Sarcopenic obesity in early breast cancer patients with metabolic syndrome: a cross-sectional study.

Aim: The importance of sarcopenic obesity (SO) in malignancy has recently been recognized. The authors aimed to investigate the clinical and body composition data of early-stage breast cancer (BC) patients by focusing on the components of metabolic syndrome (MetS) and SO. Methods: In this cross-sectional study with early-stage BC patients, the clinical and laboratory results were evaluated for diagnosing MetS. Bioimpedance analysis and muscle radiation attenuation (Hounsfield unit average calculation [HUAC]) using acquired computed tomography images were used to assess SO. Results: The age at diagnosis, BMI, visceral fat ratio, hemoglobin A1c and CEA levels in patients with MetS were significantly higher (p < 0.05). A cutoff value of 39.4 Hounsfield units was significantly related to MetS with 76.5% sensitivity and 62% specificity. The mean HUAC in patients with MetS (36.9) was significantly lower than in those without MetS (41.4; p = 0.017). Conclusion: HUAC value predicted SO in early-stage BC patients with MetS.

Older adults with colon cancer are not different from younger ones, but treated differently: Retrospective analysis from single centre.

AIM: Decision- making of the treatment of colon cancer for the older patients becomes more complicated in consequence of comorbidities and geriatric syndromes, most importantly frailty. In the present study, we aimed to investigate whether there is a difference between tumour characteristics, treatment choices, and outcomes between the younger and older adults. METHOD: The patients who were diagnosed with colorectal carcinoma in our centre between 2010 and 2015 included. Clinicopathological features of tumour, treatment choices and survivals of the patients were recorded. Patients were separated into two groups according to their chronological age. RESULTS: The present study included 465 patients, there were 173 patients aged 65 years and older. Clinicopathological features were similar in both groups. Adjuvant chemotherapy was given in similar rates. Whereas combination chemotherapies were preferred in younger patients as first-line therapy, single agents were given to the older group(p-value < 0.001). No significant differences were observed between combination therapy and monotherapy as progression-free and overall survival in older adults(p value > 0.05). It was observed that 53.2% of the older patients was not treated with any biological treatment (p-value < 0.001). DISCUSSION: Geriatric people are underrepresented in clinical trials,because of the presence of the limitations in the older patients. The results of our study revealed older patients with colon cancer patients underwent surgery less than the younger ones, they recieved monotherapy more frequently as first-line chemotherapy, and less frequently targeted therapy. Their mortality was higher. It was shown that decision-making of colon cancer therapy is influenced by age according to our results.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells.

Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. In this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: The trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.

Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells.

Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.

The Close Relationship Between Metabolic Syndrome and Hormone Receptor-Positive Early-Stage Breast Cancer.

OBJECTIVE: The primary aim of the current study was to investigate the frequency of metabolic syndrome (MS) in early-stage breast cancer patients. Additionally, clinicopathological factors, such as anthropometric measurements and hormonotherapy, were examined for their roles as potential confounders of MS in these patients. PATIENTS AND METHODS: In this retrospective cross-sectional study, all patients diagnosed with early breast cancer were included. Patients were divided into 2 groups with respect to MS diagnosis. Peripheral blood samples were obtained, clinical data were recorded, and body mass index (BMI) was calculated. RESULTS: The study was completed with a total of 207 patients of which 128 (61.8%) had MS. MS was more frequent hormone receptor positive subgroup and in recipients of adjuvant hormonotherapy. The comparison of patients with and without MS revealed significant differences in age, BMI and estrogen/progesterone receptor status. There were no significant differences between groups in terms of cancer stage, inflammatory markers, basal insulin and LDL levels, and tumor markers. CONCLUSION: MS appears to be rather widespread among women with early-stage breast cancer, and lifestyle changes, which can improve obesity-related adverse outcomes, should be more emphasized in clinical practice.

Prediction of pathological complete response to neoadjuvant chemotherapy in locally advanced breast cancer by using a deep learning model with 18F-FDG PET/CT.

OBJECTIVES: The aim of the study is 18F-FDG PET/CT imaging by using deep learning method are predictive for pathological complete response pCR after Neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC). INTRODUCTION: NAC is the standard treatment for locally advanced breast cancer (LABC). Pathological complete response (pCR) after NAC is considered a good predictor of disease-free survival (DFS) and overall survival (OS).Therefore, there is a need to develop methods that can predict the pCR at the time of diagnosis. METHODS: This article was designed as a retrospective chart study.For the convolutional neural network model, a total of 355 PET/CT images of 31 patients were used. All patients had primary breast surgery after completing NAC. RESULTS: Pathological complete response was obtained in a total of 9 patients. The study results show that our proposed deep convolutional neural networks model achieved a remarkable success with an accuracy of 84.79% to predict pathological complete response. CONCLUSION: It was concluded that deep learning methods can predict breast cancer treatment.

Prognostic Significance of Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Metastatic Colorectal Cancer.

