Cancer最新文献

{"title":"Patient-reported discordance between care goals and treatment intent in advanced cancer","authors":"Manan P. Shah MD,&nbsp;Neil S. Wenger MD, MPH,&nbsp;John Glaspy MD, MPH,&nbsp;Ron D. Hays PhD,&nbsp;Rebecca L. Sudore MD,&nbsp;Maryam Rahimi MD,&nbsp;Lisa Gibbs MD,&nbsp;Sidharth Anand MD, MBA,&nbsp;Chi-Hong Tseng PhD,&nbsp;Anne M. Walling MD, PhD","doi":"10.1002/cncr.35976","DOIUrl":"10.1002/cncr.35976","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Goal-concordant care is achieved when treatment is aligned with goals. This study describes patient-reported concordance between care goals and treatment intent in advanced cancer compared to other serious illnesses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A post hoc cross-sectional analysis of baseline survey responses was conducted in adult patients enrolled in a multisite trial of advance care planning. Patients reported whether they prefer and whether they are receiving treatment that prioritizes longevity (life-extending care) versus comfort (comfort-focused care). Concordance between care preferences and perceived treatment intent in patients with advanced cancer versus other advanced illnesses was compared. Mortality rates for patients with cancer stratified by perceived care concordance are reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1099 patients, those with advanced cancer (<i>n</i> = 231) reported similar preference for comfort-focused care (49% vs 48%, <i>p</i> = .47) and had similar 24-month mortality (16% v 13%, <i>p</i> = .25) as patients with other serious illnesses (<i>n</i> = 868). Among patients preferring comfort-focused care, patients with cancer (<i>n</i> = 113) were more likely than patients with other illnesses (<i>n</i> = 413) to report receiving (discordant) life-extending care (37% vs. 19%, <i>p</i> &lt; .001). Among patients with cancer preferring comfort-focused care, there was no statistically significant difference in 24-month mortality between those who reported receiving (discordant) life-extending versus (concordant) comfort-focused care (24% v 15%, <i>p</i> = .31).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Compared to patients with other serious illnesses, a relatively large portion of patients with advanced cancer reported that their treatment discordantly focused on longevity over comfort despite their goal to prioritize comfort over longevity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine release syndrome in solid tumors","authors":"David Synnott MB, BCh,&nbsp;David O’Reilly MB, BCh,&nbsp;Declan De Freitas MB, BCh, PhD,&nbsp;Jarushka Naidoo MB, BCh, MHS","doi":"10.1002/cncr.70069","DOIUrl":"10.1002/cncr.70069","url":null,"abstract":"<p>Cytokine release syndrome (CRS) is a common and potentially severe complication of cancer immunotherapy, including CAR T-cell therapies, bispecific T-cell engagers, and less commonly immune checkpoint inhibitors. Although extensive research has established guidelines for managing CRS in hematological malignancies, there is a growing need to address CRS in the context of solid organ tumors due to differences in tumor microenvironment, immunotherapy indications, and patient population. This review aims to provide an overview of CRS in solid tumors, outlining its pathophysiology, clinical presentation, and current management strategies. The complexities of CRS in solid tumors arise from challenges such as the immunosuppressive nature of the tumor microenvironment and the overlap of tumor-associated antigens with healthy tissues, potentially increasing the risk of severe on-target off-tumor toxicities. The review emphasizes early detection and grading of CRS as essential for patient safety and effective intervention. Management of CRS involves supportive care for mild cases, whereas severe presentations often require targeted therapies like tocilizumab, corticosteroids, and escalation to the intensive care unit for organ support. The decision to rechallenge or withhold immunotherapy requires careful consideration of patient-specific goals and risks. Emerging treatments such as other cytokine inhibitors, plasma exchange, and suicide gene systems are promising avenues for mitigating severe CRS. Future research focuses on refining risk stratification tools, novel therapeutic agents, and evaluating long-term outcomes. A deeper understanding of CRS in solid tumors will enable more personalized treatment approaches, enhancing the safety and efficacy of immunotherapies for this patient population.