Differences in Outcomes Between Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer Patients in Upper Middle-Income versus High-Income Countries: A Retrospective Study from 4 Oncology Centers.

BACKGROUND Therapeutic options for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (mBC) are developing rapidly. This study aimed to determine the differences in the survival outcomes of patients with HER2-positive mBC in relation to access to anti-HER therapy at 3 oncology centers in upper-middle-income countries (UMICs) and 1 oncology center in a high-income country (HIC). MATERIAL AND METHODS We retrospectively identified 42 patients from Croatia (HIC), 71 patients from Serbia (UMIC), and 57 from Bosnia and Herzegovina (UMIC) diagnosed with HER2-positive mBC who were treated between January 2015 and December 2020. The pathohistological features of the tumors were obtained from the pathological findings, which were made according to standard procedures for each center. Patients were treated depending on the availability of therapy, which differed for centers in different countries. We evaluated disease-free survival, progression-free survival, and overall survival (OS) based on the availability of first- and second-line anti-HER2 therapy in UMICs vs HIC. RESULTS OS in first-line therapy was better in patients treated with dual HER2 blockade than in patients treated without dual HER2 blockade, P<0.001. OS in second-line therapy was significantly better in patients treated with trastuzumab emtansine than in patients treated with other reported regimens, P=0.004. CONCLUSIONS Results of our study showed superior survival among patients who were treated with dual first-line HER2 therapy as well as second-line trastuzumab emtansine therapy than in those patients in other centers where these drugs were not available. Raising awareness about this could help improve the situation.

Use of the Depression, Anxiety and Stress Scale (DASS-21) Questionnaire to Assess Levels of Depression, Anxiety, and Stress in Healthcare and Administrative Staff in 5 Oncology Institutions in Bosnia and Herzegovina During the 2020 COVID-19 Pandemic.

BACKGROUND Providing oncology services during a pandemic can contribute to mental health challenges among healthcare workers. The present study aimed to evaluate the levels of depression, anxiety, and stress in healthcare and administrative staff in 5 oncology institutions in Bosnia and Herzegovina (BiH) in 2020 during the coronavirus disease 2019 (COVID-19) pandemic using the Depression, Anxiety and Stress Scale (DASS-21) questionnaire. MATERIAL AND METHODS A cross-sectional observational study enrolled 175 healthcare and administrative workers from 5 oncology institutions in BiH during December 2020. Data were collected using a questionnaire that captured general information about the participants and a DASS-21 questionnaire. RESULTS Statistical analysis revealed a statistically significant difference in the levels of depression, anxiety, and stress (P=0.003, P=0.011, and P=0.022, respectively) among participants with comorbidities connected with increased risk of severe illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with participants without comorbidities. There was also a statistically significant difference in the levels of stress among participants from different cities (P=0.031). Supplement intake and educational level were significantly related (P=0.012). High levels of stress and anxiety were accompanied by high levels of depression among participants (P<0.01). CONCLUSIONS The findings from the present study showed that the COVID-19 pandemic has had an effect on depression, anxiety, and stress levels in oncology staff in BiH. Monitoring these levels and providing interventions and support to oncology staff are increasingly important for their wellbeing and retention at a time of global crisis in healthcare.

The Use of Complementary and Alternative Medicine among Cancer Patients Undergoing Conventional Treatment: A Single-Centre Experience.

BACKGROUND: The alternative medicine is increasingly accepted by modern man. People realize that healing based on natural methods is much more affordable and not more aggressive than taking potent drugs of synthetic origin. The aim of this study was to collect data on the use of complementary agents and alternative medicine in cancer patients treated at the Oncology Clinic of the University Clinical Hospital in Mostar. SUBJECTS AND METHODS: We conducted a cross-sectional study that included 100 patients. Data were collected from a questionnaire compiled for this research, which comprised two groups of questions. The first group examined the sociodemographic characteristics of the respondents, and the second the modalities of using Complementary and Alternative Medicine (CAM), and health and conceptual reasons for use. RESULTS: A total of 72 patients (72.0%) had used a CAM during their anticancer treatment. Only 23% of patients had used CAM before the diagnosis of cancer. Among them, 26 (36.1%) previously discussed the topic with their oncologist. CAMs ranged from herbal medicine (58.3%), cannabinoid oil (19.4%) and different vitamins and minerals (22.2%). CAMs were mainly used to improve the health (40.3%). Among patients who used CAM only 25% find it financially demanding, 90.3% of patients were satisfied with effects of CAMs, and 78.1% would recommend it to other cancer patients. CONCLUSION: Our data showed that in our region, many patients used complementary and alternative methods of treatment. These results are very important because they provide information and give a clearer picture of the use of CAM among cancer patients and, accordingly, the right approach of the health practitioners to the patient, leading to optimized cancer therapy and increased safety.

