Causes of liver test abnormalities in newly diagnosed cancer patients and the investigation of etiological factors.

OBJECTIVES: In this study, we aimed to investigate the causes of liver test abnormalities in newly diagnosed patients naive to anti-tumoral therapy. METHOD: This study included a total of 490 patients with ALT levels > 5X ULN on liver function tests at the initial presentation to our clinic. Data from 247 (50.4%) patients diagnosed with cancer (cohort A) and 243 (49.6%) patients without cancer (cohort B) were compared with regard to the etiology of liver test abnormalities and the risk factors. RESULTS: The most common etiological factor in cohort A was presence of liver metastasis (31.2%, n = 77). In the comparison of the two groups with regard to etiological factors; the rates of liver metastasis [31.2% vs 0%, (p < 0.001)], drug-induced liver toxicity [30/4% vs 19.8%, (p = 0.007)], pancreaticobiliary pathology [21.5% vs 14%, (p = 0.03)] and chronic viral hepatitis [14.2% vs 7.4%, (p = 0.02)] were higher in the cohort A. The rate of NAFLD was higher in the cohort B [6.9% vs 42.2% (p < 0.001). CONCLUSION: In our study, the most common cause of liver test abnormalities was the presence of liver metastasis in cohort A and NAFLD in cohort B.

Comparison of Two Chemotherapy Regimens After First-Line Treatment for HER2-Negative Metastatic Gastric Cancer.

AIM: Metastatic stage gastric cancer is a disease with a poor prognosis and the likelihood of achieving a cure in these patients is low. Treatment response to subsequent-line treatments is poor. We aimed to investigate the effectiveness of the folinic acid, fluorouracil and irinotecan (FOLFIRI) and paclitaxel+carboplatin regimens, which are used in subsequent lines of therapy in advanced-stage gastric cancer. MATERIALS AND METHODS: This study included 40 patients who have metastatic stage gastric cancer and received FOLFIRI or paclitaxel+carboplatin therapy in subsequent lines of therapy between 2017 and 2022. The data of the patients were analyzed retrospectively. RESULTS: At diagnosis median age was 51 (23-88) years. The tumor was localized in the gastroesophageal junction in eight (20%) patients and in other gastric locations in 32 (80%) patients. At diagnosis, 75% (n=30) of the patients presented with the disease in the metastatic stage, while 25% (n=10) presented with stage II-III disease. Regarding the treatments received in the second and further lines of therapy, 18 (45%) patients received paclitaxel+carboplatin and 22 (55%) patients received a FOLFIRI regimen. Of these treatments, 67.5% (n=27) were given as the second line and 32.5% (n=13) were given as third-line therapy. The objective response rate (ORR) was 45.5% in the FOLFIRI arm compared to 16.7% in the paclitaxel+carboplatin arm (p=0.05). Both treatment arms had a median progression-free survival (PFS) of three months (p=0.82). The median overall survival (OS) time was seven months in the FOLFIRI arm compared to eight months in the paclitaxel+carboplatin arm (p=0.71). Side effects were similar between both treatment arms. CONCLUSION: This study determined that FOLFIRI and paclitaxel+carboplatin treatments have similar OS, PFS, and side effect profiles in subsequent line treatment of gastric cancer. The FOLFIRI treatment regimen yielded a higher ORR.

Prognostic factors and the prognostic role of inflammation indices in malignant pleural mesothelioma.

Background: In this study, we aimed to investigate the prognostic factors of malignant pleural mesothelioma and the prognostic value of inflammation indices in malignant pleural mesothelioma. Methods: Between January 2002 and December 2019, a total of 132 patients (74 males, 58 females; mean age: 55 years; range, 31 to 79 years) diagnosed with malignant pleural mesothelioma were retrospectively analyzed. Patients" demographic data and laboratory results were recorded. The prognostic value of the following five inflammation indices was evaluated: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, C-reactive protein/albumin ratio, and prognostic nutritional index. Results: Of all patients, 81% (n=107) were aged 65 or older and 61.4% (n=81) had an epithelioid histology. Of 12 variables examined in the multivariate analysis for their relationship with survival, age ≥65 years, non-epithelioid subtype, and prognostic nutritional index <40 were found to be poor prognostic factors. Based on the score constructed from these factors, the good prognostic group (score 0-1) had a median overall survival of 21 months and a one-year survival rate of 77.9%, while the poor prognostic group (score 2-3) had a median overall survival of nine months and a one-year survival rate of 29.7%. Conclusion: Our study results indicate that age ≥65 years, prognostic nutritional index <40, and non-epithelioid histological subtype are poor prognostic factors of malignant pleural mesothelioma.

