Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer

Melissa A.L. Vyfhuis, Whitney M. Burrows, Neha Bhooshan, Mohan Suntharalingam, James M. Donahue, Josephine Feliciano, Shahed Badiyan, Elizabeth M. Nichols, Martin J. Edelman, Shamus R. Carr, Joseph Friedberg, Gavin Henry, Shelby Stewart, Ashutosh Sachdeva, Edward M. Pickering, Charles B. Simone, Steven J. Feigenberg, Pranshu Mohindra

Research output: Contribution to journalArticle

Abstract

Purpose: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). Methods and Materials: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Results: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P =.004; FFR: HR 0.426, 95% CI 0.250-0.726, P =.002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P =.001; FFR: HR 0.455, 95% CI 0.266-0.778, P =.004). However, pCR did not independently impact OS (P =.918) or FFR (P =.474). Conclusions: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

Original languageEnglish (US)
JournalInternational Journal of Radiation Oncology Biology Physics
DOIs
StateAccepted/In press - Jan 1 2018

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Neoadjuvant Therapy
clearances
Non-Small Cell Lung Carcinoma
lungs
therapy
cancer
dosage
Survival
hazards
Recurrence
confidence
Confidence Intervals
intervals
mediastinum
Kaplan-Meier Estimate
Mediastinum
chemotherapy
surgery
regression analysis
Therapeutics

ASJC Scopus subject areas

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

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Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer. / Vyfhuis, Melissa A.L.; Burrows, Whitney M.; Bhooshan, Neha; Suntharalingam, Mohan; Donahue, James M.; Feliciano, Josephine; Badiyan, Shahed; Nichols, Elizabeth M.; Edelman, Martin J.; Carr, Shamus R.; Friedberg, Joseph; Henry, Gavin; Stewart, Shelby; Sachdeva, Ashutosh; Pickering, Edward M.; Simone, Charles B.; Feigenberg, Steven J.; Mohindra, Pranshu.

In: International Journal of Radiation Oncology Biology Physics, 01.01.2018.

Research output: Contribution to journalArticle

Vyfhuis, MAL, Burrows, WM, Bhooshan, N, Suntharalingam, M, Donahue, JM, Feliciano, J, Badiyan, S, Nichols, EM, Edelman, MJ, Carr, SR, Friedberg, J, Henry, G, Stewart, S, Sachdeva, A, Pickering, EM, Simone, CB, Feigenberg, SJ & Mohindra, P 2018, 'Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer', International Journal of Radiation Oncology Biology Physics. https://doi.org/10.1016/j.ijrobp.2018.02.003
Vyfhuis, Melissa A.L. ; Burrows, Whitney M. ; Bhooshan, Neha ; Suntharalingam, Mohan ; Donahue, James M. ; Feliciano, Josephine ; Badiyan, Shahed ; Nichols, Elizabeth M. ; Edelman, Martin J. ; Carr, Shamus R. ; Friedberg, Joseph ; Henry, Gavin ; Stewart, Shelby ; Sachdeva, Ashutosh ; Pickering, Edward M. ; Simone, Charles B. ; Feigenberg, Steven J. ; Mohindra, Pranshu. / Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer. In: International Journal of Radiation Oncology Biology Physics. 2018.
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title = "Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer",
abstract = "Purpose: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). Methods and Materials: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Results: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74{\%} (82 of 111 patients) and pCR rate of 48{\%} (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95{\%} confidence interval [CI] 0.272-0.763, P =.004; FFR: HR 0.426, 95{\%} CI 0.250-0.726, P =.002) and multivariate analysis (OS: HR 0.460, 95{\%} CI 0.239-0.699, P =.001; FFR: HR 0.455, 95{\%} CI 0.266-0.778, P =.004). However, pCR did not independently impact OS (P =.918) or FFR (P =.474). Conclusions: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.",
author = "Vyfhuis, {Melissa A.L.} and Burrows, {Whitney M.} and Neha Bhooshan and Mohan Suntharalingam and Donahue, {James M.} and Josephine Feliciano and Shahed Badiyan and Nichols, {Elizabeth M.} and Edelman, {Martin J.} and Carr, {Shamus R.} and Joseph Friedberg and Gavin Henry and Shelby Stewart and Ashutosh Sachdeva and Pickering, {Edward M.} and Simone, {Charles B.} and Feigenberg, {Steven J.} and Pranshu Mohindra",
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T1 - Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer

AU - Vyfhuis, Melissa A.L.

AU - Burrows, Whitney M.

AU - Bhooshan, Neha

AU - Suntharalingam, Mohan

AU - Donahue, James M.

AU - Feliciano, Josephine

AU - Badiyan, Shahed

AU - Nichols, Elizabeth M.

AU - Edelman, Martin J.

AU - Carr, Shamus R.

AU - Friedberg, Joseph

AU - Henry, Gavin

AU - Stewart, Shelby

AU - Sachdeva, Ashutosh

AU - Pickering, Edward M.

AU - Simone, Charles B.

AU - Feigenberg, Steven J.

AU - Mohindra, Pranshu

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). Methods and Materials: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Results: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P =.004; FFR: HR 0.426, 95% CI 0.250-0.726, P =.002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P =.001; FFR: HR 0.455, 95% CI 0.266-0.778, P =.004). However, pCR did not independently impact OS (P =.918) or FFR (P =.474). Conclusions: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

AB - Purpose: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). Methods and Materials: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Results: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P =.004; FFR: HR 0.426, 95% CI 0.250-0.726, P =.002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P =.001; FFR: HR 0.455, 95% CI 0.266-0.778, P =.004). However, pCR did not independently impact OS (P =.918) or FFR (P =.474). Conclusions: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

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