Citations

Purpose According to the lung cancer staging project, T1a (≤ 2 cm) non–small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. Methods We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer–specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. Results OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC ≤ 1 cm. Conclusion Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.

Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation. Atomic force microscopy microindentation demonstrated early PA stiffening in experimental PH and human lung tissue. Pulmonary artery smooth muscle cells (PASMC) grown on substrates with the stiffness of remodeled PAs showed increased proliferation, decreased apoptosis, exaggerated contraction, enhanced matrix deposition, and reduced COX-2–derived prostanoid production compared with cells grown on substrates approximating normal PA stiffness. Treatment with a prostaglandin I 2 analog abrogated monocrotaline-induced PA stiffening and attenuated stiffness-dependent increases in proliferation, matrix deposition, and contraction in PASMC. Our results suggest a pivotal role for early PA stiffening in PH and demonstrate the therapeutic potential of interrupting mechanobiological feedback amplification of vascular remodeling in experimental PH.

Abstract Patients with metastatic melanoma whose disease progresses on ipilimumab can clearly derive benefit from subsequent anti–programmed death-1 (PD-1). However, patients experience heterogeneous outcomes with ipilimumab, including rapid or delayed progression, and it is unclear whether patterns of ipilimumab progression influence subsequent clinical responses to anti–PD-1. We retrospectively reviewed data from 116 patients with metastatic melanoma who progressed on ipilimumab and were subsequently treated with pembrolizumab. The study objectives were to determine whether progression-free survival (PFS) with ipilimumab was associated with PFS, objective response rate (ORR), and clinical benefit rate (CBR; ORR + stable disease) with pembrolizumab. Patients with PFS ≥90 days after treatment with ipilimumab generally had superior outcomes with subsequent pembrolizumab treatment compared with patients with PFS <90 days (ORR, 49% vs. 35%, P = 0.12; CBR, 66% vs. 46%, P = 0.03). Patients with prolonged ipilimumab benefit (PFS ≥ 180 days) had excellent outcomes with pembrolizumab compared with rapid progressors (PFS < 45 days; ORR, 55% vs. 25%; CBR, 80% vs. 25%; median PFS, 249 vs. 50 days). Using logistic regression models, PFS with ipilimumab was independently correlated with response to pembrolizumab (odds ratio, 1.22; 95% CI, 1.02–1.51). This study shows that prolonged PFS with ipilimumab predicts excellent outcomes with subsequent pembrolizumab treatment, offering valuable prognostic information for clinicians. Cancer Immunol Res; 4(7); 569–73. ©2016 AACR.