Anders Berglund, Kosj Yamoah, Steven A. Eschrich, Rana Falahat, James J. Mulé, Sungjune Kim, Jaime Matta, Julie Dutil, Gilberto Ruiz-Deya, Carmen Ortiz Sanchez, Liang Wang, Hyun Park, Hirendra N. Banerjee, Tamara Lotan, Kathryn Hughes Barry, Ryan M. Putney, Seung Joon Kim, Clement Gwede, Jacob K. Kresovich, Youngchul Kim, Hui-Yi Lin, Jasreman Dhillon, Ratna Chakrabarti, Jong Y. Park
Introduction
Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.
Methods
This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array.
Results
Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa.
Conclusion
Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.
{"title":"Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes","authors":"Anders Berglund, Kosj Yamoah, Steven A. Eschrich, Rana Falahat, James J. Mulé, Sungjune Kim, Jaime Matta, Julie Dutil, Gilberto Ruiz-Deya, Carmen Ortiz Sanchez, Liang Wang, Hyun Park, Hirendra N. Banerjee, Tamara Lotan, Kathryn Hughes Barry, Ryan M. Putney, Seung Joon Kim, Clement Gwede, Jacob K. Kresovich, Youngchul Kim, Hui-Yi Lin, Jasreman Dhillon, Ratna Chakrabarti, Jong Y. Park","doi":"10.1002/cam4.70044","DOIUrl":"10.1002/cam4.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as <i>CD40</i>, <i>Galectin3</i>, <i>OX40L</i>, and <i>STING</i>, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as <i>COL18A1</i>, <i>S100A2</i>, <i>ITGA4</i>, <i>HLA-C</i>, and <i>ADCYAP1</i>, have previously been linked to tumor progression in PCa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003182","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}
Josh McGovern, Fraser O'Rourke, Sarah Will, Hanh Thi Ngoc Nguyen, Elise Cranfield, Charlotte Maseland, Nicholas MacLeod, John D. Maclay, Barry J. Laird, Ross D. Dolan, Donald C. McMillan
Introduction
The present study sought to examine the relationships between systemic inflammatory composite ratios/cumulative scores, magnitude of systemic inflammatory response (SIR) and survival in good performance status patients (ECOG-PS 0/1) with advanced NSCLC receiving palliative radiotherapy.
Methods
Systemic inflammatory composite ratios/cumulative scores included the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein, (CRP)-albumin ratio (CAR), neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil-platelet score (NPS), modified Glasgow prognostic score (mGPS). The magnitude of SIR was determined by serum CRP concentration, with a median CRP concentration of >10 m mg/L considered to be systemically inflamed. Relationships between systemic inflammatory composite ratios/ cumulative scores and clinicopathological characteristics were examined using chi-square analysis. Relationships between overall survival (OS) and systemic inflammatory composite ratios/ cumulative scores were examined using cox regression analysis.
Results
479 patients were included. 48% (n = 231) of patients were male and 70% (n = 338) were ≥65 years of age. 29% (n = 140) patients were ECOG-PS 0 and 71% (n = 339) were ECOG-PS 1. 98% (n = 469) of patients died during follow-up. The median survival was 5 months (2–11). A similar prevalence of systemic inflammation was noted across the various ratios/scores (NLR >3 68%; LMR <2.4 65%; PLR >150 70%; CAR >0.20 83%; NLS ≥1 66%; LMS ≥1 71%; NPS≥1 50%; PLS≥1 60% and mGPS≥1 75%). Despite not considered to be systemically inflamed, an NLR <3, LMR ≥2.4, PLR ≤150, NLS 0, LMS 0, NPS 0 and PLS 0 all had a median CRP concentration of >10 mg/L. When adjusted for ECOG-PS, CAR>0.40 (p < 0.001) and mGPS 2 (p < 0.05) remained significantly associated with OS.
Conclusion
Liver-based measures of systemic inflammation (CAR and mGPS) appear more reliable for the quantification of the magnitude of SIR and have prognostic value in patients with advanced NSCLC.
