Clinical Profile and Outcome of 806 Pediatric Oncology Patients Treated With Radiotherapy at the Serbian National Cancer Center.

Radiotherapy plays an important role in the multimodal treatment of childhood cancer. Our objective was to provide an analysis of pediatric oncology patients treated with radiotherapy in a national referral institution in Serbia. A retrospective chart review of children treated with radiotherapy between January 2007 and July 2018 was conducted. Of the 806 patients who were identified, 767 formed the basis of this study. CNS tumors (31.2%) were the most common tumors followed by leukemias (17.3%) and bone tumors (14.3%). The most common indication for radiotherapy was in adjuvant setting (69.1%). Anesthesia or sedation was performed on 115 patients. The 5-year and 10-year overall survival rates were 65.7% and 62.1%, respectively. A significant difference in survival in relation to tumor type was seen. The best survival rates were obtained in patients with retinoblastoma, followed by lymphomas and nephroblastoma, while patients with bone sarcomas had the worst survival. The intent of radiotherapy treatment was also a parameter associated with survival. Patients treated with palliative and definitive intent lived shorter than patients treated with prophylactic and adjuvant intent. Our study showed that good treatment outcomes can be achieved in specialized centers with an experienced team of professionals who are dedicated to pediatric oncology.

Management and treatment of children with medulloblastoma in Serbia, a middle-income country.

PURPOSE: The aim of this study was to present the management and treatment of children with medulloblastoma in Serbia, a middle-income country (MIC). METHODS: The data of 87 children diagnosed with medulloblastoma and treated at the Institute for Oncology and Radiology of Serbia from 2000 to 2013 were analyzed. RESULTS: The children's median age was 8.3 years (range 2.5-17.3). Eighty-two (94.2%) were 3 years or older. Sixtytwo (71.3%) patients had stage M0 medulloblastoma, 12 (13.8%) had stage M1 and 13 (14.9%) had stage M2 or M3. As of October 2015, 51 (58.6%) patients were alive and 31 (35.6%) had died. Five patients (5.7%) were lost to followup. Twenty-six patients relapsed. The median follow-up time was 58 months (range 4-187). Mean overall survival (OS) was 76.4% at 3 years, 66.2% at 5 years and 59.2% at 10 years. Mean disease-free survival (DFS) was 75.8% at 3 years, 62.8% at 5 years and 56.6% at 10 years. Mean OS of stage M0 patients was 86.4% at 3 years, 74% at 5 years and 63.1% at 10 years. The OS of stage M1, M2 and M3 patients combined was 48.9% at 3 years, 44.0% at 5 years and 37.7% at 10 years. CONCLUSION: In Serbia, a MIC, it is possible to achieve good treatment results in children with medulloblastoma using international treatment guidelines and recommendations, available resources and an experienced team of professionals dedicated to pediatric neurooncology.

Pediatric glioblastoma: a single institution experience.

PURPOSE: The aim of this study was to evaluate characteristics of childhood glioblastoma multiforme, effectiveness of treatment modalities, and detect factors related to outcome. METHODS: A detailed analysis was performed on a series of 15 patients treated between 2000 and 2013, based on their clinical, radiologic, pathologic, treatment, and follow-up data. RESULTS: Median survival time of children with glioblastoma was 13.5 months. One- and 2-year overall survival probabilities were 66.7 and 20 %, respectively. There were no significant differences in survival based on patients' gender, age, disease presentation with or without epileptic seizures, signs/symptoms of increased intracranial pressure, or tumor location. The presence of neurological deficit initially, as well as prior to radiotherapy, which was quantified by neurologic function score (NFS), had an impact on overall survival. Children with NFS 0 lived longer compared to others (p = 0.001). Survival of children that underwent gross total resection was longer than that of children that underwent subtotal resection (p = 0.030). Mean survival time of children with gross total resection was 73.5 months, compared to 13 months in children with subtotal resection. There was no significant correlation between outcome and type of radiotherapy. In four patients with gigantocellular glioblastoma, we found no evidence of a better prognosis. Two long-term survivors were recorded. Both of them underwent gross total resection and were assigned a NFS 0. CONCLUSIONS: Gross total resection is essential for longer overall survival among pediatric patients with glioblastoma and offers a possibility for long-term survival. Severity of neurologic symptoms quantified by NFS can be considered as a potential predictor of outcome.