Primary Central Nervous System Lymphoma, Treatment Outcomes - 10 Year Experience. Single Center Study.

Background: Primary central nervous system lymphoma(PCNSL) is an aggressive, rare form of Non-Hodgkin lymphoma, characterized by the absence of systemic disease. There are limited data and no strictly defined guidelines for management of PCNSL. Objective: The aim of this study was to report a 10 year experience of PCNSL treatment, to evaluate treatment outcomes and asses Progression Free and Overall Survival of these patients. Methods: Study was conducted on the Haematology Clinic, Clinical center University of Sarajevo, BH, in the period from January 2012.-December 2022. Total sample of 24 patients were enrolled. All have undergone diagnostic surgery. Patients were treated with regimens based on High dose Methotrexate, with/without whole brain radiotherapy as consolidation. Treatment response was captured by imaging techniques. Patients who have relapsed were evaluated with imaging techniques and treated according to Methotrexate-based treatment protocols. Results: We have captured equal gender distribution. The median age of patients was 59.5 years (range 20-79). Pathohistological analysis confirmed DLBCL diagnosis in 22 patients, T cell lymphoma and anaplastic large cell lymphoma, each in 1 patient. Chemotherapy, chemotherapy combined with WBRT and radiotherapy were given to 5, 18 and 1 patients, respectively. The overall complete response rate (CR) was 87,15%. Those receiving combined modality-treatment had higher CR than those receiving chemotherapy (94,4% versus 60%). Out of 24 patients, 11 of them relapsed. The median time to relapse was 29 months (from 1 to 105). After second line of the treatment, CR was 54,5%, while 45,45% of patients died during the treatment. 4 patients relapsed for the second time with median time to relapse of 9 months (from 2 to 77). 2 year OS rate was 67%, and the median OS rate was 45,9 months. 2 year PFS rate was 31%. Conclusion: The OS and PFS rates indicate the usage of new drugs and consolidation with autologous stem cell transplantation in patients with PCNSL in order to achieve better treatment outcomes.

Unmet needs in EGFR exon 20 insertion mutations in Central and Eastern Europe: reimbursement, diagnostic procedures, and treatment availability.

Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3-2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as "typical" EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations.This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions.The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.

Prognostic and predictive significance of VEGF, CD31, and Ang-1 in patients with metastatic clear cell renal cell carcinoma treated with first-line sunitinib.

The most common type of renal cell carcinoma (RCC) is clear cell renal cell carcinoma (ccRCC), which has a high metastatic potential. Even though the International Metastatic RCC Database Consortium (IMDC) risk model is conventionally utilized for selection and stratification of patients with metastatic RCC (mRCC), there remains an unmet demand for novel prognostic and predictive markers. The goal of this study was to analyze the expression of Vascular endothelial growth factor (VEGF), Cluster of Differentiation 31 (CD31) to determine microvessel density, and Angiopoietin-1 (Ang-1) in primary kidney tumors, as well as their predictive and prognostic value in patients with metastatic ccRCC (mccRCC) who were treated with first-line sunitinib. The study included 35 mccRCC patients who were treated with first-line sunitinib in period between 2009 and 2019. Immunofluorescence was used to examine biomarker expression in tissue specimens of the primary tumor and surrounding normal kidney tissue. Median disease-free survival (DFS) was longer in patients with negative and low tumor VEGF score than in patients with medium tumor VEGF score (p=0.02). Those with low tumor CD31 expression had a longer median DFS than patients with high tumor CD31 expression (p=0.019). There was no correlation between Ang-1 expression and DFS. The expression of biomarkers in normal kidney tissue was significantly lower than in tumor tissue (p<0.001). In conclusion, higher VEGF scores and greater CD31 expression were associated with longer DFS, but neither of these biomarkers correlated with progression-free survival or overall survival.

