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WOS: 000454014501235 Background: Increasing evidence leads to a ratiocination that genetic heterogeneity of the lung adenocarcinoma patients with sensitive EGFR mutations may impact clinical responses and outcomes to EGFR-TKIs. Method: We performed targeted NGS with a gene panel covering 416 cancer-related genes to profile genetic characteristics of 69 lung adenocarcinoma patients with activating EGFR mutations and assessed the contribution of targeted NGS to exploration of genetic heterogeneity of such cohort. Result: We detected total 200 actionable genetic alterations (mean 2.9 variations per patient, range: 1-7 variations) in tumor DNA and 140 actionable genetic alterations (mean 2.0 variations per patient, range: 0-5 variations) in matched plasma ctDNA, respectively. The concurrent genes with the highest mutation rate were TP53 (observed in 72.5% patients), other uncommon EGFR mutations (observed in 21.7% patients), EGFR amplification (observed in 20.3% patients), RB1 (observed in 10.1% patients), PIK3CA (observed in 7.2% patients), and MYC (observed in 5.8% patients). NGS provides EGFR mutation detection in plasma with a test sensitivity of 88.2% and specificity of 100.0%.

Yumuk, Perran Fulden/0000-0001-8650-299X; Cicin, Irfan/0000-0002-7584-3868; Arslan, Cagatay/0000-0002-3783-7432; beypinar, i/0000-0002-0853-4096; Turna, Hande/0000-0003-0558-9371; WOS:000492162203082 [No abstract available]

PurposeIn this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients.MethodsThis study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers.ResultsMedian age was 51 (22-82). Median PFS was 28.5months, while median OS was 40.3months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8m vs. 28.5m; p=0.002) and OS (26.7m vs. 40.3m; p=0.009). Patients older than 65years of age (n: 42, 13.2%) had significantly lower OS results (19.8m vs. 40.3m; p=0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure.ConclusionsOur RLP trial included only visceral metastatic, trastuzumab-naive BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date. C1 [Esin, Ece; Oksuzoglu, B.; Erdur, E.; Demirci, U.] Univ Hlth Sci, Dept Med Oncol, Dr AY Ankara Oncol Educ & Res Hosp, Ankara, Turkey. [Bilici, A.] Medipol Univ, Int Hlth Ctr, Dept Med Oncol, Istanbul, Turkey. [Cicin, I.; Kostek, O.] Trakya Univ, Dept Med Oncol, Edirne, Turkey. [Kaplan, M. A.] Dicle Univ, Dept Med Oncol, Fac Med, Diyarbakir, Turkey. [Aksoy, S.; Aktas, B. Y.] Hacettepe Univ, Dept Med Oncol, Fac Med, Ankara, Turkey. [Ozdemir, O.; Alacacioglu, A.] Izmir KC Univ, Ataturk Educ & Res Hosp, Dept Med Oncol, Izmir, Turkey. [Cabuk, D.] Kocaeli Univ, Fac Med, Dept Med Oncol, Izmit, Turkey. [Sumbul, A. T.] Baskent Univ, Dept Med Oncol, Adana Hosp, Adana, Turkey. [Sakin, A.] Istanbul Okmeydani Educ & Res Hosp, Dept Med Oncol, Istanbul, Turkey. [Paydas, S.; Yetisir, E.] Cukurova Univ, Dept Med Oncol, Fac Med, Adana, Turkey. [Er, O.; Basaran, G.] Acibadem MAA Univ, Acibadem Maslak Hosp, Dept Med Oncol, Istanbul, Turkey. [Korkmaz, T.; Oyan, B.] Acibadem MAA Univ, Acibadem Altunizade Hosp, Dept Med Oncol, Istanbul, Turkey. [Yildirim, N.] Dr Ersin Arslan Training & Res Hosp, Dept Med Oncol, Gaziantep, Turkey. [Sakalar, T.] Erciyes Univ, Dept Med Oncol, Fac Med, Kayseri, Turkey. [Demir, H.] Kayseri Educ & Res Hosp, Univ Hlth Sci, Dept Med Oncol, Kayseri, Turkey. [Artac, M.; Karaagac, M.] Necmettin Erbakan Univ, Meram Med Fac, Dept Med Oncol, Konya, Turkey. [Harputluoglu, H.; Bilen, E.] Inonu Univ, Dept Med Oncol, Turgut Ozal Med Ctr, Malatya, Turkey. [Degirmencioglu, S.] Pamukkale Univ, Dept Med Oncol, Fac Med, Denizli, Turkey. [Aliyev, A.] Bezmialem Univ, Dept Med Oncol, Fac Med, Istanbul, Turkey. [Cil, T.; Olgun, P.] Adana City Hosp, Univ Hlth Sci, Dept Med Oncol, Adana, Turkey. [Gumusay, O.] Gaziosmanpasa Univ, Dept Med Oncol, Fac Med, Tokat, Turkey. [Demir, A.] Univ Hlth Sci, Dept Med Oncol, Istanbul Okmeydani Educ & Res Hosp, Istanbul, Turkey. [Tanrikulu, E.; Yumuk, P. F.] Marmara Univ, Dept Med Oncol, Fac Med, Istanbul, Turkey. [Imamoglu, Inanc] Univ Hlth Sci, Ankara Diskapi Educ & Res Hosp, Dept Med Oncol, Ankara, Turkey. [Cetin, B.] RTE Univ, Dept Med Oncol, Fac Med, Rize, Turkey. [Haksoyler, V.] Univ Hlth Sci, Diyarbakir GY Educ & Res Hosp, Dept Med Oncol, Diyarbakir, Turkey. [Karadurmus, N.; Erturk, I.] Univ Hlth Sci, Gulhane Educ & Res Hosp, Dept Med Oncol, Ankara, Turkey. [Evrensel, T.; Yilmaz, H.] Uludag Univ, Dept Med Oncol, Fac Med, Bursa, Turkey. [Beypinar, I.] Afyon Kocatepe Univ, Dept Med Oncol, Fac Med, Afyon, Turkey. [Kocer, M.] Isparta SD Univ, Dept Med Oncol, Fac Med, Isparta, Turkey. [Pilanci, K. N.] Univ Hlth Sci, Dept Med Oncol, Haseki Educ & Res Hosp, Istanbul, Turkey. [Seker, M.; Urun, Y.] Ankara Bayindir Hosp, Dept Med Oncol, Ankara, Turkey. [Urun, Y.] Ankara Univ, Dept Med Oncol, Fac Med, Ankara, Turkey. [Yildirim, N.; Eren, T.] Univ Hlth Sci, Numune Educ & Res Hosp, Dept Med Oncol, Ankara, Turkey.