Salivary Flow Rate, Oral Yeast Colonization and Dental Status in Institutionalized and Non-Institutionalized Elderly

Elderly people, especially those institutionalized in long-term care facilities, are at risk of various oral diseases. The aim of the study was to determine the incidence of hyposalivation and colonization/oral fungal infection of oral cavity with yeasts, as well as dental status in institutionalized and non-institutionalized elderly. The study included 280 institutionalized and 61 non-institutionalized elderly people. Salivary flow rate, oral colonization with yeasts/oral infection and dental status were assessed and compared between the groups. The institutionalized elderly had a significantly lower salivary flow rate (p=0.035). Oral colonization with yeasts was more frequently found in institutionalized elderly (p<0.001) as compared with non-institutionalized elderly. A negative correlation was found between decreased salivary flow rate and oral yeast colonization and oral fungal infection in both the institutionalized (rs=-0.58; p<0.05) and non-institutionalized (rs=-0.52; p<0.05) groups. A significant difference in DMFT index was observed between the two groups (p<0.001). A negative correlation between decreased salivary flow rate and dental status was found in both the institutionalized (rs=-0.22; p<0.05) and non-institutionalized (rs=-0.56; p<0.05) groups. The results revealed a significantly higher level of hyposalivation and oral yeast colonization and poorer dental status in the institutionalized group as compared with the non-institutionalized group of elderly people.

Periodontal Health Status in Adults Exposed to Tobacco Heating System Aerosol and Cigarette Smoke vs. Non-Smokers: A Cross-Sectional Study.

Tobacco heating systems (THS) are new products on the market, advertised as a less harmful alternative for smokers, in which tobacco is heated and not burned like in conventional cigarettes. This research explored the effect on periodontal tissues in contact with heating and burning tobacco residual products (smoke and tobacco). METHODS: The sample included 66 subjects, patients of the Clinic of Dentistry in Rijeka, Croatia, aged 26-56 (median 38), 64% females. Three age- and gender-matched groups were formed (each N = 22): non-smokers, classic cigarettes smokers and THS smokers. Probing depth (PD) and clinical attachment loss (CAL) were primary research parameters. RESULTS: Three groups differed in average PD and CAL (p ≤ 0.002), with cigarette smokers having the highest and non-smokers the lowest values (p ≤ 0.002). THS consumers generally had lower values of periodontal indices than smokers, but only CAL differed significantly (p = 0.011). Periodontal indices CAL and PD were worse in THS consumers than non-smokers, but they did not reach a level of statistical significance. Cigarette smoking was the only predictor of periodontitis (average CAL ≥ 4 mm) in logistic regression models, with an odds ratio of 4.7 (95% confidence interval 1.2-18.3; p = 0.027). CONCLUSIONS: Exposure to nicotine-containing aerosol of THS in adults has a less harmful effect on periodontal tissues, measurable through periodontal indices (PD and CAL), compared to burning tobacco of conventional cigarettes. THS, presented as an alternative product to classic cigarettes, also has a detrimental effect on the periodontium.

What did COVID-19 pandemics teach us about single-fraction radiotherapy for painful bone metastases-State of the art or undertreatment?

