Assessing the clinical impact of severe lung cancer on non-small cell lung cancer: a single-center retrospective study

Introduction

The Eastern Cooperative Oncology Group performance status (PS) score is a widely recognized tool for evaluating the prognostic information, which could provide guidance for anti-cancer treatment according to patients’ physical ability in daily activities (1). A PS score of 2 or higher is generally considered ineligible for most randomized trials due to its association with poor survival (2-4). In real-world practice, approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) have been observed to develop poor PS (5).

The present of treatment-related advanced events and comorbidity limits management options for NSCLC, exerting varying degrees of influence on patients’ quality of life and leading to poor PS. Although novel therapies, including targeted therapy, immune checkpoint inhibitor (ICI) therapy and radiotherapy, have shown great promise in prolonging the overall survival (OS) of lung cancer patients, they are a double-edged sword. Treatment-related advanced events, such as checkpoint inhibitor pneumonitis (CIP) and tyrosine kinase inhibitor-associated interstitial lung disease, have been reported as life-threatening in previous reports (6,7). Chemotherapy-induced neutropenia, the most severe hematologic toxicity-related complication, can result in life-threatening infections (8). Additionally, respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis are more prevalent in the lung cancer population than in the general population, with prevalence rates of 38.7%, 12.9%, and 17.2%, respectively, underscoring the increased disease burden (9).

The development of oncotherapy has impacted the epidemiological patterns of lung cancer. Accordingly, the novel concept of severe lung cancer (SLC), which has gained consensus among international experts, describes the clinical reality and comprises three elements: (I) cause: acute and chronic co-morbidities, tumor-related complications, and anti-cancer therapy-associated adverse events; (II) course: a PS score between 2 to 4; (III) outcome: improvement in PS score following definitive therapy and supportive care (10). Therefore, “critical status” (CS), an extension of the concept of SLC, refers to a PS score between 2 to 4 caused by aforementioned factors. The first epidemiological study on SLC showed that the incidence of SLC ranged from 13.10% to 37.55%, even accounting for selection bias (11).

To address the clinical relevance of SLC in NSCLC, we conducted a single-center retrospective study of patients with advanced or metastatic NSCLC. Although the novel concept of SLC provides a concise depiction of clinical reality and has already gained international recognition, its validity remains uncertain due to its complex and multifaceted components. This study specifically aims to clarify the association between CS, SLC and survival outcomes, providing insight into the clinical significance of SLC in NSCLC management. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-71/rc).

Methods

Study design

In this single-center retrospective study, all metastatic NSCLC or unresectable locally advanced NSCLC who received at least one course of oncotherapy at the First Affiliated Hospital of Guangzhou Medical University between January 1, 2020, and March 31, 2023, were included. An additional inclusion criterion was being age 18 years or older. Data collected for included the patients encompassed baseline demographics and pathological characteristics. The last follow-up date was August 25, 2024. The clinical staging of all included patients was determined based on their basic demographic and clinical data, in accordance with the National Comprehensive Center Network (NCCN) guidelines (2024.V4) (12). The assessments were independently conducted by two researchers (H.J. and L.Y.), and any discrepancies were resolved through discussion and consensus within the investigation team (H.J., L.Y., D.F., H.D., and Q.L.). The data for this study were sourced from the medical record system. All relevant patient information was collected retrospectively, and there was no missing data, as all records were complete and available for analysis. The PS was assessed in real-time by the primary physician during each patient visit and documented in the medical records at that time. The study was conducted in accordance with the ethical standards of the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2021-38), with a waiver of patient consent due to the study’s low-risk, deidentified, retrospective nature.

Definition of CS and SLC

In this study, CS and SLC were defined to reflect the clinical progression and prognosis of patients with advanced or metastatic NSCLC. As illustrated in Figure 1A, advanced or metastatic NSCLC patients were categorized based on their clinical course and PS score. CS was defined as a clinical condition characterized by a PS score between 2 and 4, indicating a significant decline in functional capacity. This status resulted from acute or chronic complications, including but not limited to: acute exacerbation of COPD, radiotherapy toxicity, chemotherapy toxicity, infections, immune-related adverse events, and other treatment-related complications. Patients who did not experience CS maintained a sustained stable clinical course and were classified as stable lung cancer. Among patients who developed CS, those who showed improvement in their PS score after definitive therapy and supportive care were categorized as SLC. Conversely, patients whose condition continued to deteriorate despite intervention were classified as end-stage lung cancer. The definitive therapy and supportive care referred specifically to the approaches used to correct CS, encompassing both pharmacological treatments and interventional procedures, with further details provided in Table S1. The primary endpoint was the association between the development of CS, SLC, and OS.

Figure 1 The overall research design of the study. (A) Schematic representation of the relationship between severe lung cancer, end-stage lung cancer, critical status, and performance status scores. This diagram illustrates the clinical progression of lung cancer patients, categorizing them based on clinical course and performance status. Patients who experience a sustained stable clinical course are classified as stable lung cancer. Those in critical status, influenced by factors such as AECOPD, RT toxicity, chemo toxicity, infection, IrAEs, and others, may show either improvement to severe lung cancer or deterioration to end-stage lung cancer, as indicated by changes in performance status scores. The diagram also highlights the correlation between overall survival and clinical status, with end-stage lung cancer patients showing the lowest survival outcomes and stable lung cancer patients showing the best prognosis; (B) flow diagram of patient enrolment. AECOPD, acute exacerbation of chronic obstructive pulmonary disease; IrAEs, immune-related adverse events; NSCLC, non-small cell lung cancer; PS, performance status; RT, radiotherapy.

Outcomes of interest

Patients with metastatic NSCLC or unresectable locally advanced NSCLC who met the inclusion criteria of the study were investigated. Patients who develop CS during treatment were compared with those who did not. Among those who develop CS, SLC and non-SLC cases were compared. Additionally, among all patients who developed CS and those diagnosed with SLC, comparisons were made based on the different underlying causes of CS. Furthermore, subgroup analyses were conducted according to the PS score at the first occurrence of CS to evaluate how varying degrees of functional decline impacted outcomes. The primary end point was the association between the development of CS, SLC and OS. Variables associated with OS, including baseline characteristics and CS development, were further investigated. Electronic medical records were reviewed to identify CS and SLC.

Statistical analysis

Statistical analysis was conducted on August 25, 2024. Both the Pearson Chi-squared test/Fisher’s exact test and Mann-Whitney U test/Kruskal-Wallis-test were used to identify prognostic factors related to developing CS. Kaplan-Meier method and log-rank test were utilized to compare OS. OS was defined as time from oncotherapy initiation to date of death or last censored follow-up. A multivariable time-dependent Cox hazard proportional hazards regression model was conducted to OS analysis to adjust for significant difference in baseline characteristics. Correlation analysis were performed to assess the relationships between clinical factors and patient outcomes. The Pearson Correlation Coefficient, Point-Biserial Correlation Coefficient, and Phi Coefficient were used for correlation analysis in this study. Statistically significant was defined as a P value of less than 0.05 in a two-sided test. IBM SPSS Statistics Base 26 (SPSS Inc., Chicago, IL, USA) was used for analysis.

Results

Characteristics of population

A total of 254 patients with advanced or metastatic NSCLC were included in the analysis (Figure 1B). Both patients with unresectable locally advanced and metastatic NSCLC were included in this study. Clinical staging at diagnosis is detailed in Table 1. After a median follow-up of 19.4 months [95% confidence interval (CI): 24.7–29.9] from diagnosis, the median time to the initial onset of CS was 11.0 months (95% CI: 13.2–22.2), with 61 patients (23.4%) developed initial CS. Among these, 41 (67.2%) were categorized as SLC, while 20 (32.8%) were non-SLC. The median age of patients classified as SLC was 65 years [interquartile range (IQR), 59–69 years], compared to 65.5 years (IQR, 59.25–69.25 years) for those identified as non-SLC. The gender distribution showed that in the SLC group, 70.7% were men (29/41) and 29.3% were women (12/41), whereas in the non-SLC group, 95% were men (19/20) and 5% were women (1/20) (P=0.03). Among enrolled patients, most were initially diagnosed with stage IV (patients without initial CS: 140/193; patients with initial CS: 47/61). Common sites of metastasis included the brain, adrenal glands, bone, liver, and pleura, with a significantly higher proportion of patients without initial CS presenting with brain metastases compared to patients with initial CS (P=0.01). The vast majority of enrolled patients had an ECOG PS of 0 of 1 at initial diagnosis. Notably, five patients had a PS of 2, four of whom were classified into the SLC group. In terms of molecular profiling, 143 patients had no identified driver mutation, while 111 patients (43.7%) harbored oncogenic alterations, most commonly in EGFR (n=74), KRAS (n=18), and HER2 (n=8). There was a significant difference in the presence of driver mutations at diagnosis between the patients with and without initial CS (P=0.04). A majority of patients received at least one line of systemic therapy, with 177 (69.6%) having undergone first-line treatment, and a smaller proportion receiving adjuvant, neoadjuvant, second- or later-line therapies. The first-line treatment regimens varied across patients, including targeted therapy alone, targeted therapy combined with chemotherapy or anti-angiogenesis therapy, chemotherapy alone, and various immunotherapy-based combinations. Notably, a significantly higher proportion of patients without initial CS received first-line ICI-based therapy compared to those with initial CS (P<0.001). There were no significant differences between the SLC and non-SLC groups in terms of histology, clinical stage, metastatic site, ECOG PS, driver gene mutations, and treatment received.