Purpose: In this study, we aimed to describe the real-life practice outcomes of pertuzumab–trastuzumab–taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. Methods: This study was conducted by Turkish Oncology Group and included 317 patients’ data from 36 centers. Results: Median age was 51 (22–82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5–40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. Conclusions: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab–trastuzumab–taxane therapy to date. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Purpose: Solid pseudopapillary neoplasm (SPN) is a rare, low-grade neoplasm with excellent prognosis. In this study, we evaluated clinicopathological characteristics of patients diagnosed with SPN retrospectively. Methods: This is a retrospective study intended to characterize patients with the diagnosis of SPN between 2005 and 2015. Clinicopathological features, recurrence rate, and overall survival of 28 patients were recorded. Malignant SPN criteria were defined as the presence of distant metastasis (developed at diagnosis or during follow up) or lymph node involvement. Results: The mean age at diagnosis was 42 (range: 17-41). Among patients, 82% (n = 23) were female and 17.9% (n = 5) were male. The mean size of tumor was 5.81 cm (range: 2-15). The mean follow up period was 55.6 months, 1-year survival was 96.5% and 5-year survival rate was 88%. A total of 25 patients were alive at the end of follow-up period and 3 of the patients became exitus due to disease. Two patients had a metastatic presentation in livers at the diagnosis and metastasis developed in 3 patients during follow-up (liver of 1 patient, peritoneum in 1 patient and liver and peritoneum in 1 patient). The reason of admission was headache in 68% patients. The type of operation was frequently subtotal pancreatectomy (n = 11, 39.3%) and distal pancreatectomy (n = 10, 35.7%). Tumors were located frequently in body and tail regions (n = 18, 64.3%) and the number of patients with malignant criteria was 6 (21.4%). Although the mean age of malignant patients was significantly higher than benign patients (P = 0.046), there was no significant difference between 2 groups in terms of gender, tumor size, capsule invasion, perineural invasion, vascular invasion, and margin status. Conclusion: SPN is a rarely seen tumor with low malignity potential. Surgical resection provides long-term survival rate even in local invasion or metastasis conditions. (C) 2018 Elsevier Inc. All rights reserved. C1 [Ercelep, Ozlem; Ozcelik, Melike] Dr Lutfi Kirdar Kartal Educ & Res Hosp, Dept Med Oncol, Istanbul, Turkey. [Ozdemir, Nuriye] Ankara Numune Training & Res Hosp, Dept Med Oncol, Ankara, Turkey. [Turan, Nedim] Gazi Univ, Dept Med Oncol, Fac Med, Ankara, Turkey. [Topcu, Turkan Ozturk] Karadeniz Tech Univ, Dept Med Oncol, Fac Med, Trabzon, Turkey. [Uysal, Mukremin] Afyon Kocatepe Univ, Dept Med Oncol, Fac Med, Afyon, Turkey. [Tanriverdi, Ozgur] Mugla Sitki Kocaman Univ, Dept Med Oncol, Fac Med, Mugla, Turkey. [Demirci, Umut] Ankara Yurtaslan Oncol Hosp, Dept Med Oncol, Ankara, Turkey. [Taskoylu, Burcu Yapar] Pamukkale Univ, Dept Med Oncol, Fac Med, Denizli, Turkey. [Urakci, Zuhat] Dicle Univ, Dept Med Oncol, Fac Med, Diyarbakir, Turkey. [Duran, Ayse Ocak] Kayseri Erciyes Univ, Dept Med Oncol, Fac Med, Kayseri, Turkey. [Aksoy, Asude] Malatya Inonu Univ, Dept Med Oncol, Fac Med, Malatya, Turkey. [Menekse, Serkan] Celal Bayar Univ, Dept Med Oncol, Fac Med, Manisa, Turkey. [Gumus, Mahmut] Bezmi Alem Vakif Univ, Dept Med Oncol, Fac Med, Istanbul, Turkey.

Background: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). Methods: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. Results: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. Conclusions: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

The vitrification of a liquid occurs when ice crystal formation is prevented in the cryogenic environment through ultrarapid cooling. In general, vitrification entails a large temperature difference between the liquid and its surrounding medium. In our droplet vitrification experiments, we observed that such vitrification events are accompanied by a Leidenfrost phenomenon, which impedes the heat transfer to cool the liquid, when the liquid droplet comes into direct contact with liquid nitrogen. This is distinct from the more generally observed Leidenfrost phenomenon that occurs when a liquid droplet is self-vaporized on a hot plate. In the case of rapid cooling, the phase transition from liquid to vitrified solid (i.e., vitrification) and the levitation of droplets on liquid nitrogen (i.e., Leidenfrost phenomenon) take place simultaneously. Here, we investigate these two simultaneous physical events by using a theoretical model containing three dimensionless parameters (i.e., Stefan, Biot, and Fourier numbers). We explain theoretically and observe experimentally a threshold droplet radius during the vitrification of a cryoprotectant droplet in the presence of the Leidenfrost effect.

There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.

The development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of < 6 months. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10-40 %. Our aim was to identify factors predicting development of BMs and survival. We performed a retrospective analysis of 470 melanoma patients between 2000 and 2012. The logistic regression analyses were used to identify the clinicopathological features of primary melanoma that are predictive of BMs development and survival after a diagnosis of brain metastases. There were 52 patients (11.1 %) who developed melanoma BMs during the study period. The analysis of post-BMs with Kaplan-Meier curves has resulted in a median survival rate of 4.1 months (range 2.9-5.1 months). On logistic regression analysis site of the primary tumor on the head and neck (p = 0.002), primary tumor thickness (Breslow > 4 mm) (p = 0.008), ulceration (p = 0.007), and pathologically N2 and N3 diseases (p = 0.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors. Our results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic a parts per thousand yenN2 disease were found to be significant predictors of BMs development.

To investigate the relationship of the apoptosis regulators X-linked inhibitor of apoptosis (XIAP) and ubiquitin specific protease 8 (USP8) with clinical parameters, survival and response to chemotherapy in patients with advanced stages of non-small cell lung cancer (NSCLC).The study included 34 NSCLC patients (28 females, 6 males) and 44 healthy individuals (17 males, 27 females) as a control group. XIAP and USP8 levels were determined by ELISA.The median serum XIAP level of the patients and the control group showed no significant difference. USP8 level was higher in patients than in controls (p0.0001). In univariate analysis, there was no significant relationship between XIAP and USP8 serum levels and age, sex, performance status, weight loss, stage of disease, histopatological type and response to chemotherapy. Response to chemotherapy did not differ between the high and low XIAP and USP8 groups . There was no significant difference in progression- free survival (PFS) (p=0.432 and p=0.50, respectively) and overall survival (OS) (p=0.989 and p=0.90, respectively) between the low and high XIAP and USP8 groups.No relationship was found in serum XIAP and USP8 levels with clinical parameters, response to chemotherapy, PFS and OS in patients with advanced stages of NSCLC.

