Role of genetic alterations on outcomes for pulmonary resection in oligometastatic non-small cell lung cancer

Introduction

At diagnosis, approximately 50% of non-small cell lung cancer (NSCLC) patients present with metastatic disease (1,2). However, a subset of these individuals exhibits limited, rather than disseminated spread, categorized as oligometastatic disease (1). Hellman and Weichselbaum first described this state as an intermediate tumor burden level between those of locally and widely disseminated neoplastic processes (3). Thought-leaders in this space have argued that such patients can attain improved oncologic and survival outcomes with aggressive treatment of the primary tumor and all metastatic sites.

This concept has become the focus of several recent trials and retrospective studies (4-9). These investigations demonstrated that in oligometastatic (≤3 synchronous metastases) NSCLC, local therapy to all sites of disease with surgical and/or radiation therapy, described as comprehensive local consolidative therapy (cLCT), can improve progression-free survival (PFS) and overall survival (OS) compared to systemic therapy alone (4,10-18). Concurrently, the identification of genomic alterations in NSCLC, including EGFR and KRAS mutations, as well as ALK rearrangements, and others, has driven widespread testing for actionable mutations that may guide treatment strategies (17,19). While these advances have shown that the presence of specific genetic alterations has a clear impact on outcomes for lung cancer patients, minimal previous investigations characterized the influence of genomic variations, specifically EGFR, on outcomes for oligometastatic NSCLC patients undergoing cLCT (17,20-22). Furthermore, prior studies included patients who received heterogeneous cLCT modalities, leaving the outcomes for oligometastatic NSCLC patients with genomic alterations specifically undergoing lung resection as part of cLCT unclear. As such, we sought to ascertain the impact of genetic alterations on oncologic and survival outcomes in this patient population. We present this article in accordance with the REMARK reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1140/rc).

Methods

Study population

Following institutional review board approval (protocol 2023-0907; BASEC-reference number 2020-02566) with a waiver of informed consent, a retrospective review of databases prospectively maintained by the University of Texas MD Anderson Cancer Center and the University Hospital Zurich was performed. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Eligibility criteria included histological confirmation of stage IV NSCLC, treatment between January 1^st, 1996 and December 31^st, 2023, and oligometastatic disease (three or fewer synchronous metastatic lesions) at diagnosis (4-6,16). TNM-staging was defined according to the 8th Edition of the American Joint Commission on Cancer (23). All included patients underwent pulmonary resection as part of cLCT following multidisciplinary evaluation and treatment planning. Cohort identification was derived from using natural language processing (NLP) methods (10), and database/electronic-medical record (EMR) searches for those patients not flagged by NLP approaches. Collected variables were pulled from prospectively maintained databases and supplemented with EMR review.

Gathered datapoints included demographic, clinicopathologic, and treatment-related variables. Patient and tumor characteristics included sex, age at surgery, smoking history, primary tumor location, genomic alteration(s) of the primary tumor, and number of metastatic deposits. Patients were stratified by genomic alteration status: TP53, EGFR, KRAS, ALK, and no alterations. Additionally, individuals found to have 2 or more genomic alterations were distinctly categorized. The multiple genomic alterations discovered included ALK with TP53, EGFR with TP53, KRAS with TP53, as well as EGFR with KRAS. Gathered survival and oncologic outcomes included 30- and 90-day survival, PFS, and OS.

Variable and outcome definitions

As described in our previous publications, intrathoracic nodal disease, irrespective of the number of involved lymph nodes, was counted as a singular metastatic site, while multiple metastatic foci within an organ were considered as distinct sites of disease (10). Oligometastatic NSCLC was defined as three or fewer synchronous metastatic lesions, congruent with the definition utilized by prior research (4-6,16). Local consolidative therapy (LCT), may be defined as surgical resection or radiotherapy targeting the primary tumor and/or site(s) of metastases, which may or may not include all sites of disease. Comprehensive LCT, or cLCT is defined as the use of LCT modalities directed at the primary tumor and all metastatic sites, for complete consolidation (10).

OS was defined as the duration from diagnosis to patient death, while PFS measured the time from diagnosis to disease progression or recurrence. Patients alive and without disease progression or recurrence at the study’s end were censored in calculations on the last follow-up date.

Statistical analysis

Pearson chi-squared and Fisher’s exact test were utilized to analyze categorical variables, and Mann-Whitney U and Kruskal-Wallis tests were used to analyze continuous variables. OS and PFS were analyzed using the Kaplan-Meier method, while group differences were calculated using the log-rank test. Multivariable Cox regression analysis was used to determine the unadjusted and adjusted influences of clinicopathologic variables on OS and PFS. Variables included in the univariate Cox regression calculations were based on clinical importance and relevance, and included age, sex, smoking history, Eastern Cooperative Oncology Group (ECOG) performance status, genetic alteration, and neoadjuvant therapy. Statistical analyses were performed using IBM SPSS Statistics (Version 24). The P values reported are two-sided, with a P value <0.05 considered statistically significant.

Results

Patient population

In total, 87 patients met inclusion criteria, with 61 (70.1%) from MD Anderson Cancer Center and 26 (29.9%) from the University of Zurich (Table 1). EGFR mutations only (+EGFR) were identified in 12 (13.8%) individuals. Among the 75 patients with other alterations (-EGFR), identified genomic variations included TP53 (n=1/87, 1.2%), KRAS (n=11/87, 12.6%), and ALK (n=5/87, 5.7%), with no alterations found in 52 (59.8%) patients. Additionally, 6 individuals with multiple genomic alterations were found: ALK with TP53 (n=1/87, 1.2%), EGFR with TP53 (n=3/87, 3.4%), KRAS with TP53 (n=1/87, 1.2%), and EGFR with KRAS (n=1/87, 1.2%). The median age at diagnosis for the +EGFR group was 58.4 [interquartile range (IQR): 15.2] years, and 58.0 (IQR: 12.6, P=0.41) years for the −EGFR group. Both cohorts were fairly balanced by sex (+EGFR, n=7/12, 58.3%; −EGFR, n=37/75, 49.3%, P=0.56), and were predominantly White (+EGFR, n=10/12, 83.3%; −EGFR, n=64/75, 85.3%, P=0.92). Smoking history was more prevalent among individuals without EGFR mutations (n=64/75, 85.3%) compared to +EGFR patients (n=7/12, 58.3%, P=0.04). Regarding ECOG performance status, 8 (66.7%) of the +EGFR patients had an ECOG status of 0 or 1, and another 4 (33.3%) had a status of 2. Among all others, 46 (61.3%) had an ECOG status of 0 or 1, and 23 (30.7%, P=0.97) had an ECOG status of 2.

Clinical tumor status (cT) was cT1 in 4 (33.3%) +EGFR patients and 32 (42.7%) −EGFR patients, cT2 in 4 (33.3%) +EGFR patients and 27 (36.0%) −EGFR patients, cT3 in 1 (8.3%) +EGFR patients and 8 (10.7%) −EGFR patients, and cT4 in 3 (25.0%) +EGFR patients and 8 (10.7%, P=0.58, Table 2) −EGFR patients. As for clinical nodal status (cN), 6 (50.0%) of +EGFR and 44 (58.7%) −EGFR patients had cN1, 3 (25.0%) +EGFR patients and 12 (16.0%) −EGFR patients had cN2, 3 (25.0%) +EGFR patients and 16 (21.3%) −EGFR patients had cN2, and only 3 (4.0%, P=0.76) −EGFR patients had cN3. The most common location for metastatic spread for both groups was the brain (+EGFR, n=5/12, 41.7%; −EGFR, n=47/75, 62.7%, P=0.04). Other sites of metastatic involvement included bone, adrenal gland, contralateral lung, and pleura. Most individuals of both groups had one site of metastatic involvement (+EGFR, n=10/12, 83.3%; −EGFR, n=73/75, 97.3%, P=0.02).

Treatment details

Systemic therapy was commonly administered in the preoperative setting to all patients (Table 3). Among those without EGFR mutation, 34 (45.3%) received only chemotherapy, 4 (5.3%) received only targeted therapy, and 1 (1.3%) received chemotherapy and targeted therapy. As for +EGFR patients, 3 (25.0%) received only chemotherapy, 3 (25.0%) received only targeted therapy, and 2 (16.7%, P=0.03) received chemotherapy and targeted therapy. All patients underwent resection of their primary lung tumors as part of cLCT. Surgical intervention was utilized more often to consolidate distant disease among those without EGFR mutations (n=62/75, 82.7%) as compared to +EGFR patients (n=7/12, 58.3%), while rates of radiation therapy to metastatic sites were nearly equivalent between groups (+EGFR, n=8/12, 66.7%; −EGFR, n=56/75, 74.7%, P=0.60).

Thoracotomy was the most common surgical approach (+EGFR, n=6/12, 50.0%; −EGFR, n=58/75, 77.3%, P=0.07), and the majority of patients underwent lobectomy (+EGFR, n=8/12, 66.7%; −EGFR, n=59/75, 78.7%, P=0.56). R0 resection margins were achieved in most patients (+EGFR, n=10/12, 83.3%; −EGFR, n=68/75, 90.7%, P=0.65).

Among +EGFR patients, the most common pathologic tumor (pT) statuses were pT3 and pT4, each observed in 3 patients (25.0%). As for the other alteration status individuals, pT4 was the most commonly observed status (n=20/75, 26.7%, P=0.70, Table 3). Pathologic nodal (pN) status was most frequently pT0 for both groups (+EGFR, n=7/12, 58.3%; −EGFR, n=42/75, 56.0%, P=0.91), and most patients were found to have adenocarcinoma (+EGFR, n=11/12, 91.7%; −EGFR, n=62/75, 82.7%, P=0.39). While the majority of +EGFR individuals had moderately differentiated tumors (n=9/12, 75.0%%), other individuals predominantly had poorly differentiated tumors (n=47/75, 62.7%, P=0.01).

Oncologic and survival outcomes

Following lung resection, primary tumor site recurrence was uncommon among both groups (+EGFR, n=2/12, 16.7%; −EGFR, n=9/75, 12.0%, P=0.65, Table 4), as was recurrence at previously treated metastatic locations (+EGFR, n=1/12, 8.3%; −EGFR, n=20/75, 26.7%, P=0.17). Distant recurrence was common in both groups (+EGFR, n=6/12, 50.0%; −EGFR, n=41/75, 54.7%, P=0.73). Freedom from disease progression or recurrence was better among +EGFR patients (Figure 1). Median PFS in the +EGFR group was 43.1 months (95% CI: 22.14–64.07) and 19.1 months in the −EGFR group (95% CI: 16.46–31.74, P=0.58). Univariate Cox regression calculations showed no impact of EGFR alteration on PFS (HR =0.52, 95% CI: 0.20–1.34, P=0.18).

Figure 1 Kaplan-Meier curves comparing PFS between +EGFR and −EGFR groups. PFS, progression-free survival.

All 87 patients survived 30 days following pulmonary resection, and 90-day survival was achieved in 11 (91.7%) +EGFR patients and 74 (98.7%, P=0.13) other alteration status patients. Kaplan-Meier survival analyses revealed median OS of 88.9 months for +EGFR patients (95% CI: 48.46–121.28), and 30.8 months for –EGFR patients (95%CI: 12.25–49.36, P=0.20, Figure 2).

Figure 2 Kaplan-Meier curves comparing OS between +EGFR and −EGFR groups. OS, overall survival.

Notably, 3 (25.0%) +EGFR patients had bone metastasis. Among these individuals, 1 (8.3%) patient had only bone metastasis, 1 (8.3%) patient also had pleural metastasis, and 1 (8.3%) patient also had metastatic spread to the brain and adrenal gland. In terms of systemic therapy, the 2 (16.7%) individuals with bone and visceral metastases received targeted therapy in the neoadjuvant and adjuvant settings, whereas the individual with isolated bone metastasis only received adjuvant chemotherapy. The patient with only bone metastasis, as well as the patient with three total metastatic disease sites, experienced distant site recurrences following pulmonary resection. All of these individuals survived 30 and 90 days following primary tumor resection.

Multivariate Cox regression analysis was performed to determine predictors of PFS and OS (Table 5). Included covariates were those that had a significant impact on oncologic and survival outcomes in oligometastatic NSCLC. We found that the presence of EGFR alteration did not independently predict PFS (HR =0.68, 95% CI: 0.09–5.05, P=0.71) nor OS (HR =0.44, 95% CI: 0.05–7.23, P=0.62). However, cT3 and cT4 negatively impacted PFS (HR =2.99, 95% CI: 1.49–6.04, P=0.02) and OS (HR =3.48, 95% CI: 1.61–7.53, P=0.004).

Discussion

This present study represents a large, multicenter homogenous patient cohort with oligometastatic NSCLC who underwent cLCT, and to our knowledge, is the first to evaluate the impact of genomic alterations on outcomes following pulmonary resection in this patient population. Importantly, we unveiled a trend suggesting that the presence of an EGFR mutation may be associated with favorable OS when compared to other mutational statuses. Further, our findings corroborate recent reports highlighting the potential therapeutic benefits of cLCT in appropriately selected oligometastatic NSCLC patients (5,10,14,24).

Improvements in PFS and OS following LCT for oligometastatic NSCLC patients were first demonstrated in the landmark study by Gomez and colleagues (4,6). Pulmonary resection has also been shown to be a beneficial LCT modality in well-selected oligometastatic NSCLC patients, as shown by its positive impact on oncologic and survival outcomes (14). Subsequent studies revealed that LCT to the primary tumor and all sites of metastatic spread, termed cLCT, can improve OS when compared to patient populations who received LCT to only some disease sites (5). Our prior work also demonstrated substantial OS improvements with cLCT as compared to subcomprehensive LCT (21). Additionally, the presented results corroborate prior reports highlighting the feasibility of pulmonary resection as part of cLCT for oligometastatic NSCLC. Previously, we showed that pulmonary resection can enhance locoregional control while also improving oncologic and survival outcomes in a safe manner (10,25). Of key interest, recent clinical practice guidelines, building on the foundation of all previous work, recommend the consideration of LCT, including surgical consultation for all physiologically suitable patients with oligometastatic lung cancer (26).

The advent of next-generation sequencing for histologic subtypes and molecular drivers has led to the rise of targeted therapies, further transforming stage IV NSCLC care (27,28). Notably, 20% of non-Asian and 50% of Asian patients with NSCLC have tumors with EGFR mutations, and tyrosine kinase inhibitors (TKIs) have demonstrated a crucial role in improving these patients’ outcomes (29). Interestingly, compared to polymetastatic disease, oligometastatic NSCLC cases tend to express fewer genomic mutations, which highlights the significance of consolidating sites of disease (30). As such, first-line TKI, in conjunction with LCT, has been shown to provide survival benefits to oligometastatic NSCLC patients with EGFR mutations (22,31). Recently, we demonstrated that TKIs and cLCT confer the most favorable outcomes in this patient cohort, with significantly improved long-term survival (17). Moreover, brain metastases are commonly found in oligometastatic NSCLC patients with EGFR alteration, and better survival is seen in this cohort in comparison to similar patients without EGFR mutation, especially after receipt of TKI and LCT therapy (32).

In the present study, we considered the advances in systemic agents for advanced NSCLC in the contemporary era and sought to determine the impact of genomic alterations on outcomes in a large, multicenter cohort of oligometastatic NSCLC patients undergoing pulmonary resection. Importantly, and underscoring previous reports, we found that EGFR mutation of the primary tumor seemed to be associated with improved survival outcomes, though not statistically significant. Although the optimal timing of TKI and subsequent cLCT remains unclear, our results highlight the benefits of pursuing aggressive LCT strategies with pulmonary resection in carefully selected oligometastatic NSCLC patients with EGFR alteration. This is especially true in light of advances in both targeted therapies and LCT modalities. Ultimately, our findings underscore the importance of clinicians and surgeons to remain vigilant in their management of oligometastatic NSCLC patients, especially as our findings suggest that pulmonary resection may provide benefit to those with specific genetic alterations. Moreover, the Society of Thoracic Surgeons published guidelines that stress the importance of surgical decisions for stage IV NSCLC to be made in multidisciplinary settings, which should involve consideration of patient- and tumor-specific characteristics (26).

Further research is needed in order to uncover oncologic and survival differences among various genomic alterations. While targeted agent availability and efficacy can account for some observed distinctions in outcomes, the interplay among other variables, such as disease biology, patient demographics, comorbidities, and other potentially unknown factors must be investigated in order to further advance treatment paradigms for oligometastatic NSCLC. Discoveries in this space will inevitably lead to expanded therapeutic options for clinicians. Nevertheless, as a thoracic oncologic surgical community, we must maintain a commitment to aggressive management strategies while adapting to novel treatment modalities.

Despite its promising findings, this study has several limitations that must be acknowledged. The included patients were medically and surgically treated at two distinct institutions, which may have had different criteria for selecting surgical candidates. We only selected oligometastatic NSCLC patients who underwent pulmonary resection, with the inherent knowledge that these patients had baseline function and performance superior to those who did not receive lung resection. As such, these results may be less applicable to those who received alternate treatment modalities. Furthermore, the number of patients who underwent pulmonary resection, as well as the number of individuals with EGFR mutation, is part of a small sample size. Additionally, patients included in this study received treatment between 1996 and 2023. As mentioned, therapies for stage IV NSCLC have recently advanced, and their benefits would only be captured in those who received them.

Conclusions

This multicenter study evaluated the role of genomic alterations on the oncologic and survival outcomes of a homogenous cohort of oligometastatic NSCLC patients who underwent pulmonary resection as part of cLCT. Our findings support previous investigations regarding the therapeutic benefits of cLCT, along with the feasibility of performing pulmonary resection in well-selected individuals. Moreover, our results suggest that genomic alterations may play a role in the prognostication of oligometastatic NSCLC patients who undergo pulmonary resection as part of cLCT.

Acknowledgments

This study was presented as a poster at The American Association for Thoracic Surgery (AATS) 105^th Annual Meeting (AATS Annual Meeting, USA, 2025).

