{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T02:44:07Z","timestamp":1786157047958,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hamburg Cancer Society and the German Cancer Aid","award":["70114428"],"award-info":[{"award-number":["70114428"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rare or compound EGFR variants in non\u2013small-cell lung cancer (NSCLC) can create substantial therapeutic uncertainty, particularly when accompanied by additional co-alterations with potential resistance implications. In such settings, molecular tumor boards (MTBs) may integrate genomic, functional, and clinical data to guide treatment selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 59-year-old Caucasian woman was diagnosed with metastatic lung adenocarcinoma involving the lungs, bones, and lymph nodes. Histopathology showed a TTF-1 positive pulmonary adenocarcinoma with low PD-L1 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Molecular findings<\/jats:title>\n                    <jats:p>Next-generation sequencing identified a compound EGFR alteration consisting of L858R and Q701L, along with additional alterations in PIK3CA, ATM, and CTNNB1 and loss of CDKN2A\/B, MLH1, and BAP1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Functional and molecular tumor board assessment<\/jats:title>\n                    <jats:p>To resolve this uncertainty, the EGFR mutations were recreated in vitro and characterized within national Network Genomic Medicine (nNGM) preclinical platform. In Ba\/F3 models, the EGFR L858R\/Q701L co-mutation showed sensitivity to first-, second-, and third-generation EGFR tyrosine kinase inhibitors. After integrating the molecular profile, functional data, and clinical context, the institutional MTB recommended in-label therapy with Osimertinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome<\/jats:title>\n                    <jats:p>Treatment resulted in rapid clinical improvement and a radiologically confirmed partial remission followed by durable disease control for 18\u2009months. Disease progression occurred thereafter, and the patient died 23.4\u2009months after initial diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case highlights the importance of functional validation and multidisciplinary tumor board discussion in interpreting complex genomic profiles and guiding personalized therapy in NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag242","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:49:54Z","timestamp":1782992994000},"source":"Crossref","is-referenced-by-count":0,"title":["Molecular tumor board\u2013guided osimertinib therapy in EGFR L858R\/Q701L\u2013mutant lung adenocarcinoma supported by functional 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L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2977-3870","authenticated-orcid":false,"given":"Sivahari Prasad","family":"Gorantla","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Medical Center Schleswig-Holstein, and University Cancer Center Schleswig-Holstein , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Letsch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Christian-Albrechts-University, University Hospital Schleswig-Holstein , 24105 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-8506","authenticated-orcid":false,"given":"Melanie","family":"Janning","sequence":"additional","affiliation":[{"name":"DKFZ-Hector Cancer Institute at the University Medical Center 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