There are many studies on the biomarkers for the prognosis in the treatment of metastatic colorectal cancer. Neutrophil-lymphocyte radio (NLR) and platelet-lymphocyte radio (PLR) are of interest with studies revealing the relationship between inflammatory biomarkers and cancer. Our study is a retrospective file study and the contribution of NLR and PLR to progression-free survival (PFS) and overall survival (OS) before first-line chemotherapy was investigated regardless of treatment. The cutoff values of NLR and PLR were determined using ROC curve analysis. NLR and PLR were divided into two groups according to the cut-off points. OS and PFS associated with NLR and PLR were performed by the Kaplan-Meier method. In our study, we could not demonstrate the prognostic potential of pre-treatment NLR and PLR in patients with mCRC treated with first-line chemotherapy. Our study showed that the use of these biomarkers in mCRC is limited. INTRODUCTION: There are many studies on the biomarkers for the prognosis in the treatment of metastatic colorectal cancer. Neutrophil-lymphocyte radio (NLR) and platelet-lymphocyte radio (PLR) are of interest with studies revealing the relationship between inflammatory biomarkers and cancer. MATERIAL AND METHOD: Our study is a retrospective file study and the contribution of NLR and PLR to progression-free survival (PFS) and overall survival (OS) before first-line chemotherapy was investigated regardless of treatment. The cutoff values of NLR and PLR were determined using ROC curve analysis. NLR and PLR were divided into two groups according to the cut-off points. OS and PFS associated with NLR and PLR were performed by the Kaplan-Meier method. RESULT: In our study, we could not demonstrate the prognostic potential of pre-treatment NLR and PLR in patients with mCRC treated with first-linechemotherapy. CONCLUSION: Our study showed that the use of these biomarkers in mCRC is limited.

Is the Effect of Tumor Localization on Prognosis Compatible with Real-life Data in Metastatic Colon Cancer? Single-Center Experience: A Retrospective Analysis.

AIM: In recent years, the prognostic and predictive value of primary tumor localization in colon cancer has become increasingly important. This study aimed to retrospectively analyze the effect of colon cancer tumor localization on progression-free survival, overall survival, and response to treatments and present real-life data. METHOD: Retrospective evaluation was made of 465 patients who were diagnosed with metastatic colorectal carcinoma between 2010 and 2015 in our clinic. The effect of primary tumor localization on progression-free survival, overall survival, and response to therapy was investigated. RESULTS: The right colon cancer (RCC) was determined in 66 patients, 14.2% of the whole group, and left colorectal cancer (LCRC) in 399 patients which is 85.8% of patients. Mucinous adenocarcinoma was 16.7% in RCC; however, only 6.4% of LCRC had a mucinous tumor (p < 0.05). Nodal involvement in any stage (N1 and N2) was 46.9% in right colon cancer whereas in LCRC, it was 41.2% (p < 0.05). Primary tumor surgery (74.2% vs. 70.2%) and metastasectomy (33.3% vs. 19.4%) were also more common in RCC(p < 0.05). k-ras mutation status was similar in both groups (28.8% in RCC vs 26.8% in LCRC, p > 0.05). Median progression-free survival was 12.6 months in RCC, and 15.5 in LCRC (p > 0.05). Median overall survival was 28.4 months in RCC and 33.5 months in LCRC (p > 0.05). In k-ras wild-type patients, the median overall survival was 32.3 months (95% CI 25.2-39.5) in the anti-VEGF antibody treatment group and 55.1 months (95% CI 36.5-73.7) in the anti-EGFR antibody treatment group (p < 0.05). CONCLUSION: Although tumors located in the right colon have been considered to be worse in terms of progression-free and overall survival in clinical trials, the results of this study showed that in daily practice, there was no difference between left and right colon localized tumors in progression-free and overall survival. Further, in k-ras wild-type colon cancers, tumor localization predicts the treatment response. This study is important with the presentation of real-life data and compatibility with the data of the studies to daily life.

Inflammatory Prognostic Index in Metastatic Renal Carcinoma Treated with Nivolumab.

OBJECTIVE: To evaluate the utility of inflammatory prognostic index (IPI), albumin, c-reactive protein (CRP), and lactate dehydrogenase (LDH) as predictive biomarkers of oncologic outcome in metastatic renal cell cancer (mRCC) patients treated with nivolumab. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Manisa Celal Bayar University, Aydin Adnan Menderes University, Bitlis Tatvan State Hospital and Private Hatay Defne Hospital Medical Oncology Clinics, Turkey, from January 2017 to June 2020. METHODOLOGY: Seventy-five mRCC patients treated with nivolumab between January 2017 and June 2020 were enrolled. Several factors were retrospectively investigated, including IPI, CRP, LDH, and albumin level, for their association with progression-free survival (PFS) and overall survival (OS). The IPI was calculated as CRP × NLR/albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. RESULTS: When analysed according to the calculated IPI score, it is seen that the group with <2.153 has an OS duration of 96.3 months, while the group with ≥2.153 has a shorter time of 42.9 months (p=0.02). In the analysis performed according to albumin level, it was reported that those with low levels (22.8 months) had worse median OS than those with high levels (92.8 months) (p=0.004). According to the cox regression analysis results, it was determined that those with a high IPI score significantly increased the risk of death compared to those with a low score (HR:2.4, p=0.023). However, this significance could not be confirmed in the multivariate analysis. It was analysed that those with low albumin levels significantly increased the risk of death compared to both univariate analysis (HR:3.3, p=0.007) and multivariate analysis (HR:4.4, p=0.003). CONCLUSION: Those with high IPI scores and low albumin levels were associated with worse median OS. However, only the multivariate analysis analysed albumin level as an independent prognostic variable. Prospective and more extensive research is needed to consolidate the potential prognostic power of these markers. KEY WORDS: Albumin, Immune checkpoint inhibitor, IPI score, Metastatic renal cell carcinoma, Nivolumab, overall survival, Progression-free survival.