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of a geriatric assessment-guided management intervention (GAIN-S) on prognostic awareness: A randomized controlled trial","authors":"Cristiane Decat Bergerot PhD,&nbsp;Paulo Gustavo Bergerot MD,&nbsp;Marianne Razavi PhD,&nbsp;Marcos Vinicius da Silva França MD, MS,&nbsp;Jonas Ribeiro Gomes da Silva BS,&nbsp;Jose Adolfo Cerveira MD,&nbsp;William Hiromi Fuzita MD,&nbsp;Gabriel Marques dos Anjos MD,&nbsp;Renata Ferrari BS,&nbsp;Errol J. Philip PhD,&nbsp;Mariana Tosello Laloni MD,&nbsp;Carlos Gil Moreira Ferreira MD, PhD,&nbsp;Marco Murilo Buso MD,&nbsp;Sumanta K. Pal MD,&nbsp;Ryan Nipp MD, MPH,&nbsp;Areej El-Jawahri MD,&nbsp;Enrique Soto-Perez-de-Celis MD, PhD,&nbsp;William Dale MD, PhD","doi":"10.1002/cncr.70054","DOIUrl":"10.1002/cncr.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Geriatric assessment (GA)-guided supportive care (GAIN-S) may improve decision-making in older adults with cancer, but its effects on prognostic awareness remain unclear. The authors evaluated whether GAIN-S enhances prognostic awareness among older adults with metastatic cancer in Brazil.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This randomized controlled trial was conducted in Brazil (June 2022–July 2023). Adults ≥65 years old with metastatic cancer were randomized 1:1 to GAIN-S (<i>n</i> = 39) or usual care (UC; <i>n</i> = 38). GAIN-S included multidisciplinary GA review, individualized care planning, and targeted referrals. UC consisted of standard care without GA-guided interventions. Prognostic awareness was assessed using the Prognostic Awareness Impact Questionnaire, covering emotional (10 items; range, 0–30), adaptive (12 items; range, 0–36), and cognitive (2 categorical items) domains. Group differences were analyzed using <i>t</i>-tests; item-level analyses used Mann-Whitney <i>U</i>, McNemar’s, or χ² tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-seven participants were enrolled (mean age, 74.5; 56% female). Common cancers included genitourinary (29.9%), breast (24.7%), and gastrointestinal (22.1%). GAIN-S led to greater improvements in emotional (mean difference = 1.14, standard error [SE] = 0.35, <i>p</i> = .002) and adaptive (mean difference = 0.82, SE = 0.30, <i>p</i> = .008) domains compared to UC. No differences were observed in the cognitive domain. Most participants reported their oncologist had not clearly stated whether their cancer was curable (74% GAIN-S vs. 57% UC). GAIN-S participants more often reported improved coping with prognostic uncertainty, better emotional acceptance, and reduced distress (all <i>p</i> &lt; .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GAIN-S improved emotional and adaptive domains of prognostic awareness. These novel findings underscore the value of the GAIN-S intervention for older adults. Studies are needed to explore longer-term effects on decision-making, communication, and quality of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gilteritinib in FLT3-mutated acute myeloid leukemia: A real-world Italian experience","authors":"Roberto Cairoli MD,&nbsp;Lorenzo Del Castello MS,&nbsp;Silvia Imbergamo MD,&nbsp;Elisabetta Pierdomenico MD,&nbsp;Cristina Papayannidis MD,&nbsp;Erika Borlenghi MD,&nbsp;Calogero Vetro MD,&nbsp;Patrizia Chiusolo MD,&nbsp;Monica Fumagalli MD,&nbsp;Clara Minotti MD,&nbsp;Francesco Marchesi MD,&nbsp;Massimo Bernardi MD,&nbsp;Pellegrino Musto MD,&nbsp;Nicola Fracchiolla MD,&nbsp;Anna Candoni MD,&nbsp;Monia Lunghi MD,&nbsp;Maurizio Musso MD,&nbsp;Fabio Guolo MD,&nbsp;Donato Mannina MD,&nbsp;Albana Lico MD,&nbsp;Anna Maria Scattolin MD,&nbsp;Monica Crugnola MD,&nbsp;Sara Galimberti MD,&nbsp;Gianpaolo Nadali MD,&nbsp;Mauro Turrini MD,&nbsp;Patrizia Zappasodi MD,&nbsp;Elisabetta Todisco MD,&nbsp;Claudia Basilico MD,&nbsp;Giovanni Grillo MD,&nbsp;Valentina Mancini MD,&nbsp;Marta Riva MD,&nbsp;Davide Paolo Bernasconi PhD,&nbsp;Rosa Greco MD","doi":"10.1002/cncr.70055","DOIUrl":"10.1002/cncr.