The aim of this article was to investigate the effect of ambroxol on radiation lung injury and the expression of transforming growth factor beta(1) (TGF-beta(1)), as well as tumor necrosis factor alpha (TNF-alpha) in plasma. Totally, 120 patients with locally advanced lung cancer in radiotherapy were randomized into treatment and control groups. Patients in the treatment group took ambroxol orally at a dosage of 90 mg, three times per day for 3 months from the beginning of radiotherapy. The expression of TGF-beta(1) and TNF-alpha in plasma was analyzed. The clinical symptoms and lung diffusing capacity were monitored using high resolving power computed tomography. The level of TGF-beta(1) in the control group was increased (11.8 +/- 5.5 ng/ml), whereas in ambroxol-treated patients, the increase was not significant (5.6 +/- 2.6 ng/ml, P < 0.001). Radiotherapy-induced elevation of TNF-alpha levels, seen in control patients, was also abolished after treatment with ambroxol (5.1 +/- 1.0 vs. 2.4 +/- 0.8 ng/ml, P < 0.001). In the treatment group, carbon monoxide diffusion capacity was not significantly decreased at 6, 12, and 18 months post-radiotherapy, compared with the control group (P < 0.05). Ambroxol decreased the expression of TGF-beta(1) and TNF-alpha, and minimized the diminishment of lung diffusion capacity after radiotherapy.
Objective: This study aimed to determine the optimal surgical procedure for early-stage pulmonary carcinoids (PCs). Background: PCs, comprising typical carcinoids (TCs) and atypical carcinoids (ACs), are rare low-grade malignant tumors. We determine the optimal surgical management for early-stage PCs using data from the Surveillance, Epidemiology, and End Results registry. Methods: Clinical and survival data of patients with early-stage PC tumors with a diameter ≤3 cm were retrieved. The Kaplan-Meier method and logrank tests were used to assess the differences in overall survival (OS). Subgroup analyses were also performed. To reduce the inherent bias of retrospective studies, two propensity score matching (PSM) analysis with (PSM2) or without (PSM1) consideration of lymph node assessment were performed. Results: In total, 2934 patients with PCs, including 2741 (93.42%) with TCs and 193 (6.58%) with ACs, were recruited. After PSM1 analysis, TC patients in the lobectomy group had a significantly better OS than those in the sublobar resection group (P = 0.0067), which is more remarkable for patients with a tumor diameter of 2 cm < T ≤ 3 cm (P = 0.0345) and those aged < 70 years (P = 0.0032). However, survival benefits were not found after PSM2 analysis which balanced lymph node assessment. In multivariate cox analysis, age < 70 years, female, TC histology and adequate lymph node assessment were associated with better OS. Conclusions: Sublobar resection may not significantly compromise the longterm oncological outcomes in early-stage PCs ≤3 cm in size if lymph node assessment is performed adequately. Further validation in large randomized clinical trials is warranted.
(1) Background: Sublobar resection can be used as an alternative surgical strategy for early-stage non-small-cell lung cancer (NSCLC) patients. However, the choice between wedge resection and segmentectomy remains contentious. In this study, we investigated the optimal surgical procedure for sublobar resection in patients with NSCLC ≤ 2 cm with a lobe-specific analysis; (2) Methods: Data for patients with T1N0M0 with a diameter of ≤2 cm who had undergone sublobar resection were retrieved. Propensity score matching (PSM) was used to reduce the inherent bias, and the Kaplan–Meier method and log-rank tests were used to assess the differences in survival; (3) Results: A total of 1882 patients were identified after the PSM. Patients with NSCLC ≤ 2 cm who had undergone segmentectomy showed better survival than those who had undergone wedge resection. However, when NSCLC was ≤1 cm, there was no significant difference in OS between the two groups. This demonstrated an OS advantage of segmentectomy over wedge resection for patients with NSCLC tumors of 1–2 cm (p = 0.024). Further analysis indicated that this survival benefit was only observed in patients with right upper NSCLC of 1–2 cm, but not with NSCLC in the other four lobes; (4) Conclusions: Segmentectomy showed a greater survival benefit than wedge resection only in patients with NSCLC of 1–2 cm, particularly those with primary tumors in the right upper lobe. Therefore, we propose a lobe-specific sublobar resection strategy for early-stage NSCLC patients (tumors of 1–2 cm) who cannot tolerate lobectomy.
Objectives: Perioperative cisplatin-based chemotherapy decreases the risk of death over surgery alone and is a standard-of-care. Here, we examined perioperative chemotherapy indications for stage IB-III non-small cell lung cancer (NSCLC) patients according to lobe-specific analysis. Methods: Resectable NSCLC patients with stage IB–III who received perioperative chemotherapy with and without radiotherapy after lung resection were identified from the SEER database. Propensity score matching (PSM) analysis was performed to reduce the inherent bias of retrospective studies. The Kaplan–Meier method and log-rank tests were used to assess the differences in overall survival (OS). Results: The study enrolled 23,844 patients before PSM. The perioperative chemotherapy group had better OS than the non-perioperative chemotherapy group in stage IB–III NSCLC patients before and after PSM. However, subgroup analysis according to stage demonstrated that perioperative chemotherapy did not markedly benefit patients with stage IB. Furthermore, lobar subgroup analysis did not show survival advantages in primary tumors located in either the right middle lobe in stages II and III NSCLC or the right lower lobe in stage III NSCLC. Conclusions: Lobe-specific perioperative chemotherapy is recommended in NSCLC patients. For stage IB NSCLC, right middle lobe NSCLC from stage IB-III and right lower lobe NSCLC from stage III, perioperative chemotherapy might not confer survival benefits.
Background: Pulmonary carcinoids (PC), including typical (TC) and atypical carcinoids (AC), are lowgrade neuroendocrine tumors (NETs) which account for 1-5% of all lung tumors. Due to the low prevalence of PC and extreme rarity of anaplastic lymphoma kinase (ALK) rearrangements in patients with PC, the advances in targeted therapy development in PC are still limited and there is no standard treatment. Even though in patients with PC harboring ALK rearrangements there is a room for a success in targeted therapy.To our knowledge, case 1 was the first report to detect ALK gene p.I1171N mutation after taking alectinib and sensitive to ceritinib in patients with atypical carcinoid.Case Description: Herein, we report the cases of 2 non-smoking patients, 51 year-old female with tumor in left lower lobe and 49 year-old female with tumor in right upper lobe, both with metastatic PC who harbored EML4-ALK fusion and were sensitive to small-molecule ALK inhibitors. The first patient initially received alectinib, then therapy was switched to ceritinib after developing drug resistance due to the missense mutation of ALK gene p.I1171N mutation in exon 22 detected by next-generation sequencing (NGS), and finally died of intracranial disease progression. The second patient also received alectinib, and her treatment is currently ongoing with good effect and tolerance. After conducting comprehensive review of literature, we found that 14 lung NETs with ALK rearrangements have been reported to date. The clinical outcome was partial response for 6 NETs patients and 5 patients exhibited stable disease after treatment with ALK inhibitors.Conclusions: According to the effectiveness of ALK inhibitors in our cases and previous articles, we recommend alectinib for the first-line treatment of metastatic PC with EML4-ALK fusion and highlight the need for molecular profiling of metastatic lung NETs patients and that ALK inhibitors are feasible in the treatment for metastatic lung NETs patients with ALK rearrangements. Finally, further studies to assess the real prevalence of ALK gene fusions and their spectrum of sensitivity to different ALK inhibitors are needed in larger cohorts.
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