PD-L1 expression in non-small cell lung carcinoma in Latin America: a systematic review and meta-analysis

Introduction

Lung cancer is the second most diagnosed neoplasm globally and the leading cause of cancer-related deaths. In Latin America and the Caribbean, it ranks as the third most common cancer after prostate and breast cancer, with 97,601 new cases annually, and remains the leading cause of cancer deaths, claiming 86,627 lives each year (1). Recent years have seen significant advancements in clinical outcomes due to the identification of oncogenic driver mutations and the expression of programmed cell death ligand 1 (PD-L1), which have become standard-of-care due to improved clinical outcomes (2,3).

Programmed cell death 1 receptor (PD-1) and its ligand PD-L1 play an important role in physiological immune homeostasis and are involved in the pathway through which cancer cells evade the immune system (4). PD-1 is expressed on the cell surface of T and B cells, natural killer cells, macrophages, dendritic cells, and monocytes. PD-L1 is commonly expressed by macrophages, certain activated T cells, B cells, dendritic cells, and some epithelial cells, especially under inflammatory conditions and in malignant cells. The binding interaction between PD-1 and PD-L1 results in the inhibition of T cell activation, migration, proliferation, survival, and cytotoxic secretion within cancer cells (4,5). The humanized antibody blockade of PD-1/PD-L1 reverses the binding of this process and enhances antitumor immune activity. These immune checkpoint inhibitors (ICIs) have changed the treatment for many tumors with different clinical indications (6).

Currently the expression of PD-L1 is tested by immunohistochemistry (IHC) mainly on formalin-fixed paraffin-embedded (FFPE) histological specimens. Three scores are used by the pathologists depending on the malignant tumor, antibodies (28-8, 22C3, SP142, SP263), and clinical treatment. These scores are tumoral proportion score (TPS), combined positive score (CPS), and immune cell score (IC). Some tumors are positive with scores of ≥1 and others with scores of ≥10. In non-small cell lung carcinoma (NSCLC) the expression of PD-L1 is divided into <1%, 1–49%, and ≥50% and the clones used in the clinical practice are 22C3 and SP263 (7).

Several challenges to the implementation of molecular testing and treatment for NSCLC have been seen in Latino patients (8,9). Currently, checkpoint inhibitors (PD-L1) and some targeted therapies (EGFR, ALK, ROS1, KRAS, NTRK) are approved for NSCLC in Latin America (9). Recently, in a systematic review we observed that the prevalence of actionable mutations in the Latino population was different than it is in the Caucasian and Asian populations (10). The goal of the present article is to determine the prevalence of PD-L1 expression and clinicopathological features in the Hispanic/Latino (H/L) population with NSCLC. We present this article in accordance with the PRISMA reporting checklist (11) (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-223/rc).

Methods

The protocol was submitted to PROSPERO, the International Prospective Register of Systematic Reviews, under the number CRD42023488547.

Inclusion criteria

The inclusion criteria for the systematic review encompassed descriptive studies, cohorts, and clinical trials assessing the frequency of PD-L1 expression using antibodies 22C3 or SP263 in H/L patients. Articles published up to April 2024 were considered, regardless of language. When the same population was reported in multiple articles, those with the highest number of cases were selected.

Exclusion criteria

The following exclusion criteria were applied: (I) studies with inconsistencies between the text and table results; (II) studies that included patients with a specific driver mutation.

Information sources and search strategy

Detailed, tailored search strategies were employed for each of the following electronic databases: Embase, LILACS, Medline, and the Virtual Health Library. Grey literature was also retrieved using Google Scholar. All searches were conducted in April 2024. Additionally, a hand search, expert consultations, and a review of reference lists from selected articles were performed. Appropriate truncations and word combinations were applied and adjusted for each database (Table S1). Terms considered included: cancer, neoplasms, Hispanic or Latino, Spanish Origin, Latin America and anti-PD-L1. The term “Hispanic or Latino” is currently defined as a person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race. Latino patients do not necessarily come geographically from Latin America, and it is well known that in the Central and South American territory there is a significant racial and ethnic variety. Despite the above, in this review we will speak indistinctly of Hispanic or Latino referring to race based on the geographic origin of the patients.

Study selection

The eligibility of the selected articles was assessed in two phases. In phase 1, five authors (J.P.C.G., L.M., M.P.V., D.C.C., M.P.G.G.) independently screened the studies by title and abstract. In phase 2, the same authors reviewed the abstract and full text of all screened articles, excluding those that did not meet the inclusion criteria. Any disagreements were resolved by consulting another author (R.P.M.). References from relevant articles were manually searched. All included data were reviewed by the authors. The final selection was based on the full text of the publication or the abstract of the conference presentation.

Data collection process and data extraction

The following data were extracted from each article when available: author name, country of origin of the patients, year of publication, recruitment period, number of patients, PD-L1 expression categorized as <1%, 1–49%, and ≥50%, and clinical data including age, smoking status, sex, histological subtype, disease stage, metastasis, and Eastern Cooperative Oncology Group (ECOG) score. Additionally, associated mutations of EGFR, ALK and KRAS were recorded based on data availability. Disagreements were resolved by consensus. If the required data were incomplete, efforts were made to contact the authors for the missing information.

Risk of bias and applicability

To evaluate the methodological quality and applicability of the included studies, a checklist based on the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses (12) was utilized. Two reviewers (J.P.C.G., M.P.V.) independently assessed each study, answering eight questions for cross-sectional studies and 11 questions for cohort studies. Responses to each question were categorized as ‘yes’ (Y), ‘no’ (N), ‘unclear’ (U), or ‘not applicable’ (NA).

Summary measures

The primary outcome was the prevalence or incidence of PD-L1 expression. Prevalence was calculated as patients with mutations divided by <1%, 1–49%, and ≥50%.

Data synthesis and analysis

All quantitative analyses of the included studies were conducted in R using the metafor and meta packages. Meta-analyses were performed using a random effects model to determine the prevalence of PD-L1 expression. Heterogeneity was evaluated using the I² statistic, with values greater than 75% indicating high heterogeneity. The significance level was set at 5%. Heterogeneity was further assessed based on sample size, country, and study design.

Results

General search results

A total of 809 original articles were identified, with 157 being duplicates. After screening titles and abstracts, 611 articles were rejected. Ultimately, 21 articles met the inclusion and exclusion criteria and were included in the review (13-33) (Figure 1).

Figure 1 Flow chart in the systematic review.

In the case of seven articles (13,15,18-21,24) data were extracted from the abstract. Three multicenter studies were found in different countries. Two of them were based on records from the Latin American Consortium for Lung Cancer Research (CLICaP) (22,23) and the remaining ones came from the Latin American Cooperative Oncology Group (LACOG) (24). The information was extracted by country. Among the single-center studies, six articles from Brazil (14,25,27-30), four from Colombia (15,31-33), two from Mexico (17,18), and Argentina (13,26) one each from Ecuador (16), and Peru (19) were found. Two articles included Latinos residing in the USA (20,21). All the studies were published between 2017 and 2022.

General clinical information

Clinical and sociodemographic data were extracted from 19 articles (n=14,244). Information on age was available in 15 of the articles (n=12,787) and information on sex could be extracted from 16 manuscripts (n=13,364) (Table 1). The median age reported was 65.5 years and 55.2% were male (n=7,373/13,364). Regarding smoking status, 73.8% (n=2,971/4,025) were found to be smokers. It was possible to report information on the histological subtype of NSCLC in 13,072 patients and lung adenocarcinoma (LUAD) was found to be the most frequent (71%, n=9,285) followed by lung squamous cell carcinoma (LUSC) (12%, n=1,573) and adenosquamous carcinoma (4.2%, n=550).

The clinical stage of NSCLC was reported in 1,443 patients and half of the cases were stage IV (46.5%, n=681). Stages IIIA (17.7%, n=259), IIIB (12.9%, n=189), IIB (7.65%, n=112), IB (6.63%, n=97), and IIA (5.46%, n=80) were reported in smaller proportions. The other stages presented a frequency of less than 5%. When the information related to the presence of metastases was evaluated, 583 patients presented metastatic primary NSCLC. The most frequently affected by metastases organs were the lungs (lung-to-lung metastases) (52.8%, n=308), followed by the brain (38.6%, n=225), bones (5%, n=29), and liver (3.3%, n=19). The site of metastasis was not clearly reported for two patients (0.3%). Most Latino patients with NSCLC were classified as ECOG 1 (63.9%, n=956/1,496), followed by ECOG 0 (18.9%, n=283/1,496), ECOG 2 (11.7%, n=175/1,496), ECOG 3 (5%, n=75/1,496), and ECOG 4 (0.5%, n=7/1,496). The type of treatment received was reported for 323 patients. Conventional chemotherapy was given to 57.9% (n=187) of the patients and, of these, 80 patients received additional therapy with first-generation tyrosine kinase receptor inhibitors (TKIs). Of the total number of patients, 17.3% (n=56) received immunotherapy.

Clinical information on PD-L1-positive patients

Clinical and sociodemographic of patients with the PD-L1 expression evaluated were extracted from nine articles (n=11,526) (Table 2) (13,17,25-28,30-32). The mean age reported in this group was 65 years and 56.4% were male. Most patients were exposed to tobacco (73%).

The most frequent histological subtypes were adenocarcinoma, 68.4% (n=3,971/5,808) followed by squamous cell carcinoma, 15.4% (n=895/5,808). Among the adenocarcinomas, the predominant pattern in this subgroup of patients was reported in 187 cases. The most frequent pattern found was solid (66.8%, n=125/187), followed by the papillary (12.8%, n=24/187), acinar (8.6%, n=16/187), lepidic (8.6%, n=16/187), micropapillary (1.6%, n=3/187) and mucinous (1.6%, n=3/187) patterns. Regarding the oncological stage, 44.2% of the patients were stage IIIA (n=42/95) followed by 19% (n=18/95) stage IV, 17.9% (n=17/95) stage IIB, 10.5% (n=10/95) stage IB, 4.2% (n=4/95) stage IIA and 4.2% stage IIIB. One study evaluated expression in early stages (IB to IIIA-AJCC seventh edition) and found higher expression in stages IIB/IIIA (30). Forty-seven patients had metastases in the same lung, and 59.7% and 40.3% had an ECOG score of 1 and ECOG 0 respectively.

Frequency of PD-L1 expression in Latin American patients

Of the 21 articles included (n=16,486), 13,222 patients (80.2%) were evaluated for PD-L1 expression. The meta-analysis found a 55% [95% confidence interval (CI): 0.54–0.55] prevalence of PD-L1 in Latino patients with NSCLC. The prevalence was 31% (95% CI: 0.27–0.36) for subjects with TPS expression 1–49% and 23% (95% CI: 0.16–0.30) for TPS expression ≥50% (Figure 2).

Figure 2 Meta-analysis of PD-L1 expression (13-33). (A) TPS expression ≥1%. (B) TPS expression 1–49%. (C) TPS expression ≥50%. CI, confidence interval; PD-L1, programmed cell death ligand 1; TPS, tumoral proportion score.

A sensitivity analysis that excluded articles that evaluated PD-L1 expression in patients with squamous cell carcinoma of the lung [Cardona et al. (31) and Fernández-Trujillo et al. (32)] was done. No significant changes in prevalence were seen (51%, 95% CI: 0.42–0.59), nor were they seen in the patients with TPS 1–49% (31%, 95% CI: 0.26–0.36) and with ≥50% (22%, 95% CI: 0.15–0.30) (Figure S1).

Frequency of PD-L1 expression and presence of molecular alterations

Seven articles were found that evaluated both the PD-L1 expression and the presence of mutation in the EGFR gene together (13,15,17,19,26,28,30). Within those reporting PD-L1-positive TPS (n=4,500), there were 787 EGFR-positive patients (17.5%) and 3,713 EGFR-negative patients (82.5%). In contrast, there were 3,484 patients that did not have PD-L1 expression, and of these, 22.8% were EGFR positive (n=794) and 77.2% were EGFR negative (n=2,690). The analysis found an association between the PD-L1 expression and EGFR negative [odds ratio (OR) =1.54; 95% CI: 1.24–1.92].

The expression of PD-L1 with the presence of molecular alterations of the ALK gene was described in five articles (15,17,25,26,28). Of these patients, 4,324 were found to have positive PD-L1 expression and 3,610 were found to have no PD-L1 expression. The proportion of ALK molecular alterations was 5.78% (n=250) for patients with positive PD-L1 expression and 3.82% (n=138) for patients with negative PD-L1 expression. The analysis found an association between the PD-L1 expression and ALK positive (OR =1.54; 95% CI: 1.24–1.92).

Quality assessment

We evaluated the quality of 14 out of the 21 articles that were available in full text (Table S2). Bias risk assessment was conducted using two checklists tailored to the design of cross-sectional and cohort studies. Among the former, eight articles were identified. In the study published by Alarcón et al. 2021 (33), details regarding outcome measurement were not provided, and frequencies were measured inaccurately. Additionally, concerns about outcome measurement exist in the study by Cabral 2021 (29). The overall performance was adequate. Regarding analytical longitudinal studies, six cohort articles were reviewed. Overall, there was a lack of clarity in all these studies regarding the identification and control of confounding factors.

Discussion

In this study, the prevalence of PD-L1 expression in NSCLC in H/L patients was evaluated in 13,222 NSCLC patients from different Latin America countries. The prevalence calculated was 55% (95% CI: 0.54–0.55). Similar results were presented in a letter to the editor by Cardona et al. (34). They described the PD-L1 expression in 57.9% (95% CI: 55.4–60.5%) of 1,450 NSCLC patients from different Colombian regions. Our results are similar to what was observed in other population. In the EXPRESS study that included 2,368 NSCLC patients, the percentage of patients found with PD-L1 TPS ≥50% and TPS ≥1% respectively were, respectively, 22% and 52% in Europe (Austria, Denmark, Germany, Italy, Spain, Sweden, The Netherlands) (n=415), 22% and 53% in Asia Pacific (Japan, Hong Kong, Korea, Singapore, Taiwan) (n=290), 21% and 47% in the Americas (Argentina, Canada, Colombia) (n=220), and finally 24% and 55% in other countries (Russia, Saudi Arabia, Turkey) (n=139) (35,36).

The prognosis is different for patients receiving PD-1/PD-L1 inhibitor-based therapy. In a meta-analysis that included 1,020 cancer patients from 19 prospective randomized controlled clinical trials, Asian cancer patients were shown to have a significantly improved survival benefit compared to non-Asian for the first time (37). This can be explained by immune system differences among populations. A recent article by Bie et al. (38) showed that the composition of tumor-infiltrating lymphocytes (TILs) was quite different between Caucasian and Asian LUAD patients. A higher content of resting mast cells was associated with a better prognosis in Asian patients. Additionally, Caucasian patients with higher immune and estimate scores demonstrated better prognoses (P=0.021, P=0.025). However, Asian patients with higher estimate scores showed a worse prognosis (P=0.024).

In NSCLC, high PD-L1 expression has been associated with male gender, smoking, poor tumor differentiation, large tumor size, presence of lymph node metastasis, EGFR wild-type status, and KRAS mutations (39). PD-L1 expression is also associated with worse survival (40). In the preset study, the results are similar about the gender, smoking, poor tumor differentiation, and advanced stages (Table 2). Our data also found more frequent PD-L1 expression in EGFR wild-type status (82.5%) with a OR 1.54 (95% CI: 1.24–1.92) and ALK positive with (OR =1.54; 95% CI: 1.24–1.92).

It has been demonstrated that there is a change in PD-L1 expression among NSCLC subtypes. In a systematic review of 42 articles that evaluated PD-L1 expression in NSCLC subtypes published between 2010 and 2017, the expression in LUSC was found to be higher than LUAD. They found that PD-L1 ≥1% in LUSC was 41.05% (n=743/1,810) versus 34.7% (n=826/2,379) in LUAD. The frequency for PD-L1 1–49% was similar to LUSC (47.9%, n=569/1,189) and LUAD (47.3%, n=712/1,507) while the frequency for PD-L1 ≥50% change in the LUSC (16.1%, n=284/1,766) and LUAD (9.33%, n=179/1,919) (41). In the present review, few articles (13,17,25,27,28,30-32) divided the expression based on the NSCLC subtypes. Gelatti et al. (28) found similar results in a multicenter study of a Brazilian population that included 1,512 patients. The frequency for PD-L1 1–49% was 30% in LUSC (n=77) and 23.2% in LUAD (n=185) and PD-L1 ≥50% was 22.05% (n=56) in LUSC and 16.19% (n=129) in LUAD.

The molecular profile in LUSC, in turn, is different than it is in LUSC (42). Cardona et al. (31) in 26 Colombian patients with LUSC, a high prevalence of mutations was identified in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression levels were categorized as negative in 23.1% of patients, 1% in 38.5%, 2–49% in 26.9%, and ≥50% in 11.5%. Higher PD-L1 expression was significantly associated with TP53 mutations (P=0.037), and greater PD-L1 expression was related to PIK3CA alterations (P=0.05).

There are certain limitations in this study. First, clinical information on patients with PD-L1 expression was not collected in a large percentage of studies. Second, data from some Latin American countries may be limited. Third, PD-L1 expression was not assessed in all NSCLC cases included in the studies. Fourth, many authors were part of different Latin American network consortiums that shared the same patient database across various publications. To address this, we excluded most duplicate articles and selected the one with the highest number of patients with PD-L1 data. Finally, the results may have been influenced by preanalytical factors (such as time to fixation, fixation duration, and sample processing), IHC platforms, clone selections, inter-observer variability in interpretation, and the age of archival tumor tissue.

Conclusions

In conclusion, this meta-analysis provides a comprehensive overview of PD-L1 expression in NSCLC among the H/L population. Our results in prevalence and clinicopathological features are similar to those of other populations. These findings serve as a foundation for advancing personalized treatment approaches in the realm of NSCLC management, particularly in the context of Latin America and its diverse patient population. It is important to note that other factors besides PD-L1 expression may influence the likelihood and success of immunotherapy treatment. Therefore, studies to identify and describe these factors are suggested.

Acknowledgments

Funding: This research was supported by Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-223/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-223/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-223/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.

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. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
2. Yu Y, Zeng D, Ou Q, et al. Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non-Small Cell Lung Cancer: A Meta-analysis and Individual Patient-Level Analysis. JAMA Netw Open 2019;2:e196879. [Crossref] [PubMed]
3. Chen S, Zhang Z, Zheng X, et al. Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis. Front Oncol 2021;11:562315. [Crossref] [PubMed]
4. Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol 2019;12:92. [Crossref] [PubMed]
5. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res 2020;10:727-42.
6. Yi M, Zheng X, Niu M, et al. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer 2022;21:28. [Crossref] [PubMed]
7. Akhtar M, Rashid S, Al-Bozom IA. PD-L1 immunostaining: what pathologists need to know. Diagn Pathol 2021;16:94. [Crossref] [PubMed]
8. Smeltzer MP, Wynes MW, Lantuejoul S, et al. The International Association for the Study of Lung Cancer Global Survey on Molecular Testing in Lung Cancer. J Thorac Oncol 2020;15:1434-48. [Crossref] [PubMed]
9. Araujo LH, Costa FD, Parra R, et al. Adopting Molecular Testing for Solid Tumors in Latin America: Challenges and Opportunities. RAS Oncology & Therapy 2022;3:1-12.
10. Parra-Medina R, Pablo Castañeda-González J, Montoya L, et al. Prevalence of oncogenic driver mutations in Hispanics/Latin patients with lung cancer. A systematic review and meta-analysis. Lung Cancer 2023;185:107378. [Crossref] [PubMed]
11. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of Clinical Epidemiology 2009;62:e1-34. [Crossref] [PubMed]
12. Munn Z, Tufanaru C, Aromataris E. JBI's systematic reviews: data extraction and synthesis. Am J Nurs 2014;114:49-54. [Crossref] [PubMed]
13. Pilnik N, Bengio V, Canigiani M, et al. P2.15-B Update of Mutation Status and PDL1 Expression in Lung Cancer. A Multicenter Local Study. Journal of Thoracic Oncology 2019;14:S1191.
14. Andreis TF, Correa BS, Vianna FS, et al. Analysis of Predictive Biomarkers in Patients With Lung Adenocarcinoma From Southern Brazil Reveals a Distinct Profile From Other Regions of the Country. J Glob Oncol 2019;5:1-9. [Crossref] [PubMed]
15. Sua L, Lores J, Aguirre M, et al. P2.04-70 PD-L1 Expression in a Population with Non-Small Cell Lung Cancer in a Reference Healthcare Center in Latin-America. Journal of Thoracic Oncology 2019;14:S735-6.
16. Fernández Freire MÁ, Gálvez Salazar GI, Scudeler MM, et al. Actionable mutations in non-small cell lung cancer in patients at hospital de Especialidades Eugenio Espejo, Ecuador 2017-2020. Drug Metab Pers Ther 2023;38:149-53. [Crossref] [PubMed]
17. Avilés-Salas A, Flores-Estrada D, Lara-Mejía L, et al. Modifying factors of PD-L1 expression on tumor cells in advanced non-small-cell lung cancer. Thorac Cancer 2022;13:3362-73. [Crossref] [PubMed]
18. Sosa SS, Garcia TG, Martinez AM, et al. Different Prevalence of Molecular Alterations for Non-Small Cell Lung Cancer in Mexican Cohort of 200 Patients. Laboratory Investigation 2022;102:1340-1.
19. Paytan T, Ruiz R, Araujo J, et al. P09.24 Real-World Data in Non-Small Cell Lung Cancer Treated with Checkpoint Inhibitors in a Latin American Institution. Journal of Thoracic Oncology 2021;16:S300.
20. Saravia D, Basher F, Arora A, et al. P2.06 Lung Cancer Driver Mutations and PD-L1 Expression in US Latino Patients with Advanced Lung Cancer. Journal of Thoracic Oncology 2019;14:S1187.
21. Shum E, Su C, Zhu C, et al. P1.07-027 PD-L1 Expression Analysis in African American (AA) and Hispanic Lung Cancer Patients at a Minority-Based Academic Cancer Center. Journal of Thoracic Oncology 2017;12:S2006.
22. Cordeiro de Lima VC, Corassa M, Saldanha E, et al. STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP). Lung Cancer 2022;170:114-21. [Crossref] [PubMed]
23. Raez LE, Arrieta O, Chamorro DF, et al. Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP). Front Oncol 2022;12:904800. [Crossref] [PubMed]
24. Werutsky G, Arrieta O, Zukin M, et al. EP03.01-003 Clinical Features and Molecular Profile of Advanced Non-small Cell Lung Cancer in Latin America: LATINO Lung (LACOG 0116). Journal of Thoracic Oncology 2022;17:S237-8.
25. Alves da Silva AV, Martins Neto F, de Oliveira AC, et al. The frequency of high PD-L1 expression is low in lung adenocarcinoma patients from Northeast Brazil. Surgical and Experimental Pathology 2019;2:4.
26. Ruiz G, Enrico D, Mahmoud YD, et al. Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients. Thorac Cancer 2024;15:895-905. [Crossref] [PubMed]
27. Oliveira ACDSM, Silva AVAD, Alves M, et al. Molecular profile of non-small cell lung cancer in northeastern Brazil. J Bras Pneumol 2019;45:e20180181. [Crossref] [PubMed]
28. Gelatti ACZ, Cordeiro de Lima VC, Freitas H, et al. Real-World Prevalence of PD-L1 Expression Among Tumor Samples From Patients With Non-Small-Cell Lung Cancer. Clin Lung Cancer 2020;21:e511-5. [Crossref] [PubMed]
29. Cabral PA. Prevalence of ROS1 gene rearrangements in EGFR-Negative and ALK-negative nonsquamous NSCLC: analysis of a Brazilian cohort. 2021. Available online: https://accamargo.phlnet.com.br/Doutorado/2021/PACabral/PACabral.pdf
30. Alves Pinto I, de Oliveira Cavagna R, Virginio da Silva AL, et al. EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil. Oncologist 2022;27:e899-907. [Crossref] [PubMed]
31. Cardona AF, Ruiz-Patiño A, Arrieta O, et al. Genotyping Squamous Cell Lung Carcinoma in Colombia (Geno1.1-CLICaP). Front Oncol 2020;10:588932. [Crossref] [PubMed]
32. Fernández-Trujillo L, Garcia-Robledo JE, Zúñiga-Restrepo V, et al. Clinical characteristics and PD-L1 expression in primary lung squamous cell carcinoma: A case series. Respir Med Case Rep 2020;30:101114. [Crossref] [PubMed]
33. Alarcón ML, Brugés R, Carvajal C, et al. Características de los pacientes con cáncer de pulmón de célula no pequeña en el Instituto Nacional de Cancerología de Bogotá. Revista Colombiana de Cancerología 2021;25:103-9.
34. Cardona AF, Arrieta-Mercado O, Ruíz-Patiño A, et al. Carta el editor: Características de los pacientes con cáncer de pulmón de célula no pequeña en el Instituto Nacional de Cancerología de Colombia. Revista Colombiana de Cancerología 2021;25:226-31.
35. Salanova R, Dietel M, Savelov N, et al. PD.1.02 Real-World Prevalence of PD-L1 Expression in Advanced Non–Small-Cell Lung Cancer: The Global, Multicenter EXPRESS Study. Journal of Thoracic Oncology 2018;13:S155-6.
36. Dietel M, Savelov N, Salanova R, et al. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter EXPRESS study. Lung Cancer 2019;134:174-9. [Crossref] [PubMed]
37. Peng L, Qin BD, Xiao K, et al. A meta-analysis comparing responses of Asian versus non-Asian cancer patients to PD-1 and PD-L1 inhibitor-based therapy. Oncoimmunology 2020;9:1781333. [Crossref] [PubMed]
38. Bie F, Tian H, Sun N, et al. Comprehensive analysis of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor microenvironment in LUAD: differences between Asians and Caucasians. Clin Epigenetics 2021;13:229. [Crossref] [PubMed]
39. Li H, Xu Y, Wan B, et al. The clinicopathological and prognostic significance of PD-L1 expression assessed by immunohistochemistry in lung cancer: a meta-analysis of 50 studies with 11,383 patients. Transl Lung Cancer Res 2019;8:429-49. [Crossref] [PubMed]
40. Tuminello S, Sikavi D, Veluswamy R, et al. PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res 2020;9:1343-60. [Crossref] [PubMed]
41. Ullah A, Pulliam S, Karki NR, et al. PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies? Clin Pract 2022;12:653-71. [Crossref] [PubMed]
42. Kashima J, Kitadai R, Okuma Y. Molecular and Morphological Profiling of Lung Cancer: A Foundation for "Next-Generation" Pathologists and Oncologists. Cancers (Basel) 2019;11:599. [Crossref] [PubMed]