Comparative Effectiveness of Chemotherapy Alone Versus Radiotherapy-Based Regimens in Locally Advanced Pancreatic Cancer: A Real-World Multicenter Analysis (PAULA-1).

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005-2018). Survival curves were calculated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34-0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13-0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28-0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22-0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Stereotactic body radiotherapy vs conventionally fractionated chemoradiation in locally advanced pancreatic cancer: A multicenter case-control study (PAULA-1).

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut-offs:

The VEGF gene polymorphism in glioblastoma may be a new prognostic marker of overall survival.

PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumor. Vascular endothelial growth factor (VEGF) gene polymorphisms and overexpression are involved in high-grade malignant gliomas. The aim of this study was to assess the distribution of +405C>G VEGF gene polymorphism in patients diagnosed by glioblastoma and to test its association with the overall survival (OS). METHODS: Patients diagnosed for glioblastoma were randomly selected, and follow-up was conducted for a minimum of 36 months. Tissue paraffin embedded GBM samples were subjected for the VEGF polymorphism detection. The associations of the observed genotypes and clinical data were evaluated. RESULTS: The most frequent single nucleotide polymorphism (SNP) variant was G (72.58%). The GG genotype was proved to have statistically significant longer OS and patient status (alive/dead) compared to CC and CG genotypes (p=0.022 and 0.005, respectively). CONCLUSION: Our results indicate that +405C>G VEGF gene polymorphism may be used as prognostic genetic marker of OS in GBM patients.

Benefit and outcome of using temozolomide-based chemoradiotherapy followed by temozolomide alone for glioblastoma in clinical practice.

PURPOSE: Temozolomide (TEM), an oral alkylating agent, has shown promising activity in the last 10 years in the treatment of glioblastoma multiforme (GBM). Our goal was to show the benefit of concomitant therapy involving 3D conformal radiotherapy and temozolomide in clinical practice. METHODS: This was a retrospective/prospective study and included a total of 113 patients with GBM diagnosis. Forty- seven patients received postoperative radiotherapy and 66 received concomitant temozolomide plus 3D conformal radiotherapy. RESULTS: The mean overall survival of patients who received postoperative radiotherapy alone was 9.93±6.475 months, compared to statistically longer overall survival in the group of patients who received radiotherapy plus temozolomide (13.89±8.049 months) (p=0.006). The latter group was divided into two subgroups, one consisting of patients who received 6 complete cycles of temozolomide, and a second with patients who received incomplete treatment. Statistically significant longer overall survival was registered in the first subgroup compared to the second (p=0.006). CONCLUSION: The concomitant usage of temozolomide and radiotherapy was beneficial, and statistically significant difference among groups and subgroups was observed regarding overall survival.

MIA, S100 and LDH as important predictors of overall survival of patients with stage IIb and IIc melanoma.

PURPOSE: Melanoma represents the most severe form of skin cancer. Detection of specific tumor markers is an important step in disease diagnosis and treatment, contributing to personalized therapy. The purpose of this study was to evaluate the potential of MIA, S-100 and LDH as biomarkers for the estimation of overall survival and disease-free survival rate in patients with stage IIa, IIb vs stage IIc melanoma. METHODS: Selected biomarkers MIA, S-100 and LDH were prospectively evaluated in 80 patients with melanoma. Patients were divided in two groups according to tumor thickness. The first group (group A) consisted of patients with primary tumor thickness between 2.0 - 4.0 mm (N=40), i.e. IIa and IIb stage of disease (16 males; 40%, and 24 females; 60%). The second group (group B) consisted of 40 patients with primary tumor thickness over 4.0 mm, i.e. IIc stage, which is considered as high risk group (26 males; 65%, and 14 females 35%). Statistical analyses were performed to estimate overall survival and disease-free survival in both patient groups. RESULTS: In group A a significant difference in overall survival was found among MIA1, MIA2 and MIA3 scores, while the other 2 markers didn't show significant differences. In group B statistically significant differences in overall survival were found regarding all three biomarkers. Statistically significant differences in disease-free survival were found for MIA1 score compared to MIA2 and MIA3 scores. Also, very significant difference was detected in patients with S-100 below 0.106 and above 0.106. The same was confirmed for normal and increased LDH level in group B for disease-free survival. CONCLUSION: MIA score, S100 protein and LDH in the IIC group B patients might be useful in the prediction of overall survival and disease free survival.

Radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line.

AIM OF THE STUDY: Aim of the study was to compare radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line. This regime is designed to be as similar as possible to fractionated tumour radiotherapy treatment, and to provide data on radiobiological effects on human tumour cells. MATERIAL AND METHODS: The cell line used in the study was HT29 (human colorectal adenocarcinoma, American Type Culture Collection HTB-38™). Also, for comparison, the MRC5 cell line (human foetal lung fibroblasts, American Type Culture Collection CCL 171) was used. Four-day treatment in a 4 × 2 Gy regime was performed. Cell viability was evaluated by tetrazolium colorimetric MTT assay. RESULTS: Multiple low-dose pre-irradiation induced a stronger radioadaptive response compared to single low-dose application in the HT29 cell line. Multiple pre-irradiation with 0.03 Gy and 0.05 Gy caused radioadaptive effects, while in both single and multiple low-dose pre-irradiation regimes 0.07 Gy led to radiosensitivity. Radiobiological effects induced in the HT29 cell line by low-dose pre-irradiation were evidently weak during the treatment time, because a single low-dose applied only on the first day gave no radioadaptive effects. In the MRC5 cell line different effects were registered, since radioadaptive response has not been observed after multiple or single pre-irradiation. CONCLUSIONS: The obtained data are interesting, especially for the possible application of low-dose pre-irradiation in radiotherapy.

Different associations of apoE gene polymorphism with metabolic syndrome in the Vojvodina Province (Serbia).

The metabolic syndrome (MetS) is a polygenic multifactorial metabolic disorder with strong socioeconomic influence. MetS has became a worldwide epidemic, that directly increases the risk of cardiovascular diseases and type 2 diabetes mellitus. The human apoE gene, coding Apolipoprotein E, has three common polymorphisms in human population: e2, e3 and e4, which are proved to be associated with impaired lipid metabolism. The contribution of apoE polymorphism to MetS disorders has not been investigated previously in Vojvodina Province, region with the highest number of obese people in Serbia. The aim of this study was to evaluate apoE gene polymorphism in relation to MetS disorders. The healthy control group of 30 individuals and 63 MetS patients were examined for apoE variants in relation to biochemical and anthropometric parameters. The genotypes were determined by PCR-RFLP. Regarding all parameters, significantly higher values were detected in MetS group compared to control. The MetS group of patients had significantly higher frequency of e4 allele. In addition, positive relation was revealed between e4 allele presence and all measured parameters. It was found that the e4 allele was related with a significantly increased OR of MetS disorders according to the International Diabetes Federation definition. These results suggested that e4 allele may act as a one of determinants for development of metabolic syndrome.

Radiotherapy treatment planning: benefits of CT-MR image registration and fusion in tumor volume delineation.

BACKGROUND/AIM: Development of imaging techniques, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), made great impact on radiotherapy treatment planning by improving the localization of target volumes. Improved localization allows better local control of tumor volumes, but also minimizes geographical misses. Mutual information is obtained by registration and fusion of images achieved manually or automatically. The aim of this study was to validate the CT-MRI image fusion method and compare delineation obtained by CT versus CT-MRI image fusion. METHODS: The image fusion software (XIO CMS 4.50.0) was applied to delineate 16 patients. The patients were scanned on CT and MRI in the treatment position within an immobilization device before the initial treatment. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on CT alone and on CT+MRI images consecutively and image fusion was obtained. RESULTS: Image fusion showed that CTV delineated on a CT image study set is mainly inadequate for treatment planning, in comparison with CTV delineated on CT-MRI fused image study set. Fusion of different modalities enables the most accurate target volume delineation. CONCLUSION: This study shows that registration and image fusion allows precise target localization in terms of GTV and CTV and local disease control.

[Optimal postoperative radiotherapy treatment of orbital rhabdomyosarcoma].

