Nimotuzumab-vinorelbine combination therapy versus other regimens in the treatment of pediatric diffuse intrinsic pontine glioma.

PURPOSE: Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens. METHODS: After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed. RESULTS: The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months. CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.

Trans-Arterial Radioembolization with Yttrium-90 of Unresectable and Systemic Chemotherapy Resistant Hepatoblastoma in Three Toddlers.

The aim of this short communication was to report the results of transarterial radioembolization (TARE) with Yttrium-90 (Y90) loaded resin microspheres in three toddlers with unresectable and systemic chemotherapy-resistant HB hepatoblastoma (HB). Six TARE procedures were performed on the patients. The dose required for treatment was calculated using partition model. Administered doses of Y90 were 1.369, 0.851, and 1.147 GBq. Complete radiological response in two patients and partial response enabling liver resection in one patient were achieved. Neither life-threatening nor minor complications developed after the treatment. These results demonstrates that HB is a radiosensitive neoplasm, and TARE-Y90 can be used as the primary, neoadjuvant and palliative treatment method in patients with unresectable and systemic chemotherapy-resistant HBs. However, studies with higher number of patients and long-term results are required.

Bevacizumab-containing regimens for children with relapsed or refractory tumors.

Background: We aimed to evaluate the effect of bevacizumab-containing regimens (BCRs) on the survival of children with relapsed or refractory solid tumors. Materials and Methods: Files of children with relapsed or refractory solid tumors treated with BCR were retrospectively reviewed for age, gender, follow-up time, histopathological diagnosis, adverse events observed with BCR, number of chemotherapy protocols used before BCR, the best overall response obtained with BCR, time to progression, number of BCR courses given to patients, the status of patient at last visit, and outcome. Results: Thirty patients (16 boys, 14 girls) were treated with BCR. The median age at diagnosis was 8.5 (2 - 17) years and at the time of the study was 11 (3-21) years. The median follow-up time was 25.7 (5-79.4) months. The median follow-up time after the start of BCR was 3.2 (1-27) months. Histopathological diagnosis was central nervous system tumors in 25, Ewing sarcoma in two, osteosarcoma in two, and rhabdomyosarcoma in one patient. BCR was given as second-line in 21, third-line in six, and fourth-line protocol in three patients. No chemotherapy toxicity was observed in 22 (73.3%) patients. The best overall response was progressive disease in 17 (56.7%), partial response in seven (23.3%), and stable disease in 6 (20%) patients at first-response evaluation. The median time until progression was 77 (12-690) days. During the study period, 17 patients died of progressive disease. Conclusion: Our study revealed that adding antiangiogenic agent bevacizumab to cytotoxic chemotherapy provided no survival benefit in children with relapsed or refractory solid tumors.

Syrian and Turkish children with cancer: a comparison on survival and associated factors.

Cure rates of childhood cancer need to be improved in low-income countries and vulnerable populations such as refugees. We aimed to compare the outcome and associated factors in Syrian refugee and Turkish children with cancer treated at our hospital.Files of patients were reviewed for age, tumor type, stage, treatment, compliance to treatment, relapse or progression status, outcomes, secondary malignancy (SM) and treatment-related mortality (TRM). Overall (OS) and event-free survival rates (EFS) were analyzed.105 refugees and 304 Turkish children were treated between January 2012 and January 2019. Median age and median follow-up time were significantly lower in the Syrian group (p=0.046, p<0.001, respectively). Metastatic or advanced-stage disease was significantly more frequent in refugees (p=0.002). Relapse or progression and poor compliance to treatment were more common in refugees (p=0.01, p<0.001, respectively). Rates of OS were 55.7% and 69.7%, EFS were 28.9% and 55.7% in Syrian and Turkish patients. OS and EFS were lower in refugees compared to Turkish patients (p=0.01, p<0.001, respectively). EFS was significantly lower in refugees with poor compliance to treatment (p<0.001). TRM was reported in 12 (8 Syrian, 4 Turkish) patients. SM was detected in 3 (2 Turkish, 1 Syrian) children.Inferior survival rates were detected in Syrian refugee children compared to Turkish children. Besides from cancer-specific factors such as stage and tumor type, a series of barriers in accessing cancer care resulting in poor compliance to treatment might have been responsible from lower survival rates in Syrian children.

Solid pseudopapillary neoplasm of the pancreas in children: Hacettepe experience.

