Cancer最新文献

{"title":"Maintenance therapy with the FMS-like tyrosine kinase 3 inhibitor gilteritinib in patients with FMS-like tyrosine kinase 3–internal tandem duplication acute myeloid leukemia: A phase 2 study","authors":"Emmanuel Gyan MD, PhD,&nbsp;Mark D. Minden MD, PhD,&nbsp;Kohmei Kubo MD, PhD,&nbsp;Alessandro Rambaldi MD,&nbsp;Gunnar Juliusson MD,&nbsp;Martin Jädersten MD, PhD,&nbsp;Richard J. Kelly MD, PhD,&nbsp;László Szerafin MD, CSc,&nbsp;Wensheng He PhD,&nbsp;Stanley C. Gill PhD,&nbsp;Jason E. Hill PhD,&nbsp;Caroline Chen MD,&nbsp;David Delgado MD,&nbsp;Nahla Hasabou MD","doi":"10.1002/cncr.35746","DOIUrl":"https://doi.org/10.1002/cncr.35746","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The GOSSAMER phase 2 study assessed the <i>FMS</i>-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib as maintenance therapy in patients with <i>FLT3</i>–internal tandem duplication (<i>FLT3</i>-ITD) acute myeloid leukemia (AML) in first complete remission without previous hematopoietic stem cell transplantation (HSCT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients had to be within 2 months of their last consolidation cycle and have completed the recommended number of cycles per local practice. FLT3 inhibitors were allowed only during induction and/or consolidation. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS), event-free survival, and measurable residual disease (MRD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 98 patients were randomized (gilteritinib, <i>n</i> = 63; placebo, <i>n</i> = 35). RFS was not significantly different between the arms (hazard ratio, 0.74; 95% confidence interval, 0.41–1.34; <i>p</i> = .16). RFS rates for the gilteritinib and placebo arms were 68.5% and 55.3% at 1 year, 51.8% and 44.9% at 2 years, and 41.2% and 40.8% at 3 years, respectively. OS was not significantly different between the arms but may have been affected by subsequent AML therapies after discontinuation. In patients who received subsequent therapy (gilteritinib, 46.8%; placebo, 60.0%), a higher percentage of placebo-treated (57.1%) versus gilteritinib-treated patients (27.6%) underwent HSCT. At the end of treatment, 96.4% of gilteritinib-treated and 85.7% of placebo-treated patients had undetectable MRD. Relapsed placebo-treated (86.7%) versus gilteritinib-treated patients (34.8%) had a greater <i>FLT3</i> mutational burden. No new significant safety concerns were noted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The primary end point was not achieved; however, an observed trend toward potential benefit was noted in patients with <i>FLT3</i>-ITD AML who had not undergone prior HSCT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396823","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":"Relationships between patient-reported and clinician-rated toxicities and daily functioning in older adults with advanced cancer undergoing systemic therapy","authors":"Eva Culakova PhD,&nbsp;Mostafa Mohamed MD, PhD,&nbsp;Marie Flannery PhD, RN,&nbsp;Marielle Jensen-Battaglia PT, DPT,&nbsp;Zhihong Zhang PhD,&nbsp;Erika Ramsdale MD, MS,&nbsp;Rachael Tylock MS,&nbsp;Fiona Stauffer MS,&nbsp;Megan Wells MPH,&nbsp;Allison Magnuson DO,&nbsp;Kah Poh Loh MBBCh, BAO,&nbsp;Umang Gada MS,&nbsp;Michelle Janelsins PhD, MPH,&nbsp;Supriya Mohile MD, MS","doi":"10.1002/cncr.35766","DOIUrl":"https://doi.org/10.1002/cncr.35766","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Older adults with advanced cancer are at higher risk of treatment-related toxicities, which can impair function. Relationships between clinician-rated and patient-reported toxicities with functional decline remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This secondary analysis of the GAP70+ trial aimed to evaluate the associations between clinician-rated (Clinician-rated common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported toxicities (PRO-CTCAE) with changes in physical performance and functional outcomes in older adults receiving systemic therapy. Physical performance was measured using the Short Physical Performance Battery (SPPB; impairment: score ≤9). Functional capacity was assessed using activities of daily living (ADL) and instrumental ADL (IADL); impairment: any task difficulty. Toxicities were captured by CTCAE and PRO-CTCAE, which assess symptom severity and activity interferences. Generalized estimating equations evaluated the association of toxicity grades (0–1, 2, ≥3) within 3 months of treatment initiation with new functional impairments within 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients were age 70 to 96 years. At baseline, 82.9% had impaired SPPB, 51.5% had impaired IADL, and 27.4% had impaired ADL. Among patients without baseline impairments, 57.7%, 47.4%, and 31.0% developed new SPPB, IADL, and ADL impairments, respectively. No association was found between CTCAE toxicity and new SPPB impairment (<i>p</i> = .70), but higher PRO-CTCAE toxicity severity (<i>p</i> = .02) and interference (<i>p</i> = .02) were associated with new SPPB impairments. New IADL impairments were more common with higher grades of CTCAE (<i>p</i> = .02) severe PRO-CTCAE toxicities (<i>p</i> = .02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings emphasize the need to assess both clinician-rated and patient-reported toxicities to understand and mitigate functional decline in older adults with advanced cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35766","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396883","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":"Job descriptions by oncology patient navigator experience","authors":"Arti Patel Varanasi PhD, MPH, CPH,&nbsp;Linda Burhansstipanov DrPH, MSPH, OPN-CG,&nbsp;Sharon Gentry MSN, RN,&nbsp;Michelle Chappell MS,&nbsp;Carrie Dorn MPA, LMSW,&nbsp;Julie McMahon MPH,&nbsp;Kimberly Bradsher BS,&nbsp;Elba L. Saavedra Ferrer PhD, MS, OPN-CG,&nbsp;LaSonia Melvin Barnett MA,&nbsp;Marjorie Leighliter MHA, BSN, RN, OCN,&nbsp;Donna Moore Wilson MSN, RN, CBCN,&nbsp;Tracie Lewis MS","doi":"10.1002/cncr.35764","DOIUrl":"https://doi.org/10.1002/cncr.35764","url":null,"abstract":"&lt;p&gt;The American Cancer Society National Navigation Roundtable (ACS NNRT) was established in 2017.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The ACS NNRT is a national coalition of 100+ member organizations to advance navigation efforts that eliminate barriers to quality care, reduce disparities, and foster ongoing health equity across the cancer continuum. The ACS provides organizational leadership and expert staff support to the ACS NNRT. In 2024, the ACS NNRT Workforce Development Task Group (WFD) published an article that described job roles of patient navigators (PN) based on their level of expertise.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The purpose of the current article is to illustrate how the table (https://navigationroundtable.org/resource/patient-navigation-job-roles-by-levels-of-experience-workforce-development-task-group-national-navigation-roundtable/) from the published article can be used to generate job descriptions that align with roles and responsibilities of navigators. The current article is the work of the NNRT WFD and highlights insights and guidance from experts in the field. The 2024 table can provide a resource for navigators looking to advance careers and administrators creating job descriptions for navigators at different levels of proficiency. The table applies to clinical and oncology patient navigators across diverse settings and organizations (community, academic, and clinic-based).&lt;/p&gt;&lt;p&gt;Oncology patient navigation as an occupation and a health delivery support strategy has rapidly expanded over the last 3 decades with this care concept’s importance becoming widely accepted. Through the evolution of this profession, the role of the navigator has been updated to meet the needs of the community or health care system.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The profession has matured with evidence-based practices and peer-reviewed publications to support navigation titles, standards, training, qualifications, and validation of their contribution to value-based care. Efforts have also been made to standardize patient navigation roles to inform job descriptions.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; There remains a gap in standardized language to create job descriptions that patient navigation programs can use.&lt;/p&gt;&lt;p&gt;The origin of this profession started with Dr. Harold P. Freeman’s patient navigation goal to improve outcomes in populations that are medically underserved by eliminating barriers to timely cancer diagnosis and treatment in a culturally sensitive manner.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; He described “lay navigators (now defined as oncology patient navigators) as the principal navigators in our system,” but recognizes the need for other professional navigators such as social workers and nurses, to be integrated at more complex points of care.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; He acknowledges that patient navigators (now defined as “oncology patient navigators”) and clinical navigators (nurse and/or social worker) should possess specific knowledge and skill set based on patient ne","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396799","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":"Estimating cancer incidence attributable to physical inactivity in the United States","authors":"Brigid M. Lynch PhD,&nbsp;Julie K. Bassett PhD,&nbsp;Roger L. Milne PhD,&nbsp;Alpa V. Patel PhD,&nbsp;Erika Rees-Punia PhD,&nbsp;I-Min Lee MBBS, ScD,&nbsp;Steven C. Moore PhD,&nbsp;Charles E. Matthews PhD","doi":"10.1002/cncr.35725","DOIUrl":"https://doi.org/10.1002/cncr.35725","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous estimates of the number of cancers attributable to physical inactivity in the United States have typically focused on only three malignancies (colon, endometrial, and postmenopausal breast cancer). Contemporary epidemiologic evidence suggests that physical inactivity could contribute to up to 15 types of cancer, and a dose–response effect has been demonstrated for 13 of these. This study estimated the number of cancers diagnosed in the United States in 2015 due to physical inactivity for these 13 sites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from the 2005 National Health Interview Survey were used to estimate physical activity prevalence and, with the assumption of a 10-year latency period, 2015 cancer incidence data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Incidence US Cancer Statistics Public Use Database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The potential impact fraction was estimated to be 4.1%, which meant that 30,951 of 761,625 incident cancers at the 13 sites could have been prevented in the United States in 2015 if adults had increased physical activity by one category in 2005 (approximately 7.5 additional metabolic equivalent task hours per week [MET-h/week]). Theoretically, 85,415 of 761,625 incident cancers at the 13 sites (population attributable fraction, 11.2%) could have been prevented if all adults had achieved the highest level of physical activity (&gt;30 MET-h/week).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>When estimates are based on updated epidemiologic evidence regarding physical inactivity and cancer risk, substantially more cancers are attributable to physical inactivity than previously reported. A greater focus on physical activity promotion is warranted for cancer control in the United States.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396782","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":"A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma","authors":"Steven G. DuBois MD,&nbsp;Chitose Ogawa MD,&nbsp;Lucas Moreno MD,&nbsp;Yaël P. Mossé MD,&nbsp;Matthias Fischer MD,&nbsp;Anne L. Ryan MD,&nbsp;Kieuhoa T. Vo MD,&nbsp;Bram De Wilde MD,&nbsp;Alba Rubio-San-Simon MD,&nbsp;Margaret E. Macy MD,&nbsp;Lisa Howell MD,&nbsp;Suzanne Shusterman MD,&nbsp;Nadège Corradini MD,&nbsp;Roberto Luksch MD,&nbsp;Isabelle Aerts MD,&nbsp;Jennifer H. Foster MD,&nbsp;Brian D. Weiss MD,&nbsp;Chandrasekhar Pamidipati Karthik MSc,&nbsp;Eunice Yuen PhD,&nbsp;Emin Avsar PhD,&nbsp;Julie R. Park MD,&nbsp;Araz Marachelian MD","doi":"10.1002/cncr.35751","DOIUrl":"https://doi.org/10.1002/cncr.35751","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients aged 2–21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m²) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-five patients were treated. No dose-limiting toxicity occurred in monotherapy; one patient had dose-limiting toxicities in the combination therapy cohort (grade 3 mucositis and grade 4 neutropenia). The recommended phase 2 dose for both monotherapy and combination therapy was 15 mg/m². Twenty-two patients (88%) had one or more treatment-related adverse event(s) (TRAEs), and 18 (72%) experienced grade ≥3 TRAEs. Myelosuppression was the most common high-grade TRAE observed in the combination therapy cohort. At both dose levels, steady-state plasma concentrations exceeded xenograft 90% inhibitory concentration levels. In the monotherapy cohort, one patient had a minor response, and one patient had stable disease, both continuing for &gt;12 months. In the combination therapy cohort, two patients had a partial response, two had a minor response, and six had stable disease. Overall, the response rate, according to New Approaches to Neuroblastoma Therapy version 2.0 criteria, was 8%, and the disease control rate was 52%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof-of-concept clinical responses were observed, future studies with biomarker-selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388894","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":"Comparison of survival outcomes for patients with Lynch vs non-Lynch syndrome and microsatellite unstable colorectal cancer treated with immunotherapy","authors":"Cody Eslinger MD, MS,&nbsp;Daniel Walden MD,&nbsp;Alyssa McGary MS,&nbsp;Oluwadunni Emiloju MD,&nbsp;Daniel Ahn DO,&nbsp;Mohamad Bassam Sonbol MD,&nbsp;Tanios Bekaii-Saab MD,&nbsp;Mojun Zhu MD,&nbsp;Joleen Hubbard MD,&nbsp;Christina Wu MD","doi":"10.1002/cncr.35756","DOIUrl":"https://doi.org/10.1002/cncr.35756","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alterations in mismatch repair (MMR) genes like <i>MLH1</i>, <i>MSH2</i>, <i>MSH6</i>, and <i>PMS2</i> can lead to microsatellite instability–high (MSI-H) tumors. These mutations can be inherited, as in Lynch syndrome (LS), or occur de novo. Although immune checkpoint inhibitors (ICI) improves survival in MSI-H colorectal cancer (CRC) compared to chemotherapy, data comparing outcomes for patients with germline versus somatic MMR mutations are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included patients from Mayo Clinic (Arizona, Minnesota, Florida) from 2008 to 2023. A total of 81 patient records were reviewed. Patients with MMR-deficient or MSI-H CRC (<i>N</i> = 18 LS, <i>N</i> = 63 non-LS) were included for analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pembrolizumab was used in 65% of patients with LS and 94% of patients without LS, with median treatment durations of 11.7 and 8.8 months, respectively. Median overall survival (OS) for all stages was 82 months. There were no differences observed in OS for LS vs non-LS when patients in Stages II, III, and IV were analyzed separately. In Stage IV patients, <i>BRAF</i> V600E mutations were associated with worse OS compared to <i>BRAF</i> wild-type (hazard ratio, 2.69; 95% CI, 1.03–7.01, <i>p</i> = .043), with median OS of 19 vs. 113 months and progression-free survival of 12 vs. 95 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Patients with MSI-H CRC treated with ICIs exhibited similar outcomes regardless of germline or somatic MMR mutations. However, the presence of a <i>BRAF</i> V600E mutation was associated with a worse prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389003","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":"Chemotherapy dose density is prognostic for overall survival in patients with resectable pancreas cancer: A landmark analysis of SWOG 1505","authors":"Sameer H. Patel MD,&nbsp;Sarah Colby PhD,&nbsp;Davendra Sohal MD, MPH,&nbsp;Katherine A. Guthrie PhD,&nbsp;Lisa A. Kachnic MD,&nbsp;E. Gabriela Chiorean MD,&nbsp;Andrew M. Lowy MD,&nbsp;Flavio G. Rocha MD,&nbsp;Howard S. Hochster MD,&nbsp;Philip A. Philip MD, PhD,&nbsp;Syed A. Ahmad MD","doi":"10.1002/cncr.35759","DOIUrl":"https://doi.org/10.1002/cncr.35759","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chemotherapy is required to improve the overall survival (OS) of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose density (DD) on survival is difficult as a result of confounding. The objective of this study was to determine the impact of chemotherapy DD on OS in patients with resectable PDAC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a secondary analysis of SWOG 1505, a randomized phase 2 trial of perioperative chemotherapy in resectable PDAC. DD was defined as the percentage of chemotherapy dose received of the total planned. Two landmark time points for OS were used: after surgery and at 40 weeks (which encompassed the entire treatment period).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 102 eligible patients enrolled, 73 (71%) underwent surgery, and median preoperative chemotherapy DD was 89%. Patients with ≥85% DD had higher OS compared to those with &lt;85% DD (median, 38.1 vs. 17.2 months; <i>p</i> = .039). Of the 82 patients who survived to 40 weeks postrandomization, 67 underwent surgery, and median DD for all perioperative chemotherapy was 67%. In this cohort, DD ≥70% was associated with better OS (median, 32.2 vs. 14.0 months; <i>p</i> = .017). Perioperative DD was not significantly associated with pathologic response, margin status, or lymph node negativity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first study to identify a prognostic association of chemotherapy DD with OS in patients undergoing perioperative chemotherapy and surgery for resectable PDAC. Patients who received ≥85% DD preoperatively and/or ≥70% DD perioperatively survived longer than those receiving a smaller proportion of protocol therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388893","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":"Relationship between pain and nonopioid substance use in two national samples of cancer survivors","authors":"Jessica M. Powers PhD,&nbsp;Lisa R. LaRowe PhD,&nbsp;Dana Rubenstein MHS,&nbsp;Judith A. Paice PhD, RN,&nbsp;Brian Hitsman PhD,&nbsp;Christine M. Rini PhD","doi":"10.1002/cncr.35701","DOIUrl":"https://doi.org/10.1002/cncr.35701","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Pain and nonopioid substance use (tobacco, cannabis, alcohol) frequently co-occur, but have been understudied among cancer survivors. Even less work has examined whether pain and nonopioid substance use is related to other cancer treatment-related side effects, mental health, and health-related quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two national datasets were used to assess a range of variables and confirm patterns. Study 1 included 1252 adults (88% White; 55% female; 60% aged ≥65) from Wave 6 (2021) of the Population Assessment of Tobacco and Health Study, and Study 2 included 4130 adults (83% White; 56% female; <i>M</i> age = 66) from the 2020 National Health Interview Survey who reported a lifetime cancer diagnosis. Regression analyses were conducted separately by study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Study 1 results indicated that past-week pain intensity was associated with greater likelihood of using cigarettes, e-cigarettes, and cannabis (<i>p</i>s &lt; .003) and lower likelihood of using alcohol (<i>p</i> &lt; .001). Study 2 results indicated that chronic pain (vs. no chronic pain) was associated with greater likelihood of cigarette smoking (<i>p</i> &lt; .001) and lower likelihood of alcohol use (<i>p</i> &lt; .001). In both studies, cigarette smoking and pain were related to fatigue, sleep difficulties, poorer mental/physical health, and lower health-related quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pain is associated with greater likelihood of tobacco and cannabis use among cancer survivors. Given that substance use may impact cancer treatment and its side effects and contribute to pain chronification, there is an urgent need to develop tailored interventions for cooccurring pain and substance use in cancer survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380098","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":"Update on safety and feasibility of the combination of pembrolizumab and pelvic chemoradiation in locally advanced cervical cancer","authors":"Linda R. Duska MD, MPH,&nbsp;Gina R. Petroni PhD,&nbsp;Premal H. Thaker MD,&nbsp;Erin K. Crane MD,&nbsp;Laura L. Holman MD, MS,&nbsp;Debrorah K. Armstrong MD,&nbsp;Kara Romano MD,&nbsp;Jennifer Scalici MD","doi":"10.1002/cncr.35757","DOIUrl":"https://doi.org/10.1002/cncr.35757","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The addition of immune checkpoint inhibitors to standard-of-care chemoradiation (CRT) is established as the new standard of care in high-risk, locally advanced cervical cancer. However, the optimal sequencing of therapies is unknown. Defining safety and feasibility of the combination was a primary objective of this study examining concurrent versus sequential schedules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pembrolizumab was given after or during CRT in a randomized phase 2 design. Patients aged 18 years and older with locally advanced cervical cancer, stages IB–IVA (according to 2009 International Federation of Gynecology and Obstetrics