BACKGROUND: Choosing the optimal treatment approach for patients with painful bone metastases during the COVID-19 pandemic became challenging. A simple technique, single fraction radiotherapy was recommended for these patients usually referring to bone metastases as a single entity, although it is a very heterogeneous group of patients. AIM: This study aimed to analyze the response to palliative single fraction radiotherapy in relation to age, performance status, primary tumor, histopathology, and bone localization in the group of patients with painful bone metastases. METHODS: A clinical, prospective, non-randomized study was conducted at the Institute for Oncology and Radiology of Serbia, which included 64 patients with noncomplicated, painful bone metastases who underwent palliative, pain-relieving radiation therapy with a single tumor dose of 8Gy in a single hospital visit. Response to treatment was patient reported via telephone interview using visual analog scale. The response assessment was based on the international consensus panel of radiation oncologists. RESULTS: In the entire group of patients, 83% responded to radiotherapy. No statistically significant difference was observed in response to therapy, time to reach the maximum response, degree of pain reduction, nor in response duration depending on the patient's age, performance status, the primary origin of the tumor, histopathology, or location of the metastasis (bone) that was irradiated. CONCLUSION: Regardless of clinical parameters, palliative radiotherapy with a single dose of 8Gy can be considered very effective in quick pain relief in patients with noncomplicated painful bone metastases. Single fraction radiotherapy in a single hospital visit, as well as patient-reported outcome for these patients may be considered favorable beyond Covid pandemics.

Clinical profile, treatment and outcome of pediatric brain tumors in Serbia in a 10-year period: A national referral institution experience.

OBJECTIVE: This study aimed to evaluate the characteristics of children with primary brain tumors, the effectiveness of treatment modalities, and to detect factors related to the outcome. METHODS: A detailed analysis was performed on a series of 173 pediatric patients treated in a Serbian referral oncology institution between 2007 and 2016, based on their clinical, histological, treatment, and follow-up data. RESULTS: Mean survival time of all children was 94.5months. 2-, 5- and 10-year overall survival probabilities were 68.8%, 59.4%, and 52.8%, respectively. Patients with supratentorial tumors had longer survival than patients with infratentorial tumors and patients with tumors in both compartments (p = 0.011). Children with the unknown histopathology (brainstem glioma) and high-grade glioma had a shorter life than embryonal tumors, ependymoma, and low-grade glioma (p<0.001). Survival of the children who underwent gross total resection was longer than the children in whom lesser degrees of resection were achieved (p = 0.015). The extent of the disease is a very important parameter found to be associated with survival. Patients with no evidence of disease after surgery had a mean survival of 123 months, compared with 82 months in patients with local residual disease and 55 months in patients with disseminated disease (p<0.001). By the univariate analysis, factors predicting poor outcome in our series were the presentation of disease with hormonal abnormalities, tumor location, and the extent of the disease, while the factors predicting a better outcome were age at the time of diagnosis, presentation of the disease with neurological deficit, and type of resection. By the multivariate analysis, the extent of the disease remained as the only strong adverse risk factor for survival (HR 2.06; 95% CI = 1.38-3.07; p<0.001). CONCLUSIONS: With an organized and dedicated multidisciplinary team, the adequate outcomes can be achieved in a middle-income country setting. The presence of local residual disease after surgery and disseminated disease has a strong negative effect on survival.

Implementation of intensity-modulated radiotherapy and comparison with three-dimensional conformal radiotherapy in the postoperative treatment of cervical cancer.

PURPOSE: Within implementation of intensity-modulated radiotherapy (IMRT) in the postoperative irradiation of cervical cancer we evaluated and compared IMRT and three-dimensional conformal radiotherapy (3DCRT) dosimetric parameters for target volumes and organs at risk (OAR). METHODS: We randomized 95 patients with cervical cancer, UICC stage I-III, in groups depending of the type of external beam postoperative radiotherapy. Forty-five patients were treated with IMRT and 50 with 3DCRT. All patients underwent brachytherapy, and according to risk factors some of the patients had concomitant cisplatin chemotherapy. The study was done in a period of three years from December 2015. Analysis of dosimetric parameters for target volume coverage and OARs was performed. RESULTS: IMRT plans showed better conformity compared to 3DCRT plans, represented with homogenity index and conformity index, with higher maximum dose (PTV105 and D2). Both plans achieved adequate planning target volume coverage described with PTV95. Statistically significant difference between groups was found for bladder, rectum and bowel high dose regions: bladder V45 (p=0.000), rectum V40 (p=0.043) and V45 (p=0.000), bowel V45 (p=0.000), and bone marrow dosimetric parameters V20-V45; all were better in IMRT plans. Significant difference was found for volume of patient body normal tissue receiving dose of 20Gy, which was higher in IMRT. CONCLUSION: IMRT is a highly conformal technique. Satisfactory target volume coverage was achieved with both techniques, with better sparing of OARs in the IMRT group. With this technique improvement, we expect better quality of life in cervical cancer patients with good prognosis.

