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      Upfront surgery for stage IIIA/B non-small cell lung cancer: retrospective cohort study

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          Abstract

          Background

          Stage III non-small cell lung cancer is a heterogeneous disease. Several international guidelines recommend neoadjuvant treatment before surgery; however, upfront surgery is the preferred approach for technically resectable non-small cell lung cancer in East Asia. The aim of this retrospective study was to evaluate the long-term outcomes of curative-intent upfront surgery in stage IIIA/B non-small cell lung cancer.

          Methods

          Patients who underwent curative-intent upfront surgery with stage cIIIA/B non-small cell lung cancer were identified. The clinical and pathological variables and survival outcomes were evaluated.

          Results

          Overall, 664 patients were identified, of whom 320 (48.8%) had N2 disease, 66.7% were males, 49.4% had a smoking history, and 61.2% had lung adenocarcinoma. Lobectomy was the most performed surgical procedure (84.9%). A total of 40 patients (6.02%) had positive margins (R1/R2). The grade III adverse event rate was 2.0% (13 of 664). The median follow-up was 30.6 (range 1.9–97.7) months. At follow-up, the mortality rate was 13.3% (88 of 664) and 37.2% of patients (247 of 664) had recurrence. Lung (101 of 247 (40.9%)) and brain (53 of 247 (21.5%)) were the most common sites of recurrence. The median overall survival was 60.0 (95% c.i. 51.5 to 67.6) months, with overall survival probability at 1, 2, 3, and 5 years being 89.6%, 77.8%, 67.2%, and 49.0% respectively. The R0 cohort showed an improved median overall survival compared with the R1/R2 cohort (67.4 versus 26.5 months respectively; P = greater than 0.001). The multivariable analysis revealed that age greater than or equal to 65 years (HR 1.51, 95% c.i. 1.08 to 2.12; reference = age less than 65 years), tumour size (greater than or equal to 5 cm (HR 2.13, 95% c.i. 1.41 to 3.21) and greater than or equal to 3 cm but less than 5 cm (HR 1.15, 95% c.i. 0.78 to 1.71); reference = less than 3 cm), and adjuvant treatment (chemotherapy (HR 0.69, 95% c.i. 0.49 to 0.96) and targeted therapy (HR 0.30, 95% c.i. 0.12 to 0.76); reference = none) significantly predicted overall survival.

          Conclusion

          Upfront surgery is an option for the management of stage IIIA/B non-small cell lung cancer.

          Abstract

          This study provides important real-world data, with a sufficient sample size, that upfront surgery for stage IIIA/B non-small cell lung cancer could have an acceptable perioperative morbidity rate and favourable long-term survival, particularly when combined with adjuvant therapies. This study identifies specific patient characteristics that may make them more suitable candidates for upfront surgery, such as younger age, smaller tumour size, limited nodal involvement, and no distant metastases. A comprehensive literature review on the survival rates of upfront surgery in non-small cell lung cancer facilitates easy comparison with relevant research findings in this field.

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          Most cited references79

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          Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

          Background Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. Methods We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. Results Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. Conclusions Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
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            Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer

            Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.
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              The Eighth Edition Lung Cancer Stage Classification.

              Stage classification provides a nomenclature about the anatomic extent of a cancer; a consistent language provides the ability to communicate about a specific patient and about cohorts of patients in clinical studies. This paper summarizes the eighth edition of lung cancer stage classification, which is the worldwide standard as of January 1, 2017. This revision is based on a large global database, a sophisticated analysis, extensive internal validation as well as multiple assessments confirming generalizability. Practicing clinicians must be familiar with the stage classification system when managing contemporary patients with lung cancer.
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                Author and article information

                Contributors
                Journal
                BJS Open
                BJS Open
                bjsopen
                BJS Open
                Oxford University Press (US )
                2474-9842
                April 2024
                21 March 2024
                21 March 2024
                : 8
                : 2
                : zrae008
                Affiliations
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of General Internal Medicine, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                LinkDoc Technology Co. Ltd , Beijing, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health , Guangzhou, China
                Author notes
                Correspondence to: (W.L.) Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University; China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Guangzhou, 510120, China (e-mail: liangwh1987@ 123456163.com ); (J.H.) Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University; China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Guangzhou, 510120, China (e-mail: drjianxing.he@ 123456gmail.com )

                Hongsheng Deng, Jun Liu, Xiuyu Cai, Shunjun Jiang contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-4886-0889
                https://orcid.org/0000-0002-1391-8238
                https://orcid.org/0000-0003-1737-8192
                Article
                zrae008
                10.1093/bjsopen/zrae008
                10957167
                38513281
                381b58b9-9a4f-4961-92e2-bbe59d33cce5
                © The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 June 2023
                : 21 December 2023
                : 03 January 2024
                Page count
                Pages: 10
                Categories
                Original Article
                AcademicSubjects/MED00910
                Bjs/17

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