INTRODUCTION: Rhabdomyosarcoma (RMS) is the most common sarcoma of the soft tissue, mostly affecting the region of head and neck (orbit, paranasal sinus). Histological types include embryonal (66-70%) with better prognosis, and alveolar type (20%) with poorer prognosis. There are also diffuse anaplastic and undifferentiated sarcomas (10%). Due to multimodal therapy approach (surgery, chemotherapy and radiotherapy), RMS survival rate is considerably improving. Nevertheless, early diagnosis of RMS is of crucial importance for the outcome of treatment. Standard conformal radiation therapy is very complex due to closeness of many critical structures of head and neck, thus limiting optimal tumor dose coverage. CASE OUTLINE: Patient aged 59 years, surgically treated for RMS of nasal cavity several times before radiation therapy treatment. Due to relapse, patient was re-operated, when subtotal re-resection of the maxilla with exenteration of the right orbit was done. The patient received IV cycles of polychemotherapy postoperatively. Standard procedure and planning for conformal radiation therapy did not lead to acceptable irradiation plan, and hence modification in the patient's preparation was done, resulting in optimal therapeutic plan according to internationally recognized recommendations. CONCLUSION: The reported case shows a rare pediatric tumor, which often occurs in children but extremely rare in adults. The problem of inadequate isodose distribution obtained by standard conformal plan was solved by placing bolus material into the orbital cavity.The outcome of the treatment plan showed much better isodose distribution and tumor bed coverage.

Uncommon metastatic site from breast cancer.

INTRODUCTION: Breast cancer is one of the most common malignancies in women and the main leading cause of cancer death. The most frequent sites of metastases from breast cancer are bones, lungs, the central nervous system, the liver and soft tissue. Colonic metastases from breast cancer are rare. CASE REPORT: We presented a 70-year-old woman with bulky obstructing lesion of sigmoid colon. A physician in charge on our department examined the patient and past history of breast cancer was found up. Surgery was performed with removal of sigmoid colon and three of six lymph nodes were positive. Pathological examination, including immunohistochemical stains, confirmed the diagnosis of metastatic breast cancer to sigmoid colon. The multidisciplinary oncology team suggested postoperative chemotherapy. The patient received four cycles of chemotherapy with paclitaxel followed by anastrozole. On the first control visit no disease activity was detected. CONCLUSION: In patients with the past history of breast cancer the symptoms of hematochezia or anemia may indicate colonic metastases.

Application of alternative medicine in gastrointestinal cancer patients.

BACKGROUND/AIM: [corrected] Alternative medicine is a set of therapeutic procedures which are no part of official practice. At present, the use of alternative medicine among cancer patients is significant and the purpose of this study was to get more information on the methods and products of alternative medicine. Thus, the aim of the study was to determine the frequency of the use of alternative medicine among gastrointestinal cancer patients. METHODS: The research was conducted using an anonymous questionnaire in writing. We included 205 patients with the diagnosis of gastrointestinal malignancy in the study but the questionnaire was fulfilled by 193 patients and the presented data were based on their answers. The questions were about the sociodemographic characteristics of the patients, the reasons for their use of alternative medicine, and their information sources about alternative medicine. We divided existing alternative therapies into 6 categories: herbal therapy, special diets, psychotherapy, body-mind therapy, spiritual therapy, and other supplements. RESULTS: A total of 48 (24.9%) patients did not use any type of alternative therapy; 145 (75.1%) patients used at least one product and 124 (64.25%) patients used herbal preparations (beetroot juice was consumed by 110 [56.99%] patients); 136 (70.5%) patients were informed about alternative therapies by other patients; 145 (75.1%) used alternative medicine to increase the chances for cure; 88 (45.6%) of interviewed patients would like to participate in future research in this field. CONCLUSION: The use of alternative medicine is evidently significant among cancer patients. Further research should be conducted in order to find out interactions of these products with other drugs and potential advantages and disadvantages of this form of treatment.

[Pediatric femur fractures, epidemiology and treatment].

