Pub Date : 2025-11-29DOI: 10.1016/j.ejca.2025.116138
Alfredo Addeo , Daniel Dietrich , Nicolas Mach , Michael Thomas Mark , Markus Joerger , Patrizia Froesch , Martina Imbimbo , David König , Eugenio Fernandez , Annalea Patzen , Hansjörg Vees , Cristina Picardi , Martin Früh
Background
Small cell lung cancer (SCLC) is an aggressive tumour type accounting for 10–15 % of lung cancers. The role of thoracic radiotherapy (TRT) in extensive stage SCLC (ES_SCLC) in the era of checkpoint inhibitors (CPIs) is undefined.
Methods
SAKK 15–19 is a national, multicenter, single-arm prospective phase II study evaluating consolidative TRT after standard first-line chemotherapy plus durvalumab in ES-SCLC. Patients (pts) with confirmed ES-SCLC and ECOG ≤ 1 received carboplatin AUC5 (day 1), etoposide 100 mg/m² (days 1–3) and durvalumab 1500 mg (day 1) for 4 cycles, followed by maintenance durvalumab every 4 weeks for up to 2 years in pts without progression. TRT (39 Gy in 13 fractions over 2.5 weeks) was delivered within 5 weeks after chemoimmunotherapy. Prophylactic cranial irradiation was permitted. The primary endpoint was 12-month progression-free rate (PFR); secondary endpoints included progression-free survival (PFS), response rate and overall survival (OS). The study aimed at a 12-month PFR ≥ 25 % (H1) vs. ≤ 12.5 %.
Results
Forty-six pts were enrolled; 37 % had ECOG 0, 30 % had asymptomatic brain metastases. At 29-month follow-up, the 12-month PFR was 15.6 (95 % CI 7–27.5), median PFS 6.4 months (95 % CI 4.8–7.2) and median OS 15.0 months (95 % CI 10.2–22.0). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 23.9 % of pts, mainly neutropenia (23.9 %) and thrombocytopenia (8.4 %). One pt (2 %) had grade 5 sepsis; no severe TRT-related toxicities were observed.
Conclusions
Adding consolidative TRT after chemotherapy plus durvalumab in ES-SCLC didn’t meet the primary endpoint of the expected 12-month PFR. No additional severe toxicities from TRT were observed. Ongoing larger Phase III trials, including RAPTOR (LNRG LU007), will further define TRT’s role in this setting.
{"title":"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)","authors":"Alfredo Addeo , Daniel Dietrich , Nicolas Mach , Michael Thomas Mark , Markus Joerger , Patrizia Froesch , Martina Imbimbo , David König , Eugenio Fernandez , Annalea Patzen , Hansjörg Vees , Cristina Picardi , Martin Früh","doi":"10.1016/j.ejca.2025.116138","DOIUrl":"10.1016/j.ejca.2025.116138","url":null,"abstract":"<div><h3>Background</h3><div>Small cell lung cancer (SCLC) is an aggressive tumour type accounting for 10–15 % of lung cancers. The role of thoracic radiotherapy (TRT) in extensive stage SCLC (ES_SCLC) in the era of checkpoint inhibitors (CPIs) is undefined.