Guidelines for breast cancer management in Bosnia and Herzegovina.

Breast cancer is the most common cancer among women. In Bosnia and Herzegovina, accurate data on the status of breast cancer are lacking due to the absence of a central registry. Multiple international guidelines imply that institutions that monitor breast cancer patients should have optimal therapeutic options for treatment. In addition, there have been several international consensus guidelines written on the management of breast cancer. Application of consensus guidelines has previously been demonstrated to have a positive influence on breast cancer care. The importance of specialty breast centers has previously been reported. As part of the 2021 Bosnian-Herzegovinian American Academy of Arts and Sciences (BHAAAS) conference in Mostar, a round table of multidisciplinary specialists from Bosnia and Herzegovina and the diaspora was held. All were either members of BHAAAS or regularly participate in collaborative projects. The focus of the consortium was to write the first multidisciplinary guidelines for the general management of breast cancer in Bosnia and Herzegovina. Guidelines were developed for each area of breast cancer treatment and management. These guidelines will serve as a resource for practitioners managing breast cancer in the Bosnia and Herzegovina region. This might also be of benefit to the ministry of health and any future investors interested in developing breast cancer care policies in this region of the world.

Acceptance, effects, and tolerability in the vaccination process against SARS-CoV-2 among cancer patients in Bosnia and Herzegovina: A single-center cross-sectional study.

The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-COV-2 among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to completean individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of COVID-19 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population.

The Oncology Association of Bosnia and Herzegovina's recommendations for fertility preservation in oncologic patients.

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves.  Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.

2020 consensus guideline for optimal approach to the diagnosis and treatment of HER2-positive breast cancer in Bosnia and Herzegovina.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization and optimization of the procedures for the diagnosis, treatment and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a multidisciplinary tumor board comprised of at least: a medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.

The Prognostic Value of SUVmax of 18F-FDG PET/CT in Patients with Metastatic Colorectal Cancer.

OBJECTIVE: The aim of the study was to evaluate the prognostic value of the maximum standardized uptake value (SUVmax) of 18F-Fluorodeoxyglucose (18F-FDG) PET/CT in patients with metastatic colorectal cancer, and to compare it with classical prognostic markers. MATERIALS AND METHODS: The study included 70 patients with metastatic colorectal cancer who had not been treated for the metastatic disease. The patients underwent 18F-FDG PET/CT as part of their routine diagnostic reevaluation. During the analysis, the value of the largest tumor diameter and SUVmax was determined for the lesion with the highest SUVmax observed. The values of CEA and CA 19-9 were recorded 7 days before the PET/CT analysis. RESULTS: SUVmax and Carbohydrate antigen (CA)19-9 were found to be independent prognostic markers of disease progression within 12 months. Based on the Receiver Operating Characteristics (ROC) curve analysis, the patients could be divided into two groups: SUVmax≤4.1 vs. SUVmax>4.1. Patients with SUVmax values of 4.1 or less had significantly better progression-free survival within 12 months with an HR (95% CI) of 2.97 (1.4-6.3), relative to patients with SUVmax values above 4.1. CONCLUSION: SUVmax may be used as a novel prognostic marker of disease progression among patients with metastatic colorectal cancer. Values of SUVmax can be used to select patients with a more aggressive type of disease and higher risk for progression within 12 months of PET/CT analysis.

Lifestyle risk factors and comorbidities of cancer patients in a country with limited resources.

Aim To investigate quality of life and exposure to lifestyle risk factors of cancer patients in Bosnia and Herzegovina and a correlation of cancer type with lifestyle risk factors. Methods This was a cross-sectional study conducted on 200 cancer patients from the Clinical Centre of the University of Sarajevo. The respondents completed an anonymous questionnaire consisting of seven sections: basic patient information, physical activity, dietary habits including alternative medicine, tobacco use, alcohol consumption, anxiety, and comorbidities. Results A total of 150 (75%) patients were overweight with 113 (56%) of them being less physically active after the confirmed diagnosis. After the diagnosis, 79 (40%) patients ate less food, and 154 (77%) healthier; 130 (65%) reported consumption of alternative medicine and food supplements, 39 (30%) spent >1/4 of average monthly salary on these products. Majority never consumed alcohol, 135 (68%) and 101 (51%) patients reported history of tobacco use. Being obese was an independent predictor for colorectal carcinoma; being less obese was linked to a decreased risk of breast cancer diagnosis. Physical activity was linked to a decreased risk of lung cancer diagnosis. Many patients (122; 61%) reported having chronic comorbidities, mostly hypertension, while 44 (22%) patients were proven to be clinically anxious. Conclusion Our data suggest lack of public awareness of the consequences of unhealthy lifestyles. Risk factors such as alcohol consumption and tobacco use differed from other European countries. Significance of lifestyle changes after the diagnosis for reducing mortality and cancer recurrence requires further research. Prevention programs and more data are needed.

AROME-ESO Oncology Consensus Conference: access to cancer care innovations in countries with limited resources. Association of Radiotherapy and Oncology of the Mediterranean Area (AROME-Paris) and European School of Oncology (ESO - Milan).

PURPOSE: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference. METHODS: Cancer prevention and treatment strategies were discussed according to existing international guidelines. The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/middle-income Mediterranean countries. The results from the votes of 65 oncology experts, coming from 16 countries and 33 institutions have been analysed and access priorities classified accordingly. RESULTS: Ninety six percent of the proposed general recommendations concerning national health care strategies, oncology education, and treatment organization were considered to be high priorities. Regarding access to systemic treatments, 41% of the drugs without validated predictive markers and 53% of those with validated predictive markers were considered to be 1st level priority. Only 4 biological tests were considered to be 1st level priority to access to innovation. CONCLUSIONS: AROME-ESO consensus offers to cancer specialists from developing countries a basis for discussion with health authorities and payers on the prioritization of access to innovations in cancer care.

Value of Positron Emission Tomography/Computed Tomography (PET-CT) in Suspected Non-small Cell Lung Cancer Recurrence and Impact on Patient Management.

INTRODUCTION: Positron emission tomography/computed tomography (PET-CT) is very sensitive for diagnosis of recurrent NSCLC and has a significant impact on change of management. Preliminary data suggest superiority of PET-CT comparing to CT alone for lung cancer restaging. MATERIALS AND METHODS: This is a retrospective study which aim is to validate usage of PET-CT in suspected non-small cell lung carcinoma recurrence and its impact on further patient management. Total number of 31 patients with non-small cell lung carcinoma and uncertain diagnosis of recurrent disease or its extent after routine clinical and CT work-up were enrolled in this study. DISCUSSION: We found in our study that PET-CT diagnosed recurrent disease in 65% of patients who were previously presented with an indeterminante CT. In 85% of patients there were change in further management. CONCLUSION: We suggest that PET should be performed on patients who have suspected relapse after potentially curative treatment, particularly if active treatment is being considered. PET-CT improved the diagnosis of recurrent NSCLC and this resulted in a significant impact and change in further patient management.

Advantages of Combined PET-CT in Mediastinal Staging in Patients with Non-small Cell Lung Carcinoma.

INTRODUCTION: Precise mediastinal lymph node staging in patients with non-small cell lung carcinoma (NSCLC) provides important prognostic information and it is obligatory in treatment strategy planning. 18Fluoro-deoxy-glucose (18F-FDG) positron emission tomography - computerized tomography (PET-CT) based on detection of metabolic activity showed superiority in preoperative staging of lung carcinoma. MATERIALS AND METHODS: Total number of 26 patients diagnosed with NSCLC were included in this retrospective, cross-sectional study. Status of mediastinal lymph nodes was assessed in all patients comparing contrast enhanced CT and 18F-FDG PET-CT findings. DISCUSSION: We found in our study that 50% of patients had different N stage on contrast enhanced CT comparing to 18F-FDG PET-CT findings. Among the total number of patients which had different nodal status on PET-CT comparing to CT alone, we found in our study that 54% of patients had change in further therapy protocol after PET-CT change of nodal stage. CONCLUSION: Combined PET-CT which offers advantages of both modalities is excellent method for nodal (N) staging, so it is recommended in initial staging in patients with NSCLC. PET-CT used preopratively for mediastinal nodal staging has significant impact on further therapy planning and also has an consequential impact on health system savings.

Investigation of IVS14 + 1G > A polymorphism of DPYD gene in a group of Bosnian patients treated with 5-Fluorouracil and capecitabine.

Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14 + 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation.