Pub Date : 2024-11-23DOI: 10.1038/s41416-024-02900-7
Wing Ching Chan, Lili Liu, Emmanouil Bouras, Verena Zuber, Wanqing Wen, Jirong Long, Dipender Gill, Neil Murphy, Marc J. Gunter, Themistocles L. Assimes, Luis Bujanda, Stephen B. Gruber, Sébastien Küry, Brigid M. Lynch, Conghui Qu, Minta Thomas, Emily White, Michael O. Woods, Ulrike Peters, Christopher I. Li, Andrew T. Chan, Hermann Brenner, Konstantinos K. Tsilidis, Wei Zheng
Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear. Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed. Genetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02–1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05–1.21) or diabetes (OR = 1.09; 95%CI 1.02–1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets. We found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes.
{"title":"Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study","authors":"Wing Ching Chan, Lili Liu, Emmanouil Bouras, Verena Zuber, Wanqing Wen, Jirong Long, Dipender Gill, Neil Murphy, Marc J. Gunter, Themistocles L. Assimes, Luis Bujanda, Stephen B. Gruber, Sébastien Küry, Brigid M. Lynch, Conghui Qu, Minta Thomas, Emily White, Michael O. Woods, Ulrike Peters, Christopher I. Li, Andrew T. Chan, Hermann Brenner, Konstantinos K. Tsilidis, Wei Zheng","doi":"10.1038/s41416-024-02900-7","DOIUrl":"10.1038/s41416-024-02900-7","url":null,"abstract":"Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear. Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed. Genetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02–1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05–1.21) or diabetes (OR = 1.09; 95%CI 1.02–1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets. We found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"132 1","pages":"103-110"},"PeriodicalIF":6.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02900-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41416-024-02899-x
Samir H. Barghout, Nicholas Meti, Simren Chotai, Christina J. H. Kim, Devalben Patel, M. Catherine Brown, Katrina Hueniken, Luna J. Zhan, Stavroula Raptis, Faisal Al-Agha, Christopher Deutschman, Benjamin Grant, Martha Pienkowski, Patrick Moriarty, John de Almeida, David P. Goldstein, Scott V. Bratman, Frances A. Shepherd, Ming S. Tsao, Andrew N. Freedman, Wei Xu, Geoffrey Liu
The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342). We performed resource assessments, stakeholder-directed surveys and discussions, analysis of funding, research output, collaborations, and a Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis. Based on these analyses, AUPROS is an approach that is applicable to a wide range of observational study designs. The universality of AUPROS allows for multi-purpose analyses of various RWD, and the adaptive nature creates opportunities for multi-source funding and collaborations. Following AUPROS can offer cost and logistical benefits and may lead to increased research productivity. Several challenges were identified pertinent to ethics approvals, sustainability, complex coordination, and data quality that require local adaptation of these principles.
