Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience.

Background: Relapsed/refractory high-risk neuroblastoma has a dismal prognosis. Anti-GD2-mediated chemo-immunotherapy has a notable anti-tumor activity in patients with relapsed/refractory high-risk neuroblastoma. The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy in patients with relapsed/refractory high-risk neuroblastoma. Methods: All patients received the Turkish Pediatric Oncology Group NB 2009 national protocol for HR-NB treatment at the time of diagnosis. Salvage treatments were administered after progression or relapse. The patients who could not achieve remission in primary or metastatic sites were included in the study. The most common chemotherapy scheme was irinotecan and temozolomide. DB was administered intravenously for 10 days through continuous infusion with 10 mg/m2 per day. The patients received 2 to 14 successive cycles with duration of 28 days each. Disease assessment was performed after cycles 2, 4, and 6 and every 2 to 3 cycles thereafter. Results: Between January 2020 and March 2022, nineteen patients received a total of 125 cycles of DB and chemotherapy. Objective responses were achieved in 12/19 (63%) patients, including complete remission in 6/19 and partial response in 6/19. Stable disease was observed in two patients. The remaining five patients developed bone/bone marrow and soft tissue progression after 2-4 cycles of treatment. The most common Grade ≥3 toxicities were leukopenia, thrombocytopenia, hypertransaminasemia, fever, rash/itching and capillary leak syndrome, respectively. Conclusion: Our study results suggest that DB-based chemo-immunotherapy seems to be suitable with encouraging response rates in patients with relapsed/refractory high-risk neuroblastoma.

The Effect of Dose-Volume Parameters on Central Nervous System Relapse in Pediatric Patients with Acute Leukemia Receiving Prophylactic Cranial Irradiation.

AIM OF THE STUDY: To investigate the effects of dosevolume parameters of brain parenchyma, optic nerves (ONs) and cribriform plate (CP), which were determined on central nervous system (CNS) control in pediatric leukemia patients who have undergone prophylactic cranial irradiation (PCI) at our department. PATIENTS AND METHODS: In the current study, the records of 14 patients were examined retrospectively. Along with the minimum and maximum doses for brain and CP, D95% (minimal dose received by the 95% volume of a structure) and V95% (percent volume of target receiving 95% of prescribed dose) could be obtained from the dose-volume histogram. Statistical analyses were conducted using the Mann Whitney test in SPSS-15. RESULTS: ALL/AML ratio was 9/5. CNS relapse was observed only in 2 patients. The minimum dose was 1249 (1100-1782) cGy, 1036 (547-1651) cGy, 856 (308-1460) cGy and 1234 (922-1727) cGy for brain parenchyma, right ON, left ON and CP, respectively. The value of D95%/D was 1.01 (1-1.06) and 0.99 (0.92- 1.06) for brain parenchyma and CP, respectively. V95% was 99.8 % (98.6%-100%) and 98.1% (80.5%-100%) for brain parenchyma and CP, respectively. The analyses revealed that none of the target tissue dose-volume parameters for PCI affected CNS relapse (p>0.05). CONCLUSION: In our study; it was found that the dosevolume parameters of the brain, CP and ONs did not have any effect on CNS relapse. Along with the other clinical factors, the scarce number of patients included in the study might have concealed the effects of parameters related to RT.

Soft tissue sarcomas and central nervous system tumors in children with neurofibromatosis type 1.

OBJECTS: We aim to evaluate the characteristics of pediatric patients with neurofibromatosis type 1 (NF1) who developed soft tissue sarcomas (STSs) and central nervous system (CNS) tumors that have been followed up in our center. MATERIALS AND METHODS: Medical records of children with NF1 were retrospectively analyzed. RESULTS: There were 78 patients who met at least two diagnostic criteria for NF1. The median age of patients was 10 years (0.5-18), and M/F ratio was 1.3. The prevalance of the optic glioma was 11.5% (n = 9), and one patient with optic glioma also had cystic astrocytoma, one patient had brain stem tumor, and one patient had a CNS tumor (without histopathologic diagnosis). Seven of nine children were ≥ 7 years old at the time of the diagnosis of optic glioma. Visual impairment developed in four patients, and two of them were treated with radiotherapy solely on the basis of evidence of clinical and radiological progression of the tumors. Four patients developed STSs. Two of them had malignant peripheral nerve sheath tumors (MPNST), and the remaining two had bladder rhabdomyosarcoma. Three of the four patients with STSs died with progressive disease. CONCLUSION: The clinical course of malignancy in NF1 is often different from that of similar tumor types in the general population. Careful follow-up in patients with NF1 is required to enable the early diagnosis of malignancies, and the developments of new targeted therapies are needed for improvement of the outcome for patients of this group, especially with MPNST.

The variability of applicator position among high dose rate intracavitary brachytherapy applications in cervical cancer patients treated with ring & tandem applicators.

OBJECTIVE: To evaluate the interindividual and intraindividual applicator position variability in high dose rate ring and tandem intracavitary brachytherapy applications in locally advanced cervical cancer. PATIENTS AND METHODS: Eight patients with locally advanced cervical cancer formed the study population. They had been treated in Dokuz Eylül University Department of Radiation Oncology between the years 2000 and 2005 with high dose rate intracavitary brachytherapy using ring and tandem applicators. The 3-dimensional geometric variation of the applicator center in craniocaudal, mediolateral and anteroposterior directions was determined on the basis of bony reference points in 24 pairs of orthogonal films obtained in the conventional simulator. Then the following evaluations were performed: 1) the applicator position variability in all applications (interindividual variability), 2) the intraindividual applicator position variability relative to the first application, 3) the intraindividual applicator position variability relative to the average of three applications. Among the potential factors that might influence the reproducibility of ring and tandem applications, age, stage, the period between external radiotherapy and brachytherapy were evaluated by univariate analysis. RESULTS: Standard deviation of interindividual applicator variability was 3.83 mm in craniocaudal, 0.39 mm in mediolateral and 2.86 mm in anteroposterior directions. The standard deviation of intraindividual variability relative to the first application was 1.91 mm in craniocaudal, 0.4 mm in mediolateral, and 4.26 mm in anteroposterior directions. The standard deviation of intraindividual variability relative to the average of three applications was 0.95 mm in craniocaudal, 1.86 mm in mediolateral, and 1.24 mm in anteroposterior directions. According to univariate analysis, no factor influenced applicator position variability. CONCLUSIONS: In order to extract definitive conclusions about factors that affect positional reproducibility of ring and tandem applicators, studies are needed that include larger numbers of patients.

Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

Turkish people's knowledge of cancer and attitudes toward prevention and treatment.

BACKGROUND: The basic level of cancer knowledge of the population is as important in controlling cancer as diagnostic tools, screening, and new approaches to prevention, early diagnosis, and treatment. METHODS: A questionnaire consisting of 24 questions was given to 630 healthy Turkish people to determine their basic knowledge and attitudes regarding cancer. RESULTS: The majority of respondents (78%) were found to have little knowledge of cancer despite the fact that the average level of education of the sample was superior to that of the general population. Educational level was the major predictive factor influencing the basic knowledge and attitudes of the respondents. CONCLUSION: The overall education of the public as well as the basic level of knowledge of cancer must be improved in cooperation with oncology societies and media in order to overcome the cancer burden in Turkey.