Relationship between prognostic nutritional index and neutrophil lymphocyte ratio with overall survival in patients with metastatic colorectal cancer receiving regorafenib.

Aim: In this study, we aimed to analyze the effect of prognostic nutritional index and neutrophile lymphocyte ratio on the overall survival (OS) in patients treated with regorafenib. Materials and Methods: Metastatic colorectal cancer (CRC) patients who treated with regorafenib between 2016 and 2020 in a single center were evaluated retrospectively. ROC analysis was used for neutrophile lymphocyte ratio (NLR's) and prognostic nutritional index (PNI's) optimum cut-off value. The relationship between OS with PNI and NLR was investigated. Results: Fifty-two patient's data were analyzed. The median age was 57 years, 22 (41.5%) of the patients were female. The optimal cut-off value of PNI for OS was 45.7 according to ROC curve analysis. The median NLR value was accepted as 2.7. Median OS was 8.3 months. Patients who have high PNI value than 45.7 had longer OS (12.09 months vs. 6.31 months hazard ratio [HR]: 0.37 95% confidence interval [CI]: 0.19-0.73 P = 0.003) and there was a tendency for longer OS with low NLR value then median (12.05 months vs. 6.14 months HR: 0.54 95% CI: 0.29-1.23 P = 0.057). Primary tumor resected patients had longer OS than nonresected patients (12.05 months vs. 6.30 months HR: 0.34 95% CI: 0.17-0.66 P = 0.001). In multivariate analysis, high PNI value more than 45.7 (HR: 0.40 95% CI: 0.18-0.88 P = 0.02) and resection of the primary tumor (HR: 0.40 95% CI: 0.21-0.80 P = 0.01) were the only independent factors for longer OS. Conclusion: Metastatic CRC patients with high pretreatment PNI and primary tumor resected are more likely to have longer OS with regorafenib. PNI is more reliable index than NLR to predict OS in metastatic CRC patients treated with regorafenib.

Comparison of real-life data from patients with NGS panel negative and KRAS mutation positive metastatic lung adenocarcinoma.

OBJECTIVE: To evaluate clinical and demographic characteristics and the results of cytotoxic treatments of KRASG12C, KRASother, and next-generation sequencing (NGS) panel negative patients. METHODS: NGS data of 1264 patients with non-small cell lung cancer were retrospectively evaluated. Among these patients, the mutation distributions of 1081 patients with metastatic lung adenocarcinoma were analyzed. A total of 150 patients with negative NGS panel or mutant KRAS followed up in our clinic were included. Clinical features, overall survival, first-line chemotherapy responses, and progression-free survival of NGS panel negative, KRASG12C, and KRASother groups were compared. RESULTS: In 1081 patients who underwent NGS from tumor tissue with the diagnosis of metastatic lung adenocarcinoma, 296 (27%) NGS panel negative and 276 (26%) KRAS mutant patients were detected. Among these patients, 150 patients whose data were available were 71 (47.3%) NGS panel negative, 54 (36%) KRASother, and 25 (16.7%) KRASG12C. Clinical features, brain metastasis, and first-line chemotherapy response were similar among groups. Bone metastases were detected more often in the NGS panel negative group (p = 0.03). The median follow-up was 8.4 months. Overall, 107 deaths had occurred at the time of analysis. There was no difference in overall survival (p = 0.56) or progression-free survival (p = 0.71) among NGS panel negative, KRASother, and KRASG12C patients. CONCLUSION: There is no difference in overall survival, first-line chemotherapy response, or progression-free survival among patients with NGS panel negative, KRASG12C, or KRASother metastatic lung adenocarcinoma. Bone metastases were observed more frequently in the NGS panel negative group.

Prognostic nutritional index and its dynamics after curative treatment are independent prognostic factors on survival in non-metastatic nasopharyngeal carcinoma.