{"title":"Adaptive Universal Principles for Real-world Observational Studies (AUPROS): an approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research","authors":"Samir H. Barghout, Nicholas Meti, Simren Chotai, Christina J. H. Kim, Devalben Patel, M. Catherine Brown, Katrina Hueniken, Luna J. Zhan, Stavroula Raptis, Faisal Al-Agha, Christopher Deutschman, Benjamin Grant, Martha Pienkowski, Patrick Moriarty, John de Almeida, David P. Goldstein, Scott V. Bratman, Frances A. Shepherd, Ming S. Tsao, Andrew N. Freedman, Wei Xu, Geoffrey Liu","doi":"10.1038/s41416-024-02899-x","DOIUrl":"10.1038/s41416-024-02899-x","url":null,"abstract":"The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342). We performed resource assessments, stakeholder-directed surveys and discussions, analysis of funding, research output, collaborations, and a Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis. Based on these analyses, AUPROS is an approach that is applicable to a wide range of observational study designs. The universality of AUPROS allows for multi-purpose analyses of various RWD, and the adaptive nature creates opportunities for multi-source funding and collaborations. Following AUPROS can offer cost and logistical benefits and may lead to increased research productivity. Several challenges were identified pertinent to ethics approvals, sustainability, complex coordination, and data quality that require local adaptation of these principles.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"132 2","pages":"139-153"},"PeriodicalIF":6.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1038/s41416-024-02911-4
Edward Christopher Dee
{"title":"Cancer care for migrant people","authors":"Edward Christopher Dee","doi":"10.1038/s41416-024-02911-4","DOIUrl":"10.1038/s41416-024-02911-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"132 2","pages":"156-157"},"PeriodicalIF":6.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02911-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s41416-024-02903-4
A. Aleman, L. Adrien, L. Lopez-Serra, C. Cordon-Cardo, M. Esteller, T. J. Belbin, M. Sanchez-Carbayo
{"title":"Editorial Expression of Concern: Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays","authors":"A. Aleman, L. Adrien, L. Lopez-Serra, C. Cordon-Cardo, M. Esteller, T. J. Belbin, M. Sanchez-Carbayo","doi":"10.1038/s41416-024-02903-4","DOIUrl":"10.1038/s41416-024-02903-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1946-1946"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02903-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s41416-024-02889-z
Hemaasri-Neya Girithar, Shivani Krishnamurthy, Luke Carroll, Anna Guller, Ayse A. Bilgin, Laurence Gluch, Gilles J. Guillemin, Seong Beom Ahn, Benjamin Heng
Metastasis remains the major cause of death in breast cancer (BrCa) and lacks specific treatment strategies. The kynurenine pathway (KP) has been suggested as a key mechanism facilitating progression of BrCa. While KP activity has been explored in primary BrCa, its role in metastasis remains unclear. To better understand this, we examined changes in the KP of BrCa with no metastasis compared to BCa that produced local or distant metastases. Given that the cancer cell secretome plays a role in metastasis, we also investigated the relationship between changes in KP activity and serum proteins of patients with local or distant metastases. To investigate changes in the KP in BrCa, with and without metastasis, we quantified KP metabolites in blood sera collected from patients with stage 1 BrCa (n = 34), BrCa with local metastases (n = 46), BrCa with distant metastases (n = 20) and healthy controls (n = 39). The serum protein profile of the BrCa patients with local or distant metastasis was determined before correlation analyses were carried out to examine the relationship between changes in the KP and cancer serum proteins using SPSS. We found that the KP was elevated in BrCa patients with local and distant metastasis compared to healthy controls and stage 1 BrCa patients. The activity of kynurenine monooxygenase (KMO) and kynureninase (KYNU) A was positively associated with disease stage and was higher compared to healthy controls. Proteome analysis in patients with local or distant metastasis revealed the dysregulation of 14 proteins, 9 of which were up-regulated and 5 down-regulated at the distant metastasis stage. Importantly, three of these proteins have not been previously linked to BrCa metastasis. In the correlation studies between the KP profile, cancer serum proteins and metastasis status, KYNU A had the greatest number of significant associations with cancer serum protein, followed by KMO. Our findings reveal that the KP was regulated differently at various stages of BrCa and was more dysregulated in patients with local or distant metastasis. These KP activity changes showed a significant association with cancer serum proteins in BrCa patients with local or distant metastasis, highlighting the potential role of KP in BrCa metastasis.
