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WOS:000518031100008 PMID: 31970972 Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2- metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2- patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

© 2022 by Turkish Society of Medical Oncology.Objective: The development of bioinformatics and comprehensive genomic profiling (CGP) has provided insights into the ap-plicability and functionality of the genomic alterations (GA). In this study, we evaluated the impact of CGP on the treatment plan and outcomes in a significant number of patients. Material and Methods: We carried out a retrospective case-control study on 164 adult patients with advanced solid tumors from 15 oncology centers in Türkiye. Results: In all cases, CGP was performed within 23.8 [standard deviation (SD)±32.1] months of initial diagnosis. Non-small cell lung carcinoma, breast cancer, unknown primary carcinoma, colorectal carcinoma, and sarcoma were among the most common tumor types, accounting for 61.5% of all cases. CGP was performed immediately after the diagnosis of advanced cancer in 13 patients (7.9%). In 158 patients (96.4%), at least one GA was found as per the CGP report. Also, in the reports, the average tumor mutational burden (TMB) and GAs were 7.3 (SD±8.7) mut/Mb and 3.5 (SD±2.0), respectively. According to CGP reports, 58 patients had 79 evidence-based drug suggestions for their particular tumor type, whereas 97 patients had 153 evidence-based drug suggestions for another tumor type. After the primary oncologist interpreted the CGP reports, significant changes were made to the treatment of 35 (21.3%) patients. Conclusion: We strongly believe that in the future, high-TMB or other tumor-agnostic biomarkers will become much more afford-able, and CGP will serve as one of the major decision-making tools for the treatment of patients along with pathological, radiological or lab-oratory tests.

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0–55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

Background: Although HER2 is an aggressive subtype of BC, the outcomes have improved over the past two decades due to advances in targeted therapies. Here, we present data of HER2-positive subset from the multicenter registry study of the Turkish Oncology Group (TOG) for metastatic breast cancer with an evolving treatment landscape for over a decade (MBC). Methods: The study of TOG for MBC was a retrospective registry study aimed to collect the data of adult metastatic BC patients diagnosed between 2010-2019, at seven tertiary oncology clinics in Turkey. Patient and disease characteristics were recorded from chart reviews. HER2 (+) was defined as IHC scores of IHC3+ or IHC2+ and ISH (+). Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates comprising of cohorts based on disease presentation (recurrent vs de-novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010-December 2014 and Cohort II: between January 2015-December 2019). Results: Of the 1381 patients analyzed over the whole period, 333 (24.1%) HER2 (+) MBC patients were identified. 55.0% of the patients were in Cohort I. The majority (56.8%) had de novo MBC. Despite a decreasing frequency over time (63.4% in Cohort I vs 48.7% in Cohort II, p=0.007), this was the largest group with among all pathological subgroups presenting with de novo disease. 17 patients (2.4% of recurrent patients) demonstrated changes in HER2 receptor status from negative to positive between the primary tumor and subsequent metastasis. Recurrent BC patients were significantly younger than de novo MBC patients [44 (22-80) years vs 49 (20-91) years, p=0.006] and 43.1% (n=62) had relapsed within two years from initial diagnosis. Recurrent BC patients showed a higher frequency of brain metastasis as compared to de novo patients (13.2% vs 1.1%), whereas non-CNS visceral organ metastases were more common in de novo MBC patients (58.7% vs 47.9%, respectively, p< 0.001). Following conditional approval of use in de novo visceral metastatic disease in 2016, dual-HER2 blockade including pertuzumab was more frequently used in Cohort II compared to Cohort I (p< 0.001). Although overall median PFS was not statistically significant between the two cohorts (Cohort II vs I; 22 vs 17 months, respectively, p=0.609), there was a significantly higher PFS in the de novo group in Cohort II (29 vs 17 months, p=0.037). Furthermore, there was a significant improvement in median OS in Cohort II compared to Cohort I [not reached vs 48.0 (40.0-71.0) months, respectively; p=0.017]; mainly driven by the de novo group in alignment with the approval indication for dual blockade (Cohort I vs II; 3-year OS; 62.0% vs 84.7%; p=0.009); especially those with visceral metastatic presentation (59.4% vs 83.4%, p=0.020); HR (+) HER2 (+) disease (61.2% vs 89.2%; p=0.013) and age< 40 years (40.0% vs 94.7%; p=0.009). Conclusion: There was a significant survival benefit achieved in patients with metastatic HER2 (+) disease over time, regardless of high-risk factors such as visceral involvement or young age, mirroring advances in the timeline of anti-HER2 treatment. Citation Format: Yeşim ERALP, İzzet DOĞAN, Sercan Aksoy, Burcu ÇAKAR, Gül BAŞARAN, Özlem ERCELEP, Nil MOLİNAS MANDEL, Taner KORKMAZ, Erhan GÖKMEN, Adnan AYDINER, Pınar SAİP. Demographic and clinical features of patients with metastatic HER2 positive breast cancer: a retrospective multicenter registry study of the Turkish Oncology Group [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-06.

