GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

An advanced c-MET-amplified NSCLC patient that was treated with crizotinib.

INTRODUCTION: c-MET is a tyrosine kinase receptor, which is encoded in part by mesenchymal-epidermal transition (MET) exon 14. Mutations in the MET gene can cause increased c-MET signaling and oncogenic stimulation. Although c-MET mutation is rare, it is a targetable driver mutation. Although the guidelines do not recommend routine screening before treatment decision, there are drugs that can be used in patients who have c-MET mutation or amplification. CASE REPORT: We present a metastatic c-MET-amplified non-small cell lung cancer (NSCLC) patient who was treated with crizotinib. He was not eligible for chemotherapy because of poor performance score; c-MET amplification was investigated after the other common driver mutations were negative. MANAGEMENT AND OUTCOME: After c-MET amplification was shown, crizotinib 250 mg BID was started. A partial response was achieved with the initiation of crizotinib, and his performance score improved after treatment. DISCUSSION: We presented a metastatic c-MET-amplified NSCLC patient, who was not eligible for standard platin doublet chemotherapy, to emphasize the importance of investigating all driver mutations, including c-MET amplification especially in patients who cannot tolerate cytotoxic chemotherapy.

Clinicopathological characteristics, prognosis and survival outcome of gastric cancer in young patients: A large cohort retrospective study.

PURPOSE: To investigate the survival outcome of patients with gastric cancer ≤40 years of age and to compare them to older patients with gastric cancer. METHODS: The study included gastric cancer patients treated between1990 and 2014. Patient demographics, tumor histopathological characteristics and outcome were registered. Patients were classified according to the International Classification of Diseases for Oncology. Two subgroups of patients were created based on age: group 1 (40 years and less at the time of diagnosis, and group 2 (patients older than 40 years). Categorical and continuous variables were analyzed with x2 and Mann-Whitney U tests, respectively. Overall survival (OS) rates were estimated by the Kaplan-Meier method. RESULTS: Diffuse adenocarcinoma was more common in the young group (48.9%) than in the older group (28.9%) (p<0.0001). No statistically significant survival difference was noted between younger (11 months) and older patients (12 months) (p=0.79]. Early stage (p<0.0001), absence of perineural invasion (PNI) (p<0.0001), absence of lymphovascular invasion (LVI) (p<0.0001), and non-cardia tumors (p<0.0001) were associated with better OS rates in univariate analysis. Non-cardia tumors (p=0.016) and stage (p=<0.0001) were independent prognostic factors of survival outcome in multivariate analysis. CONCLUSIONS: This study demonstrated that young and older patients with gastric cancer have similar outcomes in terms of OS.

Receptor discordances after neoadjuvant chemotherapy and their effects on survival.

PURPOSE: To determine estrogen, progesterone and HER2 receptors' discordances after neoadjuvant chemotherapy in patients with locally advanced breast cancer and their effects on survival. METHODS: Data of 186 patients who were admitted to our oncology departments between 2000 and 2014, were retrospectively evaluated. Patients'status of hormone and HER2 receptors were assessed before and after neoadjuvant chemotherapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier and Log-rank tests were used, as appropriate. P<0.05 was considered as statistically significant. RESULTS: Median follow-up was 35 months. Of the patients, 20% had stage II disease and 80% stage III disease. Also, 74% showed hormone receptor positivity and 42% had HER2 overexpression. Hormone receptor discordance was detected in 63 (34%), HER2 discordance was detected in 33 (18%), and any receptor discordance was detected in 74 (40%) patients. There was a statistically significant difference regarding 5-year disease-free survival (DFS) between groups with loss of HER2 overexpression and without loss of HER2 overexpression (p=0.003). Five-year DFS was 60% with loss of any positive receptor status after chemotherapy and 72% with no change in any receptor status (p=0.023). In multivariate analysis, clinical stage (HR: 3.3, 95% CI: 1.18-9.3, p=0.022), changing HER2 status from positive to negative (HR: 2.6, 95% CI: 1.3-5.1, p=0.005), and triple-negative receptor status (HR: 2.64, 95% CI: 1.3-5.6, p=0.001) had significant impact on DFS. CONCLUSION: In patients with locally advanced breast cancer, loss of HER2 overexpression is an independent risk factor for DFS. Further studies are needed to determine the impact of receptor discordances.

Clinical Significance of Serum Membrane-Bound Mucin-2 Levels in Breast Cancer.

This study was conducted to investigate the serum levels of membrane-bound mucin 2 (MUC2) in breast cancer (BC) patients and the relationship with tumour progression and known prognostic parameters. We enrolled 127 female patients with histopathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum MUC2 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method and compared with those of 40 age and sex-matched healthy controls. Median age of diagnosis was 50 (range: 26⁻78). Twenty-eight (22%) patients were metastatic and the most frequent site of metastasis was bone (n = 17, 61%). The median serum MUC2 level of BC patients was significantly higher than that of the controls (198 vs. 54 ng/mL, p < 0.001). There was no significant difference between patients and controls according to known disease-related clinicopathological or laboratory parameters (p > 0.05). Serum MUC2 levels were not associated with survival (p = 0.65). Although serum MUC2 levels might have a diagnostic role, their predictive and prognostic role in survival in BC patients was not detected. Serum levels of MUC2 should be investigated for diagnostic or screening purposes on a larger scale.

Long-lasting response with polycythemia to third-line axitinib treatment in metastatic renal cell carcinoma: Very rare case presentation.

INTRODUCTION: Clear cell renal cell carcinoma is characterized by mutation or inactivation of Von Hippel-Lindau suppressor gene. The mutation of Von Hippel-Lindau mechanism is associated with the upregulation of the hypoxia-inducible factor protein, inducing the overexpression of proteins including erythropoietin and vascular endothelial growth factor. Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors are widely used in treatment of metastatic renal cell carcinoma. In paradoxical hematological effect with tyrosine kinase inhibitor therapies, hemoglobin level may be increased, but polycythemia requiring phlebotomy is very rare. CASE DESCRIPTION: We present here a case of renal cell carcinoma who received successive treatment with sunitinib, everolimus, and axitinib. While he had a normal hemoglobin level with prior sunitinib treatment, on the sixth week of axitinib treatment, he developed polycythemia and treatment response was seen after axitinib-associated polycythemia. CONCLUSION: Progression-free survival (PFS) was 30 months in our case with third-line treatment axitinib. Higher hemoglobin levels may be associated with longer survival. Polycythemia was the first response to treatment of axitinib in our patient. It may be an indicator of persistent treatment response.

What are the optimal treatment modalities according to age group in gastric cancer patients?

Cancer in older people has become an increasingly common problem due to the prolonged life expectancy of the general population. Cancer treatment is challenging but it can be more difficult in geriatric population. Aging is associated with progressive reduction of the body's functional capacity and increased prevalence of chronic diseases. As a result, cancer treatment could cause higher prevalence of serious side effects. In the literature there are only sparse studies about treatment modalities in geriatric gastric cancer patients, therefore our aim was to review the literature concerning this topic and reach a sound conclusion.