What has changed in the last 25 years in osteosarcoma treatment? A single center experience.

BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor in the extremities. The main purpose of this study was to determine clinical features, prognostic factors, and treatment results of patients with osteosarcoma at our center. METHODS: We retrospectively analyzed the medical records of children with osteosarcoma between the years 1994-2020. RESULTS: 79 patients were identified (54.4% male, 45.6% female). The most common primary site was the femur (62%). Twenty-six of them (32.9%) had lung metastasis at diagnosis. The patients were treated between 1995- 2013 according to the Mayo Pilot II Study protocol, while the others were treated with the EURAMOS protocol between the years 2013-2020. Sixty-nine patients underwent limb salvage surgery as a local treatment, whereas seven underwent amputation. The median follow-up time was 53 months (2.5-265 months). The event-free survival (EFS) and overall survival (OS) rates at 5 years were 52.1% and 61.5%. The 5-year EFS and OS rates were 69.4% and 80% in females; 37.1% and 45.5% in males (p=0.008/p=0.001). The 5-year EFS and OS rates of the patients without metastasis were 63.2% and 66.3%; with metastasis 28.8% and 51.8% (p=0.002/p=0.05). For good-responders, the 5-year EFS and OS rates were 80.2% and 89.1%; while for poor-responders, 35% and 46.7% (p=0.001). Mifamurtide was used in addition to chemotherapy as of the year 2016 (n=16). The 5-year EFS and OS rates were 78.8% and 91.7%, respectively for the mifamurtide group; 55.1% and 45.9%, respectively for the non-mifamurtide group (p=0.015, p=0.027). CONCLUSIONS: Metastasis at diagnosis and poor response to preoperative chemotherapy were the most important predictors of survival. Females had a better outcome than males. In our study group, the mifamurtide group`s survival rates were significantly higher. Further large studies are needed to validate the efficacy of mifamurtide.

Dysembryoplastic neuroepithelial tumors of childhood: Ege University experience.

BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are rare, low-grade tumors of the central nervous system (CNS) of childhood. It is an important cause of intractable epilepsy, and it is surgically curable. We aimed to review our institutional experience with DNET in children. METHODS: Medical records of children aged less than 18 years of age diagnosed with DNET between 2009 and 2020 at Ege University Hospital were reviewed. Clinical features of the patients including age, gender, initial symptoms, duration of symptoms, medical treatments, age at the time of surgery, tumor location, degree of surgical resection, and outcome of the patients were documented. RESULTS: We reviewed the records of 17 patients with DNETs. Twelve of them were male (70%), 5 of them female (30%). The median age was 11 years (19 months-17 years). The major symptom was a seizure in all of the patients. Thirteen patients presented with complex partial seizures, whereas 2 had a simple partial seizure, and 2 generalized tonic-clonic seizures. Seven patients had drug resistant epilepsy and had received at least two anti-epileptic drugs before surgery. The median duration of symptoms was 6.6 months (0-48 months). In surgery, total surgical resection was performed in 15 patients, and 2 patients underwent partial resection. From these 15 patients, seven patients underwent lesionectomy of the tumor while the other eight patients had extended lesionectomy. The mean follow-up time was 107 months (54-144 months), the seizure control was achieved in 14 patients (82.4%) after surgery, but 3 patients experienced tumor recurrence in the follow-up. CONCLUSION: In DNETs, the complete total resection of the lesion is generally associated with seizure-free outcomes. In the patients with partial resection and lesionectomy, MRI follow-up is recommended for recurrence.

Ifosfamide-related encephalopathy with severe clinical presentations in children with cancer.

INTRODUCTION: Ifosfamide is an alkylating agent, mostly used against variety of solid tumors in pediatric oncology practice. Although hemorrhagic cystitis is known as a common adverse effect, encephalopathy is the another one that should be kept in mind. It may occur in 2-5% of the children, and manifested by different clinical spectrums such as somnolence, lethargy, irritability, excitement, disorientation, confusion, weakness, hallucinations, seizures, movement disorders, and coma. CASE REPORT: Herein, we present two patients who developed generalized seizure activity and one who developed coma during ifosfamide infusion.Management and outcome: In the first two patients, ifosfamide infusion was discontinued and intravenous diazepam was given. Their seizure stopped in a few minutes and neurological examination was back to normal, and no focal deficits were observed. In the third patient, ifosfamide infusion was discontinued, methylene blue and thiamine were given. After the tenth dose of methylene blue, she became neurologically normal, without any mental and motor deficit. Nevertheless, later she developed febrile neutropenia, septic shock and she died. DISCUSSION: These cases highlight that pediatric oncologists and hematologists should be aware of possibility of severe neurological toxicity after administration of ifosfamide in adolescent patients. Apart from seizure, clinicians should also be prepared to notice drowsiness during ifosfamide infusions in children. Most of the time cessation of ifosfamide and hydration is enough. However, in severe toxicities there is a risk of irreversible neurological damage, and for these patients methylene blue (MB) and thiamine treatment should be kept in mind.

