Immunochemotherapy combined with surgery in oligometastatic non-small cell lung cancer: a retrospective study

Immunochemotherapy combined with surgery in oligometastatic non-small cell lung cancer: a retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Immunochemotherapy combined with surgery in oligometastatic non-small cell lung cancer: a retrospective study Zhengxuan Li, Yajie Mao, Zhiyuan Gao, Changjian Shao, Weiru Qiao, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8684499/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract BACKGROUND The purpose of this trial was to assess the effectiveness of immunochemotherapy combined with surgery in patients with oligometastatic non-small cell lung cancer (NSCLC). METHODS We retrospectively reviewed 14 patients with oligometastatic NSCLC. Patients received 3–6 cycles of immunochemotherapy on day 1 of each 21-day cycle and underwent surgical resection of primary tumor. The metastatic lesions of 7 patients underwent surgery or radiotherapy. There were 9 cases of squamous cell carcinoma, 4 cases of adenocarcinoma, and 1 case of poorly differentiated lung cancer. Primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathological response (MPR), objective response rate (ORR), event-free survival (EFS), and overall survival (OS). RESULTS The pCR and MPR rates were 64% and 71% of all patients. In 4 patients with brain metastasis (BM), the pCR and MPR rate were 75% and 100%. The ORR was 100%. The median follow-up time was 21.8 months. The median EFS was 16.8 months, 12-month and 18-month EFS rate were 85.1% and 40.9% respectively, 12-month and 18-month OS rate were 92.3% and 83.1% respectively. In 4 patients with BM, the median EFS was 15.0 months, 12-month and 18-month EFS rate was 75% and 37.5% respectively, 12-month and 18-month OS rate was 100% and 100% respectively. CONCLUSIONS The treatment of immunochemotherapy combined with surgery significantly improved pathological response rate and ORR, prolonged EFS and OS in oligometastatic NSCLC. Immunochemotherapy oligometastatic NSCLC retrospective study Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Lung cancer is the most common cancer in the world, with nearly 2.5 million new cases in 2022. 1 Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung malignancies, 2 distant metastases were diagnosed in a subset of patients. Nevertheless, traditional platinum-based chemotherapy remains inferior treatment outcomes in patients with advanced driver-negative NSCLC. Several large-scale phase III clinical trials 3 – 5 have demonstrated that immune checkpoint inhibitors (ICI), represented by programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) antibodies, in combination with chemotherapy can dramatically yield substantial clinical benefits compared to traditional chemotherapy in patients with advanced driver-negative NSCLC, with a 1.5–3.1 month numerically increase in median progression-free survival (PFS) and a 4.7–11.4 month numerically increase in median overall survival (OS). 3 – 5 PD-1/PD-L1 inhibitors are currently supported as the standard first-line setting for patients with advanced NSCLC without driver mutations. The definition of the oligometastases was hypothesized by Hellman and Weichselbaum in 1995. 6 The International Association for the Study of Lung Cancer (IASLC) defines oligometastases as a maximum of five metastases and three organs on the basis of the systematic review. 7 Surgery is one of the local therapies for patients with oligometastatic NSCLC, Hanagiri et al proved that the heterogeneity of the degree of oligometastatic NSCLC has a great influence on the survival rate after surgical resection. 8 For patients with 1–5 metastatic lesions, the 5-year survival rate was approximately 17% -50% after surgery. However, the 5-year relative survival rate was only 8% in patients with distant metastases. 2 Previous trials have validated that chemotherapy combined with surgery for patients with oligometastases has a median OS of 11–31 months. 9 – 12 However, in a single-arm Phase II clinical study that combined Pembrolizumab with locally ablative therapy (LAT), the median PFS numerically increased from 6.6 months to 19.1 months and the median OS was 41.6 months. 13 Subsequently, Jongbloed et al further revealed the efficacy of ICI combined with/without chemotherapy in patients with synchronous oligometastatic NSCLC and markedly prolonged the median OS and PFS, confirming that ICI-based systemic therapy is feasible and may possess superior survival outcomes. 14 These two trials indicate that immunotherapy may have definite advantages in the comprehensive treatment of patients with oligometastatic NSCLC. Nevertheless, the efficacy of immunochemotherapy combined with surgery in oligometastatic NSCLC remains largely unclear. Therefore, we set out to evaluate the efficacy of immunochemotherapy combined with surgery in patients with oligometastatic NSCLC. Patients and METHODS patients The study was a retrospective study in oligometastatic NSCLC patients. Eligible patients were 18 years of age or older; had stage IV A or IV B of the American Joint Committee on Cancer (AJCC 8th Edition); had to have measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1); with maximum of five metastases and three organs; received at least 3 cycles of immunochemotherapy; underwent surgical resection of primary tumor; had not received previous systemic chemotherapy. Patients were deemed ineligible if they had known EGFR mutations or ALK translocations, active autoimmune or infectious diseases. Study endpoints The primary endpoint was the proportion of patients who achieved pathological complete response (pCR), defined as an absence of viable tumor cells in the surgical specimens from the primary tumor and all sampled regional lymph nodes. Secondary endpoints included major pathological response (MPR, ≤ 10% residual viable tumor cells in the primary tumor and sampled lymph nodes), objective response rate (ORR, defined as the proportion of patients with complete response [CR] or partial response [PR] according to RECIST v.1.1), event-free survival (EFS, defined as the time from enrollment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause), and overall survival (OS, defined as the time from diagnosis to the date of death). Statistical analysis Median follow-up time was calculated using the reverse Kaplan-Meier method. EFS and OS were calculated using the Kaplan-Meier method. Continuous variables were represented by the mean and categorical variables were represented by the frequency. P-value of less than 0.05 were considered statistically significant. Table 1 Baseline characteristics of the patients (N = 14) Characteristics All Patients (N = 14) Patients with Pathologic Complete Response (N = 9) Patients without Pathologic Complete Response (N = 5) Age, Years — no. (%) Median (range) 61 (41–73) 61 (51–73) 61 (41–72) ≥ 60 Years 8 (57) 5 (56) 3 (60) <60 Years 6 (43) 4 (44) 2 (40) Sex — no. (%) Male 12 (86) 9 (100) 3 (60) Female 2 (14) 0 (0) 2 (40) BMI, kg/m2 (mean) 23.8 24.51 22.51 Smoking status — no. (%) Former or current 10 (71) 8 (89) 2 (40) Never 4 (29) 1 (11) 3 (60) Pathological type — no. (%) Squamous carcinoma 9 (64) 7 (78) 2 (40) Adenocarcinoma 4 (29) 2 (22) 2 (40) Poorly differentiated lung cancer 1 (7) 0 (0) 1 (20) Clinical disease stage — no. (%) ⅣA 11 (79) 7 (78) 4 (80) ⅣB 3 (21) 2 (22) 1 (20) Number of metastatic lesions —no. (%) 1 11 (79) 7 (78) 4 (80) 2 3 (21) 2 (22) 1 (20) Metastatic sites — no. (%) Adrenal 5 (36) 4 (44) 1 (20) Brain 4 (29) 3 (33) 1 (20) Bone 2 (14) 1 (11) 1 (20) pleura 1 (7) 0 (0) 1 (20) Lung 1 (7) 1 (11) 0 (0) Pectineus muscle 1 (7) 1 (11) 0 (0) Rectus femoris muscle 1 (7) 0 (0) 1 (20) RESULTS Patients A total of 14 patients were incorporated in this study between October 2020 and May 2023 (Table 1 ), including 12 males and 2 females, 4 of whom had no history of smoking (Table 1 ). There were 9 cases of squamous cell carcinoma, 4 cases of adenocarcinoma, and 1 case of poorly differentiated lung cancer (Table 1 ). 11 cases of stage IVA and 3 cases of stage IVB (Table 1 ) among all enrolled patients. Patients had 1–2 oligometastases of 1–2 organs, and the most common oligometastases were the adrenal (5/14 cases, 36%) and brain (4/14 cases, 29%) (Table 1 ). Table 2 Specific immunochemotherapy and local therapy regimens received by each patient. Patient no. Pathological type Preoperative chemoimmunotherapy (Cycles) Surgery of primary tumor Primary metastasis Number of metastatic lesions Local therapy of metastases (timepoint) Disease progression Response as per RECIST v.1.1 pCR/MPR P1 Squamous carcinoma Nab-paclitaxel (300mg, D1) + Nedaplatin (80mg, D1) + Sintilimab (200mg, D1) (4) VATS Bilobectomy Adrenal 1 None None PR pCR P2 Poorly differentiated lung cancer Nab-paclitaxel (400mg, D1) + Nedaplatin (120mg, D1) + Sintilimab (200mg, D1) (3) VATS Lobectomy Brain 2 Radiotherapy (before surgery of primary tumor) Brain PR MPR P3 Squamous carcinoma Nab-paclitaxel (500mg, D1) + Carboplatin (850mg, D1) + Pembrolizumab (200mg, D1) (4) VATS Lobectomy Pectineus muscle 1 None None PR pCR P4 Squamous carcinoma Nab-paclitaxel (200mg, D1,8) + Nedaplatin (120mg, D1) + Pembrolizumab (200mg, D1) (3) Thoracotomy Bilobectomy Brain 1 Radiotherapy (before surgery of primary tumor) None PR pCR P5 Adenocarcinoma Pemetrexed (800mg, D1) + Cisplatin (120mg, D1) + Pembrolizumab (200mg, D1) (3) VATS Lobectomy Adrenal 1 None Adrenal PR pCR P6 Adenocarcinoma Pemetrexed (800mg, D1) + Nedaplatin (120mg, D1) + Pembrolizumab (200mg, D1) (6) VATS Bilobectomy Pleura 1 Surgery (after surgery of primary tumor) Lung and Brain PR None P7 Adenocarcinoma Pemetrexed (800mg, D1) + Cisplatin (60mg, D1,2) + Pembrolizumab (200mg, D1) (4) VATS Lobectomy Lung 1 Surgery (after surgery of primary tumor) None PR pCR P8 Squamous carcinoma Nab-paclitaxel (400mg, D1) + Nedaplatin (130mg, D1) + Pembrolizumab (200mg, D1) (3) VATS Lobectomy Adrenal 1 Surgery (Simultaneous resection with surgery of primary tumor) Adrenal PR None P9 Squamous carcinoma Pemetrexed (900mg, D1) / Nab-paclitaxel (400mg, D1) + Nedaplatin (110mg, D1) + Pembrolizumab (200mg, D1) (3) RATS Lobectomy Brain and Adrenal 2 None None PR pCR P10 Adenocarcinoma Pemetrexed (900mg, D1) + Nedaplatin (150mg, D1) + Pembrolizumab (200mg, D1) (3) VATS Bilobectomy Bone 1 None Lung primary and Bone PR None P11 Squamous carcinoma Nab-paclitaxel (500mg, D1) + Carboplatin (500mg, D1) + Tislelizumab (200mg, D1) (3) VATS Lobectomy Adrenal 1 None None PR pCR P12 Squamous carcinoma Nab-paclitaxel (400mg, D1) + Nedaplatin (110mg, D1) + Tislelizumab (200mg,D1) (4) VATS Lobectomy Rectus femoris muscle 1 Surgery (after surgery of primary tumor) Lung primary and Pectineus muscle PR None P13 Squamous carcinoma Nab-paclitaxel (400mg, D1) + Nedaplatin (100mg, D1) + Sugemalimab (1200mg, D1) (3) VATS Lobectomy Brain 1 Radiotherapy (before surgery of primary tumor) Brain PR pCR P14 Squamous carcinoma Nab-paclitaxel (400mg, D1) + Nedaplatin (140mg, D1) + Sugemalimab (1200mg, D1) (6) VATS Lobectomy Bone 2 None Lung primary PR pCR pCR, pathological complete response; MPR, major pathological response; PR, partial response; VATS, video-assisted thoracoscopic surgery; RATS, robot assisted thoracic surgery Surgery Summary All patients underwent surgical resection of primary tumor after 3–6 cycles of immunochemotherapy on the first day of each 21-day cycle, 10 patients underwent lobectomy, while 4 patients underwent bilobectomy (Table 2 and Supplemental Table 1). 13 patients underwent video-assisted thoracic surgery/robot-assisted thoracic surgery (VATS /RATS), and 1 patient underwent thoracotomy (Table 2 and Supplemental Table 1). 7 of 14 patients received surgery or radiotherapy for metastatic tumors (Table 2 ). 4 patients received surgery of metastatic lesions (including pleural metastasis, lung metastasis, adrenal metastasis, and rectus femoris metastasis), while the metastases of 3 patients with brain metastasis received preoperative radiotherapy. The full treatment is available in Table 2 . The mean operative time was 203.6 minutes (30–440 minutes), the mean intraoperative blood loss was 403.6mL (20-2500 mL), the median postoperative hospital stay was 7 days (5–9 days), and the median duration of extubation was 4.5 days (3–7 days) (Supplemental Table 2). Efficacy 9 patients achieved pCR (64%) and 10 patients achieved MPR (71%) (Fig. 1 ). In the 4 patients with brain metastasis (BM), pCR was achieved in 3 patients (75%) and MPR in 4 patients (100%) (Fig. 1 ). The radiographic ORR was 100%, with a radiographic PR achieved in all patients after immunochemotherapy (Fig. 1 ). The median follow-up time of 14 patients was 21.8 months (15.7–24.8 months). The median EFS was 16.8 months (95%CI, 15.9–17.7 months), and the 12-month and 18-month EFS rate was 85.1% and 40.9% respectively (Fig. 2 A), the median OS was not reached (95%CI, 26.6-NE months), and the 12-month and 18-month OS rate was 92.3% and 83.1% respectively (Fig. 2 B). In 4 patients with BM, the median EFS was 15.0 months (95%CI, 9.2–20.8 months), 12-month and 18-month EFS rate was 75% and 37.5% respectively (Fig. 3 A), the median OS was not reached, 12-month and 18-month OS rate was 100% and 100% respectively (Fig. 3 B). A post hoc subgroup analysis revealed that the median EFS was not reached with patients in pCR and 16.3 months (95% CI, 13.5 to 19.1) with patients in non-pCR (HR, 0.39; 95% CI, 0.10 to 1.6; P = 0.18) (Fig. 4 A), the median OS was not reached and 23.9 months (95% CI, 17.2 to 30.6) respectively(HR, 0.30; 95% CI, 0.04 to 2.12; P = 0.26) (Fig. 4 B). Progressive disease (PD) occurred in 8 patients (57%) (3 in the pCR group and 5 in the non-pCR group) (Table 2 ). 2 patients had recurrence of metastases (adrenal, brain) and 1 patient developed PD of the primary tumor in the group of pCR patients. While in the non-pCR patient group, 2 patients had recurrence of metastases (brain, adrenal), and 3 patients developed PD of both primary tumor and metastases (lung and brain, lung primary and bone, lung primary and pectineus muscle), including 2 patients with new lesions (Table 2 ). The fraction of patients with PD after treatment in the pCR and non-pCR groups were 33% and 100% respectively (OR, 0.38 [95%CI, 0.15–0.92], P = 0.031). COMMENT We reported the efficacy of immunochemotherapy combined with surgery in patients with oligometastatic NSCLC. The expected trial results were achieved in this study, and the pCR rate was 64% of all patients. The patients enrolled in our trial were those who achieved ORR by radiographic assessments according to RECIST v.1.1 following immunochemotherapy and were eligible for surgery, that is Per-Protocol (PP) population, these patients had displayed dramatic efficacy before surgery. A meta-anvialysis 15 revealed an underlying association between MPR and ORR (OR, 6.21 [95%CI, 3.71–9.16], p < 0.00001). In addition, Boch et al 16 retrospectively studied the efficacy of immune monotherapy or immunochemotherapy combined with surgery in 13 patients with oligometastatic NSCLC. Due to the majority of patients with isolated metastases (69%) and PD-L1 TPS > 50% (62%), the pCR and MPR rate were high (54% and 69%, respectively), and the proportion of patients with isolated metastases in our study (71%) is consistent with Boch et al . Therefore, initial explanations attribute high pathologic response rate to patients experiencing high ORR preoperatively, as well as the inclusion of patients with isolated metastases (13/14, 93%). The TD-FOREKNOW 17 randomized clinical trial reported a pCR rate of 32.6% with neoadjuvant camrelizumab plus platinum-based chemotherapy in patients with IIIA-IIIB NSCLC, and a quadruplet regimen (perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy) in the TD-NeoFOUR trial 18 in patients with IIA/IIIB NSCLC had a pCR rate of 57.8%. Intriguingly, a higher pCR rate (64%) was observed in the patients with oligometastatic NSCLC we included, but the comparison was indirect. Notably, neoadjuvant ICI combined with anlotinib and chemotherapy in patients with oligometastatic NSCLC may be a potentially effective treatment option and is worth exploring. Additionally, PD was observed among 8 patients, the proportion of PD in pCR patients was dramatically lower than non-pCR patients (OR, 0.38[95% CI, 0.15–0.92], P = 0.031). Distant metastases relapse was the majority (7/8, 87.5%) among the patients with PD, and the brain was more common (42.9%), which was comparable to the pattern of postoperative recurrence NSCLC 19 . In this retrospective study, patients with oligometastatic NSCLC achieved a median EFS of 16.8 months, 12-month EFS and OS of 85.1% and 92.3%, and 18-month EFS and OS of 40.9% and 83.1%, respectively. The previous therapy for oligometastatic NSCLC patients included chemotherapy combined with surgery, 9–12,20−23 and patients who underwent surgery achieved median PFS of around 13 months, 12 along with median OS of 11–31 months, 9–12 and a 1-year OS rate of 56%-79%. 11,22,23 Our approach to adding immunotherapy before surgery in comparison to systemic chemotherapy can prolong event-free survival and survival time being superior to previous standard therapy. The PACIFIC trial 24 used durvalumab for consolidation therapy in patients with stage III, locally advanced, unresectable NSCLC after concurrent chemoradiotherapy. Results displayed the median PFS of the durvalumab consolidation therapy group was 16.8 months (95% CI, 13.0-18.1). The 12-month and 18-month PFS rate were 55.9% (95%CI, 51.0-60.4) and 44.2% (95% CI, 37.7–50.5) respectively. Notably, our trial also achieved the same median EFS and a higher 12-month EFS rate. Although the 18-month EFS rate was inferior to the PACIFIC trial, the potential explanation is that the patients we enrolled possessed worse pathological staging. Moreover, our 12-month OS rate was also comparable with the trial of LAT (including surgery, chemoradiotherapy, stereotactic radiotherapy, and/or interventional ablation) followed by pembrolizumab (12-month OS rate was 90.9%) for oligometastatic NSCLC at diagnosis (synchronous disease) or who developed oligometastatic disease after initial definitive therapy (metachronous disease). 13 This study demonstrated superior efficacy of pembrolizumab consolidation after LAT, with a median PFS of 19.1 months, nearly double improvement compared to historical data. We similarly focused on patients with synchronous oligometastatic NSCLC, excluding patients whose tumors displayed regressed to the oligometastatic state after therapy (oligoremnant disease) in our trial. Conversely, the inferior median EFS observed in our study may be attributed to the inclusion of other local therapy alongside surgery for the primary tumor in the LAT, which provided patients with other therapy options and potentially resulted in superior outcomes. Notably, what remains evident is that patients with oligometastases who underwent pembrolizumab consolidation therapy following LAT exhibited acceptable adverse events, 13 indicating that perioperative therapy may offer improved outcomes for patients with oligometastatic NSCLC. Immunotherapy plus chemotherapy can improve PFS and OS in extensively metastatic NSCLC patients, but the efficacy is limited. 3–5,25−27 As observed in the phase 3 KEYNOTE-189 4 , KEYNOTE-407 5, and GEMSTONE-302 27 study trials, compared with chemotherapy, Pembrolizumab or Sugemalimab plus chemotherapy significantly improved PFS (median 8.0–9.0 months) and OS (median 17.2–25.4 months). Higher median PFS was displayed in our trial (16.8 months), and median OS was not reached, but 12-month OS was superior to the three trials 4 , 5 , 27 (92.3% vs 69.8%, 64.7%, and 71.6%). Given the different populations (the three trials analyzed the intention-to-treat (ITT) population, whereas we were the pp population) and the superior effectiveness of surgery compared to nonsurgical approaches in oligometastatic NSCLC, 22–23 the difference in treatment efficacy is interpretable. Collectively, immunochemotherapy combined with surgery may be a potential optional treatment to improve survival benefits in contrast to previous standard therapy for patients with oligometastatic NSCLC. Similarly superior efficacy was observed in 4 patients with BM, the median EFS was 15.0 months, and the 12-month EFS and OS rate was 75% and 100% respectively. Previous studies 22 indicated the 12-month OS rate of NSCLC patients with BM who underwent bifocal surgical resection was 79%. Moreover, in the pooled analysis 28 of KEYNOTE 021, -189, -407, the median PFS of patients with NSCLC and stable BM who received pembrolizumab plus platinum-based chemotherapy was 6.9 months, the 12-month PFS and OS rates were 29.9% and 62.9%, respectively, the PFS benefit of combination therapy with pembrolizumab plus platinum-based chemotherapy in the BM group was observed in all PD-L1 expression groups ( 50%). 28 The difference is that 3 of 4 patients in our trial with brain metastases received local brain therapy before or after surgery, this may be the reason for the efficacy of patients with BM in our trial was superior compared to historical trials, suggesting that combined immunochemotherapy and local therapy during the perioperative period may have potential efficacy in patients with BM. However, this result needs to be interpreted with caution due to the small number of patients we included may introduce potential biases. In post hoc subgroup analyses, there was no statistical difference in EFS and OS between patients in pCR and non-pCR groups. Since the patients we enrolled were the PP population, patients had already achieved superior therapy before surgery, which may lead to long EFS and OS, our follow-up (median 21.8 months) was insufficient to allow positive results between the pCR and non-pCR groups. Encouragingly, patients in the non-pCR group had a median EFS of 16.3 months, which was significantly numerically higher than the progression-free survival of patients with extensively metastasized NSCLC in previous studies 4 , 5 , 27 , and a median OS of 23.9 months, which was comparable to previous studies. 4 , 5 , 27 The pCR group did not reach the study endpoint, but the proportion of patients who experienced progression of disease or death in the pCR group by the final follow-up time was less than non-pCR group, which indicated that patients in the pCR group may display a favorable prognosis. Study Limitations First, the limited patient size we include may introduce potential biases. The conclusion of the substantial clinical benefit of immunochemotherapy combined with surgery needs to be further verified by large-scale prospective studies in a larger population. Second, whether immunochemotherapy combined with surgery has different outcomes in patients with oligometastatic NSCLC with different levels of PD-L1 expression remains largely undetermined and is expected to be explored in future studies. Furthermore, the safety and feasibility of immunochemotherapy combined with surgery in patients with oligometastases NSCLC remains a substantial concern. Conclusions The efficacy of immunochemotherapy combined with surgery in patients with oligometastatic NSCLC is encouraging and has achieved better outcomes compared with previous clinical studies. Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Tangdu Hospital of Air Force Military Medical University (TDLL-202409-05) and informed consent was taken from all individual participants. The trial was conducted according to the principles of the Declaration of Helsinki. Consent for publication Not Applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests Funding This study was funded by the National Natural Science Foundation of China (82173252), Shaanxi Provincial Science and Technology Innovation Team (2023-CX-TD-64), New Technologies and Services of Tangdu Hospital (XJSXYW202122), and the Major Project of Medical Research (25YXYJZD00036). Authors' contributions ZL: Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Visualization, Writing – original draft, Writing – review & editing. YM: Formal analysis, Methodology, Project administration, Resources, Software, Validation, Visualization. ZG: Investigation, Methodology, Project administration, Software, Validation, Visualization. CS: Conceptualization, Investigation, Project administration, Resources, Software, Supervision, Validation. WQ : Resources, Software, Supervision. HD: Conceptualization, Investigation, Project administration, Resources, Supervision, Writing – review & editing. XY: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – review & editing. All authors read and approved the final manuscript. Acknowledgements Not applicable References Bray F, Laversanne M, Sung H, et al. 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N Engl J Med. 1990;322:494–500. https://doi.org/10.1056/NEJM199002223220802 . Wroński M, Lederman G, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer. 1997;80:1002–4. https://doi.org/10.1002/(sici)1097-0142(19970901)80:5%3C1002::aid-cncr30%3E3.0.co;2-c . Yuksel C, Bozkurt M, Yenigun BM, et al. The outcome of bifocal surgical resection in non-small cell lung cancer with synchronous brain metastases: results of a single center retrospective study. Thorac Cardiovasc Surg. 2014;62:605–11. https://doi.org/10.1055/s-0033-1360477 . Bonnette P, Puyo P, Gabriel C, et al. Surgical management of non-small cell lung cancer with synchronous brain metastases. Chest. 2001;119:1469–75. https://doi.org/10.1378/chest.119.5.1469 . Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377:1919–29. https://doi.org/10.1056/NEJMoa1709937 . Lu S, Wang J, Yu Y, et al. Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. J Clin Oncol. 2021;16:1512–22. https://doi.org/10.1016/j.jtho.2021.05.005 . Zhou C, Wu L, Fan Y, et al. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol. 2021;16:1501–11. https://doi.org/10.1016/j.jtho.2021.04.011 . Zhou C, Wang Z, Sun M, et al. Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC. Nat Cancer. 2023;4:860–71. https://doi.org/10.1038/s43018-023-00719-4 . Powell SF, Rodríguez-Abreu D, Langer CJ, et al. Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and – 407. J Thorac Oncol. 2021;16:1883–92. https://doi.org/10.1016/j.jtho.2021.06.020 . Additional Declarations No competing interests reported. Supplementary Files SupplementalAppendixmaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 06 Mar, 2026 Editor assigned by journal 05 Mar, 2026 Editor invited by journal 04 Feb, 2026 Submission checks completed at journal 03 Feb, 2026 First submitted to journal 03 Feb, 2026 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-8684499","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":604694095,"identity":"a4ab3cc8-a6fc-417d-b8f3-f46d549832ca","order_by":0,"name":"Zhengxuan Li","email":"","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhengxuan","middleName":"","lastName":"Li","suffix":""},{"id":604694096,"identity":"76f8b206-c45f-4e92-aecb-3343efe788c6","order_by":1,"name":"Yajie Mao","email":"","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yajie","middleName":"","lastName":"Mao","suffix":""},{"id":604694097,"identity":"f6d5d36e-7451-451c-9129-1179e0b38fef","order_by":2,"name":"Zhiyuan Gao","email":"","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhiyuan","middleName":"","lastName":"Gao","suffix":""},{"id":604694098,"identity":"dbfca0b2-3883-4036-9bf9-3d015310f852","order_by":3,"name":"Changjian Shao","email":"","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Changjian","middleName":"","lastName":"Shao","suffix":""},{"id":604694100,"identity":"77d65ae1-a0c0-4921-8429-6cf5aae82580","order_by":4,"name":"Weiru Qiao","email":"","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Weiru","middleName":"","lastName":"Qiao","suffix":""},{"id":604694101,"identity":"d2bd1fdd-6829-41e0-8201-410fd48caa68","order_by":5,"name":"Hongtao Duan","email":"","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hongtao","middleName":"","lastName":"Duan","suffix":""},{"id":604694104,"identity":"647106db-1c1d-4774-9972-6da601da1478","order_by":6,"name":"Xiaolong Yan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYLCCBAYGGSDF+KACwjcgSgsPkGI2OEO0FgaIFjYJorQYHD97TOJBjQ0Pv3T7tYqDOdsSG9ibt0kw1NzBreVMXrJBwrE0Hsk5Z8puHNx2O7GB51iZBMOxZ7i1HMgxfJDAdpjH4EZO2u2PIC0SOWYSjA2HcWs5/8bgQMI/iJYCsC3ybwhouQG0JbENpCX9GANYiwQPfi2SN94YGyT2Af0yI4dZAqjFuI0nrdgi4RhuLXznc8wkf3yzkeOXSH/4AahFtp/98MYbH2pwa1E4AGfyQKKDDUQk4NTAwCDfAGeyP8CjbhSMglEwCkYyAADFul0fOlwhDQAAAABJRU5ErkJggg==","orcid":"","institution":"Tangdu Hospital, Air Force Military Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiaolong","middleName":"","lastName":"Yan","suffix":""}],"badges":[],"createdAt":"2026-01-24 07:08:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8684499/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8684499/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104547413,"identity":"745da90d-caf5-42af-89ab-931ea4c82aaf","added_by":"auto","created_at":"2026-03-13 07:37:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":278634,"visible":true,"origin":"","legend":"\u003cp\u003eWaterfall plot. The horizontal dashed line represents partial response according to the RECIST v.1.1 criteria, and the different colors represent pathologic regression. AC, adenocarcinoma; MPR, major pathological response; pCR, pathological complete response; PR, partial response; SCC, squamous-cell carcinoma\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8684499/v1/5c924cd00cd2e58964cfd29a.png"},{"id":104781528,"identity":"84ade691-8577-44e8-98b6-dafaa9526c10","added_by":"auto","created_at":"2026-03-17 07:55:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":154727,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves of (A) event-free survival and (B) overall survival in all patients (n=14)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8684499/v1/048f984a9184d6441ecdd6a6.png"},{"id":104547414,"identity":"765b427a-4989-4465-947e-8fb8c2c91d61","added_by":"auto","created_at":"2026-03-13 07:37:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":152102,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves of (A) event-free survival and (B) overall survival in patients with single brain metastasis (n=4)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8684499/v1/3a60d03b4610c61db30bcbfa.png"},{"id":104547411,"identity":"e94028a6-4821-4f6d-b5e5-af190d18a2b0","added_by":"auto","created_at":"2026-03-13 07:37:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":137505,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves of (A) event-free survival and (B) overall survival in patients between pCR and non-pCR (n=14)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8684499/v1/407b5200edab57081846648b.png"},{"id":104835578,"identity":"651a047a-b10a-4fb4-8cf6-e310cb0242f7","added_by":"auto","created_at":"2026-03-17 17:46:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1581023,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8684499/v1/9cef8672-7eee-4400-96f7-52a711b547a7.pdf"},{"id":104547409,"identity":"6da1e94f-1949-47b0-aa66-8d352107fd92","added_by":"auto","created_at":"2026-03-13 07:37:00","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":20037,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalAppendixmaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-8684499/v1/ebc029340bc60832d836a102.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immunochemotherapy combined with surgery in oligometastatic non-small cell lung cancer: a retrospective study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eLung cancer is the most common cancer in the world, with nearly 2.5\u0026nbsp;million new cases in 2022.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung malignancies,\u003csup\u003e2\u003c/sup\u003e distant metastases were diagnosed in a subset of patients. Nevertheless, traditional platinum-based chemotherapy remains inferior treatment outcomes in patients with advanced driver-negative NSCLC.\u003c/p\u003e \u003cp\u003eSeveral large-scale phase III clinical trials\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e have demonstrated that immune checkpoint inhibitors (ICI), represented by programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) antibodies, in combination with chemotherapy can dramatically yield substantial clinical benefits compared to traditional chemotherapy in patients with advanced driver-negative NSCLC, with a 1.5\u0026ndash;3.1 month numerically increase in median progression-free survival (PFS) and a 4.7\u0026ndash;11.4 month numerically increase in median overall survival (OS).\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e PD-1/PD-L1 inhibitors are currently supported as the standard first-line setting for patients with advanced NSCLC without driver mutations.\u003c/p\u003e \u003cp\u003eThe definition of the oligometastases was hypothesized by Hellman and Weichselbaum in 1995.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The International Association for the Study of Lung Cancer (IASLC) defines oligometastases as a maximum of five metastases and three organs on the basis of the systematic review.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Surgery is one of the local therapies for patients with oligometastatic NSCLC, Hanagiri \u003cem\u003eet al\u003c/em\u003e proved that the heterogeneity of the degree of oligometastatic NSCLC has a great influence on the survival rate after surgical resection.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e For patients with 1\u0026ndash;5 metastatic lesions, the 5-year survival rate was approximately 17% -50% after surgery. However, the 5-year relative survival rate was only 8% in patients with distant metastases.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Previous trials have validated that chemotherapy combined with surgery for patients with oligometastases has a median OS of 11\u0026ndash;31 months.\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e However, in a single-arm Phase II clinical study that combined Pembrolizumab with locally ablative therapy (LAT), the median PFS numerically increased from 6.6 months to 19.1 months and the median OS was 41.6 months.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Subsequently, Jongbloed \u003cem\u003eet al\u003c/em\u003e further revealed the efficacy of ICI combined with/without chemotherapy in patients with synchronous oligometastatic NSCLC and markedly prolonged the median OS and PFS, confirming that ICI-based systemic therapy is feasible and may possess superior survival outcomes.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e These two trials indicate that immunotherapy may have definite advantages in the comprehensive treatment of patients with oligometastatic NSCLC. Nevertheless, the efficacy of immunochemotherapy combined with surgery in oligometastatic NSCLC remains largely unclear. Therefore, we set out to evaluate the efficacy of immunochemotherapy combined with surgery in patients with oligometastatic NSCLC.\u003c/p\u003e"},{"header":"Patients and METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003epatients\u003c/h2\u003e \u003cp\u003eThe study was a retrospective study in oligometastatic NSCLC patients. Eligible patients were 18 years of age or older; had stage IV A or IV B of the American Joint Committee on Cancer (AJCC 8th Edition); had to have measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1); with maximum of five metastases and three organs; received at least 3 cycles of immunochemotherapy; underwent surgical resection of primary tumor; had not received previous systemic chemotherapy. Patients were deemed ineligible if they had known EGFR mutations or ALK translocations, active autoimmune or infectious diseases.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy endpoints\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was the proportion of patients who achieved pathological complete response (pCR), defined as an absence of viable tumor cells in the surgical specimens from the primary tumor and all sampled regional lymph nodes. Secondary endpoints included major pathological response (MPR, \u0026le;\u0026thinsp;10% residual viable tumor cells in the primary tumor and sampled lymph nodes), objective response rate (ORR, defined as the proportion of patients with complete response [CR] or partial response [PR] according to RECIST v.1.1), event-free survival (EFS, defined as the time from enrollment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause), and overall survival (OS, defined as the time from diagnosis to the date of death).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eMedian follow-up time was calculated using the reverse Kaplan-Meier method. EFS and OS were calculated using the Kaplan-Meier method. Continuous variables were represented by the mean and categorical variables were represented by the frequency. P-value of less than 0.05 were considered statistically significant.\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\u003eBaseline characteristics of the patients (N\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll Patients\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients with \u003c/p\u003e \u003cp\u003ePathologic Complete Response\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePatients without \u003c/p\u003e \u003cp\u003ePathologic Complete Response\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, Years \u0026mdash; no. (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (41\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (51\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (41\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60 Years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;60 Years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex \u0026mdash; no. (%)\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 \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\u003e12 (86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (14)\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\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m2 (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status \u0026mdash; no. (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer or current\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological type \u0026mdash; no. (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly differentiated lung\u003c/p\u003e \u003cp\u003ecancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (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\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical disease stage \u0026mdash; no. (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅣA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅣB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of metastatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elesions \u0026mdash;no. (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetastatic sites \u0026mdash; no. (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epleura\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (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\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePectineus\u0026nbsp;muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRectus femoris muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (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\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eA total of 14 patients were incorporated in this study between October 2020 and May 2023 (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), including 12 males and 2 females, 4 of whom had no history of smoking (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). There were 9 cases of squamous cell carcinoma, 4 cases of adenocarcinoma, and 1 case of poorly differentiated lung cancer (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). 11 cases of stage IVA and 3 cases of stage IVB (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) among all enrolled patients. Patients had 1–2 oligometastases of 1–2 organs, and the most common oligometastases were the adrenal (5/14 cases, 36%) and brain (4/14 cases, 29%) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003ctable id=\"Tab2\" border=\"1\"\u003e \u003ccaption\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSpecific immunochemotherapy and local therapy regimens received by each patient.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003c/colgroup\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\"\u003e \u003cp\u003ePatient no.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003ePathological type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003ePreoperative chemoimmunotherapy (Cycles)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eSurgery of primary tumor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003ePrimary metastasis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eNumber of metastatic lesions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eLocal therapy of metastases (timepoint)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eDisease progression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eResponse as per\u003c/p\u003e \u003cp\u003eRECIST v.1.1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003epCR/MPR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (300mg, D1) + Nedaplatin (80mg, D1) + Sintilimab (200mg, D1) (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eBilobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003ePoorly differentiated lung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (400mg, D1) + Nedaplatin (120mg, D1) + Sintilimab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRadiotherapy (before surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eMPR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (500mg, D1) + Carboplatin (850mg, D1) + Pembrolizumab (200mg, D1) (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePectineus\u0026nbsp;muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (200mg, D1,8) + Nedaplatin (120mg, D1) + Pembrolizumab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eThoracotomy\u003c/p\u003e \u003cp\u003eBilobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRadiotherapy (before surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePemetrexed (800mg, D1) + Cisplatin (120mg, D1) + Pembrolizumab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePemetrexed (800mg, D1) + Nedaplatin (120mg, D1) + Pembrolizumab (200mg, D1) (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eBilobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePleura\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSurgery (after surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLung and Brain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePemetrexed (800mg, D1) + Cisplatin (60mg, D1,2) + Pembrolizumab (200mg, D1) (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSurgery (after surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (400mg, D1) + Nedaplatin (130mg, D1) + Pembrolizumab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSurgery (Simultaneous resection with surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePemetrexed (900mg, D1) / Nab-paclitaxel (400mg, D1) + Nedaplatin (110mg, D1) + Pembrolizumab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrain and Adrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePemetrexed (900mg, D1) + Nedaplatin (150mg, D1) + Pembrolizumab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eBilobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLung primary and Bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (500mg, D1) + Carboplatin (500mg, D1) + Tislelizumab (200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (400mg, D1) + Nedaplatin (110mg, D1) + Tislelizumab (200mg,D1) (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRectus femoris muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSurgery (after surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLung primary and Pectineus\u0026nbsp;muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (400mg, D1) + Nedaplatin (100mg, D1) + Sugemalimab (1200mg, D1) (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRadiotherapy (before surgery of primary tumor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eP14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\"\u003e \u003cp\u003eSquamous carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNab-paclitaxel (400mg, D1) + Nedaplatin (140mg, D1) + Sugemalimab (1200mg, D1) (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eLobectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLung primary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003epCR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003epCR, pathological complete response; MPR, major pathological response; PR, partial response; VATS, video-assisted thoracoscopic surgery; RATS, robot assisted thoracic surgery\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSurgery Summary\u003c/h2\u003e \u003cp\u003eAll patients underwent surgical resection of primary tumor after 3–6 cycles of immunochemotherapy on the first day of each 21-day cycle, 10 patients underwent lobectomy, while 4 patients underwent bilobectomy (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Supplemental Table\u0026nbsp;1). 13 patients underwent video-assisted thoracic surgery/robot-assisted thoracic surgery (VATS /RATS), and 1 patient underwent thoracotomy (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Supplemental Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e7 of 14 patients received surgery or radiotherapy for metastatic tumors (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). 4 patients received surgery of metastatic lesions (including pleural metastasis, lung metastasis, adrenal metastasis, and rectus femoris metastasis), while the metastases of 3 patients with brain metastasis received preoperative radiotherapy. The full treatment is available in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe mean operative time was 203.6 minutes (30–440 minutes), the mean intraoperative blood loss was 403.6mL (20-2500 mL), the median postoperative hospital stay was 7 days (5–9 days), and the median duration of extubation was 4.5 days (3–7 days) (Supplemental Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEfficacy\u003c/h3\u003e\n\u003cp\u003e9 patients achieved pCR (64%) and 10 patients achieved MPR (71%) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In the 4 patients with brain metastasis (BM), pCR was achieved in 3 patients (75%) and MPR in 4 patients (100%) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The radiographic ORR was 100%, with a radiographic PR achieved in all patients after immunochemotherapy (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The median follow-up time of 14 patients was 21.8 months (15.7–24.8 months). The median EFS was 16.8 months (95%CI, 15.9–17.7 months), and the 12-month and 18-month EFS rate was 85.1% and 40.9% respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA), the median OS was not reached (95%CI, 26.6-NE months), and the 12-month and 18-month OS rate was 92.3% and 83.1% respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). In 4 patients with BM, the median EFS was 15.0 months (95%CI, 9.2–20.8 months), 12-month and 18-month EFS rate was 75% and 37.5% respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA), the median OS was not reached, 12-month and 18-month OS rate was 100% and 100% respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB). A post hoc subgroup analysis revealed that the median EFS was not reached with patients in pCR and 16.3 months (95% CI, 13.5 to 19.1) with patients in non-pCR (HR, 0.39; 95% CI, 0.10 to 1.6; P = 0.18) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eA), the median OS was not reached and 23.9 months (95% CI, 17.2 to 30.6) respectively(HR, 0.30; 95% CI, 0.04 to 2.12; P = 0.26) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eProgressive disease (PD) occurred in 8 patients (57%) (3 in the pCR group and 5 in the non-pCR group) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). 2 patients had recurrence of metastases (adrenal, brain) and 1 patient developed PD of the primary tumor in the group of pCR patients. While in the non-pCR patient group, 2 patients had recurrence of metastases (brain, adrenal), and 3 patients developed PD of both primary tumor and metastases (lung and brain, lung primary and bone, lung primary and pectineus muscle), including 2 patients with new lesions (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The fraction of patients with PD after treatment in the pCR and non-pCR groups were 33% and 100% respectively (OR, 0.38 [95%CI, 0.15–0.92], P = 0.031).\u003c/p\u003e "},{"header":"COMMENT","content":"\u003cp\u003eWe reported the efficacy of immunochemotherapy combined with surgery in patients with oligometastatic NSCLC. The expected trial results were achieved in this study, and the pCR rate was 64% of all patients. The patients enrolled in our trial were those who achieved ORR by radiographic assessments according to RECIST v.1.1 following immunochemotherapy and were eligible for surgery, that is Per-Protocol (PP) population, these patients had displayed dramatic efficacy before surgery. A meta-anvialysis\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e revealed an underlying association between MPR and ORR (OR, 6.21 [95%CI, 3.71–9.16], p \u0026lt; 0.00001). In addition, Boch \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e16\u003c/sup\u003e retrospectively studied the efficacy of immune monotherapy or immunochemotherapy combined with surgery in 13 patients with oligometastatic NSCLC. Due to the majority of patients with isolated metastases (69%) and PD-L1 TPS \u0026gt; 50% (62%), the pCR and MPR rate were high (54% and 69%, respectively), and the proportion of patients with isolated metastases in our study (71%) is consistent with Boch \u003cem\u003eet al\u003c/em\u003e. Therefore, initial explanations attribute high pathologic response rate to patients experiencing high ORR preoperatively, as well as the inclusion of patients with isolated metastases (13/14, 93%). The TD-FOREKNOW\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e randomized clinical trial reported a pCR rate of 32.6% with neoadjuvant camrelizumab plus platinum-based chemotherapy in patients with IIIA-IIIB NSCLC, and a quadruplet regimen (perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy) in the TD-NeoFOUR trial\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e in patients with IIA/IIIB NSCLC had a pCR rate of 57.8%. Intriguingly, a higher pCR rate (64%) was observed in the patients with oligometastatic NSCLC we included, but the comparison was indirect. Notably, neoadjuvant ICI combined with anlotinib and chemotherapy in patients with oligometastatic NSCLC may be a potentially effective treatment option and is worth exploring. Additionally, PD was observed among 8 patients, the proportion of PD in pCR patients was dramatically lower than non-pCR patients (OR, 0.38[95% CI, 0.15–0.92], P = 0.031). Distant metastases relapse was the majority (7/8, 87.5%) among the patients with PD, and the brain was more common (42.9%), which was comparable to the pattern of postoperative recurrence NSCLC\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn this retrospective study, patients with oligometastatic NSCLC achieved a median EFS of 16.8 months, 12-month EFS and OS of 85.1% and 92.3%, and 18-month EFS and OS of 40.9% and 83.1%, respectively. The previous therapy for oligometastatic NSCLC patients included chemotherapy combined with surgery,\u003csup\u003e9–12,20−23\u003c/sup\u003e and patients who underwent surgery achieved median PFS of around 13 months,\u003csup\u003e12\u003c/sup\u003e along with median OS of 11–31 months,\u003csup\u003e9–12\u003c/sup\u003e and a 1-year OS rate of 56%-79%.\u003csup\u003e11,22,23\u003c/sup\u003e Our approach to adding immunotherapy before surgery in comparison to systemic chemotherapy can prolong event-free survival and survival time being superior to previous standard therapy. The PACIFIC trial\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e used durvalumab for consolidation therapy in patients with stage III, locally advanced, unresectable NSCLC after concurrent chemoradiotherapy. Results displayed the median PFS of the durvalumab consolidation therapy group was 16.8 months (95% CI, 13.0-18.1). The 12-month and 18-month PFS rate were 55.9% (95%CI, 51.0-60.4) and 44.2% (95% CI, 37.7–50.5) respectively. Notably, our trial also achieved the same median EFS and a higher 12-month EFS rate. Although the 18-month EFS rate was inferior to the PACIFIC trial, the potential explanation is that the patients we enrolled possessed worse pathological staging. Moreover, our 12-month OS rate was also comparable with the trial of LAT (including surgery, chemoradiotherapy, stereotactic radiotherapy, and/or interventional ablation) followed by pembrolizumab (12-month OS rate was 90.9%) for oligometastatic NSCLC at diagnosis (synchronous disease) or who developed oligometastatic disease after initial definitive therapy (metachronous disease).\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e This study demonstrated superior efficacy of pembrolizumab consolidation after LAT, with a median PFS of 19.1 months, nearly double improvement compared to historical data. We similarly focused on patients with synchronous oligometastatic NSCLC, excluding patients whose tumors displayed regressed to the oligometastatic state after therapy (oligoremnant disease) in our trial. Conversely, the inferior median EFS observed in our study may be attributed to the inclusion of other local therapy alongside surgery for the primary tumor in the LAT, which provided patients with other therapy options and potentially resulted in superior outcomes. Notably, what remains evident is that patients with oligometastases who underwent pembrolizumab consolidation therapy following LAT exhibited acceptable adverse events,\u003csup\u003e13\u003c/sup\u003e indicating that perioperative therapy may offer improved outcomes for patients with oligometastatic NSCLC.\u003c/p\u003e\u003cp\u003eImmunotherapy plus chemotherapy can improve PFS and OS in extensively metastatic NSCLC patients, but the efficacy is limited.\u003csup\u003e3–5,25−27\u003c/sup\u003e As observed in the phase 3 KEYNOTE-189\u003csup\u003e4\u003c/sup\u003e, KEYNOTE-407\u003csup\u003e5,\u003c/sup\u003e and GEMSTONE-302\u003csup\u003e27\u003c/sup\u003e study trials, compared with chemotherapy, Pembrolizumab or Sugemalimab plus chemotherapy significantly improved PFS (median 8.0–9.0 months) and OS (median 17.2–25.4 months). Higher median PFS was displayed in our trial (16.8 months), and median OS was not reached, but 12-month OS was superior to the three trials\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e (92.3% vs 69.8%, 64.7%, and 71.6%). Given the different populations (the three trials analyzed the intention-to-treat (ITT) population, whereas we were the pp population) and the superior effectiveness of surgery compared to nonsurgical approaches in oligometastatic NSCLC,\u003csup\u003e22–23\u003c/sup\u003e the difference in treatment efficacy is interpretable. Collectively, immunochemotherapy combined with surgery may be a potential optional treatment to improve survival benefits in contrast to previous standard therapy for patients with oligometastatic NSCLC.\u003c/p\u003e\u003cp\u003eSimilarly superior efficacy was observed in 4 patients with BM, the median EFS was 15.0 months, and the 12-month EFS and OS rate was 75% and 100% respectively. Previous studies\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e indicated the 12-month OS rate of NSCLC patients with BM who underwent bifocal surgical resection was 79%. Moreover, in the pooled analysis\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e of KEYNOTE 021, -189, -407, the median PFS of patients with NSCLC and stable BM who received pembrolizumab plus platinum-based chemotherapy was 6.9 months, the 12-month PFS and OS rates were 29.9% and 62.9%, respectively, the PFS benefit of combination therapy with pembrolizumab plus platinum-based chemotherapy in the BM group was observed in all PD-L1 expression groups (\u0026lt; 1%, 1–49%, \u0026gt; 50%).\u003csup\u003e28\u003c/sup\u003e The difference is that 3 of 4 patients in our trial with brain metastases received local brain therapy before or after surgery, this may be the reason for the efficacy of patients with BM in our trial was superior compared to historical trials, suggesting that combined immunochemotherapy and local therapy during the perioperative period may have potential efficacy in patients with BM. However, this result needs to be interpreted with caution due to the small number of patients we included may introduce potential biases.\u003c/p\u003e\u003cp\u003eIn post hoc subgroup analyses, there was no statistical difference in EFS and OS between patients in pCR and non-pCR groups. Since the patients we enrolled were the PP population, patients had already achieved superior therapy before surgery, which may lead to long EFS and OS, our follow-up (median 21.8 months) was insufficient to allow positive results between the pCR and non-pCR groups. Encouragingly, patients in the non-pCR group had a median EFS of 16.3 months, which was significantly numerically higher than the progression-free survival of patients with extensively metastasized NSCLC in previous studies\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e, and a median OS of 23.9 months, which was comparable to previous studies.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e The pCR group did not reach the study endpoint, but the proportion of patients who experienced progression of disease or death in the pCR group by the final follow-up time was less than non-pCR group, which indicated that patients in the pCR group may display a favorable prognosis.\u003c/p\u003e\u003ch2\u003eStudy Limitations\u003c/h2\u003e\u003cp\u003eFirst, the limited patient size we include may introduce potential biases. The conclusion of the substantial clinical benefit of immunochemotherapy combined with surgery needs to be further verified by large-scale prospective studies in a larger population. Second, whether immunochemotherapy combined with surgery has different outcomes in patients with oligometastatic NSCLC with different levels of PD-L1 expression remains largely undetermined and is expected to be explored in future studies. Furthermore, the safety and feasibility of immunochemotherapy combined with surgery in patients with oligometastases NSCLC remains a substantial concern.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe efficacy of immunochemotherapy combined with surgery in patients with oligometastatic NSCLC is encouraging and has achieved better outcomes compared with previous clinical studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Tangdu Hospital of Air Force Military Medical University (TDLL-202409-05) and informed consent was taken from all individual participants. The trial was conducted according to the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\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\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the National Natural Science Foundation of China (82173252), Shaanxi Provincial Science and Technology Innovation Team (2023-CX-TD-64), New Technologies and Services of Tangdu Hospital (XJSXYW202122), and the Major Project of Medical Research (25YXYJZD00036).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZL:\u0026nbsp;\u003c/strong\u003eData curation, Formal analysis, Investigation,\u0026nbsp;Methodology, Project administration, Software, Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;YM:\u0026nbsp;\u003c/strong\u003eFormal analysis, Methodology, Project administration, Resources, Software, Validation, Visualization.\u003cstrong\u003e\u0026nbsp;ZG:\u0026nbsp;\u003c/strong\u003eInvestigation, Methodology, Project administration, Software, Validation, Visualization. \u003cstrong\u003eCS:\u0026nbsp;\u003c/strong\u003eConceptualization, Investigation, Project administration, Resources, Software, Supervision, Validation. \u003cstrong\u003eWQ\u003c/strong\u003e: Resources, Software, Supervision. \u003cstrong\u003eHD:\u0026nbsp;\u003c/strong\u003eConceptualization, Investigation, Project administration, Resources, Supervision, Writing \u0026ndash; review \u0026amp; editing. \u003cstrong\u003eXY:\u0026nbsp;\u003c/strong\u003eConceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing \u0026ndash; review \u0026amp; editing.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBray F, Laversanne M, Sung H, et al. 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J Thorac Oncol. 2021;16:1883\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jtho.2021.06.020\u003c/span\u003e\u003cspan address=\"10.1016/j.jtho.2021.06.020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Immunochemotherapy, oligometastatic NSCLC, retrospective study","lastPublishedDoi":"10.21203/rs.3.rs-8684499/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8684499/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eThe purpose of this trial was to assess the effectiveness of immunochemotherapy combined with surgery in patients with oligometastatic non-small cell lung cancer (NSCLC).\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed 14 patients with oligometastatic NSCLC. Patients received 3\u0026ndash;6 cycles of immunochemotherapy on day 1 of each 21-day cycle and underwent surgical resection of primary tumor. The metastatic lesions of 7 patients underwent surgery or radiotherapy. There were 9 cases of squamous cell carcinoma, 4 cases of adenocarcinoma, and 1 case of poorly differentiated lung cancer. Primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathological response (MPR), objective response rate (ORR), event-free survival (EFS), and overall survival (OS).\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eThe pCR and MPR rates were 64% and 71% of all patients. In 4 patients with brain metastasis (BM), the pCR and MPR rate were 75% and 100%. The ORR was 100%. The median follow-up time was 21.8 months. The median EFS was 16.8 months, 12-month and 18-month EFS rate were 85.1% and 40.9% respectively, 12-month and 18-month OS rate were 92.3% and 83.1% respectively. In 4 patients with BM, the median EFS was 15.0 months, 12-month and 18-month EFS rate was 75% and 37.5% respectively, 12-month and 18-month OS rate was 100% and 100% respectively.\u003c/p\u003e\u003ch2\u003eCONCLUSIONS\u003c/h2\u003e \u003cp\u003eThe treatment of immunochemotherapy combined with surgery significantly improved pathological response rate and ORR, prolonged EFS and OS in oligometastatic NSCLC.\u003c/p\u003e","manuscriptTitle":"Immunochemotherapy combined with surgery in oligometastatic non-small cell lung cancer: a retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 07:36:55","doi":"10.21203/rs.3.rs-8684499/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-03-06T15:48:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-05T06:05:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-04T09:21:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T17:56:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-02-03T17:46:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c34c6b3f-d428-44fd-b7fd-84cc4a1c2508","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-13T07:36:55+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 07:36:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8684499","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8684499","identity":"rs-8684499","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}