Specific risks and outcomes of octogenarians post-lung cancer resection: our 5-year experience

Introduction

Background

Lung cancer is the most common form of cancer worldwide (1) accounting for 11.4% of newly diagnosed cancer cases worldwide (2). In the UK, there were 48,754 new cases of lung cancer diagnosed in 2019 (3). Despite its prevalence, lung cancer also confers a much lower 1- and 5-year survival rates (19%) compared to other equally common cancers such as bowel, breast, and prostate cancers (3). It is also accountable for 18% of cancer-related deaths worldwide (2). The past decades have seen a dramatic rise in the incidence of lung cancer in the general population worldwide, particularly in the elderly population (4). In recent years, we have seen a prominent increase in the number of octogenarians with lung cancer. With a growing body of evidence advocating the enrolment of lung cancer screening programmes (5-7), and octogenarians potentially receiving investigations for concomitant co-morbidities, the number of symptomatic and asymptomatic octogenarians with resectable lung cancers will likely increase. Nevertheless, advances in minimally invasive surgical techniques and the enrolment of sophisticated enhanced recovery programmes, have meant that those patients traditionally deemed ineligible for surgical treatment, can successfully undergo lung resections.

Rationale and knowledge gap

Higher risk octogenarians have an increased overall complication rate (8), however little is known about which specific complications can occur in patients with specific co-morbidities, many of which are modifiable and can be optimized pre-operatively.

Objective

In this study, we aim to evaluate the safety and long-term outcomes of octogenarians undergoing first-time oncological lung resections for primary non-small cell lung cancer (NSCLC). We also highlight specific percentage likelihoods of having certain complications in the face of given co-morbidities. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-703/rc).

Methods

Patient inclusion and exclusion

We identified all patients aged ≥80 years of age undergoing lung resections for suspected or confirmed lung cancer at a single-centre between January 2016 and December 2021. Out of 214 patients, 25 patients either had benign diagnoses or lung metastases at final pathology, and were therefore excluded from analysis. A final cohort of 189 patients were included in the final analysis. Concomitant lung resections in the same operation were classified according to the larger primary resection. Wedge resections were performed in selected cases where clear resection margins were achievable in low-grade cancers but where limited anaesthetic and operative times were desired owing to multiple comorbidities. Intraoperative staging mediastinal lymphadenectomy was performed video-assisted or robotically wherever possible, and included sampling of all visible ipsilateral hilar, interlobar and at least three mediastinal stations including the subcarinal station (9). Adjuvant chemotherapy was considered in those with confirmed primary NSCLC tumour size greater than 40 mm or with N1/N2 nodal disease i.e., post-operative pathological stage ≥ IIA (10).

Data collection

Data were retrospectively obtained from hospital records in which pre-, peri-, and post-operative data were inputted prospectively in an online database. Preoperative demographic data analysed included age, sex, smoking status, thoracoscore, Medical Research Council (MRC) dyspnoea grade, performance status (PS) as defined by the Eastern Cooperative Oncology Group (ECOG) Scale, pulmonary function tests, and presence of specific pre-operative comorbidities: hypertension, chronic obstructive pulmonary disease (COPD), atrial fibrillation (AF) and other cardiovascular morbidity, obesity as defined by body mass index (BMI) >30 kg/m², renal disease, anaemia and diabetes. Anaemia was defined as a haemoglobin level <120 or <130 g/dL in females and males, respectively. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m². Pre-operative inflammatory markers were also analysed. Intraoperative data was obtained from a computerised database of operation records including surgical approach [robotic-assisted thoracic surgery (RATS) vs. video-assisted thoracic surgery (VATS) vs. thoracotomy], laterality (right or left), and extent of resection. Post-operative histology of subtype and staging of tumours was obtained from regional pathology records. Post-operative complications, hospital length of stay (LOS), readmissions to the high dependency unit (HDU) or intensive therapy unit (ITU), and subsequent hospital treatment was obtained from clinical notes. Follow-up length was from the date of operation until death or 1^st April 2023. Pneumonias post-operatively were defined clinically [febrile >38 ℃, raised white cell counts (WCCs), increased oxygen requirements], and radiologically (atelectatic or consolidative changes on chest radiographs). Prolonged air leaks (PALs) were defined as those persisting for ≥7 days. Tumours were staged according to the TNM 8^th edition.

