{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:46Z","timestamp":1786115626573,"version":"build-2736575974"},"reference-count":19,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031563","name":"Leeds Hospitals Charity","doi-asserted-by":"crossref","award":["A2003681"],"award-info":[{"award-number":["A2003681"]}],"id":[{"id":"10.13039\/100031563","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Neoadjuvant chemoimmunotherapy is now a standard approach for resectable stage II\u2013III non-small cell lung cancer (NSCLC), demonstrating improved pathological response and survival. However, its safety in physiologically high-risk surgical patients is unclear, as these groups are underrepresented in trials. This study compares 30-day and 90-day mortality and oncological outcomes of neoadjuvant chemoimmunotherapy followed by surgery versus upfront surgery within a high-risk multidisciplinary team (MDT) cohort. Methods: A retrospective single-centre study was performed, including consecutive high-risk MDT patients undergoing resection for stage II -III NSCLC between January 2022 and December 2025. High-risk status was defined by established physiological, cardiopulmonary, and comorbidity criteria. Patients were stratified into neoadjuvant chemoimmunotherapy followed by surgery (Chemo-IO; n = 33) or upfront surgery (n = 57). The primary outcome was 30-day mortality. Secondary outcomes included 90-day mortality, R0 resection rate, and length of hospital stay. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline differences between groups. Results: Ninety patients were included. Patients receiving neoadjuvant therapy had a greater comorbidity burden (Charlson Comorbidity Index 3.2 \u00b1 1.5 vs. 1.4 \u00b1 1.7, p &lt; 0.001) and more advanced disease (stage III: 57.6% vs. 29.8%, p = 0.014). Thirty-day mortality was 0% in the Chemo-IO group and 1.8% following upfront surgery. After IPTW adjustment, neoadjuvant therapy was not associated with increased perioperative mortality. Ninety-day mortality was similar between groups (3.0% vs. 3.5%; IPTW OR 0.91, 95% CI 0.05\u201315.39, p = 0.948). R0 resection rates were numerically higher following Chemo-IO (87.9% vs. 78.9%; IPTW OR 3.42, 95% CI 0.71\u201316.59, p = 0.127). Median hospital stay was identical in both cohorts (6 days), with no significant difference after weighting (p = 0.722). Conclusions: Neoadjuvant chemoimmunotherapy appears safe and feasible in carefully selected high-risk patients with resectable stage II\u2013III NSCLC. Despite greater comorbidity burden and more advanced disease, short-term perioperative outcomes were not compromised, while a trend towards improved R0 resection rates was observed. These findings support the consideration of multimodal treatment strategies within high-risk MDT pathways.<\/jats:p>","DOI":"10.3390\/jcm15156069","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:38:08Z","timestamp":1785839888000},"page":"6069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is Neoadjuvant Chemoimmunotherapy Safe in Surgically High-Risk Lung Cancer Patients? A Single-Centre IPTW Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0959-1287","authenticated-orcid":false,"given":"Fathima Shafra","family":"Mubarak","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneeb","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Alvarez Gallesio","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Nardini","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8121-9121","authenticated-orcid":false,"given":"Joshil","family":"Lodhia","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Teh","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilanjan","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostas","family":"Papagiannopoulos","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Milton","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Brunelli","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1538-8493","authenticated-orcid":false,"given":"Peter","family":"Tcherveniakov","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, St James\u2019s University Hospital, Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejcsup.2013.07.021","article-title":"Surgical treatment of early-stage non-small-cell lung cancer","volume":"11","author":"Balduyck","year":"2013","journal-title":"Eur. 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