Search

Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms. [ABSTRACT FROM AUTHOR]

Simple Summary: Sublobar resection is commonly used for treating small-sized non-small-cell lung cancer (NSCLC) patients. The effectiveness of adjuvant chemotherapy for these patients, particularly those with pathological lymph node metastasis, remains unclear. A study using data from the National Cancer Database from 2004 to 2018 reviewed cases of NSCLC patients who had undergone sublobar resection with lymph node metastasis and met specific criteria, including tumor size ≤ 20 mm and no comorbidities. The study found that, after adjusting for age, sex, histologic type, and pathological lymph node status through propensity score matching, patients who received adjuvant chemotherapy had a notably longer survival than those who did not (median survival of 64.3 vs. 34.0 months). The results indicate that adjuvant chemotherapy significantly enhances survival in small-sized-NSCLC patients with lymph node involvement post-sublobar resection. Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan–Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has become a standard‐of‐care for patients with non‐small‐cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death‐1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first‐line ICI combined with or without chemotherapy. Materials and Methods: Two‐hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first‐line therapy. Cutoff value of the pretreatment PNI was set as 42.17. Results: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression‐free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51–0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32–0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). Conclusion: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first‐line ICI therapy. [ABSTRACT FROM AUTHOR]

Background: Long‐term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non‐small cell lung cancer (NSCLC). Here, we evaluated post‐recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor‐related variables, primary surgery, and treatment for recurrence was collected. After registration, follow‐up data (e.g., treatment and survival outcomes) were obtained and analyzed. Results: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation‐positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5‐year survival rates for all cases were 64 months and 53.2%, respectively. The 5‐year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence‐free for more than 3 years after recurrence with only initial treatment. Conclusions: Although radical local therapy may be curative in some patients, chemotherapy including EGFR‐TKI treatment is expected to provide long‐term survival comparable to that of radical local therapy. [ABSTRACT FROM AUTHOR]

• Role of postoperative radiation therapy in persistent N2 is unclear. • Our analysis suggests that it improved survival in those patients. • Individuals with persistent N2 may benefit from postoperative radiation. Role of adjuvant radiation therapy in stage III (N2) non-small cell lung cancer has been controversial over the decades. Recent large, randomized trials have demonstrated that adjuvant radiation did not improve overall survival or disease-free survival; however, the trials either excluded or enrolled very few cases that have undergone neoadjuvant chemotherapy. Role of adjuvant radiation after neoadjuvant chemotherapy remains unclear. Whether the use of adjuvant radiation is associated with improved overall survival in those who have received neoadjuvant chemotherapy, especially in a subgroup of patients with persistent N2, is unknown. Patients with clinical stage III (N2) non-small cell lung cancer diagnosed from 2004 through 2017 were queried to National Cancer Database. Eligibility criteria included completely resected (R0), pathological diagnosis, neoadjuvant multi-agent chemotherapy, information regarding post-surgical N2 status (persistent versus downstaged to pN0-1), adjuvant radiation (45 Gy+ versus none), and American Joint Commission on Cancer staging version (6th versus 7th). Those who have received neoadjuvant radiation with any dose or adjuvant radiation with less than 45 Gy total dose were excluded. Kaplan-Meier and log-rank tests were used for survival analyses. Propensity-score matching analysis was used for validation. All statistical analyses were two-sided, and p < 0.05 was required for statistical significance. A total of 1,855 patients met the eligibility criteria for analysis. In the overall cohort, there was a significant difference in overall survival between persistent N2 (Cohort P: N = 854, median survival 50.7 months) and downstaged N (Cohort D: N = 1,001, median survival 82.7 months). The use of adjuvant radiation showed a non-significant detrimental effect in overall survival in the overall and Cohort D (univariate p-values 0.27 and 0.077, respectively); however, both univariate and multivariate analyses demonstrated a significant improvement in overall survival in Cohort P (p = 0.004 and 0.028, respectively). These findings are also verified by propensity-score matching analysis (p = 0.0347). This large-scale retrospective analysis suggests that adjuvant radiation may still have a role in persistent N2 disease after neoadjuvant chemotherapy. Further investigations are warranted. [ABSTRACT FROM AUTHOR]

Background: Preoperative maximum standardized uptake value (SUVmax) of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early‐stage lung adenocarcinoma is not well known. Methods: We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax <2.96 and CEA ≥5.3 or SUVmax ≥2.96 and CEA <5.3) and low SC group (SUVmax <2.96 and CEA <5.3). Results: Kaplan–Meier curve analysis showed that patients with clinical stage IA lung adenocarcinoma in the high SC group had significantly shorter overall survival (OS) and recurrence‐free survival (RFS) than the other groups (p = 0.011 and p < 0.0001, respectively). Multivariate analysis showed that high SC was an independent prognostic factor of OS (p = 0.029) and RFS (p < 0.0001). Conclusions: High values of SUVmax and CEA were associated with poor OS and RFS in patients with stage IA lung adenocarcinoma. Simultaneous evaluation of SUVmax and CEA may be an effective prognostic marker to determine the optimal treatment strategy of early‐stage lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in patients with non-small cell lung cancer (NSCLC) receiving carboplatin (CBDCA)-based chemotherapy (CBDCA + pemetrexed or paclitaxel) has not been clearly described. Therefore, we attempted to evaluate whether delayed CINV could be controlled using a combination of three antiemetics and identify individual risk factors. Methods: We pooled data from two prospective observational studies, namely a nationwide survey of CINV and a prospective, observational study in Japan, to assess whether delayed CINV could be controlled using a combination of three antiemetics and identified individual risk factors via inverse probability treatment-weighted analysis. Results: In total, 240 patients were evaluable in this study (median age, 66 years; male, 173; female, 67). The three-antiemetic regimen controlled delayed nausea (31.6% vs 47.3%) and vomiting (5.1% vs 23.1%) better than two antiemetics. Younger age (< 70 years; odds ratio [OR] = 2.233), motion sickness (OR = 3.472), drinking habits (OR = 1.972), receipt of the CBDCA + pemetrexed regimen (OR = 2.041), and the use of two antiemetics (OR = 1.926) were risk factors for delayed nausea. Female sex (OR = 3.372), drinking habits (OR = 2.272), receipt of the CBDCA+ pemetrexed regimen (OR = 2.314), and the use of two antiemetics (OR = 6.830) were risk factors for delayed vomiting. Conclusion: Female sex, younger age, and receipt of the CBDCA + pemetrexed regimen increased the risk of CINV. Therefore, we recommend additional supportive antiemetics treatment for these patients. [ABSTRACT FROM AUTHOR]