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Methods</h3>\u0000 \u0000 <p>This real-world study evaluated the clinical effectiveness of gilteritinib in 205 patients with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) enrolled in the Italian expanded access since January 2018.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 205 patients, 124 (60.5%) received gilteritinib as a bridging therapy to allogeneic stem cell transplantation (allo-SCT), achieving complete remission in 52.4% (<i>n</i> = 65). The median overall survival (OS) for the entire cohort was 11.0 months, with estimated OS rates of 46.8% at 1 year and 28.5% at 3 years. Sixty patients (48% of those bridged) underwent allo-SCT after a median of 3.7 months on gilteritinib, achieving posttransplant OS rates of 65.2% at 1 year and 56.1% at 3 years. The acquisition of FLT3 mutations at relapse and the presence of TP53 co-mutations were significantly associated with inferior outcomes. Among 46 patients (22.4%) who relapsed after allo-SCT, gilteritinib treatment yielded an overall response rate (ORR) of 54.3%, a median OS of 11.1 months, and 1- and 3-year OS rates of 49.5% and 15.5%, respectively. Additionally, 35 patients (17.1%) previously treated with nonintensive chemotherapy received gilteritinib until disease progression or intolerance, achieving an ORR of 11.4%, a median OS of 5.9 months, and a 1-year OS rate of 29.0%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These real-world data confirm that clinical outcomes achieved with gilteritinib in patients with R/R FLT3-mutated AML are consistent with those observed in pivotal clinical trials. Notably, approximately half of the transplant-eligible patients were successfully bridged to allo-SCT and demonstrated encouraging long-term survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revised “iRR6” model in intermediate-1 risk myelofibrosis patients treated with ruxolitinib","authors":"Francesca Palandri MD, PhD,&nbsp;Filippo Branzanti MSc,&nbsp;Massimiliano Bonifacio MD, PhD,&nbsp;Elena M. Elli MD,&nbsp;Erika Morsia MD,&nbsp;Mirko Farina MD,&nbsp;Mario Tiribelli MD, PhD,&nbsp;Giulia Benevolo MD,&nbsp;Eloise Beggiato MD,&nbsp;Bruno Martino MD,&nbsp;Giovanni Caocci MD,&nbsp;Novella Pugliese MD,&nbsp;Alessia Tieghi MD,&nbsp;Monica Crugnola MD,&nbsp;Gianni Binotto MD,&nbsp;Francesco Cavazzini MD,&nbsp;Elisabetta Abruzzese MD,&nbsp;Alessandro Isidori MD,&nbsp;Alessandra Dedola MD,&nbsp;Emilia Scalzulli MD,&nbsp;Andrea Duminuco MD, PhD,&nbsp;Luca Tosoni MD,&nbsp;Alda Strazimiri MD,&nbsp;Roberto M. Lemoli MD, PhD,&nbsp;Daniela Cilloni MD, PhD,&nbsp;Monica Bocchia MD,&nbsp;Fabrizio Pane MD, PhD,&nbsp;Chiara Sartor MD, PhD,&nbsp;Florian H. Heidel MD, PhD,&nbsp;Massimo Breccia MD, PhD,&nbsp;Giuseppe A. Palumbo MD, PhD,&nbsp;Andrew T. Kuykendall MD","doi":"10.1002/cncr.70062","DOIUrl":"10.1002/cncr.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The response to ruxolitinib after 6 months (RR6) model allows early identification of ruxolitinib-treated myelofibrosis (MF) patients with poorer overall survival (OS); however, it is less applicable to lower-risk patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To further explore this, the authors performed a subanalysis of the “RUX-MF” study (NCT06516406) with an aim to validate the RR6 and to develop a score specific for intermediate-1 DIPSS/MYSEC-PM risk patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 776 evaluable patients, 34.4%, 47.8%, and 17.8% were at low, intermediate, and high RR6 risk, with 5-year OS of 64.1%, 51.8%, and 44.5%, respectively (<i>p</i> &lt; .001). In the 428 intermediate-1 patients, the RR6 model