BACKGROUND: Solid pseudopapillary neoplasm of the pancreas (SPNP) is mostly seen in young women in the second and third decades of life; it is quite uncommon in children. We aimed to review our institutional experience with SPNP in children. METHODS: Hospital charts of children <18 years of age diagnosed to have SPNP were reviewed for demographic characteristics, presenting symptoms, diagnostic interventions, physical examination findings, radiological data, extent of disease, diagnostic and management strategies and final outcome. RESULTS: Nineteen cases were diagnosed as SPNP between 1992 and 2017 (female: male, 16:3; median age 13 years, range 8.5-16.5). The most common symptom was abdominal pain. Physical examination was normal in 12/19 cases. Three cases were diagnosed incidentally. The most common tumour localization was the head of the pancreas. Median tumour diameter was 5 cm (1.4-15). One patient had abdominal disseminated disease, and others had localized disease. Surgical interventions were enucleations in nine, distal pancreatectomies in four and total resection in two patients; three underwent no surgery following diagnosis. Only one patient received adjuvant chemotherapy and radiotherapy. One patient died, one was lost to follow-up at 164 months and 17 were under follow-up with no events at a median of 60 months (20-308 months). CONCLUSION: In childen, SPNP demonstrates different clinical features. Complete resection is curative in most patients. In children, the optimal surgical strategy for SPNP is still debatable. Instead of radical resections, limited pancreatic resections, such as enucleations, with negative surgical margins should be attempted. For unresectable or recurrent tumours, cisplatin and 5-FU-based chemotherapy might be considered.

The Value of 18F-FDG PET/CT in Detecting Bone Marrow Involvement in Childhood Cancers.

BACKGROUND: The aim of this study was to assess the utility of F-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in the initial staging of pediatric patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), Ewing sarcoma (ES), and neuroblastoma (NB). PROCEDURE: A total of 94 patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) with newly diagnosed NHL, HL, ES, and NB between July 2014 and December 2017, who underwent BMB and F-FDG PET/CT before chemotherapy were included in this study. There were 36 patients with NHL, 27 HL, 16 ES, and 15 NB. F-FDG PET/CT and BMB results were reviewed and compared retrospectively. FINDINGS: Retrospective analysis of data from 94 pediatric patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) was performed. Of the 94 patients, 29 had BMI on F-FDG PET/CT. BMB was positive in 14, negative in 13, and insufficient in 2 of these 29 patients. In 65 patients negative on F-FDG PET/CT, BMB was also negative in 54 and insufficient in 7. For the whole group, sensitivity, specificity, and positive and negative predictive values of F-FDG PET/CT in detecting bone marrow metastasis at the time of diagnosis were 90.6%, 100%, 100%, and 95.4% and those of BMB were 53.1%, 87.1%, 94.4%, and 80.6%, respectively. CONCLUSION: Our study demonstrates that F-FDG PET/CT predicts BMI better than BMB. F-FDG PET/CT may be used at initial staging of pediatric patients with NHL, HL, ES, and NB.

Prevalence and Related Factors of Euthyroid Sick Syndrome in Children with Untreated Cancer According to Two Different Criteria

OBJECTIVE: In this study, we evaluated the frequency of euthyroid sick syndrome (ESS) among patients with childhood cancer and its association with the stage of disease, nutritional parameters and cytokines levels. METHODS: Eighty newly diagnosed children were included in the study. ESS was assessed in two different ways. According to criteria 1 ESS was present if free triiodothyronine (fT3) was below the lower limit and free thyroxine was within the normal or low limits, thyroid-stimulating hormone (TSH) was in the normal range. According to criteria 2, in addition to the above, it was required that reverse triiodothyronine (rT3) be performed and was higher than normal limits. RESULTS: Three of our pediatric patients had subclinical hypothyroidism and two had subclinical hyperthyroidism. Out of 75 patients, ESS was identified in 14 (17.3%) according to criteria 1 and in eight (10.6%) according to criteria 2. Only fT3 levels were significantly different in the ESS (+) and ESS (-) groups (p<0.05) according to criteria 1. A significantly negative correlation between interleukin (IL)-6 and fT3 was found, according to both sets of criteria. tumor necrosis factor alpha was negatively correlated with fT3 levels only in the criteria 1 group. There were no correlations between IL-1ß and fT3, free thyroxine, rT3 and TSH levels. CONCLUSION: ESS may occur in childhood cancer and thyroid function testing should be performed routinely when cancer is diagnosed.