What is known and objective Erlotinib is a small molecule tyrosine kinase inhibitor which blocks the activation of epidermal growth factor receptor (EGFR), a transmembrane receptor that is upregulated in many cancer types. Inhibition of angiogenesis with consequent impairments in intratumoral microcirculation is one of the mechanisms through which EGFR inhibition halts the progression of cancer. A consequence of impaired microcirculation is intratumoral hypoxia, which results in increases in serum uric acid levels. The goal of this study was to investigate the relationship between serum uric acid levels and response to erlotinib in metastatic non-small-cell lung cancer (NSCLC). Methods A total of 56 patients with metastatic non-small-cell lung cancer who received erlotinib for a duration of at least 3 months were included in this retrospective cohort study. Demographic characteristics, progression status, baseline serum uric levels and 3-month serum uric acid levels were recorded and analysed. Results and discussion Of the study population, 21 (37.5%) were female and 35 (62.5%) were male patients. No significant difference in above demographic characteristics was observed among exitus, survivor with progression and survivor without progression groups. Patients who responded favourably to erlotinib with no progression of their disease had significantly increased uric acid levels at 3-month follow-up (P = .01). Such a correlation was not observed if the patient was exitus (P = .47) or had progressed on erlotinib therapy (P = .19). What is new and conclusion In conclusion, this study is the first to demonstrate significant increases in serum uric acid levels in patients with metastatic NSCLC who responded favourably to erlotinib and had no progression under erlotinib therapy. Further studies are required to confirm and characterize serum uric acid as a novel biomarker in predicting the outcome in those with metastatic NSCLC. Türkiye Cumhuriyeti Kalkınma Bakanlığı

PURPOSE In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy. MATERIALS AND METHODS Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread. RESULTS There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)max, SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P

Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation.Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.Results: Of 163 patients 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13 months disease follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. Conclusion: Osimertinib is a highly effective option in second or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p, NA

Amaç: Kliniğimize Küçük Hücreli Dışı Akciğer Kanseri (KHDAK) tanısı ile başvuran ve bu tanı ile neoadjuvan ve adjuvan tedavi alan hastaların hastalıksız ve genel sağkalım sonuçlarını değerlendirmek ve erken evre KHDAK’de hasta ve tümör karakteristiklerinin prognoza etkisini belirlemektir.Gereç ve Yöntem: Kliniğimize Ocak 2005-Haziran 2010 tarihleri arasında başvuran KHDAK hastalarının dosyaları retrospektif olarak taranarak, hasta ve tümör karakteristikleri, hastalıksız ve genel sağkalım verileri, hasta ve tümör özelliklerinin prognoza etkisi incelendi.Bulgular: Neoadjuvan grup 47 hastadan, primer opere olan grup da 135 hastadan oluşuyordu. Adjuvan kemoterapi evre III hastalarda hem hastalıksız sağkalım (p=0,001) ve hem de genel sağkalım (p

