Changes in Pulmonary Function Tests After Neoadjuvant Therapy Predict Postoperative Complications

doi:10.1016/j.athoracsur.2009.06.013

The Annals of Thoracic Surgery

Volume 88, Issue 3, September 2009, Pages 930-936

Presented at the Forty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 26–28, 2009.

https://doi.org/10.1016/j.athoracsur.2009.06.013 Get rights and content

Background

Neoadjuvant chemotherapy or chemoradiotherapy increases the risk of pulmonary resection. Changes in specific pulmonary function tests may be predictive.

Methods

A retrospective review of a prospective database of patients with non–small cell lung cancer who underwent neoadjuvant therapy, had pulmonary function tests performed both before and after therapy, and then underwent elective pulmonary resection was performed. Final values and change in the pulmonary function tests before and after treatment were entered as independent variables into a multivariate model in which the dependent variable was major or respiratory morbidity.

Results

There were 132 patients. The mean duration between pretherapy and posttherapy pulmonary function tests was 4.1 months. The mean change in the percent forced expiratory volume in 1 second, in the percent diffusion capacity of the lung for carbon monoxide, and in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume was +1.0, −6.4%, and −6.6%, respectively. Fifty-five patients (42%) experienced a postoperative complication, and 39 of those patients experienced a major or respiratory complication. There were 7 (5.3%) operative mortalities (5 were respiratory related). On multivariate analysis the change in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume was the only factor associated with major or respiratory morbidity (p = 0.028). When the posttherapy percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume fell by 8% or more, there was an increased likelihood of major morbidity (p = 0.01).

Conclusions

A decrease in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume after neoadjuvant chemotherapy or chemoradiotherapy may predict increased risk for pulmonary resection, especially if the decrease is 8% or greater. These results should be considered in the preoperative risk assessment of patients who are to undergo pulmonary resection after induction therapy.

Section snippets

Patients

This is a retrospective review of a prospective database of a single university-based general thoracic surgeon. Patients who were 19 years of age or older, had PFTs performed within 8 weeks of the start of neoadjuvant chemotherapy or chemoradiotherapy, had repeat PFTs after the completion of their medical therapy, and then underwent elective pulmonary resection were included in this study. The University of Alabama at Birmingham's institutional review board approved this study as well as the

Results

There were 404 patients who underwent elective pulmonary resection after induction chemotherapy or chemoradiotherapy by one general thoracic surgeon between January 1999 and June 2008. However, only 132 of these patients met the entry criteria for this study. The most common reason for exclusion was the lack of both pretherapy and posttherapy PFTs. Patient characteristics are shown in Table 2. The most common indication for the use of neoadjuvant chemoradiotherapy was N2 disease; the most

Comment

The decision to operate on a patient after he or she has received neoadjuvant chemotherapy or chemoradiotherapy is based on several factors that assess the risks compared with the benefits of surgery. The benefits of surgery are based on the oncologic advantage of undergoing pulmonary resection and removal of the mediastinal and hilar lymph nodes. The debates hinges on the patient's true pathologic stage before the induction of therapy. However, too often patients are only clinically staged,

References (22)

R.J. Cerfolio et al.
The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives
Ann Thorac Surg
(2008)
M.K. Ferguson et al.
The role of diffusing capacity and exercise tests
Thorac Surg Clin
(2008)
M.K. Ferguson et al.
Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease
Ann Thorac Surg
(2008)
A. Brunelli et al.
Predicted versus observed FEV₁ and Dlco after major lung resection: a prospective evaluation at different postoperative periods
Ann Thorac Surg
(2007)
W.C. Fowler et al.
Postoperative complications after combined neoadjuvant treatment of lung cancer
Ann Thorac Surg
(1993)
M.P. Rivera et al.
Impact of preoperative chemotherapy on pulmonary function tests in resectable early-stage non-small cell lung cancer
Chest
(2009)
F. Leo et al.
Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?
Ann Thorac Surg
(2004)
S. Takeda et al.
Fall in diffusing capacity associated with induction therapy for lung cancer: a predictor of postoperative complication?
Ann Thorac Surg
(2006)
R.M. Abou-Jawde et al.
Impact of induction concurrent chemoradiotherapy on pulmonary function and postoperative acute respiratory complications in esophageal cancer
Chest
(2005)
R.J. Cerfolio et al.
Different diffusing capacity of the lung for carbon monoxide as predictors of respiratory morbidity
Ann Thorac Surg
(2009)

R.K. Ramanathan et al.

Pulmonary infiltrates following administration of paclitaxel

Chest

(1996)

Cited by (46)

Performance Comparison of Pulmonary Risk Scoring Systems in Lung Resection
2023, Journal of Cardiothoracic and Vascular Anesthesia
To validate and compare the performance of different pulmonary risk scoring systems to predict postoperative pulmonary complications (PPCs) in lung resection surgery.
Retrospective cohort study
A historic single-center cohort of lung resection surgeries
Adult patients undergoing lung resection surgery under 1-lung ventilation.
None.
The accuracy of the following pulmonary risk scoring systems were used to predict pulmonary complications: the ARISCAT (Assess respiratory RIsk in Surgical patients in CATalonia), the LAS VEGAS (Local Assessment of VEntilatory management during General Anesthesia for Surgery), the SPORC (Score for Prediction of Postoperative Respiratory Complications), and a recent thoracic-specific risk score, named CARDOT. Discrimination and calibration were assessed using the concordance (c) index and the intercept of LOESS (locally estimated scatterplot)–smoothed curves, respectively. Additional models were constructed that incorporated predicted postoperative forced expiratory volume (ppoFEV1) into each scoring system. Of the 2,104 patients undergoing lung surgery, 123 developed postoperative pulmonary complications (PPCs; 5.9%). All scoring systems had poor discriminatory power to predict PPCs (ARISCAT c-index 0.60, 95% confidence interval [CI] 0.55-0.65; LAS VEGAS c-index 0.68, 95% CI 0.63-0.73; SPORC c-index 0.63, 95% CI 0.59-0.68; CARDOT c-index 0.64, 95% CI 0.58-0.70), but the inclusion of ppoFEV1 slightly improved the performance of LAS VEGAS (c-index 0.70, 95% CI 0.66-0.75) and CARDOT (c-index 0.68, 95% CI 0.62-0.73). Analysis of calibration showed a slight overestimation when using ARISCAT (intercept $-$ 0.28) and LAS VEGAS (intercept $-$ 0.27).
None of the scoring systems appeared to have adequate discriminatory power to predict PPCs among patients undergoing lung resection. An alternative risk score is necessary to better predict patients at risk of PPCs after thoracic surgery.
Postinduction therapy pulmonary function retesting is necessary before surgical resection for non–small cell lung cancer
2022, Journal of Thoracic and Cardiovascular Surgery
Pretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non–small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC.
We retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO <50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points.
In multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P < .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy.
Reduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality.
Definition and assessment of high risk in patients considered for lobectomy for stage I non–small cell lung cancer: The American Association for Thoracic Surgery expert panel consensus document
2021, Journal of Thoracic and Cardiovascular Surgery
Lobectomy is a standard treatment for stage I non–small cell lung cancer, but a significant proportion of patients are considered at high risk for complications, including mortality, after lobectomy and might not be candidates. Identifying who is at risk is important and in evolution. The objective of The American Association for Thoracic Surgery Clinical Practice Standards Committee expert panel was to review important considerations and factors in assessing who is at high risk among patients considered for lobectomy.
The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an expert panel that developed an expert consensus document after systematic review of the literature. The expert panel generated a priori a list of important risk factors in the determination of high risk for lobectomy. A survey was administered, and the expert panel was asked to grade the relative importance of each risk factor. Recommendations were developed using discussion and a modified Delphi method.
The expert panel survey identified the most important factors in the determination of high risk, which included the need for supplemental oxygen because of severe underlying lung disease, low diffusion capacity, the presence of frailty, and the overall assessment of daily activity and functional status. The panel determined that factors, such as age (as a sole factor), were less important in risk assessment.
Defining who is at high risk for lobectomy for stage I non–small cell lung cancer is challenging, but remains critical. There was impressive strong consensus on identification of important factors and their hierarchical ranking of perceived risk. The panel identified several key factors that can be incorporated in risk assessment. The factors are evolving and as the population ages, factors such as neurocognitive function and frailty become more important. A minimally invasive approach becomes even more critical in this older population to mitigate risk. The determination of risk is a clinical decision and judgement, which should also take into consideration patient perspectives, values, preferences, and quality of life.