Neoadjuvant Therapy and Factors Influencing Survival in Locally Advanced Non-Small Cell Lung Cancer.

AIM: We aimed to investigate the effectiveness of neoadjuvant therapy (NAT) and clinicopathological characteristics in locally advanced non-small cell lung cancer (NSCLC) (IIIA-IIIB), as well as the influence of the post-NAT treatment modalities on survival. MATERIALS AND METHODS: This study included patients who presented to the Dicle University Medical Oncology Clinic and received NAT for a diagnosis of locally advanced NSCLC between 2004 and 2020. Clinicopathological and radiological data of the 57 patients whose data could be retrieved from the hospital archive system were retrospectively reviewed. Patients' overall survival (OS) and failure-free survival (FFS) times and the factors influencing these times were evaluated. RESULTS: This study included a total of 57 patients consisting of five (8.8%) females and 52 (91.2%) males. The median patient age at diagnosis was 58 (30-75) years. All patients had received four courses of chemotherapy during the neoadjuvant period. When the factors influencing OS were evaluated, the post-NAT modality was found to have a statistically significant effect on survival. FFS times were 12, 13, and 16 months in the chemotherapy, chemoradiotherapy, and surgery arms, respectively (log-rank p=0.035). FFS was longer in those who underwent surgery (Hazard ratio (HR): 0.33, 95 % CI: 0.14-0.77, (p=0.01)). OS times were 20, 21, and 55 months in the chemotherapy, chemoradiotherapy, and surgery arms, respectively (log-rank p=0.05). OS was longer in the arm undergoing surgery compared to the other arms (HR: 0.36, 95% CI: 0.14-0.87, (p=0.02)). Five-year survival rates for the chemotherapy, chemoradiotherapy, and surgery arms were 14.3%, 21.4%, and 40%, respectively. CONCLUSIONS: This study shows that achieving an operable status is the most important indicator of survival and that patients undergoing surgery have a marked advantage in OS and FFS compared with patients receiving chemoradiotherapy or palliative chemotherapy.

18 F-FDG PET/CT parameters for prediction of response to neoadjuvant therapy and prognosis in rectal cancer.

OBJECTIVE: This study aims to investigate the role of F-18 fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) parameters in the prediction of treatment response and the prognosis in locally advanced rectal cancer. METHODS: We investigated the relationship of 18F-FDG PET/CT parameters [rectal metabolic tumor volume (MTV), rectal total lesion glycolysis (TLG), rectal standard uptake value (SUV) max, rectal highest peak SUV, lymph node MTV, lymph node TLG, lymph node highest peak SUV] with the pathological response and disease-free survival (DFS) in 60 patients who received neoadjuvant therapy for a diagnosis of locally advanced rectal cancer. Patients with a total score of 0 were assigned to the low-risk group, patients with a score of 1 were assigned to the intermediate-risk group and patients with a score of 2 were assigned to the high-risk group. RESULTS: The multivariate analysis revealed that, from baseline PET CT parameters, lymph node highest peak SUV strongly predicted the pathological response at a cutoff value of 2.23. DFS was predicted by the lymph node highest peak SUV at a cutoff value of 3.13 and by the MTV value at a cutoff value of 27 cm 3 . The risk scoring performed with regard to rectal MTV and lymph node highest peak SUV values determined a median DFS of 19 months in patients with a risk score of 2, whereas the median DFS was not reached in patients with risk scores of 0 and 1 (P < 0.001). CONCLUSION: This study determined that rectal MTV and lymph node highest peak SUV predicted the response to neoadjuvant therapy and DFS.

Factors influencing HER2 discordance in nonmetastatic breast cancer and the role of neoadjuvant therapy.