e13646 Background: Most of the frequent cancers present a large number of very rare targetable genomic alterations. Moreover, some oncogenic drivers are shared across several diseases, and their targeting could improve outcome. We think that testing a large number of genes across all tumor types could improve outcomes in patients with “hard-to-treat” advanced cancers. The most important factor for the cancer patient to benefit from precision medicine therapy is the detection of the targeted driver mutations. The objective of this study is to determine clinical advantages of hybrid capture based comprehensive genomic profiling over classical diagnostic methods in the treatment strategies of patients with advanced stage diverse solid tumors in Turkey. Methods: This study was designed as a national, multicenter, descriptive, non-drug, retrospective cohort study. Study data were collected from medical files of patients. Besides, a survey was conducted to investigate the impact of CGP results on the treatment decisions of the clinicians. Results: The study included the data of 118 patients (55; %46.6 female, 63; %53.4 male). The mean period between the diagnosis and CGP analysis was 748 days. For either due to progression (97; 75.2%) or intolerance to therapy (12; 9.3%), the treatment of some cases was discontinued after CGP analysis. The results of the electronic survey for the clinicians indicated that the 57;48.3% of the clinicians change their treatment approach based on the results of the CGP analysis, of these 24; 42.1% preferred on-label treatments,3; 5.3% clinical trials and the 30; 52.6% preferred off-label treatments. 59;69.8% of the clinicians declared that their patients can reach to the revised treatment. 48;42.1% of the clinicians expressed that CGP support was very important in the last treatment decision. This is the interim descriptive statistics of the study. Conclusions: This is the preliminary results of the study. Conclusions will be done after the final analysis of the study

We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption.The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP).We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram-negative infections decreased (from 43% to 20%, P = .003). In the multivariate analysis, appropriate continuation or de-escalation or discontinuation was increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR, 0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased significantly.After implementation of the ASP, the case fatality rate among the patients with FN decreased. Appropriate antimicrobial use increased and overall antimicrobial consumption was reduced. Bacterial infections and Candida infections decreased.

Purpose Awareness of advances in the nutritional aspects of cancer care and translation of this information into clinical practice are important for oncology practitioners to effectively couple oncologic and nutritional approaches throughout the cancer journey. The goal of this consensus statement by a panel of medical oncologists was to provide practical and implementable guidance addressing nutritional aspects of cancer care from the perspective of the medical oncologist. Methods A panel of medical oncologists agreed on a series of statements supported by scientific evidence and expert clinical opinion. Findings Participating experts emphasized that both poor nutritional intake and metabolic alterations underlie cancer-related malnutrition. The use of liquid and high energy-dense oral nutritional supplements may enable better patient compliance, whereas higher efficacy is more likely with the use of pharmaconutrient-enriched oral nutritional supplements in terms of improved weight, lean body mass, functional status, and quality of life, as well as better tolerance to antineoplastic treatment. A multimodal approach is currently believed to be the best option to counteract the catabolism leading to cancer-related malnutrition; this treatment is scheduled in parallel with anticancer therapies and includes nutritional interventions, multitarget drug therapies, and exercise and rehabilitation programs. Participating experts emphasized the role of the oncologist as a reference professional figure in the coordination of nutritional care for patients with cancer within the context of complex and different clinical scenarios, particularly for permissive-adjunctive nutritional support. Implications This review article provides practical guidance addressing major nutritional aspects of cancer care from the medical oncologist's perspective. Thus, this document is expected to assist oncology practitioners in terms of awareness of advances in the nutritional aspects of cancer care and translation of this information into their clinical practice to effectively couple oncologic and nutritional approaches as part of the continuum of care for patients with cancer.

The various types of ER-positive and HER-2-negative breast cancers have different treatment modalities. There are two options for the treatment of locally advanced breast cancer: chemotherapy or hormonal therapy. Chemotherapy can be particularly toxic for elderly postmenopausal patients, and neoadjuvant hormonal therapy (NHT) is an alternative for patients with hormone receptor-positive, locally advanced, postmenopausal breast cancer. This treatment is also highly beneficial for patients with comorbidities and can comprise tamoxifen and steroidal or nonsteroidal aromatase inhibitors (AIs). The best activities in clinical trials are observed with AIs. NHT produces good response rates (RRs) as well as adequate downstaging of tumor size such that breast-conserving surgery (BCS) may become an option. The optimal duration of such treatments should not be less than 4 months and may be continued for as long as 8 months.