{"title":"The prevalence and prognostic value of systemic inflammation in good performance status patients with advanced, inoperable non-small cell lung cancer receiving palliative radiotherapy: Comparison of composite ratios and cumulative scores","authors":"Josh McGovern, Fraser O'Rourke, Sarah Will, Hanh Thi Ngoc Nguyen, Elise Cranfield, Charlotte Maseland, Nicholas MacLeod, John D. Maclay, Barry J. Laird, Ross D. Dolan, Donald C. McMillan","doi":"10.1002/cam4.70139","DOIUrl":"10.1002/cam4.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The present study sought to examine the relationships between systemic inflammatory composite ratios/cumulative scores, magnitude of systemic inflammatory response (SIR) and survival in good performance status patients (ECOG-PS 0/1) with advanced NSCLC receiving palliative radiotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Systemic inflammatory composite ratios/cumulative scores included the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein, (CRP)-albumin ratio (CAR), neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil-platelet score (NPS), modified Glasgow prognostic score (mGPS). The magnitude of SIR was determined by serum CRP concentration, with a median CRP concentration of >10 m mg/L considered to be systemically inflamed. Relationships between systemic inflammatory composite ratios/ cumulative scores and clinicopathological characteristics were examined using chi-square analysis. Relationships between overall survival (OS) and systemic inflammatory composite ratios/ cumulative scores were examined using cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>479 patients were included. 48% (<i>n</i> = 231) of patients were male and 70% (<i>n</i> = 338) were ≥65 years of age. 29% (<i>n</i> = 140) patients were ECOG-PS 0 and 71% (<i>n</i> = 339) were ECOG-PS 1. 98% (<i>n</i> = 469) of patients died during follow-up. The median survival was 5 months (2–11). A similar prevalence of systemic inflammation was noted across the various ratios/scores (NLR >3 68%; LMR <2.4 65%; PLR >150 70%; CAR >0.20 83%; NLS ≥1 66%; LMS ≥1 71%; NPS≥1 50%; PLS≥1 60% and mGPS≥1 75%). Despite not considered to be systemically inflamed, an NLR <3, LMR ≥2.4, PLR ≤150, NLS 0, LMS 0, NPS 0 and PLS 0 all had a median CRP concentration of >10 mg/L. When adjusted for ECOG-PS, CAR>0.40 (<i>p</i> < 0.001) and mGPS 2 (<i>p</i> < 0.05) remained significantly associated with OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Liver-based measures of systemic inflammation (CAR and mGPS) appear more reliable for the quantification of the magnitude of SIR and have prognostic value in patients with advanced NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007904","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}
Iwona Wnętrzak, Mateusz Czajkowski, Klaudia Barańska, Marta Miklewska, Urszula Wojciechowska, Roman Sosnowski, Joanna A. Didkowska
Objectives
To examine the epidemiology of penile cancer in Poland compared to other European countries.
Materials and Methods
Incidence and mortality data were acquired from the national cancer registries in Europe and WHO Mortality Database, respectively. The data are presented as age-standardised morbidity and mortality rates, calculated according to the standard population of the world. We utilised Joinpoint analysis to assess the trends in morbidity and mortality and calculated the average rate of increase or decrease (Annual Percentage Change, Average Annual Percentage Change). Additionally, we estimate the proxy survival rates for each country.
Results
Our study is the first to cover the incidence of penile cancer in many European countries and estimates an approximate survival rate for large populations, which is rarely cited in the literature. The 40+ age group presented graphically in the article covered more than 90% of penile cancer cases and deaths. In the countries examined, there was an excess of deaths over incidence in the oldest age groups (75 years or older). Poland had intermediate incidence and mortality rates.
Conclusions
Unlike many European countries, Poland is witnessing an increasing trend of penile cancer mortality. The higher death toll among those aged 75 years or older may suggest a lack of recognition of cancer symptoms and inadequate attention to elderly patients by the healthcare system. There is also evidence of underreporting penile cancer cases. Establishing centralised healthcare systems for rare cancers is a commendable development that should be emulated by other European countries, including Poland.
