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PurposeAmplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon.Experimental designTumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases.ResultsOverall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months.ConclusionWe define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy.Implications for practiceCoamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects. [ABSTRACT FROM AUTHOR]

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%. [ABSTRACT FROM AUTHOR]

According to current evidence, testing for germline BRCA pathogenic variants in newly diagnosed breast cancer (BC) patients has the potential to reduce the burden of the disease through targeted therapies and secondary prevention. A personalized approach to testing can lead to improved individual outcomes for patients. Despite the proven clinical utility and therapeutic impact of BRCA1/2 tests in shaping therapy for metastatic BC, awareness and access to these tests are limited in many developing countries, including Türkiye. This limitation impacts the healthcare economy as delayed or missed interventions can lead to increased long-term costs. The limited access is mainly due to fear of stigmatization among patients, country-specific legislation and costs, a lack of awareness, vagueness surrounding the tests and access restrictions. This review offers a perspective for policymakers and healthcare providers in Türkiye to establish pathways that integrate the patient experience into comprehensive care pathways and national cancer control plans. Recent studies show that testing for a specific gene change in people newly diagnosed with breast cancer can help reduce the impact the disease has on their life as they can be given special treatments. When tests are tailored to each person, they can get better results. However, in many countries, including Türkiye, not many people know about or can get these tests. This is because of concerns about being judged, rules in the country, the cost, confusion about the tests and limited access. Not having these tests can make healthcare more expensive in the long run. This article suggests ways for Türkiye's leaders and health workers to make these tests a regular part of cancer care and planning. Gene testing in new breast cancer patients can reduce disease impact with tailored treatments. Yet, many in countries like Türkiye lack access due to various barriers. Let's integrate these tests into national care plans! #BreastCancer #GeneTesting [ABSTRACT FROM AUTHOR]

Introduction: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. Methods: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). Results: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI+ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p=0.012) and DCR (82.8% vs. 53.4%, p=0.008). The median OS was 13.47 (95% CI: 7.79–19.15) months, and the six and 12- month survival rates were 71% and 52%. The median duration of response was 16.59months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06months (95% CI: 3.42– 6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). Conclusion: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors. [ABSTRACT FROM AUTHOR]

The use of tyrosine kinase inhibitors has made a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Recently, lorlatinib, a third-generation tyrosine kinase inhibitor, has demonstrated significant systemic and intracranial activity in both first-line and subsequent-line therapy in ALK-positive NSCLC patients. In this review, general characteristics of lorlatinib, its efficacy in the treatment of ALK-positive NSCLC patients and the safety of lorlatinib, particularly addressing central nervous system adverse events, are discussed. Management of central nervous system adverse events, which seem to be specific to lorlatinib therapy, is outlined. Lung cancer is a common disease and affects patients badly. Lorlatinib is a new and useful drug for this disease. But this drug has also some undesirable effects for the brain. These effects are generally mild and can be treated. This article discusses the undesirable effects of this drug on the brain and how to cope with these effects. [ABSTRACT FROM AUTHOR]

Objectives: Inflammatory indexes are shown to have clinical significance in cancer. We aimed to determine the prognostic significance of a novel scale index as combined inflammatory index (CII) including leukocyte/lymphocyte ratio(LLR) & prognostic nutritional index(PNI) in nodular lymphocyte predominant Hodgkin Lymphoma(NLPHL) comparing them with well-known prognostic factors. Methods: 101 patients were evaluated retrospectively. Cut-offs were 3.9 for LLR and 53.5 for PNI by ROC analyses. A novel scale-index ('combined inflammatory index-CII') was obtained by the combination of LLR and PNI. Results: There was a moderate negative correlation between PNI and LLR (r=-0,66). In univariate analyses, advanced stage, bone marrow infiltration(BMI), B symptoms, lymphocytopenia, hypoalbuminemia, higher LLR(=3.9) and lower PNI(=53.5) were found to be significant prognostic factors. In multivariate analyses, LLR, PNI and CII were found to be independent significant risk factors for PFS while the models were standardized by age, stage, anemia, hypoalbuminemia, B symptoms & bulky disease. Conclusion: Prognostic score examining LLR and PNI besides other clinical parameters showed that patients in high risk group (higher LLR and lower PNI) had shortest PFS. In conclusion, a scoring system combining LLR and PNI is a novel scoring system in NLPHL.Combined inflammatory index-CII can be used as a prognostic factor in NLPHL. [ABSTRACT FROM AUTHOR]

To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time. [ABSTRACT FROM AUTHOR]

Objective: Neuroendocrine neoplasms(NENs) originate from the diffuse neuroendocrine cell system and constitute a heterogeneous group of tumors exhibiting diverse clinical and biological characteristics. NENs include well‑differentiated neuroendocrine tumors(NETs) and poorly differentiated neuroendocrine carcinomas (NECs). In the present study, we performed a retrospective analysis of patients diagnosed with NET to evaluate clinicopathological characteristics, treatment and outcomes. Material and Methods: Data from 153 patients diagnosed with NET who were treated and followed up at three tertiary care centers from November 2002 to June 2021 were retrospectively evaluated. Clinicopathological and prognostic factors, treatment modalities and survival data were analyzed. Kaplan–Meier analysis was used to assess survival data and comparisons were performed using the logrank test. Results: Median age (IQR) was 53 (18–80) years. 85.6% of the patients had gastro‑entero‑pancreatic (GEP)‑NET. The primary tumor was resected in 95 patients (62.1%) and metastasectomy were performed in 22 patients (14.4%). Seventy‑eight patients received systemic therapy for metastatic disease. Patients were followed up for a median of 22 (IQR = 33.8) months. The estimated one‑year and three‑year survival rate was 89.8% and 74.4%, respectively. Median progression‑free survival (PFS) were 10.1, 8.5, and 4.2 months after first‑, second‑ and third‑line therapy, respectively. Conclusion: The number of systemic treatment options and diagnostic tools for NETs has significantly improved in the last few years. NET classification, which treatment will be more appropriate for which group of patients, the molecular basis of this disease and the development of treatment strategies are open‑ended questions that still need to be investigated. [ABSTRACT FROM AUTHOR]

Objectives: Advanced stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients.Methods: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed.Results: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall-survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice (p < 0.001 HR:0.70 CI95% 0.55-0.9), performance status (p < 0.001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = 0.02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < 0.001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < 0.001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = 0.002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < 0.001 HR:0.55 CI 95% 0.38-0.79; p = 0.007 HR:0.51 CI95% 0.31-0.83, respectively).Conclusion: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions. [ABSTRACT FROM AUTHOR]

A rare condition in adults, Ewing sarcoma (EWS) has no standard treatment during the relapse--refractory period. In our study, we aimed to identify the treatment-related side effects of high-dose chemotherapy (HDC) and salvage autologous stem cell transplantation (ASCT) in adult patients with relapsed or refractory EWS and their survival rates. In a retrospective study, we recorded the clinical characteristics of patients with relapsed or refractory EWS treated with HDC in the hospital's patient registry to determine their objective response rate (ORR), progression-free survival (PFS), 6-month PFS rate, overall survival (OS), 6-month OS rate, transplantation-related mortality (TRM) and treatment-related side effects. In our sample of 29 patients (72.4% male), the mean age was 26.41 years (SD=9.35). The most common primary tumour site was the lower extremities (31%), 69% of patients had lung metastases, and 48.1% had undergone surgical resection, adjuvant radiotherapy and chemotherapy. The ORR to HDC was 31%. Median PFS (IQR) was 5.35 (6.79) months (95% confidence interval =4.23--8.28), whereas the 6-month PFS rate was 38.9%. Median OS (IQR) was 9.46 (14.45) months (95% confidence interval = 8.52--15.82), whereas the 6-month OS rate was 68.1%. Mortality from HDC or other causes occurred in five patients within the first 100 days after ASCT. Grade 3 febrile neutropenia and thrombocytopenia were present in all patients until engraftment following ASCT. Amongst adults with relapsed or refractory EWS, HDC has successful survival and response rates and a manageable side-effects profile [ABSTRACT FROM AUTHOR]

Objectives: To aim to show the survival outcomes of ifosfamide, carboplatin and etoposide (ICE) therapy and the characteristics of treatment-related hematological side effects in patients with relapsed/refractory bone sarcomas (BSs) and soft tissue sarcomas (STSs). Methods: Patients who were treated at the Department of Medical Oncology, Gulhane School of Medicine between January 2017 and June 2021 were included. Post-ICE progression-free survival (PFS), overall survival (OS) rates and treatment-related hematological side effects were determined. Results: Fifty-six adult patients were included (thirty-four of them BSs). PFS was determined as 6.7 ± 4.4 months and 7.1±3.6 months for STSs and BSs, respectively. OS was 11.4±5.6 monhts and 12.6±7.1 for STSs and BSs, respectively. PFS and OS were not found to be better between groups (p=0.84 and p=0.517, respectively). The median OS and PFS after ICE protocol in patients with two or less systemic chemotherapy lines were significantly higher than those who received three or more lines (7.85±1.66 vs 3.74 ±2.89, p=0.001 and 13.80±8.45 vs 6.73, p=0.001). Conclusion: In addition to its contribution for all patients, ICE may contribute to longer survival, especially in patients receiving ≤2 lines of systemic chemotherapy [ABSTRACT FROM AUTHOR]

Aim: To evaluate the immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy. Methods: This multicenter, prospective, observational study was conducted with 47 patients receiving active systemic therapy for cancer. CoronaVac was administered as two doses (3 μg/day) on days 0 and 28. Antibody level higher than 1 IU/ml was defined as 'immunogenicity.' Results: The immunogenicity rate was 63.8% (30/47) in the entire patient group, 59.5% (25/42) in those receiving at least one cytotoxic drug and 100% (five of five) in those receiving monoclonal antibody or immunotherapy alone. Age was an independent predictive factor for immunogenicity (odds ratio: 0.830; p = 0.043). Conclusion: More than half of cancer patients receiving active systemic therapy developed immunogenicity. [ABSTRACT FROM AUTHOR]

Introduction and aim: To demonstrate the real-life data about patients who underwent AHSCT due to GCT. Methods: Between November 2016 and April 2020, 64 patients who received CE as high-dose chemotherapy for AHSCT in the Gulhane Education and Research Hospital were included in the study. Sixty-one patients received one AHSCT with CE chemotherapy regimen. Survival data and clinical characteristics were evaluated retrospectively. Results: The mean age of the patients were 31.9 ± 9 (min-max:18–55). With a median follow-up of 10.7 ± 8.7 months, the 1-year progression-free survival (PFS) rate was 57.8%, and the 1-year overall survival rate was 77.5%. Median overall survival (OS) and progression-free survival (PFS) times were 21.5 ± 1.8 (95% CI: 14.5–33.4) and 20 ± 2 months, respectively. The response rate was 72%. There were three treatment-related deaths. Conclusion: This sizeable single-centre study shows that patients with relapsed metastatic GCT are curable by CE as high dose chemotherapy plus AHSCT with reliable toxicity even for a single cycle. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey.Material and Methods: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity.Results: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%).Conclusions: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy. [ABSTRACT FROM AUTHOR]

Background: This study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods: In this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers. Results: Cost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Conclusions: Our findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments. [ABSTRACT FROM AUTHOR]

Background: To describe the prognostic value of neutrophil–lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma. Methods: We retrospectively analyzed 331 patients. The cut-off value of neutrophil–lymphocyte ratio was specified as "3" which is mostly close—and also clinically easily applicable—to the median neutrophil–lymphocyte ratio level of our study group. High group is identified as neutrophil–lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil–lymphocyte ratio ≤3 (n = 163). Results: A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil–lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37–0.65), p < 0.001). Conclusion: In conclusion, the pre-treatment value of elevated neutrophil–lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Introduction and aim: To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer. Methods: We retrospectively analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis. Results: The median overall survival was 39 months (95% CI 26.1–51.8), 28 months (95% CI 17.9–38) and 7 months (95% CI 4.7–9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5–14.5) in the low-prognostic nutritional index (prognostic nutritional index ≤38.5) group, and 41 months (95% CI 30.5–51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival. Conclusion: In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has a high mortality rate and metastatic BC is almost incurable despite hormonal therapy and chemotherapy. The second and third lines of chemotherapies usually yield transient responses and the median survival is generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have been extensively investigated in this setting. The presence of immune mediated anti-tumor effects referred to as graft-versus-tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have been clearly defined. The advantages of allogeneic HSCT over autologous HSCT for metastatic BC are i) cancer-free graft and ii) immune-mediated GvT effects mediated by human leukocyte antigen compatible donor T-cells. In conclusion, a GvT effect does exist against metastatic BC and play a key role in tumor response. This review aims to describe the background, rationale, and clinical results of allogeneic HSCT as a potential alternative treatment in metastatic BC. [ABSTRACT FROM AUTHOR]

Objective: Even though the primary mediastinal extragonadal germ cell tumors (EGCTs) are rare, they are noteworthy in the differential diagnosis of mediastinal masses. In this study, we aimed to identify the clinical features of mediastinal malignant GCTs and compare the results of hematopoietic stem cell transplantation between mediastinal and nonmediastinal malignant EGCTs. Method: Data of the patients with EGCT who were treated and underwent hematopoietic stem cell transplantation at our hospital between 1988 and 2015 were retrieved retrospectively. Results were compared between mediastinal and nonmediastinal EGCTs. Results: Data of 65 patients diagnosed with EGCT (37 [56.92%] cases with mediastinal EGCT and 28 [43.07%] cases with nonmediastinal EGCT) were assessed. The clinical stages, frequency of pretransplant status, mean pretransplant time, and mean number of chemotherapy lines before hematopoietic stem cell transplantation were not significantly different between groups. Although the overall survival did not significantly differ between groups, the 5-year survival was significantly higher in mediastinal EGCTs (P=0.02). Yolk sac tumor was significantly more common in mediastinal EGCTs (P=0.05). Mortality rates were higher in seminomas and yolk sac tumors in all cases, higher in embryonal carcinomas in mediastinal EGCT group and higher in yolk sac tumors in nonmediastinal EGCT group. While choriocarcinomas had more aggressive courses in mediastinal EGCTs, seminomas and yolk sac tumors had poorer prognosis in nonmediastinal EGCTs. Short pretransplant time and persistence of elevated posttransplant βhCG and AFP levels were the significant mortality risk factors both in mediastinal and nonmediastinal EGCTs. Conclusion: Mediastinal placement of EGCT was not a poor prognostic factor; furthermore, the 5-year survival was significantly higher in mediastinal EGCTs. According to our knowledge, this is the first study that compares the clinical outcomes of hematopoietic stem cell transplantation of mediastinal and nonmediastinal malignant EGCTs. [ABSTRACT FROM AUTHOR]

Ovarian germ cell tumors (GCT) are derived from primordial germ cells of the ovary. Choriocarcinomas are more commonly of placental than ovarian origin in a woman. Vaginal choriocarcinoma is seen very rare in the literature. If the germ cell tumors are relapsed or refractory to the salvage chemotherapy, autologous hematopoietic stem cell transplantation (AHSCT) can be used for the treatment. Our aim is to present a rare vaginal choriocarcinoma patient who underwent AHSCT due to the relapsed disease. A 46-year-old woman who had two vaginal deliveries 18 years ago, presented with a vaginal mass. The diagnosis was made as choriocarcinoma after abscess drainage. Due to the elevated levels of β-HCG, she had undergone chemotherapy. After the four lines chemotherapy serum tumor markers remained high. Because of that reason, AHSCT was performed and after the transplantation, the β-HCG level has decreased. The patient was observed with a very good partial response. According to current literature, AHSCT is a reasonable treatment option for relapsed or resistant cases. In conclusion, our case is the first and unique who has undergone AHSCT. AHSCT is an effective and tolerable treatment for ectopic relapsed and refractory choriocarcinoma cases. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) is an important area of involvement for both highgrade, aggressive primary and secondary lymphomas. Although follicular lymphoma represents a low-grade histology, it may rarely present with CNS involvement. Here, we describe a patient diagnosed with follicular lymphoma who was presented with cerebellar involvement. [ABSTRACT FROM AUTHOR]

Aim: Both of the diagnosis and treatment evaluation are time-consuming conditions in patients with pulmonary and pleural tuberculosis. The aim of this study was to establish the validity of tumor markers CA 125, CA 15-3, and CA 19-9 in the diagnosis of pulmonary and pleural TB and to verify the success of the treatment protocol. Patients and methods: The levels of tumor markers CA 125, CA 15-3, and CA 19-9 were measured before and after treatment in 67 TB patients, 54 of whom had pulmonary TB and 13 of whom had pleural TB. All values were compared with the results of a healthy control group of 44 subjects. Results: CA 125 and CA 15-3 levels were significantly high when compared with those of the healthy control group and there was a significant decrease in both tumor marker levels after treatment in patients with pulmonary TB (P < 0.001 and P < 0.004, respectively). However, the difference found in CA 19-9 levels before and after treatment in patients with pulmonary TB was not statistically significant (P < 0.08). When the CA 125, CA 15-3, and CA 19-9 values of the pulmonary TB group before treatment were compared with that of the healthy control group, the results were statistically significant in all parameters except CA 19-9 (P < 0.001, P < 0.001, and P < 0.09 for CA 125, CA 15-3, and CA 19-9, respectively). In the patients with pleural TB, CA 125, CA 15-3, and CA 19-9 values did not change significantly after treatment. Conclusion: The authors suggest that CA 125 and CA 15-3 tumor markers may be important for verification of the success of treatment protocol in pulmonary TB, as the differences found for these tumor markers between the pre- and the posttreatment periods are statistically significant. [ABSTRACT FROM AUTHOR]