Pub Date : 2026-01-29DOI: 10.1016/j.ejca.2026.116254
Sveva Castelli, Franziska Schulze, Theresa M Thole-Kliesch, Kathy Astrahantseff, Giuseppe Barone, Maja Beck-Popovic, Pablo Berlanga, Selim Corbacioglu, Matthias Fischer, Marion Gambart, Sally L George, Louis Chesler, Juliet C Gray, Barbara Hero, Annette Künkele, Tim Flaadt, Peter Lang, Holger N Lode, Jan J Molenaar, Gudrun Schleiermacher, Carolina Rosswog, Lucas Moreno, Cormac Owens, Alba Rubio-San-Simón, Johannes H Schulte, Thorsten Simon, Deborah A Tweddle, Hedwig E Deubzer, Angelika Eggert
More than 50 % of patients with high-risk neuroblastoma (HRNB) will relapse despite intensive multimodal therapy. Most relapses occur within 2 years of diagnosis. Overall survival at relapse is 20 % at 4 years, but long-term survival can be achieved in a patient subset. A biopsy at relapse with in-depth molecular characterization should now become accepted as standard of care to confirm active neuroblastoma and identify potential targets for biomarker-based targeted therapy or immunotherapy. No clear consensus currently exists about optimal therapy because the field lacks umbrella trials covering all phases of relapse treatment (re-induction, consolidation, maintenance) in a homogenous strategy. Recruitment into clinical trials (e.g. BEACON2) should be prioritized. Current evidence supports starting re-induction therapy with a camptothecin-based chemotherapy regimen combined with monoclonal antibody therapy targeting GD2 or VEGF (or ALK inhibitors if ALK-aberrant) as the first choice. The RIST regimen is a promising first choice for MYCN-amplified disease. After an objective response to re-induction therapy, GD2-directed immunotherapy or cellular therapies harnessing the immune system (haploidentical stem cell transplantation, CAR T cells) are of high interest as a consolidation strategy. Long-term maintenance therapy must be feasible as outpatient treatment, have a low toxicity profile and be well-tolerable to suit patients with relapsed HRNB. For optimal care, new options must be tested as maintenance therapy in randomized trials. The most promising salvage options for patients responding insufficiently to treatment are the chemotherapy combinations, topotecan/vincristine/doxorubicin (TVD), topotecan/cyclophosphamide/etoposide (TCE), ifosfamide/carboplatin/etoposide (ICE) or topotecan/cyclophosphamide (TopoCy), or [131I]-mIBG therapy. Early-phase clinical trials are also a possible option in this setting.
{"title":"Current treatment strategies for first relapse of high-risk neuroblastoma.","authors":"Sveva Castelli, Franziska Schulze, Theresa M Thole-Kliesch, Kathy Astrahantseff, Giuseppe Barone, Maja Beck-Popovic, Pablo Berlanga, Selim Corbacioglu, Matthias Fischer, Marion Gambart, Sally L George, Louis Chesler, Juliet C Gray, Barbara Hero, Annette Künkele, Tim Flaadt, Peter Lang, Holger N Lode, Jan J Molenaar, Gudrun Schleiermacher, Carolina Rosswog, Lucas Moreno, Cormac Owens, Alba Rubio-San-Simón, Johannes H Schulte, Thorsten Simon, Deborah A Tweddle, Hedwig E Deubzer, Angelika Eggert","doi":"10.1016/j.ejca.2026.116254","DOIUrl":"https://doi.org/10.1016/j.ejca.2026.116254","url":null,"abstract":"<p><p>More than 50 % of patients with high-risk neuroblastoma (HRNB) will relapse despite intensive multimodal therapy. Most relapses occur within 2 years of diagnosis. Overall survival at relapse is 20 % at 4 years, but long-term survival can be achieved in a patient subset. A biopsy at relapse with in-depth molecular characterization should now become accepted as standard of care to confirm active neuroblastoma and identify potential targets for biomarker-based targeted therapy or immunotherapy. No clear consensus currently exists about optimal therapy because the field lacks umbrella trials covering all phases of relapse treatment (re-induction, consolidation, maintenance) in a homogenous strategy. Recruitment into clinical trials (e.g. BEACON2) should be prioritized. Current evidence supports starting re-induction therapy with a camptothecin-based chemotherapy regimen combined with monoclonal antibody therapy targeting GD2 or VEGF (or ALK inhibitors if ALK-aberrant) as the first choice. The RIST regimen is a promising first choice for MYCN-amplified disease. After an objective response to re-induction therapy, GD2-directed immunotherapy or cellular therapies harnessing the immune system (haploidentical stem cell transplantation, CAR T cells) are of high interest as a consolidation strategy. Long-term maintenance therapy must be feasible as outpatient treatment, have a low toxicity profile and be well-tolerable to suit patients with relapsed HRNB. For optimal care, new options must be tested as maintenance therapy in randomized trials. The most promising salvage options for patients responding insufficiently to treatment are the chemotherapy combinations, topotecan/vincristine/doxorubicin (TVD), topotecan/cyclophosphamide/etoposide (TCE), ifosfamide/carboplatin/etoposide (ICE) or topotecan/cyclophosphamide (TopoCy), or [<sup>131</sup>I]-mIBG therapy. Early-phase clinical trials are also a possible option in this setting.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"116254"},"PeriodicalIF":7.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.ejca.2026.116260
Umberto Leone Roberti Maggiore, Francesco Fanfani, Ilaria Capasso, Emanuele Perrone, Giuseppe Parisi, Gian Franco Zannoni, Francesca Falcone, Alessandra Di Giovanni, Mario Malzoni, Anna Myriam Perrone, Francesco Mezzapesa, Pierandrea De Iaco, Simone Garzon, Pier Carlo Zorzato, Stefano Uccella, Maria Grazia Centurioni, Fabio Barra, Simone Ferrero, Dorella Franchi, Tommaso Bianchi, Tommaso Grassi, Robert Fruscio, Filippo Ferrari, Giovanni Roviglione, Marcello Ceccaroni, Fulvio Borella, Stefano Cosma, Alberto Revelli, Jvan Casarin, Anna Giudici, Fabio Ghezzi, Matteo Marchetti, Giulia Spagnol, Roberto Tozzi, Francesca Filippi, Claudia Frittitta, Giovanna Scarfone, Biagio Paolini, Savio Eliotropio, Salvatore Lopez, Gennaro Cormio, Stefano Fucina, Antonino Ditto, Stefano Restaino, Giuseppe Vizzielli, Elena Puzzi, Eugenio Solima, Michele Vignali, Stefano Bergamini, Luca Lalli, Benedetta Zambetti, Simone Bruni, Lorenzo Ceppi, Luca Sorrentino, Valentina Chiappa, Giorgio Bogani, Francesco Raspagliesi
Background: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy.