{"title":"Breast cancer metastasis progression is associated with elevated activity of kynurenine monooxygenase and kynureninase","authors":"Hemaasri-Neya Girithar, Shivani Krishnamurthy, Luke Carroll, Anna Guller, Ayse A. Bilgin, Laurence Gluch, Gilles J. Guillemin, Seong Beom Ahn, Benjamin Heng","doi":"10.1038/s41416-024-02889-z","DOIUrl":"10.1038/s41416-024-02889-z","url":null,"abstract":"Metastasis remains the major cause of death in breast cancer (BrCa) and lacks specific treatment strategies. The kynurenine pathway (KP) has been suggested as a key mechanism facilitating progression of BrCa. While KP activity has been explored in primary BrCa, its role in metastasis remains unclear. To better understand this, we examined changes in the KP of BrCa with no metastasis compared to BCa that produced local or distant metastases. Given that the cancer cell secretome plays a role in metastasis, we also investigated the relationship between changes in KP activity and serum proteins of patients with local or distant metastases. To investigate changes in the KP in BrCa, with and without metastasis, we quantified KP metabolites in blood sera collected from patients with stage 1 BrCa (n = 34), BrCa with local metastases (n = 46), BrCa with distant metastases (n = 20) and healthy controls (n = 39). The serum protein profile of the BrCa patients with local or distant metastasis was determined before correlation analyses were carried out to examine the relationship between changes in the KP and cancer serum proteins using SPSS. We found that the KP was elevated in BrCa patients with local and distant metastasis compared to healthy controls and stage 1 BrCa patients. The activity of kynurenine monooxygenase (KMO) and kynureninase (KYNU) A was positively associated with disease stage and was higher compared to healthy controls. Proteome analysis in patients with local or distant metastasis revealed the dysregulation of 14 proteins, 9 of which were up-regulated and 5 down-regulated at the distant metastasis stage. Importantly, three of these proteins have not been previously linked to BrCa metastasis. In the correlation studies between the KP profile, cancer serum proteins and metastasis status, KYNU A had the greatest number of significant associations with cancer serum protein, followed by KMO. Our findings reveal that the KP was regulated differently at various stages of BrCa and was more dysregulated in patients with local or distant metastasis. These KP activity changes showed a significant association with cancer serum proteins in BrCa patients with local or distant metastasis, highlighting the potential role of KP in BrCa metastasis.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1881-1892"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s41416-024-02905-2
Yijia Sun, Dezheng Huo
Proteome-wide association studies (PWAS) address gaps in post-transcriptional modifications that previous genome- and transcriptome-wide association studies could not capture. Zhao and colleagues conducted the first breast tissue-based PWAS and identified proteins associated with breast cancer risk, providing insights into the role of protein expression in breast cancer development.
{"title":"Understanding genetic architecture of breast cancer: how can proteome-wide association studies contribute?","authors":"Yijia Sun, Dezheng Huo","doi":"10.1038/s41416-024-02905-2","DOIUrl":"10.1038/s41416-024-02905-2","url":null,"abstract":"Proteome-wide association studies (PWAS) address gaps in post-transcriptional modifications that previous genome- and transcriptome-wide association studies could not capture. Zhao and colleagues conducted the first breast tissue-based PWAS and identified proteins associated with breast cancer risk, providing insights into the role of protein expression in breast cancer development.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1869-1870"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02905-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s41416-024-02907-0
N. M. Mhaidat, X. D. Zhang, J. Allen, K. A. Avery-Kiejda, R. J. Scott, P. Hersey
{"title":"Editorial Expression of Concern: Temozolomide induces senescence but not apoptosis in human melanoma cells","authors":"N. M. Mhaidat, X. D. Zhang, J. Allen, K. A. Avery-Kiejda, R. J. Scott, P. Hersey","doi":"10.1038/s41416-024-02907-0","DOIUrl":"10.1038/s41416-024-02907-0","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1947-1947"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02907-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1038/s41416-024-02836-y
Peter Sasieni, Rebecca Smittenaar, Earl Hubbell, John Broggio, Richard D. Neal, Charles Swanton
{"title":"Correction: Modelled mortality benefits of multi-cancer early detection screening in England","authors":"Peter Sasieni, Rebecca Smittenaar, Earl Hubbell, John Broggio, Richard D. Neal, Charles Swanton","doi":"10.1038/s41416-024-02836-y","DOIUrl":"10.1038/s41416-024-02836-y","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1942-1944"},"PeriodicalIF":6.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02836-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.1038/s41416-024-02874-6
Robert D. Morgan, Xin Wang, Bethany M. Barnes, Laura Spurgeon, Aurore Carrot, Daniel Netto, Jurjees Hasan, Claire Mitchell, Zena Salih, Sudha Desai, Joseph Shaw, Brett Winter-Roach, Helene Schlecht, George J. Burghel, Andrew R. Clamp, Richard J. Edmondson, Benoit You, D. Gareth R. Evans, Gordon C. Jayson, Stephen S. Taylor
High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm’s chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. Of 586 eligible patients, 393 underwent DPS and had a CRS reported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95–4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14–0.91; P = 0.0291). Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.