PURPOSE: We aimed to identify the prognostic and predictive values of post-treatment prognostic nutritional index (PNI) and PNI dynamics in nasopharyngeal cancer patients (NPC) in this study. METHODS: One hundred seven non-metastatic NPC patients were included. PNI was calculated by using the following formula: [10 × serum albumin value (gr/dL)] + [0.005 × total lymphocyte count (per mm3)]. ROC analysis was used for determining prognostic PNI values and univariate and multivariate statistical analyses for prognostic characterization of PNI. RESULTS: The statistically significant cut-off values for pre- and post-treatment PNI were 50.65 and 44.75, respectively. Of the pre-treatment PNI analysis, PNI ≤ 50.65 group had shorter loco-regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Furthermore, for post-treatment PNI analysis, PNI ≤ 44.75 group had shorter LRRFS and OS. In univariate analysis, only pre-treatment PNI was associated with LRRFS and DMFS, while pre- and post-treatment PNI were both associated with OS. In multivariate analysis, both PNI were independent prognostic markers for OS. In the combined analysis, pre- and post-treatment PNI, differences between the groups were statistically significant, and the PNI dynamics was an independent prognostic indicator for OS. CONCLUSION: PNI is a useful, independent prognostic marker for non-metastatic NPC patients. It is used for either pre- or post-treatment patients. Furthermore, changes in pre-treatment PNI value after curative treatment is a significant indicator for OS.

Prognostic Factors for Survival in Transverse Colon Cancers.

BACKGROUND: Transverse colon cancer (TCC) is a rare condition that accounts for 10% of all colon cancers. TCC was accepted more likely right-sided colon cancers. We aimed to investigate whether TCC differs from other colon tumors by using clinical, pathological, and molecular prognostic factors known to be important in colon cancer and if it differs in its own anatomical structure. PATIENTS AND METHODS: We evaluated local and locally advanced TCC patients between 2007 and 2020 years for demographics data, symptoms, treatment status, and histopathological and molecular features. RESULTS: Overall, 107 TCC patients were included in this study. According to the molecular data analysis of 44, 35, and 23 patients for MSI, RAS, and BRAF status, respectively, 7 (15.9%) were MSI-H, 13 (37.1%) were RAS mutant, and 11 (47.8%) had BRAF V600E mutation. The median follow-up time was 31.5 months. Median disease-free survival (DFS) was 5.19 months, and median OS was 88.3 months for the whole study population. The tumor stage was the most significant prognostic factor for DFS and OS. Although BRAF mutation was not a significant marker for DFS, it was an independent prognostic marker for OS (HR 3.90 95% CI 1.42-10.7). There were no statistically significant differences between proximal two-thirds and distal one-third tumor location. CONCLUSION: TCC has molecular features and prognostic factors more likely RCC and no differences between proximal and distal sub-parts. BRAF V600E mutation status is an independent predictor of survival even in the early stages of TCC.

Is early change in systemic inflammatory markers associated with treatment response in patients who received pazopanib?

PURPOSE: To demonstrate whether early changes in systemic inflammatory markers are related with pazopanib treatment response in soft tissue sarcoma and renal cell carcinoma. METHODS: Forty-one patients with metastatic clear cell renal carcinoma (mRCC) (n=22) and advanced stage soft tissue sarcoma (STS) (n=19) were assessed. Systemic inflammatory markers such as neutrophils, lymphocytes, c-reactive protein (CRP), mean platelet volume (MPV), lactate dehydrogenase (LDH) and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at both baseline and 1-month of pazopanib treatment were obtained and their relation with the first radiological response about 3-months later after pazopanib treatment was evaluated. RESULTS: Disease control rate (DCR) at the first initial radiological evaluation was 58.5 % for all, it was 77.3% for the RCC group and 36.8% in the STS group. Serum neutrophil, NLR and CRP levels were significantly decreased from baseline in RCC patients who had DCR with pazopanib treatment. Also, serum CRP levels after pazopanib treatment was significantly lower in RCC patients who had DCR (+) rather than those who progressed. CONCLUSIONS: Early decline in serum CRP, neutrophil and NLR levels in RCC patients who received pazopanib at the first month was significantly associated with disease control, assuming a predictive role for the first radiological assessment. However, there was no significant association between change in serum inflammatory marker levels and disease control in STS patients.

Real-life data on first-line Sunitinib and Pazopanib therapy in metastatic renal cell carcinoma patients: a single center experience.

