Role of Intrapulmonary Lymph Nodes in Patients With NSCLC and Visceral Pleural Invasion

Lung Cancer Clinical Trial

Official title:

Role of Intrapulmonary Lymph Nodes in Patients With NSCLC and Visceral Pleural Invasion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05596578
• Other study ID #: 2022.10.Thx
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: December 31, 2029

Study information

• Verified date: January 2023
• Source: Luzerner Kantonsspital
• Contact: Fabrizio Minervini, MD, PhD
• Phone: +410412051111
• Email: fabriziominervini[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: Lung cancer is the leading cause of cancer related death worldwide. More than 80% of all lung tumors are Non-Small Cell Lung Cancers (NSCLC). Lymph node staging has a prognostic value and is crucial to establish the optimal treatment strategy in individual patients. It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) is necessary for accurate staging and prognostication. Although suggested by several guidelines, these peripheral lymph nodes are not routinely examined in clinical routine for several reasons. Moreover, the prognostic significance of the visceral pleural invasion is controversial. Some studies showed a negative impact on OS and DFS in patients with histologic proved visceral pleura invasion.

The mechanism to explain this negative effect is not fully understood. Given that the visceral pleura is very rich in lymphatic vessels, with an intercommunicating "network" arranged over the lung surface and penetrating into the lung parenchyma to join the bronchial lymph vessels with drainage to the various hilar nodes, we assume that the worse OS and DFS observed in these patients could be explained with the presence of metastatic lymph nodes (Station 13-14) that are not routinely examined. Methods: This is a prospective, multicenter study based on ad-hoc created prospectively database. The incidence of N1 lymph node metastasis overall and the incidence of metastasis to the different lymph node stations (Hilar 10/11, Lobar 12, Sublobar 13/14) will be calculated by dividing the number of the respective events by the patient years separately. To investigate the association between visceral pleural invasion and the presence of metastatic lymph nodes univariate and multivariate logistic regression models will be fitted to the data.

Discussion: The primary outcome is to investigate the incidence of N1 metastases (especially stations 12,13,14) and his relationship with visceral pleural invasion. The secondary outcomes is to evaluate the impact of N1 metastases and/or visceral pleural invasion on long-term outcomes (OS and DFS) along with incidence and pattern of recurrence. DFS is defined as the time of surgical intervention to tumor recurrence or death, and OS is defined as the time of surgical intervention to death

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 958
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Anatomical resection for NSCLC <3 cm (lobectomy, bilobectomy, segmentectomy)

• Samples from the intrapulmonary stations 12, 13, and 14 lymph nodes

• Resection of lymphnodes station 10 and 11 during hilar separation.

• R0 resection

Exclusion Criteria:

• Prior or synchronous lung cancer

• pN2

• Pneumonectomy

• R1/R2 resection

• M1

• Neoadjuvant treatment

Related Conditions & MeSH terms

• Lung Cancer
• Lymph Node Metastasis
• Lymphatic Metastasis

Locations

Country	Name	City	State
Switzerland	Kantonsspital Luzern	Lucerne

Sponsors (1)

Lead Sponsor	Collaborator
Luzerner Kantonsspital

Country where clinical trial is conducted

Switzerland, 

References & Publications (7)

Bi L, Zhang H, Ge M, Lv Z, Deng Y, Rong T, Liu C. Intrapulmonary lymph node (stations 13 and 14) metastasis in peripheral non-small cell lung cancer. Medicine (Baltimore). 2021 Jul 9;100(27):e26528. doi: 10.1097/MD.0000000000026528. — View Citation

Fibla JJ, Cassivi SD, Brunelli A, Decker PA, Allen MS, Darling GE, Landreneau RJ, Putnam JB. Re-evaluation of the prognostic value of visceral pleura invasion in Stage IB non-small cell lung cancer using the prospective multicenter ACOSOG Z0030 trial data set. Lung Cancer. 2012 Dec;78(3):259-62. doi: 10.1016/j.lungcan.2012.09.010. Epub 2012 Oct 3. — View Citation

Huang H, Wang T, Hu B, Pan C. Visceral pleural invasion remains a size-independent prognostic factor in stage I non-small cell lung cancer. Ann Thorac Surg. 2015 Apr;99(4):1130-9. doi: 10.1016/j.athoracsur.2014.11.052. Epub 2015 Feb 20. — View Citation

Nitadori JI, Colovos C, Kadota K, Sima CS, Sarkaria IS, Rizk NP, Rusch VW, Travis WD, Adusumilli PS. Visceral pleural invasion does not affect recurrence or overall survival among patients with lung adenocarcinoma </= 2 cm: a proposal to reclassify T1 lung adenocarcinoma. Chest. 2013 Nov;144(5):1622-1631. doi: 10.1378/chest.13-0394. — View Citation

Park S, Cho S, Yum SW, Kim K, Jheon S. Comprehensive analysis of metastatic N1 lymph nodes in completely resected non-small-cell lung cancer. Interact Cardiovasc Thorac Surg. 2015 Nov;21(5):624-9. doi: 10.1093/icvts/ivv209. Epub 2015 Aug 4. — View Citation

Seok Y, Lee E. Visceral Pleural Invasion Is a Significant Prognostic Factor in Patients with Partly Solid Lung Adenocarcinoma Sized 30 mm or Smaller. Thorac Cardiovasc Surg. 2018 Mar;66(2):150-155. doi: 10.1055/s-0036-1586757. Epub 2016 Aug 12. — View Citation

Wightman SC, Lee JY, Ding L, Atay SM, Shemanski KA, McFadden PM, David EA, Kim AW. Adjuvant chemotherapy for visceral pleural invasion in 3-4-cm non-small-cell lung cancer improves survival. Eur J Cardiothorac Surg. 2022 Jun 15;62(1):ezab498. doi: 10.1093/ejcts/ezab498. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	N1	Overall incidence of N1 pathological lymph nodes (Hilar 10/11, Lobar 12, Sublobar 13/14)	January 2023-December 2024
Primary	VPI	Incidence of N1 pathological lymph nodes (Hilar 10/11, Lobar 12, Sublobar 13/14) in patients with pathological evidence of visceral pleural invasion	January 2023-December 2024
Secondary	OS	Overall Survival (1-3-5 Years)	January 2023- December 2029
Secondary	DFS	Disease free survival (1-3-5 Years)	January 2023-December 2029
Secondary	Tumor recurrence	pattern : local, regional, distant	January 2023-December 2029