Background: Desmoid tumors are uncommon and benign mesenchymal neoplasms. The optimal treatment of patients with desmoid tumors is still controversial. Surgery is the primary treatment for locally invasive or recurrent desmoid tumors. Also, radiotherapy is a treatment option for patients at high risk for local failure such as those with positive margins or recurrent and unresectable tumors. Aims: To report our institutional experience and long-term results of patients with desmoid tumors who received radiotherapy. Study Design: Retrospective cross-sectional study. Methods: Between 1980 and 2009, 20 patients who received radiotherapy (RT) in our institution were analyzed. The majority of patients (80%) were referred with a recurrent tumor after previous surgery. Thirteen patients underwent marginal resection, 4 had wide local excision and 3 patients had only biopsy. Resection margin was positive in 15 (75%) patients. All patients received radiation therapy. The median prescribed dose was 60 Gy. Five patients received less than 54 Gy. Results: The median follow-up time was 77.5 months (28-283 months). Nine patients developed local recurrence after RT. Seven local failures (78%) were in field. Time to local recurrence ranged from 3-165 months (median 33 months). The 2-5 year local control (LC) rates were 80% and 69%, respectively. On univariate analysis, the 5 year local control rate was significantly better in the patients treated with ≥54 Gy than in patients who received

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) or hyperthermic intrapleural chemotherapy (HIC) has been established as the new treatment modality for selected patients with peritoneal and pleural malignancies. The purpose of the study was to compare the development of acute kidney injury (AKI) in patients who received intravenous cisplatin alone, HIPEC and underwent surgery.This retrospective study included 104 patients who underwent different therapeutic procedures including systemic cisplatin, surgery and HIPEC or HIC using cisplatin for the treatment of peritoneal carcinomatosis from a variety of primary tumors at Koc University Hospital and American Hospital between January 2015 to December 2017.AKI developed in 18 (17.3%) patients. Baseline creatinine was significantly increased in 3 groups after therapies. The development of AKI was highest in patients treated with HIPEC compared to patients treated with intravenous cisplatin and patients who underwent surgery. AKI developed 31.2% in the HIPEC group (10 of 32 patients), 11.7% in the surgery group (4 of 34 patients) and 10.5% in intravenous cisplatin group (4 of 38 patients), respectively (p 0.04).HIPEC may not be so safe with regard to kidney function. Every attempt should be taken to decrease kidney damage during this procedure.

Objective: To analyze the extent of visceral pleural invasion (VPI) and its effect on survival along with its place in determining the T descriptor in TNM staging in our patients. Methods: A total of 233 patients underwent lung resection. The data were retrospectively analyzed in terms of sex, age, histopathologic type, stage of the tumor, extent of VPI, and survival. Patients who had neoadjuvant chemotherapy or chemoradiotherapy, distant metastasis, parietal pleural invasion, and operative mortality were excluded. Results: The median follow-up was 59 months (range 4–126). The extent of VPI was PL0 in 119 (65.7%) patients, PL1 in 47 (26%) patients, and PL2 in 15 (8%) patients. The median survival rates were 65 (range 43–96) months for PL0, 54 (range 37–72) months for PL1, and 39 (range 12–69) months for PL2. The 5-year overall survival rates were 74.7% for PL0, 77.8% for PL1, and 53.3% for PL2. There were statistically significant differences in overall survival among PL0, PL1, and PL2 ( p = 0.03). In subgroup analysis, the difference was insignificant in PL0 vs PL1 ( p = 0.81), but significant in PL0 vs PL2 ( p = 0.02) and PL1 vs PL2 ( p = 0.04) groups. Conclusions: This study emphasizes that the presence of VPI is related with poor prognosis independent of lymph node positivity, histologic subtypes, and tumor size. As the study shows, PL0 and PL1 have similar survival rates and these two groups may be considered as VPI (−) patients whereas PL2 disease affects survival outcomes.

Background: The phosphatidylinositol 3’-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. Materials and Methods: Fifty-four HER2positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient’s breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc). This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid) which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC) who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3rd, 6th, 9th, and 12th months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.

The gold standard of muscle-invasive bladder cancer is radical cystectomy. Before surgery three cycles of neoadjuvant chemotherapy can improve the overall survival and decrease the risk of recurrence. For operated high-risk without neoadjuvant therapy patients, adjuvant chemotherapy can be a good option. The primary treatment of metastatic bladder cancer is cisplatin-based chemotherapy. However, even though it is considered sensitive to chemotherapy, the average survival is 15 months and even less if there is an organ metastasis. For these patients 5-year survival rate is 5–20%. Several studies have shown different mutations in muscle-invasive bladder cancer. These mutations are being studied as a targeted therapy option for cases where chemotherapy is not sufficient. Although there is not a specifically approved treatment model for metastatic bladder cancer, targeted therapy is becoming a significant choice. According to the mutation analysis of the Cancer Genome Atlas (TCGA) project, there are three major pathway abnormalities in metastatic bladder cancer: regulation of cell cycle, RTK/RAS/PIK3, and chromatin abnormalities. The studies about the treatment of bladder cancers with cell cycle regulators, mTOR inhibitors, and EGFR inhibitors will be highly important in the future. Immunotherapy with the checkpoint inhibitors (an anti-PD1 therapy with atezolizumab, durvalumab) improves survival.