</div></div><div><h3>Methods</h3><div>SAKK 15–19 is a national, multicenter, single-arm prospective phase II study evaluating consolidative TRT after standard first-line chemotherapy plus durvalumab in ES-SCLC. Patients (pts) with confirmed ES-SCLC and ECOG ≤ 1 received carboplatin AUC5 (day 1), etoposide 100 mg/m² (days 1–3) and durvalumab 1500 mg (day 1) for 4 cycles, followed by maintenance durvalumab every 4 weeks for up to 2 years in pts without progression. TRT (39 Gy in 13 fractions over 2.5 weeks) was delivered within 5 weeks after chemoimmunotherapy. Prophylactic cranial irradiation was permitted. The primary endpoint was 12-month progression-free rate (PFR); secondary endpoints included progression-free survival (PFS), response rate and overall survival (OS). The study aimed at a 12-month PFR ≥ 25 % (H1) vs. ≤ 12.5 %.</div></div><div><h3>Results</h3><div>Forty-six pts were enrolled; 37 % had ECOG 0, 30 % had asymptomatic brain metastases. At 29-month follow-up, the 12-month PFR was 15.6 (95 % CI 7–27.5), median PFS 6.4 months (95 % CI 4.8–7.2) and median OS 15.0 months (95 % CI 10.2–22.0). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 23.9 % of pts, mainly neutropenia (23.9 %) and thrombocytopenia (8.4 %). One pt (2 %) had grade 5 sepsis; no severe TRT-related toxicities were observed.</div></div><div><h3>Conclusions</h3><div>Adding consolidative TRT after chemotherapy plus durvalumab in ES-SCLC didn’t meet the primary endpoint of the expected 12-month PFR. No additional severe toxicities from TRT were observed. Ongoing larger Phase III trials, including RAPTOR (LNRG LU007), will further define TRT’s role in this setting.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116138"},"PeriodicalIF":7.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676906","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 : 2025-11-29DOI: 10.1016/j.ejca.2025.116160
Mélanie Debiais , Anthony Tarabay , Sarah Blanchet-Deverly , Géraldine M. Camilleri , Alexandre Megherbi , Laura Diebakate , Maxime Collin , Antoine Hollebecque , Cristina Smolenschi , Marine Valéry , Thomas Pudlarz , Alina Cristina Fuerea , Valérie Boige , Michel Ducreux , Alice Boilève
Background
Metastatic pancreatic adenocarcinoma (mPDAC) has a poor prognosis. FOLFIRINOX (FFX) and gemcitabine nab-paclitaxel (GN) are the preferred first line (L1) regimens. We evaluated real-world outcomes of L1 therapies.
Methods
Retrospective analysis of all patients who received L1 chemotherapy for mPDAC between 2010 and 2024 at a single academic comprehensive cancer center.
Results
A total of 1012 patients were included: 48 % women, median age 63 years, 91 % ECOG 0–1. Synchronous metastases occurred in 66 % of patients. Liver (67 %), lung (20 %) and peritoneum (20 %) were the most frequent sites of metastasis.
L1 regimens were FFX (n = 621, 61 %), gemcitabine (Gem) (141, 14 %), GN (78, 8 %), and others (n = 172, 17 %). Compared with GN, FFX recipients were younger (61 vs 65 years, p < 0.0001) with better ECOG (≥ 2 in 4 % vs 13 %, p < 0.0001).
Median OS was 14.5 months (95 %CI [13.3–15.8]) with FFX, 12.4 [9.4–21.9] with GN, 7.9 [6.5–10.7] with Gem and 9.2 [7.2–13.1] with others (p < 0.0001). Respective median PFS were 7.0 months [95 %CI: 6.5–7.9], 5.4 [4.0–8.3], 4.9 [3.6–6.0] and 5.6 [3.6–7.0] (p < 0.05).
Conclusions
In this large real-world cohort, FFX was associated with superior response rate, PFS, and OS compared with other L1 regimens, supporting its use as standard first-line therapy for mPDAC.
{"title":"Metastatic pancreatic adenocarcinoma: Real-world efficacy of first line treatment","authors":"Mélanie Debiais , Anthony Tarabay , Sarah Blanchet-Deverly , Géraldine M. Camilleri , Alexandre Megherbi , Laura Diebakate , Maxime Collin , Antoine Hollebecque , Cristina Smolenschi , Marine Valéry , Thomas Pudlarz , Alina Cristina Fuerea , Valérie Boige , Michel Ducreux , Alice Boilève","doi":"10.1016/j.ejca.2025.116160","DOIUrl":"10.1016/j.ejca.2025.116160","url":null,"abstract":"<div><h3>Background</h3><div>Metastatic pancreatic adenocarcinoma (mPDAC) has a poor prognosis. FOLFIRINOX (FFX) and gemcitabine nab-paclitaxel (GN) are the preferred first line (L1) regimens. We evaluated real-world outcomes of L1 therapies.</div></div><div><h3>Methods</h3><div>Retrospective analysis of all patients who received L1 chemotherapy for mPDAC between 2010 and 2024 at a single academic comprehensive cancer center.</div></div><div><h3>Results</h3><div>A total of 1012 patients were included: 48 % women, median age 63 years, 91 % ECOG 0–1. Synchronous metastases occurred in 66 % of patients. Liver (67 %), lung (20 %) and peritoneum (20 %) were the most frequent sites of metastasis.</div><div>L1 regimens were FFX (n = 621, 61 %), gemcitabine (Gem) (141, 14 %), GN (78, 8 %), and others (n = 172, 17 %). Compared with GN, FFX recipients were younger (61 vs 65 years, p < 0.0001) with better ECOG (≥ 2 in 4 % vs 13 %, p < 0.0001).</div><div>Median OS was 14.5 months (95 %CI [13.3–15.8]) with FFX, 12.4 [9.4–21.9] with GN, 7.9 [6.5–10.7] with Gem and 9.2 [7.2–13.1] with others (p < 0.0001). Respective median PFS were 7.0 months [95 %CI: 6.5–7.9], 5.4 [4.0–8.3], 4.9 [3.6–6.0] and 5.6 [3.6–7.0] (p < 0.05).</div></div><div><h3>Conclusions</h3><div>In this large real-world cohort, FFX was associated with superior response rate, PFS, and OS compared with other L1 regimens, supporting its use as standard first-line therapy for mPDAC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116160"},"PeriodicalIF":7.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676922","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 : 2025-11-28DOI: 10.1016/j.ejca.2025.116120
Damien Roos-Weil , Cécile Tomowiak , Stéphanie Poulain , Florence Nguyen-Khac , Florian Bouclet , Marine Armand , Thérèse Aurran , Eric Durot , David Ghez , Bénédicte Hivert , Kamel Laribi , Magali Le Garff Tavernier , Stéphane Lepretre , Lydia Montes , Amine Moslemi , Laurence Simon , Véronique Leblond , Pierre Morel , Olivier Tournilhac
Waldenström’s macroglobulinemia (WM) is a rare, indolent B-cell lymphoma that predominantly affects older adults. In recent years, significant progress has been made in understanding its pathogenesis, identifying relevant biomarkers, and developing novel therapeutic approaches to complement traditional chemoimmunotherapy—collectively reshaping the management landscape of WM. In this article, we provide comprehensive, evidence-based recommendations for the diagnosis, molecular evaluation, and treatment of WM, including strategies for both frontline and relapsed disease. These guidelines are informed by the latest clinical research, expert consensus, and current practice standards, with the goal of equipping clinicians with a practical and effective framework for delivering optimal care to patients with WM.
{"title":"Waldenström’s macroglobulinemia: The LYSA pragmatic guidelines","authors":"Damien Roos-Weil , Cécile Tomowiak , Stéphanie Poulain , Florence Nguyen-Khac , Florian Bouclet , Marine Armand , Thérèse Aurran , Eric Durot , David Ghez , Bénédicte Hivert , Kamel Laribi , Magali Le Garff Tavernier , Stéphane Lepretre , Lydia Montes , Amine Moslemi , Laurence Simon , Véronique Leblond , Pierre Morel , Olivier Tournilhac","doi":"10.1016/j.ejca.2025.116120","DOIUrl":"10.1016/j.ejca.2025.116120","url":null,"abstract":"<div><div>Waldenström’s macroglobulinemia (WM) is a rare, indolent B-cell lymphoma that predominantly affects older adults. In recent years, significant progress has been made in understanding its pathogenesis, identifying relevant biomarkers, and developing novel therapeutic approaches to complement traditional chemoimmunotherapy—collectively reshaping the management landscape of WM. In this article, we provide comprehensive, evidence-based recommendations for the diagnosis, molecular evaluation, and treatment of WM, including strategies for both frontline and relapsed disease. These guidelines are informed by the latest clinical research, expert consensus, and current practice standards, with the goal of equipping clinicians with a practical and effective framework for delivering optimal care to patients with WM.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116120"},"PeriodicalIF":7.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681642","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 : 2025-11-25DOI: 10.1016/j.ejca.2025.116135
Alexander HR Varey, Serigne N. Lo, John F. Thompson
{"title":"Letter Re: Critical evaluation of sentinel lymph node biopsy in pT1b and pT2a melanoma patients: A nationwide population-based study","authors":"Alexander HR Varey, Serigne N. Lo, John F. Thompson","doi":"10.1016/j.ejca.2025.116135","DOIUrl":"10.1016/j.ejca.2025.116135","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116135"},"PeriodicalIF":7.1,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647785","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 : 2025-11-22DOI: 10.1016/j.ejca.2025.116133
Kathrin Heinrich , Sebastian Stintzing , Ludwig Fischer von Weikersthal , Thomas Decker , Alexander Kiani , Florian Kaiser , Salah-Eddin Al-Batran , Tobias Heintges , Christoph Lerchenmüller , Christoph Kahl , Gernot Seipelt , Frank Kullmann , Markus Moehler , Werner Scheithauer , Andreas Jung , Julian W. Holch , Swantje Held , Dominik Paul Modest , Volker Heinemann
Background
Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespectively of sex. However, differences relating to safety and efficacy in the treatment of mCRC between male and female patients are of growing interest.
Methods
The randomized FIRE-3 study compared first-line treatment with folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) plus cetuximab to FOLFIRI plus bevacizumab in patients with RAS wildtype (RAS WT) mCRC. The present analysis focusses on the impact of sex and primary tumor (PT) sidedness on outcome parameters.
Results
Of 352 patients with RAS WT tumors, 249 (71 %) were male and 103 (29 %) female.
In male patients with left-sided RAS/BRAF WT tumors, a significant benefit from cetuximab was noted with regard to ORR (OR 1.15; P = 0.035) and OS (0.66; P = 0.010), while in right-sided patients cetuximab improved ORR (OR 2.92) and had no significant effect on PFS or OS.
In female patients with left-sided, RAS/BRAF WT PT, a comparable effect of cetuximab versus bevacizumab was observed with regard to ORR (OR 1.05; P > 0.999), while a numerical OS benefit was noted in the cetuximab-arm (HR 0.78; P = 0.385).
By contrast, in female patients with right-sided PT, a clearly detrimental effect of cetuximab-based therapy was observed for ORR (OR 0.44; P = 0.617), PFS (HR 4.95; P = 0.005), and OS (HR 2.58; P = 0.080).
In the bevacizumab arm, neutropenia grade ≥ 3 was more frequent in female versus male patients (30.6 % versus 18.3 %; P = 0.063). Otherwise, there was no significant difference of grade ≥ 3 adverse events between male and female patients.
Conclusions
The exploratory analysis of FIRE-3 suggests that the efficacy of cetuximab combined with FOLFIRI in RAS wild-type mCRC is related to sex and primary tumor sidedness. The results support the inclusion of patient sex into the design of future trials.
背景：转移性结直肠癌（mCRC）的临床试验通常是不分性别进行的。然而，男性和女性患者在治疗mCRC的安全性和有效性方面的差异越来越引起人们的兴趣。方法：在随机的火-3研究中，比较一线治疗的叶酸、5-氟尿嘧啶和伊立替康（FOLFIRI）加西妥昔单抗与FOLFIRI加贝伐单抗对RAS野生型（RAS WT） mCRC患者的疗效。目前的分析集中在性别和原发肿瘤（PT）侧性对结果参数的影响。结果352例RAS WT肿瘤患者中，男性249例（71 %），女性103例（29 %）。在男性左侧RAS/BRAF WT肿瘤患者中，西妥昔单抗在ORR （OR 1.15; P = 0.035）和OS （0.66; P = 0.010）方面有显著益处，而在右侧患者中，西妥昔单抗改善了ORR (OR 2.92)，对PFS或OS没有显著影响。在女性左侧RAS/BRAF WT PT患者中，观察到西妥昔单抗与贝伐单抗在ORR方面的相当效果（OR 1.05; P >； 0.999），而西妥昔单抗组的数值OS获益（HR 0.78; P = 0.385）。相反，在女性右侧PT患者中，以西妥昔单抗为基础的治疗对ORR （OR 0.44, P = 0.617）、PFS （HR 4.95, P = 0.005）和OS （HR 2.58, P = 0.080）有明显的不利影响。在贝伐单抗组中，中性粒细胞减少等级≥ 3的女性患者比男性患者更常见（30.6 %对18.3 %;P = 0.063）。除此之外，男女患者≥ 3级不良事件发生率无显著差异。结论FIRE-3的探索性分析提示西妥昔单抗联合FOLFIRI治疗RAS野生型mCRC的疗效与性别和原发肿瘤的侧性有关。结果支持将患者性别纳入未来试验的设计。
{"title":"Impact of sex on efficacy and safety of 1st-line treatment with FOLFIRI plus cetuximab or bevacizumab in RAS/BRAF wildtype metastatic colorectal cancer – A subgroup analysis of the FIRE-3 (AIO KRK-0306) trial","authors":"Kathrin Heinrich , Sebastian Stintzing , Ludwig Fischer von Weikersthal , Thomas Decker , Alexander Kiani , Florian Kaiser , Salah-Eddin Al-Batran , Tobias Heintges , Christoph Lerchenmüller , Christoph Kahl , Gernot Seipelt , Frank Kullmann , Markus Moehler , Werner Scheithauer , Andreas Jung , Julian W. Holch , Swantje Held , Dominik Paul Modest , Volker Heinemann","doi":"10.1016/j.ejca.2025.116133","DOIUrl":"10.1016/j.ejca.2025.116133","url":null,"abstract":"<div><h3>Background</h3><div>Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespectively of sex. However, differences relating to safety and efficacy in the treatment of mCRC between male and female patients are of growing interest.</div></div><div><h3>Methods</h3><div>The randomized FIRE-3 study compared first-line treatment with folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) plus cetuximab to FOLFIRI plus bevacizumab in patients with <em>RAS</em> wildtype (<em>RAS</em> WT) mCRC. The present analysis focusses on the impact of sex and primary tumor (PT) sidedness on outcome parameters.</div></div><div><h3>Results</h3><div>Of 352 patients with <em>RAS</em> WT tumors, 249 (71 %) were male and 103 (29 %) female.</div><div>In male patients with left-sided <em>RAS/BRAF</em> WT tumors, a significant benefit from cetuximab was noted with regard to ORR (OR 1.15; P = 0.035) and OS (0.66; P = 0.010), while in right-sided patients cetuximab improved ORR (OR 2.92) and had no significant effect on PFS or OS.</div><div>In female patients with left-sided, <em>RAS/BRAF</em> WT PT, a comparable effect of cetuximab versus bevacizumab was observed with regard to ORR (OR 1.05; P > 0.999), while a numerical OS benefit was noted in the cetuximab-arm (HR 0.78; P = 0.385).</div><div>By contrast, in female patients with right-sided PT, a clearly detrimental effect of cetuximab-based therapy was observed for ORR (OR 0.44; P = 0.617), PFS (HR 4.95; P = 0.005), and OS (HR 2.58; P = 0.080).</div><div>In the bevacizumab arm, neutropenia grade ≥ 3 was more frequent in female versus male patients (30.6 % versus 18.3 %; P = 0.063). Otherwise, there was no significant difference of grade ≥ 3 adverse events between male and female patients.</div></div><div><h3>Conclusions</h3><div>The exploratory analysis of FIRE-3 suggests that the efficacy of cetuximab combined with FOLFIRI in <em>RAS</em> wild-type mCRC is related to sex and primary tumor sidedness. The results support the inclusion of patient sex into the design of future trials.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116133"},"PeriodicalIF":7.1,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615944","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 : 2025-11-22DOI: 10.1016/j.ejca.2025.116137
Beibei Jiang , Harriet L. Lancaster , Michael P.A. Davies , Jan-Willem C. Gratama , Mario Silva , Daiwei Han , Jaeyoun Yi , Carlijn M. van der Aalst , Anand Devaraj , Marjolein A. Heuvelmans , John K. Field , Matthijs Oudkerk
Aim
To validate an artificial intelligence (AI) software for automated assessment of nodule growth by volume doubling time measurement (VDT) on protocol-mandated follow-up low-dose CT (LDCT) scans from the UK lung cancer screening (UKLS) trial.
Methods
This validation study included 710 UKLS participants with 939 LDCT follow-up scans (361 3-month and 578 12-month). Follow-up scans were assessed independently by both AI and human readers. A positive finding warranting referral was defined as the largest nodule with a solid component ≥ 100 mm3 showing VDT ≤ 400 days at follow-up. Performance was benchmarked against the European expert panel (reference standard) and then the histological outcomes (gold standard).
Results
Against the expert panel, AI achieved the lowest 3-month negative misclassification (NM) rate (1/11, 9.1 %), versus human readers (range: 18.2–63.6 %). AI’s positive misclassification (PM) rate was initially 7.8 % (28/361) at 3 months but decreased to 0.9 % (5/578) at 12 months. Against histological outcomes of 9 screen-detected lung cancers, AI identified VDT ≤ 400 days in all 4 cancers also deemed positive by the expert panel at the earliest 3-month follow-up, while human readers missed or delayed referrals in 1–3 of these. AI also identified VDT ≤ 400 days in 3 of 5 cancers that the panel classified as negative, primarily due to their sub-threshold volume (<100mm³).
Conclusions
The automated AI system showed strong VDT assessment performance in follow-up screening, outperforming human readers in the early identification of rapid growth in histologically-confirmed cancers, thus supporting its potential to enhance risk stratification and facilitate earlier lung cancer detection.
{"title":"AI performance for nodule volume doubling time in the follow-up of the UKLS lung cancer screening study compared to expert consensus and histological validation","authors":"Beibei Jiang , Harriet L. Lancaster , Michael P.A. Davies , Jan-Willem C. Gratama , Mario Silva , Daiwei Han , Jaeyoun Yi , Carlijn M. van der Aalst , Anand Devaraj , Marjolein A. Heuvelmans , John K. Field , Matthijs Oudkerk","doi":"10.1016/j.ejca.2025.116137","DOIUrl":"10.1016/j.ejca.2025.116137","url":null,"abstract":"<div><h3>Aim</h3><div>To validate an artificial intelligence (AI) software for automated assessment of nodule growth by volume doubling time measurement (VDT) on protocol-mandated follow-up low-dose CT (LDCT) scans from the UK lung cancer screening (UKLS) trial.</div></div><div><h3>Methods</h3><div>This validation study included 710 UKLS participants with 939 LDCT follow-up scans (361 3-month and 578 12-month). Follow-up scans were assessed independently by both AI and human readers. A positive finding warranting referral was defined as the largest nodule with a solid component ≥ 100 mm<sup>3</sup> showing VDT ≤ 400 days at follow-up. Performance was benchmarked against the European expert panel (reference standard) and then the histological outcomes (gold standard).</div></div><div><h3>Results</h3><div>Against the expert panel, AI achieved the lowest 3-month negative misclassification (NM) rate (1/11, 9.1 %), versus human readers (range: 18.2–63.6 %). AI’s positive misclassification (PM) rate was initially 7.8 % (28/361) at 3 months but decreased to 0.9 % (5/578) at 12 months. Against histological outcomes of 9 screen-detected lung cancers, AI identified VDT ≤ 400 days in all 4 cancers also deemed positive by the expert panel at the earliest 3-month follow-up, while human readers missed or delayed referrals in 1–3 of these. AI also identified VDT ≤ 400 days in 3 of 5 cancers that the panel classified as negative, primarily due to their sub-threshold volume (<100mm³).</div></div><div><h3>Conclusions</h3><div>The automated AI system showed strong VDT assessment performance in follow-up screening, outperforming human readers in the early identification of rapid growth in histologically-confirmed cancers, thus supporting its potential to enhance risk stratification and facilitate earlier lung cancer detection.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116137"},"PeriodicalIF":7.1,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615943","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 : 2025-11-21DOI: 10.1016/j.ejca.2025.116136
Antonius W. Schurink, Robert C. Stassen, Astrid A.M. van der Veldt, Dirk J. Grünhagen
{"title":"Response to letter Re: Critical evaluation of sentinel lymph node biopsy in pT1b and pT2a melanoma patients: A nationwide population-based study","authors":"Antonius W. Schurink, Robert C. Stassen, Astrid A.M. van der Veldt, Dirk J. Grünhagen","doi":"10.1016/j.ejca.2025.116136","DOIUrl":"10.1016/j.ejca.2025.116136","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116136"},"PeriodicalIF":7.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647791","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 : 2025-11-21DOI: 10.1016/j.ejca.2025.116134
Patricia Blickle , Lisa M. Storz , Martina E. Schmidt , Jens Lehmann , Micha J. Pilz , Marlena Milzer , Imad Maatouk , Johannes M. Giesinger , Karen Steindorf
Objective
Cancer-related fatigue is among the most burdensome side-effects of cancer and its treatment. The Fatigue Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-FA12) is a widely used measure to assess fatigue multidimensionally. However, interpretation of its scores can be challenging. Therefore, thresholds for clinical importance (TCI) for the three fatigue dimensions assessed by this questionnaire were developed.
Methods
A standardized approach was followed for the derivation of TCI. Three anchor items regarding limitations in daily life, need for help/care, and worries to the patient, their partner and/or family were completed by patients with various cancer types, in addition to the EORTC QLQ-FA12. Receiver Operating Characteristic curves and Youden's J were estimated to determine the most suitable TCIs.
Results
Complete data of the EORTC QLQ-FA12 and the anchor items were available for N = 1111 patients (age 67.2 ± 12.6 years; 61.2 % female) from two observational studies. The derived TCIs for the physical, emotional, and cognitive fatigue scores (scale 0–100) were 43, 28, and 25, respectively. Subgroup analyses, categorized by gender and age, yielded consistent results. The sensitivity of the thresholds ranged from 0.87 to 0.94; the specificity from 0.67 to 0.80. Areas under the curve were all ≥ 0.89.
Conclusion
The analyses established TCIs for the three dimensions of the EORTC QLQ-FA12. TCIs can be used in research and clinical practice to facilitate interpretation of individual patient scores at a single point in time. TCIs may indicate which patients experience a fatigue level that warrants additional clinical attention.
{"title":"Facilitating the interpretation of the multidimensional EORTC QLQ-FA12 fatigue questionnaire: Establishing thresholds for clinical importance","authors":"Patricia Blickle , Lisa M. Storz , Martina E. Schmidt , Jens Lehmann , Micha J. Pilz , Marlena Milzer , Imad Maatouk , Johannes M. Giesinger , Karen Steindorf","doi":"10.1016/j.ejca.2025.116134","DOIUrl":"10.1016/j.ejca.2025.116134","url":null,"abstract":"<div><h3>Objective</h3><div>Cancer-related fatigue is among the most burdensome side-effects of cancer and its treatment. The Fatigue Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-FA12) is a widely used measure to assess fatigue multidimensionally. However, interpretation of its scores can be challenging. Therefore, thresholds for clinical importance (TCI) for the three fatigue dimensions assessed by this questionnaire were developed.</div></div><div><h3>Methods</h3><div>A standardized approach was followed for the derivation of TCI. Three anchor items regarding limitations in daily life, need for help/care, and worries to the patient, their partner and/or family were completed by patients with various cancer types, in addition to the EORTC QLQ-FA12. Receiver Operating Characteristic curves and Youden's J were estimated to determine the most suitable TCIs.</div></div><div><h3>Results</h3><div>Complete data of the EORTC QLQ-FA12 and the anchor items were available for <em>N</em> = 1111 patients (age 67.2 ± 12.6 years; 61.2 % female) from two observational studies. The derived TCIs for the physical, emotional, and cognitive fatigue scores (scale 0–100) were 43, 28, and 25, respectively. Subgroup analyses, categorized by gender and age, yielded consistent results. The sensitivity of the thresholds ranged from 0.87 to 0.94; the specificity from 0.67 to 0.80. Areas under the curve were all ≥ 0.89.</div></div><div><h3>Conclusion</h3><div>The analyses established TCIs for the three dimensions of the EORTC QLQ-FA12. TCIs can be used in research and clinical practice to facilitate interpretation of individual patient scores at a single point in time. TCIs may indicate which patients experience a fatigue level that warrants additional clinical attention.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116134"},"PeriodicalIF":7.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615942","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 : 2025-11-21DOI: 10.1016/j.ejca.2025.116131
Ursula M. Vogl , Sara Merler , Antonio Angrisani , Fabio Turco , Ian D. Davis , Jason A. Efstathiou , Karim Fizazi , Nicholas D. James , Neal Shore , Eric J. Small , Matthew R. Smith , Christopher J. Sweeney , Bertrand Tombal , Thomas Zilli , Ken Herrmann , Aurelius Omlin , Silke Gillessen , on behalf of the APCCC 2024 expert panel
Background
The Advanced Prostate Cancer Conference (APCCC) addresses many aspects of advanced prostate cancer management, including areas lacking high-level evidence. The 2024 APCCC conference defined consensus as ≥ 75 % agreement among the expert panellists, which was not reached for many questions.
Methods
An invited panel of 120 experts (“panellists”) voted via a web-based survey on 183 multiple-choice questions prior to the APCCC 2024 conference. Consensus was not reached for 143 (78 %) of the questions, highlighting persistent evidence gaps. We reviewed clinicaltrials.gov and clinicaltrialsregister.eu to identify relevant ongoing phase 3 trials in these areas of non-consensus.
Results
Numerous ongoing phase 3 trials were identified that may help address some of the gaps identified by expert voting. However, several topics without consensus are not currently being investigated in clinical trials.
Conclusions
Lack of consensus may stem from absent or limited high-level evidence, differing interpretations of existing data, or complete gaps in available data. The large number of questions without consensus at APCCC 2024 underscores the complexity of advanced prostate cancer care and the urgent need for trials generating robust evidence to guide practice. Furthermore, ongoing progress to improve our understanding of prostate cancer disease biology, including the identification of novel therapeutic targets, will likely identify additional areas of uncertainty. This manuscript highlights key directions for research by mapping areas without consensus against the landscape of current clinical trials.
{"title":"A roadmap for future clinical research in advanced prostate cancer: Findings from the Advanced Prostate Cancer Consensus Conference (APCCC) 2024","authors":"Ursula M. Vogl , Sara Merler , Antonio Angrisani , Fabio Turco , Ian D. Davis , Jason A. Efstathiou , Karim Fizazi , Nicholas D. James , Neal Shore , Eric J. Small , Matthew R. Smith , Christopher J. Sweeney , Bertrand Tombal , Thomas Zilli , Ken Herrmann , Aurelius Omlin , Silke Gillessen , on behalf of the APCCC 2024 expert panel","doi":"10.1016/j.ejca.2025.116131","DOIUrl":"10.1016/j.ejca.2025.116131","url":null,"abstract":"<div><h3>Background</h3><div>The Advanced Prostate Cancer Conference (APCCC) addresses many aspects of advanced prostate cancer management, including areas lacking high-level evidence. The 2024 APCCC conference defined consensus as ≥ 75 % agreement among the expert panellists, which was not reached for many questions.</div></div><div><h3>Methods</h3><div>An invited panel of 120 experts (“panellists”) voted via a web-based survey on 183 multiple-choice questions prior to the APCCC 2024 conference. Consensus was not reached for 143 (78 %) of the questions, highlighting persistent evidence gaps. We reviewed clinicaltrials.gov and clinicaltrialsregister.eu to identify relevant ongoing phase 3 trials in these areas of non-consensus.</div></div><div><h3>Results</h3><div>Numerous ongoing phase 3 trials were identified that may help address some of the gaps identified by expert voting. However, several topics without consensus are not currently being investigated in clinical trials.</div></div><div><h3>Conclusions</h3><div>Lack of consensus may stem from absent or limited high-level evidence, differing interpretations of existing data, or complete gaps in available data. The large number of questions without consensus at APCCC 2024 underscores the complexity of advanced prostate cancer care and the urgent need for trials generating robust evidence to guide practice. Furthermore, ongoing progress to improve our understanding of prostate cancer disease biology, including the identification of novel therapeutic targets, will likely identify additional areas of uncertainty. This manuscript highlights key directions for research by mapping areas without consensus against the landscape of current clinical trials.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"233 ","pages":"Article 116131"},"PeriodicalIF":7.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773941","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号