did not discriminate between intermediate and low-risk patients (5-year OS: 74.4% vs. 72.0%, <i>p</i> = .24). The intermediate-1 specific RR6 (iRR6) model was therefore developed by incorporating new variables: underdosed ruxolitinib with respect to platelet count at one or more time points (hazard ratio [HR], 3.91; <i>p</i> &lt; .001), absence of palpable spleen reduction by ≥50% at 6 months (HR, 1.45; <i>p</i> = .02), and red blood cell transfusion requirement at all time points (HR, 1.85; <i>p</i> = .01). The iRR6 model stratified patients into three risk categories: low (score 0, 20.3%), intermediate (score 1–2, 45.8%), and high-risk (score &gt;2, 33.9%), with 5-year OS of 84.8%, 76.4%, and 56.6%, respectively (<i>p</i> &lt; .0001). The iRR6 model was validated in a cohort of 95 intermediate-1 risk patients from the Moffitt Cancer Center, yielding stratification into the same three risk categories, with 5-year OS of 83.3% (low-risk), 71.7% (intermediate-risk), and 54.5% (high-risk) (<i>p</i> = .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The iRR6 model provides a more refined tool for the identification of intermediate-1 MF patients who may benefit from early therapy shift.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of gastroenteropancreatic neuroendocrine neoplasms in Taiwan: A multicenter registry study—TCOG T1214 study","authors":"Hui-Jen Tsai MD PhD,&nbsp;Ming-Huang Chen MD PhD,&nbsp;Hsiu-Po Wang MD,&nbsp;Chin-Fu Hsiao PhD,&nbsp;Yen-Yang Chen MD PhD,&nbsp;Jen-Shi Chen MD,&nbsp;Mei-Due Yang MD PhD,&nbsp;Chin-Yuan Tzen MD PhD,&nbsp;Yan-Shen Shan MD PhD,&nbsp;Li-Yaun Bai MD PhD,&nbsp;De-Chuan Chan MD,&nbsp;Pei-Yi Chu MD PhD,&nbsp;Ching-Liang Ho MD,&nbsp;Youngsen Yang MD,&nbsp;Johnson Lin MD,&nbsp;Hsuan-Yu Lin MD,&nbsp;Cheng-Shyong Chang MD,&nbsp;Chuan-Cheng Wang MD,&nbsp;Tsann-Long Hwang MD,&nbsp;Li-Tzong Chen MD PhD","doi":"10.1002/cncr.70019","DOIUrl":"10.1002/cncr.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) account for more than 50% of all NENs. The survival of patients with GEP-NENs has improved based on early diagnosis and improved treatment strategies. The real-world data of GEP-NENs in Taiwan are limited. A multicenter registry study was conducted to obtain real-world data on GEP-NENs in Taiwan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with pathologically diagnosed GEP-NENs were enrolled. Data were on the baseline characteristics, treatment strategies, and patient survival. Also evaluated was the expression status of six biomarkers, including SSTR2, SSTR5, PDX-1, CDX-2, mASH1, and NeuroD, in tumors. Overall survival (OS) was analyzed and plotted via the Kaplan–Meier method. Cox regression analysis was used to analyze the prognostic factors of OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 600 GEP-NEN patients were enrolled. Pancreatic NENs accounted for 43.0% of all patients. The 5-year and 10-year OS rates of all patients were 70.9% and 61.3%, respectively. In the multivariable Cox regression analysis, older age (hazard ratio [HR] = 1.02; 95% CI, 1.01–1.03), higher Eastern Cooperative Oncology Group performance status score, higher tumor grade (World Health Organization classification) and stage 4 disease (HR = 6.22; 95% CI, 3.60–10.76) were associated with poor OS. Positive SSTR2 expression (HR = 0.53; 95% CI, 0.31–0.91) was associated with better OS according to multivariate Cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides real-world data on 600 GEP-NENs in Taiwan and identifies age, Eastern Cooperative Oncology Group performance status score, tumor grade, tumor stage, and SSTR2 expression as prognostic factors for the survival of GEP-NENs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CodeBreaK or code blue? Assessing sotorasib's vital signs in metastatic colorectal cancer","authors":"Samuel X. Stevens MBBS (Hons), B App Sc, M Bioethics, FRACP,&nbsp;Bishal Gyawali MD, PhD, FASCO","doi":"10.1002/cncr.70056","DOIUrl":"10.1002/cncr.70056","url":null,"abstract":"&lt;p&gt;The ability to therapeutically target Kirsten rat sarcoma viral oncogene homolog (KRAS)–long considered an &lt;i&gt;undruggable&lt;/i&gt; oncogenic driver of nonsmall cell lung cancer (NSCLC) and gastrointestinal (GI) cancer—is one of the most important biomedical discoveries of the past decade. Therefore, sotorasib, the first KRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation inhibitor to reach the clinic was heralded as a triumph of precision oncology.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Yet the path of sotorasib from preclinical discovery to US Food and Drug Administration (FDA) approval offers a cautionary tale for a field increasingly immersed in molecularly targeted therapies. Although heralded as a success of precision oncology, precision oncology is not merely the right drug for the right target. It also entails the right dose at the right time for the right duration, to which one could arguably add right reporting. However, after reading the results from the recent CodeBreak 300 trial of sotorasib in colorectal cancer (ClinicalTrials.gov identifier NCT05198934), we believe sotorasib has fallen short in many domains of this definition. The case of sotorasib also highlights how regulators have not encouraged the conditions needed to deliver the real promise of precision oncology to patients.&lt;/p&gt;&lt;p&gt;CodeBreaK 300 is a phase 3 trial evaluating the efficacy and safety of sotorasib in combination with panitumumab versus treatment of investigator's choice (TIC) in patients with advanced colorectal cancer harboring a KRAS G12C mutation who progressed on chemotherapies.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Although the included patient population and choice of control arm in this trial were appropriate, a striking feature of this trial is the uncertainty about the appropriate dose level for sotorasib. Doses for registration trials are typically established in early phase clinical trials to minimize the number of participants exposed to potentially ineffective or toxic dosages. Thus it is notable that this phase 3 trial appears to conduct a dose-finding exercise, with separate arms for the 240-mg and 960-mg doses, respectively. The justification of &lt;i&gt;nonlinear pharmacokinetics&lt;/i&gt;, although not untrue, is perhaps only a part of the story.&lt;/p&gt;&lt;p&gt;Having shown promise in early phase trials, sotorasib received FDA Accelerated Approval for use in KRAS G12C mutant NSCLC in 2021. However, the FDA noted that preliminary trials were “hampered by a lack of robust dose exploration,” mandating further exploration in postmarketing studies&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and highlighting the tension between speed and certainty in drug development. Appropriately, the 960-mg and 240-mg dosages underwent further evaluation, with no statistically significant difference in efficacy but with higher treatment-related adverse events for the 960-mg dose.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Although published in 2024, evidence from patent applications suggests that this was known to the sponsor as early a","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical fitness and clinically assessed disease burden in long-term childhood cancer survivors—The SURfit study","authors":"Anna K. Mayr Pract Med,&nbsp;Simeon Zürcher PhD,&nbsp;Iris Bänteli PhD,&nbsp;Helge Hebestreit MD,&nbsp;Rahel Kasteler MD, PhD,&nbsp;Nicolas X. von der Weid MD,&nbsp;Susi Kriemler MD,&nbsp;Christina Schindera MD, PhD,&nbsp;Corina S. Rueegg PhD","doi":"10.1002/cncr.70051","DOIUrl":"10.1002/cncr.