Management and prognosis of patients with cancer of unknown primary: 20 years of experience.

Background/aim: Cancer of unknown primary (CUP) is a difficult clinical entity to manage. The aim of the study was to investigate the sociodemographic and pathological characteristics, treatment options, and factors affecting overall survival (OS) in CUP patients whose primary tumor was not detected during follow-up. Materials and methods: A total of 243 CUP patients whose primary tumors could not be detected during follow-up were included in the study. Their demographic characteristics, survival outcomes, and prognostic factors were investigated. Results: Of the 243 patients included in this study, 61.7% were male and 38.3% were female, and the median age was 61 (range: 19-90) years. The most common histological type was adenocarcinoma (79%). The median follow-up time of the patients was 30.3 months (95% CI: 11.4-49.3), the median OS time was 9.1 months (95% CI: 7.2-11.0), and 72.4% of the patients received at least 1 line of chemotherapy (CT). The difference in survival between the patients who did and did not receive CT was statistically significant (median OS: 10.1 vs. 4.2 months, p = 0.003). According to the multivariate analysis, the presence of cholestasis (HR: 0.48, 95% CI: 0.29-0.79, p = 0.004), lung metastasis (HR: 0.69, 95% CI: 0.51-0.95, p = 0.001), second-line chemotherapy (HR: 1.69, 95% CI: 1.14-2.49, p < 0.001), and Eastern Cooperative Oncology Group (ECOG) performance status (HR: 0.20, 95% CI: 0.10-0.40, p < 0.001) were independent prognostic factors influencing OS. Conclusion: CUP patients who receive multiple lines of chemotherapy tend to have longer survival. This is the first study to report cholestasis as a prognostic factor in CUP patients. In addition, the presence of lung metastases, not receiving second-line chemotherapy, and ECOG performance status (≥2) were found to be independent poor prognostic factors.

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.

"Swords and Shields" against COVID-19 for patients with cancer at "clean" and "pandemic" hospitals: are we ready for the second wave?

PURPOSE: COVID-19 will continue to disrupt the diagnosis-treatment process of cancer patients. Dr. Abdurrahman Yurtaslan Ankara Oncology Hospital has been considered as a 'non-pandemic' center ('clean') in Ankara, the capital city of Turkey. The other state hospitals that also take care of cancer patients in Ankara were defined as 'pandemic' centers. This study aimed to evaluate hospital admission changes and the precautionary measures in clean and pandemic centers during the pandemic. The effect of these measures and changes on COVID-19 spreading among cancer patients was also evaluated. METHODS: The patients admitted to the medical oncology follow-up, new diagnosis, or chemotherapy (CT) outpatient clinics during the first quarter of pandemic period (March 15-June 1, 2020) of each center were determined and compared with the admissions of the same frame of previous year (March 15-June 1, 2019). COVID-19 PCR test results in clean and pandemic centers were compared with each other. Telemedicine was preffered in the clean hospital to keep on follow-up of the cancer patients as 'noninfected'. RESULTS: In the clean hospital, COVID-19-infected patients that needed to be hospitalized were referred to pandemic hospitals. COVID-19 test positivity rate was eight-fold higher for outpatient clinic admissions in pandemic hospitals (p < 0.001). The number of patients admitted new diagnosis outpatient clinics in both clean and pandemic hospitals decreased significantly during the pandemic compared with the previous year. CONCLUSION: We consider that local strategic modifications and defining 'clean' hospital model during infectious pandemic may contribute to protect and treat cancer patients during pandemic.

Does primary tumor resection contribute to overall survival in unresectable synchronous metastatic colorectal cancer?

