ESMO Gastrointestinal Oncology最新文献

{"title":"The South Australian 177Lu-DOTATATE peptide receptor radionuclide therapy service: an 11-year review of toxicity, health-related quality of life, and survival","authors":"L.M. Altus ,&nbsp;J.C. Forster ,&nbsp;J. Mercurio ,&nbsp;M. Kitchener ,&nbsp;N. Corsini ,&nbsp;M. Nenke ,&nbsp;T. Price ,&nbsp;D. Patel ,&nbsp;R. Chew ,&nbsp;D. Moffat ,&nbsp;S. Unger ,&nbsp;G. Cehic","doi":"10.1016/j.esmogo.2025.100146","DOIUrl":"10.1016/j.esmogo.2025.100146","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study was to audit clinical and patient-reported outcomes of patients treated with [¹⁷⁷Lu]-DOTA-octreotate (¹⁷⁷Lu-DOTATATE) at a single Australian centre over an 11-year period.</div></div><div><h3>Methods</h3><div>A retrospective analysis of 189 patients with metastatic or locally advanced neuroendocrine neoplasms or tumours (NENs/NETs) or other somatostatin receptor-positive tumour treated with ¹⁷⁷Lu-DOTATATE at The Queen Elizabeth Hospital from 2011 to 2022 was carried out. Toxicity, radiological response, health-related quality of life (hr-QoL), and overall survival (OS) were summarised.</div></div><div><h3>Results</h3><div>Gastroenteropancreatic (NET) origin accounted for 75% of cases. The median age of diagnosis was 59 years and median age at first cycle of ¹⁷⁷Lu-DOTATATE at The Queen Elizabeth Hospital was 64.7 years (range 16.5-92.6 years). Of the 182 patients who commenced induction peptide receptor radionuclide therapy (iPRRT), 143 (79%) completed four or five induction cycles. There were 52 patients who received retreatment PRRT (rPRRT). When radiological response was assessed following completion of a full iPRRT course (≥four cycles, 131 patients), radiologically stable disease was seen in 76% of patients. A completed hr-QoL questionnaire was available for 760 cycles (92%). Significant improvements were found across multiple domains after iPRRT. Eight patients (4.2%) developed a haematological malignancy. Renal function declined at long-term but not short-term follow-up. Median duration of follow-up was 37.6 months (range 0.0-134.6 months) with a median OS from first cycle of PRRT 48.4 months (95% confidence interval 42.5-57.3 months).</div></div><div><h3>Conclusion</h3><div>Patients with advanced NEN/NET or other somatostatin receptor-positive malignancies treated with ¹⁷⁷Lu-DOTATATE at our centre had improved hr-QoL following iPRRT, with comparable toxicity and OS to other centres.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous imaging to evaluate growth and drug responses of patient-derived colorectal tumouroids","authors":"B.C. Sakshaug ,&nbsp;E. Folkesson ,&nbsp;T.H. Haukaas ,&nbsp;M.S. Sigfúsdóttir ,&nbsp;H.H. Trøen ,&nbsp;S.B. Sperstad ,&nbsp;H.C.H. Bwanika ,&nbsp;C. Ringers ,&nbsp;I.A. Bergstrøm ,&nbsp;G. Klinkenberg ,&nbsp;T. Visnes ,&nbsp;Å. Flobak","doi":"10.1016/j.esmogo.2025.100137","DOIUrl":"10.1016/j.esmogo.2025.100137","url":null,"abstract":"<div><h3>Background</h3><div>The use of patient-derived tumouroids is expected to have major implications in preclinical drug testing and clinical decision support. Data acquisition from these samples in drug screens, however, is often limited by time-consuming procedures, scarce screening material, and destructive, single-parameter endpoint measurements.</div></div><div><h3>Design</h3><div>We seek to increase data collected from patient-derived tumouroids and here present a method for non-destructive, continuous image-based analysis of colorectal tumouroid growth and shape under chemotherapeutic perturbations, conducted within a clinically relevant timeframe.</div></div><div><h3>Results</h3><div>We assessed several readouts automatically derived from continuous imaging data and concluded that tumouroid growth, and the effect of growth inhibiting drugs, can be robustly monitored by measuring the total tumouroid-covered area in images. We also found that measures of average tumouroid size, diameter, and perimeter provide complementary insights.</div></div><div><h3>Conclusions</h3><div>Our tumouroid analysis method offers a strategy to maximise data extraction from non-destructive imaging techniques while preserving tumouroids for future research, all within a clinically relevant timeframe.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100137"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)","authors":"T. Shirakawa ,&nbsp;M. Shimokawa ,&nbsp;T. Otsuka ,&nbsp;Y. Shinohara ,&nbsp;K. Toyodome ,&nbsp;W. Kusano ,&nbsp;J. Nakazawa ,&nbsp;T. Kodama ,&nbsp;M. Kawahira ,&nbsp;H. Shimokawa ,&nbsp;T. Koike ,&nbsp;F. Koga ,&nbsp;S. Yunotani ,&nbsp;S. Nakashita ,&nbsp;N. Oza ,&nbsp;S. Noge ,&nbsp;K. Murayama ,&nbsp;H. Oda ,&nbsp;N. Mitsui ,&nbsp;R. Kawasaki ,&nbsp;K. Mitsugi","doi":"10.1016/j.esmogo.2025.100150","DOIUrl":"10.1016/j.esmogo.2025.100150","url":null,"abstract":"<div><h3>Background</h3><div>Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer (urPC). However, limited prospective clinical data on the efficacy and safety of NFF in a real-world setting have been presented. Therefore, we conducted this observational, real-world study to investigate the efficacy and safety of NFF.</div></div><div><h3>Patients and methods</h3><div>We collected prospective data of urPC patients treated with NFF in 17 hospitals in Japan from 2021 to 2023. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate, disease control rate, progression-free survival, dose intensity, and adverse events (AEs).</div></div><div><h3>Results</h3><div>NFF was administered to 150 patients with a mean age of 72 years. The median follow-up period was 7.2 months. All patients had previously received gemcitabine-based therapy. The median OS was 7.8 months; median progression-free survival was 3.7 months; median overall response rate was 11%; and median disease control rate was 56%. Median relative dose intensity was 72.7% with nanoliposomal irinotecan and 79.4% with fluorouracil. Grade 3/4 hematological and nonhematological AEs occurred in 52 and 70 patients, respectively. Neutropenia (28%) and anorexia (19%) were common grade 3/4 AEs. Subanalysis of patients with second-line and third- or later-line therapy demonstrated no significant difference in OS (7.4 versus 7.8 months, respectively; <em>P</em> = 0.88). Integrated analysis of the prospective and retrospective phases of the study showed that median OS was 8.0 months.</div></div><div><h3>Conclusions</h3><div>NFF has an appropriate efficacy and safety profile and is a candidate for second- or later-line therapy for urPC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is survival influenced by metastatic site in synchronous metastatic pancreatic adenocarcinoma (PDAC)? A prospective real-world BACAP study","authors":"E. Alouani ,&nbsp;C. Canivet ,&nbsp;B. Bournet ,&nbsp;L. Buscail ,&nbsp;J. Selves ,&nbsp;B. Napoleon ,&nbsp;L. Palazzo ,&nbsp;N. Flori ,&nbsp;P. Guibert ,&nbsp;A.-C. Brunac ,&nbsp;C. Maulat ,&nbsp;F. Muscari ,&nbsp;F.-Z. Mokrane ,&nbsp;S. Gourgou ,&nbsp;L. Roca ,&nbsp;R. Guimbaud ,&nbsp;N. Fares","doi":"10.1016/j.esmogo.2025.100144","DOIUrl":"10.1016/j.esmogo.2025.100144","url":null,"abstract":"<div><h3>Background</h3><div>Advanced pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis with a 5-year survival rate of 3%. While treated as an even population, previous retrospective studies suggested significantly different survival rates for patients with lung-only metastases when compared with other patients. This study aims to explore prospectively the difference in survival outcome based on initial site of metastases in synchronous metastatic PDAC.</div></div><div><h3>Patients and methods</h3><div>This is a prospective observational study including all adult patients with synchronous metastatic PDAC in BACAP (national Anatomo-Clinical Database on Pancreatic Adenocarcinoma). Data regarding patients’ demographics, tumor characteristics and survival outcomes were analyzed.</div></div><div><h3>Results</h3><div>Overall, 559 patients were included (52.8% male, mean age 69 years) of which 26 (4.7%), 65 (11.6%), 299 (53.5%) and 169 (30.2%) patients had lung-only, peritoneal-only, liver-only and multi-site metastases at diagnosis, respectively. The median overall survival (OS) was significantly different according to metastatic site (<em>P</em> &lt; 0.001) with a median OS for lung-only, peritoneum-only, liver-only and multi-site of 12.6 months [95% confidence interval (CI) 9.7-16.9 months], 8.6 months (95% CI 5.4-11.5 months), 7.9 months (95% CI 6.5-8.9 months) and 4.5 months (95% CI 3.9-5.8 months), respectively. The median progression-free survival (PFS) was also significantly different according to metastatic site (<em>P</em> &lt; 0.01) with a median PFS of 6.3 months (95% CI 2.7-9.1 months), 5.1 months (95% CI 3.7-6.2 months), 4.7 months (95% CI 3.3-5.7 months) and 3.2 months (95% CI 2.6-4.1 months), respectively.</div></div><div><h3>Conclusions</h3><div>Patients with lung-only metastases represented 4.7% of synchronous metastatic PDAC patients and exhibited improved survival. These results suggest that a subset of patients with synchronous metastatic PDAC could benefit from more aggressive locoregional treatments.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical efficacy of nivolumab-based therapy for HER2-negative diffuse-type advanced gastric or gastroesophageal junction adenocarcinoma with peritoneal dissemination","authors":"Y. Suzuki ,&nbsp;K. Shimozaki ,&nbsp;S. Udagawa ,&nbsp;K. Chin ,&nbsp;H. Osumi ,&nbsp;S. Fukuoka ,&nbsp;K. Yoshino ,&nbsp;M. Tamba ,&nbsp;T. Wakatsuki ,&nbsp;M. Ogura ,&nbsp;E. Shinozaki ,&nbsp;K. Yamaguchi ,&nbsp;A. Ooki","doi":"10.1016/j.esmogo.2025.100143","DOIUrl":"10.1016/j.esmogo.2025.100143","url":null,"abstract":"<div><h3>Background</h3><div>Diffuse-type gastric or gastroesophageal junctional cancers (DGC) often presents with peritoneal dissemination, leading to poor prognosis. This study assessed the efficacy of nivolumab-based therapies in patients with human epidermal growth factor receptor 2-negative DGC with peritoneal dissemination.</div></div><div><h3>Materials and methods</h3><div>This retrospective analysis included patients with DGC treated between June 2017 and March 2024. One cohort (<em>n</em> = 185) received nivolumab monotherapy as a third- or later-line treatment; the other (<em>n</em> = 117) received nivolumab plus chemotherapy as a first-line treatment.</div></div><div><h3>Results</h3><div>In the monotherapy cohort, 150 (81%) of 185 patients had peritoneal dissemination, which was significantly associated with worse progression-free survival (1.6 versus 2.5 months, <em>P</em> = 0.03) and overall survival (OS: 4.5 versus 7.2 months, <em>P</em> = 0.01) compared with those without peritoneal dissemination. In the first-line cohort, 74 (63%) of 117 patients had peritoneal dissemination. No significant differences were observed in progression-free survival (6.5 versus 9.6 months, <em>P</em> = 0.14) and OS (15.5 and 25.0 months, <em>P</em> = 0.47) between patients with and without peritoneal dissemination. Patients with peritoneal dissemination exhibited poor disease control in both cohorts, but those achieving complete or partial response had longer OS. The modified Glasgow Prognostic Score significantly impacted prognostic outcomes in both cohorts, while programmed death-ligand 1 status showed no statistical significance. Adverse events were manageable, with no treatment-related deaths.</div></div><div><h3>Conclusions</h3><div>First-line nivolumab plus chemotherapy demonstrated limited efficacy in human epidermal growth factor receptor 2-negative DGC with peritoneal dissemination but achieved a comparable OS to patients without peritoneal dissemination, supporting its potential as a first-line treatment.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic management of advanced HCC: an increasingly complex game","authors":"A. Martirena ,&nbsp;P. Lombardi ,&nbsp;D.J. Pinato ,&nbsp;L. Rimassa ,&nbsp;A. Lamarca","doi":"10.1016/j.esmogo.2025.100139","DOIUrl":"10.1016/j.esmogo.2025.100139","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100139"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluating population-level screening recommendations to address increasing early-onset colorectal cancer rates in Australia: a modelling study☆","authors":"J.-B. Lew ,&nbsp;J. Worthington ,&nbsp;H. Ge ,&nbsp;Q. Luo ,&nbsp;E. Feletto ,&nbsp;K. Canfell ,&nbsp;T. Price ,&nbsp;Cancer Council Australia Colorectal Cancer Screening Working Party","doi":"10.1016/j.esmogo.2025.100136","DOIUrl":"10.1016/j.esmogo.2025.100136","url":null,"abstract":"<div><h3>Background</h3><div>The National Bowel Cancer Screening Program (NBCSP) sends free immunochemical faecal occult blood tests (iFOBTs) to eligible Australians aged 50-74 every 2 years. Rising early-onset colorectal cancer (CRC) rates in people under 50 have raised questions around optimising the NBCSP, contributing to the rationale for updating Australian CRC screening guidelines. To support this, alternative screening age ranges and approaches were evaluated.</div></div><div><h3>Methods</h3><div>A microsimulation model was used to estimate the impact of 2-yearly iFOBT screening starting at age 40, 45 or 50 and/or stopping at 74, 79, or 84 in cohorts with rising incidence rates. Yearly iFOBT screening and 5-yearly stool biomarker testing were also analysed.</div></div><div><h3>Results</h3><div>Lowering screening start ages to 45 or 40 could reduce CRC mortality rates by 5% and 10%, respectively, while extending stop ages to 79 or 85 could reduce CRC mortality rates by 3% and 5%, respectively. Lowering the start age would be more cost-effective and have a more favourable balance of benefits to harms versus raising the stop age.</div></div><div><h3>Conclusion</h3><div>As early-onset CRC rates increase, lowering the screening start age could reduce CRC burden while remaining cost-effective and limiting harms. Based on these findings and implementation considerations, the Cancer Council Australia Colorectal Cancer Screening Working Party determined that 2-yearly iFOBT screening from age 45 to 74 was the most favourable. These analyses supported the 2023 <em>Clinical practice guidelines for the prevention, early detection and management of colorectal cancer: Population Screening</em>, which led to the NBCSP including people aged 45-49 on an opt-in basis from July 2024.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD147-expressed small extracellular vesicles enhance the detection of colorectal neoplasia with fecal immunochemical test","authors":"L.-C. Chang ,&nbsp;B.-R. Lin ,&nbsp;H.-M. Chiu ,&nbsp;M.-S. Wu ,&nbsp;T. Ochiya ,&nbsp;T.-L. Shen","doi":"10.1016/j.esmogo.2025.100140","DOIUrl":"10.1016/j.esmogo.2025.100140","url":null,"abstract":"<div><h3>Background</h3><div>Blood testing increases adherence to colorectal cancer (CRC) screening. The suboptimal detection of advanced adenoma (AA) and early-stage CRC by blood tests limits their application. The current study aims to investigate the diagnostic performance of CD147-expressed small extracellular vesicles (CD147) in the serum in combination with the fecal immunochemical test (FIT) for detecting AA and CRC.</div></div><div><h3>Patients and methods</h3><div>The case-control study enrolled 15 healthy controls and 50 CRC patients in the training cohort and 120 healthy controls, 50 non-AA patients, 50 AA patients, and 60 CRC patients in the validation cohort. CD147 was detected using the ExoScreen assay. The sensitivity and specificity of CD147 alone and combined with the FIT for detecting colorectal neoplasia were compared.</div></div><div><h3>Results</h3><div>CD147 could detect AA and CRC with a sensitivity of 58.0% and 71.7%, respectively. Combined with a 1-day FIT, the sensitivity for detecting AA and CRC would increase to 78.0% and 93.3%, respectively. Moreover, CD147 with 1-day FIT had a higher sensitivity than 1-day FIT alone for detecting proximal CRC (100% versus 89.5%). Besides, CD147 may detect 57.7% and 50.0% of the AA and CRC that FIT failed to detect, respectively. However, the specificity and false-positive rate of CD147 were inferior to those of FIT for detecting AA and CRC.</div></div><div><h3>Conclusions</h3><div>CD147 is superior to FIT for detecting AA and proximal neoplasia. Moreover, CD147 can increase the sensitivity of FIT for detecting either AA or CRC by combinatory use. However, false positivity is the concern of CD147, which should be further resolved in the future.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular analysis in pancreatic adenocarcinoma: a real-world study from high-volume French centres (CAPANCOBIO study)","authors":"C. Evrard ,&nbsp;M. Brugel ,&nbsp;G. Piessen ,&nbsp;G. Roth ,&nbsp;N. Williet ,&nbsp;V. Hautefeuille ,&nbsp;H. Trelohan ,&nbsp;M. Muller ,&nbsp;O. Bouché ,&nbsp;D. Tougeron","doi":"10.1016/j.esmogo.2025.100142","DOIUrl":"10.1016/j.esmogo.2025.100142","url":null,"abstract":"<div><h3>Background</h3><div>In pancreatic adenocarcinoma (PA) it is crucial to better understand the molecular biology and identify targetable molecular alterations to obtain therapeutic improvements.</div></div><div><h3>Methods</h3><div>The aim of the CAPANCOBIO study was to assess routine clinical practice regarding tumour somatic molecular analysis (SMA) in patients with unresectable PA. Tumour SMAs for patients with advanced PA were collected in nine high-volume French centres from September 2019 to October 2021 to identify factors influencing the prescription of SMA.</div></div><div><h3>Results</h3><div>Among the 397 patients included in the CAPANCOBIO study, 70 had an SMA (17.6%). The most frequent tests were next-generation sequencing analysis (70.0%). Among the 70 patients with SMA, 31 (44.3%) had at least one alteration detected, but only 6 patients had targetable alterations. Among these, only one patient (<em>n</em> = 1/6, 16.6%) was included in a clinical trial. Patients with SMA were younger (<em>P</em> &lt; 0.0001), more often female (<em>P</em> = 0.007), and more frequently had a family history of the <em>BRCA</em> cancer spectrum (<em>P</em> = 0.017).</div></div><div><h3>Conclusions</h3><div>Few patients with advanced PA had SMA of the tumour. Despite patients with targetable molecular alterations identified, very few patients were treated with targeted therapy and/or included in a clinical trial. It is essential to increase SMA for advanced PA in routine clinical practice to increase the use of targeted therapy and inclusions in clinical trials.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A stratified two-stage tumor molecular profiling algorithm to identify clinically actionable molecular alterations in pancreatic cancer☆","authors":"S. Hussung ,&nbsp;D. Akhoundova ,&nbsp;C. Pistoni ,&nbsp;D. Lenggenhager ,&nbsp;A. Töpfer ,&nbsp;C. Pauli ,&nbsp;B. Pestalozzi ,&nbsp;C. Britschgi ,&nbsp;M. Zoche ,&nbsp;M. Rechsteiner ,&nbsp;H. Moch ,&nbsp;A. Weber ,&nbsp;R. Fritsch","doi":"10.1016/j.esmogo.2025.100134","DOIUrl":"10.1016/j.esmogo.2025.100134","url":null,"abstract":"<div><h3>Background</h3><div>Tumor molecular profiling (TMP) for pancreatic cancer (PC) is recommended by current international guidelines, yet no testing standards exist. Moreover, the magnitude of benefit and the cost-effectiveness of comprehensive next-generation sequencing panels for PC are under debate.</div></div><div><h3>Materials and methods</h3><div>We implemented a stratified two-stage TMP algorithm for advanced PC. Stage 1 comprised immunohistochemistry for mismatch repair deficiency and targeted sequencing employing a 33-gene next-generation sequencing panel covering common PC drivers and DNA damage response genes. Based on pre-specified events (<em>KRAS</em> wild type, mismatch repair deficiency, molecular tumor board recommendation), subsequent comprehensive molecular testing was carried out (stage 2). We report molecular findings and patient outcomes.</div></div><div><h3>Results</h3><div>A total of 94 PC patients were included in the study. Some 63/94 (67.0%) patients underwent TMP according to the algorithm, of which 5/63 (7.9%) fulfilled criteria for subsequent stage 2 comprehensive testing. A total of 31/94 (33%) patients underwent upfront comprehensive molecular testing outside the algorithm based on referring physician’s request. Compared with algorithm testing, upfront comprehensive testing detected a higher number of pathogenic molecular alterations/patient (median: five versus three, <em>P</em> = 0.0005), however no additional actionable alterations. Actionable alterations were identified in 25/94 (26.6%) cases, including DNA damage response gene alterations, KRAS G12C and targetable drivers in <em>KRAS</em> wild type tumors. Patients receiving targeted therapy based on molecular profile showed superior survival (progression-free survival, overall survival) compared with patients without targeted treatment.</div></div><div><h3>Conclusions</h3><div>Stratified two-stage TMP reliably identifies actionable alterations in PC patients, with potential therapeutic benefit. The proposed TMP algorithm might be as effective, yet more feasible and economic compared with comprehensive upfront testing.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}