Methods: This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS).
Results: Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal.
Conclusion: Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.
背景：子宫平滑肌肿瘤是一种临床表现难以预测的罕见肿瘤。最佳处理，特别是育龄妇女，仍然存在争议，比较保留生育能力与子宫切除术的安全性的数据有限。方法：这项多中心回顾性队列研究纳入了2010年至2023年在意大利17家妇科肿瘤中心接受组织学证实的树桩治疗的18-85岁女性。患者接受保留生育能力的手术（子宫肌瘤切除术或宫腔镜切除）或最终手术（子宫切除术±输卵管卵巢切除术）。Kaplan-Meier和Cox模型用于比较无复发生存期（RFS）和总生存期（OS）。结果：中位（范围）随访时间为51（1-291）个月。在401名女性中，106名（26.4 %）接受了保留生育能力的治疗（平均[±SD]年龄：35.3 ± 6.8岁），295名（73.6 %）接受了最终手术（平均[±SD]年龄：47.7 ± 9.2）。在总随访中，复发发生率为12. %，主要发生在骨盆内。最终手术后的中位RFS比保留生育能力手术后的中位RFS更长（50.0个月vs 42.5个月；HR 2.39[95 % CI 1.36-4.19]），尽管排除良性（平滑肌瘤）复发后这种差异消失（HR 1.74[95 % CI 0.90-3.34]）。在最后一次随访中，97.5 %的患者存活，治疗组间OS无显著差异（HR 0.22[95 % CI 0.27-1.79]）。绝经状态和同时切除附件的结果具有可比性。结论：最终手术降低了复发风险，但在适当选择的残肢残肢患者中，保留生育能力的手术后的长期生存率同样很好。对于希望生育的患者，保守治疗是一个合理的选择，前提是他们接受关于复发风险、诊断不确定性和需要长期监测的咨询。
{"title":"Fertility-sparing vs hysterectomy for uterine STUMP: A pragmatic clinical study.","authors":"Umberto Leone Roberti Maggiore, Francesco Fanfani, Ilaria Capasso, Emanuele Perrone, Giuseppe Parisi, Gian Franco Zannoni, Francesca Falcone, Alessandra Di Giovanni, Mario Malzoni, Anna Myriam Perrone, Francesco Mezzapesa, Pierandrea De Iaco, Simone Garzon, Pier Carlo Zorzato, Stefano Uccella, Maria Grazia Centurioni, Fabio Barra, Simone Ferrero, Dorella Franchi, Tommaso Bianchi, Tommaso Grassi, Robert Fruscio, Filippo Ferrari, Giovanni Roviglione, Marcello Ceccaroni, Fulvio Borella, Stefano Cosma, Alberto Revelli, Jvan Casarin, Anna Giudici, Fabio Ghezzi, Matteo Marchetti, Giulia Spagnol, Roberto Tozzi, Francesca Filippi, Claudia Frittitta, Giovanna Scarfone, Biagio Paolini, Savio Eliotropio, Salvatore Lopez, Gennaro Cormio, Stefano Fucina, Antonino Ditto, Stefano Restaino, Giuseppe Vizzielli, Elena Puzzi, Eugenio Solima, Michele Vignali, Stefano Bergamini, Luca Lalli, Benedetta Zambetti, Simone Bruni, Lorenzo Ceppi, Luca Sorrentino, Valentina Chiappa, Giorgio Bogani, Francesco Raspagliesi","doi":"10.1016/j.ejca.2026.116260","DOIUrl":"https://doi.org/10.1016/j.ejca.2026.116260","url":null,"abstract":"<p><strong>Background: </strong>Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy.</p><p><strong>Methods: </strong>This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS).</p><p><strong>Results: </strong>Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal.</p><p><strong>Conclusion: </strong>Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"116260"},"PeriodicalIF":7.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.ejca.2026.116252
Jorge Hernando , Carlos Lopez , Alejandro Garcia-Alvarez , Santiago Aguín Losada , Olga Martínez-Sáez , Carlos Gonzalez-Perez , Ricardo López-Almaraz , Raúl Sánchez Morillas , Joseba Rebollo Liceaga , Laura Ferreira Freire , Miriam Pavon-Mengual , María Ruiz Vico , Miriam López-Gómez , Idoia Morilla , Delvys Rodríguez-Abreu , Jaume Capdevila
Background
Larotrectinib is a first-in-class, selective tropomyosin receptor kinase (TRK) inhibitor with proven activity across solid tumors. This study aimed to describe larotrectinib's effectiveness in patients with solid tumors in Spain.