BACKGROUND: Primary tumor resection (PTR) in metastatic colorectal cancer (mCRC) has not been suggested by guidelines, since new systemic chemotherapy options have improved overall survival. However, the effect of PTR is still controversial in mCRC. In this study, we aimed to evaluate the effect of PTR on survival in unresectable mCRC. MATERIALS AND METHODS: Two hundred and fifty-two patients with unresectable mCRC were screened retrospectively between January 2007 and December 2017 and a total of 147 patients who met inclusion criteria were included. The patients with emergency or elective PTR and the patients without surgery were compared for baseline features and overall survival. RESULTS: The median follow-up time was 15.6 months (range; 1.2-78.9) in whole patients. There were 91 patients in nonsurgical (NS) group and 56 patients in PTR group. The median overall survival was significantly longer in PTR group compared NS group (21.8 vs. 17.0 months, P = 0.01), but it was not associated to better overall survival in multivariate Cox analysis (hazard ratio: 0.65, 95% confidence interval: 0.41-1.02, P = 0.06). There was no significant difference in overall survival between emergency and elective surgery subgroups (22.9 vs. 16.1 months, respectively, P = 0.9). CONCLUSION: PTR did not offer an overall survival benefit in this study. Although it is debated, we think that it is better to start treatment with chemotherapy and biological agent combinations in patients with asymptomatic mCRC. Thus, the patients can be protected from the morbidity and mortality of the surgery.

Progesterone receptor status in determining the prognosis of estrogen receptor positive/ HER2 negative breast carcinoma patients.

PURPOSE: To evaluate the impact of progesterone receptor (PR) status on estrogen receptor (ER)-positive and HER2-negative breast cancer. METHODS: A total of 1673 operable breast cancer patients, diagnosed from June 1984 to June 2011 were retrospectively reviewed and 400 patients with ER-positive and HER2-negative tumors were identified and evaluated. ER-positive and HER2-negative patients were classified into two groups: group A: ER+/PR-/HER2- and group B : ER+/PR+/HER2- according to PR status. RESULTS: Median follow-up was 14.2 years (range 10.1-18.2). The ratio of postmenopausal patients was significantly higher in group A (68.2%, p=0.015). Grade 1 tumor and stage I disease were significantly higher in group B (15%, p=0.007 and 15%, p=0.005, respectively). Mean overall survival (OS) and disease free survival (DFS) were significantly better in group B (15.3±1.5 years vs 8.7±0.8 years, p=0.032; 10.5±1.6 years vs 5.7±0.5 years, p=0.022) as compared with group A. Relative risk for recurrence and death were two-fold higher in group A (p=0.05 and p=0.01, respectively). CONCLUSION: PR status exerts a significant impact on prognosis of ER+/HER2- breast cancer.

KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.

PURPOSE: Adding targeted therapies to chemotherapy in metastatic colorectal cancer (CRC) improves response rates and survival. KRAS is a predictive indicator for anti-epidermal growth factor receptor (EGFR) treatments. The most important reasons for KRAS discordance are intratumoral heterogeneity and incorrect mutation analysis. Evaluating the status of KRAS in primary and metastatic lesions becomes even more crucial to ensure efficient usage of anti-EGFR treatments. METHODS: Patients with metastatic CRC, whose primary disease and liver and/or lung metastases were operated, were retrospectively evaluated, and KRAS assessment was performed on 31 patients who were suitable for DNA analysis. Pyrosequencing with polymerase chain reaction (PCR) was used for KRAS analysis. RESULTS: The median age of 31 patients diagnosed with rectal cancer (N=13) and colon cancer (N=18) was 63 years (range 33-73). Metastasectomy locations included the liver (N=27), lung (N=3), and both lung and liver (N=1). KRAS discordance was detected in 22% (7/31) of the patients. While 3 patients with detected discordance had mutated KRAS in the primary material, wild type KRAS was detected in their liver or lung lesions. On the other hand, while 4 patients had wild type KRAS in the primary material, mutated KRAS was determined in their liver or lung lesions. The McNemar test revealed no significant discordance between primary and metastatic disease (p=1.00). No progression free survival (PFS) difference was detected between patients with determined discordance and patients with undetermined discordance (10.6 vs 14.7 months, p=0.719). CONCLUSION: This is the first study to evaluate KRAS discordance between primary and metastasis in CRC patients, who underwent metastasectomy, together with survival data. In the literature and recent studies with large patient numbers in which modern KRAS tests were used, the KRAS discordance rate varies between 3-12%. In our study, a higher KRAS discordance (22%) was detected, and no survival difference was determined between patients with or without discordance. In recent years, the rising interest in borderline resectable disease may bring forward discussions related to which material the KRAS status should be analyzed.

Sunitinib-induced severe hypoglycemia in a diabetic patient.

