Prognostic value of translationally controlled tumor protein in colon cancer.

The translationally controlled tumor protein (TCTP) is a highly conserved protein involved in a variety of normal cell functions and disease processes. Preclinical studies revealed that TCTP has anti-apoptotic properties, promotes cell growth and division and is involved in cancer progression by promoting invasion and metastasis. The present study explored the potential value of TCTP as a prognostic marker in colon cancer. A retrospective analysis of 74 patients with colon cancer was performed. Using immunohistochemistry, TCTP levels in the primary tumor were assessed semi-quantitatively by the calculation of cytoplasmic and nuclear H-score. Cytoplasmic TCTP levels in the primary tumor had no statistically significant association with disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) in the present patient population. Patients whose primary tumors had a negative nuclear TCTP expression had significantly improved clinical outcomes. The PFS for the negative nuclear TCTP expression group was 7.7 months [95% confidence interval (CI), 5.8-9.5] compared with 5.5 months (95% CI, 3.2-7.8) in the group with positive nuclear expression (P=0.023, Mantel-Cox log-rank). Patients with a negative nuclear expression of TCTP had a significantly higher median OS (22.2 months; 95% CI, 16.1-28.3) compared with those with positive TCTP nuclear expression (median 13.2 months; 95% CI, 10.1-16.3; P=0.008, Mantel-Cox log-rank). In a multivariate Cox regression model, a positive nuclear TCTP H-score was an independent risk factor for worse PFS and OS. The 1-year OS rate in the group with negative nuclear TCTP expression was 86.3% compared with 56.5% in patients with positive nuclear TCTP expression (P=0.008). The present study suggested that semiquantitative H-score measurement of TCTP levels in the nuclei of tumor cells from the primary tumor is a potential prognostic marker for clinical outcomes in patients with colon cancer.

Real-World Testing Practices, Treatment Patterns and Clinical Outcomes in Patients from Central Eastern Europe with EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Retrospective Chart Review Study (REFLECT).

The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored EGFR/T790M testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here. This physician-led chart review study was conducted in patients with confirmed-EGFRm NSCLC initiating 1L 1G/2G EGFR TKIs between 2015-2018. The CEE cohort included 389 patients receiving 1L erlotinib (37%), afatinib (34%), and gefitinib (29%). Overall, 320 (82%) patients discontinued 1L, and 298 (77%) progression events were registered. Median progression free survival on 1L TKIs was 14.0 (95% CI: 12.6-15.6) months. Median overall survival from 1L start was 26.6 (95% CI: 24.1-29.0) months. Attrition rate between 1L and next line was 30%. Among patients with 1L progression, 200 (67%) were tested for T790M and 58% were positive. This first CEE analysis of treatments and outcomes in EGFRm NSCLC patients highlights the importance of using the most efficacious therapies currently available in 1L to reduce attrition and improve patient outcomes.

Impact of travel burden on clinical outcomes in lung cancer.

PURPOSE: Our study explores the influence of travel burden (measured as travel distance and travel time) on clinical outcomes in lung cancer patients. METHODS: A retrospective analysis of a single Bulgarian center was performed. A total of 9240 lung cancer patients were included in the study. Travel distance and travel time between patients' city of residence and the treating facility were calculated with an online tool to determine the shortest route for travel using the existing road network. The probability of survival was estimated using the Kaplan-Meier method, and differences in survival in each subgroup were evaluated with a log-rank test. RESULTS: About one third of all included patients were living in the same city as the treating facility (n = 2746, 29.7%). Overall survival in our patient population was significantly lower with increasing travel distance (p < 0.001, Mantel-Cox log rank) and travel time (p < 0.001, Mantel-Cox log rank). The 1-year OS rate according to travel distance was 27.1% in the same city group, 22.4% in < 50-km group, and 20.5% in ≥ 50-km group (p < 0.001). The corresponding values for the 5-year OS rate were 2.9%, 2.6%, and 1.4% (p < 0.001). CONCLUSION: In this retrospective study, we discovered significant differences in the overall survival of patients with lung cancer depending on travel distance and travel time to the treating oncological facility. Despite having similar clinical and pathological characteristics (age, sex, stage at initial diagnosis, histologic subtype), the median overall survival was significantly lower in those subgroups of patients with a higher travel burden.

Treatment patterns, testing practices, and outcomes in the pre-FLAURA era for patients with EGFR mutation-positive advanced NSCLC: a retrospective chart review (REFLECT).

INTRODUCTION: For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval. METHODS: Retrospective chart review (NCT04031898) of European/Israeli adults with EGFRm unresectable locally advanced/metastatic NSCLC, initiating 1 L 1G/2G EGFR-TKIs 01/01/15-30/06/18 (index date). RESULTS: In 896 patients (median follow-up of 21.5 months), the most frequently initiated 1 L EGFR-TKI was afatinib (45%). Disease progression was reported in 81%, including 10% (86/896) who died at 1 L. By the end of study, most patients discontinued 1 L (85%), of whom 33% did not receive 2 L therapy. From index, median 1 L real-world progression-free survival was 13.0 (95% confidence interval (CI): 12.3-14.1) months; median overall survival (OS) was 26.2 (95% CI: 23.6-28.4) months. 71% of patients with 1 L progression were tested for T790M; 58% were positive. Of those with T790M, 95% received osimertinib in 2 L or later. Central nervous system (CNS) metastases were recorded in 22% at index, and 15% developed CNS metastases during treatment (median time from index 13.5 months). Median OS was 19.4 months (95% CI: 17.1-22.1) in patients with CNS metastases at index, 24.8 months (95% CIs not available) with CNS metastases diagnosed during treatment, and 30.3 months (95% CI: 27.1, 33.8) with no CNS metastases recorded. CONCLUSION: REFLECT is a large real-world study describing treatment patterns prior to 1 L osimertinib availability for EGFRm advanced NSCLC. Given the attrition rates highlighted in the study and the impact of CNS progression on outcomes, offering a 1 L EGFR-TKI with CNS penetration may improve patient outcomes in this treatment setting.

