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{"title":"Long-term cardiac outcomes in breast cancer patients treated with helical tomotherapy: Evaluating the applicability of 3D-based dose constraints for intensity modulated radiation therapy.","authors":"Pierre Loap, Abdelkarim Uakkas, Jihane Bouziane, Alain Fourquet, Youlia Kirova","doi":"10.1002/ijc.35474","DOIUrl":"10.1002/ijc.35474","url":null,"abstract":"<p><p>Adjuvant breast radiotherapy has been associated with cardiac toxicity due to older 2D and 3D techniques, with a linear relationship between mean heart dose (MHD) and ischemic cardiac events. Cardiac dose distribution differs with modern techniques like intensity-modulated radiotherapy (IMRT), potentially affecting this relationship. This study evaluates long-term cardiac toxicity in breast cancer patients treated with tomotherapy to reassess 3D-derived dose constraints. Breast cancer patients treated with tomotherapy at Institut Curie from August 2010 to December 2015 were included. Patients had undergone breast-conserving surgery or mastectomy, with some receiving chemotherapy or trastuzumab. Tomotherapy was used for anatomically challenging cases. The primary endpoint was cardiac toxicity correlated with MHD; secondary endpoints were overall and disease-specific survival. Statistical analyses included logistic regression and Cox models. Among 179 patients, the median MHD was 7.04 Gy, with 95.6% having an MHD above 5 Gy. Sixty-six patients had cardiovascular risk factors, and 28.5% were obese. Over a median follow-up of 9.1 years, eight patients (4.5%) experienced cardiovascular events-all with pre-existing risks or obesity. No significant correlation was found between MHD and major coronary events (p = 0.607) or heart failure (p = 0.800). Cardiac mortality was absent, and 10-year overall and disease-specific survival were 88.0% and 94.3%, respectively. Cardiac events in patients treated with tomotherapy were rare and driven by pre-existing risk factors. The linear MHD-toxicity relationship observed in 3D radiotherapy may not apply to IMRT, potentially leading to overestimated risks. Long-term studies are needed to refine IMRT dose constraints.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1386-1394"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126133","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":"p16^INK4a and HPV E4 immunohistochemistry for the prediction of regression of cervical intraepithelial neoplasia grade 2-A historical cohort study.","authors":"Rikke Damgaard, David Jenkins, Mark H Stoler, Miekel van de Sandt, Maurits N C de Koning, Wim G V Quint, Johnny Kahlert, Patti E Gravitt, Torben Steiniche, Lone K Petersen, Anne Hammer","doi":"10.1002/ijc.35469","DOIUrl":"10.1002/ijc.35469","url":null,"abstract":"<p><p>Cervical intraepithelial neoplasia grade 2 (CIN2) is a heterogeneous diagnosis with a high likelihood of spontaneous regression. Therefore, active surveillance for CIN2 has been implemented as an option in younger women in many countries. Yet, little is known about markers that may accurately predict the likelihood of regression to support active surveillance. Here, we aimed to assess whether p16^INK4a and HPV E4 status are associated with the likelihood of CIN2 regression. We conducted a historical cohort study on women aged 23-40 diagnosed with untreated CIN2 following cytology-based screening. Women were diagnosed at Aarhus University Hospital, Denmark from January 2000 to December 2010. Archived tissue samples were sectioned for p16^INK4a and HPV E4 immunohistochemistry and HPV genotyping. We used a modified Poisson model to estimate the relative risk of regression, adjusting for age and cytology (aRR). A total of 443 women with CIN2 were included. Most women (73.8%) were aged ≤30, and half had a high-grade cytology (48.8%). Overall, 47.6% regressed, and regression was less likely in p16^INK4a-positive compared to p16^INK4a-negative women (aRR 0.77; 95% CI 0.64-0.94). Among p16^INK4a-positive women, the risk of regression varied by HPV type and HPVE4 status, with lower risk in HPV16-positive women compared to those without (aRR 0.54; 95% CI 0.40-0.75) and in HPVE4-negative compared to HPVE4 positive women (aRR 0.73; 95% CI 0.54-0.98). When we restricted to expert-confirmed CIN2, the risk of regression did not vary by p16^INK4a or HPVE4 status, while HPV16 positive remained at a lower risk of regression compared to women without HPV16.