Methods
SPAINTRK (NCT06837090) was a retrospective study including adult and pediatric patients with solid neoplasms treated with larotrectinib through compassionate use, between European Medicines Agency (EMA) approval and commercialization in Spain. TRK fusions were determined as part of standard care using next-generation sequencing (NGS), fluorescence in situ hybridization, or immunohistochemistry plus a confirmatory molecular test. The primary endpoint was duration of response (DoR). No formal sample size was calculated.
Results
From February to June 2025, 20 patients aged ten months to 81 years were included. Eight solid tumor types with TRK fusions were included involving NTRK1 gene in 8 patients (40 %), NTRK2 in 5 (25 %), and NTRK3 in 7 (35 %). NGS was used in 65 %. Median DoR was 24.5 months (95 % CI: 11.1- not reached) and objective response rate was 60 % (95 % CI: 36.1–80.9). At one year, 75 % of responses (9 out of 12) were ongoing, and 12 patients (60 %) remained progression-free. At data cutoff (median follow-up of 24.4 months (95 % CI: 13.2–35)), 41.7 % of the patients with a response were disease-free and/or remained on treatment. Treatment-related neutropenia and transaminitis were reported in 15 % of patients each.
Conclusions
Larotrectinib evoked broad and durable antitumor activity in a plethora of solid tumors with NTRK fusions. Safety profile was consistent with that of clinical trials, even after long-term administration. While NGS use is increasing, broader access is needed.
{"title":"Larotrectinib in patients with tropomyosin receptor kinase fusion solid tumors in Spain (SPAINTRK)","authors":"Jorge Hernando , Carlos Lopez , Alejandro Garcia-Alvarez , Santiago Aguín Losada , Olga Martínez-Sáez , Carlos Gonzalez-Perez , Ricardo López-Almaraz , Raúl Sánchez Morillas , Joseba Rebollo Liceaga , Laura Ferreira Freire , Miriam Pavon-Mengual , María Ruiz Vico , Miriam López-Gómez , Idoia Morilla , Delvys Rodríguez-Abreu , Jaume Capdevila","doi":"10.1016/j.ejca.2026.116252","DOIUrl":"10.1016/j.ejca.2026.116252","url":null,"abstract":"<div><h3>Background</h3><div>Larotrectinib is a first-in-class, selective tropomyosin receptor kinase (TRK) inhibitor with proven activity across solid tumors. This study aimed to describe larotrectinib's effectiveness in patients with solid tumors in Spain.</div></div><div><h3>Methods</h3><div>SPAINTRK (NCT06837090) was a retrospective study including adult and pediatric patients with solid neoplasms treated with larotrectinib through compassionate use, between European Medicines Agency (EMA) approval and commercialization in Spain. TRK fusions were determined as part of standard care using next-generation sequencing (NGS), fluorescence in situ hybridization, or immunohistochemistry plus a confirmatory molecular test. The primary endpoint was duration of response (DoR). No formal sample size was calculated.</div></div><div><h3>Results</h3><div>From February to June 2025, 20 patients aged ten months to 81 years were included. Eight solid tumor types with TRK fusions were included involving <em>NTRK1</em> gene in 8 patients (40 %), <em>NTRK2</em> in 5 (25 %), and <em>NTRK3</em> in 7 (35 %). NGS was used in 65 %. Median DoR was 24.5 months (95 % CI: 11.1- not reached) and objective response rate was 60 % (95 % CI: 36.1–80.9). At one year, 75 % of responses (9 out of 12) were ongoing, and 12 patients (60 %) remained progression-free. At data cutoff (median follow-up of 24.4 months (95 % CI: 13.2–35)), 41.7 % of the patients with a response were disease-free and/or remained on treatment. Treatment-related neutropenia and transaminitis were reported in 15 % of patients each.</div></div><div><h3>Conclusions</h3><div>Larotrectinib evoked broad and durable antitumor activity in a plethora of solid tumors with <em>NTRK</em> fusions. Safety profile was consistent with that of clinical trials, even after long-term administration. While NGS use is increasing, broader access is needed.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"236 ","pages":"Article 116252"},"PeriodicalIF":7.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The SORASTOP study reports long-term outcomes following planned sorafenib discontinuation in responding patients with extremity desmoid-type fibromatosis (DTF).
Materials and methods
In this prospective, single-arm phase 2 Simon’s two-stage trial, adults with non-progressive, extremity DTF, ESAS pain < 2, after ≥ 12 months of sorafenib were enrolled. Sorafenib was stopped and patients were monitored with MRI, ESAS, and EORTC QLQ-C30, ACE-III. Progression was defined as ≥ 20 % tumour increase or ≥ 10 % increase with ESAS pain score > 5. The primary endpoint was 1-year PFS.