Footnote

Reporting Checklist: The authors have completed the REMARK reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1140/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1140/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1140/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1140/coif). R.R. serves as an unpaid Associate Editor-in-Chief of Journal of Thoracic Disease from May 2024 and April 2026. M.B.A. serves as an unpaid editorial board member of Journal of Thoracic Disease from August 2024 and July 2026. R.W. received speaking fee from Astra Zeneca and MSD, and served as the Advisory board member at MSD. D.R. received grant funding from Intuitive Surgical, Inc. A.V. served as the consultant and director for American Board of Thoracic Surgery, and served as the director of Society of Thoracic Surgeons. I.O. reports the following conflicts of interest: Roche (Institutional Grant), AstraZeneca (Advisory Board and Steering Committee), MSD (Advisory Board), BMS (Advisory Board), Medtronic (Institutional Grant and Advisory Board), Intuitive (Proctorship and Speakers Fee), Sanofi (Speakers Fee), Regeneron (Advisory Board), XVIVO (Institutional Grant), Siemens (Speakers Fee), Astellas (Speakers Fee). I.O. is IASLC Board Director, Member of the Thoracic Clinical Practice Standards Committee and the Thoracic Education Committee of AATS, iMig Board Member and JTCVS Associate Editor. She is also in the Stiftungsrat Schulthessklinik and an Advisory Board Member at Med Uni Wien for Comprehensive Center for Chest Diseases (CCCD). The other 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 and its subsequent amendments. The study was approved by the institutional review boards of University of Texas MD Anderson Cancer Center (Protocol 2023-0907) and the University Hospital Zurich (BASEC-reference number 2020-02566). 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. Blumenthaler AN, Antonoff MB. Classifying Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel) 2021;13:4822. [Crossref] [PubMed]
2. Abdel-Rahman O. Validation of the prognostic value of new sub-stages within the AJCC 8th edition of non-small cell lung cancer. Clin Transl Oncol 2017;19:1414-20.
3. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995;13:8-10. [Crossref] [PubMed]
4. Gomez DR, Tang C, Zhang J, et al. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. J Clin Oncol 2019;37:1558-65. [Crossref] [PubMed]
5. Mitchell KG, Farooqi A, Ludmir EB, et al. Improved Overall Survival With Comprehensive Local Consolidative Therapy in Synchronous Oligometastatic Non-Small-Cell Lung Cancer. Clin Lung Cancer 2020;21:37-46.e7. [Crossref] [PubMed]
6. Gomez DR, Blumenschein GR, Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. The Lancet Oncol 2016;17:1672-82. [Crossref] [PubMed]
7. Fleckenstein J, Petroff A, Schäfers HJ, et al. Long-term outcomes in radically treated synchronous vs. metachronous oligometastatic non-small-cell lung cancer. BMC Cancer 2016;16:348. [Crossref] [PubMed]
8. Heymach J. Nivolumab and Ipilimumab With or Without LCT in Treatment Patients With Stage IV NSCLC. Clinicaltrials.gov identifier: NCT03391869. Updated October 24, 2024. Accessed October 28, 2024. NCT03391869.
9. Gandhi, S. Osimertinib, Surgery, and Radiation Therapy in Treating Patients with Stage IIIB or IV NSCLC with EGFR Mutations, NORTHSTAR Study. Clinicaltrials.gov identifier: NCT03410043. Updated June 24, 2024. Accessed October 28, 2024. NCT03410043.
10. Deboever N, Mitchell KG, Farooqi A, et al. Perioperative and oncologic outcomes of pulmonary resection for synchronous oligometastatic non-small cell lung cancer: Evidence for surgery in advanced disease. J Thorac Cardiovasc Surg 2024;167:1929-35.e2. [Crossref] [PubMed]
11. Socinski MA, Evans T, Gettinger S, et al. Treatment of stage IV non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e341S-68S.
12. Yang JC, Lee DH, Lee JS, et al. Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor‒Resistant, EGFR-Mutant, Metastatic Nonsquamous Non-Small Cell Lung Cancer. J Clin Oncol 2024;42:4029-39. [Crossref] [PubMed]
13. Iyengar P, Wardak Z, Gerber DE, et al. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol 2018;4:e173501. [Crossref] [PubMed]
14. Mitchell KG, Farooqi A, Ludmir EB, et al. Pulmonary resection is associated with long-term survival and should remain a therapeutic option in oligometastatic lung cancer. J Thorac Cardiovasc Surg 2021;161:1497-504.e2. [Crossref] [PubMed]
15. Kuang L, Zhang Y, Wang H, et al. Prognostic factors influencing overall survival in stage IV EGFR-mutant NSCLC patients treated with EGFR-TKIs. BMC Pulm Med 2025;25:114. [Crossref] [PubMed]
16. Sheu T, Heymach JV, Swisher SG, et al. Propensity score-matched analysis of cLCT for oligometastatic NSCLC that did not progress after front-line chemotherapy. Int J Radiat Oncol Biol Phys 2014;90:850-7. [Crossref] [PubMed]
17. De B, Farooqi AS, Mitchell KG, et al. Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveals EGFR Mutations to Be Associated With Longer Overall Survival. JCO Precis Oncol 2023;7:e2200540. [Crossref] [PubMed]
18. Palma DA, Olson R, Harrow S, et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol 2020;38:2830-8. [Crossref] [PubMed]
19. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018;378:113-25. [Crossref] [PubMed]
20. Elamin YY, Gomez DR, Antonoff MB, et al. Local Consolidation Therapy (LCT) After First Line Tyrosine Kinase Inhibitor (TKI) for Patients With EGFR Mutant Metastatic Non-small-cell Lung Cancer (NSCLC). Clin Lung Cancer 2019;20:43-7. [Crossref] [PubMed]
21. Xu Q, Zhou F, Liu H, et al. Consolidative Local Ablative Therapy Improves the Survival of Patients With Synchronous Oligometastatic NSCLC Harboring EGFR Activating Mutation Treated With First-Line EGFR-TKIs. J Thorac Oncol 2018;13:1383-92. [Crossref] [PubMed]
22. Lim JU. Management of Oligometastasis and Oligoprogression in Patients with Epidermal Growth Factor Receptor Mutation-Positive NSCLC in the Era of Third-Generation Tyrosine Kinase Inhibitors. Clin Lung Cancer 2021;22:e786-92. [Crossref] [PubMed]
23. Edge SB, Byrd DR, Compton CC, et al. editors. AJCC cancer staging handbook: from the AJCC cancer staging manual. New York, NY: Springer; 2010.
24. Rasco DW, Yan J, Xie Y, et al. Looking beyond surveillance, epidemiology, and end results: patterns of chemotherapy administration for advanced non-small cell lung cancer in a contemporary, diverse population. J Thorac Oncol 2010;5:1529-35. [Crossref] [PubMed]
25. Antonoff MB, Feldman HA, Mitchell KG, et al. Surgical Complexity of Pulmonary Resections Performed for Oligometastatic NSCLC. JTO Clin Res Rep 2022;3:100288. [Crossref] [PubMed]
26. Antonoff MB, Mitchell KG, Kim SS, et al. The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer. Ann Thorac Surg 2025;119:495-508. [Crossref] [PubMed]
27. Paz-Ares L, Tan HE, O’Byrne K, et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced NSCLC: Overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol 2017;28:270-7. [Crossref] [PubMed]
28. Abughanimeh O, Kaur A, El Osta B, et al. Novel targeted therapies for advanced NSCLC. Semin Oncol 2022;49:326-36. [Crossref] [PubMed]
29. Chen WC, Cheng WC, Chen CL, et al. Assessing EGFR-mutated NSCLC with bone metastasis: Clinical features and optimal treatment strategy. Cancer Med 2024;13:e7152. [Crossref] [PubMed]
30. Chang JY, Verma V. Optimize Local Therapy for Oligometastatic and Oligoprogressive Non-Small Cell Lung Cancer to Enhance Survival. J Natl Compr Canc Netw 2022;20:531-9. [Crossref] [PubMed]
31. Hu F, Li C, Xu J, et al. Additional local consolidative therapy has survival benefit over EGFR tyrosine kinase inhibitors alone in bone oligometastatic lung adenocarcinoma patients. Lung Cancer 2019;135:138-44. [Crossref] [PubMed]
32. Borghetti P, Bonù ML, Giubbolini R, et al. Concomitant radiotherapy and TKI in metastatic EGFR- or ALK-mutated non-small cell lung cancer: a multicentric analysis on behalf of AIRO lung cancer study group. Radiol Med 2019;124:662-70. [Crossref] [PubMed]