Safety of Eicosapentaenoic Acid in Cancer Treatment: Effect on Cancer Cells and Chemotherapy in Vitro.

Eicosapentaenoic acid (EPA) is a long-chain polyunsaturated fatty acid that has been used to treat cachectic cancer. However, its efficacy and safety with regard to cancer cells remain unclear. The present study comprised an In Vitro investigation of the effects of EPA on cancers. The effects of 0.01-300 µg/mL of EPA on the proliferation and death of cells after 24, 48, and 72 h were explored. The study included cell lines representing neuroblastoma (Kelly, SH-SY5Y, C1300); acute lymphoblastic leukemia (ALL); Burkitt's lymphoma; acute myeloid leukemia (AML); adult cancer cell lines of the pancreas, colon, and prostate; and a fibroblast cell line. EPA caused 4.4%-7% proliferation of fibroblasts, but did not protect them from the toxic effect of cisplatin. It did not induce proliferation in the neuroblastoma cells, and did not reduce the cytotoxic effect of cisplatin. EPA also did not cause proliferation in ALL, Burkitt's lymphoma, and AML cells, and did not alter the cytotoxic effects of L-asparaginase, cyclophosphamide, and cytosine arabinoside, respectively. Our results were similar in the adult cancer cell lines. EPA is safe because it has no effects on the proliferation of cancer cells or on chemotherapy In Vitro.

Comparison of malnutrition and malnutrition screening tools in pediatric oncology patients: A cross-sectional study.

OBJECTIVES: The aim of this study was to determine the prevalence of malnutrition, to compare nutritional evaluation tools, and to highlight the importance of nutritional status in pediatric oncology patients. METHODS: This study evaluated the nutritional status, based on height, weight, and midupper arm circumference, of 170 patients ages 5 months to 18 years who were hospitalized at the Ege University Hospital Pediatric Oncology Clinic. The prevalence of malnutrition was determined using the malnutrition screening tools, STRONGkids (SK) and Pediatric Yorkhill Malnutrition Score (PYMS). Correlations, sensitivity, specificity, and the positive and negative predictive values between the screening tools were calculated. RESULTS: In all, 68.2% of the patients were diagnosed with a solid tumor. According to SK, 59.4% had a moderate risk of malnutrition, and 40.6% had a high risk. According to PYMS, 30.6% of patients had a low to moderate risk of malnutrition, and 69.4% had a high risk of malnutrition. Minimal agreement was noted between SK and PYMS (Kappa value: 0.40 and 0.18, respectively). The sensitivity of PYMS was higher than that of SK (92.68 and 78.05, respectively). In total, 22.9% of the patients had a body mass index of <5%, and 21.2% had a midupper arm circumference of <5. CONCLUSIONS: The present findings show that, in general, pediatric oncology patients have a high risk of malnutrition. Although SK and PYMS do not differ significantly, PYMS has higher sensitivity for detecting malnutrition. The nutritional status of pediatric oncology patients should be monitored using appropriate screening techniques throughout their treatment.

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.

Intestinal Protozoan Parasitic Infections in Immunocompromised Child Patients with Diarrhea.

Intestinal protozoan parasites are common causes of infectious diarrhea in children receiving anticancer therapy or undergoing transplantation. Additionally, immunosuppression therapy in such patients may exacerbate the symptoms related to these parasitic infections. The aim of this study was to evaluate the prevalence and diagnostic importance of parasitic protozoan infections in children treated for malignancies or undergoing transplantation, and to highlight the control of intestinal parasitic infections for immunosuppressed patients at a hospital in Izmir, Turkey. In total, 82 stool samples from 62 patients were analyzed by microscopic examination and polymerase chain reaction (PCR) for the presence of coccidian parasites. Our results showed that Cryptosporidium, Cyclospora, and Cystoisospora were present in 22.5% (14/62), 9.6% (6/62), and 3.2% (2/62) of the cases using either method, respectively. The prevalence of these coccidian parasites identified with both methods was 35.4% (20/62). Other intestinal parasites (Blastocystis, Giardia, and Entamoeba coli) were detected in 10 patients. PCR analysis showed the presence of all coccidian parasites in the same stool sample for one patient. Finally, both PCR and microscopic examination of the stools revealed that there is a higher prevalence of Cryptosporidium, Cyclospora, and Cystoisospora in immunocompromised children. These examinations allowed an early start of appropriate antibiotic treatments and led to an increased percentage of correctly treated patients.