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional board of ethics of Golden Jubilee National Hospital (No. 1966) and clinical governance and individual consent for this retrospective analysis was waived. The authors have ensured the article has been sufficiently anonymized to cause no harm to the patients or their families.

Statistical analysis

Demographic and operative data are presented as categorical variables reported as counts and percentages. Continuous variables are reported as medians and ranges or means where appropriate and were analysed using two-tailed t-tests or Mann-Whitney U tests where appropriate; and analysis of variance (ANOVA) or Kruskal-Wallis tests for more than two variables. Categorical variables were compared using a Chi-square or Fisher’s exact test where appropriate. Survival was analysed using the Kaplan-Meier method. Comparison of survival curves was performed using a log-rank test. Statistical significance was deemed at P<0.05. Statistical analysis was performed using Microsoft Excel and GraphPad^® Prism 9 statistical software.

Results

Demographics

A total of 189 patients were included in this study [median age 82 years (range, 80–89 years). Twenty-nine (15.3%) patients were 85 or older. There were 93 (49.2%) males in this study population. No patients had a PS greater than 1. One hundred and seventy-eight patients had pre-operative co-morbidities. Additional demographic and operative characteristics are summarised in Tables 1,2, respectively. Right-sided lesions were present in 116 (61.4%) patients and 73 (38.6%) patients had left-sided lesions. One hundred and forty patients underwent a minimally invasive approach to their lung resection (19 RATS and 121 VATS). Forty-nine patients underwent an open thoracotomy either as planned due to tumour bulk or converted from a minimally invasive approach due to intraoperative bleeding, adhesions or a higher risk resection. 132 patients underwent a single lobectomy, eleven patients underwent a further lung resection greater than a lobectomy (n=2 pneumonectomy and n=9 bi-lobectomy). Forty-six patients underwent a sub-lobar resection (n=6 segmentectomy and n=40 wedge resection). None of the patients over 85 years underwent resections larger than a single lobectomy. The majority of patients had adenocarcinoma as the predominant tumour subtype. One patient had a microscopically incomplete resection (R1). There were no patients with a macroscopically incomplete resection (R2).

Overall post-operative complications

There were no intraoperative deaths in the study population. 99 (52.3%) patients suffered postoperative complications. Rates of overall complications occurring in patients with different comorbidities are demonstrated in Table 3. Demographic factors including sex, PS, and smoking history did not significantly affect complications rates. Generally, complications were more likely to occur in patients with high WCC (P=0.03) and COPD (P=0.02). Squamous cell carcinoma subtype significantly impacted the likelihood of overall complications (P=0.009). Those who underwent wedge resections had fewer complications (P=0.049).

Specific post-operative complications

Differences in the incidences of specific complications according to pre-operative co-morbidities, intraoperative factors and histological type were further analysed in the cohort (Table 4). Chest infection (18.5%), persistent air leak (PAL) (15.3%), and AF (12.7%) occurred most commonly. Major adverse complications such as cerebrovascular accident (CVA) and reintubation remained low (1.6% and 2.1%, respectively). 2.6% of patients required escalation to HDU or ITU, 2.6% of patients had renal failure and 1.6% of patients had chronic pain post-operatively.

AF: AF was more prevalent in larger resections up to and including a bi-lobectomy compared to sublobar resections (P=0.001). AF was also more prevalent in those with pre-existing cardiovascular disease. CVA: again, larger lung resections conferred a higher prevalence of CVA compared to sublobar resections (P=0.04). PAL: PAL was more likely in patients with a smoking history (P=0.02) and COPD (P=0.003). Sublobar resections had a higher percentage of PAL (P=0.003). Chest infection: chest infections were more prevalent in those with COPD (P=0.002) and those with a squamous cell carcinoma (30.4%) or adenocarcinoma (13.2%) (P=0.01). Raised inflammatory markers pre-operatively did not confer a statistically significant higher risk of post-operative chest infection. HDU/ITU care: patients with tumours of IA3 (23.8%) had a higher number of readmissions to HDU or ITU care (P<0.001), however other comorbidities had no correlation with HDU/ITU admissions. Reintubation: COPD patients conferred a higher chance of reintubation (P=0.03). The majority of reintubations occurred in right-sided lobectomies performed via thoracotomy for squamous cell carcinomas (n=2), however with no statistical significance. Renal failure: pre-operative anaemia conferred a higher chance of post-operative renal failure (P=0.01). Chronic pain: patients with no prior smoking history (6.8%) were more likely to have chronic post-operative pain (P=0.003). Histological subtypes other than adenocarcinoma or squamous cell carcinoma (11.1%) conferred a greater likelihood of chronic pain. In the 29 patients aged ≥85 years, 15 (51.7%) had complications post-operatively, mainly chest infections (24.1%), PAL (10.3%), and AF (20.7%).

Hospital LOS

The median LOS for the whole study population was 6 days (range, 1–183 days). Median LOS in those with lobar resections and more was 7 days (range, 2–183 days) compared to 6 days in sublobar resections (range, 2–104 days) (P=0.01). Minimally invasive approaches conferred a lower LOS: robotic (mean, 6 days), VATS (mean, 10 days), thoracotomy (mean, 12 days) (P=0.02). Thoracotomy patients had a LOS that was twice as long as those in the robotic group. The median LOS was 7 days (range, 2–65 days) for those aged ≥85 years.

Survival

All-cause mortality was 55.1% at a median follow-up of 4.6 years. The median overall survival (OS) was 3.5 years, with a 1-, 3-, and 5-year survival of 82.5%, 57.1%, and 38.2%, respectively. The overall 90-day mortality was 6/189 (3.2%), 4 of whom died in hospital, due to cardiac arrest (n=2) or respiratory failure (n=2). As expected, OS worsened with increasing tumour stage (P=0.001) (Figure 1). The median OS at 1-, 3-, and 5-year for each stage are as follows: IA1 (76.9%, 53.8%, and 36.9%), IA2 (93.6%, 69.7%, and 40.0%), IA3 (71.4%, 65.9%, and 40.0%), IB (81.0%, 62.8%, and 43.9%), IIA (84.6%, 53.8%, and 38.4%), IIB (84.0%, 57.7%, and 34.6%), IIIA (52.4%, 25.0%, and 9.4%), and IIIB (71.4%, 28.6%, and 1.0%). Statistically significant predictors of a worse survival rate included obesity (P=0.046), higher pathological tumour stage (P=0.002) and incomplete resection (R1 or R2) (P=0.02). Patients who underwent a thoracotomy did not confer a worse survival to those who had a minimally invasive approach (P=0.60). There was also no statistically significant difference in OS with sublobar vs. lobar and more resections (P=0.78), tumour subtype (P=0.40) or adjuvant chemotherapy (P=0.67). The median OS in lobectomies was 3.7 years compared to 2.8 years for wedge resections (P=0.40). In patients who underwent lobectomies, the median OS for RATS, VATS and thoracotomy approaches were 3.5, 3.6, and 3.7 years, respectively (P=0.50). Median OS for over 85s was 5.10 years, with 1-, 3-, and 5-year survivals being 89.6%, 65.8%, and 41.5%, respectively.

Figure 1 Kaplan Meier graph showing OS accompanied by median OS and DFS in years according to pathological tumour stage. OS, overall survival; DFS, disease-free survival.

Recurrence data was only available for 172 patients. The median disease-free survival (DFS) for 172 patients, was 2.4 years (Figure 1). The 1-, 3-, and 5-year DFS was 76.0%, 43.6%, and 33.6%, respectively. The median DFS at 1-, 3-, and 5-year for each stage are as follows: IA1 (75.5%, 33.6%, and 1.0%), IA2 (90.7%, 52.5%, 44.5%), IA3 (64.2%, 28.1%, and 18.7%), IB (72.8%, 60.2%, and 34.8%), IIA (75.0%, 65.6%, and 54.7%), IIB (77.3%, 34.3%, and 22.9%), IIIA (41.9%, 30.0%, and 15.3%), and IIIB (66.7%, 16.7%, and 1.0%). Statistically significant predictors of a reduced DFS rate and therefore likelihood of recurrence, included: reduced PS (P=0.03), baseline anaemia (P=0.04), a higher pathological staging (P<0.001) and incomplete resection (R>1) (P<0.001). Extent of lung resection, tumour subtype and adjuvant chemotherapy made no statistically significant difference to DFS (P=0.97, P=0.91, P=0.98). The median DFS in lobectomies was 3.0 years compared to 2.3 years for wedge resections (P=0.80). In patients who underwent lobectomies, the median OS for RATS, VATS and thoracotomy approaches were 3.0, 3.1, and 2.1 years, respectively (P=0.60). Median DFS for over 85s was 5.10 years with 1-, 3-, and 5-year DFS being 79.2%, 56.5%, and 44.4%, respectively.

Discussion

As the proportion of octogenarians in the general population increases in the Western world, we are seeing more and more octogenarians who are eligible for oncological lung resections, despite a greater likelihood of comorbidities. With these changing demographics, studies have reported morbidity and survival outcomes in octogenarians (11,12), however there is still paucity in outcome data with regards to specific risks associated with certain comorbidities. Our study addresses this deficit in the literature by describing likelihoods of certain complications in octogenarians with specific comorbidities.

Survival

There is still debate regarding extent of lung resection in octogenarians specifically weighing up risks and benefits. Lobectomy is still considered the preferable form of lung resection in NSCLC, conferring a superior 5-year survival compared to sublobar resection even in octogenarians (13). Owing to more post-operative complications occurring in already co-morbid octogenarians following lobectomies, sublobar resections such as segmentectomies and wedge resections are becoming more frequent with comparable results in OS and DFS (14). Interestingly, Mimae et al. found a lower incidence of death due to causes other than lung cancer with wedge resections compared to lobectomies in octogenarians (15). Lobectomies in our population conferred an additional 1-year OS but only 0.7 years DFS over wedge resections with no statistical significance. The OS and DFS were comparable between the surgical approaches in lobectomy patients and our OS and DFS rates comparable to Mimae et al. showing no difference in 3-year survival rates in early- stage NSCLC (16). Our 90-day mortality was 3.2% and our 30-day mortality was 1.6% compared to 3.9% 30-day mortality in patients from another UK-based major thoracic centre study from Saftic et al. (8). Our 5-year survival (38.2%) is also comparable to theirs of 40.8%, with no intraoperative deaths in either study (11). This could be explained by the good level of pre-operative fitness which our octogenarians population have, which suggests that curative lobectomy or sublobar resection, can offer a good prognostic outcome in carefully selected patients. In recent years, stereotactic body radiotherapy (SBRT) has been successfully used for prevention of local spread in NSCLC (17) and is an attractive choice in operable cancers for both clinicians and patients owing to a reduced perioperative disease burden as a result of a less invasive nature (18). However, SBRT showed inferior results compared to lobar and sublobar resections, both for OS and freedom from recurrence in a recent metanalysis (19). Razi et al. found that in octogenarians, lobectomy with rigorous staging lymphadenectomy conferred an additional 21 months OS compared to SBRT, meaning they could achieve more accurate staging and potentially offer adjuvant therapy earlier (20). They reported a median OS of 6.2 years, which without rigorous lymphadenectomy, dropped to 4.4 years, a figure comparable to our median OS of 3.7 years in the lobectomy cohort. This would suggest that in healthy octogenarians with a good functional status, SBRT or surgical resection can be offered safely, with good long-term outcomes, however outcomes in carefully selected individuals can be more favourable with surgery provided complete staging lymphadenectomy is undertaken at operation. In our experience, patients often expressed a preference for surgery over SBRT as it reduces the psychological burden of having a cancerous tumour if resected and treatment can be completed in a single hospital admission rather than multiple trips to a regional centre which can involve long distance travelling for some of our elderly patients.

Complications

A similar Japanese study by Ijima et al., identified smoking history and a histological subtype of squamous cell carcinoma as negative predictors of complications (14). Our study echoes these results with regards to squamous cell carcinoma subtype, as well as identifying COPD as a statistically significant risk factor for overall complications, something which Saftic et al. also identified with a similar level of statistical significance (8). Our study adds a further analysis of percentage rates of specific complications if a patient has a particular comorbidity. A recent Atlantan study by Lou et al. shows a LOS of 5.1 days in octogenarians which was no worse compared to younger cohorts (21). Geographical logistics can account for our longer LOS rates of 6 days however this is still comparable. By identifying comorbidities such as COPD and smoking history that pose a statistically significant risk of specific complications such as PAL, chest infection and admission to HDU/ITU care, we can better counsel octogenarians towards surgery, and optimise them pre-operatively to limit post-operative complications. None of our patients were of a pre-operative PS above 1 and with excellent average lung function [mean forced expiratory volume in the first second (FEV1) 94% predicted], suggesting that their low complication rates could in part be attributable to a good pre-operative functional status. It is suggested that a predicted FEV1 ≥70% can reduce the rate of post-operative pulmonary complications in all ages (22). Hence, a thorough clinical assessment and patient selection is mandatory before performing surgery in octogenarians. Given the survival outcomes described previously, naturally many patients could choose less invasive therapies with fewer complications, however the incidence of serious life-changing complications was ≤2%, mostly attributable to pre-existing modifiable conditions such as COPD and high markers of inflammation making post-operative complications more likely. Hence, in the face of less invasive therapies, carefully selected octogenarians whose comorbidities can be identified and optimized, can have fewer short-term complications, and improved long-term outcomes post-surgical resection. Integration of risk assessment and prehabilitation in the form of breathing exercises and walking, into local protocols, as we have trialled at our institution, may help towards achieving such outcomes.

Limitations

Our study was a retrospective study which inevitably limits overall analysis. In particular, it limits our ability to analyse the number of lymph nodes sampled at operation and its impact on OS and DFS, however even without this information our OS and DFS results are comparable with lobectomies compared to other alternative treatments such as SBRT. Additionally, the ease of dissection and accessibility that RATS provides compared to VATS and thoracotomy, complete lymphadenectomy protocols can be integrated into everyday practice, in order to confer the most benefit to those octogenarians who are surgically fit and likely to do well post-operatively. We therefore hope that our study stimulates the generation of further evidence from other centres nationally surrounding the role of surgical resections in octogenarians, to validate our conclusions.

Conclusions

Curative surgery is safe and feasible with good long-term outcomes in carefully selected octogenarians. Negative predictors of specific complications can be identified and optimised in order to improve post-operative outcomes. The percentage risk of specific complications may be used to counsel patients better pre-operatively. Surgical resection in those patients with NSCLC, surgery should be offered at an earlier pathological stage and if carefully selected, these patients can have very favourable outcomes.

Acknowledgments

We offer special thanks to Miss Ruth McCormick, data coordinator for help with data extraction.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-703/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-703/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-703/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-703/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional board of ethics of Golden Jubilee National Hospital (No. 1966) and clinical governance and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. World Health Organization. Lung cancer. 2023. Available online: https://www.who.int/news-room/fact-sheets/detail/lung-cancer?gad_source=1&gclid=CjwKCAiAi6uvBhADEiwAWiyRdpcUQaKPi1U6sgA-5Dvu3cjj97MPm0aFh7F0Arz8ek0WoETQ15NyxhoCdvQQAvD_BwE
2. Global Cancer Observatory. Trachea, Bronchus and Lung Factsheet. Accessed 11th February 2024. Available online: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
3. World Cancer Research Fund. UK Cancer Statistics. Accessed 11th February 2024. Available online: https://www.wcrf-uk.org/preventing-cancer/uk-cancer-statistics/?gclid=CjwKCAjwrJ-hBhB7EiwAuyBVXSgvldnRzZ__6ZtplhRNUqv6NtF71oz-kD_Gs-ySAVLEWn1pDG80ERoCfdEQAvD_BwE#Source2
4. Gibson GJ, Loddenkemper R, Lundbäck B, et al. Respiratory health and disease in Europe: the new European Lung White Book. Eur Respir J 2013;42:559-63. [Crossref] [PubMed]
5. Silva M, Milanese G, Ledda RE, et al. European lung cancer screening: valuable trial evidence for optimal practice implementation. Br J Radiol 2022;95:20200260. [Crossref] [PubMed]
6. Field JK, Duffy SW, Baldwin DR, et al. The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer. Health Technol Assess 2016;20:1-146. [Crossref] [PubMed]
7. NHS England. Targeted screening for lung cancer with low radiation dose computed tomography. 2019. Accessed 11th February 2024. Available online: https://www.england.nhs.uk/publication/targeted-screening-for-lung-cancer/
8. Saftic I, Bille A, Asemota N, et al. Risks and rewards of the surgical treatment of lung cancer in octogenarians. Interact Cardiovasc Thorac Surg 2021;33:905-12. [Crossref] [PubMed]
9. Lardinois D, De Leyn P, Van Schil P, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg 2006;30:787-92. [Crossref] [PubMed]
10. Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351-60. [Crossref] [PubMed]
11. Dominguez-Ventura A, Allen MS, Cassivi SD, et al. Lung cancer in octogenarians: factors affecting morbidity and mortality after pulmonary resection. Ann Thorac Surg 2006;82:1175-9. [Crossref] [PubMed]
12. Dominguez-Ventura A, Cassivi SD, Allen MS, et al. Lung cancer in octogenarians: factors affecting long-term survival following resection. Eur J Cardiothorac Surg 2007;32:370-4. [Crossref] [PubMed]
13. Chan EY, Amirkhosravi F, Nguyen DT, et al. Lobectomy Provides the Best Survival for Stage I Lung Cancer Patients Despite Advanced Age. Ann Thorac Surg 2022;114:1824-32. [Crossref] [PubMed]
14. Iijima Y, Iwai S, Yamagata A, et al. Is lung resection appropriate for late octogenarians? Surgical outcomes of patients aged ≥ 80 years with lung cancer. Clin Transl Oncol 2021;23:1585-92. [Crossref] [PubMed]
15. Mimae T, Miyata Y, Yoshimura K, et al. Risk of death due to other causes is lower among octogenarians with non-small cell lung cancer after wedge resection than lobectomy/segmentectomy. Jpn J Clin Oncol 2021;51:1561-9. [Crossref] [PubMed]
16. Mimae T, Saji H, Nakamura H, et al. Survival of Octogenarians with Early-Stage Non-small Cell Lung Cancer is Comparable Between Wedge Resection and Lobectomy/Segmentectomy: JACS1303. Ann Surg Oncol 2021;28:7219-27. [Crossref] [PubMed]
17. Hopmans W, Damman OC, Porsius JT, et al. Treatment recommendations by clinicians in stage I non-small cell lung cancer: A study of factors that influence the likelihood of accounting for the patient's preference. Patient Educ Couns 2016;99:1808-13. [Crossref] [PubMed]
18. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015;16:630-7. Erratum in: Lancet Oncol 2015;16:e427. [Crossref] [PubMed]
19. Ijsseldijk MA, Shoni M, Siegert C, et al. Oncologic Outcomes of Surgery Versus SBRT for Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis. Clin Lung Cancer 2021;22:e235-92. [Crossref] [PubMed]
20. Razi SS, Kodia K, Alnajar A, et al. Lobectomy Versus Stereotactic Body Radiotherapy in Healthy Octogenarians With Stage I Lung Cancer. Ann Thorac Surg 2021;111:1659-65. [Crossref] [PubMed]
21. Lou X, Sanders A, Wagh K, et al. Safety and Feasibility of Thoracoscopic Lung Resection for Non-Small-Cell Lung Cancer in Octogenarians. Innovations (Phila) 2021;16:68-74. [Crossref] [PubMed]
22. Kim ES, Kim YT, Kang CH, et al. Prevalence of and risk factors for postoperative pulmonary complications after lung cancer surgery in patients with early-stage COPD. Int J Chron Obstruct Pulmon Dis 2016;11:1317-26. [Crossref] [PubMed]