Multimodality Approach for Locally Advanced Lung Cancer: When Is Surgery Most Beneficial?

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Riad Amin Abdeljalil, Ahed Al-odwan, Sakhr Alshwayyat, Leen Osama Nemrawi, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6302087/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Dec, 2025 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Stage III non-small cell lung cancer (NSCLC) is a complex and challenging disease due to its variability and the absence of standardized treatment protocols. This study aimed to investigate the role of surgical resection as part of a multimodal treatment approach to improve overall survival (OS) and disease-free survival (DFS) in resource-limited settings. Methods: The medical records of 309 patients who underwent surgery for confirmed primary lung cancer at the King Hussein Cancer Center (KHCC) in Amman, Jordan, between 2016 and 2022 were reviewed. 59 of them diagnosed with Stage III NSCLC underwent curative surgeries. Patients were grouped into three categories: surgery alone, neoadjuvant therapy followed by surgery, and surgery combined with adjuvant therapy. Demographic, clinical, and survival data were statistically analyzed to compare the outcomes across these groups. Results: The study cohort consisted predominantly of males (86.4%), with adenocarcinoma being the most common histological subtype (54.2%). Patients who underwent surgery alone had the lowest recurrence rate and highest three-year OS and DFS rates (66.7%). Improved OS and DFS were observed in patients with pN0 status and no evidence of lymphovascular invasion (LVI). Minimally invasive surgical approaches such as VATS were associated with better perioperative outcomes than open surgery. Conclusion: Surgical resection, particularly when achieving negative margins (R0) in patients with N0 disease, is critical for improving survival in patients with Stage III NSCLC. Multimodal strategies can enhance these benefits further. However, challenges related to healthcare access in resource-limited settings highlight the need for customized treatment protocols and broader access to advanced medical therapies. Combined Modality Therapy Disease Free Survival Neoadjuvant Therapy locally advanced Non-Small-Cell Lung Carcinoma Resource Limited Settings Video Assisted Thoracic Surgery Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1.0 Introduction Stage III non-small cell lung cancer (NSCLC) is a diverse condition affecting approximately 20–30% of patients with NSCLC worldwide ( 1 ). Its heterogeneity in tumor biology, patient characteristics, and treatment outcomes presents significant challenges for diagnosis and management. Despite progress, there remains a lack of universally accepted guidelines highlighting the difficulty in optimizing treatment approaches. Collaborative approaches have led to substantial improvements in patient outcomes. Research from Denmark showed a median overall survival (OS) of 24.4 months for patients receiving curative-intent therapy compared to 9.8 months for those receiving palliative care ( 2 ). A French national study emphasized the value of invasive staging and combined treatments, including chemoradiotherapy (CRT) followed by consolidation immunotherapy, in alignment with updated guidelines ( 3 ). Surgical removal in selected patients yielded promising results, with complete resection achieved in 85% of the cases ( 3 ). In Japan, real-world evidence indicated that surgery, though less commonly employed, resulted in superior OS (median 43.4 months) compared to CRT or radiotherapy alone ( 4 ). In China, targeted approaches, such as EGFR mutation testing and PD-L1 expression evaluation, have guided treatment in resectable Stage III cases, thereby enhancing therapeutic effectiveness ( 5 ). Advanced radiomic analysis has also improved survival predictions, offering noninvasive methods to assess tumor heterogeneity ( 6 ). Pre- and post-surgical therapies have transformed the treatment paradigms for Stage III NSCLC. Studies have shown that neoadjuvant chemoimmunotherapy significantly enhances resectability and pathological responses, with event-free survival rates exceeding 75% ( 7 , 8 ). Adjuvant therapies, including targeted agents such as osimertinib and immunotherapies such as atezolizumab, have further reduced recurrence risks and extended disease-free survival, although debates regarding their long-term efficacy continue ( 9 , 10 ). Worldwide disparities in lung cancer outcomes underscore the impact of health care inequities. Patients in developed nations benefit from early diagnosis and access to advanced therapies, whereas those in resource-limited settings face challenges of late-stage presentations and restricted treatment options ( 11 , 12 ). Addressing these inequities through clinical trial access and cost-effective interventions is a global priority. This study aimed to assess the impact of surgical intervention on overall survival (OS) and disease-free survival (DFS) in Stage III NSCLC management in a developing country where expensive systemic treatment is not usually available. We examined patient outcomes based on treatment strategies, tumor characteristics, and multimodal approaches to address the lack of standardized guidelines for optimal patient selection and treatment pathways, with the aim of contributing to the global discussion on personalized and multidisciplinary management of Stage III NSCLC. 2.0 Methods This retrospective observational study was conducted at King Hussein Cancer Center (KHCC), a large tertiary cancer center. This study was approved by the KHCC Institutional Review Board (Proposal No. 21 KHCC 115) and the requirement for informed consent was waived because of its retrospective nature. The medical records of 309 patients who underwent surgery for confirmed primary lung cancer at the King Hussein Cancer Center (KHCC) in Amman, Jordan between 2016 and 2022 were retrospectively studied. 59 patients with stage III lung cancer who underwent curative lung resection were included in the final detailed analysis. We divided them into three groups: Group 1, patients who underwent upfront surgery followed by adjuvant treatment; Group 2, those who underwent neoadjuvant treatment followed by surgery; and Group 3, those who underwent surgery alone. Baseline data, including demographic information, tumor characteristics and treatment data were collected from medical records. OS was defined as the time from the first treatment to death or loss to follow-up. The DFS was defined as the time from the first treatment to disease recurrence or progression. Statistical analysis was performed using R software (v4.2.2). Categorical variables were summarized as frequencies and percentages, while continuous variables were reported as means, medians, and standard deviations. OS and DFS were estimated using the Kaplan-Meier method, and significance was assessed using the log-rank test. Collinearity was evaluated using Chi-square and Fisher’s exact tests. Statistical significance was set at P < 0.05. significant. 3.0 Results 3.1 Patient Demographics and Baseline Characteristics The study cohort consisted predominantly of male patients across all groups (86.4%), with the Surgery Alone group having 100% male patients compared to 89.5% in the Surgery + Neoadjuvant group and 82.4% in the Surgery + Adjuvant group. The distribution of age at diagnosis was similar among the groups, with 47.5% of the patients under 61 years of age, and no significant difference was observed between the groups (P = 0.876) Table 1 . Table 1 Patient Demographics and Baseline Characteristics Patient Demographics and Baseline Characteristics Surgery + Adjuvant Treatment (N = 34) Surgery + Neoadjuvant Treatment (N = 19) Surgery Alone (N = 6) Overall (N = 59) P-value Gender Female 6 (17.6%) 2 (10.5%) 0 (0%) 8 (13.6%) 0.665 Male 28 (82.4%) 17 (89.5%) 6 (100%) 51 (86.4%) Age at diagnosis = 61 years 18 (52.9%) 9 (47.4%) 4 (66.7%) 31 (52.5%) BMI categories Normal 14 (41.2%) 7 (36.8%) 4 (66.7%) 25 (42.4%) 0.95 obesity 0 (0%) 1 (5.3%) 0 (0%) 1 (1.7%) Obesity 8 (23.5%) 3 (15.8%) 0 (0%) 11 (18.6%) Overweight 11 (32.4%) 6 (31.6%) 2 (33.3%) 19 (32.2%) under weight 0 (0%) 1 (5.3%) 0 (0%) 1 (1.7%) Under weight 1 (2.9%) 1 (5.3%) 0 (0%) 2 (3.4%) Smoking status Former 8 (23.5%) 2 (10.5%) 2 (33.3%) 12 (20.3%) 0.868 No 4 (11.8%) 4 (21.1%) 1 (16.7%) 9 (15.3%) Yes 22 (64.7%) 13 (68.4%) 3 (50.0%) 38 (64.4%) Hypertension No 23 (67.6%) 12 (63.2%) 6 (100%) 41 (69.5%) 0.384 Yes 11 (32.4%) 7 (36.8%) 0 (0%) 18 (30.5%) Diabetes mellitus No 25 (73.5%) 14 (73.7%) 5 (83.3%) 44 (74.6%) 0.966 Yes 9 (26.5%) 5 (26.3%) 1 (16.7%) 15 (25.4%) Cardiovascular diseases No 28 (82.4%) 15 (78.9%) 4 (66.7%) 47 (79.7%) 0.853 Yes 6 (17.6%) 4 (21.1%) 2 (33.3%) 12 (20.3%) COPD No 34 (100%) 16 (84.2%) 6 (100%) 56 (94.9%) 0.084 Yes 0 (0%) 3 (15.8%) 0 (0%) 3 (5.1%) Dyslipidemia No 29 (85.3%) 18 (94.7%) 6 (100%) 53 (89.8%) 0.584 Yes 5 (14.7%) 1 (5.3%) 0 (0%) 6 (10.2%) Renal diseases No 33 (97.1%) 17 (89.5%) 6 (100%) 56 (94.9%) 0.613 Yes 1 (2.9%) 2 (10.5%) 0 (0%) 3 (5.1%) Vitamin D at diagnosis (ng/mL) Deficiency 8 (23.5%) 2 (10.5%) 1 (16.7%) 11 (18.6%) 0.954 Insufficiency 7 (20.6%) 2 (10.5%) 1 (16.7%) 10 (16.9%) Normal 7 (20.6%) 5 (26.3%) 1 (16.7%) 13 (22.0%) Severe deficiency 4 (11.8%) 3 (15.8%) 2 (33.3%) 9 (15.3%) Missing 8 (23.5%) 7 (36.8%) 1 (16.7%) 16 (27.1%) Other malignancy No 26 (76.5%) 17 (89.5%) 5 (83.3%) 48 (81.4%) 0.711 Yes 8 (23.5%) 2 (10.5%) 1 (16.7%) 11 (18.6%) In terms of BMI categories, most patients had a normal BMI (42.4%), followed by overweight (32.2%), and obesity (18.6%), with no significant differences between the groups (P = 0.950) Table 1 . Smoking status varied slightly, with current smokers being the largest group overall (64.4%). Former smokers were more common in the Surgery Alone group (33.3%), while non-smokers accounted for 15.3% of the cohort. Hypertension was present in 30.5% of patients, diabetes mellitus in 25.4%, and cardiovascular diseases in 20.3%, with no significant differences across the groups (P = 0.384, P = 0.966, and P = 0.853, respectively). COPD was only observed in the Surgery + Neoadjuvant group (15.8%) Table 1 . Dyslipidemia (10.2%) and renal disease (5.1%) were relatively uncommon, with no significant group differences (P = 0.584 and P = 0.613, respectively). The vitamin D levels at diagnosis showed varying degrees of deficiency, with 22.0% having normal levels and 18.6% being deficient Table 1 . Severe deficiency was most notable in the surgery alone group (33.3%). Other malignancies were reported in 18.6% of patients, with similar distributions across the groups (P = 0.711). 