Results
33 patients (median age 30 years; 54.5 % female) were enrolled between 2021–2023. At 12 months, 31 (93.9 %) were evaluable; at 24 months, 30 (90.9 %). After 12 months of discontinuation, 4/31 (12.9 %) had PR, 24/31 (77.4 %) SD and 3/31 (9.6 %) PD and at 24 months 8/30 (26.6 %) had PR, 16/30 (53.3 %) SD and 6/30 (20 %) PD (RECIST v1.1). ESAS pain showed a transient rise: pain-free patients (ESAS=0) decreased from 69.7 % at baseline to 35.5 % at 12 months, recovering to 66.7 % at 24 months. Nine patients (27 %) progressed; four required sorafenib re-initiation and five were managed conservatively, all ultimately achieving disease stabilisation. PFS at 12, 24 and 36 months were 90.8 %, 74.5 % and 74.5 % respectively; with median follow-up of 37 months. EORTC QLQ-C30 showed stable global health status and improvements in emotional, physical, and cognitive functioning, with reductions in fatigue and pain.
Conclusion
Planned sorafenib discontinuation in responding extremity DTF patients is feasible, yields durable disease control, and improves QoL. Patients who progressed were successfully managed with sorafenib re-challenge or observation.
{"title":"Clinico-radiological outcomes after discontinuation of sorafenib in non-abdominal desmoid-type fibromatosis: Final results from a phase-II SORASTOP study from India","authors":"Kinjal Singh , Sameer Rastogi , Akash Singh , Simran Kaur , Shivanand Gamanagatti , Stanzin Spalkit , Ghazal Tansir , Bharath B. Gangadharaiah , Vikas Garg , Adarsh Barwad , Sandeep Bhoriwal , Puneet Tanwar","doi":"10.1016/j.ejca.2026.116253","DOIUrl":"10.1016/j.ejca.2026.116253","url":null,"abstract":"<div><h3>Introduction</h3><div>The SORASTOP study reports long-term outcomes following planned sorafenib discontinuation in responding patients with extremity desmoid-type fibromatosis (DTF).</div></div><div><h3>Materials and methods</h3><div>In this prospective, single-arm phase 2 Simon’s two-stage trial, adults with non-progressive, extremity DTF, ESAS pain < 2, after ≥ 12 months of sorafenib were enrolled. Sorafenib was stopped and patients were monitored with MRI, ESAS, and EORTC QLQ-C30, ACE-III. Progression was defined as ≥ 20 % tumour increase or ≥ 10 % increase with ESAS pain score > 5. The primary endpoint was 1-year PFS.</div></div><div><h3>Results</h3><div>33 patients (median age 30 years; 54.5 % female) were enrolled between 2021–2023. At 12 months, 31 (93.9 %) were evaluable; at 24 months, 30 (90.9 %). After 12 months of discontinuation, 4/31 (12.9 %) had PR, 24/31 (77.4 %) SD and 3/31 (9.6 %) PD and at 24 months 8/30 (26.6 %) had PR, 16/30 (53.3 %) SD and 6/30 (20 %) PD (RECIST v1.1). ESAS pain showed a transient rise: pain-free patients (ESAS=0) decreased from 69.7 % at baseline to 35.5 % at 12 months, recovering to 66.7 % at 24 months. Nine patients (27 %) progressed; four required sorafenib re-initiation and five were managed conservatively, all ultimately achieving disease stabilisation. PFS at 12, 24 and 36 months were 90.8 %, 74.5 % and 74.5 % respectively; with median follow-up of 37 months. EORTC QLQ-C30 showed stable global health status and improvements in emotional, physical, and cognitive functioning, with reductions in fatigue and pain.</div></div><div><h3>Conclusion</h3><div>Planned sorafenib discontinuation in responding extremity DTF patients is feasible, yields durable disease control, and improves QoL. Patients who progressed were successfully managed with sorafenib re-challenge or observation.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116253"},"PeriodicalIF":7.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.ejca.2026.116244
Michael Sandherr , Enrico Schalk , Werner J. Heinz , Philipp Köhler , Stefan W. Krause , Blasius Liss , Lea Kausche , Hartmut Link , Sibylle C. Mellinghoff , Martin Schmidt-Hieber , Nikolai Schuelper , Karsten Spiekermann , Rosanne Sprute , Ruth Seggewiss-Bernhardt
Introduction
Febrile neutropenia, a common complication of systemic antineoplastic therapy, varies in risk depending on malignant disease, treatment, and patient factors. The risk increases with the depth and duration of neutropenia and can be reduced with prophylactic use of G-CSF. International guidelines are conflicting in several aspects and do not reflect all patient groups. We therefore updated the 2014 Infectious Diseases Working Party (AGIHO) guideline of the German Society of Hematology and Medical Oncology (DGHO) on evidence-based recommendations for the use of G-CSF in patients with cancer.
Materials and Methods
After a systematic literature search from January 2014 to December 2024 on PubMed and Medline several consensus meetings were held by an expert panel of the AGIHO to evaluate, discuss and consent on the level of evidence and strength of recommendation for the use of G-CSF in patients with cancer based on ESCMID criteria.
Results
Results from eligible (randomized) studies were grouped in evidence tables. Recommendations for different entities, risk groups, new G-CSF formulations and emerging strategies in immunotherapy were set up and put into comparison to 2014.
Discussion
Comprehensive literature search and expert panel consensus confirm most of the key recommendations of 2014. New recommendations on the use of G-CSF in immunotherapy settings provide insight and support for day-by-day clinical decision making in the care of patients with cancer.
{"title":"Evidence-based AGIHO guideline update on prophylaxis of infectious complications with granulocyte-stimulating factors (G-CSF) for the treatment of adult patients with cancer","authors":"Michael Sandherr , Enrico Schalk , Werner J. Heinz , Philipp Köhler , Stefan W. Krause , Blasius Liss , Lea Kausche , Hartmut Link , Sibylle C. Mellinghoff , Martin Schmidt-Hieber , Nikolai Schuelper , Karsten Spiekermann , Rosanne Sprute , Ruth Seggewiss-Bernhardt","doi":"10.1016/j.ejca.2026.116244","DOIUrl":"10.1016/j.ejca.2026.116244","url":null,"abstract":"<div><h3>Introduction</h3><div>Febrile neutropenia, a common complication of systemic antineoplastic therapy, varies in risk depending on malignant disease, treatment, and patient factors. The risk increases with the depth and duration of neutropenia and can be reduced with prophylactic use of G-CSF. International guidelines are conflicting in several aspects and do not reflect all patient groups. We therefore updated the 2014 Infectious Diseases Working Party (AGIHO) guideline of the German Society of Hematology and Medical Oncology (DGHO) on evidence-based recommendations for the use of G-CSF in patients with cancer.</div></div><div><h3>Materials and Methods</h3><div>After a systematic literature search from January 2014 to December 2024 on PubMed and Medline several consensus meetings were held by an expert panel of the AGIHO to evaluate, discuss and consent on the level of evidence and strength of recommendation for the use of G-CSF in patients with cancer based on ESCMID criteria.</div></div><div><h3>Results</h3><div>Results from eligible (randomized) studies were grouped in evidence tables. Recommendations for different entities, risk groups, new G-CSF formulations and emerging strategies in immunotherapy were set up and put into comparison to 2014.</div></div><div><h3>Discussion</h3><div>Comprehensive literature search and expert panel consensus confirm most of the key recommendations of 2014. New recommendations on the use of G-CSF in immunotherapy settings provide insight and support for day-by-day clinical decision making in the care of patients with cancer.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116244"},"PeriodicalIF":7.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.ejca.2026.116245
Lise J. van de Velde , W.F. Julius Scheurleer , Michal D. Czerwinski , Lia G. Verhoef , Marco Ferrari , Rita De Berardinis , Mohssen Ansarin , Tamer Soror , Laura Motisi , Christian M. Meerwein , Bruno Fionda , Vittorio Rampinelli , Maurizio Bignami , Paolo Battaglia , Giampiero Parrinello , Florian Chatelet , Alessandro Vinciguerra , Zoltán Takácsi-Nagy , Monik Patel , Tsu-Hui (Hubert) Low , Francesco Bussu
Study aim
Cancer of the nasal vestibule (CNV) is an underrecognized head and neck malignancy, lacking a distinct ICD-O-3 topography code, and a specific T classification. The goal of this study was to assess which of the currently used T classifications provides the most accurate predictive and discriminatory accuracy.
Methods
The four currently used classifications (UICC Sinonasal, UICC NMSC, Wang and Rome) were assessed in a retrospective multicenter cohort established within the Head & Neck and Skin Groupe Européen de Curiethérapie / European SocieTy for Radiotherapy & Oncology Working Group. Through multivariable disease-specific and recurrence-free survival analyses, it was evaluated which staging system was most valuable.
Results
609 CNV cases were retrieved from 21 tertiary care centers. Only the Wang and New Rome systems provided accurate prognostic stratification as they showed diminishing survival rates and increasing hazards of disease-specific death and disease recurrence with each successive T category. Compared to Wang, the New Rome system employs more objective criteria and, since it includes four T categories, it can easily be integrated with cN stage to obtain a specific clinical staging for the CNV, which has also resulted superior compared to the current UICC/AJCC systems in this study.
Conclusion
The New Rome classification exhibits a superior predictive and descriptive precision compared to the Wang and both UICC/AJCC systems. The New Rome’s T category structure would allow an integration into the wider UICC/AJCC system once the nasal vestibule is acknowledged as a different subsite.