{"title":"Epidemiology of penile cancer in Poland compared to other European countries","authors":"Iwona Wnętrzak, Mateusz Czajkowski, Klaudia Barańska, Marta Miklewska, Urszula Wojciechowska, Roman Sosnowski, Joanna A. Didkowska","doi":"10.1002/cam4.70092","DOIUrl":"10.1002/cam4.70092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To examine the epidemiology of penile cancer in Poland compared to other European countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Incidence and mortality data were acquired from the national cancer registries in Europe and WHO Mortality Database, respectively. The data are presented as age-standardised morbidity and mortality rates, calculated according to the standard population of the world. We utilised Joinpoint analysis to assess the trends in morbidity and mortality and calculated the average rate of increase or decrease (Annual Percentage Change, Average Annual Percentage Change). Additionally, we estimate the proxy survival rates for each country.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study is the first to cover the incidence of penile cancer in many European countries and estimates an approximate survival rate for large populations, which is rarely cited in the literature. The 40+ age group presented graphically in the article covered more than 90% of penile cancer cases and deaths. In the countries examined, there was an excess of deaths over incidence in the oldest age groups (75 years or older). Poland had intermediate incidence and mortality rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Unlike many European countries, Poland is witnessing an increasing trend of penile cancer mortality. The higher death toll among those aged 75 years or older may suggest a lack of recognition of cancer symptoms and inadequate attention to elderly patients by the healthcare system. There is also evidence of underreporting penile cancer cases. Establishing centralised healthcare systems for rare cancers is a commendable development that should be emulated by other European countries, including Poland.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007939","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}
Kevin T. Liou, Sheila N. Garland, Salimah H. Meghani, Nadia M. Kaye, Embree Thompson, Q. Susan Li, Jun J. Mao
Background
Racial disparities in sleep are well-documented. However, evidence-based options for addressing these disparities are lacking in cancer populations. To inform future research on sleep interventions, this study aims to understand racial differences in treatment responses to acupuncture and cognitive behavioral therapy for insomnia (CBT-I) among Black and White cancer survivors.
Methods
We conducted a secondary analysis of a comparative effectiveness trial evaluating acupuncture versus CBT-I for insomnia in cancer survivors. We compared insomnia severity, sleep characteristics, and co-morbid symptoms, as well as treatment attitudes, adherence, and responses among Black and White participants.
Results
Among 156 cancer survivors (28% Black), Black survivors reported poorer sleep quality, longer sleep onset latency, and higher pain at baseline, compared to White survivors (all p < 0.05). Black survivors demonstrated lower adherence to CBT-I than White survivors (61.5% vs. 88.5%, p = 0.006), but their treatment response to CBT-I was similar to white survivors. Black survivors had similar adherence to acupuncture as white survivors (82.3% vs. 93.4%, p = 0.16), but they had greater reduction in insomnia severity with acupuncture (−3.0 points, 95% CI −5.4 to 0.4, p = 0.02).
Conclusion
This study identified racial differences in sleep characteristics, as well as treatment adherence and responses to CBT-I and acupuncture. To address racial disparities in sleep health, future research should focus on improving CBT-I adherence and confirming the effectiveness of acupuncture in Black cancer survivors.
{"title":"Racial differences in treatment adherence and response to acupuncture and cognitive behavioral therapy for insomnia among Black and White cancer survivors","authors":"Kevin T. Liou, Sheila N. Garland, Salimah H. Meghani, Nadia M. Kaye, Embree Thompson, Q. Susan Li, Jun J. Mao","doi":"10.1002/cam4.7344","DOIUrl":"10.1002/cam4.7344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Racial disparities in sleep are well-documented. However, evidence-based options for addressing these disparities are lacking in cancer populations. To inform future research on sleep interventions, this study aims to understand racial differences in treatment responses to acupuncture and cognitive behavioral therapy for insomnia (CBT-I) among Black and White cancer survivors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a secondary analysis of a comparative effectiveness trial evaluating acupuncture versus CBT-I for insomnia in cancer survivors. We compared insomnia severity, sleep characteristics, and co-morbid symptoms, as well as treatment attitudes, adherence, and responses among Black and White participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 156 cancer survivors (28% Black), Black survivors reported poorer sleep quality, longer sleep onset latency, and higher pain at baseline, compared to White survivors (all <i>p</i> < 0.05). Black survivors demonstrated lower adherence to CBT-I than White survivors (61.5% vs. 88.5%, <i>p</i> = 0.006), but their treatment response to CBT-I was similar to white survivors. Black survivors had similar adherence to acupuncture as white survivors (82.3% vs. 93.4%, <i>p</i> = 0.16), but they had greater reduction in insomnia severity with acupuncture (−3.0 points, 95% CI −5.4 to 0.4, <i>p</i> = 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified racial differences in sleep characteristics, as well as treatment adherence and responses to CBT-I and acupuncture. To address racial disparities in sleep health, future research should focus on improving CBT-I adherence and confirming the effectiveness of acupuncture in Black cancer survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.7344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003183","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}
Charlotte W. Duinkerken, Sabrina Chiodo, Katrina Hueniken, Michael Hauptmann, Katarzyna Jóźwiak, Dangxiao Cheng, Andrew Hope, Geoffrey Liu, Charlotte L. Zuur
Background
Concomitant high-dose cisplatin with radiotherapy is commonly used for treating head and neck squamous cell carcinoma (HNSCC). Cisplatin, often used with radiotherapy, is known for causing irreversible sensorineural hearing loss, with individual variability suggesting a genetic component. This study aims to enhance the predictive ability of the clinical prediction model for cisplatin-induced hearing loss (CIHL) in HNSCC patients, as outlined in Theunissen et al., by incorporating significant genetic variants.
Methods
Conducted at the Netherlands Cancer Institute, this retrospective study included 74 patients treated between 1997 and 2011. Thirty-one SNPs that were previously associated with CIHL or other cisplatin-induced toxicities were identified and incorporated into the model. The primary outcome measured was the change in decibels at posttreatment 1-2-4 kHz hearing levels per additional minor allele of these SNPs, evaluated using linear mixed-effects regression models. The model's predictive accuracy was determined by the area under the curve (AUC) using 10-fold cross-validation.
Results
The rs2289669 SNP in the SLC47A1/MATE1 gene was linked to a significant 2.67 dB increase in hearing loss per allele (95% CI 0.49–4.86, p = 0.017). Incorporating rs2289669 improved the model's AUC from 0.78 to 0.83, a borderline significant improvement (p = 0.073).
Conclusions
This study underscores the importance of the rs2289669 SNP in CIHL and demonstrates the potential of combining genetic and clinical data for enhanced predictive models in personalized treatment strategies.
{"title":"The role of genetic variants in the prediction of hearing loss due to cisplatin chemoradiotherapy","authors":"Charlotte W. Duinkerken, Sabrina Chiodo, Katrina Hueniken, Michael Hauptmann, Katarzyna Jóźwiak, Dangxiao Cheng, Andrew Hope, Geoffrey Liu, Charlotte L. Zuur","doi":"10.1002/cam4.7465","DOIUrl":"10.1002/cam4.7465","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Concomitant high-dose cisplatin with radiotherapy is commonly used for treating head and neck squamous cell carcinoma (HNSCC). Cisplatin, often used with radiotherapy, is known for causing irreversible sensorineural hearing loss, with individual variability suggesting a genetic component. This study aims to enhance the predictive ability of the clinical prediction model for cisplatin-induced hearing loss (CIHL) in HNSCC patients, as outlined in Theunissen et al., by incorporating significant genetic variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Conducted at the Netherlands Cancer Institute, this retrospective study included 74 patients treated between 1997 and 2011. Thirty-one SNPs that were previously associated with CIHL or other cisplatin-induced toxicities were identified and incorporated into the model. The primary outcome measured was the change in decibels at posttreatment 1-2-4 kHz hearing levels per additional minor allele of these SNPs, evaluated using linear mixed-effects regression models. The model's predictive accuracy was determined by the area under the curve (AUC) using 10-fold cross-validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The rs2289669 SNP in the <i>SLC47A1/MATE1</i> gene was linked to a significant 2.67 dB increase in hearing loss per allele (95% CI 0.49–4.86, <i>p</i> = 0.017). Incorporating rs2289669 improved the model's AUC from 0.78 to 0.83, a borderline significant improvement (<i>p</i> = 0.073).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study underscores the importance of the rs2289669 SNP in CIHL and demonstrates the potential of combining genetic and clinical data for enhanced predictive models in personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.7465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003185","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}
This study aimed to verify if intraoperative radiotherapy (IORT) can achieve the same survival outcome as whole-breast external beam radiotherapy (EBRT) in early breast cancer after breast-conserving surgery (BCS), and to explore the suitable candidates that can safely receive IORT after BCS.
Methods
Eligible post-BCS patients who received IORT or EBRT were included in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2018. Risk factors that affected 5-year overall survival (OS) or breast cancer specific survival (BCSS) were identified by Cox proportional hazards regression analysis. Clinical characteristics, OS, and BCSS were comparatively analyzed between the two treatment modalities.
Results
The survival analysis after propensity score matching confirmed that patients who received IORT (n = 2200) had a better 5-year OS than those who received EBRT (n = 2200) (p = 0.015). However, the two groups did not differ significantly in 5-year BCSS (p = 0.381). This feature persisted even after multivariate analyses that took into account numerous clinical characteristics. Although there was no significant difference in BCSS between different subgroups of patients treated with IORT or EBRT, patients over 55 years of age, with T1, N0, non-triple negative breast cancers, hormone receptor-positive, and histologic grade II showed a better OS after receiving IORT.
Conclusion
In low-risk, early-stage breast cancer, IORT was not inferior to EBRT considering 5-year BCSS and OS. Considering the equivalent clinical outcome but less radiotoxicity, IORT might be a reasonable alternative to EBRT in highly selective patients undergoing BCS.
{"title":"Intraoperative radiotherapy: An alternative to whole-breast external beam radiotherapy in the management of highly selective breast cancer: A SEER database analysis","authors":"Dexun Sun, Guanhua Lu, Fenmei Liang, Wangjian Zhang, Tao Zeng, Yun Ling, Haojie Peng, Ting Xia, Meilin Hu, Xinxin Chen","doi":"10.1002/cam4.7458","DOIUrl":"10.1002/cam4.7458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to verify if intraoperative radiotherapy (IORT) can achieve the same survival outcome as whole-breast external beam radiotherapy (EBRT) in early breast cancer after breast-conserving surgery (BCS), and to explore the suitable candidates that can safely receive IORT after BCS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible post-BCS patients who received IORT or EBRT were included in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2018. Risk factors that affected 5-year overall survival (OS) or breast cancer specific survival (BCSS) were identified by Cox proportional hazards regression analysis. Clinical characteristics, OS, and BCSS were comparatively analyzed between the two treatment modalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The survival analysis after propensity score matching confirmed that patients who received IORT (<i>n</i> = 2200) had a better 5-year OS than those who received EBRT (<i>n</i> = 2200) (<i>p</i> = 0.015). However, the two groups did not differ significantly in 5-year BCSS (<i>p</i> = 0.381). This feature persisted even after multivariate analyses that took into account numerous clinical characteristics. Although there was no significant difference in BCSS between different subgroups of patients treated with IORT or EBRT, patients over 55 years of age, with T1, N0, non-triple negative breast cancers, hormone receptor-positive, and histologic grade II showed a better OS after receiving IORT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In low-risk, early-stage breast cancer, IORT was not inferior to EBRT considering 5-year BCSS and OS. Considering the equivalent clinical outcome but less radiotoxicity, IORT might be a reasonable alternative to EBRT in highly selective patients undergoing BCS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.7458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999001","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}
The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients.
Methods
Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan–Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction.
Results
A total of 170 patients were enrolled, with a median age of 60 years (range 43–77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs.
Conclusions
Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.
{"title":"Radiotherapy and chemoradiotherapy for postoperative recurrence in patients with esophageal squamous cell carcinoma","authors":"Qing Liu, Xue-Hua Tu, Rui-Xuan Yu, Hong-Ying Wen, Xiao-Guang Guo, Dai-Yuan Ma, Kai-Yuan Jiang, Dong Tian","doi":"10.1002/cam4.70108","DOIUrl":"10.1002/cam4.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan–Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 170 patients were enrolled, with a median age of 60 years (range 43–77). No significant difference was found in the median PRS between the salvage RT and CRT groups (<i>p</i> > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all <i>p</i> < 0.05) for PRS. Salvage treatment was not associated with PRS (<i>p</i> = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (<i>p</i> = 0.043) and had no significant differences in toxic reactions compared to RT (<i>p</i> = 0.924). In addition, RT showed better prognoses (<i>p</i> = 0.020) and lower toxic reactions (<i>p</i> = 0.030) than CRT in patients with positive LNs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003184","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}
Aihong Zheng, Yiwen Wang, Shuang Li, Yingjie Wang, Hong'en Xu, Jieni Ding, Bingchen Chen, Tao Song, Lei Lai
Objective
To compare the survival discrimination of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma (ASCC) treated nonsurgically and suggest a simple revised staging system with data from the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
Overall survival (OS) was the primary endpoint. Survival comparisons between the T and N stages and the different staging systems were performed using the Kaplan–Meier method and log-rank test, followed by correlation analysis and variable importance analysis (VIA). Additionally, multivariate analysis was employed to identify significant predictors, which were further visualized using a nomogram. Finally, calibration curve, C-index, and decision curve analysis (DCA) were applied to assess the performance of the different staging systems.
Results
A total of 5384 patients with ASCC were analyzed, revealing superior discrimination OS by the TNM9th edition compared to that by the TNM8th edition. Multivariate analysis identified the T and N stages as significant OS predictors (all p < 0.001). However, ambiguity persisted in stage III subgroups within the TNM9th edition, showing OS times of 102 months for stage IIIA disease, 88 months for stage IIIB disease, and 128 months for stage IIIC disease (all p > 0.05). Correlation analysis demonstrated an increased correlation for the T stage between the TNM8th and 9th editions (ρ value from 0.7 to 0.89), while the N stage correlation decreased (ρ value from 0.84 to 0.56). VIA and the prognostic nomogram highlighted the greater importance of the T stage over the N stage. Based on these findings, a new staging system was developed, and its clinical utility was confirmed through calibration curves, C-index values (from 0.598 to 0.604), and DCAs.
Conclusions
Our new staging system exhibited slightly better prognostic value compared to the TNM9th staging systems for nonmetastatic ASCC and warrants further validation.
目的比较TNM第9版和第8版对非手术治疗的局部和局部晚期肛门鳞状细胞癌（ASCC）的生存判别，并利用监测、流行病学和最终结果（SEER）数据库中的数据提出一个简单的修订分期系统：方法：以总生存期（OS）为主要终点。采用卡普兰-梅耶法和对数秩检验对T期和N期以及不同分期系统进行生存率比较，然后进行相关性分析和变量重要性分析（VIA）。此外，还采用了多变量分析来确定重要的预测因素，并使用提名图进一步将其直观化。最后，应用校准曲线、C指数和决策曲线分析（DCA）来评估不同分期系统的性能：结果：共对5384例ASCC患者进行了分析，结果显示TNM9版的分辨OS优于TNM8版。多变量分析发现，T分期和N分期是预测OS的重要指标（均为P 0.05）。相关性分析表明，TNM 第 8 版和第 9 版之间的 T 分期相关性增加（ρ 值从 0.7 升至 0.89），而 N 分期相关性降低（ρ 值从 0.84 降至 0.56）。VIA 和预后提名图强调了 T 分期比 N 分期更重要。基于这些发现，我们开发了一套新的分期系统，并通过校准曲线、C指数值（从0.598到0.604）和DCA证实了其临床实用性：结论：与 TNM9th 分期系统相比，我们的新分期系统对非转移性 ASCC 的预后价值略高，值得进一步验证。
{"title":"Comparison of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma treated nonsurgically and proposal of a new stage grouping system","authors":"Aihong Zheng, Yiwen Wang, Shuang Li, Yingjie Wang, Hong'en Xu, Jieni Ding, Bingchen Chen, Tao Song, Lei Lai","doi":"10.1002/cam4.70119","DOIUrl":"10.1002/cam4.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the survival discrimination of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma (ASCC) treated nonsurgically and suggest a simple revised staging system with data from the Surveillance, Epidemiology, and End Results (SEER) database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Overall survival (OS) was the primary endpoint. Survival comparisons between the T and N stages and the different staging systems were performed using the Kaplan–Meier method and log-rank test, followed by correlation analysis and variable importance analysis (VIA). Additionally, multivariate analysis was employed to identify significant predictors, which were further visualized using a nomogram. Finally, calibration curve, C-index, and decision curve analysis (DCA) were applied to assess the performance of the different staging systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 5384 patients with ASCC were analyzed, revealing superior discrimination OS by the