Cisplatin ototoxicity in children: risk factors and its relationship with polymorphisms of DNA repair genes ERCC1, ERCC2, and XRCC1.

PURPOSE: We aimed to investigate the cisplatin-related hearing toxicity and its possible relationship with polymorphic variants in DNA repair genes, ERCC1, ERCC2, and XRCC1. METHODS: Fifty patients treated with cisplatin in the past were included in the study. There were 29 females and 21 males; mean age 13.4 ± 6.0 years). The polymorphism in DNA repair genes was studied using primer and probes in Light Cycler device after DNA isolation was carried out with PCR technique. The polymorphisms and clinical risk factors were evaluated using Chi square test and logistic regression modelling. RESULTS: The patients had hearing loss in 44%. For ERCC1 gene, the patients with hearing loss had 50% of GG (wild type), 40.9% of AG and 9.1% of AA genotypes, while the patients without hearing loss had 28.6% of GG, 53.5% of AG, and 17.9% of AA genotypes. For ERCC2 gene, the patients with hearing loss had 18.2% of GG (wild type), 40.9% of TG, and 40.9% of TT genotypes, while the patients without hearing loss had 10.7% of GG 39.3% of TG, and 50% of TT genotypes. For XRCC1 gene, the patients with hearing loss had 18.2% of CC (wild type), 59.1% of CT, and 22.7% of TT genotypes, while the patients without hearing loss had 35.7% of CC, 50% of CT, and 14.3% of TT genotypes. There was no statistically significant association among the groups (p = 0.24). CONCLUSION: We did not find a relationship between DNA repair gene polymorphisms and hearing toxicity of cisplatin.

Unusual presentation of diffuse large B-cell non-Hodgkin's lymphoma in children: bilateral ureteral involvement.

Non-Hodgkin's lymphomas (NHL) are common malignant tumors in children and adolescents. Among them diffuse large B-cell lymphomas (DLBCL) are relatively rare as compared to non-cleaved small cell lymphoma (mostly Burkitt's-BL) and lymphoblastic lymphoma (LL). While BL has abdominal or cervical site predilection, LL (mostly T-cell) tends to have mediastinal involvement. However, diffuse large B-cell lymphomas may involve abdomen, peripheral lymph nodes, skin, bone, other rare sites. Ureteral NHLs are extremely rare in children; however, many cases have been reported in adults. In adults the histopathology is usually follicular lymphoma. Only one case of unilateral ureter DLBCL has been reported in an adolescent in the past. Here we report a case of bilateral ureteral DLBCL to highlight the unusual presentation of NHLs and that it should be considered in the differential diagnosis of acute renal insufficiency.

Nasogastric Tube Feeding Experiences in Pediatric Oncology Patients and Their Mothers: A Qualitative Study.

The aim of this qualitative research study is to reveal children's and their mothers' views and experiences related to nasogastric tube feeding, which is the most frequently performed nutrition delivery method in pediatric oncology. The present study was carried out at an university pediatric oncology inpatient service. A total of three children and 14 mothers participated in the study. The analysis of the data was conducted according to Kolcaba's Comfort Theory. The findings resulting from the content analysis were explained under four main themes: (1) physical: includes the inability to be fed orally, nasogastric tube intervention, comfort because of feeding, medication administration, and satisfaction; (2) psychospiritual: includes anxiety, fear, distorted body image, and compliance; (3) sociocultural: includes conflicts with the child about feeding and advice on feeding via the nasogastric tube to other mothers and children; and (4) environmental: includes unrestricted/freedom of feeding. Gastroenterology professionals can also provide basic counseling and resources to children and mothers about the importance of maintaining an optimal weight and of enteral nutrition.

Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey.

BACKGROUND/AIMS: A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations. MATERIALS AND METHODS: The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart. RESULTS: In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas. CONCLUSION: After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.