INTRODUCTION: Sunitinib is an oral inhibitor of tyrosine kinase that was used for the treatment of mRCC. The general side effects are fatigue, asthenia, diarrhea, mucositis, nausea, vomiting, skin changes, hypertension, hypothyroidism and hematologic side effects. In addition, sunitinib-induced hypoglycemia has also been reported. There are limited number of case reports related to sunitinib-induced hypoglycemia. CASE PRESENTATION: In this case report, we have presented a patient with type 2 diabetes mellitus (DM) with emerging severe hypoglycemia after sunitinib treatment. It was shown that blood glucose levels were normalized two weeks after the interruption of sunitinib. CONCLUSION: Although the underlying mechanism of sunitinib-induced hypoglycemia is not completely understood, sunitinib can be regarded to have an antidiabetic effect. In the literature, there are some reports about sunitinib/other TKI induced hypoglycemia; however, life threatening hypoglycemia is rare. There is no case report of severe hypoglycemia due to imatinib; however, there are two case reports with severe hypoglycemia due to sunitinib treatment. Symptomatic hypoglycemic episodes due to sunitinib may lead to hospital admission. Diabetic patients may develop severe hypoglycaemia and it should be kept in mind that the discontinuation of antihyperglycemic treatment may be required. Therefore, blood glucose levels should be closely monitored in diabetic patients with mRCC during sunitinib therapy.

Treatment decision plans matter in elderly patients with gastrointestinal cancer: suboptimal or optimal?

PURPOSE: Aging is an important risk factor for cancer. Molecular changes and defective immunity associated with aging result in increased susceptibility to many carcinogens of the gastrointestinal system (GIS). Comorbidities and changes in drug metabolism in elderly patients make the treatment of GIS cancers difficult. METHODS: Between January 2009 and December 2012, a total of 790 patients diagnosed with GIS cancers were retrospectively evaluated. Among them, 357 patients aged ≥ 65 years constituted the study population in which the patient characteristics, disease location, TNM stage, ECOG PS, co-morbidities, chemotherapy regimens and overall survival (OS) were assessed. RESULTS: The patient median age was 71 years (range 65-94). Cancer localizations were colorectal cancer (CRC), gastric cancer, and the pancreaticobiliary system (PBS) cancer in 178 (49.9%), 124 (34.7%), and 55 (15.4%) patients, respectively. A total of 260 (69%) patients underwent chemotherapy: 167 (64.3%) patients received optimal chemotherapy, and 93 (35.7%) suboptimal chemotherapy. The median OS was 47, 14, and 11 months in CRC, gastric, and PBS cancers, respectively. OS was better in the optimally-treated group than in the suboptimally-treated group among patients with all types of cancer. OS was 67 vs 19 months (p<0.001), 17 vs 8 months (p=0.004), and 12 vs 10 months (p=0.46) in CRC, gastric, and PBS cancers in the optimal and suboptimal chemotherapy groups, respectively. Multivariate analysis showed that the disease stage in all cancer types and optimal chemotherapy in the CRC group were important predictors of survival (p<0.001 and p=0.021, respectively). CONCLUSION: Cancer is usually in advanced stage at the time of diagnosis in these elderly patients and screening programs might improve outcomes in this age group. Patients with GIS cancers (especially CRC and gastric cancer) should be encouraged to receive optimal chemotherapy regimens.

Effects of comorbidities and functional living activities on survival in geriatric breast cancer patients.