Purpose: The extra benefit of adding chemotherapy to effective endocrine therapy (ET) has not been clearly or consistently identified in patients older than 70 years with estrogen receptor (ER) positive and node positive breast cancer. The aim of this study was to evaluate the efficacy of adjuvant ET vs chemotherapy plus endocrine therapies (Chemo/ET) in such patients. Methods: In this retrospective multicenter study 191 patients >= 70 years with operated hormone receptor positive breast cancer, who were administered adjuvant ET or Chemo/ET were assessed. Results: The median patient follow-up time was 29.0 months (range 1-252). Therefore disease free survival (DFS) and overall survival (OS) analysis was limited, due to the rather short median follow-up, and only 30-month cumulative percentages are reported herein. The 30-month DFS rates were 50.0% in the ET arm and 49.0% in the Chemo/ET arm (p=0.79). The 30-month OS rates were 86% in the ET arm and 96.0% in the Chemo/ET arm (p=0.08). Cox proportional hazard model showed that only surgery was independent prognostic factor for survival (p=0.047), while tumor size showed a strong trend for statistical significance (p=0.051). Conclusion: The addition of chemotherapy to endocrine therapy in older patients has no significant impact on DFS and OS.

Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. The present study retrospectively evaluated the data pertinent to 282 patients who were examined and treated in 11 different medical oncology centers in Turkey. There were 161 males (57.1 %) and 121 females (42.9 %), with a mean age of 56.38 ± 12.07 years. Surgery was used in 74 patients, 21 patients (28.4 %) received only chemotherapy and 28 patients (37.8 %) received chemoradiotherapy after surgery. The median survival in patients who were administered adjuvant therapy after surgery was 24 months, while the median survival in patients who had only surgery was 6 months (p = 0.029). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. Median survival, 1- and 2-year survival rates in patients who received platinum analogues and pemetrexed or gemcitabine combinations were found statistically similar (p = 0.15). The median survival for all patients with MPM in our study was 18 months. The main factors influencing the overall survival were stage of the disease (p = 0.020), performance status (p < 0.001), asbestos exposure (p = 0.030) and mesothelioma histological subtypes (p < 0.001). Results of our study suggest that multi-modality treatment regimens consisting of surgery, radiotherapy and chemotherapy prolong overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar. © 2012 Springer Science+Business Media, LLC.

Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. The present study retrospectively evaluated the data pertinent to 282 patients who were examined and treated in 11 different medical oncology centers in Turkey. There were 161 males (57.1 %) and 121 females (42.9 %), with a mean age of 56.38 +/- A 12.07 years. Surgery was used in 74 patients, 21 patients (28.4 %) received only chemotherapy and 28 patients (37.8 %) received chemoradiotherapy after surgery. The median survival in patients who were administered adjuvant therapy after surgery was 24 months, while the median survival in patients who had only surgery was 6 months (p = 0.029). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. Median survival, 1- and 2-year survival rates in patients who received platinum analogues and pemetrexed or gemcitabine combinations were found statistically similar (p = 0.15). The median survival for all patients with MPM in our study was 18 months. The main factors influencing the overall survival were stage of the disease (p = 0.020), performance status (p < 0.001), asbestos exposure (p = 0.030) and mesothelioma histological subtypes (p < 0.001). Results of our study suggest that multi-modality treatment regimens consisting of surgery, radiotherapy and chemotherapy prolong overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.

To retrospectively evaluate the efficacy and tolerability of mitomycin-C (MMC) in combination with fluoropyrimidines as salvage 3rd -or 4th-line therapy in metastatic colorectal cancer (MCRC) patients.All patients in this study had previously failed oxaliplatin and irinotecan-based chemotherapy. Patients were treated with MMC (6 mg/m(2) intravenously/i.v.) on day 1 in combination with either oral UFT (500 mg/m(2)) and oral leucovorin (LV) (30 mg) on days 1-14 every 3 weeks (group A) or infusional 5-fluorouracil (5-FU) by deGramont regimen with i.v. LV (200 mg/m(2)) on days 1 and 2, every 2 weeks (group B).Thirty-nine MCRC patients were analyzed. Twenty-two of them were in group A and 17 in group B. Thirty-three were evaluable for clinical efficacy. The clinical benefit in the intent-to-treat (ITT) population was 30.8%. Median progression free survival (PFS) was 6 months (95% confidence interval/ CI 4-8) and median overall survival (OS) 9 months (95% CI 6.5-11.5). Median PFS was 3 months (95% CI 2.4-3.6) in group A and 7 months (95% CI 5.1-8.9) in group B (p=0.009). Median OS was 7 months (95% CI 4.3-9.7) in group A and 12 months (95% CI 5.4-18.6) in group B (p=0.422). The combination of MMC and fluoropyrimidines was generally well tolerated. The most common severe toxicities were nausea and vomiting, neutropenia, hepatotoxicity and diarrhea.MMC in combination with fluoropyrimidines is safe and active in heavily-pretreated MCRC patients. This combination remains a viable option in these patients. However, better therapies are urgently needed.