Radiological nodule behavior: A critical parameter in the surgical management of pediatric pulmonary metastases.

Divarci E, Arslan S, Dökümcü Z, Kantar M, Demirag B, Öniz H, Ertan Y, Alper H, Erdener A, Özcan C. Radiological nodule behavior: A critical parameter in the surgical management of pediatric pulmonary metastases. Turk J Pediatr 2018; 60: 372-379. Radiological nodule behavior (RNB) means the course of nodule appearance on consecutive CT scans. In this study, we aimed to discuss the effects of RNB on prognosis of patients with pulmonary metastasis. Retrospective analysis of patients who underwent pulmonary metastasectomy (PM) between 2005-2015 was performed. RNBs were grouped as stable, enlarging or new rising nodules. The effects of RNBs were analyzed on recurrence, 1- and 3-year event free survival (EFS) and mortality. Twenty-seven patients (18 male) underwent PM with a median age of 15 years (3-18 years). The diagnoses were listed as osteosarcoma (13), Wilms` tumor (7), Ewing`s sarcoma (3), synovial sarcoma (2), rabdomyosarcoma (1) and mixed germ cell tumor of testis (1). RNBs were new rising in 15 patients (55%), enlarging in seven patients (26%) and stable in five patients (19%). Vital tumor metastasis was detected in all of the patients with enlarging nodules (100%); in 10 of the 15 patients with new rising nodules (66%) and none of the patients with stable nodules. None of the patients with stable nodules developed recurrence or died after PM (p˂0.05). In patients with enlarging nodules, metastases recurred and they died in the postoperative period. These findings were similar in different types of tumors. RNB could be used as a critical parameter in deciding surgical management strategies of pulmonary metastases. Stabile nodules should be observed by close follow-up with serial CT scans without surgery. All of the suspected new rising nodules should undergo surgical sampling to avoid unnecessary chemotherapy. Nodule progression under chemotherapy is a poor prognostic criteria for overall survival.

The role of radiotherapy in local control of nonextremity Ewing sarcomas.

PURPOSE: To evaluate the results of radiotherapy and the prognostic factors affecting local control in nonextremity Ewing sarcomas. METHODS: Between 1995 and 2011, 44 patients with nonextremity Ewing sarcomas were treated with radiotherapy. Tumor localizations were pelvis in 23, spine in 13, thoracic region in 5, and cranium in 3 patients. Tumor size was ≥8 cm in 56.8% of patients. Distant metastases were present in 19 of the patients at the time of diagnosis (43.1%). All patients were treated with 12 weeks of neoadjuvant chemotherapy followed by surgery and radiotherapy (45-54 Gy) or radiotherapy alone (54-64.8 Gy). Radiotherapy was applied due to microscopic residue (R1) in 5 patients after the operation and macroscopic tumor in 39 patients (macroscopic residue [R2] and nonresectable tumor). RESULTS: Median follow-up was 49 months (range 9-195). Local failures developed in 7 patients (15.9%) and local control at 5 years was 81.4%. Local recurrence was detected in 6 patients (6/38) who did not have residual tumor after RT. Progression was detected in 1 patient (1/6) who had residual tumor. All those patients with local failure experienced further distant metastases. Possible prognostic factors such as age (≤17 vs >17), tumor localization, tumor volume (≤8 cm vs >8 cm), and M status at diagnosis (0 vs 1) were not related to local control. CONCLUSIONS: Radiotherapy, either alone or adjuvant to surgery, provides local control in 80% of nonextremity Ewing sarcomas and plays an important role in treatment.

Cutaneous side effects of chemotherapy in pediatric oncology patients.

Pediatric oncology patients can present with various skin lesions related to both primary disease and immunosuppressive treatments. This study aimed to evaluate the cutaneous side effects of chemotherapy in pediatric oncology patients. Sixty-five pediatric oncology patients who were scheduled to undergo chemotherapy from May 2011 to May 2013 were included in the study. Three patients were excluded from the results, as 2 patients died during treatment and 1 patient withdrew from the study; therefore, a total of 62 patients were evaluated for mucocutaneous findings. Patients were grouped according to their oncological diagnoses and a statistical analysis was performed. There was no statistical significance in the incidence of cutaneous side effects of chemotherapy among the different diagnostic groups. Awareness among dermatologists of the possible cutaneous side effects of chemotherapy in pediatric patients and their causes can promote early diagnosis and treatment in this patient population.