Objective: The rates of and the factors influencing HER2 discordance in patients receiving neoadjuvant therapy for breast cancer are investigated. Methods: This study retrospectively examines the rates of HER2 and hormone receptor discordance between the biopsy and postoperative resection specimens of 400 female early-stage breast cancer patients. Results: 133 (33.3%) patients had received neoadjuvant therapy. The rate of HER2 discordance between biopsy and resection specimens was 1.7% in the control group and 5.3% in the neoadjuvant therapy group (p = 0.018). The rate of HER2 discordance was higher in younger patients and in patients with T1 tumors in the neoadjuvant therapy group. Conclusion: Neoadjuvant therapy, age <40 years and smaller tumor size were independent risk factors for HER2 discordance.

HER2 is an important and targetable molecule in breast cancer. In the early stages of breast cancer, a treatment modality called neoadjuvant therapy, which now includes anti-HER2 therapies, is administered before surgery in order to achieve disease regression and make the patient suitable for a more minor operation. In breast cancer, HER2 status may be positive in the initial biopsy specimen and negative in the surgical specimen. HER2 status plays an important role in treatment decisions. In this study, we investigated the factors causing HER2 status to change in early-stage breast cancer. This study has a retrospective design and includes 400 female patients with early-stage breast cancer. The results of the study identified the factors causing HER2 status to change to negative as receipt of neoadjuvant therapy, small tumor size and younger age.

Evaluation of Factors Predicting the Effectiveness of Regorafenib in the Treatment of Metastatic Colorectal Cancer.

OBJECTIVE: Regorafenib is a multikinase inhibitor, the effectiveness of which was demonstrated in metastatic colorectal cancer. This study aimed to investigate the factors that could predict the effectiveness of regorafenib. MATERIALS AND METHODS: This study retrospectively reviewed the clinical characteristics, tumor characteristics, and previous therapies in 62 patients who presented to our center between 2016 and 2020 and used regorafenib for metastatic colorectal cancer. The effects of the investigated variables on the response obtained with regorafenib use were evaluated. RESULTS: This study included a total of 62 patients diagnosed with metastatic colorectal cancer, of whom 30 (48.4%) were males and 32 (51.6%) were females. Patients' median age at diagnosis was 49 years (18- 68). Regorafenib therapy yielded a disease control rate of 64% [complete response=0, partial response= 14 (28%), and stable disease=18 (36%)]. Objective response was obtained in 28% of patients [complete response=0 and partial response=14 (28%)]. Progression-free survival was 4 months. The evaluation of the effects of patients' age, sex, performance status, previous treatments, metastatic sites, and RAS mutation status on the disease control rate and progression-free survival did not determine any positive or negative effects on progression-free survival. However, left-sided tumors had a positive effect on disease control rate (69.8% vs. 28.6%, P=.029). and previous use of cetuximab had a negative effect on disease control rate [76.5% vs. 37.5% (P=.007)]. CONCLUSION: In our study, tumor localization and previous cetuximab use were found to be correlated with the disease control rate in patients on regorafenib. However, the need for novel biomarkers that will predict the effectiveness of regorafenib in metastatic colorectal cancer treatment persists.

A Low Body Fat Mass Ratio Predicts Poor Prognosis in Patients with Advanced Non-Small Cell Lung Cancer.

PURPOSE: The aim of this study was to investigate the effect of the body fat mass ratio on survival and prognosis in advanced non-small-cell lung cancer patients. METHODS: The study includes 200 patients who were diagnosed with advanced non-small-cell lung cancer between 2014 and 2018 and whose body fat mass percentage and body mass index (BMI) were determined using the Tanita Body Composition Analyzer during admission. RESULTS: All patients had advanced incurable non-small-cell lung cancer (30% had locally advanced disease, 70% were stage IV). In the univariate and multivariate analyses, age, gender, histopathological type, smoking history, comorbidities, weight loss in the last six months and body mass index had no statistically significant effect on survival (p > 0.05). However, the performance status (p = 0.008), metastatic status (p = 0.003) and body fat mass ratio (p = 0.01) were found to have a significant effect on overall survival (OS): the median OS was 16.4 mo, in patients with the BFM ratio ≤ 22% and 29.2 mo, in those with > 22% (p = 0.01). CONCLUSION: In this study, it was found that the body fat mass ratio was an important prognostic factor in patients with advanced non-small-cell lung cancer.

The effect of exercise on disease-free survival and overall survival in patients with breast cancer.

BACKGROUND: Positive effects of exercise in cancer patients have been reported. AIM: To investigate whether intensity, duration, and timing of exercise affect disease relapse and mortality risk in patients with breast cancer (BC). METHODS: Patients with local or locally advanced stages of BC between January 2018 and January 2020 were recruited in the study. Sociodemographic and clinicopathological characteristics of patients were recorded. Exercise evaluation was performed by preparing a questionnaire and asking the patients face-to-face questions in the outpatient clinic. RESULTS: Risk of relapse was 58% lower in patients who exercised than inactive patients (p = 0.004). Patients who exercised for 2 to 5 days per week had a 63% lower relapse risk than inactive patients (p = 0.010). Risk of relapse was 66% lower in the patients who exercised for less than 1 h or 3 metabolic equivalent of task (MET)-hours per week when compared to inactive patients (p = 0.037). Similarly, relapse risk was 62% lower in patients who exercised between 1 to 3 h or 3 to 8.9 MET-hours per week than inactive patients (p = 0.026). Mortality risk was lower in patients who exercised than patients who did not (p = 0.027). A significantly decreased mortality risk was found in both groups that included patients who exercised for 1 to 5 days per week and patients who exercised for less than 3 h or 9 MET-hours per week when compared to inactive patients. CONCLUSION: Exercise was associated with decreased relapse and mortality rates in patients with BC. Therefore, exercise should be recommended to BC patients as a significant component of the treatment.

The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients: A Multicenter Real-Life Study.

OBJECTIVE: The aim of the study is to compare the efficacy and safety of 3 chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer. METHODS: A total of 218 patients were included in this multicenter study. Gemcitabine (Gem, n = 71), gemcitabine-cisplatin (Gem-Cis, n = 91), and FOLFIRINOX (a combination of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin [FFX], n = 56) treatments were compared. RESULTS: Overall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (P = 0.010). Median progression-free survival (8.4 vs 4.6 and 5.5 months, respectively, P < 0.001) and overall survival (16.4 vs 8.1 and 8.7 months, respectively, P = 0.002) were significantly longer in the FFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46 (64.8%), 56 (61.5%), and 49 (87.5%) patients in the Gem, Gem-Cis, and FFX groups, respectively (P = 0.003). CONCLUSIONS: In our study, FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.

Survival impact of optimal treatment for elderly patients with colorectal cancer: A real world study.

BACKGROUND: In this real-life practice study, we aimed to find whether elderly colorectal cancer (CRC) patients in our center were treated optimally and also if this has an effect on overall survival (OS) or not. METHODS: We have retrospectively screened 150 CRC patients older than 65 years, diagnosed in our institution between 2010 and 2018. As study variables, patient characteristics, tumor location, tumor, nodes, metastases stage, Eastern Cooperative Oncology Group performance status (ECOG PS), comorbidities, adjuvant or metastatic chemotherapy regimens, and treatment toxicity were recorded, and the OS rate of patients was assessed. RESULTS: The median age was 72 (range 65 - 89) years and 48 (32%) patients had metastatic disease at the time of diagnosis. The median OS (mOS) in the suboptimal adjuvant treatment group was 31.5 (range 20.7-42.3) months, whereas mOS was not reached during the median follow-up time in the optimal treatment group (P = 0.036). The addition of oxaliplatin to chemotherapy had no benefit on mOS (P = 0.318). In the metastatic setting, the mOS in the optimal and suboptimal treatment group was 27.2 (range 10.7-43.7) months and 13.4 (range 7.5-18.8) months respectively, and was statistically significant (P = 0.001). CONCLUSION: Our study revealed that optimal treatment had a significant effect on the mOS of elderly CRC patients and it was well tolerated. Advanced age alone is not a sufficient parameter for precluding effective therapy in elderly patients with CRC.

Efficacy of 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting response to second-generation androgen receptor axis-targeted therapy, and the prognosis in metastatic hormone-refractory prostate cancer patients.

INTRODUCTION: The present study investigates the role of 68Ga-PSMA PET/CT-derived whole-body metabolic and volumetric parameters in the prediction of treatment response and prognosis among metastatic hormone-refractory prostate cancer patients undergoing second-generation androgen receptor axis-targeted therapy (abiraterone or enzalutamide). MATERIALS AND METHODS: This retrospective study included 44 metastatic hormone-refractory prostate cancer patients undergoing 68Ga-PSMA PET/CT, including 29 enzalutamide-treated and 15 abiraterone-treated patients. RESULTS: Of the 44 patients included in the study, 29 received enzalutamide and 15 received abiraterone. During treatment, the changes in PET parameters were correlated with the PSA (biochemical) response. More specifically, a positive correlation was noted between PSA response and percent change in TLP (ΔTLP) response, and there was concordance between the results (r = 0.652, k = 0.42, P < 0.001). Baseline PSA (P =0.05), high MTVw (P = 0.005), the increase in ΔPSA (P = 0.036), ΔTLP (P = 0.039) and percent change in MTV (ΔMTV) (P = 0.049) values were identified as factors associated with mortality risk.Multivariate analysis showed that PSA1 [odds ratio (OR): 1.005, 95% confidence interval (CI) 1.002-1.008, P = 0.004], ΔPSA (OR: 14.7, 95% CI 1.50-143.7, P = 0.02) and MTVw1 (OR: 11.4, 95% CI 1.11-116, 6, P = 0.04) were independent prognostic factors associated with mortality risk. CONCLUSION: A statistically significant concordance and correlation was noted between 68Ga-PSMA PET/CT-derived whole-body metabolic parameters (ΔTLP and ΔMTV) and ΔPSA. In addition, the baseline PSA, ΔPSA, ΔTLP, ΔMTV and TMTV were identified as predictive factors for mortality risk.

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

The role of basal 18F-FDG PET/CT maximum standard uptake value and maximum standard uptake change in predicting pathological response in breast cancer patients receiving neoadjuvant chemotherapy.

OBJECTIVE: The aim of this study was to determine the role of 18F-FDG PET/CT in predicting pathological response among patients diagnosed with local or locally advanced breast cancer and receiving neoadjuvant chemotherapy (NAC). METHODS: Basal SUVmax value were analyzed in 212 patients and 142 of these patients had posttreatment SUVmax value. Overall pathological complete response (pCRC) was defined as no evidence of residual invasive cancer in breast (pCRB) and axilla (pCRA). Basal SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and change in SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cutoff value of SUVmax and ΔSUVmax were determined by receiver operating characteristic curve analysis. RESULTS: The number of patients with pCRB was 85 (40.1%), pCRA was 76 (42.5%) and pCRC was 70 (33%). In the artificial neural network-based analysis the ΔSUVmaxB (100%) was the most important variable for predicting pCRB. ΔSUVmaxA (100%) was the most important variable in estimation of pCRA. When pCRC was evaluated, the highest relation was found with ΔSUVmaxB. When the ΔSUVmaxB cutoff value for pCRB and pCRC accepted as ≤-87.9%, its sensitivity was 82.3 and 82.4%, and specificity was 72.5% and 65.9%, respectively (P < 0.001 and P < 0.001, respectively). When the ΔSUVmaxA cutoff value for pCRA and pCRC accepted as ≤-86.6%, its sensitivity was 94.3% and 97.6%, and specificity was 31.3% and 28.2%, respectively (P = 0.017 and P = 0.024, respectively). CONCLUSION: Albeit varies according to the molecular subtypes of the breast cancer during NAC, ΔSUVmax value seems to be the most strong factor associated with pCR.

Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non-small cell lung cancer.

PURPOSE: The optimal chemotherapy regimen for concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) remains unclear. Cisplatin-etoposide regimen related toxicity is high, weekly regimens have been investigating. We aimed to compare the efficacy and safety of different concurrent chemotherapy regimens in the context. METHODS: A total of 225 patients with locally advanced, unresectable stage III NSCLC were included. Patients who were treated with weekly docetaxel-platin (DP), paclitaxel-platin (PP) and standard dose etoposide-platin (EP) chemotherapy regimens were selected and divided into groups for the comparison of toxicity, response rate, progression free survival (PFS), and overall survival (OS) times. RESULTS: There was a statistically significant difference between overall response rate of each treatment groups (DP: 96.1%, PP: 94% and EP: 76.7%, p < 0.001). The median PFS time of patients who were treated with DP, PP and EP was 16, 15 and 13.3 months, respectively (p = 0.435). The median OS time of patients treated with DP, PP and EP was 19.2, 29.7 and 28.3 months, respectively (p < 0.001). The rates of adverse events such as nausea, vomiting, neuropathy and anaphylaxis was similar. Grade 1-2 mucositis or esophagitis, anemia, pneumonitis were significantly higher in PP group than other groups. However, hematologic toxicities were higher in the EP group than other groups. CONCLUSIONS: Compared to the weekly chemotherapy regimens with the standard dose, our study demonstrated similar PFS, but a prolonged OS with the EP regimen. The clinical response rate of weekly regimens was better than the full-dose regimen. Adverse events and toxicity rates were different and depended on the type of chemotherapy regimen used.