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1294-1303"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952172","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":"Association between prediagnostic serum metabolites and pancreatic ductal adenocarcinoma risk in two prospective cohorts.","authors":"Ting Zhang, Steven C Moore, Sheng Fu, Xiaoyu Wang, Demetrius Albanes, Stephanie J Weinstein, Kai Yu, Rachael Z Stolzenberg-Solomon","doi":"10.1002/ijc.35479","DOIUrl":"10.1002/ijc.35479","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is highly fatal, with incidence rising worldwide. Metabolomics may provide insight into etiology and mechanisms contributing to pancreatic carcinogenesis. We examined associations between 1483 prediagnostic (up to 24 years) serum metabolites and PDAC in nested case-control studies within a cohort of male Finnish smokers and another of American men and women (n = 732 matched pairs). We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals per standard deviation increase in log-metabolite level within each cohort and combined using fixed-effect meta-analyses. We performed elastic net regression (EN) to select metabolites and calculated area under the curve (AUC) for established PDAC risk factors (smoking, diabetes, and overweight/obesity), selected metabolites, and their combination. Sixty-six metabolites were associated with PDAC at false discovery rate <0.05, with 26 below Bonferroni threshold (p < 3.4 × 10^-5) and 38 not reported previously. Notable findings include fibrinopeptide B (1-9); 13 modified, di- or poly-peptides; 11 tobacco-chemical related xenobiotics; glycolysis-gluconeogenesis-tricarboxylic acid (TCA) cycle metabolites (aspartate, glutamate, lactate, α-ketoglutarate, and pyruvate); and four secondary and two primary bile acids that were positively (OR = 1.18-1.58) and five fibrinogen cleavage peptides that were inversely (OR = 0.70-0.84) associated with PDAC. AUCs for combined metabolites-risk factors outperformed known risk factors (p ≤ .01) but not metabolites (p ≥ .31) alone. Systemic metabolism is prospectively associated with PDAC. New metabolite associations include those related to immune response, tobacco, microbiome, glycolysis-gluconeogenesis and TCA cycle, and adiposity or diabetes. The EN selected metabolites were more sensitive indicators of prediagnostic metabolic processes and exposures associated with PDAC than established risk factors.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1304-1315"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118470","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 perioperative outcomes of retroperitoneal lymph node dissection in Germany for patients with testicular cancer: Results from the GRAND study.","authors":"Nikolaos Pyrgidis, Maria Apfelbeck, Marc Kidess, Philipp Weinhold, Julian Marcon, Gerald B Schulz, Yannic Volz, Benedikt Ebner, Peter Maximilian Sparwasser, Igor Tsaur, Marcus Hentrich, Christian G Stief, Michael Chaloupka","doi":"10.1002/ijc.35486","DOIUrl":"10.1002/ijc.35486","url":null,"abstract":"<p><p>We aimed to assess the current trends and outcomes of retroperitoneal lymph node dissection (RPLND) in patients with testicular cancer in Germany, as well as to provide evidence on the role of the type of surgical approach, prior chemotherapy, and annual hospital caseload. We used the GeRmAn Nationwide inpatient Data, provided by the Research Data Center of the Federal Bureau of Statistics (2005-2022). We assessed trends and perioperative outcomes (mortality, intensive care unit [ICU] admission, transfusion, acute embolism, and length of hospital stay) based on the surgical approach (robotic, laparoscopic, and open), prior chemotherapy, and annual hospital caseload (with cut-offs of three and 10 cases/year) with a multivariable regression analysis. Overall, 6673 patients underwent RPLND for testicular cancer. Of them, 5570 (83%) received open, 819 (12%) laparoscopic, and 284 (5%) robot-assisted surgery. Patients had previously received chemotherapy in 1908 (29%) cases. Accordingly, 4431 (66%) patients underwent surgery in centers performing more than 3 cases/year, and 1325 (20%) in centers performing more than 10 cases/year. Over the past 18 years, the number of patients undergoing RPLND has decreased by half. In the multivariate regression analysis, a robotic and a laparoscopic approach was associated with lower odds of ICU admission, transfusion, and shorter hospital stay (p < .001) compared to an open approach. Patients undergoing surgery after prior chemotherapy presented similar perioperative outcomes compared to those who had not previously received chemotherapy. Similarly, patients undergoing surgery at high-volume centers presented comparable perioperative outcomes to those in low-volume centers based on the cut-off of three and 10 cases/year. Still, our findings were mitigated by selection bias. Overall, the number of annual RPLND cases in Germany has decreased over time.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1333-1341"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214496","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":"Microglial Activation and Inflammatory Responses in Parkinson's Disease Models Are Attenuated by TRPM2 Depletion.","authors":"Ana Flávia F Ferreira, Zhong-Ping Feng, Hong-Shuo Sun, Luiz Roberto G Britto","doi":"10.1002/glia.70055","DOIUrl":"10.1002/glia.70055","url":null,"abstract":"<p><p>Inflammation, and particularly microglial cells, has become a central feature in Parkinson's disease (PD) pathology. The transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable nonselective channel involved in the pathological mechanism of several inflammatory and neurodegenerative diseases. However, the role of TRPM2 in inflammation and microglial activation in the context of PD remains unclear. Here, we combined both in vivo and in vitro PD models to investigate that question. Male and female TRPM2 partial and complete knockout mice were submitted to the 6-hydroxidopamine mouse model of PD. We assessed microglia and lysosome-associated protein (CD68) density levels, microglial morphology and cluster classification, CD68 area in individual microglial cells, and the protein levels of six different cytokines in the substantia nigra pars compacta and the striatum. Our results indicate that TRPM2 deletion reduced microglial density, rescued its morphology, decreased CD68 staining area within microglia, and lowered pro-inflammatory cytokines levels in both male and female mice. To better understand TRPM2 involvement in PD pathology, we selectively knocked-down TRPM2 in neurons, microglia, or both cells in a human neuron-microglia co-culture PD model. An improvement in cell viability and a decrease in cell death were observed across the different experimental approaches. Lastly, TRPM2 deletion revealed reduced microglial phagocytosis and decreased expression of inflammation-related molecules. For the first time, we demonstrated that TRPM2 is a critical mediator of microglial function in the context of PD. Thus, this study suggests that TRPM2 inhibition may offer a novel therapeutic target for PD modification.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2035-2056"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641336","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":"Astrocytic-HSP60 Depletion Contributed to Autophagy Defects of Astrocytes and Depressive-Like Behaviors in Male Mice.","authors":"Weifen Li, Wenhui Zhu, Zi Zhu, Haier Xie, Tahir Ali, Zhijian Yu, Shupeng Li","doi":"10.1002/glia.70060","DOIUrl":"10.1002/glia.70060","url":null,"abstract":"<p><p>Depression, a prevalent mental health disorder, is multifaceted in its etiology. Growing evidence suggests that dysregulation of heat shock protein 60 (HSP60) contributes to neurological dysfunction, but its role in astrocyte-mediated depressive-like behaviors and neuroinflammation remains poorly understood. Here, we sought to investigate whether astrocyte-specific HSP60 depletion disrupts cellular homeostasis and is associated with astrocyte dysfunction that contributes to depressive-like behaviors and related inflammatory signaling, with a particular emphasis on the role of autophagy. Employing animal models, we demonstrate that chronic stress could dysregulate HSP60 in the brain of mice concurrent with inducing depressive-like symptoms in mice. Furthermore, astrocyte-specific HSP60 depletion (HSP60 cKO) male mice exhibited depressive-like behaviors, alongside significant disruption in astrocyte morphology and impaired autophagic processes within the cortex. Remarkably, these deleterious effects of HSP60 depletion were mitigated by triggering autophagy via urolithin A (UA) treatment, both in the brains of HSP60 cKO mice and in primary astrocytes derived from these mice. These findings shed light on the intricate interplay between astrocytes, HSP60, and autophagy in the etiology of depression, offering potential avenues for therapeutic strategies aimed at modulating astrocytic function and autophagic pathways to alleviate depressive symptoms and astrocyte-associated neuroinflammation.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2130-2146"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606945","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":"Randomised trial on treatment of vaginal high-grade squamous intraepithelial lesion: Self-administered vaginal imiquimod and laser vaporisation.","authors":"Mari Kiviharju, Annika Riska, Ilkka Kalliala, Maija Jakobsson, Annu Heinonen, Joakim Dillner, Pekka Nieminen, Karoliina Aro","doi":"10.1002/ijc.35497","DOIUrl":"10.1002/ijc.35497","url":null,"abstract":"<p><p>High grade vaginal squamous intraepithelial lesion (HSIL) (or vaginal intraepithelial neoplasia; VAIN) is a rare human papillomavirus (HPV)-related cancer precursor, which is commonly treated with laser vaporisation or other surgical methods to prevent progression to invasion. Vaginal HSIL has a substantial tendency to relapse despite treatment, for which HPV persistence is a known risk factor. Imiquimod is a topically applied immunomodulator and has shown promise in the treatment of high-grade HPV-related genital cancer precursors. The aim of this study was to assess the efficacy and patient compliance of self-administered vaginal imiquimod in comparison to laser vaporisation in the treatment of vaginal HSIL. We recruited 56 women with histological vaginal HSIL into a randomised controlled trial of laser vaporisation and self-administered vaginal imiquimod with follow-up up to 6 months. Follow-up visits included colposcopy, punch biopsies, and cervical or vaginal swabs for HPV genotyping. In per protocol analyses of 26 women in the laser arm and 27 women in the imiquimod arm, 53.8% and 77.8% (p = 0.07), respectively, showed histological regression at the end of the study. No progressions to invasion were detected during the study period. Genotype-specific post-treatment negativity for HPV occurred in 16.7% of the laser group and in 39.1% of the imiquimod group (p = 0.12). Imiquimod had short-term adverse effects, but 93% completed treatment as instructed. We conclude that vaginal imiquimod is an effective treatment for vaginal HSIL and could be considered an alternative to laser vaporisation.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1458-1464"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197779","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":"Diverse Subpopulations of Reactive Astrocytes Following Chronic Toxoplasma Infection.","authors":"Zoe A Figueroa, Jose L Martin, Arzu Ulu, William Agnew-Svoboda, Teresa Ubina, Martin M Riccomagno, Todd A Fiacco, Emma H Wilson","doi":"10.1002/glia.70053","DOIUrl":"10.1002/glia.70053","url":null,"abstract":"<p><p>Astrocytes provide physical and metabolic support for neurons, regulate the blood-brain barrier, and react to injury, infection, and disease. When astrocytes become reactive, maintenance of the inflammatory state and its functional implications throughout chronic neuroinflammation are all poorly understood. Several models of acute inflammation have revealed astrocyte subpopulations that go beyond a two-activation state model, instead encompassing distinct functional subsets. However, how reactive astrocyte (RA) subsets evolve over time during chronic inflammatory disease or infection has been difficult to address. Here we use a prolific human pathogen, Toxoplasma gondii, that causes lifelong infection in the brain alongside a Lcn2CreERT2 reporter mouse line to examine reactive astrocyte subsets during chronic neuroinflammation. Single-cell RNA sequencing revealed diverse astrocyte populations including transcriptionally unique Lcn2CreERT2+ RAs which change over the course of infection in a subset-dependent manner. In addition to an immune-regulating Lcn2CreERT2+ astrocyte population enriched with gene transcripts encoding chemokines CCL5, CXCL9, CXCL10, and receptors CCR7 and IL7R, a specific subset of Lcn2CreERT2+ astrocytes highly expressed transthyretin (Ttr), a secreted carrier protein involved in glycolytic enzyme activation and potential vasculature regulation and angiogenesis. These findings provide novel information about the evolution and diversity of reactive astrocyte subtypes and functional signatures at different stages of infection, revealing an undocumented role for transthyretin-expressing astrocytes in immune regulation at the central nervous system (CNS) vasculature.