Evaluation of Risk for Thoracic Surgery
2020, Surgical Oncology Clinics of North America
Citation Excerpt :
A similar recent analysis from the National Cancer Database of more than 130,000 patients undergoing lung resection for lung cancer found an increased incidence of 30-day and 90-day mortality after neoadjuvant treatment.31 Neoadjuvant chemotherapy has been found to be associated with structural changes in the lung leading to decreased diffusion capacity, which in turn may predispose to development of postoperative respiratory complications.32–35 The evidence from the literature warrants a re-evaluation of the pulmonary function after completion of the chemotherapy treatment and before lung resection to evaluate possible changes, particularly in diffusion capacity.3,4
After neoadjuvant chemoradiation therapy, predicted pulmonary function may be reduced by 10%
2018, Journal of Thoracic and Cardiovascular Surgery
Impact of induction chemoradiotherapy on pulmonary function after lobectomy for lung cancer
2018, Journal of Thoracic and Cardiovascular Surgery
Citation Excerpt :
Although the patients in the present study were treated with lobectomy not pneumonectomy, our data showed that compensatory lung growth also occurred after lobectomy on the contralateral lung, even after ICRT. The limitations of the present study are as follows: (1) we could only match the confounders, for which there is evidence of association with postoperative pulmonary function, for making a sufficient match balance, (2) of the potential confounders that were not used for matching, the tumor size and N-stage might directly affect the resected lobe function causing the difference of postoperative pulmonary function between the groups, but they could not be matched because of complete different treatment indications for tumor stage between the groups, (3) preoperative SPECT lung perfusion in the ICRT group was conducted only after ICRT but not before ICRT, which did not allow us to address the short-term effects of ICRT before surgery, (4) survival bias between the groups (ie, whereas 3 patients in the ICRT group [4%] suffered surgery-related death, only 1 in the non-ICRT group [0.6%] died), and (5) DLCO was not examined in the present study, which has been reported to be a more sensitive measure of lung injury by ICRT than PFT.6-8 Regarding the first issue, the sensitivity analysis showed consistent results for the potential confounders, which were excluded from the matching.
Our study aim was to determine whether there are differential changes in whole-lung and regional lung functions after lobectomy for lung cancer between propensity score-matched patients treated with and without induction chemoradiotherapy, by using single-photon emission computed tomography lung perfusion.
This study was a retrospective matched cohort study of consecutively acquired data. Pulmonary function test and perfusion scintigraphy were conducted before lobectomy and 6 months after lobectomy in patients treated with induction therapy (n = 72) and in those not treated (n = 170), for measuring functional changes of whole lung, contralateral lung, and lobes. After exact matching on resected lobe site, propensity scores for age, smoking status, preoperative pulmonary functions, and predicted postoperative pulmonary function were used to match the groups.
After the matching, 46 patients were selected from the groups. Standardized mean differences of the 5 matched variables were <0.1. Whole lung function significantly decreased after lobectomy in the induction therapy group than in the noninduction therapy group (P < .001). Although ipsilateral preserved lobe function before surgery was not different between the groups (P = .33), postoperative value was significantly lower in the induction therapy group than in the noninduction therapy group (P < .001). Although both groups showed a significant increase of contralateral lung function after lobectomy (P < .01), the increases were not significantly different between the groups (P = .81).
Induction chemoradiotherapy was associated with reduced pulmonary function after lobectomy because of a decrease in ipsilateral preserved lobe function, which could be caused by the chronic effects of the induction chemoradiotherapy.

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Original articleGeneral thoracicChanges in Pulmonary Function Tests After Neoadjuvant Therapy Predict Postoperative Complications

Background

Methods

Results

Conclusions

Section snippets

Patients

Results

Comment

Ann Thorac Surg

Thorac Surg Clin

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Chest

Ann Thorac Surg

Ann Thorac Surg

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Ann Thorac Surg

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Original article
General thoracic
Changes in Pulmonary Function Tests After Neoadjuvant Therapy Predict Postoperative Complications