Prognostic importance of tumor location and anti-EGFR therapy in patients with K-RAS wild type metastatic colorectal cancer.

PURPOSE: To compare anti-EGFR and anti-VEGF agents in patients with K-RAS wild-type metastatic colorectal cancer (mCRC) with regards to tumor location. METHODS: 450 patients diagnosed with mCRC, who applied to our center were included in this retrospective study. Of 450 patients, 303 underwent K-RAS mutation tests, assessed as having right-sided or left-sided mCRC and grouped according to localization of right and left colon. Sixty-five Patients with K-RAS wild-type mCRC, who were treated with first line anti-EGFR or anti-VEGF containing combination therapies of fluorouracil with leucovorin and either irinotecan or oxaliplatin were compared. RESULTS: 393 (87%) out of 450 mCRC patients had left-sided colon cancers, and 57(13%) had right-side colon cancers. K-RAS analysis was performed in 303 of 450 patients with mCRC, 186 (61.4%) patients had K-RAS wild-type and 117 (38,6%) had K-RAS mutant. Median survival for right-sided cancers was 23.3 months and 29.4 months for left-sided cancers (p=0.309). Median progression-free survival (PFS) was 10.4 months (95% CI 7.3-13.4) in the anti-EGFR containing regimens group and 9.7 months (8.2-11.1) in the anti-VEGF containing regimens group (p=0.037); however, median overall survival (OS) was 18.4 months (95% CI 11.7-25.1) in the anti-EGFR containing regimens group and 19.3 months (95% CI 15.7-22.9) in the anti-VEGF containing regimens group (p=0.635). CONCLUSION: Addition of anti-EGFR in left sided K-RAS wild-type mCRC regarding PFS was beneficial, however there was no difference in terms of OS.

The importance of serum and pleural fluid level of vascular endothelial growth factor (VEGF) and VEGF fluid/serum ratio in the differential diagnosis of malignant mesothelioma-related pleural effusion.

AIM OF THE STUDY: Vascular endothelial growth factor (VEGF) is one of the parameters that has been studied in differential diagnosis of malignant fluids. This study is aimed at evaluate applicability of serum, fluid VEGF level and fluid to serum VEGF ratio in the diagnosis of malignant pleural mesothelioma (MPM). MATERIAL AND METHODS: The patients with pleural effusion over age of 18, between 2011 and 2015 were included in the study. They were divided into three groups: group 1 - mesothelioma patients; group 2 - other malignancies; and group 3 - benign aetiologies. Group 1 and 2 were termed as the malignant group. Fluid, serum VEGF levels, and the ratio of fluid/serum VEGF level were studied to evaluate the fluid/serum VEGF ratio in all groups. RESULTS: Twenty cases with mesothelioma, 44 cases with other malignancies, and 20 cases with benign aetiologies were included in this study. No statistically significant difference was found according to serum VEGF levels for all groups, (group 1: 437 ±324 pg/ml, group 2: 354 ±223 pg/ml, group 3: 373 ±217 pg/ml, p = 0.836), while fluid VEGF levels showed a statistically significant difference (group 1: 3359 ±700 pg/ml, group 2: 2175 ±435 pg/ml, group 3: 1092 ±435 pg/ml, p = 0.041). The ratio of fluid to serum VEGF levels showed a difference, at the significance limit, between the malignant (group 1 and group 2) and benign (group 3) groups (8.83 ±1.29 vs. 4.57 ±1.07, p = 0.059) but showed a statistically significant difference between the mesothelioma and benign groups (12.11 ±1.68 vs. 4.57 ±1.07, p = 0.044). CONCLUSIONS: The VEGF fluid/serum ratio may be an applicable parameter in the differential diagnosis of malignant fluids, especially MPM.

Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

PURPOSE: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. METHODS: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. RESULTS: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). CONCLUSIONS: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab.

PURPOSE: The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab. METHODS: Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. RESULTS: Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. CONCLUSIONS: In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.

Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study.

BACKGROUND: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. MATERIALS AND METHODS: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. RESULTS: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. CONCLUSIONS: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.