Single institution experience on cancer among adolescents 15-19 years of age.

Yagci-Küpeli B, Akyüz C, Yalçin B, Varan A, Kutluk T, Büyükpamukçu M. Single institution experience on cancer among adolescents 15-19 years of age. Turk J Pediatr 2017; 59: 1-5. Adolescent cancers differ from other age groups in terms of cancer types, treatment and outcome. We aimed to present our institutional data on survival of certain types of cancer in adolescents. Hospital files were retrospectively evaluated for distribution of tumor types, clinical features, and overall and event-free survival (OS and EFS) rates in adolescents with malignant tumors. Two hundred ninety-three cases between 15-19 years who were diagnosed with malignant tumor at our department in the last 38 years were included in the study. Mean age was 15.3 and median age was 15 years at time of diagnosis. Male/female ratio was found to be 1.8/1. The most common cancers were non-Hodgkin lymphoma (NHL) (20.5%), Hodgkin's lymphoma (HL) (19.8%), central nervous system (CNS) tumors (10.9%), osteosarcoma (10.6%), Ewing sarcoma/primitive neuroectodermal tumors (EWN/PNET (9.9%) nasopharyngeal carcinoma (NPC) (9.6%). Non-compliance to medical treatment was observed in 10.9% of cases with significantly high non-compliance in NHL and osteosarcoma (p=0.02). Overall survival was 57.6% and EFS was 45.7% at a median follow-up time of 8.75 years. In adolescents, lower OS and EFS rates than the younger age group are observed. The most appropriate management plan should be made according to the physical and psychosocial needs of patients in this age group.

Pediatric Lyme Neuroborreliosis: Different clinical presentations of the same agent; Single center experience.

OBJECTIVES: Lyme disease is a vector-associated infectious disease, caused by the agent, spirochete Borrelia burgdorferi. Neurologic findings are observed in approximately 12% of the cases and termed Lyme neuroborreliosis (LNB). Lyme neuroborreliosis may manifest with different clinical neurologic manifestations. METHODS: The study was conducted at tertiary training and research hospital. From January 2014 to September 2015, a total of 75 patients diagnosed with encephalitis, ataxia, Guillain Barre Syndrome (GBS), facial paralysis, acute disseminated encephalomyelitis (ADEM), pseudotumorcerebri were evaluated for inclusion to the study. Among these patients whom investigations of B. burgdorferi antibody IgM and/or IgG ELISA and Western Blot (WB) were detected to be positive, were assessed. Epidemiologic data, tick bite histories, duration of symptoms, clinical findings, radiologic findings, treatment durations and prognosis were investigated. RESULTS: Totally 7 patients had been treated with the diagnosis of Lyme neuroborreliosis. The mean age was 9.14±4.91 years; duration of symptoms before admission was 8.0±4.50 days; and the duration of antibiotic use was 2.85±0.89 weeks. All patients had received ceftriaxone and intravenous immunoglobulin (IVIG); 3 patients had received plasmapheresis (42.9%) and one patient had received pulse corticosteroid therapy. While the patient with the diagnosis of encephalomyeloneuritis and atypical GBS had partially improved, the other patients were completely cured. CONCLUSION: In this article, we report pediatric LNB patients, B. burgdorferi should also be considered in patients with atypical or severe neurologic involvement or a history of tick bite; it is known that the prognosis is good with appropriate and early treatment.

Cerebral salt wasting in pediatric critical care; not just a neurosurgical disorder anymore.