Psychometric properties of the oncology module of the KINDL scale: first results.

PURPOSE: The objective of this study was to assess the reliability and validity of the Oncology module of the generic KINDL scale (having 24 items with 6 domains). METHODS: The psychometric properties of the KINDL Oncology module were evaluated from the aspect of internal consistency, reliability, and construct validity on an inpatient sample of 103 Turkish children (mean age 10.0 ± 4.01 years) who had various oncological disorders. RESULTS: The KINDL Oncology module (24 items) showed acceptable α coefficients ranging from .57 (physical well-being) to .87 (treatment) for each domain. In confirmatory factor analysis of the original 4-domain structure, Root Mean Square Error of Approximation was found as .086, and Comparative Fit Index was .87. Good known groups results supported the construct validity of the instrument. Correlations between the domains of the mother KINDL and the domains of its oncology module were significantly high, indicating a satisfactory convergent validity. CONCLUSION: The Turkish version of the KINDL Oncology module showed good reliability and questionable validity in this study. However, further research on other language versions of the module is needed for its global use.

Determination of school-related problems in children treated for cancer.

This descriptive and case-control study was carried out in a pediatric oncology outpatient clinic to determine the school-related physical, social, and psychological problems and problems experienced in academic achievement of children treated for cancer. The sample of the study consisted of 56 Turkish patients with cancer, aged 7-18 years, who were in remission and attending school as well as their parents, a control group of patients who did not have cancer, and their teachers. A Child Information Form, a Child Health Questionnaire Parent's Form of 50 questions, a Behavior Evaluation Scale for Children, and Young People and a Teacher's Report Form were used as data collection tools in the study. Of the children, 30.3% experienced various physical difficulties stemming from cancer therapy that affected their school life. The number of late enrollments, the number of children repeating a grade, and the rates of school absenteeism were also found to be higher in the survivors than in the controls.

Experiences of parents with the physical care needs at home of children with cancer: a qualitative study.

BACKGROUND: Between cancer treatment courses, children who have not developed any complications or neutropenia are sent home until the start of the next treatment protocol. OBJECTIVE: The aim of this study was to describe the experiences of parents in the home care of children who had been recently diagnosed with cancer and were undergoing cancer treatment but had been discharged from the hospital between treatment protocols. METHODS: The study was carried out at Ege University, Turkey. Twelve parents of 12 children between 0 and 18 years of age participated in an in-depth interview. The data were analyzed according to Orem's Self-care Deficit Theory. RESULTS: The main themes were basic conditioning factors, self-care agency, and self-care needs. Some parents changed their place of residence because of the cancer treatment, focused on the recovery of the child, and experienced fear, perception difficulties, and difficulties related to self-care needs. CONCLUSIONS: Parents report difficulties with extreme emotions and dilemmas in maintaining their daily routines of life secondary to fear of infection and challenges with feeding their children. IMPLICATIONS FOR NURSING: A well-planned discharge education, home visits, and telephone consultation interventions are essential to meet the needs of children and their parents who are at home between treatment courses.

Quality of life and chemotherapy-related symptoms of Turkish cancer children undergoing chemotherapy.

This cross-sectional and descriptive study was designed to determine symptoms emerging due to chemotherapy treatment and their effects on children's quality of life. The research was carried out between February 2008 and February 2009 at the pediatric oncology clinics in four hospitals, focusing on 93 patients receiving chemotherapy. A survey form, the Pediatric Quality of Life Inventory (PedsQL 4.0) and the Memorial Symptom Assessment Scale (MSAS) were used as data collection tools. Chi-square and Student t tests were performed for data analysis. Some 51.6% of the children were aged 13-15 years old, and 51.8% were boys and 50.5% were diagnosed as having solid tumors. There were significant relations between: antimetabolite chemotherapeutics and feeling irritable and worrying (p=0.001, p=0.030); vinkoalkaloid and numbness/tingling in hands/feet (p=0.043); antracyclines and lack of energy and skin changes (p=0.021, p=0.004); and corticosteroids and lack of appetite, nausea and sadness (p=0.008, p=0.009, p=0.009). Several symptoms such as feeling sad, worrying and feeling irritable caused a significant decrease in the total domain of quality of life scores (p=0.034, p=0.012, p=0.010, respectively). Chemotherapeutic drugs can cause symptoms that can seriously affect quality of life in children.