Objective: To evaluate the long term results among patients with soft tissue sarcoma of the thoracic wall. Materials and Methods: Twenty-six patients who were treated with pre-or postoperative radiotherapy between December 1980-December 2007, with a diagnosis of soft tissue sarcoma of the thoracic wall were retrospectively evaluated. Results: The median age was 44 years (14-85 years) and 15 of them were male. A total of 50% of patients were grade 3. The most common histologic type of tumor was undifferentiated pleomorphic sarcoma (26.9%). Tumor size varied between 2-25 cm (median 6.5 cm). Seventeen of the cases had marginal and 9 had wide local resection. Four cases received preoperative radiotherapy and 22 postoperative radiotherapy. Six of the patients with large and high grade tumors received chemotherapy. Median follow-up time was 82 months (9-309 months). Local recurrence and metastasis was detected in 34.6% and 42.3% of patients, respectively. Fiveyear local control (LC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) were 62%, 38%, 69%, and 76% respectively. On univariate analysis, the patients with positive surgical margins had a markedly lower 5-year LC rate than patients with negative surgical margin, but the difference was not significant (43% vs 78%, p=0.1). Five-year DFS (66% vs 17%) and DSS (92% vs 60%) rates were significantly worse for the patients who had high grade tumors (p=0.01, p=0.008 respectively). Conclusions: Tumor grade and surgical margin are essential parameters for determining the prognosis of thoracic wall soft tissue sarcoma both in our series and the literature.

There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors.From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics.The median age was 21 years (range, 13-50). Most patients (74%) were17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients17 years of age, tumor size8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis.We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

Background: To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Materials and Methods: Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses. Results: Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7%, 47%, 69.8%, and 80%, 60%, 60% in the chemoradiotherapy and radiotherapy groups, respectively. On univariate analysis, patients who were treated with hypofractionation experienced significantly superior LC, DFS and CSS rates with similar rates of late toxicity when compared with patients who were treated with conventional fractionation and statistical significance was retained on multivariate analysis. Conclusions: Treatment results are consistent with the literature. As neoadjuvant chemoradiotherapy provides effective LC and CSS with acceptable morbidity, it should be preferred for patients with large and borderline resectable STS.

We investigated predictive values of BRAF, PI3K and PTEN in cetuximab responses in KRAS wild-type (+) chemotherapy refractory, metastatic colorectal cancer (CRC) patients. Primary tumour tissues of 41 KRAS wild-type mCRC patients receiving cetuximab-based chemotherapy were investigated for PI3K, PTEN, KRAS and BRAF mutations. Progression-free survival (PFS) and overall survival (OS) periods were calculated with Kaplan-Meier method and the Cox proportional hazards model was used. PTEN and PI3K expressions were 63 and 42 %, respectively. BRAF mutation was observed as 9.8 % among patients. Tumours with BRAF mutation had statistically lower response rates (RR) for cetuximab-based treatment than tumours with BRAF wild type (0 vs. 58 %, p = 0.02). PTEN expressing tumours had statistically higher RR for cetuximab-based treatment than tumours with PTEN loss (42 vs. 12 %, p = 0.04). PI3K expression had worse significant effect on cetuximab RR than PI3K non-expressed tumours (15 vs. 44 %, p = 0.023). Median PFS was significantly longer in patients with PTEN expression (14 months) than in patients with PTEN loss (5 months) (HR, 0.4; p = 0.028). Median PFS was significantly longer in patients with PI3K non-expression (15.2 months) than in patients with PI3K expression (4.1 months) (HR, 0.31; p = 0.001). Significant difference in PFS and OS between patients with BRAF mutated and BRAF wild-type tumours was not detected. However, patients with PTEN expression had significantly longer OS (15.1 months) than patients with PTEN loss tumour (9.9 months) (HR, 0.34; p = 0.008). Patients without PI3K expression had significantly longer OS (18.2 months) than patients with PI3K expression (10.1 months) (HR, 0.27; p = 0.001). Multivariate analyses revealed that PTEN expression (HR, 0.48; p = 0.02) and absence of PI3K expression (HR, 0.2; p = 0.001) were independent prognostic factors for increased PFS. Similarly, PTEN overexpression (HR, 0.62; p = 0.03) and absence of PI3K expression (HR, 0.27; p = 0.005) were independent prognostic factors for increased OS. In PTEN loss, PI3K expression may be used as biomarkers to further select KRAS wild-type patients undergoing anti-epidermal growth factor receptor treatment.

