Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival

John M. Varlotto*, Aaron N. Yao, Malcom McAvoy DeCamp Jr, Satvik Ramakrishna, Abe Recht, John Flickinger, Adin-Cristian Andrei, Michael F. Reed, Jennifer W. Toth, Thomas J. Fizgerald, Kristin Higgins, Xiao Zheng, Julie Shelkey, Laura N. Medford-Davis, Chandra Belani, Christopher R. Kelsey

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

Original languageEnglish (US)
Pages (from-to)765-773
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume91
Issue number4
DOIs
StatePublished - Mar 15 2015

Fingerprint

Non-Small Cell Lung Carcinoma
lungs
cancer
Recurrence
Survival
hazards
confidence
intervals
radiation therapy
tumors
histology
chemotherapy
Confidence Intervals
mediastinum
Radiotherapy
lymphatic system
Neoplasms
Histology
death
wedges

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Varlotto, John M. ; Yao, Aaron N. ; DeCamp Jr, Malcom McAvoy ; Ramakrishna, Satvik ; Recht, Abe ; Flickinger, John ; Andrei, Adin-Cristian ; Reed, Michael F. ; Toth, Jennifer W. ; Fizgerald, Thomas J. ; Higgins, Kristin ; Zheng, Xiao ; Shelkey, Julie ; Medford-Davis, Laura N. ; Belani, Chandra ; Kelsey, Christopher R. / Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival. In: International Journal of Radiation Oncology Biology Physics. 2015 ; Vol. 91, No. 4. pp. 765-773.
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abstract = "Purpose Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95{\%} confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95{\%} CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95{\%} CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95{\%} CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.",
author = "Varlotto, {John M.} and Yao, {Aaron N.} and {DeCamp Jr}, {Malcom McAvoy} and Satvik Ramakrishna and Abe Recht and John Flickinger and Adin-Cristian Andrei and Reed, {Michael F.} and Toth, {Jennifer W.} and Fizgerald, {Thomas J.} and Kristin Higgins and Xiao Zheng and Julie Shelkey and Medford-Davis, {Laura N.} and Chandra Belani and Kelsey, {Christopher R.}",
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Varlotto, JM, Yao, AN, DeCamp Jr, MM, Ramakrishna, S, Recht, A, Flickinger, J, Andrei, A-C, Reed, MF, Toth, JW, Fizgerald, TJ, Higgins, K, Zheng, X, Shelkey, J, Medford-Davis, LN, Belani, C & Kelsey, CR 2015, 'Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival', International Journal of Radiation Oncology Biology Physics, vol. 91, no. 4, pp. 765-773. https://doi.org/10.1016/j.ijrobp.2014.12.028

Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival. / Varlotto, John M.; Yao, Aaron N.; DeCamp Jr, Malcom McAvoy; Ramakrishna, Satvik; Recht, Abe; Flickinger, John; Andrei, Adin-Cristian; Reed, Michael F.; Toth, Jennifer W.; Fizgerald, Thomas J.; Higgins, Kristin; Zheng, Xiao; Shelkey, Julie; Medford-Davis, Laura N.; Belani, Chandra; Kelsey, Christopher R.

In: International Journal of Radiation Oncology Biology Physics, Vol. 91, No. 4, 15.03.2015, p. 765-773.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival

AU - Varlotto, John M.

AU - Yao, Aaron N.

AU - DeCamp Jr, Malcom McAvoy

AU - Ramakrishna, Satvik

AU - Recht, Abe

AU - Flickinger, John

AU - Andrei, Adin-Cristian

AU - Reed, Michael F.

AU - Toth, Jennifer W.

AU - Fizgerald, Thomas J.

AU - Higgins, Kristin

AU - Zheng, Xiao

AU - Shelkey, Julie

AU - Medford-Davis, Laura N.

AU - Belani, Chandra

AU - Kelsey, Christopher R.

PY - 2015/3/15

Y1 - 2015/3/15

N2 - Purpose Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

AB - Purpose Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

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