Journal of the National Cancer Institute最新文献

{"title":"ATR inhibitor, camonsertib, dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study)","authors":"Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer, Devalingam Mahalingam, Adrian J Fretland, Joseph D Schonhoft, Ian M Silverman, Marisa Wainszelbaum, Yi Xu, Danielle Ulanet, Maria Koehler, Timothy A Yap","doi":"10.1093/jnci/djae098","DOIUrl":"https://doi.org/10.1093/jnci/djae098","url":null,"abstract":"Background Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus dose/schedule optimization requires extended follow-up to assess prolonged treatment effects. Methods Long-term safety/tolerability and antitumor efficacy of three camonsertib monotherapy dose levels/schedules were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on/4 off (160 3/4; the preliminary recommended phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on/1 off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating-tumor-DNA (ctDNA)-based molecular response rate. Results The analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (HR = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity. Conclusion The 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering significantly reduced anemia incidence without any compromise to efficacy.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Executing plans to enhance diversity across cancer centers in the United States: Opportunities and challenges","authors":"Christopher I Li, Sherise Chantell Rogers, Carol J Bult, Carmen E Guerra, Angela Talton, Lovoria B Williams, Wendy Law","doi":"10.1093/jnci/djae100","DOIUrl":"https://doi.org/10.1093/jnci/djae100","url":null,"abstract":"Background Lack of diversity in the cancer research workforce persists which the new requirement for all NCI-designated cancer centers to have a Plan to Enhance Diversity (PED) seeks to address. However, it is not well understood how different cancer centers are approaching the development and execution of these plans. Our objective was to assess how cancer centers are establishing and pursuing their PED. Methods We conducted a cross-sectional survey of members of the Cancer Center DEI Network which includes all NCI-designated cancer centers and several emerging centers. 62 cancer centers (75% of those invited), including 58 NCI-designated cancer centers (81% of those with this designation), participated and completed a questionnaire that assessed PED leadership, major challenges, implementation strategies, and approach to evaluate PED progress. Results The most common PED challenge identified is recruiting diverse faculty (68% of centers) and the most common strategy currently used to address this is reviewing and revising faculty recruitment practices (67%). The most common approach centers are using to measure PED progress are shifts in demographics (68%), and data on the demographics of faculty, leadership, and trainees are available at 79%, 81%, and 75% of centers, respectively. Conclusion(s) While almost all centers have established a PED leadership structure, there is considerable variation in the approaches used to realize PED goals, and in the resources provided to support PED work. Realizing opportunities to share and implement common best practices and exemplar programs has the potential to elevate the impact of PED efforts nationally.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of TP53 germline variants in pediatric patients undergoing tumor testing: strategy and prevalence","authors":"Minjie Luo, Derek Wong, Kristin Zelley, Jinhua Wu, Jeffery Schubert, Elizabeth H Denenberg, Elizabeth A Fanning, Jiani Chen, Daniel Gallo, Netta Golenberg, Maha Patel, Laura K Conlin, Kara N Maxwell, Gerald B Wertheim, Lea F Surrey, Yiming Zhong, Garrett M Brodeur, Suzanne P MacFarland, Marilyn M Li","doi":"10.1093/jnci/djae102","DOIUrl":"https://doi.org/10.1093/jnci/djae102","url":null,"abstract":"Background TP53 alterations are common in certain pediatric cancers, making identification of putative germline variants through tumor genomic profiling crucial for patient management. Methods We analyzed TP53 alterations in 3123 tumors from 2788 pediatric patients sequenced using tumor-only or tumor-normal paired panels. Germline confirmatory testing was performed when indicated. Somatic and germline variants were classified following published guidelines. Results In 248 tumors from 222 patients, 284 Tier 1/2 TP53 sequence and small copy number variants were detected. Following germline classification, 73.9% of 142 unique variants were pathogenic/likely pathogenic (P/LP). Confirmatory testing on 118 patients revealed germline TP53 variants in 28 patients (23 P/LP and 5 uncertain significance), suggesting a minimum Li-Fraumeni syndrome (LFS) incidence of 0.8% (23/2788) in this cohort, 10.4% (23/222) in patients with TP53 variant-carrying tumors, and 19.5% (23/118) with available normal samples. About 25% (7/28) of patients with germline TP53 variants did not meet LFS diagnostic/testing criteria while 20.9% (28/134) with confirmed or inferred somatic origins did. TP53 biallelic inactivation occurred in 75% of germline carrier tumors and was also prevalent in other groups, causing an elevated tumor-observed variant allelic fraction (VAF). However, somatic evidence including low VAF correctly identified only 27.8% (25/90) of patients with confirmed somatic TP53 variants. Conclusion The high incidence and variable phenotype of LFS in this cohort highlights the importance of assessing germline status of TP53 variants identified in all pediatric tumors. Without clear somatic evidence, distinguishing somatic from germline origins is challenging. Classifying germline and somatic variants should follow appropriate guidelines.