OBJECTIVE: Cerebral salt-wasting syndrome (CSWS) is a hypovolemic hyponatremia caused by natriuresis and diuresis, of which the exact pathogenesis is unknown. Although CSWS has been more commonly described to be associated with neurosurgical disorders, increasing numbers of patients are diagnosed and new etiological factors are being identified as the awareness of it increases. METHODS: The files of the patients who had been hospitalized and treated with the diagnosis of CSWS at the pediatric critical care unit during the last three years were retrospectively reviewed. RESULTS: Totally 9 patients had been treated with the diagnosis of CSWS. The causes of CSWS were identified as tuberculosis meningitis in two patients, status epilepticus in two patients, ketamine infusion in one patient, medulloblastoma in one patient, sepsis in one patient, brain oedema following child abuse in one patient, and cerebral infarct in one patient. All of the patients had received isotonic saline and hypertonic saline while 77.7% of them had received fludrocortisone. The mean time to correction of hyponatremia was 20.37±14.73 days. One patient had died. CONCLUSION: Cerebral salt-wasting syndrome is increasingly described in the etiology of hyponatremia that is commonly seen in children hospitalized especially at critical care units. Serum sodium, urinary sodium and polyuria should be primarily considered in the diagnosis, and supportive laboratory tests such as uric acid and brain natriuretic peptide (BNP) should not be stipulated. At hospitals providing inpatient care services, clinical and laboratory characteristics of CSWS should be known in detail especially at pediatric critical care units.

The first report of cabergoline-induced immune hemolytic anemia in an adolescent with prolactinoma.

Prolactinomas are common pituitary tumors that can cause gonadal dysfunction and infertility related to hyperprolactinemia. Dopamine agonists are the first-line treatment in these patients. Cabergoline leads to significant reduction in serum prolactin levels and tumor size in patients with prolactinoma. Dopamine agonists have been associated with adverse effects such as nausea, vomiting and psychosis. We report here a case with cabergoline-induced immune hemolytic anemia. The patient had cabergoline treatment history for prolactinoma and presented with weakness, fatigue, nausea, and paleness. Laboratory findings revealed severe anemia-related immune hemolysis. There were no causes identified to explain hemolytic anemia except cabergoline. Therefore, cabergoline therapy was stopped and subsequently hemolytic anemia resolved and did not occur again. This is the first reported pediatric case with prolactinoma and cabergoline-induced hemolytic anemia. Clinicians should be watchful for this rare side effect induced by cabergoline.

Educational achievement, employment, smoking, marital, and insurance statuses in long-term survivors of childhood malignant solid tumors.

BACKGROUND/OBJECTIVE: Survivors of childhood cancer experience many social adaptation problems. We aimed to identify social, educational, and occupational issues of this growing population. PATIENTS AND METHODS: Survivors treated for childhood malignant solid tumors who were older than 18 years and in remission for at least 3 years were surveyed. The educational achievement, employment, type of habitation, marital status, parenthood, social insurance, and smoking status of the patients were inquired and recorded. RESULTS: Two hundred one patients (126 male patients/75 female patients) were included in the study between 2007 and 2009. The median ages at the time of diagnosis and at the time of study were 10 years (range, 0 to 19 y) and 23 years (range, 18 to 39 y), respectively. The median follow-up duration was 13.5 years (range, 3 to 31 y). Nearly half of the participants were lymphoma survivors. One hundred eleven (55.5%) survivors were high school graduates and 47 (23%) were university graduates. Unemployment rate was 36.8%. Public social insurance rate was 90.5%. Fifty-three (26.4%) survivors had independent habitation. Thirty percent of survivors were married and 7.5% had at least 1 child. Marriage rates were significantly higher in survivors who were older than 23 years, had a follow-up duration of >13 years, had a job, and lived independently (for each parameter P=0.001). University degree was significantly lower in survivors who were treated for central nervous system tumors. CONCLUSIONS: Our results have drawn a more marked picture with lower educational achievement and marital rates when compared with the results of large survivorship studies conducted in developed countries. However, they can be interpreted as intriguing when limited resources are taken into account.

Tissue Doppler and myocardial deformation imaging to detect myocardial dysfunction in pediatric cancer patients treated with high doses of anthracyclines.

AIM: To detect subtle changes in myocardial function in pediatric cancer patients treated with high dose anthracyclines. METHODS: In all, 19 pediatric cancer patients with no cardiotoxicity findings treated with a cumulative anthracycline dose of ≥350 mg/m(2) and healthy participants of the same age were included in the study. Transthoracic echocardiography measurements, pulsed-wave tissue Doppler from the basal portions of all walls and strain and strain rate imaging of all walls from basal portion were obtained. RESULTS: A total of 19 patients (13 boys and six girls) and 17 participants (10 boys and seven girls) in the control group were enrolled. Three patients had subnormal ejection fraction (EF) and fractional shortening (FS) values. There was no significant difference in EF and FS between the two groups. The left ventricle isovolumic relaxation time was prolonged (P = 0.02) and the mitral color propagation velocity was decreased in patients (P = 0.001). Peak systolic strain and strain rates of the right ventricle, septal, lateral and inferior wall basal region of the left ventricle were significantly lower in patients than controls (all P < 0.05). Tissue Doppler measurements of early and late diastolic myocardial velocities of the right ventricular free wall, lateral wall of left ventricle and septum, and peak systolic myocardial velocity of the left ventricle anterior wall were significantly lower in patients (all P < 0.05). CONCLUSION: Myocardial Doppler and deformation imaging techniques provide a thorough evaluation of cardiac functions with the advantage of detecting subtle early changes before a global cardiac functional impairment occurs.