{"title":"Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer","authors":"Robert D. Morgan, Xin Wang, Bethany M. Barnes, Laura Spurgeon, Aurore Carrot, Daniel Netto, Jurjees Hasan, Claire Mitchell, Zena Salih, Sudha Desai, Joseph Shaw, Brett Winter-Roach, Helene Schlecht, George J. Burghel, Andrew R. Clamp, Richard J. Edmondson, Benoit You, D. Gareth R. Evans, Gordon C. Jayson, Stephen S. Taylor","doi":"10.1038/s41416-024-02874-6","DOIUrl":"10.1038/s41416-024-02874-6","url":null,"abstract":"High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm’s chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. Of 586 eligible patients, 393 underwent DPS and had a CRS reported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95–4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14–0.91; P = 0.0291). Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 12","pages":"1919-1927"},"PeriodicalIF":6.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02874-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.1038/s41416-024-02868-4
Craig Gerrand, Fernanda Amary, Hanny A. Anwar, Bernadette Brennan, Palma Dileo, Maninder Singh Kalkat, Martin G. McCabe, Anna Louise McCullough, Michael C. Parry, Anish Patel, Beatrice M. Seddon, Jennifer M. Sherriff, Roberto Tirabosco, Sandra J. Strauss
This document is an update of the British Sarcoma Group guidelines (2016) and provides a reference standard for the clinical care of UK patients with primary malignant bone tumours (PMBT) and giant cell tumours (GCTB) of bone. The guidelines recommend treatments that are effective and should be available in the UK, and support decisions about management and service delivery. The document represents a consensus amongst British Sarcoma Group members in 2024. Key recommendations are that bone pain, or a palpable mass should always lead to further investigation and that patients with clinical or radiological findings suggestive of a primary bone tumour at any anatomic site should be referred to a specialist centre and managed by an accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow-up schedules are suggested.
{"title":"UK guidelines for the management of bone sarcomas","authors":"Craig Gerrand, Fernanda Amary, Hanny A. Anwar, Bernadette Brennan, Palma Dileo, Maninder Singh Kalkat, Martin G. McCabe, Anna Louise McCullough, Michael C. Parry, Anish Patel, Beatrice M. Seddon, Jennifer M. Sherriff, Roberto Tirabosco, Sandra J. Strauss","doi":"10.1038/s41416-024-02868-4","DOIUrl":"10.1038/s41416-024-02868-4","url":null,"abstract":"This document is an update of the British Sarcoma Group guidelines (2016) and provides a reference standard for the clinical care of UK patients with primary malignant bone tumours (PMBT) and giant cell tumours (GCTB) of bone. The guidelines recommend treatments that are effective and should be available in the UK, and support decisions about management and service delivery. The document represents a consensus amongst British Sarcoma Group members in 2024. Key recommendations are that bone pain, or a palpable mass should always lead to further investigation and that patients with clinical or radiological findings suggestive of a primary bone tumour at any anatomic site should be referred to a specialist centre and managed by an accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow-up schedules are suggested.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"132 1","pages":"32-48"},"PeriodicalIF":6.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02868-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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