Background: Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal system. The most common primary site of GIST is the stomach. The treatment is primarily surgery, and the standard medical therapy is imatinib. Long-term survival can be obtained with good follow-up and treatment. Materials and Methods: In this study, data entry was performed using a web-based patient registry system for patients who were referred to 3 centers and retrospectively were diagnosed with GIST. Results: The study cohort consisted of 249 patients, including 160 men (64.3%) and 89 women (35.7%). The mean age was 59 years (range 21–90 years). Initially, 69.9% of the patients had local disease, while 30.1% had metastatic disease. The tumor was located in the stomach in 45.6% of patients. According to the Fletcher risk classification, the very low risk group included 8 subjects (3.2%), the low risk group included 40 subjects (16.1%), the moderate risk group included 56 subjects (22.5%), and the high risk group included 117 subjects (47%); the unspecified group included 28 subjects (11.5%). Conclusion: These data are important for revealing the clinicopathologic characteristics and survival data of patients with GIST, who are treated and followed up in Turkey.

Gastrointestinal stromal tumors (GISTs) are common tumors of the gastrointestinal tract. Their most frequent location is the stomach. Although the clinical and pathological characteristics of the disease are well-known, the clinical and pathological characteristics and the response to treatment are not clear in elderly patients. The purpose of this study was to evaluate the characteristics of GISTs in elderly patients with an aim at improving the therapeutic methodology and survival.In this study, clinicopathological characteristics, evaluation of treatments administered and survival analyses were performed in patients aged 65 years or above, whose data were registered via a web-based patient records system following admission to three centers.A total of 85 patients aged 65 years or above were included in the study. According to the risk classification, 24 (28.2%) were in the low risk group, 20 (23.5%) in the moderate risk group, and 41 (48.3%) in high risk group, while no patient was in the very low risk group. At baseline, 70% of the patients had localized disease and 30% metastatic disease. The tumor was located in the stomach in the majority of the patients (45.6%). The tumor size most commonly seen was 5-10 cm (N=31; 36.4%). Of the 85 patients 23 (27%) were treated with imatinib 400 mg/d. Eight patients (9.4%) with metastatic disease switched from imatinib to sunitinib. At a median follow-up of 76 months (range 1-323), median overall survival (OS) was 72 months, without significant difference between elderly and younger patients.Clinicopathological characteristics and their prognostic impact on the disease course of elderly GIST patients should be elucidated in depth. Since age didn't show prognostic importance, other parameters should be used as prognostic/predictive factors in the tyrosine kinase inhibitors era in order to obtain improved therapeutic results.

The standard of care for early stage non-small cell lung cancer is surgery. However, even though it is at an early stage, more than half of the patients present with local recurrences or systemic metastases within the first 2 years. In order to prevent such possibilities, adjuvant treatment is suggested. Doublet regimens that include platinum are the most commonly used ones. Even though the benefit of such treatment for stage IA is not proven, it is highly recommended for stages IB, II, and resected III. If the treatment is performed prior to surgery, it is called neoadjuvant chemotherapy. Such treatment is mostly prescribed to patients who have local progressive disease. For stages IIIA and IIIB, neoadjuvant treatment with or without radiotherapy or induction chemotherapy is performed. NSCLC patients are mostly diagnosed at later stages (stage IV), and in such cases, platinum-based systemic chemotherapy is recommended. However, in the light of the latest researches, targeted therapies depending on the molecular specialties are introduced as the first line of treatment. For patients with EGFR-mutated nonsquamous adenocarcinoma subtype, erlotinib, gefitinib, and afatinib and for ALK-mutated patients, crizotinib can be prescribed. The standard of care as the second-line treatment is docetaxel, pemetrexed, and erlotinib. For the nonsquamous subtypes, it is shown that anti-VEGFR treatments increase the response rates, prolonging the overall survival. Recently, checkpoint inhibitors (PD-1 and PDL-1 inhibitors) have been introduced, showing an increase in the overall survival.