Acute toxicity of postoperative intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cervical cancer: The role of concomitant chemotherapy.

PURPOSE: The toxicity of postoperative radiotherapy for cervical cancer affects patients' quality of life. We evaluated acute toxicity in postoperative intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) as well as the influence of dosimetric parameters and concomitant chemotherapy. METHODS: A total of 45 patients with early operable cervical cancer underwent postoperative IMRT with 40-45 Gy. The control group of 50 patients was treated with 3DCRT. Brachytherapy and concomitant cisplatin chemotherapy were performed in all patients according to pathologic and histologic findings. The patients were monitored for acute gastrointestinal, urological and hematological toxicity classified according to the RTOG acute radiation morbidity scoring criteria. We also analyzed the influence of dosimetric parameters on acute toxicity. RESULTS: Significant differences were found in overall acute toxicity (p=0.018), acute genitourinary toxicity (p=0.029), anemia (p=0.043) and neutropenia (p=0.027) but not in acute gastrointestinal toxicity between the IMRT and 3DCRT groups. In all patients, regarding chemotherapy administration, differences were found between the chemoradiotherapy and radiotherapy group as far as overall acute toxicity (CHRT vs RT; p=0.011) and hematological toxicity were concerned (p=0.001). Patients with ≥3 cycles of chemotherapy showed increased hematologic toxicity. In the IMRT group according to the administration of chemotherapy (chemoradiotherapy vs radiotherapy), statistically significant difference for leukopenia (p=0.009) was found and in the 3DCRT group for anemia (p=0.021) and neutropenia (p=0.029). According to chemotherapy administration (chemoradiotherapy vs radiotherapy), a statistically significant difference in leukopenia (p=0.009) was found in the IMRT group while in the 3DCRT group the differences were in anemia (p=0.021) and neutropenia (p=0.029). CONCLUSION: IMRT is associated with lower acute toxicity and better dosimetric parameters in organs at risk (OAR) compared to 3DCRT. Higher hematological toxicity occurred when concomitant chemotherapy was performed, regardless of RT technique. Further reduction of toxicity is expected with protocol and technical improvement and research of gene-related toxicity.

Treatment outcome of childhood nasopharyngeal carcinoma: A single institution experience.

OBJECTIVES: Nasopharyngeal carcinoma is a rare malignancy in children. The aim of this study was to provide analysis of children with nasopharyngeal carcinoma treated in a single institution. METHODS AND MATERIALS: Between 1999 and 2016, fourteen pediatric patients with a diagnosis of undifferentiated nasopharyngeal carcinoma were treated in our institution, and the patients' clinical characteristics, treatment modality, outcome, and toxicity were analyzed. RESULTS: The median age at diagnosis was 15,5 years. The gender ratio was 1:1. The majority of patients had regionally and/or locally advanced tumors and one had bone metastases at the time of diagnosis. All patients received chemotherapy before radiotherapy, with partial response in thirteen patients and complete response in one. Radiation dose to the primary tumor and involved cervical lymph nodes was 55-60 Gy, uninvolved cervical and supraclavicular regions received prophylactic radiation with dose of 45-50 Gy. Ten patients received adjuvant chemotherapy. Three-year progression-free rate and three-year overall survival (OS) rates were 75% and 73% respectively. Five-year progression-free rate was 65% and OS 63% respectively, and after ten years progression-free rate and OS remained the same. At the end of follow-up period, ten patients were alive, and four died. All of the patients that had distant metastases died. Most common late complications were skin fibrosis and xerostomia. CONCLUSIONS: Multimodal therapy of children with nasopharyngeal carcinoma is associated with long-term survival. It is expected that further advances in the management of these patients, with improved radiotherapy and chemotherapy, will reduce acute and late toxicity and improve quality of life of treated children.