AIM OF THE STUDY: We evaluated the possible effects of comorbid diseases and functional capacity on the survival of elderly female patients with breast cancer. MATERIAL AND METHODS: The study included 159 breast cancer patients aged 65 years or older. Functional status of the patients was evaluated using Katz's index of activities of daily living (ADL) and Lawton and Brody's Instrumental ADL (IADL) scale. RESULTS: ADL-based evaluation revealed 121 patients (76.1%) were independent, 34 (21.4%) semi-dependent and 4 (2.5%) dependent whereas IADL-based evaluation showed 69 patients (43.4%) were independent, 67 patients (42.1%) semi-dependent and 23 patients (14.5%) dependent. Among the patients, 69 (43.4%) had one comorbid disease, 62 (39.0%) had two and 26 (16.4%) had three or more. Of the entire cohort, 60.4% received adjuvant chemotherapy. Based on ADL index, overall survival (OS) was significantly better in semi-dependent and independent patients than in dependent patients (p = 0.001). In the upfront non-metastatic patient subgroup, disease-free survival (DFS) was favourable in the independent patients according to ADL index (p = 0.001). Having more than one comorbid disease had an unfavourable effect on OS. In the multiple regression analysis of non-metastatic patients, stage, triple-negative histology and ADL index remained significant in terms of OS (p = 0.008, HR: 3.17, CI: 1.35-7.44; p = 0.027, HR: 2.78, CI: 1.172-6.91; and p = 0.006, HR: 0.29, CI: 0.12-0.70, respectively). CONCLUSIONS: In elderly patients with breast cancer, evaluation of daily living activities and comorbid diseases are as important as staging and subclassification of breast cancer in the determination of prognosis and survival.

Impact of 68Ga-PSMA PET/CT on Survival and Management in Prostate Cancer.

BACKGROUND: 68Ga-labeled prostate-specific membrane antigen positron emission tomography-computed tomography (68Ga-PSMA PET/CT) has led to altered treatment plans for prostate cancer (PCa) patients. OBJECTIVE: This study aimed to investigate the impact of 68Ga-PSMA PET/CT on overall survival (OS) and management in PCa. METHODS: Consecutive 100 patients who had 68Ga-PSMA PET/CT and conventional imaging (CI) were included in this retrospective study. Disease stages and treatment plans according to both CI and 68Ga-PSMA PET/CT were compared. The effect of 68Ga-PSMA PET/CT on OS was assessed. RESULTS: After 68Ga-PSMA PET/CT, the stage changed in 64 patients (64%). By the reason of 68Ga-PSMA PET/CT findings, treatment plans based on CI were changed in 73 patients (73%). According to the ROC analysis, patients with a PSA value below 8 had higher rates of change in staging (p<0.0001) and treatment (p=0.034). Both a PSA below 8 (OR 8.79 95% CI (2.72-28.43), p<0.001), and having a hormone-sensitive disease at the time of imaging (OR 5.6 95% CI (1.35-23.08), p=0.017) were significant independent factors predicting change in staging with 68Ga-PSMA PET/CT. The results of a phi correlation coefficient analysis showed a significant relationship between therapy and changes in staging (ϕ=0.638, p<0.0001). Two-year OS was statistically different in hormone-sensitive patients with and without treatment change (95% vs 81%, p=0.006). CONCLUSION: 68Ga-PSMA PET/CT has the effect of changing the treatment in 73% of PCa patients. There is a positive correlation between the changes in staging and treatment. Survival of hormone sensitive patients has improved due to treatment changes based on PET/CT findings.

Comparison of the second-line treatment efficacy in advanced gastric cancer patients previously treated with taxane-based triplet chemotherapy: a Turkish Oncology Group Study.

OBJECTIVE: This study aimed to assess the efficacy and safety of FOLFIRI and paclitaxel in patients with advanced gastric cancer (AGC) who were previously treated with first-line modified docetaxel, cisplatin, 5-fluorouracil (mDCF), or 5-fluorouracil, oxaliplatin, docetaxel (FLOT). METHODS: Patients who received a triplet regimen in the first line setting and were treated with FOLFIRI or paclitaxel in the second-line treatment were included. RESULTS: The study included 198 patients, with 115 receiving FOLFIRI and 83 receiving paclitaxel. The median age was 58 (range = 24-69). The median progression-free survival (mPFS) was 5.2 [95% confidence interval (CI) = 4.4-5.5] months in the FOLFIRI arm, and 4.1 (95% CI = 3.3-4.6) months in the paclitaxel arm (p = .007). The median overall survival (mOS) was 9.4 (95% CI = 7.4-10.5) months in the FOLFIRI arm and 7.2 (95% CI = 5.6-8.3) months in the paclitaxel arm (p = .008). Grade 3-4 neuropathy was higher in patients receiving paclitaxel compared to those receiving FOLFIRI (p = .04). Grade 3-4 diarrhea was 8% in the FOLFIRI arm and 2.4% in the paclitaxel arm (p = .02). CONCLUSION: Beyond progression with docetaxel-based triplet chemotherapy, FOLFIRI may be preferred as a second-line treatment over paclitaxel due to its longer mPFS and mOS.

Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Prognostic factors for recurrence-free survival in patients with HER2-positive early-stage breast cancer treated with adjuvant trastuzumab.

BACKGROUND: The objective of this study was to identify prognostic factors affecting the recurrence-free survival (RFS) in patients who received a 52-week trastuzumab therapy for HER2-positive early stage breast cancer (EBC). PATIENTS AND METHODS: The medical records of all patients with EBC from 10 centers were analyzed. Pathologic and clinical tumor characteristics were evaluated in 424 female patients who received 52 weeks of adjuvant trastuzumab for HER2-positive EBC. Survival was estimated using the Kaplan-Meier method. Univariate analyses of RFS were performed with the log-rank test. Independent prognostic and predictive factors affecting RFS were assessed by Cox regression analysis. RESULTS: Median follow-up time was 33.1 months (range 9.2-75.9 months). 3-year RFS and overall survival were 87 and 97%, respectively. In multivariate analysis, patients aged 70 years or over (p = 0.017, relative risk (RR) 2.7, 95% confidence interval (CI) 1.19-6.13), patients with > 9 positive lymph nodes (p = 0.001, RR 2.52, 95% CI 1.42-4.46), and those with progesterone receptor-negative tumors (p = 0.006, RR 2.33, 95% CI 1.27-4.27) had worse RFS. CONCLUSION: In spite of a 52-week adjuvant trastuzumab treatment, classic poor prognostic factors for invasive EBC remained as such in patients with HER2-positive EBC.

Isolated ovarian metastasis of gastric cancer: Krukenberg tumor.

INTRODUCTION: Gastric cancer, one of the most common cancers in the world, rarely metastasizes to the ovaries. Ovarian metastases of gastric signet ring cell cancer (SRCC) are referred to as Krukenberg tumors and account for 1-2% of all ovarian cancers. Here, we analyze the characteristics, treatment, and prognosis of patients with Krukenberg tumors. MATERIAL AND METHODS: We retrospectively analyzed the demographic characteristics, treatment modalities, progression-free survival (PFS), and overall survival (OS) of patients who were diagnosed with Krukenberg tumors of gastric cancer origin and who underwent treatment and follow-up between January 2005 and January 2012 in the Ankara Oncology Education and Research Hospital. RESULTS: Among 1755 patients diagnosed with gastric cancer between January 2005 and January 2012, eight patients (0.45%) with histopathologically identified Krukenberg tumors were enrolled. The median age of the eight patients was 42.2 years (range, 32-69 years). Two (25%) of the patients were stage 3A, two (25%) were stage 3C, and four (50%) were stage 4 at the time of diagnosis. The median PFS was 13.2 months (1-25 months), the median OS after the original diagnosis was 16.7 months (1-41 months), and the median OS after ovarian metastasis was 3.6 months (1-10 months). DISCUSSION: Krukenberg tumors were seen particularly in young patients and more frequently during the premenopausal period. The prognosis was poor. When only the ovaries were affected, metastasectomy prolonged the survival time.

The effectiveness of adjuvant treatment approaches for resectable esophageal cancer: A single-center experience.

AIMS AND BACKGROUND: In general, neoadjuvant treatment is the standard for clinical stage II/III esophageal cancer (EC), whereas the effect of adjuvant treatment on survival still remains controversial. The aim of this study was to investigate the efficacy of adjuvant treatment modalities on the survival of EC patients. PATIENTS AND METHODS: A total of 63 patients with stage II-IVA EC who had undergone curative surgery between the years 2002 and 2020 were included in the study. Patients' data were retrospectively collected from oncologic follow-up files. Various treatment regimens were administered during this period, including chemotherapy and chemoradiotherapy. RESULTS: The median age was 56 years (24-73), and the number of males was slightly higher than females (male/female: 33/30). While 32 (51%) patients received postoperative adjuvant treatment, the remaining 31 (49%) patients underwent surgery alone. The median overall survival (OS) was 45.9 months (95% confidence interval [CI]: 25.1-66.8) in patients receiving adjuvant therapy and 37.6 months (95% CI: 20.9-54.4) in patients not receiving adjuvant therapy. The 8.3-month survival difference was statistically insignificant (P = 0.54). The 1-, 3-, and 5-year OS rates were 87.5% versus 77.4%, 58.4% versus 51.6%, and 40.8% versus 27.6% for patients with and without adjuvant therapy, respectively. Pathological stage (P = 0.028) and lymph node status (P = 0.044) were significant prognostic factors for survival. CONCLUSIONS: This study did not support the benefit of adjuvant treatment compared with surgery alone in completely resected EC patients. The reason for this result may be related to the small sample size and different treatment regimens due to the change in treatment options over time.