TNM9th edition compared to that by the TNM8th edition. Multivariate analysis identified the T and N stages as significant OS predictors (all <i>p</i> < 0.001). However, ambiguity persisted in stage III subgroups within the TNM9th edition, showing OS times of 102 months for stage IIIA disease, 88 months for stage IIIB disease, and 128 months for stage IIIC disease (all <i>p</i> > 0.05). Correlation analysis demonstrated an increased correlation for the T stage between the TNM8th and 9th editions (<i>ρ</i> value from 0.7 to 0.89), while the N stage correlation decreased (<i>ρ</i> value from 0.84 to 0.56). VIA and the prognostic nomogram highlighted the greater importance of the T stage over the N stage. Based on these findings, a new staging system was developed, and its clinical utility was confirmed through calibration curves, C-index values (from 0.598 to 0.604), and DCAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our new staging system exhibited slightly better prognostic value compared to the TNM9th staging systems for nonmetastatic ASCC and warrants further validation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998999","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}
Despite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5-fluorouracil (5-FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5-FU with Lut in PDACs.
Methods and Results
PDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5-FU. The xenograft tumors of DPYD-overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA-seq analysis of the DPYD-overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity—MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5-FU on DPYD-overexpressing xenograft tumors and PDAC of Pdx1-Cre; LSL-KrasG12D/+; Trp53flox/flox(KPPC) mice. Neither single administration of 5-FU nor Lut showed significant inhibitory effects; however, the combined administration of 5-FU and Lut exhibited a significant tumor-suppressive effect in both the xenograft tumors and KPPC models.
Conclusion
We have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5-FU resistance, in PDACs. The combination therapy of Lut and 5-FU holds the potential for enhanced efficacy against PDACs.
{"title":"The role of DPYD and the effects of DPYD suppressor luteolin combined with 5-FU in pancreatic cancer","authors":"Hiroyuki Kato, Motonori Sato, Aya Naiki-Ito, Shingo Inaguma, Makoto Sano, Masayuki Komura, Yuko Nagayasu, Kuang Xiaochen, Akihisa Kato, Yoichi Matsuo, Hideaki Ijichi, Satoru Takahashi","doi":"10.1002/cam4.70124","DOIUrl":"10.1002/cam4.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5-fluorouracil (5-FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5-FU with Lut in PDACs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>PDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5-FU. The xenograft tumors of DPYD-overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA-seq analysis of the DPYD-overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity—MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5-FU on DPYD-overexpressing xenograft tumors and PDAC of <i>Pdx1-Cre</i>; <i>LSL-KrasG12D/+</i>; <i>Trp53flox/flox(KPPC)</i> mice. Neither single administration of 5-FU nor Lut showed significant inhibitory effects; however, the combined administration of 5-FU and Lut exhibited a significant tumor-suppressive effect in both the xenograft tumors and <i>KPPC</i> models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5-FU resistance, in PDACs. The combination therapy of Lut and 5-FU holds the potential for enhanced efficacy against PDACs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999003","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}
Megan H. Wong, Veronica C. Jones, Wai Yu, Linda D. Bosserman, Sayeh M. Lavasani, Niki Patel, Mina S. Sedrak, Daphne B. Stewart, James R. Waisman, Yuan Yuan, Joanne E. Mortimer
Background
Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2-negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity.
Methods
In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68).
Results
We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple-negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression.
Conclusion
This retrospective, real-world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes.
{"title":"UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan","authors":"Megan H. Wong, Veronica C. Jones, Wai Yu, Linda D. Bosserman, Sayeh M. Lavasani, Niki Patel, Mina S. Sedrak, Daphne B. Stewart, James R. Waisman, Yuan Yuan, Joanne E. Mortimer","doi":"10.1002/cam4.70096","DOIUrl":"10.1002/cam4.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2-negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (<i>N</i> = 68).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple-negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This retrospective, real-world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999004","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}
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