研究目的鼻前庭癌（CNV）是一种未被充分认识的头颈部恶性肿瘤，缺乏明确的ICD-O-3地形编码和特定的T分类。本研究的目的是评估目前使用的T分类中哪一种提供了最准确的预测和区分准确性。方法对目前使用的四种分类（UICC Sinonasal、UICC NMSC、Wang和Rome）进行回顾性多中心队列评估，该队列由欧洲颈部和皮肤组织(Head & Neck and Skin Group) /欧洲放射与肿瘤学会（European SocieTy for radiation & Oncology Working Group）建立。通过多变量疾病特异性和无复发生存分析，评估哪种分期系统最有价值。结果21个三级医疗中心共收集到609例CNV病例。只有Wang和New Rome系统提供了准确的预后分层，因为它们显示每一个连续的T分类生存率降低，疾病特异性死亡和疾病复发的风险增加。与Wang相比，新罗马系统采用了更客观的标准，由于它包括四个T类别，它可以很容易地与cN分期相结合，以获得CNV的特定临床分期，这也导致了本研究中与当前UICC/AJCC系统相比的优势。结论与Wang和UICC/AJCC系统相比，New Rome分类系统具有更高的预测和描述精度。一旦鼻前庭被确认为不同的子站点，新罗马的T类结构将允许集成到更广泛的UICC/AJCC系统中。
{"title":"International multicentric validation of a novel T classification system for cancer of the nasal vestibule","authors":"Lise J. van de Velde , W.F. Julius Scheurleer , Michal D. Czerwinski , Lia G. Verhoef , Marco Ferrari , Rita De Berardinis , Mohssen Ansarin , Tamer Soror , Laura Motisi , Christian M. Meerwein , Bruno Fionda , Vittorio Rampinelli , Maurizio Bignami , Paolo Battaglia , Giampiero Parrinello , Florian Chatelet , Alessandro Vinciguerra , Zoltán Takácsi-Nagy , Monik Patel , Tsu-Hui (Hubert) Low , Francesco Bussu","doi":"10.1016/j.ejca.2026.116245","DOIUrl":"10.1016/j.ejca.2026.116245","url":null,"abstract":"<div><h3>Study aim</h3><div>Cancer of the nasal vestibule (CNV) is an underrecognized head and neck malignancy, lacking a distinct ICD-O-3 topography code, and a specific T classification. The goal of this study was to assess which of the currently used T classifications provides the most accurate predictive and discriminatory accuracy.</div></div><div><h3>Methods</h3><div>The four currently used classifications (UICC Sinonasal, UICC NMSC, Wang and Rome) were assessed in a retrospective multicenter cohort established within the Head & Neck and Skin Groupe Européen de Curiethérapie / European SocieTy for Radiotherapy & Oncology Working Group. Through multivariable disease-specific and recurrence-free survival analyses, it was evaluated which staging system was most valuable.</div></div><div><h3>Results</h3><div>609 CNV cases were retrieved from 21 tertiary care centers. Only the Wang and New Rome systems provided accurate prognostic stratification as they showed diminishing survival rates and increasing hazards of disease-specific death and disease recurrence with each successive T category. Compared to Wang, the New Rome system employs more objective criteria and, since it includes four T categories, it can easily be integrated with cN stage to obtain a specific clinical staging for the CNV, which has also resulted superior compared to the current UICC/AJCC systems in this study.</div></div><div><h3>Conclusion</h3><div>The New Rome classification exhibits a superior predictive and descriptive precision compared to the Wang and both UICC/AJCC systems. The New Rome’s T category structure would allow an integration into the wider UICC/AJCC system once the nasal vestibule is acknowledged as a different subsite.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116245"},"PeriodicalIF":7.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/j.ejca.2026.116246
Thomas Budolfsen , Rene Horsleben Petersen , Lars Borgbjerg Møller , Jette Brabrand , Zaigham Saghir , Morten Quist
Background
Surgical resection is first-line treatment for patients with stage I–IIIA non-small cell lung cancer (NSCLC), yet a substantial proportion are managed without surgery. The reasons for non-operative management and the role of objective functional assessment are insufficiently described.
Methods
This retrospective registry-based cohort study included patients diagnosed with stage I–IIIA NSCLC in 2022 in the Capital Region of Denmark. Data were retrieved from the Danish Lung Cancer Registry and electronic medical records. Patients were categorized into “Surgery” and “No surgery” groups. Demographic variables, lung function, ECOG performance status, comorbidities, and MDT justifications were extracted. Multivariable logistic regression identified factors associated with not receiving surgery, and one-year overall survival (OS) was estimated using Kaplan–Meier methods.
Results
Among 524 patients, 178 (34 %) did not undergo surgery. Non-surgical management was independently associated with age ≥ 80 years, stage IIIA disease, poorer ECOG performance status, comorbidities, and reduced or unregistered DLco, whereas FEV1 and DLco ≥ 80 % predicted were negatively associated. MDT justifications were low lung function or poor performance status (29.2 %), comorbidities (18.0 %), and N2 disease (11.8 %); in 19.7 % no justification was documented. No documentation of preoperative exercise testing was identified. One-year OS was higher after surgery than no surgery (95.7 % vs. 82.0 %), unadjusted.
Conclusions
One third of patients with stage I–IIIA NSCLC were treated without surgery, mainly due to impaired functional status, comorbidity, or advanced stage. The absence of documented exercise testing highlights a gap between guideline recommendations and clinical practice.
{"title":"Why are patients with non-small cell lung cancer in stage I-IIIA considered inoperable? A registry-based study from the capital region of Denmark","authors":"Thomas Budolfsen , Rene Horsleben Petersen , Lars Borgbjerg Møller , Jette Brabrand , Zaigham Saghir , Morten Quist","doi":"10.1016/j.ejca.2026.116246","DOIUrl":"10.1016/j.ejca.2026.116246","url":null,"abstract":"<div><h3>Background</h3><div>Surgical resection is first-line treatment for patients with stage I–IIIA non-small cell lung cancer (NSCLC), yet a substantial proportion are managed without surgery. The reasons for non-operative management and the role of objective functional assessment are insufficiently described.</div></div><div><h3>Methods</h3><div>This retrospective registry-based cohort study included patients diagnosed with stage I–IIIA NSCLC in 2022 in the Capital Region of Denmark. Data were retrieved from the Danish Lung Cancer Registry and electronic medical records. Patients were categorized into “Surgery” and “No surgery” groups. Demographic variables, lung function, ECOG performance status, comorbidities, and MDT justifications were extracted. Multivariable logistic regression identified factors associated with not receiving surgery, and one-year overall survival (OS) was estimated using Kaplan–Meier methods.</div></div><div><h3>Results</h3><div>Among 524 patients, 178 (34 %) did not undergo surgery. Non-surgical management was independently associated with age ≥ 80 years, stage IIIA disease, poorer ECOG performance status, comorbidities, and reduced or unregistered DLco, whereas FEV1 and DLco ≥ 80 % predicted were negatively associated. MDT justifications were low lung function or poor performance status (29.2 %), comorbidities (18.0 %), and N2 disease (11.8 %); in 19.7 % no justification was documented. No documentation of preoperative exercise testing was identified. One-year OS was higher after surgery than no surgery (95.7 % vs. 82.0 %), unadjusted.</div></div><div><h3>Conclusions</h3><div>One third of patients with stage I–IIIA NSCLC were treated without surgery, mainly due to impaired functional status, comorbidity, or advanced stage. The absence of documented exercise testing highlights a gap between guideline recommendations and clinical practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116246"},"PeriodicalIF":7.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.ejca.2026.116224
A. Addeo , M. Früh
{"title":"Corrigendum to “Thoracic radiotherapy plus maintenance durvalumab after first line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ES-SCLC) - A multicenter single arm open label phase II trial (SAKK 15/19)” [Eur J Cancer 2025 Nov 29:232:116138]","authors":"A. Addeo , M. Früh","doi":"10.1016/j.ejca.2026.116224","DOIUrl":"10.1016/j.ejca.2026.116224","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116224"},"PeriodicalIF":7.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.ejca.2026.116230
Alessandra Spata , Joana M. Ribeiro , Paolo Vigneri , Alberto Zambelli , Jean Zeghondy , Chayma Bousrih , Thomas Grinda , Alessandro Viansone , Alexandre J. Vivanti , Michaël Grynberg , Bruno Achutti Duso , Fabrice André , Barbara Pistilli , Elie Rassy
Pregnancy-Associated Breast Cancer (PABC) accounts for pregnancy-related breast cancer (PrBC), occurring during pregnancy and the first postpartum year, and postpartum breast cancer (PPBC), arising up to 5–10 years after childbirth. It represents an increasingly oncological challenge as delayed childbearing trends extend maternal reproductive age. Occurring in approximately 1:3000 pregnancies, PABC accounts for 0.2–3.8 % of all breast cancer cases. PABC is often associated with aggressive clinic-biological characteristics, including higher prevalence of triple-negative subtypes, increased lymph node involvement, and more frequent advanced-stage presentation compared to age-matched non-pregnant controls. The complex mammary microenvironment during pregnancy, lactation, and postpartum involution undergoes extensive hormonal-driven remodeling that creates a biphasic landscape, initially providing a permissive environment for carcinogenesis while conferring long-term protective effects. The molecular mechanisms underlying this transformation remain incompletely understood and represent an active area of investigation. Molecular profiling of PABC reveals enhanced proliferative signaling pathways, metabolic reprogramming, tumor-promoting inflammatory responses, and compromised DNA damage repair mechanisms. While PABC shares similar genomic architecture with non-pregnancy-associated breast cancers, distinct gene expression signatures have been identified that may contribute to its aggressive phenotype. This comprehensive review examines the physiological breast changes occurring throughout the reproductive cycle and their relationship to PABC carcinogenesis. We analyze the molecular profile and clinicopathological features that distinguish PABC from conventional breast cancer, while addressing the therapeutic challenges posed by fetal safety considerations. Additionally, we evaluate the safety profiles of novel therapeutic agents during pregnancy and lactation, highlighting the critical need for new pregnancy-compatible treatment strategies.
