Predicting Trifluridine/Tipiracil Treatment Outcomes in Refractory Metastatic Colorectal Cancer Patients: A Multicenter Exploratory Analysis.

INTRODUCTION: There are no recommended biomarkers to identify patients with refractory metastatic colorectal cancer (mCRC) who would benefit the most from trifluridine/tipiracil (TTP). The exploratory analysis of the RECOURSE trial revealed that patients with low tumor burden and indolent disease derive greater benefit in terms of both progression-free survival (PFS) and overall survival (OS). Nevertheless, the final answer on the TTP real impact on the well-being of patients with late-stage mCRC will come from real-world data. METHODS: The aim of this retrospective exploratory study was to investigate the effectiveness of TTP in mCRC with regard to the duration of standard treatment and other influencing variables. The study included 260 patients from the three largest Croatian oncology centers who began treatment with TTP in the third or fourth line between 2018 and 2020. RESULTS: The median OS and PFS for the entire cohort were 6.53 and 2.50 months, respectively. Patients with more aggressive disease, defined as those whose time to progression on the first two lines of standard therapy was less than 18 months, had significantly shorter PFS (2.40 vs. 2.57 months, hazard ratio [HR] 1.34, 95% confidence interval [CI]: 1.03-1.84). There was also a tendency toward shorter OS (6.10 vs. 6.30 months, HR 1.32, 95% CI: 0.99-1.78) but without statistical significance. Patients with ECOG PS 0, without liver metastases, and with RAS mutation had both longer OS and PFS. No influence was detected from other variables including age, sex, primary tumor location, and tumor burden. CONCLUSION: With regard to the results of the previously conducted trials, the study concludes that indolent disease, good general condition, and absence of liver metastases are positive predictive factors for TTP treatment.

Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia.

The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Predictors of outcomes of docetaxel treatment in de novo metastatic hormone-sensitive prostate cancer: A single-center cohort study.

Six cycles of docetaxel in addition to androgen deprivation therapy (ADT) are currently one of the treatment options for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Since the outcomes in patients with high-volume (HV) disease remain modest, we aimed to identify patients for more intensified treatment. We report a cohort of 73 consecutive patients with de novo mHSPC treated with early docetaxel at the Department of Oncology and Radiotherapy, University Hospital of Split, Croatia, from October 2015 until March 2020. The outcomes analyzed were the occurrence of castration-resistant disease (CRPC) and death from any cause (OS). The median follow-up was 54 (50-73) months. Forty-six (63%) patients developed CRPC and 34 (47%) died during the follow-up. The median time to CRPC and median OS were 16.2 and 58.4 months, respectively. The risk of CRPC was higher for patients with high (above median) values of serum alkaline phosphatase (ALP) (HR=2.4; 95% CI [1.4-4.5]), lactate dehydrogenase (LDH) (HR=1.98; 95% CI [1.1-3.7]), prostate-specific antigen (PSA) (HR=1.8; 95% CI [1.1-3]), ECOG performance status >1 (HR=2; 95% CI [1.2-3.3]) and HV disease (HR=1.9; 95% CI [1.1-3.1]). The risk of any-cause death was higher in patients with high values of ALP, LDH, and ECOG performance status >1. The predictive value of LDH was independent of disease volume. A set of baseline characteristics could be used in conjunction with disease volume in deciding on the optimal treatment strategy for patients with de novo mHSPC.

The relevance of macrocytosis induction during neoadjuvant dose-dense chemotherapy in breast cancer patients.

The aim of this study was to explore the red blood cell changes that occur during neoadjuvant dose-dense chemotherapy (NAC) of breast cancer. Also, we investigated the role of macrocytosis as a predictive biomarker for pathological complete response and disease-free survival (DFS) in these patients. A retrospective analysis of 82 breast cancer patients' data treated with anthracycline-cyclophosphamide-paclitaxel (AC-T) NAC in three oncology institutions in south Croatia from 2013 to 2020 was carried out. During chemotherapy mean corpuscular volume increased with time, with a median increase of 7.25 fl. Macrocytosis was induced in 38% of patients overall. Development of macrocytosis did not correlate with DFS [hazard ratio = 0.525; 95% confidence interval (CI), 0.074-3.768; P = 0.525]. Higher percentage of patients in macrocytosis group achieved PCR, 39% vs. 29% in no macrocytosis group, but this difference was not statistically significant. The relevance of macrocytosis induction during dose-dense neoadjuvant chemotherapy in breast cancer should be further explored.

COVID-19 Pandemic Effects on Breast Cancer Diagnosis in Croatia: A Population- and Registry-Based Study.