Contribution of "complete response to treatment" to survival in patients with unresectable metastatic colorectal cancer: A retrospective analysis.

BACKGROUND: The aim of the study is to reveal the contribution of complete response (CR) to treatment to overall survival (OS) in patients with unresectable metastatic colorectal cancer. In addition, to evaluate progression-free survival (PFS) in patients who attained CR to treatment and to examine the clinicopathologic features of the patient group with CR. METHODS: This article is a retrospective chart review. Patients diagnosed with metastatic colorectal cancer were divided into two groups. The systemic treatment was compared with the patients who received a full response according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) and those who did not attain CR (progression partial response and stable response) in terms of both PFS and OS data, and the effect of attaining CR to treatment on prognosis was evaluated. RESULTS: A total of 222 patients were included in the study. 202 of 222 patients could be evaluated in terms of complete response. All data from their files were tabulated and analyzed retrospectively. The mean age of diagnosis of the study group was 60.13 ± 12.52 years. The total number of patients who attained CR to treatment was 31 (15.3%); 171 (84.6%) patients did not attain CR. Patients who had a CR had longer median PFS times than patients who did not have a CR (15.2 vs. 7.4 months, P<0.001). Patients who had CR had longer median survival times than patients who did not have a CR (39.2 vs. 16.9 months, P<0.001). In subgroup patients who underwent primary surgery, the number of patients who attained CR was statistically higher compared with the number of patients who did not attain CR (p<0.001). Complete response was less common in the presence of liver metastasis and bone metastasis (p = 0.041 and p = 0.046, respectively), had a negative prognostic effect. In other words, 89.1% of patients with liver metastasis, 100.0% of patients with bone metastasis, and 88.7% of those who died did not have a CR to the treatment. According to multivariate analysis, CR to treatment, primary surgery, first-line chemotherapy (combination compared with fluoropyrimidine), and no bone metastasis were found to be predictors for OS. CONCLUSION: Providing CR with systemic treatment in patients with unresectable metastatic colorectal cancer (mCRC) contributes to prognosis. The primary resection in our secondary acquisitions from the study, the number of metastatic regions and the combination therapy regimens also contributed to the prognosis.

Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors.

PURPOSE: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. METHODS: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-L1 and mRNA was evaluated with IHC. RESULTS: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). CONCLUSION: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas.

Pazopanib: a novel treatment option for aggressive fibromatosis.

BACKGROUND: Aggressive fibromatosis (AF), also known as desmoid tumor, is an uncommon soft tissue neoplasm. AF does not metastasize, but it is locally invasive and its propensity for recurrence after conservative resection is well documented. No effective cytotoxic treatment has been reported, hence there is a need for novel treatment strategies. CASE PRESENTATION: We present the case of an AF successfully treated with an oral tyrosine kinase inhibitor, pazopanib, with mild side effects. As far as we know, this is the first case of AF with complete response to pazopanib. CONCLUSION: Pazopanib might be an effective treatment option for AF.

Leptomeningeal carcinomatosis of gastric adenocarcinoma.

Gastric cancer is the third most common malignancy among gastrointestinal malignancies. With the advance of new treatments, overall survival in gastric cancer is extending, and metastasis to atypical sites is seen more commonly. Leptomeningeal metastasis is one such atypical metastasis for gastric cancer. We report a case of gastric adenocarcinoma with leptomeningeal metastasis as an atypical involvement. A 39-year-old female, presenting with headache, vertigo, horizontal gaze palsy, visual disturbances, and seizures, was admitted to our hospital in August 2009. The funduscopic examination revealed the presence of bilateral papilledema. Magnetic resonance imaging of the brain showed diffuse leptomeningeal enhancement and biventricular dilatation. Cytological examination of the cerebrospinal fluid revealed malignant cells. These findings were consistent with leptomeningeal carcinomatosis. Six months before, she was diagnosed as having gastric cancer by upper gastrointestinal tract endoscopy, which was performed as a part of the diagnostic work-up to clarify the cause of her abdominal ascites. She received six cycles of docetaxel-cisplatin-5-fluorouracil for metastatic gastric cancer, and she developed the above-mentioned symptoms under chemotherapy. She was included in a craniospinal radiotherapy program and received intrathecal methotrexate treatment. We present this case report since leptomeningeal carcinomatosis of gastric cancers is a rare clinical entity, and treatment strategies remain challenging for clinicians.