We describe here a patient with a metastatic malignant melanoma displaying crescentic lesions in the glomeruli. A 64-year-old woman was referred to our hospital because of a sudden increase of serum creatinine. Clinical diagnosis suggested rapidly progressive glomerulonephritis. Renal biopsy revealed diffuse crescentic lesions containing metastatic melanoma cells. These cells were also seen in the glomerular capillary lumina and tubules, and a few scattered tumor cells were also present in the interstitium. Glomerular metastasis is a very rare entity. To the best of our knowledge, this patient is the first to be described in the English language literature showing intraglomerular metastasis of malignant melanoma as demonstrated by needle biopsy and is only the second patient with intraglomerular metastasis presenting with acute renal failure.

A 37-year-old woman presented to the Internal Medicine Clinic with complaints of abdominal pain and constipation which had begun 3 months earlier. A colonoscopy was performed, and wall thickening of the sigmoid colon was detected. A biopsy of the sigmoid colon revealed a poorly differentiated, mucin-producing adenocarcinoma with a signet-ring pattern. No distant metastasis was detected. The patient was treated with chemotherapy consisting of 5-fluorouracil, leucovorin, and oxaliplatin. One and a half years later, a painless mass, which was not fixed to the skin, measuring 1 cm in diameter, was found in the lower outer quadrant of the left breast. A core biopsy of the mass was performed, and a histopathological report confirmed metastasis to the breast from mucinous adenocarcinoma of an intestinal primary.

Objective. The aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas. Study Design. Retrospective record review. Setting. Istanbul University, Cerrahpasa Medical Faculty, medical oncology outpatient clinic. Subjects and Methods. There were 3 stage A tumors, 5 stage B and 11 stage C according to the Kadish staging system. There were 5 grade I/II and 12 grade III/IV according to the Hyams' histopathologic system. Involvement to orbita was detected in eight patients at the time of diagnosis. Results. The median follow-up period was 23.7 months. The 5-year survival rate for the whole group was 26%. The stage A/B groups exhibited a better survival rate than the C group with 2-year survival rates being 25 versus 71% respectively (P=.008). The grade I/II groups exhibited a better survival rate than the grade III/IV groups with 2-year survival rates being 50 versus 16% respectively (P=.001). The group who had orbital involvement exhibited a poor survival rate than the group of patients who had no involvement of the orbital. Conclusion. In our study, tumor stage, histopathologic grading, involvement of the orbita, brain and bone marow metastases were the statistically significant prognostic factors.

We report a 53-year-old male patient who underwent paravertebral mass excision at the D10–11–12 vertebral levels in 2007. The histopathological evaluation of the mass showed the presence of neuroblastoma. The patient was diagnosed with stage IV neuroblastoma. He received 6 courses of chemotherapy and exhibited a stable course until March 2010. When he was reevaluated in March 2010, progression in the metastatic lesion as well as local recurrence was detected. The patient, who was restarted on chemotherapy, developed progressive weakness and loss of sensation of the lower extremity. The neurosurgical investigation revealed an irreversible loss in motor functions. The patient is currently on symptomatic treatment.

Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the PNET/Ewing's sarcoma family. We hereby report a case of PNET of the ovary, which was detected at the second trimester of pregnancy. Chemotherapy was administered and a healthy baby was delivered by cesarean section. After the pregnancy, the mother was found to have metastatic disease. Chemotherapy was continued, but she died due to progressive disease 13 months after the initial diagnosis. In this case report, we discuss chemotherapy options during pregnancy and the importance of multidisciplinary approach to unusual presentations of rare tumors

WOS: 000385182500005 PubMed ID: 26781472 Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.

The addition of the immunotherapeutic agent rituximab (R) to chemotherapy improved the response rates in diffuse large B cell lymphoma (DLBCL) [1]. However, despite major progress in the treatment,...

The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage IIIII CRC patients who were treated with adjuvant therapy.Data of patients with high risk stage IIall stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test.PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect.This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

PubMedID: 24338610 Background: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey. Methods: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab. Results: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370–1.231; p = 0.200). Cardiac toxicity defined as a ?15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050). Conclusion: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials. © 2013, The Japanese Breast Cancer Society.