BACKGROUND: Our objective was to assess the effects of COVID-19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers in the Republic of Croatia. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective, population- and registry-based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases. RESULTS: The average monthly percent change after the initial lockdown measures were introduced was -11.0% (95% confidence interval - 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017-2019. CONCLUSION: It seems that national health care system measures for controlling the spread of COVID-19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID-19 control measures were relaxed, and it has not reoccurred during the second COVID-19 wave. Although the COVID-19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020. IMPLICATIONS FOR PRACTICE: It is possible to compensate for the adverse effects of COVID-19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non-negligible extent.

Real-world safety and efficacy of nivolumab for ≥ 2nd line treatment of metastatic renal cell carcinoma: A retrospective cohort study in Croatia, Hungary, and Malta.

The objective of our study was to assess the real-world safety and efficacy of nivolumab in the second- or later-line treatment of metastatic renal cell carcinoma (mRCC). We conducted a multicenter, retrospective, observational study of real-world data from patients who were treated with nivolumab under a patient expanded access program from 2015 to 2017 in Croatia, Hungary, and Malta. The primary safety endpoint was the discontinuation of therapy because of adverse events. The primary efficacy endpoint was overall survival (OS). We collected data from 87 patients with a median (interquartile range (IQR)) age of 63 (57-68) years, and 21% were females. The median (IQR) follow-up was 11 (5-31) months. Treatment was discontinued because of toxicity in 4 (5%) patients. Four (5%) patients experienced treatment-related adverse events of grade 3 or 4. The OS was 18.0 (95% CI: 11.0 to 28.6) months, and the PFS was 8.5 (95% CI: 4.9 to 12.1) months. Our study indicated a good safety and efficacy profile of nivolumab in the second- or later-line treatment of mRCC patients in a real-world clinical practice environment, which is comparable with the findings of the registrational trial.

Predictors of resistance to abiraterone acetate or enzalutamide in patients with metastatic castration-resistant prostate cancer in post-docetaxel setting: a single-center cohort study.

Treatment with abiraterone acetate or enzalutamide is one of the approved approaches in men with metastatic castration-resistant prostate cancer (mCRPC) in the post-docetaxel setting. However, a significant fraction of patients do not respond to treatment, and we aimed to determine their characteristics. From April 2015 to May 2019, 71 patients with mCRPC were treated with abiraterone acetate (N = 34) or enzalutamide (N = 37) at our institution. Resistance to treatment was defined as radiological or scintigraphic progression within 3 months, as documented at the first control. After a median follow-up of 14.9 months, resistance was detected in 22 patients (31%). Many of the baseline characteristics differed between responders and nonresponders but did not serve as predictors with clinically acceptable certainty. To overcome this, the resistance score was defined as the number of positive out of the following six predictors: Most patients with resistance and a few responders had >3 positive predictors. Therefore, by using a cutoff of four positive predictors, the resistance score showed both a high sensitivity of 82% [57-96%; 95% confidence interval (CI)] and a specificity of 88% (74-96%; 95% CI). The proposed resistance score integrates the diagnostic performances of multiple predictors and may serve to decide which patients with mCRPC should be offered treatments other than hormonal therapy.

Predictors of outcome in elderly patients with metastatic colorectal cancer: the final results of a prospective phase II study of bevacizumab in combination with capecitabine as first-line treatment.

In 2011, we demonstrated that bevacizumab in combination with capecitabine as first-line treatment is effective in elderly patients with metastatic colorectal cancer (mCRC). We present the final results of the study with data on tumor molecular biology, sidedness and postprogression therapy. Forty patients with mCRC aged ≥70 years, initially treated with bevacizumab and capecitabine, were followed from the start of the treatment of metastatic disease to death. Tumor tissue samples were retrospectively analyzed for RAS, BRAF and microsatellite status. After a median follow-up time of 20.5 months, the median progression-free survival (PFS) and overall survival (OS) were 9.8 and 20.5 months, respectively and the objective response rate (ORR) was 65%. Twelve patients had mutation in RAS and four patients in BRAF gene, which coexisted with MSI in two cases. Patients with the right-sided tumor had apparently, but not statistically significantly lower PFS (8.6 vs. 13 months, P = 0.14) and statistically significantly lower OS (13 vs. 23.1 months, P = 0.046). Twelve patients with one or more postprogression therapy lines had significantly better ORR (12/12 = 100% vs. 14/28 = 50%, P = 0.003), median PFS (17.2 vs. 8.5 months, P < 0.001) and median OS (42 vs. 13 months, P < 0.001) than patients who received just first-line study treatment. Elderly patients with mCRC responded favorably to bevacizumab and capecitabine, especially the subgroup with the left-sided primary tumor. In the further subset of this group, characterized by RAS/BRAF wild-type and MSS tumors, the application of postprogression therapies was feasible and resulted in significant prolongation of survival.

Expenditures on Oncology Drugs and Cancer Mortality-to-Incidence Ratio in Central and Eastern Europe.

BACKGROUND: There is a steady decline in cancer mortality in Western Europe (WE), but this trend is not so obvious in Central and Eastern Europe (CEE). One of the largest discrepancies between WE and CEE is the level of investment in cancer care. The objective of our analysis was to examine the correlation between mortality-to-incidence (M/I) ratio and expenditures on oncology drugs in CEE and WE. MATERIALS AND METHODS: This cross-sectional analysis was done on publicly available data. Data on expenditures for oncology drugs were obtained from QuintilesIMS, and data on M/I ratio from Globocan. The main outcome was mortality-to-incidence ratio, and the primary analysis was performed by Spearman's rank correlation. RESULTS: There is a large discrepancy in expenditure on oncology drugs per cancer case between WE and CEE, and within CEE. Average expenditure on oncology drugs per capita as well as per new cancer case was 2.5 times higher in WE than in CEE. Availability of oncology drugs was highest in Germany (100%), relatively similar in WE (average of 91%), but in CEE it ranged from 37% to 86%, with an average of 70%. Annual expenditures on all oncology drugs per new cancer case was significantly negatively correlated with the M/I ratio (Spearman's ρ = -0.90, p < .001). CONCLUSION: There is a financial threshold for oncology drugs per cancer case needed to increase survival. Based on significantly lower expenditures for oncology drugs in CEE in comparison with WE, more investment for drugs as well as better, more organized, value- oriented consumption is needed. IMPLICATIONS FOR PRACTICE: Cancer is not treated equally successfully in Western Europe (WE) and in Central and Eastern Europe (CEE). This study showed that success in treatment of cancer is associated with the amount of money invested in oncology drugs. CEE countries spend on average 2.5 times less than WE countries for oncology drugs per new cancer case. These findings should be used by health care providers and oncologists struggling for more resources and better, more organized, evidence-based allocation of these resources as well as better oncology outcomes.

Efficacy and safety of palbociclib in heavily pretreated patients with HR+/HER2- metastatic breast cancer.

AIM: CDK4/6 inhibitors in the first and second treatment line in patients with HR+/HER2- metastatic breast cancer (mBC) in combination with hormonal therapy improve progression-free survival. Role of CDK4/6 inhibitors in further treatment lines remains unclear. METHODS: Retrospective analysis of 24 HR+/HER2- heavily pretreated mBC patients is presented. RESULTS: A total of 58.3% patients achieved stable disease. No objective response was observed. Median progression-free survival was 4.8 months; median overall survival was 11 months. Treatment was well tolerated. CONCLUSION: Favorable toxicity profile and efficacy of palbociclib/aromatase inhibitors combination in heavily pretreated luminal mBC patients in this study emphasize the need for further investigation of such drugs in this population.

Is macrocytosis a potential biomarker of the efficacy of dose-dense paclitaxel-carboplatin combination therapy in patients with epithelial ovarian cancer?

The aims of this study were to investigate a clinical observation that patients with epithelial ovarian cancer treated with first-line platinum-paclitaxel chemotherapy combination (TP) develop macrocytosis and to explore the possible predictive role of macrocytosis in response rate, progression-free survival (PFS), and overall survival. A retrospective analysis of laboratory and clinical data on 184 consecutive ovarian cancer patients treated with first-line TP chemotherapy in a single oncology center from 2004 to 2015 was carried out. Macrocytosis was defined as an increase in mean corpuscular volume of peripheral red blood cells above 97.2 fl during the treatment and/or 30 days after the last chemotherapy cycle. One hundred and forty-one patients were treated with a conventional 3-weekly TP schedule, whereas 43 patients were treated with a dose-dense schedule. Macrocytosis was induced in 35% of patients overall. It was induced significantly more often in patients treated with the dose-dense schedule than in those treated with the 3-weekly schedule (67 vs. 26%, P=1.29×10). Macrocytosis did not correlate with PFS and overall survival in the overall patient population, nor in patients treated with the 3-weekly schedule. It correlated with PFS (hazard ratio=0.42, 95% confidence interval=0.18-0.94, P=0.036) and objective response on therapy in patients treated with the dose-dense schedule (P=0.0285). Dose-dense TP chemotherapy induces macrocytosis significantly more often than does a 3-weekly schedule in ovarian cancer patients. In patients treated with a dose-dense schedule, macrocytosis can potentially be predictive for longer PFS and better response rate. This finding needs further confirmation, preferentially in a prospective study.

The role of the multidisciplinary team in the decision making process in stage one testicular cancer - retrospective cohort analysis.

PURPOSE: To analyze the role of a multidisciplinary team (MDT) in the decision-making process in clinical stage one (CS I) testicular cancer (TC). METHODS: We retrospectively evaluated data on 115 consecutive patients with CS I TC (excluding stage IS) who were referred to the Department of Oncology, University Hospital of Split, Croatia, from 2003 to 2012. Fifty-six patients (48.7%) were referred between 2003 and 2007, before the introduction of the MDT and 59 patients (51.3%) between 2008 and 2012, after the introduction of the MDT. We evaluated the overall treatment outcome (cure rate) and the total number of patients with CS I TC who were treated or monitored: in seminoma (SA) group adjuvant radiotherapy (ART) vs adjuvant chemotherapy (ACT) or active surveillance (AS) and in non-seminoma (NSA) group retroperitoneal lymphadenectomy (RPLND) vs ACT or AS. RESULTS: After the introduction of the MDT we stopped using ART for CS I SA, and significantly increased the usage of ACT and AS (p<0.001). RPLND in CS I NSA was used significantly less often after the introduction of the MDT while the usage of ACT and AS increased (p=0.047). CONCLUSION: With the MDT introduction we significantly changed the approach to patients with CS I TC. More aggressive and more toxic forms of the postoperative treatment were replaced by AS or less toxic ACT. Despite less aggressive adjuvant treatment approach, significant changes in the cure rate between two time periods were not noticed.

A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer.

BACKGROUND: We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC) and report the first prospective extended RAS analysis in a phase 3 trial. METHODS: Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6 mg kg-1 Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central laboratory testing. The primary endpoint was OS in wild-type KRAS exon 2 mCRC; OS in wild-type RAS mCRC (KRAS and NRAS exons 2, 3, and 4) was a secondary endpoint. RESULTS: Three hundred seventy seven patients with wild-type KRAS exon 2 mCRC were randomised. Median OS was 10.0 months with panitumumab plus BSC vs 7.4 months with BSC (HR=0.73; 95% CI=0.57-0.93; P=0.0096). RAS ascertainment was 86%. In wild-type RAS mCRC, median OS for panitumumab plus BSC was 10.0 vs 6.9 months for BSC (HR=0.70; 95% CI=0.53-0.93; P=0.0135). Patients with RAS mutations did not benefit from panitumumab (OS HR=0.99; 95% CI=0.49-2.00). No new safety signals were observed. CONCLUSIONS: Panitumumab significantly improved OS in wild-type KRAS exon 2 mCRC. The effect was more pronounced in wild-type RAS mCRC, validating previous retrospective analyses.

Cancer Control in Central and Eastern Europe: Current Situation and Recommendations for Improvement.

: The incidence of many cancers is higher in Western European (WE) countries, but mortality is frequently higher in Central and Eastern European (CEE) countries. A panel of oncology leaders from CEE countries participating in the South Eastern European Research Oncology Group (SEEROG) was formed in 2015, aiming to analyze the current status and trends of oncology care in CEE and to propose recommendations leading to improved care and outcomes. The SEEROG panel, meeting during the 11th Central European Oncology Congress, proposed the following: (a) national cancer control plans (NCCPs) required in all CEE countries, defining priorities in cancer care, including finance allocation considering limited health care budgets; (b) national cancer registries, describing in detail epidemiological trends; (c) efforts to strengthen comprehensive cancer centers; (d) that multidisciplinary care should be mandated by the NCCPs; (e) that smaller hospitals should be connected to multidisciplinary tumor boards via the Internet, providing access to specialized expertise; (f) nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption and centrally evaluated secondary prevention programs for cervical, colorectal, and breast cancers; (g) prioritize education for all involved in cancer care, including oncology nurses, general practitioners, and palliative care providers; (h) establish outpatient care in day hospitals to reduce costs associated with the current inpatient model of care in CEE countries and to improve patients' quality of life; (i) long-term pharmacoeconomic evaluations of new therapies in CEE countries; (j) increase national oncology budgets in view of the higher mortality rates in CEE compared with WE countries; and (k) CEE countries urgently need help from the European Union to increase and monitor overall investment in cancer care. IMPLICATIONS FOR PRACTICE: Significant differences in cancer incidence and mortality have been observed between European countries. While the incidence of many cancer types is higher in Western European (WE) countries, the mortality is generally higher in Central and Eastern Europe (CEE). The primary purpose of this review was to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians, regulators, and payers, and to propose the most needed changes in order to make the oncology care in CEE closer to the WE standards.

GUIDELINES FOR THE PREVENTION, DETECTION AND THERAPY OF VITAMIN D DEFICIENCY IN ADULTS.

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin D.

Bisphosphonates in patients with renal cell carcinoma and bone metastases: a sunitinib global expanded-access trial subanalysis.

AIM: To investigate retrospectively the effects of bone metastases and bisphosphonates in sunitinib-treated metastatic renal cell carcinoma patients. PATIENTS & METHODS: Patients in Groups (Gp) 1 and 2, but not Gp3, had bone metastases. Gp2 received bisphosphonates following standard practice. RESULTS: Gp2 had less favorable prognosis than Gp1. Gp3 had fewer metastases and the best prognosis. More serious adverse events occurred in Gp2 versus Gp1. The difference in overall survival between Gp1 and Gp2 was not significant after adjusting for covariates. Significantly shorter overall survival in Gp1 versus Gp3 persisted after adjusting for covariates. CONCLUSION: Bone metastases may have a negative prognostic impact in metastatic renal cell carcinoma. Bisphosphonates may have delayed early disease progression for prognostically worse sunitinib/bisphosphonate-treated patients.

Long follow-up of patients with locally advanced cervical cancer treated with concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy.

OBJECTIVES: Locally advanced cervical cancer (LACC) is one of the leading health problems of the developing countries. We present long-term outcomes of treatment with a concomitant chemobrachyradiotherapy followed by consolidation chemotherapy regimen. MATERIALS AND METHODS: We treated 118 patients with LACC (International Federation of Gynecology and Obstetrics stages IB2-IVA) with external radiotherapy (50 Gy in 25 fractions) and concomitant chemobrachyradiotherapy (low-dose rate). Chemotherapy was applied during brachyradiotherapy (cisplatin on day 1 in combination with 24-hour infusion of ifosfamide and mesna uroprotection). Four cycles of consolidation chemotherapy were given starting 4 weeks after the second concomitant chemobrachyradiotherapy cycle. RESULTS: After median follow-up period of 99.3 months, we observed acceptable acute and late toxicity, local control rate of 97.5%, and an overall survival of 74.6% at 96 months. CONCLUSIONS: Chemobrachyradiotherapy regimen followed by consolidation chemotherapy described in this article is a valuable treatment option for LACC.

Combination of adjuvant radiotherapy and androgen deprivation therapy after radical prostatectomy in high risk prostate cancer patients - results from retrospective analysis.

PURPOSE: We retrospectively evaluated the outcome in prostate cancer (PCa) patients receiving combination of adjuvant radiotherapy (ART) and androgen deprivation therapy (ADT) after radical prostatectomy (RP). METHODS: Between 2004 and 2012, 132 patients were referred for ART to the Department of Oncology, University Hospital, Split. Fifty-six consecutive patients with at least one proven or possible adverse prognostic factor such as pelvic lymph nodes invasion (LNI), lymphovascular invasion (LVI), high tumor grade and high preoperative prostatic specific antigen (PSA) level received combination of ART and ADT, while 76 patients received ART alone. The ADT consisted of a luteinizing hormone releasing hormone (LHRH) agonist or bicalutamide at a dose of 150 mg per day. The duration of ADT was left at the discretion of the treating physician and it lasted 6 to 36 months (median 24).The effect of combination of ART and ADT on biochemical relapse-free survival (bRFS), metastases-free survival (mFS), disease-specific survival (DSS) and overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: After a median follow-up time of 61 months (range 13.6-113), the 5- and 7-year bRFS were 90.5 and 77.2%, respectively. Distant relapse occurred in 5 patients, resulting in 5- and 7-year mFS of 95.9 and 81.7%, respectively. During follow-up, 7 patients died (2 PCa deaths), resulting in 5- and 7-year DSS and OS of 100% and 94.7% and 90.6 and 81.5%, respectively. CONCLUSIONS: This retrospective study shows high bRFS, mFS, DSS and OS rates with the combination of ART and ADT in high-risk PCa patients.

[CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER--CROATIAN ONCOLOGY SOCIETY]. / KLINICKE UPUTE HRVATSKOGA ONKOLOSKOG DRUSTVA ZA DIJAGNOZU, LIJECENJE I PRACENJE BOLESNICA/KA OBOLJELIH OD INVAZIVNOG RAKA DOJKE.

Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia.