周一“星”视角|脏层胸膜浸润对表现为磨玻璃影的≤3cmNSCLC的预后价值；JAK抑制剂联合PD-1免疫治疗可用于NSCLC患者

01

Zhenyu Yang MD1#, Yiming Li MD1#, Chenglin Guo MD 1#, Yikai Xing MM1, Chengwu Liu MD1, Jian Zhang PhD1, Qiang Pu MD1*, Lunxu Liu MD PhD1* 

1 Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China

# These authors contributed equally to this work.

*Corresponding author.

Background: 

Visceral pleural infiltration (VPI) has been identified as an important risk factor in non-small cell lung cancer (NSCLC) for many decades. However, for patients who present with ground glass opacity (GGO), the prognostic value of VPI is still elusive. We aimed to investigate whether the VPI is a significant prognostic factor in surgically resected ≤3 cm stage I NSCLC who presented with GGO.

Materials and Methods: 

Patients with primary NSCLC who underwent surgical resection between December 2009 and December 2018 were collected. Stage I tumors that presented as GGO nodule with a tumor size of less than 3 cm were included and divided into two groups based on VPI status (positive and negative). Clinical, pathological, and prognostic data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using the Cox proportional hazards model and Kaplan-Meier method.

Results: 

A total of 2043 patients were included in this study (VPIs were found in 196 patients). After IPTW weighting, all factors between the two groups were balanced. The median follow-up time was 67.3 months. According to the multivariable Cox models, the VPI was not a significant prognostic factor for OS (HR = 2.00, 95% CI, 0.96-4.17; P= 0.063), but was significant for RFS (HR =2.00, 95% CI, 1.12-3.55; P= 0.019). In subgroup analysis, we found VPI was significant for OS (HR=3.17, 95%CI: 1.09-9.26, P=0.035) and RFS (HR=4.07, 95%CI: 1.76-9.40, P=0.001) in patients with a tumor size >1 cm and a consolidation to tumor ratio (CTR) >50%. For patients with a tumor size ≤1cm or a CTR ≤50%, the VPI was not significant.

Conclusions:

VPI may be a significant risk factor for GGOs in NSCLC patients with a tumor size >1 cm and a CTR >50%. Further prospective studies conducted across multi-centers with a larger sample size are needed.

[CITATION]: Yang Z, Li Y, Guo C, et al. The prognostic value of visceral pleural infiltration in ≤3cm non-small cell lung cancer presenting with ground glass opacity: An inverse probability of treatment weighting study. Int J Surg. 2024 Jun 24.

[DOI]: 10.1097/JS9.0000000000001803.

[IF]: 12.5

02

Divij Mathew1,2,3, Melina E Marmarelis4, Caitlin Foley4,5,6, Joshua M Bauml4, Darwin Ye3,5,6,7, Reem Ghinnagow5,6,7, Shin Foong Ngiow1,2,3, Max Klapholz1,5,6,7, Soyeong Jun8, Zhaojun Zhang9, Robert Zorc1, Christiana W Davis4, Maximillian Diehn8, Josephine R Giles1,2,3, Alexander C Huang2,3, Wei-Ting Hwang10, Nancy R Zhang9, Adam J Schoenfeld11, Erica L Carpenter4, Corey J Langer4, E John Wherry1,2,3,6, Andy J Minn2,3,5,6,7‍‍‍‍‍‍‍‍‍

1 Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

2 Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

3 Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

4 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

5 Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

6 Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

7 Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

8 Department of Radiation Oncology and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

9 Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.

10 Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

11 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 

Abstract

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression.

We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer.

Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease.

Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics.

[CITATION]: Divij Mathew, Melina E Marmarelis, Caitlin Foley, et al. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science. 2024 Jun 21;384(6702):eadf1329.

[DOI]: 10.1126/science.adf1329.

[IF]: 44.7