PURPOSE: In this study, we aimed to compare the data of sunitinib and pazopanib used in the first-line treatment of metastatic renal cell carcinoma (RCC) cases and to evaluate the effective factors in terms of survival. METHODS: The records of 125 patients with metastatic RCC admitted between January 2005 and February 2018 were retrospectively analyzed and 63 patients who received pazopanib or sunitinib were included in the study while 62 patients were excluded due to insufficient data. Clinical and histological characteristics, treatment responses, progression-free survival (PFS), and overall survival (OS) of the patients were compared. RESULTS: Patients with metastatic RCC who received pazopanib or sunitinib as tyrosine kinase inhibitors (TKI) in first-line treatment were analyzed; 45 (71.4%) were male while 18 (28.6%) were female, and the median age was 60. 43 (68.3%) patients were treated with sunitinib and 20 (31.7%) with pazopanib. PFS ​​of pazopanib and sunitinib were 10.6 and 7.2 months, respectively. Median OS was 14.5 months in patients receiving pazopanib and 13.6 months in those receiving sunitinib. There was no statistical difference in PFS and OS between both treatments. The median OS of clear-cell RCC was 15.2 months, while of non-clear-cell RCC was 7.7months. CONCLUSIONS: High ECOG score, non-clear-cell histology, presence of liver metastasis in metastatic RCC patients were found to be associated with shorter OS and PFS. Sunitinib and pazopanib produced similar OS and PFS rates in first-line treatment of metastatic RCC.

Skeletal muscle loss during anti-epidermal growth factor receptor therapy is an independent prognostic factor on non-small cell lung cancer patients survival.

PURPOSE: We aimed to assess whether skeletal muscle loss during EGFR thyrosine kinase inhibitor therapy of advance non-small cell lung cancer patients is an independent prognostic factor for progression-free survival (PFS) and overal survival (OS). METHODS: A total of 45 patients who had computed tomography images were retrospectively evaluated at the diagnosis and during the treatment period before progression occurs. RESULTS: During treatment 19 patients (42.2%) had skeletal muscle loss. Objective response rates in muscle loss group and muscle stable group were 36.8% and 73.0%, respectively (p<0.01). Median follow-up time was 18.9 months (14.8-32.1). Median PFS was 14.7 months (95% CI 12.1-17.3) in muscle stable group and 7.6 months (95% CI 6.7-8.5) in muscle loss group (p<0.01). Median OS was 18.3 months (95% CI 16.5-20.2) in muscle loss group while it was 30.1 months (95% CI 22.1-38.2) in muscle stable group (p<0.01). In multivariate analysis for both PFS and OS, skeletal muscle loss was an independent prognostic factor. Hazard ratios (HR) for PFS and OS were 12.2 (95% CI 4.3-34.4) and 3.51 (95% CI 1.41-8.73) respectively. CONCLUSION: On CT imaging skeletal muscle loss before progression is an independent prognostic factor for both PFS and OS in advance non-small cell lung cancer patients who received EGFR tyrosine kinase inhibitor therapy.

The relation between tissue galectin-3 level and platinum resistance in neoadjuvant bladder cancer treatment.

PURPOSE: This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy. METHODS: The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above. RESULTS: There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37). CONCLUSION: The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.

Contrast nephropathy in cancer patients receiving anti-VEGF therapy: a prospective study.

OBJECTIVES: Contrast nephropathy risk has been increasing in cancer patients. Nephrotoxic side effects of anti-vascular endothelial growth factor/receptor (anti-VEGF/R) drugs used in oncologic treatment are also prominent. The purpose of this study was to identify the possible association among anti-VEGF/R drugs use and development of the contrast-induced nephropathy (CIN) in patients with cancers. METHODS: A total of 92 patients were included in this prospective cross-sectional study. Patients whose glomerular filtration rate (GFR) of < 50 ml/min, hemoglobin of < 10 g/dl, and eastern cooperative oncology group (ECOG) score of ≥ 2 and had received nephrotoxic drugs were not included in the study. Blood samples were collected baseline at pre computed tomography (CT) and day 2, day 3 and day 7 later CT imaging. CIN was defined as either an increased serum creatinine value of 0.5 mg/dl or increased 25% to baseline. CIN frequency between groups receivingand not receiving anti-VEGF/R was compared using the chi-squared test. CIN frequency between bevacizumab and other anti-VEGF/R was also analyzed. RESULTS: There were 39 patients in the anti-VEGF/R (+) group and 53 patients in the anti-VEGF/R (-) group. Eleven patients (28%) in the anti-VEGF/R (+) group and 3 patients (5.6%) in the anti-VEGF/R (-) group had CIN (p = 0.006). In the anti-VEGF/R (+) group, 23 patients received bevacizumab (combined with FOLFOX/FOLFIRI), while 16 patients received other anti-VEGF/R (sunitinib, axitinib, regorafenib, aflibercept) effective treatments. CIN ratio in patients who received bevacizumab or other anti-VEGFR therapy was similar (p = 0 = 50). Of the patients, one patient had acute kidney injury leading to death. CONCLUSION: CIN was significantly more frequent in cancer patients who receiving anti-VEGF/R drugs than those not receiving anti-VEGF/R drugs.