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"2003-2024"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598997","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":"Trifluoperazine Elevates Intracellular Ca²⁺ Levels and Locks Open the Store-Operated Calcium Entry Channels in Astrocytes.","authors":"Jiwoon Lim, Wongu Youn, C Justin Lee","doi":"10.1002/glia.70052","DOIUrl":"10.1002/glia.70052","url":null,"abstract":"<p><p>Trifluoperazine (TFP), a known inhibitor of Ca²⁺-bound calmodulin (Ca²⁺/CaM), has been reported to elevate cytosolic Ca²⁺ levels by disinhibiting inositol 1,4,5-triphosphate receptor 2 (IP₃R2), thereby suppressing glioblastoma invasion and inducing apoptosis. Interestingly, TFP induces a sustained Ca²⁺ plateau, sensitive to extracellular Ca²⁺, suggesting involvement of Ca²⁺ entry such as store-operated calcium entry (SOCE). However, the underlying molecular mechanism remains elusive. Here, we report that TFP induces sustained Ca²⁺ signals by blocking the Ca²⁺/CaM-dependent desensitization of SOCE channels in cortical astrocyte cultures. TFP induces a prolonged Ca²⁺ response, with distinct kinetics compared to other Ca²⁺ modulators such as TFLLR-NH₂ (a G_αq-coupled GPCR agonist) and thapsigargin (a sacro/endoplasmic reticulum Ca²⁺-ATPase inhibitor). Under extracellular Ca²⁺-free conditions, Ca²⁺ levels increase without reaching a plateau, suggesting that the sustained Ca²⁺ signal relies on Ca²⁺ influx. Pharmacological analysis shows that sustained Ca²⁺ signals by TFP are CaM-dependent. Gene silencing targeting STIM1 and Orai1-3 confirmed their essential roles in the sustained response. We find that TFP effectively \"locks open\" SOCE channels by inhibiting their desensitization, maintaining SOCE activity. This effect is also observed in ex vivo hippocampal dentate gyrus astrocytes. Structural modeling supports a mechanism in which TFP disrupts the interaction between Ca²⁺/CaM and the SOAR domain of STIM1. Together, these findings indicate that TFP elevates cytosolic Ca²⁺ levels by maintaining SOCE activation, offering novel insights into the molecular actions of this drug. TFP can be a pharmacological tool for SOCE research as it locks SOCE channels open.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":"1989-2002"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300779","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":"Patient factors and modifications to intended chemotherapy for women with Stages I-IIIA breast cancer.","authors":"Jenna Bhimani, Peng Wang, Grace B Gallagher, Kelli O'Connell, Victoria Blinder, Rachael Burganowski, Isaac J Ergas, Jennifer J Griggs, Narre Heon, Tatjana Kolevska, Yuriy Kotsurovskyy, Candyce H Kroenke, Cecile A Laurent, Raymond Liu, Kanichi G Nakata, Sonia Persaud, Janise M Roh, Sara Tabatabai, Emily Valice, Elisa V Bandera, Erin J Aiello Bowles, Lawrence H Kushi, Elizabeth D Kantor","doi":"10.1002/ijc.35494","DOIUrl":"10.1002/ijc.35494","url":null,"abstract":"<p><p>Modifications to intended chemotherapy regimens may be due to various reasons and may impact patient outcomes. Understanding which factors are associated with chemotherapy modifications can help inform treatment planning and improve cancer care. We examined the association between patient/tumor factors and modifications to intended chemotherapy in women with Stages I-IIIA breast cancer who were treated at Kaiser Permanente Northern California and Kaiser Permanente Washington from 2005 to 2019. Modifications were defined as any dose reductions in the first cycle or throughout chemotherapy, regimen change, treatment delay (single delay >14 days) or receiving fewer cycles of any drugs than expected. We used generalized linear models of the Poisson family with a log-link function to calculate prevalence ratios (PRatios). Of 9700 women receiving adjuvant chemotherapy, 34.6% had chemotherapy modifications. Selected results are shown: positive associations were observed with age (PRatio_{80+ vs. 18-39}: 1.93; 95% confidence interval [CI]: 1.50-2.50; p-trend <.001), body mass index (BMI) (PRatio_{≥35 vs. 18.5 to <25}: 1.53; 95% CI: 1.41-1.65; p-trend <.001), and Charlson comorbidity index (PRatio_{3+ vs. 0}: 1.33; 95% CI: 1.19-1.48; p-trend <.001), while more recent years of diagnosis were associated with decreased prevalence of treatment modifications (PRatio_{2015-2019 vs. 2005-2009}: 0.65; 95% CI: 0.61-0.69; p-trend <.001). Stage was also positively associated (PRatio_{Stage IIIA vs. I}: 1.24; 95% CI: 1.13-1.35; p-trend <.001), as was human epidermal growth factor-2 positive status (PRatio: 1.99; 95% CI: 1.89-2.10). In conclusion, patients with the highest likelihood of chemotherapy modifications represent those who may have more complex prescribing needs, including those of older age, higher BMI, and more comorbidity. Further understanding of how modifications could impact outcomes within these groups can inform and improve cancer care.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1342-1353"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197778","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}