staging) were randomized 1:1 to treatment regimens. CRT was identical for both arms. Pembrolizumab was administered every 3 weeks for three doses; no maintenance was allowed. Safety assessments included the incidence and severity of adverse events (AEs), and feasibility was measured by the completion of treatment in a predefined timeframe. Translational specimens (blood and tissue) were collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 94 evaluable patients completed treatment. Treatment-related grade ≥2 toxicity was experienced by 85 of 94 patients (90%); 40 patients (43%) had at least one grade 3 AE, and 22 (23%) had at least one grade 4 AE. There were no grade 5 AEs. Eighty percent of patients completed radiotherapy within 56 days, and 85% completed five or six doses of cisplatin and three doses of pembrolizumab (74 of 94 patients; 79%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The final results of this study support the safety and feasibility of adding pembrolizumab to pelvic CRT, concurrently and sequentially. Progression-free and overall survival were not affected or different between treatment arms. An analysis of the translational end points is ongoing and will inform future study designs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370080","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":"Olaparib in treatment-refractory isocitrate dehydrogenase 1 (IDH1)– and IDH2-mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial","authors":"Michael Cecchini MD,&nbsp;Mary Jo Pilat PhD, MS, PA,&nbsp;Nataliya Uboha MD, PhD,&nbsp;Nilofer S. Azad MD,&nbsp;May Cho MD,&nbsp;Elizabeth J. Davis MD,&nbsp;Jordi Rodon Ahnert MD, PhD,&nbsp;Gabriel Tinoco MD,&nbsp;Geoffrey I. Shapiro MD, PhD,&nbsp;Simon Khagi MD,&nbsp;Benjamin Powers MD,&nbsp;Kristen Spencer DO,&nbsp;Roman Groisberg MD,&nbsp;Jan Drappatz MD,&nbsp;Li Chen PhD,&nbsp;Biswajit Das PhD,&nbsp;Xun Bao PhD,&nbsp;Jing Li PhD,&nbsp;Azeet Narayan PhD,&nbsp;Dennis Vu BS,&nbsp;Abhijit Patel MD, PhD,&nbsp;Monica Niger MD,&nbsp;Deborah Doroshow MD, PhD,&nbsp;Diane Durecki MS,&nbsp;Scott A. Boerner MS,&nbsp;Ranjit Bindra MD, PhD,&nbsp;Percy Ivy MD,&nbsp;Derek Shyr PhD,&nbsp;Yu Shyr PhD,&nbsp;Patricia M. LoRusso DO","doi":"10.1002/cncr.35755","DOIUrl":"https://doi.org/10.1002/cncr.35755","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neomorphic isocitrate dehydrogenase (<i>IDH</i>) mutations lead to the accumulation of 2-hydroxyglutarate (2-HG), an oncometabolite implicated in tumor progression via inhibitory effects on alpha-ketoglutarate. Moreover, mutant <i>IDH</i>–dependent accumulation of 2-HG results in homologous recombination deficiency (HRD), which preclinically renders tumors sensitive to poly(adenosine diphosphate ribose) polymerase inhibitors. Here, the results of the cholangiocarcinoma (CCA) arm of the National Cancer Institute (NCI) 10129 olaparib in <i>IDH</i>-mutant solid tumors basket trial are reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Olaparib 300 mg twice daily was evaluated in an open-label, phase 2 clinical trial for treatment-refractory <i>IDH</i>-mutant solid tumors. Patients in the <i>IDH</i>-mutant CCA arm enrolled in two cohorts: (1) IDH inhibitor (IDHi) pretreated and (2) IDHi untreated, with a primary end point of overall response rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NCI 10129 enrolled 30 patients with <i>IDH</i>-mutant CCA with no objective responses seen, and recruitment was closed early. Median progression-free survival (PFS) was 2.4 months (95% CI, 1.9 to 6.5 months) and median overall survival was 12.9 months (95% CI, 6.3 months to not reached). Eight patients (27%) had clinical benefit (CB), with a PFS of ≥6 months. Patients with CB had lower baseline 2-HG levels compared to those without CB (1.4 vs. 5.9 µmol/L; <i>p</i> = .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Olaparib does not have sufficient single-agent activity to warrant further development in <i>IDH</i>-mutant CCA. However, a subgroup of patients demonstrated CB, and exploratory analysis revealed this subgroup to be enriched for lower baseline 2-HG levels. Future clinical trials leveraging the HRD properties of <i>IDH</i> mutations are warranted with enhanced patient selection and novel combination therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362497","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}