Health-related quality of life in pediatric cancer survivors: a multifactorial assessment including parental factors.

AIM: We aimed to evaluate the health-related quality of life (HRQOL) and the effect of associated factors such as cancer type, treatment strategies, sex, age, and parental factors like education and psychopathology in pediatric cancer survivors and make a comparison with healthy children. PATIENTS AND METHODS: "Pediatric Quality of Life Inventory (PedsQL) 4.0 TM, Generic Core Scale" for children and parents, and "Brief Symptom Inventory" for parents were used. Three hundred and two survivors without major mental or motor deficit and 272 healthy controls of 8 to 18 years of age were enrolled to study. RESULTS: Comparison of scores according to child self-report between survivor and control groups revealed lower points in physical and school subscale of survivor group (P<0.01 and P<0.001, respectively). Female survivors had reported significantly worse HRQOL in physical and emotional subscales of PedsQL than male survivors (P<0.001). Female survivors of ≥16 years of age had reported worse scores in school subscale than females of younger age groups and male survivors of same age group. Parents of control group reported better results in school subscales (P<0.001) and social functioning subscales (P<0.05) than parents of survivor group. Brief Symptom Inventory score had significant effect on child self-report and parent proxy-report of physical functioning (P<0.001), emotional functioning (P<0.001), social functioning (P<0.001), and school subscales (P<0.001) of PedsQL. Significantly better scores of physical functioning subscale in the survivors whose parents are university graduate than the survivors whose parents are primary school graduate were detected (P<0.001). The survivors with central nervous system tumors had reported lower scores in the social, emotional, physical, and school functioning subscales of PedsQL than patients with non-Hodgkin and Hodgkin lymphoma (P<0.001). Child self-report school subscale scores were lower in survivors treated with radiotherapy in combination or as sole therapy than survivors in whom radiotherapy was not given (P<0.001). CONCLUSIONS: Our study has provided evidence about less-studied determinants of HRQOL like parental factors such as psychopathology or educational level in childhood cancer survivors. Future research can build on this evidence to obtain additional factors other than well-known medical and treatment-related factors.

Comparison of sulbactam-cefoperazone with carbapenems as empirical monotherapy for febrile neutropenic children with lymphoma and solid tumors.

Febrile neutropenia (FEN) is a leading complication of intensive chemotherapy. With this prospective randomized study, the authors aimed to compare the effectiveness of sulbactam-cefoperazone (SC) versus carbapenems, as empirical monotherapy in febrile neutropenic children with lymphoma and solid tumors. Febrile neutropenic children (age ≤16 years) hospitalized at the authors' center for lymphomas or solid tumors between March 2007 and June 2009 were included in the study. Patients randomly received SC or carbapenem. Patients were reevaluated at 72 hours and in case of persistent fever, an aminoglycoside and/or a glycopeptide was added to the antibiotic treatment. When a resistant pathogen was isolated, the antibiotic therapy was modified. Treatment responses was defined as success without modification, overall success, or failure. Two hundred and eight episodes were documented in 128 patients (F/M: 56/72), with a median age of 7 years (0.5-17.4 years). Absolute neutrophil count and duration of neutropenia in patients treated with SC and carbapenems were 133/mm(3) (0-500) and 113/mm(3) (0-500), and 4 days (1-21) and 5 days (2-20), respectively. In the SC and carbapenem groups, 82 (78.8%) and 84 episodes (80.7%) improved with treatment, whereas 21 (20.2%) and 19 (18.3%) episodes required treatment modification respectively. One patient from each treatment group died according to febrile neutropenia. The overall success rates were 99% in both groups (P = .94). Empiric SC therapy was found to be as effective as carbapenem monotherapy in pediatric febrile neutropenic patients with lymphoma and solid tumors.