key: cord-0829939-y4ome6bc
authors: Brunelli, Alessandro; Chaudhuri, Nilanjan; Kefaloyannis, Manos; Milton, Richard; Pompili, Cecilia; Tcherveniakov, Peter; Papagiannopoulos, Kostas
title: Eurolung risk score is associated with long-term survival following curative resection for lung cancer
date: 2020-08-24
journal: J Thorac Cardiovasc Surg
DOI: 10.1016/j.jtcvs.2020.06.151
sha: 2103b43595a5f0c240b1f1c52c3701572b57d844
doc_id: 829939
cord_uid: y4ome6bc

ABSTRACT Objective To verify whether the Eurolung score was associated with long term prognosis after lung cancer resection. Methods 1359 consecutive patients undergoing anatomic lung resection (1136 lobectomies, 103 pneumonectomies, 120 segmentectomies) (2014-2018) were analysed. The parsimonious aggregate Eurolung2 score was calculated for each patient. Median follow up was 802 days. Survival distribution was estimated by the Kaplan-Meier method. Cox proportional hazard regression and competing risk regression analyses were used to assess the independent association of Eurolung with overall and disease specific survival. Results Patients were grouped into 4 classes according to their Eurolung scores (A 0-2.5, B 3-5, C 5.5-6.5, D 7-11.5). Most patients were in class A (52%) and B (33%), 8% were in class C and 7% in class D. Five-year overall survival decreased across the categories (A: 75%; B: 52%; C: 29%; D: 27%, log rank p<0.0001). The score stratified well the 3-year overall survival in patients with either pT1 (p<0.0001) or pT>1 (p<0.0001). In addition, the different classes were associated with incremental risk of long-term overall mortality in patients with pN0 (p<0.0001) and with positive nodes (p=0.0005). Cox proportional hazard regression and competing regression analyses showed that Eurolung aggregate score remained significantly associated with overall (HR 1.19,p<0.0001) and disease specific survival after adjusting for pT and pN stage (HR 1.09,p=0.005). Conclusions Eurolung aggregate score was associated with long-term survival after curative resection for cancer. This information may be valuable to inform the shared decision-making process and the multidisciplinary team discussion assisting in the selection of the most appropriate curative treatment in high-risk patients.

The Eurolung is a model developed from the ESTS database to stratify the risk of immediate 153 postoperative mortality based on patient and surgical related characteristics (1) . Recent 154 evidence has shown that different physiologic and patient related factors may influence not 155 only perioperative outcomes but also long-term survival after curative treatment for cancer 156

(2-6). As the Eurolung model includes non oncologic factors potentially associated with 157 prognosis it may represent a valuable tool to estimate not only the immediate risk of death 158 following surgery but also the long-term mortality after curative resection. 159

The objective of this study was therefore to verify whether the Eurolung aggregate score was 160 associated with overall and disease-specific survival after lung cancer resection. 161

This is a retrospective single center analysis performed on prospectively collected data. 1359 163 consecutive patients undergoing anatomic lung resection for non-small cell lung cancer (1136 164 lobectomies, 103 pneumonectomies, 120 segmentectomies) from April 2014 through 165

December 2018 were analysed. 166

The study was reviewed by the Research and Innovation Department of the hospital and 167 classified as service evaluation not requiring review by an NHS Research Ethics Committee. 168

All patients were selected for operation following discussion in a multidisciplinary tumour 169 board. A patient was deemed unfit for surgery in case of a ppoFEV1 and ppoDLCO<30% of 170 predicted associated with VO2max<10 ml/kg/min, according to published guidelines (7). dedicated thoracic surgery unit following surgery. Only patients with pathologically staged 176 R0 resections were included in the analysis. A systematic lymph node dissection was 177 performed in all patients. Patients were staged according to the 8 th edition of the TNM 178 staging system. 179 follow up. 449 patients were alive at more than 3 years following surgery. 229

The median Eurolung score was 2.5 (IQR 1-4.5) and ranged from 0 to 11.5 points. 230

Most patients were in class A (52%) and B (33%), 8% were in class C and 7% were in class 231

There was an incremental 30 day mortality rate across the Eurolung categories (A: 0.9%, B: 233 5.4%, C: 9.7%, and D: 14%, p<0.0001). The score stratified well the 3-year OS in patients with either pT1 (p<0.0001) or pT greater 247 than 1 (p<0.0001) (Figure 2a and 2b ). In addition, the different classes were associated with 248 incremental risk of long-term mortality in patients with negative nodal disease (p<0.0001) 249 and in those with positive nodes (p=0.0007). (Figure 3a and The Eurolung score was developed to stratify the risk of postoperative 30 day morbidity and 280 mortality (1). The model includes several patient-related and surgical-related variables such 281 as age, gender, ppoFEV1, BMI, extent of resection and surgical access. Some of these factors 282 are clearly associated with patient frailty and co-morbidities and others reflect the complexity 283 of the operation often dictated by the locally advanced stage of disease. In addition, the extent 284 of surgery may lead to further disabilities leading in turn to increased long term morbidity 285 and mortality. For this reason, we hypothesized that a cumulative score such as Eurolung 286 may be associated not only with short term outcome but also with long term survival 287 following curative surgery. The rationale is to develop an additional tool which can be used 288 in combination with the most traditional oncologic prognostic factors (such as stage of 289 disease) to enhance the prediction of long-term mortality to more specifically tailor curative 290 treatment to individual patients. 291

The main finding of this study was that the Eurolung aggregate score was associated with an 293 incremental risk of long-term overall and lung cancer specific mortality. Patients in class D 294 had 64% and 73% 3-and 5-year overall mortality rate, which was 3-fold higher than the one 295 observed in class A (with the lowest risk). 296

The incremental risk of long-term death is in line with the incremental risk of perioperative 297 mortality shown in the original study (1) and also found in this set of patients. This is in part 298 frailty of patients which may have an impact not only on the short-term outcomes but also on 300 the long-term survival. Older age, reduced pulmonary function and lower BMI encapsulating 301 the risk of sarcopenia as well as being a potential marker of more advanced disease, are well 302 known adverse prognostic factors in lung cancer patients. Even more interesting is the 303 finding that Eurolung is associated with lung cancer specific mortality. This may be 304 The concept of using risk models including patient and treatment related variables in order to 335 stratify the prognosis following lung cancer resection has been tested in previous studies (24-336 28). In general, these studies showed that these "mixed models" were able to stratify both the 337 risk of all cause death and lung cancer specific death, in line with our findings. 338

The study may have potential limitations. 340

First, the Eurolung was not specifically developed to predict long term survival. The different 341 factors compounding the score were originally weighed on their association with 342 postoperative 30 day mortality. Unfortunately, the ESTS database does not collect long term 343 follow up preventing to develop a more specific score for survival. 344

Although the use of a score to stratify prognosis is appealing, it must be interpreted with 345 caution as it likely represents a surrogate measure of patient frailty and extent of disease. It 346 would be desirable that more precise parameters or measures will be developed and used in the future to improve prognostic stratification following curative treatment of lung cancer. 348

The IASLC has recently recognized this need and expanded their staging committee to 349 include a prognostic sub-committee with the aim to identify methods and instruments to 350 develop specific prognostic models incorporating patient, tumor, environment and treatment-351 specific factors (https://www.iaslc.org/About-IASLC/IASLC-Committees). Although 352

Eurolung has proven to be associated with OS and DSS, in order to be reliably used in the 353 context of multifactorial prognostic instruments it needs to be re-calibrated to that specific Shaded areas represent 95% confidence intervals. 563 

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