near future, but our pediatric patients and their families will continue to face stressors related to displacement and financial concerns for some time to come.

Preliminary results of propranolol treatment for patients with infantile hemangioma.

Propranolol, a non-selective beta-blocker, has recently been introduced as a treatment for infantile hemangiomas. In this study, we evaluated the effect of propranolol in 12 infants with hemangioma. Twelve infants (9 girls) with a median age of 4.5 months were included in the study. All of the patients in the study group received short-term (1-9 weeks, median: 4 weeks) systemic corticosteroids as a first-line therapy. All patients received propranolol 2 mg/kg/day, divided into three doses. They were treated in an inpatient setting for the first 72 hours of the treatment. Vital signs, blood pressure and blood glucose were monitored. Propranolol treatment was given for 4-9 months (median: 5 months). In the study group, regression rate of the mean dimension of the lesion was 38% +/- 15 (range 15%-50, median 45%) at the 2nd month of therapy. Over 9 months, which was the maximum follow-up period, the regression rate of the mean dimension of the lesion was 55% +/- 31 (range 20%-80, median 50%). One patient had transient bradycardia, which improved spontaneously. No other side effect was observed in the study population. Propranolol appears to be an effective drug for infantile hemangiomas with good clinical tolerance. We suggest that propranolol is the preferable drug as the first-line therapy for infantile hemangiomas.

Clinical practice of a genetics referral selection tool in pediatric cancer patients.

There are few guidelines for genetic counseling and management of pediatric cancer patients with probable cancer predisposition. In this study, we used a previously proposed patient selection tool by Jongmans and discussed the findings in regard to pediatric cancer patients we treated. Pediatric solid tumor patients who were treated in Kocaeli University Department of Pediatric Oncology were evaluated with the five main questions in Jongmans' referral tool. All of the patients and records of diagnostic imaging were examined and analyzed. One-hundred-twenty-three patients participated in the study. The most common indication for genetic counseling was 'consanguinity of the parents' with '≥2 malignancies at childhood age' following it. Fifty-two (42.28%) patients had indication for genetic counseling. We recommend developing and using genetics counseling selection tools such as Jongmans' which helps clinicians differentiate patients with probable cancer predisposition.

Magnetic resonance image-guided stereotactic body radiation therapy for liver rhabdoid tumor in infancy: A case report.

Extracranial malignant rhabdoid tumors are rare and aggressive tumors that typically occur in the pediatric age group and have a poor prognosis. Herein, we report a case of a one year and five months old male infant who was referred with the diagnosis of malignant rhabdoid tumor of the liver. Magnetic resonance guided stereotactic body radiotherapy was administered with concomitant chemotherapy. Treatment was well tolerated with no severe acute side effects. A 40.8% volumetric reduction of the tumor was observed at the last fraction of MR guided radiotherapy.

Hepatic adenomatosis in a 7-year-old child treated earlier with a Fontan procedure.

Patients who undergo a Fontan procedure experience some degree of liver disease. Hemodynamic changes such as central venous hypertension, depressed dynamic cardiac output, and late ventricular dysfunction combined with long-standing hypoxia preceding the Fontan procedure all are recognized risk factors for hepatic injury. The histopathologic changes associated with cardiac hepatopathy include chronic passive congestion, centrilobular necrosis, and cardiac cirrhosis. However, hepatic adenoma and hepatic adenomatosis (HA) are not well-known pathologies during the course of cardiac hepatopathy. This study focused on a 7-year-old girl with chronic hepatic changes and HA who had undergone a Fontan procedure. Hepatic adenomatosis was diagnosed on the basis of magnetic resonance imaging (MRI) and MRI-guided liver biopsy. To the best of the authors' knowledge, this case involved the youngest patient with hepatocellular adenomatosis documented in the literature. It was a unique case because the patient experienced HA after a Fontan procedure.