Prognostic impact of noninvasive areas in resected pathological stage IA lung adenocarcinoma

Abstract Main Problems In non‐small‐cell lung cancer, ground‐glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma. Methods We analyzed 402 patients with pathological stage (p‐Stage) IA lung adenocarcinoma who underwent surgery in 2013–2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity‐score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p‐T), p‐Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non‐LPA), the prognostic impact of NIAs was evaluated. Results Patients were divided into NIA‐present (N = 231) and NIA‐absent (N = 171) groups. Multivariable analysis showed that NIA‐present was strongly associated with earlier p‐T, earlier p‐Stage, LPA, and epidermal growth factor receptor mutation. Kaplan–Meier survival analysis showed that the NIA‐present group displayed a better prognosis than the NIA‐absent group in disease‐free survival (DFS) and overall survival (OS) (5‐year DFS 94.6% vs. 87.2%, 5‐year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA‐present and NIA‐absent groups (5‐year DFS 92.4% vs 89.6%, 5‐year OS 95.6% vs 94.3%). Conclusions Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors

Biochemical failure after radical prostatectomy in intermediate-risk group men increases with the number of risk factors

Introduction: We aimed to determine whether the number and type of risk factors are associated with biochemical recurrence-free survival after radical prostatectomy in men with D'Amico intermediate-risk prostate cancer. Materials and Methods: Between August 1998 and May 2013, 481 Japanese patients underwent antegrade radical prostatectomy. The relationships between the rate of PSA failure after radical prostatectomy and the number and type of risk factors were examined in the intermediate-risk group. Results: According to the D'Amico criteria, the low-, intermediate-, and high-risk groups comprised 107, 222, and 152 patients, respectively. The median follow-up period after surgery was 54.1 months. The 5-year PSA failure-free rates in the low-, intermediate-, and high-risk groups were 96.5%, 88.9%, and 72.6%, respectively (P < 0.001). The 5-year PSA failure-free rate in the intermediate-risk group with one, two, and three intermediate risk factors was 94.9%, 88.4%, and 49.0%, respectively (P < 0.001). The difference between the high- and intermediate-risk group with three intermediate risk factors was statistically significant based on the log-rank test (P = 0.039). Conclusion: The number of intermediate risk factors is significantly associated with the PSA failure-free survival rate after radical prostatectomy in the intermediate-risk group. Patients classified into the intermediate-risk group based on all three intermediate risk factors are less likely to achieve a complete cure through surgery alone

Efficacy of 3-day versus 5-day aprepitant regimens for long-delayed chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is an ongoing problem. While effectiveness of triplet antiemetic regimens in the delayed CINV phase (24–120 hours after administration of chemotherapy) has been studied, their effectiveness in the long-delayed phase (120–168 hours post-administration) is unknown. We compared the efficacy of 3- and 5-day courses of a triplet antiemetic prophylaxis containing aprepitant (APR) in controlling long-delayed CINV after cisplatin (CDDP)-based chemotherapy. We obtained patient-level data from a nationwide, multicenter, prospective observational study in Japan. The incidence and timing of CINV after 3- and 5-day APR-containing regimens were compared using inverse probability treatment weighting. The analysis included 380 patients. The incidence rates of long-delayed nausea and vomiting were significantly reduced for the 5-day compared with the 3-day regimen (29.1% vs. 22.2%, p = 0.0042; 6.7% vs. 0%, p  A 5-day regimen triplet antiemetic prophylaxis with APR decreased long-delayed vomiting compared with a 3-day regimen in patients receiving CDDP-based chemotherapy. However, the 5-day regimen showed no advantage over the 3-day regimen against long-delayed nausea.</p

The association and prognostic impact of enhancer of zeste homologue 2 expression and epithelial-mesenchymal transition in resected lung adenocarcinoma.

ObjectivesEpithelial-mesenchymal transition (EMT) and the histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2) are important regulators of lung cancer progression and metastasis. Although recent studies support the correlation between EZH2 expression and EMT, no reports have investigated their association using immunohistochemistry or explored their prognostic impact on lung adenocarcinoma. The aim of this study was to elucidate the association between EZH2 and EMT, and their prognostic significance.MethodsEZH2 and the EMT markers E-cadherin and Vimentin were examined by IHC in lung adenocarcinoma specimens that were resected from 2003-2012. Associations between EZH2 and EMT markers and their correlations with survival were analyzed.ResultsWe enrolled 350 patients, approximately 70% of whom were diagnosed as pathological stage I. The rates of positive E-cadherin, Vimentin, and EZH2 expression were 60.3%, 21.4%, and 52.0%, respectively. There was a significant positive correlation between EZH2 and Vimentin expression (p = 0.008), and EZH2 scores were higher in the Mesenchymal group (p = 0.030). In multivariate analysis, EZH2 was an independent predictor of Vimentin expression, and vice versa. EMT and EZH2 overexpression were significantly correlated with poor disease-free and overall survival. Furthermore, the Epithelial group with high EZH2 expression had significantly worse disease-free and overall survival. Positive staining for EMT markers was unfavorable regarding disease-free survival among patients with low EZH2 expression.ConclusionsEMT and high EZH2 expression were associated with poor NSCLC prognoses. Vimentin is a key factor linking EMT and EZH2 in lung adenocarcinoma

Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival