ESMO Gastrointestinal Oncology最新文献

{"title":"Real-world outcomes of trifluridine/tipiracil for heavily pretreated patients with advanced gastric cancer","authors":"K. Fukuda ,&nbsp;I. Nakayama ,&nbsp;A. Ooki ,&nbsp;D. Kamiimabeppu ,&nbsp;K. Shimozaki ,&nbsp;H. Osumi ,&nbsp;S. Fukuoka ,&nbsp;K. Yoshino ,&nbsp;M. Ogura ,&nbsp;T. Wakatsuki ,&nbsp;K. Chin ,&nbsp;E. Shinozaki ,&nbsp;K. Yamaguchi ,&nbsp;D. Takahari","doi":"10.1016/j.esmogo.2024.100046","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100046","url":null,"abstract":"<div><h3>Background</h3><p>Trifluridine (FTD)/tipiracil (TPI) is a standard salvage treatment for advanced gastric cancer (AGC). This study aimed to assess the efficacy and safety of FTD/TPI in heavily pretreated patients with AGC in clinical practice.</p></div><div><h3>Materials and methods</h3><p>This retrospective cohort study conducted at a single Japanese institute between November 2019 and May 2022 included patients with inoperable advanced or recurrent gastric cancer (GC) who received FTD/TPI with or without ramucirumab (RAM) in the third-line or later setting. Univariate and multivariate analyses were carried out to examine the clinical factors associated with disease progression and survival.</p></div><div><h3>Results</h3><p>A total of 98 consecutive patients, including 2 patients treated with RAM, were enrolled. Eighty-five patients had prior immune checkpoint inhibitor administration before FTD/TPI and 86 patients were treated with FTD/FPI as the fourth or later line of treatment. Objective response rate was 2.3% (2/87), and disease control rate was 40.2% (35/87). Nausea, anorexia, and diarrhea were the observed adverse events (AEs) in 45, 24, and 19 patients, respectively. The most common grade 3 or 4 AE was neutropenia. Multivariate analysis revealed that performance status (PS) ≥1, elevated serum carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) levels, and primary tumor location were independently associated with shorter progression-free survival. In terms of overall survival, PS ≥1, elevated serum CEA and/or CA19-9, and the presence of moderate to severe ascites demonstrated statistically significant associations with poorer survival.</p></div><div><h3>Conclusions</h3><p>FTD/TPI could be a therapeutic option for AGC patients previously treated with nivolumab in clinical practice. AEs associated with FTD/TPI were manageable in heavily pretreated patients with AGC.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000074/pdfft?md5=c649638d7d986b9f9642a3ade7226e2f&pid=1-s2.0-S2949819824000074-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067374","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 wind of change in upper gastrointestinal cancers: updates from ESMO 2023","authors":"A. Cammarota ,&nbsp;A.R. Siebenhüner ,&nbsp;M.A. Maqueda ,&nbsp;T. Fleitas-Kanonnikoff ,&nbsp;H. van Laarhoven ,&nbsp;C. de la Fouchardière ,&nbsp;R. Obermannova ,&nbsp;M. Moehler ,&nbsp;E.C. Smyth","doi":"10.1016/j.esmogo.2023.100035","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100035","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294981982300050X/pdfft?md5=bbe0f1f7b79c5fdcdbaf7aa45fa0988a&pid=1-s2.0-S294981982300050X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140188244","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":"The Liver Frailty Index predicts survival in systemic therapy for hepatocellular carcinoma: a multicentre prospective cohort study","authors":"K.M.J. Waller ,&nbsp;D.S. Prince ,&nbsp;E.H.Y. Lai ,&nbsp;M.T. Levy ,&nbsp;S.I. Strasser ,&nbsp;G.W. McCaughan ,&nbsp;M.L.P. Teng ,&nbsp;D.Q. Huang ,&nbsp;K. Liu","doi":"10.1016/j.esmogo.2024.100043","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100043","url":null,"abstract":"<div><h3>Background</h3><p>Systemic therapy for hepatocellular carcinoma (HCC) can prolong survival, but outcomes vary, and predictors of response are not fully defined. Frailty is associated with worse outcomes in cirrhosis and liver transplantation, but its impact on patients with advanced HCC is unknown.</p></div><div><h3>Patients and methods</h3><p>An international, multicentre, prospective, observational cohort of adults commencing systemic therapy for HCC from 2019 to 2022 was analysed. Frailty was assessed by the Liver Frailty Index (LFI). The primary outcome was overall survival; secondary outcomes were disease progression, adverse events, and treatment discontinuation.</p></div><div><h3>Results</h3><p>Among 102 patients, 80% were male and the median age was 67 years [interquartile range (IQR) 60-73 years]. Most had viral hepatitis (hepatitis C virus 39%, hepatitis B virus 29%), were Child–Pugh A (75%), Eastern Cooperative Oncology Group (ECOG) 0-1 (89%), and Barcelona Centre Liver Cancer (BCLC) stage C (59%). Similar proportions received tyrosine kinase inhibitors (54%) and immunotherapy (46%). The median LFI was 4.13 (IQR 3.81-4.43): 4% were robust (LFI &lt;3.2), 75% were pre-frail (LFI 3.2-&lt;4.5), and 22% were frail (LFI 4.5+). LFI was independently associated with death (adjusted hazard ratio 1.74, 95% confidence interval 1.17-2.59, <em>P</em> = 0.006), after adjustment for Child–Pugh score and albumin–bilirubin grade. The optimal cut-off for survival at 1 year was LFI 4.2 (area under the curve 0.658), significant on univariable and multivariable analyses at predicting death. Frailty was associated with earlier systemic therapy discontinuation, despite similar rates of disease progression and adverse events; cessation of treatment due to functional decline was more common among frail patients. Sensitivity analysis excluding patients above Child–Pugh B8 or ECOG 2 did not change results.</p></div><div><h3>Conclusion</h3><p>The LFI is an independent predictor of death among patients with HCC undergoing systemic therapy.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000049/pdfft?md5=5b23993ef9b436cf939f6aaccd640ba2&pid=1-s2.0-S2949819824000049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139915515","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":"Improving gastrointestinal cancer therapy by uniting stakeholders","authors":"M. Quante ,&nbsp;A. Saborowski ,&nbsp;C.B. Westphalen ,&nbsp;2023 Translational and Precision GI-Oncology—Bench to Bedside Meeting","doi":"10.1016/j.esmogo.2024.100040","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100040","url":null,"abstract":"<div><p>Gastrointestinal (GI) cancer—an umbrella term for cancers that affect the digestive system and other abdominal organs—includes some malignancies with the lowest survival rates. To improve patient outcomes, patients must have access to optimal treatment including precision oncology, a method of determining the most effective treatment for an individual cancer patient by identifying predictive biomarkers through the use of advanced molecular diagnostics. While many powerful molecular profiling technologies have already been developed, their uptake in the management of GI cancers could be improved. To bridge this gap, better coordination among three interdependent stakeholders—scientists, clinicians, and industry professionals—is essential. The first Translational and Precision GI-Oncology—Bench to Bedside Meeting was held on 23-28 April 2023 in Freiburg, Germany. The 3-day meeting offered the opportunity for scientists, clinicians, and industry professionals in the field of GI cancer to exchange ideas about how to improve the translation of basic science into clinical practice. One-hundred and twenty participants attended the meeting, which featured 47 presentations covering the following five topics: bedside, analytical approaches for treatment and real-world data, new ideas and biomarkers, novel technologies, and drugs. A summary of the 2023 meeting is provided in this report.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000013/pdfft?md5=fbd11b3e91e0ad4592d2416f056d14cd&pid=1-s2.0-S2949819824000013-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744272","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: Study protocol for the OligoMetastatic Esophagogastric Cancer (OMEC) project: a multidisciplinary European Consensus project on the definition and treatment for oligometastatic esophagogastric cancer","authors":"G.S.E. Tan ,&nbsp;D.K.A. Chia ,&nbsp;J.B.Y. So","doi":"10.1016/j.esmogo.2024.100041","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100041","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000025/pdfft?md5=ac51431ffbe49b83b529bfdfdb02e5ff&pid=1-s2.0-S2949819824000025-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139726558","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":"Recurrence monitoring using ctDNA in patients with metastatic colorectal cancer: COSMOS-CRC-03 and AURORA studies","authors":"E. Oki ,&nbsp;R. Nakanishi ,&nbsp;K. Ando ,&nbsp;I. Takemasa ,&nbsp;J. Watanabe ,&nbsp;N. Matsuhashi ,&nbsp;T. Kato ,&nbsp;Y. Kagawa ,&nbsp;M. Kotaka ,&nbsp;K. Hirata ,&nbsp;M. Sugiyama ,&nbsp;T. Kusumoto ,&nbsp;Y. Miyamoto ,&nbsp;K. Toyosaki ,&nbsp;J. Kishimoto ,&nbsp;Y. Kimura ,&nbsp;T. Yoshizumi ,&nbsp;Y. Nakamura","doi":"10.1016/j.esmogo.2023.100034","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100034","url":null,"abstract":"<div><p>International treatment guidelines recommend tumor resection for patients with oligometastatic colorectal cancer (CRC). Despite this, recurrence occurs in ∼60% of patients post-surgery, indicating that the role and optimal type of perioperative systemic therapy has not been fully defined. In the COSMOS-oligo trials, comprising two studies, we are evaluating the potential role of circulating tumor DNA (ctDNA) analysis in clinical decision making and exploring adjuvant therapy strategies for patients with resectable metastatic CRC. The COSMOS-CRC-03 study aims to evaluate the prognostic value of post-operative minimal residual disease as detected by ctDNA and to explore the role of ctDNA in detecting disease recurrence. We plan to assess the predictive accuracy of ctDNA results for recurrence using blood collected 28 days post-surgery. We will additionally explore whether regular post-operative ctDNA test can detect recurrence earlier than standard imaging. Post-operative adjuvant therapy will not be administered to ctDNA-negative patients. The complementary AURORA trial is a randomized phase II study designed to test whether post-operative mFOLFOXIRI plus bevacizumab is superior to standard mFOLFOX6 for patients with metastatic CRC when the ctDNA status is positive after curative-intent surgery for patients enrolled in the COSMOS-CRC-03 study. Both studies will only include patients with resectable distant metastases of CRC. We designed these studies to stratify patients based on the results of a ctDNA assay and to determine the optimal treatment for patients at the highest risk for recurrence.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000493/pdfft?md5=6da3d0d74393cdcf5b559f202a86e8e1&pid=1-s2.0-S2949819823000493-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674894","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":"Higher rate of pathologic complete response in patients with early-onset locally advanced rectal cancer","authors":"J. Suarez ,&nbsp;M. Alsina ,&nbsp;N. Castro ,&nbsp;G. Marin ,&nbsp;C. Llanos ,&nbsp;B. Oronoz ,&nbsp;E. Mata ,&nbsp;R. Aznárez ,&nbsp;G. Jiménez ,&nbsp;M.I. Martínez ,&nbsp;R. Vera","doi":"10.1016/j.esmogo.2023.100033","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100033","url":null,"abstract":"<div><h3>Background</h3><p>Although incidence and mortality rates of colorectal cancer have progressively decreased during the past decades, early-onset rectal cancer (EORC; &lt;50 years old) is rising alarmingly. EORC is often diagnosed at advanced stages and presents intrinsic molecular alterations. New strategies are necessary to increase early diagnosis and to improve therapeutic management. We present the analysis of our locally advanced EORC patients evaluating their specific response to chemoradiotherapy.</p></div><div><h3>Materials and methods</h3><p>Patients diagnosed with locally advanced rectal cancer (LARC) and treated with curative surgery after neoadjuvant treatment (NAT) with chemoradiotherapy were retrospectively analysed, comparing differences between EORC and late-onset rectal cancer (LORC). Incidence rates between 2001 and 2020, as well as diagnostic and treatment response variables, were compared.</p></div><div><h3>Results</h3><p>Up to 1140 patients were diagnosed with rectal cancer and underwent curative surgery. From them, there were 399 patients with LARC who received NAT before surgery, and 9% of them had EORC (36 patients). The incidence of locally advanced EORC increased from 6.6% to 12.7% (2001-2020). No differences were found considering diagnostic variables between the early- and late-onset cohorts, although slightly more deficient mismatch repair tumours were found within the EORC cohort. Mean disease-free survival and mean cancer-specific survival were similar. Notwithstanding, EORC patients achieve higher rates of pathological complete responses (pCRs), compared with LARC (36.3% versus12.4%; <em>P</em> = 0.000).</p></div><div><h3>Conclusions</h3><p>Our analyses confirm the increase in incidence of EORC from 2001 to 2020 in Navarra. EORC patients achieved a higher pCR rate, thus suggesting that the role of organ preservation strategies should be further investigated in this unique population.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000481/pdfft?md5=3576098a2ef62db0e156e4bc4966e1c1&pid=1-s2.0-S2949819823000481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674863","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":"Comparative efficacy of PD-1 blockade in patients with dMMR/MSI-H metastatic colorectal or gastric cancer: a global retrospective study","authors":"G. Mazzoli ,&nbsp;F. Nichetti ,&nbsp;K. Shitara ,&nbsp;R. Cohen ,&nbsp;S. Lonardi ,&nbsp;C. Cremolini ,&nbsp;M.E. Elez ,&nbsp;J. Chao ,&nbsp;M. Fakih ,&nbsp;S.J. Klempner ,&nbsp;P. Jayachandran ,&nbsp;S. Maron ,&nbsp;D. Cowzer ,&nbsp;L. Fornaro ,&nbsp;L. Salvatore ,&nbsp;V. Zhu ,&nbsp;Y. Aoki ,&nbsp;R. Cerantola ,&nbsp;F. Bergamo ,&nbsp;M. Salati ,&nbsp;F. Pietrantonio","doi":"10.1016/j.esmogo.2023.100037","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100037","url":null,"abstract":"<div><h3>Background</h3><p>Programmed cell death protein 1 (PD-1) blockade improved the survival of patients with mismatch repair deficient (dMMR) and/or microsatellite instability-high (MSI-H) tumors, leading to tumor-agnostic approval of pembrolizumab in this population. Whether anti-programmed death (ligand)-1 [PD-(L)1] agents may achieve similar efficacy in dMMR/MSI-H metastatic gastric cancer (mGC) compared to metastatic colorectal cancer (mCRC) is unclear.</p></div><div><h3>Materials and methods</h3><p>We conducted a multicenter cohort study to collect data on patients with dMMR/MSI-H mGC or mCRC treated with anti-PD-(L)1 monotherapy globally at 17 tertiary cancer centers. Clinical features were balanced according to tumor type through the inverse probability of treatment weighting (IPTW) method. The primary endpoint was overall survival (OS), as evaluated from the first anti-PD-(L)1 administration.</p></div><div><h3>Results</h3><p>The cohort included 398 mCRC and 121 mGC patients, with a median follow-up of 34.6 and 25.1 months, respectively. The two populations differed for several baseline clinical features: patients with mCRC had younger age (60 versus 68 years, <em>P</em> &lt; 0.001), better performance status (PS 0: 46% versus 34%, <em>P</em> = 0.062), higher frequency of primary tumor resection (82% versus 49%, <em>P</em> &lt; 0.001) and liver metastases (38% versus 24%, <em>P</em> = 0.005), yet lower rates of distant nodal metastases (57% versus 83%, <em>P</em> &lt; 0.001) and synchronous presentation (51% versus 76%, <em>P</em> &lt; 0.001). After IPTW adjustment, patients with mGC showed no significant difference in progression-free survival (PFS) and OS compared to those with mCRC [PFS: hazard ratio (HR) 0.55, <em>P</em> = 0.077; OS: HR 0.65, <em>P</em> = 0.200].</p></div><div><h3>Conclusions</h3><p>Despite patients with dMMR/MSI-H mGC being enriched with poor prognostic factors as compared to the mCRC counterpart, anti-PD-(L)1 monotherapy’s efficacy appears similar in the two tumor types.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000523/pdfft?md5=cea6871fb62a02c29d127d006f57ab8e&pid=1-s2.0-S2949819823000523-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674862","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":"Unleashing the power of anti-HER2 therapies in metastatic colorectal cancer: paving the way for a brighter future","authors":"A. Babkoff ,&nbsp;A. Zick ,&nbsp;A. Hubert ,&nbsp;P. Tarantino ,&nbsp;A. Grinshpun","doi":"10.1016/j.esmogo.2023.100032","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100032","url":null,"abstract":"<div><p>Colorectal cancer (CRC) constitutes a significant portion of cancer-related deaths in the United States, topping cancer-related mortality among males under 50 years of age. Despite an increase in overall survival throughout the years, the prognosis of metastatic CRC remains poor. In addition to the classic molecular targets in CRC that include epidermal growth factor receptor, BRAF, and vascular endothelial growth factor pathways, human epidermal growth factor receptor 2 (HER2) amplification is an emerging target that has been successfully targeted in advanced CRC, particularly with anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. With the introduction of potent HER2-directed antibody–drug conjugates, the number of patients who might be eligible for anti-HER2 therapy is expected to increase dramatically as tumors with lower expression of HER2 (termed HER2 low) have shown relevant response rates across several histologies. Yet, several challenges remain to be addressed in this field, including the standardized method to define HER2-low disease and the most efficient payload in this setting, among others. Future studies will help to further characterize HER2-low CRCs, identify additional predictive biomarkers, and assist in the development of better treatments.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294981982300047X/pdfft?md5=1690015eac51e90ec9e38e88274965be&pid=1-s2.0-S294981982300047X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674861","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":"Codon-specific KRAS mutations predict survival in advanced pancreatic cancer","authors":"A. Boilève ,&nbsp;A. Rousseau ,&nbsp;M. Hilmi ,&nbsp;A. Tarabay ,&nbsp;J.R.R. Mathieu ,&nbsp;J. Cartry ,&nbsp;S. Bedja ,&nbsp;N. Goudarzi ,&nbsp;C. Nicotra ,&nbsp;M. Ngo-Camus ,&nbsp;V. Boige ,&nbsp;M. Valéry ,&nbsp;T. Pudlarz ,&nbsp;M.-A. Bani ,&nbsp;P. Dartigues ,&nbsp;L. Tselikas ,&nbsp;A. Italiano ,&nbsp;S. Cosconea ,&nbsp;M. Gelli ,&nbsp;E. Fernandez-de-Sevilla ,&nbsp;M. Ducreux","doi":"10.1016/j.esmogo.2023.100030","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100030","url":null,"abstract":"<div><h3>Background</h3><p>How distinct <em>KRAS</em> alterations in pancreatic adenocarcinoma (PDAC) influence tumor initiation and outcomes remains unclear. Moreover, <em>KRAS</em> is now partly targetable with novel specific inhibitors targeting <em>KRAS</em>_G12 (G12C or G12D), but specific outcomes of these subgroups of patients is poorly described. In this study, we compared clinical/genomic characteristics and outcomes of PDAC depending on codon-specific <em>KRAS</em> mutant (G12 versus others), as well as gene expression profiles and <em>in vitro</em> drug sensibility using organoids.</p></div><div><h3>Patients and methods</h3><p>All metastatic patients with PDAC and available molecular profile from 2015 to 2022 were eligible, and patients with <em>KRAS</em> mutation were included. Transcriptomic data from 69 <em>KRAS</em>-mutated tumors were also analyzed.</p></div><div><h3>Results</h3><p>Overall, 263 patients were included—239 <em>KRAS</em>_G12 (91%) and 24 (9%) <em>KRAS</em>_other. There was no difference between <em>KRAS</em>_G12 and <em>KRAS</em>_other regarding clinicopathological characteristics and potentially actionable alterations, except for <em>BRAF</em> that was found in 13% of <em>KRAS</em>_other (<em>P</em> = 0.01). <em>G protein subunit alpha S</em> (<em>GNAS</em>) was found more altered in <em>KRAS</em>_other tumors (<em>P</em> = 0.002) suggesting potential intraductal papillary mucinous neoplasm precursors. The median overall survival from metastatic diagnosis was 16.7 months [95% confidence interval (CI) 14.3-18.3 months] in <em>KRAS</em>_G12 and 24.9 months (95% CI 17.4-43.4 months) in <em>KRAS</em>_other [hazard ratio (ref: <em>KRAS</em>_G12) = 0.56 (0.34-0.94), <em>P</em> = 0.04 adjusted]. The first-line treatment response was not different between groups (overall response rate and progression-free survival), as confirmed with a similar organoid <em>in vitro</em> sensibility. Transcriptomic analyses showed a significant and exclusive up-regulation of immune pathways in <em>KRAS</em>_G12 tumors.</p></div><div><h3>Conclusions</h3><p>Codon-specific <em>KRAS</em> mutations are not equal and we report that <em>KRAS</em>_G12 patients have a worst prognosis than <em>KRAS</em>_other patients in PDAC. These results warrant to be confirmed in larger-scale studies.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000456/pdfft?md5=c2cf56bd7b06bdb14c542a5c496df425&pid=1-s2.0-S2949819823000456-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139548939","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}