Fast time perception is associated with high levels of anxiety in cancer patients prior to starting chemotherapy.

Our study explored the potential relationship between time perception and the level of anxiety in cancer patients prior to starting chemotherapy. Time perception was assessed in 162 chemonaïve patients with solid tumors by evaluating each subject's prospective estimation of how fast one minute passed compared to the actual amount of time passed. The median value of time perception was used to stratify the patients into two categories of fast and slow time perception. We used the generalized anxiety disorder questionnaire (GAD-7) as a screening tool for detecting levels of anxiety. Scores ≥ 10 were considered high. In total, 45 (27.8%) patients had high levels of anxiety. The pattern of the time perception distributions significantly changed according to the reported levels on the GAD-7 scale. Scores ≥ 10 correlated with fast time perception and the female gender. Patients with a fast time perception had significantly higher levels of anxiety (8.44 ± 5.1) than patients with a slow time perception (3.49 ± 4.3). ROC analysis revealed that at the optimal cut-off value of time perception, clinically significant levels of anxiety can be discriminated with an AUC = 0.78 (95% CI: 0.70-0.85, p < 0.001), a sensitivity of 82.2% and a specificity of 64.1%. Moreover, in a multivariate logistic regression model, fast time perception was an independent predictor of clinically significant levels of anxiety (OR: 8.24; 95% CI: 3.16-21.41, p < 0.001). Time perception is a novel potent indicator for high levels of anxiety in cancer patients.

One-minute time interval estimation as a novel ultrashort tool for distress screening.

PURPOSE: Our study explores the potential relationship between time estimation and level of distress in cancer patients prior to starting chemotherapy. METHODS: Time estimation was assessed in 262 chemonaïve patients with solid tumors by evaluating each subject's prospective estimation of how fast 1 min passed compared to the actual time. The median value (40 s) of time estimation was used to stratify the patients into two categories of fast and slow time estimation. The National Comprehensive Cancer Network Distress Thermometer was used at the beginning of treatment to evaluate levels of distress. Patients scoring 4 or above (51.9%) were regarded as having high levels of distress. RESULTS: The pattern of the time estimation distributions significantly changed according to the level of distress. Patients with a fast time estimation had significantly higher levels of distress (4.55 ± 3.1) than patients with a slow time estimation (3.3 ± 2.9) (p = 0.001). ROC analysis revealed that at the optimal cutoff value of time estimation, patients with low and high distress levels can be discriminated with an AUC = 0.60 (95% CI: 0.53-0.67, p = 0.005) and with a sensitivity of 62.5% and specificity of 53.2%. Moreover, in a multivariate logistic regression model, fast time estimation was an independent predictor of high levels of distress. CONCLUSION: Time estimation is a novel potent indicator of high levels of distress in cancer patients. This test is an easily performed, time-saving, and nonintrusive ultrashort screening tool that is even suitable for patients who are not willing to reveal their level of distress via direct questionnaires.

The EGFR ligands amphiregulin and heparin-binding egf-like growth factor promote peritoneal carcinomatosis in CXCR4-expressing gastric cancer.

PURPOSE: Peritoneal carcinomatosis, often associated with malignant ascites, is the most frequent cause of death in patients with advanced gastric cancer. We previously showed that the CXCR4/CXCL12 axis is involved in the development of peritoneal carcinomatosis from gastric cancer. Here, we investigated whether epidermal growth factor receptor (EGFR) ligands are also involved in the development of peritoneal carcinomatosis from gastric cancer. EXPERIMENTAL DESIGN: The functional involvement of expression of the ErbB family of receptors and/or EGFR ligands was examined in CXCR4-expressing human gastric cancer cells and fibroblasts, clinical samples (primary tumors and ascites), and an animal model. RESULTS: High concentration of the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF), as well as of CXCL12, were present in malignant ascites. Human gastric cancer cell lines and primary gastric tumors, with high potential to generate peritoneal carcinomatosis, expressed high levels of EGFR and CXCR4 mRNA and protein. Both amphiregulin and HB-EGF enhanced the proliferation, migration, and functional CXCR4 expression in highly CXCR4-expressing gastric cancer NUGC4 cells. Amphiregulin strongly enhanced the proliferation of NUGC4 cells, whereas HB-EGF markedly induced the migration of fibroblasts. Moreover, HB-EGF and CXCL12 together enhanced TNFα-converting enzyme (TACE)-dependent amphiregulin shedding from NUGC4 cells. In an experimental peritoneal carcinomatosis model in mice, cetuximab effectively reduced tumor growth and ascites formation. CONCLUSIONS: Our results strongly suggest that the EGFR ligands amphiregulin and HB-EGF play an important role, interacting with the CXCL12/CXCR4 axis, in the development of peritoneal carcinomatosis from gastric cancer, indicating that these two axes may be potential therapeutic targets for peritoneal carcinomatosis of gastric carcinoma.