Characterization of CS and SLC

A total of 61 patients (23.4%) developed initial CS during the study period. The median time to the onset of initial CS was 11.03 months (IQR, 4.7–28.8 months). Among these, pulmonary infection was the most frequent event, occurring in 13 patients (21.3%). As illustrated in Figure 2, the distribution of CS causes differed between the SLC and non-SLC groups. In the SLC group (n=41), the most common cause of CS was malignant pleural effusion (MPE, 19.5%), followed by pulmonary infection (17.1%) and CIP (9.8%). Conversely, in the non-SLC group (n=20), pulmonary infection was even more predominant, accounting for 30% of cases, with lower proportions of MPE (5%) and hemoptysis (15%). Other causes such as airway stenosis, chemotherapy-induced cytopenia, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) showed similar distributions across both groups. Despite the differences in the proportions of individual causes, no significant difference in the overall distribution of CS causes was observed between the SLC and non-SLC groups (Figure 2). This suggests that while the frequency of specific complications varies, the overall pattern of critical events leading to CS remains consistent across both groups. Additionally, the specific causes of initial CS onset and the corresponding treatments for each patient are shown in Table S1. Figure 3A illustrates the time points of initial CS onset and the full treatment trajectory for each patient in the SLC and non-SLC groups. Additionally, 3/41 and 3/41 experienced initial CS during changes in treatment regimens and treatment cessation. In the non-SLC group, 1/20 patients experienced initial CS at initial diagnosis, while 12/20, 4/20, and 2/20 experienced initial CS during first-line, second-line, and third-line treatments, respectively, and 1/20 experienced initial CS during changes in treatment regimens. Among the patients, 92% of those in the SLC group and 20% in the non-SLC group continued anti-tumor therapy after experiencing initial CS.

Figure 2 Proportional distribution of causes of critical status events in severe lung cancer group and non-severe lung cancer group. AECOPD, acute exacerbation of chronic obstructive pulmonary disease; Acq-ILD, acute interstitial lung disease; CIP, checkpoint inhibitor pneumonitis; CNS rad. injury, central nervous system radiation injury; CS, critical status; HF, heart failure; ILD, interstitial lung disease; MPE, malignant pleural effusion; Multi. events, multiple events; Non-SLC, non-severe lung cancer; Pulm. infect, pulmonary infection; Post-surg. injury, post-surgical injury; Rad-pneum, radiation pneumonitis; SLC, severe lung cancer; VTE, venous thromboembolism.

Figure 3 Swimmer plot and Kaplan-Meier survival curves. (A) Swimmer plot of full anti-tumor therapy trajectories and outcomes over time for patients who initially met the CS; (B) Kaplan-Meier survival curve comparing the CS population and the stable population; (C) Kaplan-Meier survival curve comparing non-severe lung cancer and severe lung cancer groups; (D) Kaplan-Meier survival curve comparing the severe lung cancer group and the stable population. (E) Kaplan-Meier survival curve for CS patients stratified by performance status scores (PS =2, 3, and 4). (F) Kaplan-Meier survival curve for SLC patients stratified by performance status scores (PS=2, 3, and 4). (G) Kaplan-Meier survival curve for CS patients stratified by the causes of CS, including acute and chronic co-morbidities, tumor-related complications, and anti-cancer therapy-associated adverse events. (H) Kaplan-Meier survival curve for SLC patients stratified by the causes of CS, including acute and chronic co-morbidities, tumor-related complications, and anti-cancer therapy-associated adverse events. CS, critical status; PS, performance status; SLC, severe lung cancer.

Survival outcomes after CS development

Figure 3A presents a swimmer plot illustrating the distinct survival outcomes between the SLC and non-SLC groups following the onset of initial CS. This visualization highlights the variability in survival duration across patients, where individuals in the SLC group demonstrated more prolonged survival compared to the non-SLC group after developing CS. As shown in Figure 3B, the median OS for patients in the CS population was significantly shorter at 44.3 months (95% CI: 20.2–68.5) compared to the stable population, whose median OS was not reached (P<0.001). Further analysis in Figure 3C reveals that within the CS population, patients with SLC had a significantly longer median OS compared to those with non-SLC. Specifically, the median OS for the SLC group was not reached, whereas it was only 17.8 months (95% CI: 3.3–32.2) for the non-SLC group (P<0.001), suggesting better survival outcomes in the SLC group despite the onset of CS. Moreover, as shown in Figure 3D, although the median OS was not reached for both the stable population and the SLC group, the survival probability remained significantly worse in the SLC group compared to the stable population (P=0.01). Figure 3E stratifies survival outcomes based on the PS scores at the onset of CS. Patients with a PS score of 2 had a significantly better survival compared to those with higher PS scores (PS =3 or PS =4) (P=0.01). Figure 3F further stratifies survival in the SLC group by PS scores. While survival appeared worse in patients with higher PS scores (PS =3 and PS =4), the difference was not statistically significant (P=0.12). Figure 3G examines survival outcomes based on different causes of CS across all patients. Although patients with acute and chronic co-morbidities had worse survival outcomes compared to those with treatment-related complications and cancer therapy-associated adverse events, the difference was not statistically significant (P=0.21). Similarly, Figure 3H explores the survival impact of different causes of CS within the SLC group. Patients who developed CS due to acute and chronic co-morbidities tended to have worse survival than those with treatment-related complications, but this difference also did not reach statistical significance (P=0.14). Figure 4 presents the survival outcomes of SLC patients recovering from different PS scores. Figure 4A shows that the median OS has not been reached for patients whose PS score improved from 2 to 1, 3 to 1, or 3 to 2. Median OS of subgroup whose PS score improved from 4 to 3 was 17.3 months (95% CI: not available). Figure 4A shows the comparison among the four groups is statistically significant (P=0.03. No significant difference in OS was observed across three groups (2 to 1, 3 to 1, and 3 to 2) (P=0.07) (Figure 4B). Figure 4C shows no significant difference in OS between the subgroups of 2 to 1 and 3 to 1, while Figure 4C shows no significant difference in OS between the subgroups of 3 to 2 and 4 to 3.

Figure 4 Kaplan-Meier survival curves. (A) Kaplan-Meier survival curve for SLC patients stratified by the performance status improvement from 2 to 1, 3 to 1, 3 to 2, and 4 to 3. (B) Kaplan-Meier survival curve for SLC patients stratified by the performance status improvement from 2 to 1, 3 to 1, and 3 to 2. (C) Kaplan-Meier survival curve for SLC patients stratified by the performance status improvement from 2 to 1, and 3 to 1. (D) Kaplan-Meier survival curve for SLC patients stratified by the performance status improvement from 3 to 1, and 3 to 2. SLC, severe lung cancer.

Variables associated with OS

To further evaluate the association between potential prognostic factors and OS among patients, a Cox proportional hazards regression analysis was performed (Table 2). Developing CS was independently associated with poorer OS [hazard ratio (HR), 21.9 (95% CI: 6.6–73.8); P<0.001]. Both SLC (HR, 5.4; 95% CI: 1.2–24.3; P=0.03) and non-SLC (HR, 101.2; 95% CI: 23.2–441.6; P<0.001) were also independently associated with worse OS. In contrast, patients on second-line treatment had better survival outcomes compared to those on first-line treatment (HR, 0.3; 95% CI: 0.1–0.9; P=0.04). Additionally, patients with other pathological types of cancer had better survival outcomes compared to those with lung adenocarcinoma (HR, 4.5; 95% CI: 1.5–14.0; P=0.009) (Table 2).

Variables associated with progression of CS

To determine whether there are associations among different variables and to assess the strength of these associations, correlation tests were performed. As shown in the correlation heatmap in Figure 5, there is a strong negative correlation between palliative treatment for the cause of CS and CS development (correlation coefficient: −0.71), and this association is statistically significant (P<0.001). A significantly moderate correlation was observed between PS score at initial CS, receiving first-line ICI-based therapy and CS development (PS score at initial CS: correlation coefficient: 0.42, P<0.001; receiving first-line ICI-based therapy: correlation coefficient: −0.32, P=0.01). Additionally, a weak negative correlation was found between gender and CS development (correlation coefficient: −0.28, P=0.03).

Figure 5 Correlation heatmap with P values between variables in the study. CS, critical status; ICI, immune checkpoint inhibitor; PS, performance status.

Discussion

To our knowledge, this study is the first to highlight the clinical significance of SLC, while also identifying the risk threshold associated with initial CS for OS in NSCLC. Our findings emphasize that early and aggressive treatment of initial CS may provide a therapeutic window in tumor management, potentially improving patient outcomes and extending their quality of life.

The concept of SLC was first introduced by Zhou et al. (10). SLC refers to patients at high risk of death from potentially fatal but manageable causes who receive timely intervention and subsequently become stabilized. SLC, non-SLC, and stable populations exhibit three distinct survival prognoses. Our study found that patients who experienced their first CS had a mortality risk 21.9 times higher than stable patients. Compared to stable patients, the non-SLC group had a mortality risk 101.2 times higher, suggesting that these patients, even with supportive treatment during CS, did not experience an improvement in PS and are therefore in the terminal stage of lung cancer. In contrast, the SLC group, who received timely supportive care and showed improvements in their PS scores, had a lower mortality risk than the non-SLC group (HR =5.4). Despite the statistical difference, their Kaplan-Meier survival curve trended parallel to that of the stable population. However, this observation is based on a small cohort, and further research is needed to validate these findings and explore their clinical implications in larger patient populations. SLC patients had previously experienced a CS stage with PS scores ranging from 2 to 4. According to NCCN guidelines, patients with a PS score of 3 or 4 should only receive supportive care, with no recommendation for anti-tumor treatment. For patients with a PS score of 2, treatment decisions should consider the patient’s overall health, comorbidities, and the risks and expected outcomes of treatment (12). Nevertheless, PS scores are reversible, depending on whether the underlying causes of PS deterioration can be corrected. Once the PS scores in SLC patients improved, anti-tumor treatment could continue, thereby extending survival. This study aims to further elucidate the definition of SLC. Our findings indicate that improvements in PS from 2 to 1, 3 to 1, or 3 to 2 did not result in a significant difference in survival outcomes. In contrast, the subgroup of patients with a PS improvement from 4 to 3 demonstrated a significantly poorer survival compared to the other groups. Consequently, a PS improvement of at least 1 point can be considered as SLC. However, given the limitations of the small sample size, this conclusion warrants further validation through well-designed, large-scale cohort studies in the future. Although the definition of SLC appears somewhat broad, subgroup analysis has shown no significant statistical differences in survival related to PS scores or the causes of CS during the first event. However, while no statistical differences were observed among subgroups in out cohort, it is important to acknowledge that clinically meaningful differences may still exist. For example, patients who developed CS due to radiation pneumonitis in the setting of locally advanced, unresectable disease may follow a distinct clinical trajectory compared to those with cytopenia resulting from late-line chemotherapy. Similarly, the prognosis associated with cancer-related deterioration during first-line treatment initiation is likely to be more favorable than in third- or fourth-line settings. These distinctions, though not captured statistically in the present analysis, warrant further investigation in larger cohorts. In conclusion, the concept of SLC provides a concise reflection of clinical phenomena, and its definition is not only clinically relevant but also logically sound.