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Identifying disease burden among childhood cancer survivors (CCS) can guide tailored care. Physical fitness predicts health and mortality and may help reduce disease burden in CCS. This study aimed to 1) describe the burden of clinically ascertained adverse health outcomes in long-term CCS, and 2) investigate the association between physical fitness and adverse health outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used baseline data of the SURfit study, a randomized controlled physical activity trial. The authors included 163 CCS, diagnosed &lt;16 years, ≥16 years at enrollment, and ≥5 years since last cancer diagnosis. Clinically assessed health outcomes were categorized using the Common Terminology Criteria for Adverse Events. Physical fitness was assessed by cardiopulmonary-exercise-test (CPET), hand-grip strength, and the 1-minute sit-to-stand test (STS). Using multivariable Poisson regression models, this study investigated the association between physical fitness and adverse health outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants (30.5 ± 8.6 years old, time since diagnosis 22.9 ± 9 years) had 1170 adverse health outcomes, with 99% CCS having at least one. Musculoskeletal disorders were most common (130 of 163 [80%]). Higher levels of physical fitness were associated with fewer adverse health outcomes of any grade (CPET: prevalence rate ratio [PRR], 0.71 per watt/kg bodyweight, 95% confidence Interval [CI], 0.63–0.81, <i>p</i> &lt; .001; hand-grip: PRR, 0.60 kg/kg bodyweight; 95% CI, 0.35–1.03, <i>p</i> = .063; STS: PRR, 0.95 per five repetitions; 95% CI, 0.93–0.97, <i>p</i> &lt; .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CCS participating in an exercise intervention trial experienced a high burden of adverse health outcomes. Increased physical fitness was associated with reduced disease burden for all survivors, emphasizing the importance of encouraging fitness improvements, regardless of cancer history.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and accuracy of targeted axillary dissection by carbon tattooing in biopsy-proven node-positive breast cancer: A prospective study","authors":"Minyan Chen MD,&nbsp;Zhenhu Lin MD,&nbsp;Xiaobin Chen MM,&nbsp;Jie Zhang MD,&nbsp;Wenhui Guo MD,&nbsp;Lili Chen MD,&nbsp;Yuxiang Lin MD,&nbsp;Xiaowen Chen MM,&nbsp;Cong Chen MM,&nbsp;Fangmeng Fu MD, PhD,&nbsp;Chuan Wang MD, PhD","doi":"10.1002/cncr.70047","DOIUrl":"10.1002/cncr.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Targeted axillary dissection (TAD) is used for less-invasive axillary staging in patients with initially node-positive breast cancer undergoing neoadjuvant chemotherapy (NACT). However, the efficacy of TAD using carbon suspension remains unclear. Here, the aim was to evaluate the feasibility and accuracy of TAD, combining sentinel lymph node biopsy (SLNB) using a single blue dye tracer with target lymph node biopsy (TLNB) using carbon suspension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective single-institution study enrolled patients with biopsy-proven T1 to 3 N1 to 3 breast cancer between March 2020 and December 2022. Pre-NACT, black carbon suspension was injected into pathologically confirmed positive axillary lymph nodes. Post-NACT, single tracer–based SLND combined with TLNB was performed, followed by axillary lymph node dissection. Detection rates, false-negative rates, and negative predictive values were calculated for TAD, SLNB, and TLNB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 268 patients enrolled, 254 were included in the final evaluation, of which 86 and 93 had cN2/3 and HER2-positive disease, respectively. Detection rates were SLNB, 87.4%; TLNB, 96.9%; and TAD, 85.4%. The overall axillary pathological complete response rate was 42.1% (107 patients). False-negative rates were SLNB, 7.8%; TLNB, 12.7%; and TAD, 6.3%, with negative predictive values of 90.3%, 85.1%, and 91.9%, respectively. In seven of eight false-negative TAD cases, only one had lymph node metastasis; most showed micrometastases or isolated tumor cells. Retrieving ≥3 lymph nodes using TAD reduced the false-negative rates to 3.8%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TAD based on carbon suspension marking and single blue dye tracer is feasible and accurate for axillary staging in initially pN+ patients with breast cancer post-NACT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Neoadjuvant chemotherapy is often used for patients with breast cancer who have positive lymph nodes. This