Comparison of skeletal muscle mass loss in patients with metastatic colorectal cancer treated with regorafenib or TAS-102.

PURPOSE: To assess whether regorafenib and TAS-102 treatments are associated with a change in Skeletal Muscle Area (SMA) as well as to compare Skeletal Muscle Mass (SMM) loss levels between regorafenib and TAS-102 treatments and prognostic significance in the patients with metastatic colorectal cancer (mCRC). METHODS: A total of 36 mCRC patients, who received regorafenib or TAS-102 in the third-line and subsequent settings were assessed in the analysis. SMM changes were assessed with CT scans findings, and they were categorized into two groups as SMM-loss (SMM decrease ≥2%) and SMM-stable (SMM change <2%). RESULTS: The SMM change after regorafenib therapy was significantly worse compared with TAS-102 therapy (p=0.001). The median overall survival (OS) was longer in SMM-stable group than in SMM-loss group (12.8 months; 95%CI:9.8-15.7) vs. 6.4 months; 95%CI:5.2-7.7, respectively;p=0.04). Cox regression analysis showed that SMM loss was independent prognostic indicator for OS (HR, 2.87; 95%CI: 1.07-7.42, p=0.03). CONCLUSION: Although patients who received regorafenib had more SMM loss than those who received TAS-102, there was no difference in OS between drugs.

Is the Charlson Comorbidity Index a Prognostic Indicator for Toxicity and Mortality in Elderly Patients with Locally Advanced Rectal Cancer?

BACKGROUND: Aging is significantly related to multiple comorbidities. Even with a good performance score, some elderly patients may have poor survival outcomes. We aimed to evaluate the prognostic value of the Charlson comorbidity index (CCI) for mortality and toxicity in elderly patients with locally advanced rectal cancer (LARC). METHODS: Seventy-two elderly patients with LARC who were treated with neoadjuvant chemoradiotherapy (CRT) were included. Based on their CCI score, severity of the comorbidity was categorized into 2 groups: CCI<7 and CCI≥7. RESULTS: The overall survival (OS) at 5 years was 54.4 percent in patients treated with neoadjuvant CRT. Median OS was not reached for all patients as well as patients with CCI score <7, but median OS was 25 (95% CI 1.0-62.1) months in patients with CCI≥7 (P=0.002). The OS at 2 years was 79.1 percent in the patients with CCI <7 and 50.0 percent in the patients with CCI score ≥7 (P=0.002). Moreover, there was a trend toward, patients with higher CCI score who had more treatment related to grade 3 or 4 toxicity compared to those with CCI score <7 (33.3% vs 13.3%, respectively, P=0.09). Multivariable analysis indicated that the CCI score ≥7, presence of down-staging after therapy and clinical stage (III) independently predict mortality (HR 6.14, 95%CI 2.45-15.35, P<0.001) in patients with LARC. CONCLUSION: Although CCI score was not significantly associated with both toxicity and disease-free survival (DFS), we suggest that baseline CCI score might be a valuable prognostic indicator for physicians to evaluate elderly patiens with LARC for optimal treatment.

Changes in skeletal muscle area and lean body mass during pazopanib vs sunitinib therapy for metastatic renal cancer.