Treatment Outcomes and Prognostic Factors in N3 Stage Gastric Cancer After Curative Resection: A Real World Data.

Purpose: N3 gastric cancer is characterized by a fairly high lymph node metastasis burden and poor outcome despite optimal therapy. Given the limitations of TNM classification, a comprehensive evaluation tool is necessary to predict the prognosis of patients with N3 gastric cancer who underwent curative surgery. This study aims to explore the outcomes and clinicopathologic prognostic factors affecting the overall survival (OS) of patients with N3 gastric cancer after surgery. Methods: Data on patients with N3 gastric cancer who underwent (sub)total gastrectomy and regional lymph node dissection between November 2005 and September 2018 (n = 169) were analyzed by Cox regression to determine the independent prognostic factors for OS. Results: The multivariable analysis established that gender, patient performance status, metastatic lymph node ratio (MLNR), tumor grade, and adjuvant chemotherapy are significantly associated with OS. The five-year OS of the study population was 15%. Adjuvant chemoradiotherapy was applied to 72% of the patients, which resulted in an improvement in recurrence-free survival but not OS. Recurrence occurred in 103 (75%) patients, in which the most frequent recurrence site was distant metastasis. Conclusion: Male gender, poor performance status, grade 3 tumor, MLNR > 0.37, and not receiving adjuvant chemotherapy are predictors of poor prognosis in N3 gastric cancer after curative resection. Considering the high recurrence rates of this group, prospective studies are needed to optimize treatment strategies.

Simple and easily accessible prognostic markers in ewing sarcoma; neutrophil-lymphocyte ratio, neutrophil-platelet score and systemic-inflammation index.

Background: Inflammation markers are the new point of view in cancer due to increasing data on the interaction of immune system with tumor cells and their prognostic and predictive importance were found in many different types of solid tumors. Therefore, we aimed to evaluate the prognostic value of neutrophil-lymphocyte ratio (NLR), neutrophil-platelet score (NPS), and systemic inflammation index (SII) in Ewing sarcoma patients in which risk groups are still not clearly defined. Methods and Results: A total of 64 patients were evaluated retrospectively. Receiver operating characteristic analysis was performed to find cut-off values for NLR and SII. Survival analysis was calculated by using Kaplan-Meier method. Cox regression analysis was performed to determine prognostic factors such as age, stage, and neoadjuvant chemotherapy were statistically significant prognostic factors for OS in multivariate analysis. While patients with low NLR and SII had longer OS (P = 0.003 and P = 0.018), patients with high NPS score had shorter OS (67.7 vs 21.7 months, P = 0.001). Conclusion: Patients with lower NLR, NPS, and SII score have a better prognosis compared with those with higher NLR, NPS, and SII score and these simple parameters may be monitoring tools of the tumor microenvironment.

The Prognostic and Functional Impact of Sprouty 2 Expression in Non-small Cell Lung Cancer.