3.2 Tumor and Disease Characteristics Adenocarcinoma accounted for 54.2% of the overall cases, followed by squamous cell carcinoma (33.9%) and other tumor types (11.9%), with no significant differences between the groups (P = 0.967) Table 2 . Most tumors were classified as pT4 (47.5%), particularly in the surgery-alone group (83.3%), whereas earlier stages (pT1 and 2) were more frequent in the Surgery + Neoadjuvant group (47.4%). Nodal status was predominantly N2 (35.6%), followed by N1 (33.9%), with N0 observed in 30.5% of patients, showing no significant variation (P = 0.464). All the patients in the cohort had M0 disease. Regarding the overall stage, most patients were stage IIIA (83.1%), and 16.9% were stage IIIB Table 2 . Table 2 Tumor and Disease Characteristics Tumor and Disease Characteristics Surgery + Adjuvant Treatment (N = 34) Surgery + Neoadjuvant Treatment (N = 19) Surgery Alone (N = 6) Overall (N = 59) P-value Type of tumor Adenocarcinoma 19 (55.9%) 9 (47.4%) 4 (66.7%) 32 (54.2%) 0.967 Others 4 (11.8%) 3 (15.8%) 0 (0%) 7 (11.9%) Squamous Cell Carcinoma 11 (32.4%) 7 (36.8%) 2 (33.3%) 20 (33.9%) pT I 3 (8.8%) 4 (21.1%) 0 (0%) 7 (11.9%) 0.449 II 4 (11.8%) 5 (26.3%) 0 (0%) 9 (15.3%) III 9 (26.5%) 5 (26.3%) 1 (16.7%) 15 (25.4%) IV 18 (52.9%) 5 (26.3%) 5 (83.3%) 28 (47.5%) pN N0 10 (29.4%) 4 (21.1%) 4 (66.7%) 18 (30.5%) 0.464 N1 11 (32.4%) 7 (36.8%) 2 (33.3%) 20 (33.9%) N2 13 (38.2%) 8 (42.1%) 0 (0%) 21 (35.6%) pM M0 34 (100%) 19 (100%) 6 (100%) 59 (100%) < 0.001 pStage IIIA 28 (82.4%) 15 (78.9%) 6 (100%) 49 (83.1%) 0.691 IIIB 6 (17.6%) 4 (21.1%) 0 (0%) 10 (16.9%) Stage progression Down stage 2 (5.9%) 6 (31.6%) 1 (16.7%) 9 (15.3%) 0.318 Persistent 21 (61.8%) 10 (52.6%) 4 (66.7%) 35 (59.3%) Up stage 11 (32.4%) 3 (15.8%) 1 (16.7%) 15 (25.4%) Extranodal extension No 24 (70.6%) 11 (57.9%) 4 (66.7%) 39 (66.1%) 0.903 Not studied 1 (2.9%) 2 (10.5%) 0 (0%) 3 (5.1%) Yes 9 (26.5%) 6 (31.6%) 2 (33.3%) 17 (28.8%) LVI No 16 (47.1%) 15 (78.9%) 3 (50.0%) 34 (57.6%) 0.155 Yes 18 (52.9%) 4 (21.1%) 3 (50.0%) 25 (42.4%) LN stations harvested 1–3 5 (14.7%) 0 (0%) 0 (0%) 5 (8.5%) 0.28 4–6 24 (70.6%) 13 (68.4%) 6 (100%) 43 (72.9%) 7–9 5 (14.7%) 6 (31.6%) 0 (0%) 11 (18.6%) Extranodal extension was present in 28.8% of cases, with no significant differences across the groups (P = 0.903) Table 2 . Lymph vascular invasion (LVI) was observed in 42.4% of the patients, with the highest proportion in the Surgery + Adjuvant group (52.9%). Most patients (72.9%) had 4–6 lymph node stations harvested, 18.6% had 7–9 stations, and 8.5% had 1–3 stations, with no significant variation between the groups (P = 0.28). 3.3 Surgical Details The surgical approaches included open procedures (54.2%) and VATS (45.8%), with no significant difference across the groups (P = 0.826) Table 3 . Lobectomy was the most common type of surgical resection, performed in 94.9% of the patients, with wedge resection and pneumonectomy being rare at 3.4% and 1.7%, respectively (P = 0.888). Table 3 Surgical Details Surgical Details Surgery + Adjuvant Treatment (N = 34) Surgery + Neoadjuvant Treatment (N = 19) Surgery Alone (N = 6) Overall (N = 59) P-value VATS VS Open Open 17 (50.0%) 12 (63.2%) 3 (50.0%) 32 (54.2%) 0.826 VATS 17 (50.0%) 7 (36.8%) 3 (50.0%) 27 (45.8%) Type of surgical resection Lobar 31 (91.2%) 19 (100%) 6 (100%) 56 (94.9%) 0.888 Pneumectomy 1 (2.9%) 0 (0%) 0 (0%) 1 (1.7%) Wedge 2 (5.9%) 0 (0%) 0 (0%) 2 (3.4%) R0 No 6 (17.6%) 0 (0%) 0 (0%) 6 (10.2%) 0.178 Yes 28 (82.4%) 19 (100%) 6 (100%) 53 (89.8%) R1 No 28 (82.4%) 19 (100%) 6 (100%) 53 (89.8%) 0.178 Yes 6 (17.6%) 0 (0%) 0 (0%) 6 (10.2%) R2 No 34 (100%) 19 (100%) 6 (100%) 59 (100%) < 0.001 Complete resection with negative margins (R0) was achieved in 89.8% of patients overall, with all patients in the Surgery + Neoadjuvant and Surgery Alone groups achieving R0 resection, compared with 82.4% in the Surgery + Adjuvant group (P = 0.178). No macroscopic residual disease (R2) was observed in any group Table 3 . 3.4 Treatment and Outcomes Adjuvant immunotherapy was used in 13.6% of the patients, with similar proportions in the Surgery + Adjuvant (14.7%) and Surgery + Neoadjuvant (15.8%) groups Table 4 . Table 4 Treatment and Outcomes Treatment and Outcomes Surgery + Adjuvant Treatment (N = 34) Surgery + Neoadjuvant Treatment (N = 19) Surgery Alone (N = 6) Overall (N = 59) P-value Neoadjuvant immunotherapy No 34 (100%) 18 (94.7%) 6 (100%) 58 (98.3%) 0.544 Yes 0 (0%) 1 (5.3%) 0 (0%) 1 (1.7%) Adjuvant immunotherapy No 29 (85.3%) 16 (84.2%) 6 (100%) 51 (86.4%) 0.787 Yes 5 (14.7%) 3 (15.8%) 0 (0%) 8 (13.6%) Complications No 31 (91.2%) 11 (57.9%) 4 (66.7%) 46 (78.0%) 0.039 Yes 3 (8.8%) 8 (42.1%) 2 (33.3%) 13 (22.0%) Recurrence No 26 (76.5%) 17 (89.5%) 6 (100%) 49 (83.1%) 0.419 Yes 8 (23.5%) 2 (10.5%) 0 (0%) 10 (16.9%) Postoperative complications occurred in 22.0% of patients overall, with the highest rate in the Surgery + Neoadjuvant group (42.1%), followed by the Surgery Alone group (33.3%), and the Surgery + Adjuvant group (8.8%), showing a statistically significant difference (P = 0.039) Table 4 . Disease recurrence was observed in 16.9% of patients, with the highest rate in the Surgery + Adjuvant group (23.5%). The surgery alone group had no recurrence, although this difference was not statistically significant (P = 0.419). 3.5 Survival analysis Survival analysis was performed to investigate potential differences in OS and DFS among the three groups. The highest three-year OS rate was observed in group 3 (66.7%), followed by group 1 (64.2%), and group 2 (57.9%). Group 1 demonstrated the longest median OS (55.51 months), while Group 2 had the shortest (42.26 months). This difference was not statistically significant (P = 0.96) ( Fig. 1 A ). Figure 1 B shows that Group 3 achieved the highest three-year DFS rate (66.7%), followed by Group 2 (34.4%), and Group 1 (24.1%). Group 1 had a notably shorter median DFS of 12.20 months (P = 0.5943). Figure 2 A shows the OS based on pN status. Patients with pN0 showed the most favorable outcomes, with a 83.1% three-year OS rate and 55.51 months median survival. In comparison, pN1 and pN2 patients had lower three-year OS rates (48.0% and 59.4%, respectively). The p-value was 0.39. DFS across the pN categories is illustrated in Fig. 2 B. pN0 patients exhibited the best outcomes, with a 61.6% three-year DFS rate. Three-year DFS rates decreased markedly for pN1 (35.7%) and pN2 (6.76%), with median DFS values of 16.72 and 11.90 months, respectively. The p-value was 0.0561. Figure 3 A illustrates the OS stratified by LVI status. Patients without LVI (LVI-N) demonstrated superior OS, with a 76.4% three-year rate, compared to 42.7% for those with LVI (LVI-Y). Figure 3 B shows DFS stratified by LVI status. Patients with LVI-N had better DFS, with a 42.5% three-year rate, compared to 14.6% for those with LVI (LVI-Y). Median DFS was considerably longer for LVI-N (33.67 months) than LVI-Y (9.77 months), with a p-value of 0.0084. The OS comparison between the VATS and open surgery groups is shown in Fig. 4 A. VATS patients had a higher three-year OS rate (72.3%) than open surgery patients (54.1%) (p = 0.2611). Figure 4 B shows the DFS for VATS versus open surgery. The three-year DFS rate was higher for VATS (34.2%) than for open surgery (26.1%) (p = 0.4841). The metastasis-free survival rates across the three patient groups are shown in Fig. 5 . Group 3 showed the highest three-year metastasis-free survival rate of 66.7% (95% CI: 27.8%, 95.4%), followed by Group 2 at 47.7% (95% CI: 21.2%, 74.9%), and Group 1 at 38.1% (95% CI: 20.6%, 57.2%). 4.0 Discussion The management of Stage III NSCLC remains a significant challenge because of its heterogeneity and the lack of universally accepted guidelines. Debate persists over the optimal integration of surgical resection, systemic therapies, and radiation into treatment protocols. Multimodal approaches have demonstrated potential to improve patient survival. However, factors such as patient comorbidities, tumor biology, and healthcare disparities complicate their implementation. Our study aimed to address this complexity by investigating the role of surgery in a multidisciplinary setting, particularly in resource-limited environments, and its effects on OS and DFS. Comorbidities substantially influenced the treatment outcomes in our cohort, including hypertension (30.5%), diabetes (25.4%), and COPD (15.8%). These findings align with broader literature, emphasizing the importance of managing comorbid conditions to optimize cancer outcomes. For example, COPD exacerbates pulmonary complications during chemoradiotherapy and surgery, contributing to higher treatment discontinuation rates and poorer DFS rates ( 13 ). Diabetes can diminish the efficacy of chemotherapy and immunotherapy through hyperglycemia-induced immune impairment ( 14 , 15 ). Addressing these conditions using a multidisciplinary approach can improve treatment readiness and OS ( 14 , 15 ). Tumor biology plays an important role in determining the prognosis and tailoring treatment strategies. In our cohort, adenocarcinoma was the predominant subtype (54.2%), followed by squamous cell carcinoma (33.9%), which is consistent with global patterns. The pN status has emerged as a critical prognostic factor, with pN2 disease significantly lowering OS and DFS. Advanced nodal stages (e.g., pN2–N3) are well-documented predictors of poor outcomes due to increased recurrence risk, particularly in the absence of multimodal therapies ( 16 ). In our study, LVI was observed in 42.4% of patients with markedly lower DFS (9.77 months) than in those without LVI (33.67 months). These findings align with the evidence correlating LVI with increased recurrence and reduced survival, particularly in adenocarcinoma subtypes ( 17 ). Emerging diagnostic tools, such as artificial intelligence-based imaging and transcriptomic analyses, now offer improved LVI detection, enabling tailored postsurgical therapies ( 18 , 19 ) Surgical resection remains a cornerstone in the management of resectable Stage III NSCLC, particularly when integrated into multimodal treatment strategies. Our study demonstrated the critical role of R0 resection, as patients with negative margins exhibited superior outcomes. This aligns with findings from the Extended Resection Study (2022), which reported a 5-year OS rate of 44% for advanced NSCLC cases treated with induction therapy and achieving R0 status( 20 ). Salvage surgeries for recurrent or residual disease also highlight the potential for achieving long-term survival benefits, with a median OS of 69 months reported in selected cases ( 21 ). Minimally invasive techniques, such as VATS, have improved surgical outcomes by reducing perioperative morbidity without compromising oncological effectiveness. Studies comparing VATS and open thoracotomy, including those by Hireche et al. (2023)( 22 ) and Cao et al. (2023)( 23 ), reported equivalent OS and DFS, but superior perioperative outcomes with VATS, such as reduced blood loss and shorter recovery times. However, complications remain a concern, particularly in salvage procedures where circulatory issues are prevalent in up to 80.9% of patients ( 24 ). These findings underscore the need for careful patient selection to optimize surgical outcomes. Neoadjuvant and adjuvant therapies have become integral to improving outcomes in Stage III NSCLC, particularly enhancing resectability and reducing recurrence risks. Neoadjuvant chemoimmunotherapy facilitates tumor downstaging and increases the likelihood of achieving R0 margins, with major pathological response rates reaching 58.1% in real-world settings ( 25 ). Similarly, adjuvant therapies, such as durvalumab, as demonstrated in the PACIFIC trial, have established new standards of care by significantly improving OS and PFS after concurrent chemoradiotherapy ( 26 ). Emerging combinations, such as durvalumab with oleclumab or monalizumab, aim to further enhance antitumor immune responses ( 27 ). Adjuvant treatments have also proven to be effective in addressing micrometastatic disease, which is critical for long-term disease control. For example, incorporating postoperative radiotherapy and chemotherapy significantly reduced locoregional recurrence rates compared with surgery alone, as evidenced by recurrence rates of 7.1% for PORT versus 31.6% for surgery alone ( 28 ). These findings highlight the importance of integrating systemic and local therapies to optimize outcomes in aggressive or advanced disease settings. While controlled clinical trials provide essential insights, real-world evidence highlights the variability in treatment outcomes owing to differences in healthcare infrastructure, patient profiles, and access to therapies. For instance, the findings of the PACIFIC trial were replicated in real-world settings, emphasizing the role of biomarkers such as PD-L1 expression and gene signatures such as KEAP1 and STK11 mutations in predicting treatment responses ( 29 , 30 ). However, several challenges remain, particularly in resource-limited settings. Developing countries face significant barriers in implementing advanced therapies, including limited access to FDG PET/CT, immune checkpoint inhibitors (ICIs), and multidisciplinary teams. Financial constraints and insufficient public health investment further exacerbate these disparities, leading to late-stage diagnoses and suboptimal outcomes ( 31 , 32 ). Addressing these challenges requires international collaboration, adoption of cost-effective solutions, and tailored strategies such as metronomic chemotherapy to improve care delivery and outcomes in low- and middle-income countries. This study provides valuable insights into the management of Stage III NSCLC, highlighting the importance of surgical resection within a multidisciplinary framework, particularly in resource-limited countries. Its strength lies in analyzing patient outcomes in a clinical setting, where healthcare disparities and limited access to advanced treatments are significant. By evaluating comorbidities, tumor characteristics, and surgery with multimodal therapies, this study addressed the critical factors for optimizing treatment strategies. However, the retrospective design introduces limitations, such as potential selection bias and a small cohort size, affecting statistical power and generalizability. Additionally, the lack of standardized protocols for adjuvant therapies and long-term follow-up data limit the assessment of the impact of emerging therapies on disease progression and survival. Future prospective studies with larger cohorts are needed to validate and expand these findings. 5.0 Conclusion Our study emphasizes the pivotal role of surgical resection as part of a multimodal strategy for managing Stage III NSCLC, particularly in resource-constrained environments. These findings emphasize the importance of achieving R0 resection, optimizing the management of comorbidities, and integrating systemic therapies to enhance patient outcomes. While surgery alone offers considerable survival benefits, the inclusion of neoadjuvant or adjuvant therapies further improves survival, especially in patients with pN0 status and no LVI. Despite the challenges posed by healthcare disparities, these results highlight the importance of multidisciplinary approaches and adoption of cost-effective strategies to enhance care delivery. Future research should focus on standardizing treatment protocols and exploring innovative therapies to address the complexity of Stage III NSCLC, ultimately advancing equitable and effective cancer care on a global scale. Abbreviations DFS – Disease-Free Survival FDG PET/CT – Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography ICI – Immune Checkpoint Inhibitor KHCC – King Hussein Cancer Center LVI – Lymphovascular Invasion M0 – No Distant Metastases NSCLC – Non-Small Cell Lung Cancer OS – Overall Survival pN – Pathologic Nodal Status PFS – Progression-Free Survival R0 – Complete Tumor Resection with Negative Margins R2 – Macroscopic Residual Disease VATS – Video-Assisted Thoracoscopic Surgery Declarations Data availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Acknowledgements Not applicable. Funding Not applicable. Author Contribution R.A.A. conceptualized the study, drafted the original manuscript, and supervised the work. S.A. conducted formal analysis, developed the software, and contributed to drafting the manuscript. A.A., T.A.H., K.A., S.Y., H.A.J., J.K., A.A.N., and H.A.H. drafted the original manuscript and provided resources. L.O.N. curated the data and contributed resources. All authors reviewed the manuscript. Ethics approval and consent to participate This study was approved by the local Ethics Committee of the KHCC on August 29th, 2021 (Proposal No. 21 KHCC 115). The need for informed consent was waived due to the retrospective analysis of routinely collected patient data. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A 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(3). Meldgaard P, Kristensen M, Conte S, Kaae Andersen K, Jovanovic A, Meldgaard E. Improved overall survival for Stage III NSCLC patients treated with curative-intended therapy from 2010 to 2018–a cohort study in Denmark. Acta Oncol (Madr). 2023;62(12). Auliac JB, Greillier L, Martin E, Falcoz PE, Boisselier P, Ano S et al. Profiles, diagnostic process, and patterns of care of patients with stage III non-small cell lung cancer: A French national study. Respir Med Res. 2024;85. Murakami H, Horinouchi H, Harada H, Sobue T, Kato T, Atagi S et al. Deciphering the clinical features of heterogeneous stage III non-small cell lung cancer in Japanese real-world clinical practice: Expanded cohort of the SOLUTION study. Lung Cancer. 2022;165. Luo W, Zhong R, Yang M, Zhou Q. Interpretation of expert consensus on treatment for stage III non-small cell lung cancer. Med Adv. 2023;1(1). Luna JM, Barsky AR, Shinohara RT, Roshkovan L, Hershman M, Dreyfuss AD et al. Radiomic Phenotypes for Improving Early Prediction of Survival in Stage III Non-Small Cell Lung Cancer Adenocarcinoma after Chemoradiation. Cancers (Basel). 2022;14(3). Wang T, Li L, Huang L, Wei Liu J, Xing Zhu D, Si Dong J et al. A phase II study of tislelizumab (TIS) and chemotherapy as neoadjuvant therapy for potentially resectable stage IIIA/IIIB non-small cell lung cancer (NSCLC). 2024. Qi Y, Sun Y, Zhu H, Guo H. Efficacy and surgical safety of sequential surgical resection after neoadjuvant chemoimmunotherapy for unresectable stage III NSCLC. 2024. Passaro A, Mok TSK, Attili I, Wu YL, Tsuboi M, De Marinis F et al. Adjuvant Treatments for Surgically Resected Non-Small Cell Lung Cancer Harboring EGFR Mutations: A Review. 9, JAMA Oncol. 2023. Faivre-Finn C, Edwards JG, Hatton M. Postoperative Radiation Therapy Should Not Be Used for the Therapy of Stage III-N2 NSCLC. 17, J Thorac Oncol. 2022. Erol C, Hizal M, Kahraman S, Bardakci M, Sener Dede D, Bulent Akinci M et al. Are the clinical trials in lung cancer an advantage for patients in developing countries? 2024. Guo L, Zhu C, Cai L, Zhang X, Fang Y, Chen H et al. Global burden of lung cancer in 2022 and projected burden in 2050. Chin Med J (Engl). 2024. Sekine Y, Behnia M, Fujisawa T. Impact of COPD on pulmonary complications and on long-term survival of patients undergoing surgery for NSCLC. In: Lung Cancer. 2002. Leshem Y, Dolev Y, Siegelmann-Danieli N, Sharman Moser S, Apter L, Chodick G et al. Association between diabetes mellitus and reduced efficacy of pembrolizumab in non–small cell lung cancer. Cancer. 2023;129(18). Cortellini A, D’Alessio A, Cleary S, Buti S, Bersanelli M, Bordi P et al. Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer. Clin Cancer Res. 2023;29(14). Vu N, Tien Manh D, Viet Cuong N, Hong Son N, Quoc Viet T, Onishi H et al. Long-term survival outcome of radiation therapy for unresectable, locally advanced non-small cell lung cancer: Single center experience at Hospital 175. 2024. Suaiti L, Sullivan TB, Rieger-Christ KM, Servais EL, Suzuki K, Burks EJ. Vascular Invasion Predicts Recurrence in Stage IA2-IB Lung Adenocarcinoma but not Squamous Cell Carcinoma. Clin Lung Cancer. 2023;24(3). Huang X, Feng Y, Li Y, Ding H, Huang X, Chen C et al. A novel transcriptomic signature associated with lymphovascular invasion predicts clinical outcomes, tumor microenvironment, and therapeutic response in lung adenocarcinoma. Int Immunopharmacol. 2024;127. Zuo Z, Fan X, Tang Y, Zhang Y, Peng X, Zeng W et al. Deep learning-powered 3D segmentation derives factors associated with lymphovascular invasion and prognosis in clinical T1 stage non-small cell lung cancer. Heliyon. 2023;9(4). Furrer K, Weder W, Eboulet EI, Betticher D, Pless M, Stupp R et al. Extended resection for potentially operable patients with stage III non–small cell lung cancer after induction treatment. In: J Thorac Cardiovasc Surg. 2022. Werner RS, Furrer K, Lauk O, Caviezel C, Hillinger S, Schneiter D et al. Salvage Surgery in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Br J Surg. 2023;110(Supplement_5). Hireche K, Lounes Y, Bacri C, Solovei L, Marty-Ané C, Canaud L et al. VATS versus Open Lobectomy following Induction Therapy for Stage III NSCLC: A Propensity Score-Matched Analysis. Cancers (Basel). 2023;15(2). Cao J, Zhang C, Zhang X, Liu L, Li X, He J et al. The Clinical Outcomes of Thoracoscopic Versus Open Lobectomy for Non–Small-Cell Lung Cancer After Neoadjuvant Therapy: A Multi-Center Retrospective Cohort Study. Clin Lung Cancer. 2024;25(3). Kasprzyk M, Sławiński G, Musik M, Marciniak Ł, Dyszkiewicz W, Piwkowski C et al. Completion pneumonectomy and chemoradiotherapy as treatment options in local recurrence of non-small-cell lung cancer. Kardiochirurgia i Torakochirurgia Polska. 2015;12(1). Yang Z, Wang S, Yang H, Jiang Y, Zhu L, Zheng B et al. Treatment patterns and clinical outcomes of patients with resectable non–small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World). J Thorac Cardiovasc Surg. 2024. Orosz Z, Kovács Á. The role of chemoradiotherapy and immunotherapy in stage III NSCLC. Pathology and Oncology Research. Volume 30. Frontiers Media SA; 2024. Käsmann L, Eze C, Taugner J, Roengvoraphoj O, Dantes M, Schmidt-Hegemann NS et al. Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: Immunological rationale and current clinical trials establishing a novel multimodal strategy. 15, Radiat Oncol. 2020. Solodkiy VA, Sotnikov VM, Trotsenko SD, Kharchenko VP, Chkhikvadze VD, Nudnov NV et al. Non-small cell lung cancer recurrences after surgical and combined modality treatment with postoperative radiation therapy. Med Radiol Radiation Saf. 2018;63(6). Manapov F, Nieto A, Käsmann L, Taugner J, Kenndoff S, Flörsch B et al. Five years after PACIFIC: update on multimodal treatment efficacy based on real-world reports. Expert Opin Investig Drugs. 2023;32(3). Katherina C, Chua. Assieh Saadatpour; Ariel Chen; Aisha Hasan; Bevan Emma Huang; Stewart Bates. Evaluating biomarkers of immunotherapy response in a real-world metastatic NSCLC cohort. Cancer Res. 2024. Konert T, Vogel WV, Paez D, Polo A, Fidarova E, Carvalho H et al. Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial. Eur J Nucl Med Mol Imaging. 2019;46(11). Jiwnani S, Penumadu P, Ashok A, Pramesh CS. Lung Cancer Management in Low and Middle-Income Countries. Vol. 32, Thoracic surgery clinics. 2022. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Dec, 2025 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted Editorial decision: Revision requested 13 Sep, 2025 Reviews received at journal 24 Jun, 2025 Reviews received at journal 05 Jun, 2025 Reviewers agreed at journal 04 Jun, 2025 Reviewers agreed at journal 04 Jun, 2025 Reviewers invited by journal 02 Jun, 2025 Editor assigned by journal 26 Mar, 2025 Submission checks completed at journal 26 Mar, 2025 First submitted to journal 25 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6302087","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":466604681,"identity":"15eb3b92-f9a6-4ae6-8b53-7648abc0f0de","order_by":0,"name":"Riad Amin Abdeljalil","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYBACe2YGhgMfKtjk+Hl4QHw2wloM2xsYH844w2cs2UOsFoMzB5iNOVvkEjec4SHSYQY3EtikGRvMjI3PnD344QcDnxxxWgp3pMmZne1LluxhYDMmTsvMM8eMzc7zmAGDgi2xgaCW+w/YpHnb/idu7iday40EZmPeNrbEDbw9RGoxnJHYCAxkNmOJM2eAAW1AhF/sJZIPQKKyJ8fww4+KY4RDjIGBEdklBseI0IEGakjXMgpGwSgYBcMeAAAmoDutw6yM5gAAAABJRU5ErkJggg==","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Riad","middleName":"Amin","lastName":"Abdeljalil","suffix":""},{"id":466604683,"identity":"6f683b5c-5c04-4a5f-b0e9-fb2a9cca0763","order_by":1,"name":"Ahed Al-odwan","email":"","orcid":"","institution":"King Hussein Cancer Centre","correspondingAuthor":false,"prefix":"","firstName":"Ahed","middleName":"","lastName":"Al-odwan","suffix":""},{"id":466604686,"identity":"a44f98ef-9592-4523-b921-57894f2e305c","order_by":2,"name":"Sakhr Alshwayyat","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Sakhr","middleName":"","lastName":"Alshwayyat","suffix":""},{"id":466604687,"identity":"0973c003-28ee-472a-a4ab-fe28e180a484","order_by":3,"name":"Leen Osama Nemrawi","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Leen","middleName":"Osama","lastName":"Nemrawi","suffix":""},{"id":466604688,"identity":"1d6c86dd-3ef3-4600-a30c-15dc8a11d5f1","order_by":4,"name":"Taher Abu Hejleh","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Taher","middleName":"Abu","lastName":"Hejleh","suffix":""},{"id":466604689,"identity":"87291a06-483f-40eb-9beb-db3ee882110e","order_by":5,"name":"Kamal Alrabi","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Kamal","middleName":"","lastName":"Alrabi","suffix":""},{"id":466604690,"identity":"aef65387-7e5e-43d8-9ef5-4b0928b9880c","order_by":6,"name":"Sameer Yaser","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Sameer","middleName":"","lastName":"Yaser","suffix":""},{"id":466604691,"identity":"9ff3f1d3-3c65-4611-a274-8c18b67c5b10","order_by":7,"name":"Husam Abu Jazar","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Husam","middleName":"Abu","lastName":"Jazar","suffix":""},{"id":466604692,"identity":"a8219a14-9f42-43df-b6ef-7a0936dcd12a","order_by":8,"name":"Jamal Khader","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Jamal","middleName":"","lastName":"Khader","suffix":""},{"id":466604693,"identity":"8f1e4b86-ba50-4c44-bb2f-a75b82bc7095","order_by":9,"name":"Anoud Al-Nsour","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Anoud","middleName":"","lastName":"Al-Nsour","suffix":""},{"id":466604694,"identity":"53cb937a-be40-4a02-ba2b-318fb51b085e","order_by":10,"name":"Husam Al-Haddad","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Husam","middleName":"","lastName":"Al-Haddad","suffix":""}],"badges":[],"createdAt":"2025-03-25 09:08:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6302087/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6302087/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13019-025-03752-9","type":"published","date":"2025-12-22T15:58:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84207499,"identity":"6c998ac7-9aad-47b7-a92d-b9c8ec211447","added_by":"auto","created_at":"2025-06-09 09:27:20","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":68743,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Kaplan-Meier curve of overall survival (OS) and (B) disease-free survival (DFS) among the three groups.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6302087/v1/29ffcecc7614e259673880a4.jpg"},{"id":84207938,"identity":"24e2d48e-298a-4f3f-9c3a-a09bf11ad263","added_by":"auto","created_at":"2025-06-09 09:35:20","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":82322,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Kaplan-Meier curve of overall survival (OS) and (B) disease-free survival (DFS) stratified by pN status.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6302087/v1/373c0fc16ba69778183dbb87.jpg"},{"id":84207939,"identity":"dbf86a4e-6fcc-41f8-92f3-882f3916a4ab","added_by":"auto","created_at":"2025-06-09 09:35:20","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":95655,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Kaplan-Meier curve of overall survival (OS) and (B) disease-free survival (DFS) stratified by lymphovascular invasion (LVI) status.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6302087/v1/04d2142f12237b6dc458d9e7.jpg"},{"id":84209193,"identity":"fe4e8980-949b-42e2-9ac8-e7bf69ea2991","added_by":"auto","created_at":"2025-06-09 09:43:20","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":88889,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Kaplan-Meier curve of overall survival (OS) and (B) disease-free survival (DFS) comparing video-assisted thoracoscopic surgery (VATS) and open surgery.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6302087/v1/c5e668265fd8e47e16fd0e2e.jpg"},{"id":84207937,"identity":"e32f5eac-dae6-45f6-bb41-a4f6bd7ce3d2","added_by":"auto","created_at":"2025-06-09 09:35:20","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":58980,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of metastasis-free survival across the three groups.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6302087/v1/5a419cce2465201149c8b725.jpg"},{"id":99172506,"identity":"35114b34-a3c5-4f05-8ed8-fd8624161d15","added_by":"auto","created_at":"2025-12-29 16:10:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1957158,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6302087/v1/8876db99-6cad-426a-993b-325c35825c1d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Multimodality Approach for Locally Advanced Lung Cancer: When Is Surgery Most Beneficial?","fulltext":[{"header":"1.0 Introduction","content":"\u003cp\u003eStage III non-small cell lung cancer (NSCLC) is a diverse condition affecting approximately 20\u0026ndash;30% of patients with NSCLC worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Its heterogeneity in tumor biology, patient characteristics, and treatment outcomes presents significant challenges for diagnosis and management. Despite progress, there remains a lack of universally accepted guidelines highlighting the difficulty in optimizing treatment approaches.\u003c/p\u003e \u003cp\u003eCollaborative approaches have led to substantial improvements in patient outcomes. Research from Denmark showed a median overall survival (OS) of 24.4 months for patients receiving curative-intent therapy compared to 9.8 months for those receiving palliative care (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). A French national study emphasized the value of invasive staging and combined treatments, including chemoradiotherapy (CRT) followed by consolidation immunotherapy, in alignment with updated guidelines (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Surgical removal in selected patients yielded promising results, with complete resection achieved in 85% of the cases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn Japan, real-world evidence indicated that surgery, though less commonly employed, resulted in superior OS (median 43.4 months) compared to CRT or radiotherapy alone (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In China, targeted approaches, such as EGFR mutation testing and PD-L1 expression evaluation, have guided treatment in resectable Stage III cases, thereby enhancing therapeutic effectiveness (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Advanced radiomic analysis has also improved survival predictions, offering noninvasive methods to assess tumor heterogeneity (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePre- and post-surgical therapies have transformed the treatment paradigms for Stage III NSCLC. Studies have shown that neoadjuvant chemoimmunotherapy significantly enhances resectability and pathological responses, with event-free survival rates exceeding 75% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Adjuvant therapies, including targeted agents such as osimertinib and immunotherapies such as atezolizumab, have further reduced recurrence risks and extended disease-free survival, although debates regarding their long-term efficacy continue (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWorldwide disparities in lung cancer outcomes underscore the impact of health care inequities. Patients in developed nations benefit from early diagnosis and access to advanced therapies, whereas those in resource-limited settings face challenges of late-stage presentations and restricted treatment options (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Addressing these inequities through clinical trial access and cost-effective interventions is a global priority.\u003c/p\u003e \u003cp\u003eThis study aimed to assess the impact of surgical intervention on overall survival (OS) and disease-free survival (DFS) in Stage III NSCLC management in a developing country where expensive systemic treatment is not usually available. We examined patient outcomes based on treatment strategies, tumor characteristics, and multimodal approaches to address the lack of standardized guidelines for optimal patient selection and treatment pathways, with the aim of contributing to the global discussion on personalized and multidisciplinary management of Stage III NSCLC.\u003c/p\u003e"},{"header":"2.0 Methods","content":"\u003cp\u003eThis retrospective observational study was conducted at King Hussein Cancer Center (KHCC), a large tertiary cancer center. This study was approved by the KHCC Institutional Review Board (Proposal No. 21 KHCC 115) and the requirement for informed consent was waived because of its retrospective nature.\u003c/p\u003e \u003cp\u003eThe medical records of 309 patients who underwent surgery for confirmed primary lung cancer at the King Hussein Cancer Center (KHCC) in Amman, Jordan between 2016 and 2022 were retrospectively studied. 59 patients with stage III lung cancer who underwent curative lung resection were included in the final detailed analysis. We divided them into three groups: Group 1, patients who underwent upfront surgery followed by adjuvant treatment; Group 2, those who underwent neoadjuvant treatment followed by surgery; and Group 3, those who underwent surgery alone.\u003c/p\u003e \u003cp\u003eBaseline data, including demographic information, tumor characteristics and treatment data were collected from medical records. OS was defined as the time from the first treatment to death or loss to follow-up. The DFS was defined as the time from the first treatment to disease recurrence or progression.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using R software (v4.2.2). Categorical variables were summarized as frequencies and percentages, while continuous variables were reported as means, medians, and standard deviations. OS and DFS were estimated using the Kaplan-Meier method, and significance was assessed using the log-rank test. Collinearity was evaluated using Chi-square and Fisher\u0026rsquo;s exact tests. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. significant.\u003c/p\u003e"},{"header":"3.0 Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Patient Demographics and Baseline Characteristics\u003c/h2\u003e \u003cp\u003eThe study cohort consisted predominantly of male patients across all groups (86.4%), with the Surgery Alone group having 100% male patients compared to 89.5% in the Surgery\u0026thinsp;+\u0026thinsp;Neoadjuvant group and 82.4% in the Surgery\u0026thinsp;+\u0026thinsp;Adjuvant group. The distribution of age at diagnosis was similar among the groups, with 47.5% of the patients under 61 years of age, and no significant difference was observed between the groups (P\u0026thinsp;=\u0026thinsp;0.876) Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Demographics and Baseline Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient Demographics and Baseline Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Adjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Neoadjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurgery Alone\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.665\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51 (86.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;61 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (52.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e28 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.876\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;= 61 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (47.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e31 (52.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI categories\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (41.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eobesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (15.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19 (32.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunder weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnder weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (64.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (68.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e38 (64.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (67.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (63.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e41 (69.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e18 (30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (73.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (73.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e44 (74.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.966\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCardiovascular diseases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (78.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47 (79.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.853\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCOPD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (84.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56 (94.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (15.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDyslipidemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (85.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (94.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e53 (89.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.584\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRenal diseases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (97.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56 (94.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVitamin D at diagnosis (ng/mL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.954\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13 (22.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (15.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16 (27.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOther malignancy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (76.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e48 (81.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn terms of BMI categories, most patients had a normal BMI (42.4%), followed by overweight (32.2%), and obesity (18.6%), with no significant differences between the groups (P\u0026thinsp;=\u0026thinsp;0.950) Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Smoking status varied slightly, with current smokers being the largest group overall (64.4%). Former smokers were more common in the Surgery Alone group (33.3%), while non-smokers accounted for 15.3% of the cohort.\u003c/p\u003e \u003cp\u003eHypertension was present in 30.5% of patients, diabetes mellitus in 25.4%, and cardiovascular diseases in 20.3%, with no significant differences across the groups (P\u0026thinsp;=\u0026thinsp;0.384, P\u0026thinsp;=\u0026thinsp;0.966, and P\u0026thinsp;=\u0026thinsp;0.853, respectively). COPD was only observed in the Surgery\u0026thinsp;+\u0026thinsp;Neoadjuvant group (15.8%) Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Dyslipidemia (10.2%) and renal disease (5.1%) were relatively uncommon, with no significant group differences (P\u0026thinsp;=\u0026thinsp;0.584 and P\u0026thinsp;=\u0026thinsp;0.613, respectively).\u003c/p\u003e \u003cp\u003eThe vitamin D levels at diagnosis showed varying degrees of deficiency, with 22.0% having normal levels and 18.6% being deficient Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Severe deficiency was most notable in the surgery alone group (33.3%). Other malignancies were reported in 18.6% of patients, with similar distributions across the groups (P\u0026thinsp;=\u0026thinsp;0.711).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Tumor and Disease Characteristics\u003c/h2\u003e \u003cp\u003eAdenocarcinoma accounted for 54.2% of the overall cases, followed by squamous cell carcinoma (33.9%) and other tumor types (11.9%), with no significant differences between the groups (P\u0026thinsp;=\u0026thinsp;0.967) Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Most tumors were classified as pT4 (47.5%), particularly in the surgery-alone group (83.3%), whereas earlier stages (pT1 and 2) were more frequent in the Surgery\u0026thinsp;+\u0026thinsp;Neoadjuvant group (47.4%). Nodal status was predominantly N2 (35.6%), followed by N1 (33.9%), with N0 observed in 30.5% of patients, showing no significant variation (P\u0026thinsp;=\u0026thinsp;0.464). All the patients in the cohort had M0 disease. Regarding the overall stage, most patients were stage IIIA (83.1%), and 16.9% were stage IIIB Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTumor and Disease Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor and Disease Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Adjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Neoadjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurgery Alone\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of tumor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (55.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (47.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.967\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (15.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquamous Cell Carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (33.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (29.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (33.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (38.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (35.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (78.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49 (83.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.691\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage progression\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDown stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.318\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePersistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (61.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (52.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (59.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUp stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (15.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtranodal extension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (70.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39 (66.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.903\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot studied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (78.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34 (57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLN stations harvested\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (70.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (68.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43 (72.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eExtranodal extension was present in 28.8% of cases, with no significant differences across the groups (P\u0026thinsp;=\u0026thinsp;0.903) Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Lymph vascular invasion (LVI) was observed in 42.4% of the patients, with the highest proportion in the Surgery\u0026thinsp;+\u0026thinsp;Adjuvant group (52.9%). Most patients (72.9%) had 4\u0026ndash;6 lymph node stations harvested, 18.6% had 7\u0026ndash;9 stations, and 8.5% had 1\u0026ndash;3 stations, with no significant variation between the groups (P\u0026thinsp;=\u0026thinsp;0.28).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Surgical Details\u003c/h2\u003e \u003cp\u003eThe surgical approaches included open procedures (54.2%) and VATS (45.8%), with no significant difference across the groups (P\u0026thinsp;=\u0026thinsp;0.826) Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Lobectomy was the most common type of surgical resection, performed in 94.9% of the patients, with wedge resection and pneumonectomy being rare at 3.4% and 1.7%, respectively (P\u0026thinsp;=\u0026thinsp;0.888).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgical Details\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical Details\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Adjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Neoadjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurgery Alone\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVATS VS Open\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (63.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27 (45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of surgical resection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLobar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (91.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56 (94.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.888\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWedge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 (89.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 (89.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eComplete resection with negative margins (R0) was achieved in 89.8% of patients overall, with all patients in the Surgery\u0026thinsp;+\u0026thinsp;Neoadjuvant and Surgery Alone groups achieving R0 resection, compared with 82.4% in the Surgery\u0026thinsp;+\u0026thinsp;Adjuvant group (P\u0026thinsp;=\u0026thinsp;0.178). No macroscopic residual disease (R2) was observed in any group Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Treatment and Outcomes\u003c/h2\u003e \u003cp\u003eAdjuvant immunotherapy was used in 13.6% of the patients, with similar proportions in the Surgery\u0026thinsp;+\u0026thinsp;Adjuvant (14.7%) and Surgery\u0026thinsp;+\u0026thinsp;Neoadjuvant (15.8%) groups Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment and Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment and Outcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Adjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Neoadjuvant Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurgery Alone\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant immunotherapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (94.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e58 (98.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjuvant immunotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (85.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (84.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51 (86.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (15.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (91.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46 (78.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13 (22.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (76.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e49 (83.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePostoperative complications occurred in 22.0% of patients overall, with the highest rate in the Surgery\u0026thinsp;+\u0026thinsp;Neoadjuvant group (42.1%), followed by the Surgery Alone group (33.3%), and the Surgery\u0026thinsp;+\u0026thinsp;Adjuvant group (8.8%), showing a statistically significant difference (P\u0026thinsp;=\u0026thinsp;0.039) Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Disease recurrence was observed in 16.9% of patients, with the highest rate in the Surgery\u0026thinsp;+\u0026thinsp;Adjuvant group (23.5%). The surgery alone group had no recurrence, although this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.419).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Survival analysis\u003c/h2\u003e \u003cp\u003eSurvival analysis was performed to investigate potential differences in OS and DFS among the three groups. The highest three-year OS rate was observed in group 3 (66.7%), followed by group 1 (64.2%), and group 2 (57.9%). Group 1 demonstrated the longest median OS (55.51 months), while Group 2 had the shortest (42.26 months). This difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.96) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB shows that Group 3 achieved the highest three-year DFS rate (66.7%), followed by Group 2 (34.4%), and Group 1 (24.1%). Group 1 had a notably shorter median DFS of 12.20 months (P\u0026thinsp;=\u0026thinsp;0.5943).\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA shows the OS based on pN status. Patients with pN0 showed the most favorable outcomes, with a 83.1% three-year OS rate and 55.51 months median survival. In comparison, pN1 and pN2 patients had lower three-year OS rates (48.0% and 59.4%, respectively). The p-value was 0.39. DFS across the pN categories is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB. pN0 patients exhibited the best outcomes, with a 61.6% three-year DFS rate. Three-year DFS rates decreased markedly for pN1 (35.7%) and pN2 (6.76%), with median DFS values of 16.72 and 11.90 months, respectively. The p-value was 0.0561.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA illustrates the OS stratified by LVI status. Patients without LVI (LVI-N) demonstrated superior OS, with a 76.4% three-year rate, compared to 42.7% for those with LVI (LVI-Y). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB shows DFS stratified by LVI status. Patients with LVI-N had better DFS, with a 42.5% three-year rate, compared to 14.6% for those with LVI (LVI-Y). Median DFS was considerably longer for LVI-N (33.67 months) than LVI-Y (9.77 months), with a p-value of 0.0084.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe OS comparison between the VATS and open surgery groups is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA. VATS patients had a higher three-year OS rate (72.3%) than open surgery patients (54.1%) (p\u0026thinsp;=\u0026thinsp;0.2611). Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB shows the DFS for VATS versus open surgery. The three-year DFS rate was higher for VATS (34.2%) than for open surgery (26.1%) (p\u0026thinsp;=\u0026thinsp;0.4841).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe metastasis-free survival rates across the three patient groups are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Group 3 showed the highest three-year metastasis-free survival rate of 66.7% (95% CI: 27.8%, 95.4%), followed by Group 2 at 47.7% (95% CI: 21.2%, 74.9%), and Group 1 at 38.1% (95% CI: 20.6%, 57.2%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4.0 Discussion","content":"\u003cp\u003e The management of Stage III NSCLC remains a significant challenge because of its heterogeneity and the lack of universally accepted guidelines. Debate persists over the optimal integration of surgical resection, systemic therapies, and radiation into treatment protocols. Multimodal approaches have demonstrated potential to improve patient survival. However, factors such as patient comorbidities, tumor biology, and healthcare disparities complicate their implementation.\u003c/p\u003e \u003cp\u003eOur study aimed to address this complexity by investigating the role of surgery in a multidisciplinary setting, particularly in resource-limited environments, and its effects on OS and DFS. Comorbidities substantially influenced the treatment outcomes in our cohort, including hypertension (30.5%), diabetes (25.4%), and COPD (15.8%). These findings align with broader literature, emphasizing the importance of managing comorbid conditions to optimize cancer outcomes. For example, COPD exacerbates pulmonary complications during chemoradiotherapy and surgery, contributing to higher treatment discontinuation rates and poorer DFS rates (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Diabetes can diminish the efficacy of chemotherapy and immunotherapy through hyperglycemia-induced immune impairment (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Addressing these conditions using a multidisciplinary approach can improve treatment readiness and OS (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTumor biology plays an important role in determining the prognosis and tailoring treatment strategies. In our cohort, adenocarcinoma was the predominant subtype (54.2%), followed by squamous cell carcinoma (33.9%), which is consistent with global patterns. The pN status has emerged as a critical prognostic factor, with pN2 disease significantly lowering OS and DFS. Advanced nodal stages (e.g., pN2\u0026ndash;N3) are well-documented predictors of poor outcomes due to increased recurrence risk, particularly in the absence of multimodal therapies (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, LVI was observed in 42.4% of patients with markedly lower DFS (9.77 months) than in those without LVI (33.67 months). These findings align with the evidence correlating LVI with increased recurrence and reduced survival, particularly in adenocarcinoma subtypes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Emerging diagnostic tools, such as artificial intelligence-based imaging and transcriptomic analyses, now offer improved LVI detection, enabling tailored postsurgical therapies (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSurgical resection remains a cornerstone in the management of resectable Stage III NSCLC, particularly when integrated into multimodal treatment strategies. Our study demonstrated the critical role of R0 resection, as patients with negative margins exhibited superior outcomes. This aligns with findings from the Extended Resection Study (2022), which reported a 5-year OS rate of 44% for advanced NSCLC cases treated with induction therapy and achieving R0 status(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Salvage surgeries for recurrent or residual disease also highlight the potential for achieving long-term survival benefits, with a median OS of 69 months reported in selected cases (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMinimally invasive techniques, such as VATS, have improved surgical outcomes by reducing perioperative morbidity without compromising oncological effectiveness. Studies comparing VATS and open thoracotomy, including those by Hireche et al. (2023)(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) and Cao et al. (2023)(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), reported equivalent OS and DFS, but superior perioperative outcomes with VATS, such as reduced blood loss and shorter recovery times. However, complications remain a concern, particularly in salvage procedures where circulatory issues are prevalent in up to 80.9% of patients (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). These findings underscore the need for careful patient selection to optimize surgical outcomes.\u003c/p\u003e \u003cp\u003eNeoadjuvant and adjuvant therapies have become integral to improving outcomes in Stage III NSCLC, particularly enhancing resectability and reducing recurrence risks. Neoadjuvant chemoimmunotherapy facilitates tumor downstaging and increases the likelihood of achieving R0 margins, with major pathological response rates reaching 58.1% in real-world settings (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Similarly, adjuvant therapies, such as durvalumab, as demonstrated in the PACIFIC trial, have established new standards of care by significantly improving OS and PFS after concurrent chemoradiotherapy (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEmerging combinations, such as durvalumab with oleclumab or monalizumab, aim to further enhance antitumor immune responses (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Adjuvant treatments have also proven to be effective in addressing micrometastatic disease, which is critical for long-term disease control. For example, incorporating postoperative radiotherapy and chemotherapy significantly reduced locoregional recurrence rates compared with surgery alone, as evidenced by recurrence rates of 7.1% for PORT versus 31.6% for surgery alone (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). These findings highlight the importance of integrating systemic and local therapies to optimize outcomes in aggressive or advanced disease settings.\u003c/p\u003e \u003cp\u003eWhile controlled clinical trials provide essential insights, real-world evidence highlights the variability in treatment outcomes owing to differences in healthcare infrastructure, patient profiles, and access to therapies. For instance, the findings of the PACIFIC trial were replicated in real-world settings, emphasizing the role of biomarkers such as PD-L1 expression and gene signatures such as KEAP1 and STK11 mutations in predicting treatment responses (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). However, several challenges remain, particularly in resource-limited settings.\u003c/p\u003e \u003cp\u003eDeveloping countries face significant barriers in implementing advanced therapies, including limited access to FDG PET/CT, immune checkpoint inhibitors (ICIs), and multidisciplinary teams. Financial constraints and insufficient public health investment further exacerbate these disparities, leading to late-stage diagnoses and suboptimal outcomes (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Addressing these challenges requires international collaboration, adoption of cost-effective solutions, and tailored strategies such as metronomic chemotherapy to improve care delivery and outcomes in low- and middle-income countries.\u003c/p\u003e \u003cp\u003eThis study provides valuable insights into the management of Stage III NSCLC, highlighting the importance of surgical resection within a multidisciplinary framework, particularly in resource-limited countries. Its strength lies in analyzing patient outcomes in a clinical setting, where healthcare disparities and limited access to advanced treatments are significant. By evaluating comorbidities, tumor characteristics, and surgery with multimodal therapies, this study addressed the critical factors for optimizing treatment strategies. However, the retrospective design introduces limitations, such as potential selection bias and a small cohort size, affecting statistical power and generalizability. Additionally, the lack of standardized protocols for adjuvant therapies and long-term follow-up data limit the assessment of the impact of emerging therapies on disease progression and survival. Future prospective studies with larger cohorts are needed to validate and expand these findings.\u003c/p\u003e"},{"header":"5.0 Conclusion","content":"\u003cp\u003eOur study emphasizes the pivotal role of surgical resection as part of a multimodal strategy for managing Stage III NSCLC, particularly in resource-constrained environments. These findings emphasize the importance of achieving R0 resection, optimizing the management of comorbidities, and integrating systemic therapies to enhance patient outcomes. While surgery alone offers considerable survival benefits, the inclusion of neoadjuvant or adjuvant therapies further improves survival, especially in patients with pN0 status and no LVI. Despite the challenges posed by healthcare disparities, these results highlight the importance of multidisciplinary approaches and adoption of cost-effective strategies to enhance care delivery. Future research should focus on standardizing treatment protocols and exploring innovative therapies to address the complexity of Stage III NSCLC, ultimately advancing equitable and effective cancer care on a global scale.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDFS – Disease-Free Survival\u003c/p\u003e\n\u003cp\u003eFDG PET/CT – Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography\u003c/p\u003e\n\u003cp\u003eICI – Immune Checkpoint Inhibitor\u003c/p\u003e\n\u003cp\u003eKHCC – King Hussein Cancer Center\u003c/p\u003e\n\u003cp\u003eLVI – Lymphovascular Invasion\u003c/p\u003e\n\u003cp\u003eM0 – No Distant Metastases\u003c/p\u003e\n\u003cp\u003eNSCLC – Non-Small Cell Lung Cancer\u003c/p\u003e\n\u003cp\u003eOS – Overall Survival\u003c/p\u003e\n\u003cp\u003epN – Pathologic Nodal Status\u003c/p\u003e\n\u003cp\u003ePFS – Progression-Free Survival\u003c/p\u003e\n\u003cp\u003eR0 – Complete Tumor Resection with Negative Margins\u003c/p\u003e\n\u003cp\u003eR2 – Macroscopic Residual Disease\u003c/p\u003e\n\u003cp\u003eVATS – Video-Assisted Thoracoscopic Surgery\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eR.A.A. conceptualized the study, drafted the original manuscript, and supervised the work. S.A. conducted formal analysis, developed the software, and contributed to drafting the manuscript. A.A., T.A.H., K.A., S.Y., H.A.J., J.K., A.A.N., and H.A.H. drafted the original manuscript and provided resources. L.O.N. curated the data and contributed resources.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the local Ethics Committee of the KHCC on August 29th, 2021 (Proposal No. 21 KHCC 115). The need for informed consent was waived due to the retrospective analysis of routinely collected patient data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A 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(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeldgaard P, Kristensen M, Conte S, Kaae Andersen K, Jovanovic A, Meldgaard E. Improved overall survival for Stage III NSCLC patients treated with curative-intended therapy from 2010 to 2018\u0026ndash;a cohort study in Denmark. Acta Oncol (Madr). 2023;62(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAuliac JB, Greillier L, Martin E, Falcoz PE, Boisselier P, Ano S et al. Profiles, diagnostic process, and patterns of care of patients with stage III non-small cell lung cancer: A French national study. Respir Med Res. 2024;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurakami H, Horinouchi H, Harada H, Sobue T, Kato T, Atagi S et al. Deciphering the clinical features of heterogeneous stage III non-small cell lung cancer in Japanese real-world clinical practice: Expanded cohort of the SOLUTION study. Lung Cancer. 2022;165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo W, Zhong R, Yang M, Zhou Q. Interpretation of expert consensus on treatment for stage III non-small cell lung cancer. Med Adv. 2023;1(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuna JM, Barsky AR, Shinohara RT, Roshkovan L, Hershman M, Dreyfuss AD et al. Radiomic Phenotypes for Improving Early Prediction of Survival in Stage III Non-Small Cell Lung Cancer Adenocarcinoma after Chemoradiation. Cancers (Basel). 2022;14(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang T, Li L, Huang L, Wei Liu J, Xing Zhu D, Si Dong J et al. A phase II study of tislelizumab (TIS) and chemotherapy as neoadjuvant therapy for potentially resectable stage IIIA/IIIB non-small cell lung cancer (NSCLC). 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQi Y, Sun Y, Zhu H, Guo H. Efficacy and surgical safety of sequential surgical resection after neoadjuvant chemoimmunotherapy for unresectable stage III NSCLC. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePassaro A, Mok TSK, Attili I, Wu YL, Tsuboi M, De Marinis F et al. Adjuvant Treatments for Surgically Resected Non-Small Cell Lung Cancer Harboring EGFR Mutations: A Review. 9, JAMA Oncol. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaivre-Finn C, Edwards JG, Hatton M. Postoperative Radiation Therapy Should Not Be Used for the Therapy of Stage III-N2 NSCLC. 17, J Thorac Oncol. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErol C, Hizal M, Kahraman S, Bardakci M, Sener Dede D, Bulent Akinci M et al. Are the clinical trials in lung cancer an advantage for patients in developing countries? 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo L, Zhu C, Cai L, Zhang X, Fang Y, Chen H et al. Global burden of lung cancer in 2022 and projected burden in 2050. Chin Med J (Engl). 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSekine Y, Behnia M, Fujisawa T. Impact of COPD on pulmonary complications and on long-term survival of patients undergoing surgery for NSCLC. In: Lung Cancer. 2002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeshem Y, Dolev Y, Siegelmann-Danieli N, Sharman Moser S, Apter L, Chodick G et al. Association between diabetes mellitus and reduced efficacy of pembrolizumab in non\u0026ndash;small cell lung cancer. Cancer. 2023;129(18).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCortellini A, D\u0026rsquo;Alessio A, Cleary S, Buti S, Bersanelli M, Bordi P et al. Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer. Clin Cancer Res. 2023;29(14).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVu N, Tien Manh D, Viet Cuong N, Hong Son N, Quoc Viet T, Onishi H et al. Long-term survival outcome of radiation therapy for unresectable, locally advanced non-small cell lung cancer: Single center experience at Hospital 175. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuaiti L, Sullivan TB, Rieger-Christ KM, Servais EL, Suzuki K, Burks EJ. Vascular Invasion Predicts Recurrence in Stage IA2-IB Lung Adenocarcinoma but not Squamous Cell Carcinoma. Clin Lung Cancer. 2023;24(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang X, Feng Y, Li Y, Ding H, Huang X, Chen C et al. A novel transcriptomic signature associated with lymphovascular invasion predicts clinical outcomes, tumor microenvironment, and therapeutic response in lung adenocarcinoma. Int Immunopharmacol. 2024;127.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZuo Z, Fan X, Tang Y, Zhang Y, Peng X, Zeng W et al. Deep learning-powered 3D segmentation derives factors associated with lymphovascular invasion and prognosis in clinical T1 stage non-small cell lung cancer. Heliyon. 2023;9(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFurrer K, Weder W, Eboulet EI, Betticher D, Pless M, Stupp R et al. Extended resection for potentially operable patients with stage III non\u0026ndash;small cell lung cancer after induction treatment. In: J Thorac Cardiovasc Surg. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWerner RS, Furrer K, Lauk O, Caviezel C, Hillinger S, Schneiter D et al. Salvage Surgery in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Br J Surg. 2023;110(Supplement_5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHireche K, Lounes Y, Bacri C, Solovei L, Marty-An\u0026eacute; C, Canaud L et al. VATS versus Open Lobectomy following Induction Therapy for Stage III NSCLC: A Propensity Score-Matched Analysis. Cancers (Basel). 2023;15(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao J, Zhang C, Zhang X, Liu L, Li X, He J et al. The Clinical Outcomes of Thoracoscopic Versus Open Lobectomy for Non\u0026ndash;Small-Cell Lung Cancer After Neoadjuvant Therapy: A Multi-Center Retrospective Cohort Study. Clin Lung Cancer. 2024;25(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKasprzyk M, Sławiński G, Musik M, Marciniak Ł, Dyszkiewicz W, Piwkowski C et al. Completion pneumonectomy and chemoradiotherapy as treatment options in local recurrence of non-small-cell lung cancer. Kardiochirurgia i Torakochirurgia Polska. 2015;12(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Z, Wang S, Yang H, Jiang Y, Zhu L, Zheng B et al. Treatment patterns and clinical outcomes of patients with resectable non\u0026ndash;small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World). J Thorac Cardiovasc Surg. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrosz Z, Kov\u0026aacute;cs \u0026Aacute;. The role of chemoradiotherapy and immunotherapy in stage III NSCLC. Pathology and Oncology Research. Volume 30. Frontiers Media SA; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eK\u0026auml;smann L, Eze C, Taugner J, Roengvoraphoj O, Dantes M, Schmidt-Hegemann NS et al. Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: Immunological rationale and current clinical trials establishing a novel multimodal strategy. 15, Radiat Oncol. 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSolodkiy VA, Sotnikov VM, Trotsenko SD, Kharchenko VP, Chkhikvadze VD, Nudnov NV et al. Non-small cell lung cancer recurrences after surgical and combined modality treatment with postoperative radiation therapy. Med Radiol Radiation Saf. 2018;63(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManapov F, Nieto A, K\u0026auml;smann L, Taugner J, Kenndoff S, Fl\u0026ouml;rsch B et al. Five years after PACIFIC: update on multimodal treatment efficacy based on real-world reports. Expert Opin Investig Drugs. 2023;32(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatherina C, Chua. Assieh Saadatpour; Ariel Chen; Aisha Hasan; Bevan Emma Huang; Stewart Bates. Evaluating biomarkers of immunotherapy response in a real-world metastatic NSCLC cohort. Cancer Res. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKonert T, Vogel WV, Paez D, Polo A, Fidarova E, Carvalho H et al. Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial. Eur J Nucl Med Mol Imaging. 2019;46(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiwnani S, Penumadu P, Ashok A, Pramesh CS. Lung Cancer Management in Low and Middle-Income Countries. Vol. 32, Thoracic surgery clinics. 2022.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Combined Modality Therapy, Disease Free Survival, Neoadjuvant Therapy, locally advanced Non-Small-Cell Lung Carcinoma, Resource Limited Settings, Video Assisted Thoracic Surgery","lastPublishedDoi":"10.21203/rs.3.rs-6302087/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6302087/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eStage III non-small cell lung cancer (NSCLC) is a complex and challenging disease due to its variability and the absence of standardized treatment protocols. This study aimed to investigate the role of surgical resection as part of a multimodal treatment approach to improve overall survival (OS) and disease-free survival (DFS) in resource-limited settings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThe medical records of 309 patients who underwent surgery for confirmed primary lung cancer at the King Hussein Cancer Center (KHCC) in Amman, Jordan, between 2016 and 2022 were reviewed. 59 of them diagnosed with Stage III NSCLC underwent curative surgeries. Patients were grouped into three categories: surgery alone, neoadjuvant therapy followed by surgery, and surgery combined with adjuvant therapy. Demographic, clinical, and survival data were statistically analyzed to compare the outcomes across these groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe study cohort consisted predominantly of males (86.4%), with adenocarcinoma being the most common histological subtype (54.2%). Patients who underwent surgery alone had the lowest recurrence rate and highest three-year OS and DFS rates (66.7%). Improved OS and DFS were observed in patients with pN0 status and no evidence of lymphovascular invasion (LVI). Minimally invasive surgical approaches such as VATS were associated with better perioperative outcomes than open surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eSurgical resection, particularly when achieving negative margins (R0) in patients with N0 disease, is critical for improving survival in patients with Stage III NSCLC. Multimodal strategies can enhance these benefits further. However, challenges related to healthcare access in resource-limited settings highlight the need for customized treatment protocols and broader access to advanced medical therapies.\u003c/p\u003e","manuscriptTitle":"Multimodality Approach for Locally Advanced Lung Cancer: When Is Surgery Most Beneficial?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-09 09:27:15","doi":"10.21203/rs.3.rs-6302087/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-13T17:11:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-24T19:56:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-05T08:59:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39808605113356912527370257192814583484","date":"2025-06-04T13:55:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"241801874636009312832376519614335047748","date":"2025-06-04T11:37:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-02T17:51:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-26T09:32:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-26T09:29:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2025-03-25T08:54:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f068ef05-a81c-4b29-bf55-72a676d45045","owner":[],"postedDate":"June 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-29T16:06:35+00:00","versionOfRecord":{"articleIdentity":"rs-6302087","link":"https://doi.org/10.1186/s13019-025-03752-9","journal":{"identity":"journal-of-cardiothoracic-surgery","isVorOnly":false,"title":"Journal of Cardiothoracic Surgery"},"publishedOn":"2025-12-22 15:58:33","publishedOnDateReadable":"December 22nd, 2025"},"versionCreatedAt":"2025-06-09 09:27:15","video":"","vorDoi":"10.1186/s13019-025-03752-9","vorDoiUrl":"https://doi.org/10.1186/s13019-025-03752-9","workflowStages":[]},"version":"v1","identity":"rs-6302087","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6302087","identity":"rs-6302087","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}