BACKGROUND/AIM: Femur fractures in children most often occur as a consequence of traffic accidents, during play and sport activities, and due to different pathological states. Diagnosis is rather simple and it includes physical and radiographical examination. Femur fractures treatment in children can be operative and unoperative, depending on several facts: age, localisation and type of fracture, joint injuries of soft tissues, the presence of other injuries (in polytrauma), economical and social aspects, ect. The aim of this study was to present epidemiological characteristics of pediatric femur fractures, that is in the stage of development, including a special analysis of the used treatment techniques, as well as the comparison of the obtained data with those from the literature. METHODS: The evaluation included following parameters: age, gender, cause, localisation and type of femur fracture, applied treatment and hospitalisation duration. RESULTS: Among the presented 143 patients with femur fracture, 109 were boys and 34 were girls (3.2:1 ratio; p = 0.0001). Average age for both genders was 8.6 years, and no difference between boys and girls were found for the age (p = 0.758). In total, the most common fracture was diaphyseal fracture of femur in 93 (65.03%) patients. The second was proximal fracture in 30 (20.98%) patients, and the last distal fracture of the femur in 20 (13.99%) patients (p = 0.0001). Three main causes of femur fracture can be distinguished: during play and sport activities in 67 (46.8%) children, in traffic accidents in 64 (44.8%) children, and pathological fractures in 12 (8.4%) children. Inoperative treatment was applied in 82 (57.3%) patients, and operative one in 61 (42.7%) patients. The most common treatment was traction, in 71 (49.6%) patients, followed by immobilization by hip spica cast mostly in young children. Intramedullar elastic nailing was applied in 16 (11.2%) cases, and intra-medullar rigid nailing (Küntscher) in 19 (13.3%) cases. Significantly longer hospitalization period was detected after traction (21 days) comparing to other ways of treatment, mainly operative or hip spica cast (5 to 10 days). CONCLUSION: In young children the standard treatment was hip spica cast after traction. Intramedullar elastic nailing is a modern trend accepted as standard in our approach to femur fracture treatment in children.

Osteoid osteoma: fluoroscopic guided percutaneous excision technique - our experience.

Osteoid osteoma is a small benign bone lesion. It generally affects children and young adults. Traditional treatment of osteoid osteoma includes excision either by wide resection, or by the removal of the nidus using curettes and burrs after opening the overlying cortex. Newly developed techniques involve percutaneous ablation of the tumor by computed tomography-guided core-drill excision and destruction of the nidus by thermocoagulation. Fluoroscopic guided percutaneous extirpation and drilling resection procedures have been performed at the Institute for Health Care of Children and Youth, Pediatric Surgery Clinic in Novi Sad, Serbia. Some modifications in the methods were made and implemented, which resulted in an excellent cost-benefit ratio, shorter period of hospitalization, and faster recovery. The aim of this paper is to present the experience gained in the treatment of osteoid osteomas in the last 5 years at the Pediatric Surgery Clinic in Novi Sad and to describe the modifications to the percutaneous biopsy technique of osteoid osteoma that have been implemented.

Cystic echinococcosis in children - the seventeen-year experience of two large medical centers in Serbia.

Cystic echinococcosis (CE) is a public health problem in countries having such endemic areas. Epidemiological studies of CE, especially pediatric, are rare. The aim of this study was to evaluate epidemiological and clinical characteristics of CE in children in Serbia. Data were obtained retrospectively from the case records of patients under the age of 18 years admitted for surgical treatment of CE at two large pediatric medical institutions in the period 1990-2006. Patients' age, number of cysts and their anatomic location were evaluated in relation to differences by patients' gender and socio-geographic status (urban or rural origin). The study included 149 children with 272 hydatid cysts. The mean age of patients was 10.1+/-3.8 years. There were no significant differences in the number of patients in relation to gender and urban:rural origin. There were no significant differences in patients' age at the time of surgery or the number of cysts per patient when patients' gender or socio-geographic status was evaluated. The anatomic location of cysts was as follows: liver (N=165; 60.7%), lungs (N=82; 30.1%), and other locations (N=25; 9.2%). Multiple cysts, and combined liver/lung involvement were identified in 34.2% (N=51), and 6.0% (N=9) of patients, respectively. Hepatic cysts were significantly more common in girls than in boys. There were no significant differences in anatomic location of cysts between socio-geographic groups. The large number of infected children during a long period of investigation indicates an active transmission of disease and a lack of program for control and prevention of CE in Serbia.