study aimed to check if a method called targeted axillary dissection, involving the use of carbon suspension and a blue dye, is effective in identifying biopsied nodes. The researchers marked lymph nodes with carbon before treatment and performed surgeries after chemotherapy. The results showed that targeted axillary dissection is a feasible and accurate method to identify positive lymph nodes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 17","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal cancer treatments show promise","authors":"Mary Beth Nierengarten","doi":"10.1002/cncr.70000","DOIUrl":"10.1002/cncr.70000","url":null,"abstract":"&lt;p&gt;New treatments for metastatic colorectal cancer (mCRC) over the past year continue to show advancements in precision medicine, including targeting the &lt;i&gt;KRAS&lt;/i&gt;&lt;sup&gt;G12C&lt;/sup&gt; mutation (MT), microsatellite instability–high (MSI-H) status, or deficient mismatch repair (dMMR) status in locally advanced mCRC. Here are a couple of promising examples of the evolution of CRC treatment.&lt;/p&gt;&lt;p&gt;The recent publication of the overall survival (OS) analysis of the CodeBreaK 300 study showed a strong trend for improvement in OS in patients with &lt;i&gt;KRAS&lt;/i&gt;&lt;sup&gt;G12C&lt;/sup&gt;–mutated, chemorefractory mCRC treated with sotorasib plus panitumumab versus the investigator’s choice (trifluridine/tipiracil or regorafenib).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Although not statistically significant, the trend suggests a potential 30% relative reduction in the risk of death in favor of sotorasib plus panitumumab (hazard ratio [HR], 0.70; 95% CI, 0.41–1.18).&lt;/p&gt;&lt;p&gt;“This is promising for an incurable disease with a critical unmet need for molecularly selected therapies providing survival benefits,” state the investigators.&lt;/p&gt;&lt;p&gt;The senior author, Marwan G. Fakih, MD, a professor in the Department of Medical Oncology and Therapeutics Research and the division chief of GI Medical Oncology at the City of Hope Comprehensive Cancer Center in Duarte, California, points out that although statistical significance was not seen, it is important to note that the study was not powered for that endpoint. “In addition, about a quarter of the patients on the control arm received KRAS&lt;sup&gt;G12C&lt;/sup&gt; inhibitors at progression, further confounding the overall survival endpoint.”&lt;/p&gt;&lt;p&gt;The finding builds on prior results showing significantly prolonged progression-free survival (PFS) with sotorasib plus panitumumab versus the investigator’s choice (median PFS, 5.6 vs. 2.0 months), which represents a 52% reduction in the risk of disease progression or death in favor of sotorasib plus panitumumab, as well as a high overall response rate with a 30% durable response.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; These results supported the approval by the US Food and Drug Administration (FDA) of sotorasib and panitumumab for patients who have received prior oxaliplatin, irinotecan, and a fluoropyrimidine for &lt;i&gt;KRAS&lt;/i&gt;&lt;sup&gt;G12C&lt;/sup&gt; mCRC and also provided support for the National Comprehensive Cancer Network guidelines on using sotorasib and panitumumab in the second- and third-line treatment of &lt;i&gt;KRAS&lt;/i&gt;&lt;sup&gt;G12C&lt;/sup&gt; mCRC, says Dr Fakih.&lt;/p&gt;&lt;p&gt;The phase 3 CodeBreaK 300 trial included 160 patients with &lt;i&gt;KRAS&lt;/i&gt;&lt;sup&gt;G12C&lt;/sup&gt;–mutated, chemorefractory mCRC who were randomly assigned to receive sotorasib (960 mg) and panitumumab (&lt;i&gt;n&lt;/i&gt; = 53), sotorasib (240 mg) and panitumumab (&lt;i&gt;n&lt;/i&gt; = 53), or the investigator’s choice (&lt;i&gt;n&lt;/i&gt; = 54).&lt;/p&gt;&lt;p&gt;Commenting on the study, Cathy Eng, MD, the David H. Johnson Endowed Chair in Surgical and Medical Oncology and a professor of medicine, hematology, and oncology at Vander","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 16","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}