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer control Co-benefits of the Climate-Related provisions in the American inflation reduction act","authors":"Kilan C Ashad-Bishop, K Robin Yabroff, Leticia Nogueira","doi":"10.1093/jnci/djae101","DOIUrl":"https://doi.org/10.1093/jnci/djae101","url":null,"abstract":"The American Inflation Reduction Act (IRA) of 2022 contains climate-related provisions that may have significant implications for cancer control and prevention. This commentary assesses the potential co-benefits of the IRA for cancer control efforts, specifically policies and programs to reduce carcinogen exposure via air quality monitoring and air pollution reduction. Allocations through the IRA for air quality improvement, paired with its environmental justice provisions, holds promise for advancing cancer prevention by targeting resources to communities most susceptible to environmental hazards. Moreover, climate resilience measures dictated by the IRA are crucial for oncology professionals grappling with the dual challenges of climate change and cancer care. Climate-driven extreme weather events can exacerbate carcinogen exposure and disrupt access to cancer care, underscoring the need for resilient healthcare infrastructure. The IRA's provisions for clean energy incentives and infrastructure upgrades offer oncology care institutions opportunities to mitigate emissions and bolster resilience against climate-related disruptions, ultimately improving cancer outcomes. Climate-related initiatives funded by the IRA present a unique and timely avenue to advance equitable cancer control efforts. This commentary underscores the critical intersection between climate resilience policy and oncology care, highlighting the potential to promote a healthier and more resilient future for all.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine for pancreatic cancer: Characterizing the clinico-genomic landscape and outcomes of KRAS G12C-mutated disease","authors":"Fergus Keane, Joanne F Chou, Henry Walch, Joshua Schoenfeld, Anupriya Singhal, Darren Cowzer, Emily Harrold, Catherine O’Connor, Wungki Park, Anna Varghese, Imane El Dika, Fiyinfolu Balogun, Kenneth H Yu, Marinela Capanu, Nikolaus Schultz, Rona Yaeger, Eileen M O’Reilly","doi":"10.1093/jnci/djae095","DOIUrl":"https://doi.org/10.1093/jnci/djae095","url":null,"abstract":"Background Mutated KRAS is the most common oncogene alteration in pancreatic cancer (PDAC), and KRAS G12C mutations (KRAS G12Cmut) are observed in 1-2%. Several inhibitors of KRAS G12C have recently demonstrated promise in solid tumors, including PDAC. Little is known regarding clinical, genomics and outcome data of this population. Methods Patients with PDAC and KRAS G12Cmut were identified at Memorial Sloan Kettering Cancer Center (MSK), and via the AACR Project GENIE database. Clinical, treatment, genomic and outcomes data were analysed. A cohort of patients at MSK with non-G12C KRAS PDAC was included for comparison. Results Among 3,571 patients with PDAC, 39 with KRAS G12Cmut were identified (1.1%). Median age was 67 years, 56% were female. Median BMI was 29.2 kg/m2, 67% had a smoking history. Median OS 13 months (9.4, not reached (NR)) for stage IV, and 26 months (23, NR) for stage I-III. Complete genomic data (via AACR GENIE) was available for N = 74. Most common co-alterations included: TP53 (73%), CDKN2A (33%), SMAD4 (28%), and ARID1A (21%). Compared with a large cohort (N = 2931) of non-G12C KRAS-mutated PDAC, ARID1A co-mutations were more frequent in KRAS G12Cmut (P < .05). OS did not differ between KRAS G12Cmut and non-G12C KRAS PDAC. Germline pathogenic variants were identified in 17%. N = 2 received KRAS G12C-directed therapy. Conclusion PDAC and KRAS G12Cmut may be associated with a distinct clinical phenotype. Genomic features are similar to non-G12C KRAS-mutated PDAC, although enrichment of ARID1A co-mutations was observed. Targeting of KRAS G12C in PDAC provides a precedent for broader KRAS targeting in PDAC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding active living after cancer to underserved cancer survivors and their caregivers","authors":"Scherezade K Mama, Stacy J Mitchell, Patricia V Tracy, Luz Y Pena, Carolina D Moreno, Adriana Valdes, Yue Liao, Che Young Lee, Ashley Alexander, Margaret R Raber, Lorna H Mcneill, Karen Basen-Engquist","doi":"10.1093/jnci/djae097","DOIUrl":"https://doi.org/10.1093/jnci/djae097","url":null,"abstract":"Background Physical activity (PA) improves physical and psychological health in cancer survivors. This study evaluated Active Living After Cancer (ALAC), a community-based program to improve PA, physical function, and quality of life (QOL) in minority and medically underserved cancer survivors and their caregivers. Methods Participants completed 12 weekly ALAC sessions and assessments of PA, physical functioning, and QOL at baseline and follow-up (week 12). Paired samples t-tests were used to assess changes in outcomes over time. Results 540 cancer survivors (M age = 61.1 years, SD = 11.3) and 87 caregivers (M age = 62.3 years, SD = 13.1) were enrolled. Most were women (91.4%), Hispanic (61.1%) or non-Hispanic Black (19.3%), and medically underserved (86.4%). The percent of cancer survivors meeting PA recommendations increased from 28.9% to 60.2% (d = 0.75), and the number of sit-to-stand repetitions in a 30-second period increased from 12.3 to 14.3 (d = 0.39) from 0-12 weeks. Cancer survivors reported significant improvements in physical (T-score Δ = 1.7, d = 0.06) and mental (T-score Δ = 2.3, d = 0.31) health-related QOL. Caregivers also improved their PA, physical function, and QOL, and there were no statistically significant differences between breast and other cancer survivors and between cancer survivors and caregivers. Conclusions The ALAC program demonstrated increased PA, physical function, and QOL in medically underserved cancer survivors and their caregivers. Furthermore, ALAC was successfully implemented by community partners and serves as a good model for reaching medically underserved cancer survivors and improving survivorship. Additional efforts are warranted to further extend reach, improve cancer survivorship, and reduce cancer health disparities among underserved cancer survivors.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growing the global cancer care system: success stories from around the world and lessons for the future","authors":"Edward Christopher Dee, C S Pramesh, Christopher M Booth, Fidel Rubagumya, Miriam Mutebi, Erin Jay G Feliciano, Michelle Ann B Eala, Giovanni G Cerri, Ophira Ginsburg, Bishal Gyawali, Fabio Ynoe de Moraes","doi":"10.1093/jnci/djae087","DOIUrl":"https://doi.org/10.1093/jnci/djae087","url":null,"abstract":"Despite significant biomedical advancements in various realms of oncology, the benefits of these developments are not equitably distributed, particularly in under-resourced settings. While much work has described the challenges and systemic barriers in global cancer control, in this essay we focus on success stories. This piece describes clinical care delivered at Rwanda’s Butaro Cancer Center of Excellence, the cancer research collaborations under India’s National Cancer Grid, and the efforts of Latin America’s Institute of Cancer of São Paulo in advancing cancer care and training. These examples highlight the potential of strategic collaborations and resource allocation strategies in improving cancer care globally. We emphasize the critical role of partnerships between physicians and allied health professionals, funders, and policymakers in enhancing access to treatment and infrastructure, advancing contextualized research and national guidelines, and establishing regional and global collaborations. We also draw attention to challenges faced in diverse global settings and outline benchmarks to measure success in the fight against cancer.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RE: Potential role of cannabis in ameliorating observed racialized disparities in cancer pain management.","authors":"R. Giusti, Giampiero Porzio","doi":"10.1093/jnci/djae090","DOIUrl":"https://doi.org/10.1093/jnci/djae090","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of healthcare contact days with physical function and survival in CCTG/AGITG CO.17","authors":"Arjun Gupta, Christopher J O'Callaghan, Liting Zhu, Derek J Jonker, Ralph P W Wong, Bruce Colwell, Malcolm J Moore, Christos S Karapetis, Niall C Tebbutt, Jeremy D Shapiro, Dongsheng Tu, Christopher M Booth","doi":"10.1093/jnci/djae077","DOIUrl":"https://doi.org/10.1093/jnci/djae077","url":null,"abstract":"Introduction While contact days—days with healthcare contact outside home—are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes, and the prognostic ability of contact days. Methods We conducted a secondary analysis of CO.17 that evaluated cetuximab vs supportive care in patients with advanced colorectal cancer. CO.17 collected EORTC-QLQ-C30 instrument data. We assessed the association between number of contact days in a window and changes in physical function and global health status, and the association between number of contact days in the first 4 weeks with overall survival (OS). Results There was a negative association between the number of contact days and change in physical function (per each additional contact day at 4 weeks, 1.50 point decrease; and 8 weeks, 1.06 point decrease, p < .0001 for both), but not with global health status. This negative association was seen in patients receiving cetuximab, but not supportive care. More contact days in the first 4 weeks was associated with worse OS for all comers and patients receiving cetuximab (per each additional contact day; all comers, aHR 1.07, 95% CI, 1.05- 1.10; and cetuximab, aHR 1.08, 95%CI 1.05- 1.11, p < .0001 for both). Conclusions In this secondary analysis of a clinical trial, more contact days early in the course was associated with declines in physical function and worse survival in all-comers and in participants receiving cancer-directed treatment. Trial registration ClinicalTrials.gov number, NCT00079066","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"164 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complexities of PM2.5, greenspace, and childhood cancer.","authors":"Rena R Jones","doi":"10.1093/jnci/djae069","DOIUrl":"https://doi.org/10.1093/jnci/djae069","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}