Aleksandar Dagovic

Background: Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Very few cases of coexistence of GIST and adenocarcinoma in other organs have been described. Case presentation: We present the case of a 63-year-old female patient diagnosed with breast cancer. After five years of the diagnosis, the findings of colon adenocarcinoma and GIST in stage IA were discovered incidentally during surgical treatment of the colon carcinoma. This tumor display: mixed spindle-epithelioid cell cytological type, of moderate cellularity, mitotic index (1/10) with low anaplasia, low proliferative status (Ki-67 index 12%), without necrosis and immunophenotype profile: antiendomysial antibody (EMA)-, vimentin+++, CD117++, CD34+++, alpha-smooth muscle actin (alpha-SMA)+, desmin+/-, S-100-, CD68-. Conclusions: The present case is extremely rare since the patient has adenocarcinoma with GIST in a previously diagnosed breast carcinoma. Based on this, in clinical practice should always think about possibility occurrence of synchronous and metachronous tumors.

Breast metastases from an extra-mammary malignancy are rare. Among the lung malignancies that metastasise in the breasts, previous literature has described approximately 30 cases of NSCLC and only a few cases of SCLC. Here, we present a 54-year-old woman with metachronous breast metastasis from pulmonary small cell carcinoma. She presented with a soft tissue mass in the right lung hilum. After bronchoscopy with biopsy, SCLC was verified. Th e patient was given 4 cycles of etoposide and cisplatin followed by radiation therapy. Seven months after the diagnosis of primary lung cancer, the patient palpated a mass in her right breast. Clinical examination and further diagnostics revealed the suspected malignancy, and a radical mastectomy was performed. Immunohistochemical findings suggested metastatic SCLC in the breast. Differentiation between primary and metastatic cancer in the breast is very important for therapeutic planning

Trends and Patterns of Disparities in Oral Cavity and Pharyngeal Cancer in Serbia: Prevalence and Economic Consequences in a Transitional Country

Aim: To evaluate the costs and survival estimates of metastatic colorectal carcinoma patients treated with conventional cytostatic protocols and adjuvant monoclonal antibodies (mAbs). Methods: Retrospective randomized case series and cost-of-illness analysis was used. Metastatic colorectal carcinoma cases (62) were randomly selected from the archive of the largest university military hospital in Southeastern Europe. Results: A 6-month longer survival was attributed to mAbs (p = 0.581). Conventional protocols incurred (sic)5137 (95% CI: (sic)3758-(sic)6517) versus (sic)22,113 (95% CI: (sic)16,201-(sic)28,025) total direct medical costs in mAb-based group. ICER of (sic)32,108 per life year gained attributable to mAbs three-fold exceeded informal willingness to pay threshold of Serbia. Conclusion: mAbs adjuvant protocols had modest positive impact on 5-year survival rates. Costs were driven by targeted biologicals, but significantly higher costs of care were recorded in mAb-treated group in other domains, as well. More selective prescription and reimbursement criteria should be applied to increase cost-effectiveness of targeted oncology agents.

Healthcare financing in Serbia has faced many challenges over the past few decades. One of the most severe challenges is a global macroeconomic recession whose far-reaching consequences deserve particular attention from policymakers in cases of the most demanding major prosperity diseases, such as cancer. The objective of the study was to assess the precise cost matrix of oncology medical care and its chronological evolution during the key years of the macroeconomic recessionary period during 2010-2013.A retrospective database of hospital discharge invoices was analysed, encompassing 37, 978 hospital admissions and 12, 505 patients during a four-year period. Insight into microeconomic patterns of consumption across groups of medical services was provided. A payer's perspective and one-year time horizon have been adopted.Total hospital direct medical costs of cancer diagnostics and treatment in the observed tertiary care facility decreased from €7, 411, 446 in 2010 to €5, 715, 884 in 2012 and then increased to an extraordinary €8, 536, 364 in 2013. The costs of oncology nursing care, imaging diagnostics and radiotherapy have increased considerably while those of pharmaceuticals and surgery have decreased radically - completely transforming the resource allocation landscape of public cancer care.The financial burden of cancer in Serbia is considerable and, unfortunately, expected to increase further in the coming years. Worldwide economic recession and consecutive domestic policy constraints of reimbursement limitations have heavily affected the affordability of cancer treatment for ordinary citizens. Promising signs of market recovery are clearly visible in 2013, which will likely improve both access and equity of medical care in Serbian oncology clinics.

Current radiation therapy capacities in Serbia and most of Eastern Europe are heavily lagging behind population needs. The primary study aim was assessment of direct costs of cancer medical care for patients suffering from cancer with assigned radiotherapy-based treatment protocols. Identification of key cost drivers and trends during 2010-2013 comparing brachytherapy and teleradiotherapy was a secondary objective of the study. Retrospective, bottom-up database analysis was conducted on electronic discharge invoices. Payer's perspective has been adopted with a 1-year long time horizon. Total sample size was 2544 patients during a 4-years long observation period (2010-2013). The sample consisted of all patients with confirmed malignancy disorder receiving inpatient radiation therapy in a large university hospital. Diagnostics and treatment cost of cancer in the largest Western Balkans market of Serbia were heavily dominated by radiation therapy related direct medical costs. Total costs of care as well as mean cost per patient were steadily decreasing due to budget cuts caused by global recession. The paradox is that at the same time the budget share of radiotherapy increased for almost 15% and in value-based terms for €109 per patient (in total €109,330). Second ranked cost drivers were nursing care and imaging diagnostics. Costs of high-tech visualizing examinations were heavily dominated by nuclear medicine tests. The budget impact of radiation oncology to the large tertiary care university clinics of the Balkans is likely to remain significant in the future. Brachytherapy exhibited a slow growth pattern, while teleradiotherapy remained stable in terms of value-based turnover of medical services. Upcoming heavy investment into the national network of radiotherapy facilities will emphasize the unsatisfied needs. Huge contemporary budget share of radiotherapy coupled with rising cancer prevalence brings this issue into the hot spot of the ongoing cost containment efforts by local governments.

Background: The aims of this article were to report findings of domestic research related to assessment of hospital treatment costs of Serbian patients suffering from cancer and show similar study results among foreign trials. The authors also intended to suggest likely strategies to improve local cost containment in future. Cost-of-illness studies of most high-income economies have proven that malignant disorders belong to top five disorders according to their overall financial burden. Methods: Our trial was conducted as an in depth, retrospective, bottom-up, trend analysis of services con?sumption patterns and expenses relative to diagnosis at discharge, from perspective of the third party payer. Discounting rates were calculated according to the average official exchange rates of the National Bank of Serbia in respective years. Financial value of medical goods and services consumed was taken out of current price lists of the National Republic Institute on Health Insurance on a day when particular service was provided. Results: There were 434 patients and 4850 admissions processed in 2007, consuming 48,483,740.49 RSD (?613,562.90) while in 2010 there were 539 patients and 9509 admissions, consuming 68,880,953.27 RSD (?658,832.65). In total, drugs value accounts for only 5%, radiotherapy 54% and the rest of expenditure 41% (consulta?tions, surgery, consumables, nursing care, other). Average overall cost per patient treated was 125,922.34 RSD and per hospital admission, it was 8,297.99 RSD. Cancer-related medical care costs, in domestic currency, increased by almost one third in only four-year time span. Conclusion: Higher awareness of clinicians on cost limitations and necessity of prioritization in funding health care, would provide wiser resource allocation and more care with money available.

Background: Bevacizumab is an anti-VEGF, humanized mAb that is the most advanced agent of its class in clinical development. Several studies have examined bevacizumab in combination with chemotherapy in the first- and second-line settings in patients with metastatic CRC. Despite of that, there is lack of information concerning the extent to which bevacizumab can be used to treat metastatic CRC. We still need more evidence related to efficacy and safety of bevacizumab in different settings, or sequential treatments. The aim of this study was to investigate efficacy and safety of bevacizumab added to different chemotherapy in patients with metastatic CRC. Methods: This was a controlled, prospective, multicentre, cohort study. Thirty patients with advanced colorectal cancer were enrolled into this study. Bevacizumab was applied with oxaliplatin-, irinotecan-, 5FU- or capecitabine -based chemotherapy in the first-, second- or third-therapy lines. Totally 261 cycles were applied. The median number of applied cycles per patient was 8 (range 2-16). Results: Objective tumor response (RR) was seen in 11 patients 37% (95%CI 19-69%) calculated on an intention-to-treat basis. The median duration of response was 12 months. Three of 11 patients (27%) with PR had secondary surgery. RR was seen in 9 of 16 patients (56%) who received bevacizumab in the first-line treatment and in 2 of 14 patients (14%) who received therapy in the second+ lines (p=0.02). Clinical benefit (PR+SD) was seen in 22 (74%) patients. 75% of patients achieved clinical benefit in the first-line and 74% in the second+ chemotherapy lines. The median time to progression (TTP) of the patients is was 9 + months (95%CI 7 - + ?) at the moment of this analysis. The median TTP of patients who received bevacizumab in the first line was 11 months (95%CI 8 - + ?). The median TTP of patients who received bevacizumab in the second+ lines was 5.5 months (95%CI 4 - + ?) (p=0.015). The median survival time (OS) for all patients was 9 + months (95%CI 7 - + ?). The median OS at the moment of analysis was 11 months (95%CI 9 - + ?) for patients receiving bevacizumab in the first line, and 7 months for patients receiving the drug in the second+ lines (95%CI 6 - + ?) (p=0.024). The incidence of any toxicity grade 3-4 was less than 10%. Bevacizumab associated incidence of grade 3-4 side effects did not exceed 5%. Hypertension 5% and thromboembolism 5% were the most frequent events. Gastrointestinal perforation did not occur. There was one toxic death due to sepsis and not directly associated with bevacizumab toxicity. Conclusion: Bevacizumab can safely be added to different chemotherapeutic regimens in first- and second+ line. The conferred benefit in overall survival, TTP and response rate obviously requires randomized trials.

We investigated the influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). During 3 randomized phase III and 1 phase II study, a total of 536 patients were treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred eighty-five patients were treated with IFI of 4.5–5.0 hours, while 251 patients were treated with IFI of 5.5–6.0 hours. “Shorter” (4.5–5.0 hours) IFI led to better overall survival (OS) (P = 0.0000) and local recurrence-free survival (LRFS) (P = 0.0000). Multivariate analyses showed IFI to be an independent prognosticator of both OS and LRFS. These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409). Various RT-related high-grade acute toxicity was not different between the 2 IFI, but patients treated with shorter IFI had a significantly higher incidence of hematological toxicity (P = 0.002). None of the late high-grade toxicities were different between the 2 interfraction intervals. Using regression analysis, it was shown that IFI was not a significant predictor of any of acute or late high-grade (≥3) toxicity. IFI is an important prognosticator of OS and LRFS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of hematological toxicity, but was not predictive of any acute or late high-grade (≥3) toxicity. A carefully designed randomized trial seems necessary to give better insight into the issue of optimal IFI in this disease.