OBJECTIVE: We represent Sprouty 2 (Spry2) expression analysis and its association with key driver mutations and clinical features of patients with non-small cell lung cancer as the largest ex vivo data. METHODS: The strength of Spry2 expression was evaluated using the immunoreactivity score (IRS), which was calculated using the following formula: IRS=(staining intensity score) SI×(percentage of positively stained cells) PP. The median IRS score was defined as the cutoff value. Patients were grouped as "weak immunoreactivity score" (IRS: 0 to 4) or "strong immunoreactivity score" (IRS: ≥4) with respect to the IRS score. RESULTS: The intensity and percentage of Spry2 staining were significantly lower in tumor tissues than in normal lung tissues ( P <0.0001). Patients' characteristics were similar for both groups, except for smoking status and, brain and lymph node metastasis. Overall survival of patients with a strong immunoreactivity score was significantly lower than those with a weak immunoreactivity score among metastatic patients (6.9 mo vs. 13.6, P =0.023) and adenocarcinoma histology (7.0 mo vs. not reached, P =0.003). CONCLUSION: Spry2 expression was lower in tumor tissues than in normal lung parenchyma. Increased expression of Spry2 is associated with poor prognosis. There were no significant associations between epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1 rearrangement and Spry2 expression. Despite the absence of KRAS mutational analysis, the clinical and epidemiological features of patients suggested that KRAS mutation might be an underlying determinant factor of the functional role of Spry2 in non-small cell lung cancer.

Albumin-to-Alkaline Phosphatase Ratio: Does It Predict Survival in Grade 1 and Grade 2 Neuroendocrine Tumors?

OBJECTIVES: Neuroendocrine tumors (NETs) are very heterogeneous tumors. This study aimed to evaluate prognostic value of an albumin-to-alkaline phosphatase (ALP) ratio (AAPR) in well-differentiated NETs. METHODS: A total of 110 patients were included in this study. Albumin-to-alkaline phosphatase ratio was calculated by dividing albumin concentration (g/dL) to ALP level (U/L). Cutoff value for AAPR was determined by receiver operating characteristic analysis. Survival analysis was performed by Kaplan-Meier method with the log-rank test. A P value of less than 0.05 was considered statistically significant. RESULTS: The optimum cutoff value for AAPR was 0.028. Patients were divided into 2 groups as patients with AAPR of 0.028 or less (n = 22, 20%) and with AAPR of greater than 0.028 (n = 88, 80%). Patients with AAPR of greater than 0.028 had statistically longer overall survival compared with patients with 0.028 or less (not reached vs 96.8 months, P = 0.001). In addition, AAPR has been shown to be an independent prognostic factor for overall survival in multivariate analysis (hazard ratio, 3.99; 95% confidence interval, 1.26-12.61, P = 0.018). CONCLUSIONS: Patients with higher AAPR had more favorable prognosis compared with patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.

The evaluation of the role of BMI and insulin resistance on inflammatory markers, PAI-1 levels and arterial stiffness in newly diagnosed type 2 diabetes mellitus patients.

BACKGROUND: Increased cardiovascular risk, represented by endothelial inflammation, probably starts with the very first course of type-2 diabetes (T2DM). Almost 85.2% of all T2DM patients are overweight or obese. Thrombosis accounts 80% of all deaths in patients with diabetes. The thrombotic-fibrinolytic equilibrium shifts in favor of thrombosis by plasminogen activator inhibitor-1 (PAI-1). PAI-1 secretion is induced primarily by CRP. PAI-1 overexpression predisposes unstable plaque development. The contribution of obesity and diabetes to this process is not clearly understood. In this study, we aimed to investigate comparison of inflammatory markers, PAI-1 levels and arterial stiffness according to BMI and impaired glucose metabolism in patient with newly diagnosed T2DM. METHODS: Newly diagnosed 60 T2DM patients were enrolled. Demographics and measurements were noted. Liver (AST, ALT), kidney (urea, creatinine, albumin/creatinine ratio), metabolic (fasting blood glucose, post-prandial blood glucose, insulin, c-peptide, HbA1c, total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglyceride) parameters, inflammatory markers [hsCRP, fibrinogen]), PAI-1 levels and pulse wave velocity was measured from all participants. The results were compared. RESULTS: Inflammatory markers and PAI-1 levels were significantly elevated in obese group compared to overweight participants. The correlation analysis showed that waist and hip circumferences, high-sensitive CRP, fibrinogen and PAI-1 levels were positively correlated with BMI but not with HbA1c levels. CONCLUSIONS: The results of our study showed that lipid levels, glycemic and blood pressure values of the obese and overweight patients were similar. BMI affects inflammatory markers and PAI-1 levels independent of glucose regulation and insulin resistance in newly diagnosed T2DM. According to the current study BMI is found to be more prominent in terms of inflammatory markers and PAI-1 levels compared to insulin resistance and impaired glucose metabolism in newly diagnosed T2DM.