The survival prognosis of patients with advanced-stage NSCLC is closely related to their ability to withstand the initial CS, and this ability may be associated with the process of anti-tumor treatment. According to our research findings, the main distinction between SLC patients and those with terminal-stage lung cancer lies in whether the PS score improves after timely supportive treatment. Our correlation analysis shows a significant negative correlation between supportive therapy and CS progression, indicating that the earlier CS is detected and treated, the higher the likelihood of a patient being classified as SLC, thereby minimizing the mortality risk associated with CS. We further compared the characteristics of the two groups (SLC and terminal-stage lung cancer) to analyze the factors influencing the distribution of these populations. We found significant differences in gender composition and the distribution of patients receiving first-line ICI-based therapy. Patients with terminal-stage lung cancer were more likely to be male and to receive non-ICI-based first-line treatment. Cox proportional hazards regression analysis showed that patients who received second-line therapy had better OS compared to those receiving only first-line treatment (HR, 0.3; 95% CI: 0.1–0.9; P=0.04). The second-line therapy rates were similar between the SLC and non-SLC groups, at 31.7% and 35%, respectively. This result may be explained by the fact that SLC patients are more likely to recover from CS and, therefore, better tolerate second-line therapy, which allows for more effective tumor control and improved prognosis. However, due to the limitations of the small sample size, these results may not fully reflect the differences in treatment selection and response between the two groups. Further studies with larger cohort sizes are needed to validate these observations. Correlation analysis revealed a weak but statistically significant association between gender and CS progression, while the correlation with receiving first-line ICI-based treatment was moderately significant. These results suggest that differences in the anti-tumor treatment process may lead to disparities in the ability of the two groups to withstand the initial challenge of CS, thereby affecting their survival prognosis. Gender differences also play an important role in the selection of treatment plans, particularly in terms of the biological characteristics of lung cancer. Non-smoking women are more likely to present with epidermal growth factor receptor (EGFR) mutations, making them the preferred group for EGFR-targeted therapy (13,14). Additionally, gender may influence the tolerance to different treatment regimens, with women often showing better tolerance to the side effects of certain chemotherapy drugs, while men may achieve better outcomes with immunotherapy (15,16).

Patients with advanced NSCLC may also achieve long-term stable survival. Previous studies have shown that the median OS of advanced NSCLC patients who have undergone multiple treatments is approximately 12 to 24 months (17,18), with some patients achieving up to 51 months following effective targeted therapy and immunotherapy (19). However, in the field of cancer treatment, most attention is focused on the direct impact of cancer therapies on patient survival, while the effect of correcting PS on survival is often overlooked. After 3 years of follow-up, our survival analysis indicates that both SLC patients and stable populations have not yet reached median survival time, suggesting that timely treatment of CS and cancer therapy play equally important roles in the overall management of advanced NSCLC patients.

There are several limitations in this study. Firstly, its retrospective design and the small sample size may not fully capture the true distribution of SLC in NSCLC. Additionally, due to the retrospective nature of the design, there is heterogeneity in the exact PS scores, which could lead to variability in patient assessments. Consequently, the study might under-report the total number of CS cases in NSCLC patients, particularly among those with no or mild symptoms who did not require treatment. Furthermore, the follow-up period was insufficient, and many stable patients had not yet experienced their first CS episode, potentially affecting the representativeness of the data. Another limitation is that the study only analyzed the impact of the first CS episode on survival. Given the fluctuations and reversibility of PS scores, patients may experience subsequent episodes of CS, such as a second or third episode, but these were not analyzed in the present study. Future research should address this aspect to provide more comprehensive insights. Additionally, because of the retrospective design, the PS scores at the time of CS occurrence were obtained from medical records, where they were subject to assessment by the attending physicians at that moment, introducing a degree of subjectivity. There is also a selection bias, as some patients had poor PS at the time of receiving systemic oncotherapy, which increases the risk of death due to CS and reduces our ability to assess the true risk of CS in a population with better PS. However, due to the limited data available on this issue, our study can still offer clinical value by introducing SLC as a novel concept and addressing a common clinical dilemma. Our research provides real-world data that generate new insights and aims to draw the attention of oncologists and pulmonary clinicians.

Conclusions

In summary, based on our findings, we recommend that oncologists and pulmonologists prioritize the early identification and management of CS caused by tumor-related emergencies to improve patient outcomes. The study highlights the significant differences between SLC and non-SLC patients, particularly in terms of their PS scores and response to supportive care. Timely and appropriate supportive treatment can substantially reduce the risk of mortality associated with CS, even among those with compromised immune systems due to cancer or its treatment. Therefore, clinicians should maintain a high index of suspicion for early signs of CS and consider proactive measures to stabilize patients’ conditions. Moreover, as the findings suggest a need for more personalized management strategies, future prospective studies with larger and more diverse cohorts are essential to validate our observations and further refine the management protocols for NSCLC patients experiencing tumor-related emergencies.

Acknowledgments

The abstract was in part presented at European Respiratory Society Congress 2024.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-71/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-71/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-71/prf

Funding: The present study was supported by grants from Guangzhou Science and Technology Major Clinical Project (No. 2023C-DZ06).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-71/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 ethical standards of the Declaration of Helsinki and its subsequent amendments, and the applicable regulatory requirements. This retrospective study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2021-38). The requirement for informed consent was waived for this retrospective analysis.

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/.

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