PURPOSE: To evaluate whether sunitinib and pazopanib treatments are associated with change in skeletal muscle area (SMA) and total lean body mass (LBM) as well as to compare their efficacies and safety profiles in patients with metastatic renal cell cancer (mRCC). METHODS: Thirty-six patients treated with a tyrosine kinase inhibitor were included. Eighteen of them received sunitinib and the rest/remaining received pazopanib in the first line of mRCC treatment. Baseline and follow-up computed tomography studies of the patients were performed to measure cross-sectional areas (cm2) of muscle tissues. RESULTS: About 69% of patients were male and median age was 60 (49-68) years. Median time interval between two CT imagings was 6.1 (3.1-7.7) months and it was similar between the two groups (for sunitinib, 4.9 (2.5-6.9) months vs for pazopanib, 7.3 (3.2-9.5) months, p = 0.16, respectively). Disease control rate was 77.7% in all patients. Of these, 66.6% in sunitinib group was consisted of four partial responses and eight stable diseases. In addition, 88.8% in pazopanib group was consisted of three partial responses and 13 stable diseases. A significant decrease in SMA and LBM was observed after sunitinib therapy, whereas SMA and LBM values of pazopanib group did not change significantly (p = 0.02 and p = 0.70, respectively). No significant differences were observed between patients with sunitinib, and pazopanib group median PFS [11.9 (95% CI 6.1-17.6) vs 8.1 months (95% CI 7.2-9.1), respectively; p = 0.28] and median OS [28.6 (95% CI 24.3-32.9) vs 25.5 months (95% CI 18.9-52.7), respectively; p = 0.42]. Dose-limiting toxicities were significantly more frequent in sunitinib group than in pazopanib group (66.7% vs 22.2%, p = 0.02, respectively). CONCLUSIONS: Loss of SMA and LBM with sunitinib was more substantial than with pazopanib. Treatment efficacies of both drugs were similar, but dose-limiting toxicity was more frequent in sunitinib group. Loss of SMA had no significant association with prognosis. Further studies are needed to clarify the possible association between SMA and prognosis in mRCC patients who receive sunitinib or pazopanib.

Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

PURPOSE: To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting. MATERIALS AND METHODS: The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months. RESULTS: A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16-0.54, p < 0.001). Median OS was 12.0 months (95% CI 8.1-15.9) in rechallenge versus 6.6 months (95% CI 6.0-7.3) in regorafenib group (p < 0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16 months (95% CI 7.15-11.18) versus with that recorded in the regorafenib group of 3.41 months (95% CI 3.01-3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand-foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge. CONCLUSIONS: Rechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.

Value of MRI apparent diffusion coefficient for assessment of response to sorafenib in hepatocellular carcinoma.

PURPOSE: Efficient and adequate evaluation of therapeutic response in hepatocellular carcinoma (HCC) is an evolving field. We aimed to evaluate apparent diffusion coefficient (ADC) values in the prediction of response to sorafenib and prognosis in patients with advanced HCC. METHODS: Baseline magnetic resonance (MR) imaging was performed before treatment. After sorafenib started, clinical and radiological response were evaluated at approximately 3 months later. ADC measurements were performed by a 12- year experienced radiologist who evaluated MR before and after sorafenib therapy. RESULTS: A total of 17 patients (median age 60 years, range 51-66 and M/F ratio=3.25/1) were analyzed. A significant increase in ADC levels in responders was observed 3 months after sorafenib therapy. Baseline and post-sorafenib ADC values were not significantly associated with mortality (hazard ratio/HR baseline ADC=1.003, p=0.98) and after sorafenib (HR 0.480, p=0.48, respectively). CONCLUSION: Advanced HCC patients with a favorable response to sorafenib had a significant increase in ADC value at the first radiological evaluation. The predictive and prognostic role of ADC for overall survival is still unknown and further research is needed to investigate any possible association.

Clinical features of the patient with multiple primary tumors: Single center experience.

OBJECTIVE: Multiple primary tumors are the ones that develop in the same patient at the same or different times. They are usually examined under two groups. If the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is named as metachronous tumor. If it is diagnosed in 6 months after the first diagnosis, it is called as synchronous tumor. The malignancy of tumors should be proved histologically. At least 2 cm of solid tissue should be present between two tumors. If they are at localized at the same place, a gap of at least 5 years should be present between them. Metastatic disease should be eliminated. This study aimedto review the clinical, demographic, and pathological features of multiple primary tumors, detect the prevalence, compare the results with literature findings, and evaluate and improve the approach to multiple primary tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors were included in this study. Patient data were obtained from pathology and medical reports of the patients. RESULTS: Most of the multiple primary tumors were metachronous. The number of male patients was more than that of female patients. The median time between double tumors was 3 monthsforsynchronous tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest prevalence of comorbidity were lung-larynx and lung-colon, whereas metachronous tumors with the highest prevalence of comorbidity were lung-bladder, lung-larynx, breast-endometrium, and breast-colon. The history of smoking and alcohol was found to be higher in male patients andsynchronous tumors. CONCLUSION: The detection of the first tumor in the metastatic stage and an accompanying synchronous secondary tumor was found to be a poor prognostic factor. The treatment of the first tumor, smoking, squamous cell histology, and male gender were among the other factors negatively affecting survival, although they were not statistically significant.

Targeted therapy with anaplastic lymphoma kinase inhibitors in non-small cell lung cancer even with brain metastasis.

The incidence of brain metastases has increased as a result of improved systemic disease control and advances in imaging. Brain metastasis can occur approximately in 25-40% of the patients with non-small cell lung cancer (NSCLC) and it is a frequent cause of death. Stereotactic radiosurgery, whole-brain radiotherapy (WBRT) or surgical resection are the local treatment modalities for brain metastases which are feasible either alone, in combination, or as sequential treatments. Resistance to systemic therapy for brain metastasis poses significant clinical problems. In anaplastic lymphoma kinase (ALK)-positive NSCLC patients; ALK inhibitors may provide a new treatment option for brain metastasis and could improve overall survival (OS). Even in patients with crizotinib-resistant disease, second generation ALK inhibitors display prominent clinical activity. There is rapidly emerging preclinical and clinical data showing improvement in this issue. In this article we reviewed the latest literature data concerning the brain metastases and intracranial efficacy of ALK inhibitors in patients with ALK-positive NSCLC.

K-RAS and N-RAS mutations in testicular germ cell tumors.

Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5 non-seminoma cases (26%) [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer.

BACKGROUND: Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. AIMS: We investigated the KRAS mutation status in SCLC and EPSCC. STUDY DESIGN: Mutation research. METHODS: Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. RESULTS: Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). CONCLUSION: In previous studies, the incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC.

Post progression survival analysis of metastatic gastric and gastroesophageal junction cancer patients after second-line treatment.

PURPOSE: The aim of this study was to define the factors that -affect response and post-progression survival of metastatic gastric cancer (MGC) and gastroesophageal junction cancer (GEJ) -patients treated with second-line chemotherapy. METHODS: We retrospectively reviewed the data of 59 patients with MGC or GEJ adenocarcinoma who received second-line treatment. RESULTS: The median age was 54 years old (26-77). Response to second-line treatment was strongly associated with disease control with first-line treatment (p < 0.01). Median progression-free survival (PFS), overall survival (OS) and post-progression survival (PPS) were 3.2 (95% CI : 2.63-3.80), 6.5 (95% CI : 3.78-9.35) and 2.7 months (95% CI : 1.89-3.68), respectively. PFS (r = 0.55, p < 0.01) and PPS (r = 0.89, p < 0.01) were correlated with OS. Response to second-line treatment was independently related to PFS (HR : 0.12 95%CI : 0.53-0.26, p < 0.001). Having an ECOG 0 performance status (HR : 0.42 ; 95%CI : 0.21-0.86, p = 0.02) and response to second-line therapy (HR : 0.47 ; 95%CI : 0.25-0.85, p = 0.01) were independently associated with OS. CONCLUSION: PPS and PFS were correlated with OS after second-line treatment of MGC. Response to second-line treatment prolonged OS by increasing PFS, and having an ECOG 0 PS prolonged OS by increasing PPS.

Unknown primary adenocarcinomas: a single-center experience.

This study aimed to elucidate the clinical and prognostic characteristics of a homogeneous group of patients with cancer of unknown primary (CUP). Between 1999 and 2014, CUP was diagnosed in 159 (1.3%) of 11,742 cancer patients at Trakya University Hospital (Edirne, Turkey). Ninety-seven (61%) of the 159 patients were retrospectively reviewed. Among these, 61 (62.8%) patients with adenocarcinoma were included in this study. The most frequently predicted primary tumor site was the lung (37.7%), and 59% of the patients were smokers. There was a significant relationship between smoking and the lung as a potential primary cancer site (p = 0.042). The most frequent site of metastasis was the liver (60.7%). The median number of metastases per patient was two, but patients with liver metastases had a median of five metastases. The overall median survival time was 7 months. Median survival was significantly longer in patients with a predicted primary site than in patients without the predicted site (7 vs. 6 months, respectively; p = 0.038). When the patients with predicted ovarian and peritoneal tumors were excluded from the comparison, the statistical p value was still close to significant (p = 0.07). Multivariate analysis revealed that smoking, liver metastasis, serum alkaline phosphatase ≥92 U/L, and progression in response to chemotherapy were independent predictors of a poor prognosis. The present study identified several independent prognostic factors in patients with unknown primary adenocarcinomas who received chemotherapy. Smoking, the presence of liver metastasis, and response to chemotherapy were independent risk factors for both progression-free and overall survival.