{"title":"Comprehensive review of pregnancy associated breast cancer: Clinical features, molecular characteristics and novel therapies","authors":"Alessandra Spata , Joana M. Ribeiro , Paolo Vigneri , Alberto Zambelli , Jean Zeghondy , Chayma Bousrih , Thomas Grinda , Alessandro Viansone , Alexandre J. Vivanti , Michaël Grynberg , Bruno Achutti Duso , Fabrice André , Barbara Pistilli , Elie Rassy","doi":"10.1016/j.ejca.2026.116230","DOIUrl":"10.1016/j.ejca.2026.116230","url":null,"abstract":"<div><div>Pregnancy-Associated Breast Cancer (PABC) accounts for pregnancy-related breast cancer (PrBC), occurring during pregnancy and the first postpartum year, and postpartum breast cancer (PPBC), arising up to 5–10 years after childbirth. It represents an increasingly oncological challenge as delayed childbearing trends extend maternal reproductive age. Occurring in approximately 1:3000 pregnancies, PABC accounts for 0.2–3.8 % of all breast cancer cases. PABC is often associated with aggressive clinic-biological characteristics, including higher prevalence of triple-negative subtypes, increased lymph node involvement, and more frequent advanced-stage presentation compared to age-matched non-pregnant controls. The complex mammary microenvironment during pregnancy, lactation, and postpartum involution undergoes extensive hormonal-driven remodeling that creates a biphasic landscape, initially providing a permissive environment for carcinogenesis while conferring long-term protective effects. The molecular mechanisms underlying this transformation remain incompletely understood and represent an active area of investigation. Molecular profiling of PABC reveals enhanced proliferative signaling pathways, metabolic reprogramming, tumor-promoting inflammatory responses, and compromised DNA damage repair mechanisms. While PABC shares similar genomic architecture with non-pregnancy-associated breast cancers, distinct gene expression signatures have been identified that may contribute to its aggressive phenotype. This comprehensive review examines the physiological breast changes occurring throughout the reproductive cycle and their relationship to PABC carcinogenesis. We analyze the molecular profile and clinicopathological features that distinguish PABC from conventional breast cancer, while addressing the therapeutic challenges posed by fetal safety considerations. Additionally, we evaluate the safety profiles of novel therapeutic agents during pregnancy and lactation, highlighting the critical need for new pregnancy-compatible treatment strategies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116230"},"PeriodicalIF":7.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-small cell lung cancer (NSCLC) patients with comorbid interstitial pneumonia (IP) are at high risk for drug-induced pneumonitis, and previous reports suggest a lower frequency of common driver mutations such as EGFR. This may discourage genetic testing, potentially overlooking prevalent, targetable mutations like KRAS, BRAF, and MET. This study aimed to elucidate the real-world status of genetic testing, the frequency of oncogenic drivers, and the safety and efficacy of targeted therapies in patients with NSCLC and comorbid IP.
Methods
This multicenter, retrospective study analyzed 1256 patients with advanced or recurrent NSCLC and comorbid chronic fibrosing IP from 37 Japanese institutions (Registry number: UMIN000055609).
Results
The rate of any genetic testing was 59.2 % (95 % confidence interval [CI], 56.5–62.0), with multigene testing performed in only 41.0 % (95 %CI, 38.3–43.8). Among patients with NSCLC undergoing multigene testing (N = 515), the most frequent mutations were KRAS (4.7 %; G12C, 1.9 %), followed by EGFR (2.9 %), BRAF V600E (1.6 %), and MET exon 14 skipping (1.6 %). The incidence of drug-induced pneumonitis was 0 % (0/6) for sotorasib, 50 % (4/8) for osimertinib, 33 % (1/3) for alectinib, and 25 % (1/4) for both dabrafenib plus trametinib and tepotinib. Patients with actionable oncogenic drivers receiving targeted therapy had the longest overall survival, followed by those not receiving it, and then driver-negative/unknown patients (median: 39.2, 24.0, and 13.8 months, respectively).
Conclusions
Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.
{"title":"Targeting driver mutations in lung cancer with interstitial pneumonia: A nationwide study in Japan","authors":"Satoshi Ikeda , Takashi Ogura , Toshihiro Misumi , Yasuhiko Nishioka , Seishu Hashimoto , Kazuya Ichikado , Aya Fukuizumi , Saori Takata , Taku Itoh , Yuki Sato , Kyoichi Okishio , Kazuhiro Yatera , Noriho Sakamoto , Motoyasu Kato , Ryota Kikuchi , Takayuki Honda , Naozumi Hashimoto , Koji Murakami , Takuma Isshiki , Mayuka Yamane , Kazuma Kishi","doi":"10.1016/j.ejca.2026.116232","DOIUrl":"10.1016/j.ejca.2026.116232","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-small cell lung cancer (NSCLC) patients with comorbid interstitial pneumonia (IP) are at high risk for drug-induced pneumonitis, and previous reports suggest a lower frequency of common driver mutations such as <em>EGFR</em>. This may discourage genetic testing, potentially overlooking prevalent, targetable mutations like <em>KRAS</em>, <em>BRAF</em>, and <em>MET</em>. This study aimed to elucidate the real-world status of genetic testing, the frequency of oncogenic drivers, and the safety and efficacy of targeted therapies in patients with NSCLC and comorbid IP.</div></div><div><h3>Methods</h3><div>This multicenter, retrospective study analyzed 1256 patients with advanced or recurrent NSCLC and comorbid chronic fibrosing IP from 37 Japanese institutions (Registry number: UMIN000055609).</div></div><div><h3>Results</h3><div>The rate of any genetic testing was 59.2 % (95 % confidence interval [CI], 56.5–62.0), with multigene testing performed in only 41.0 % (95 %CI, 38.3–43.8). Among patients with NSCLC undergoing multigene testing (N = 515), the most frequent mutations were <em>KRAS</em> (4.7 %; G12C, 1.9 %), followed by <em>EGFR</em> (2.9 %), <em>BRAF V600E</em> (1.6 %), and <em>MET exon 14 skipping</em> (1.6 %). The incidence of drug-induced pneumonitis was 0 % (0/6) for sotorasib, 50 % (4/8) for osimertinib, 33 % (1/3) for alectinib, and 25 % (1/4) for both dabrafenib plus trametinib and tepotinib. Patients with actionable oncogenic drivers receiving targeted therapy had the longest overall survival, followed by those not receiving it, and then driver-negative/unknown patients (median: 39.2, 24.0, and 13.8 months, respectively).</div></div><div><h3>Conclusions</h3><div>Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"235 ","pages":"Article 116232"},"PeriodicalIF":7.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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