Pub Date : 2024-12-16DOI: 10.1016/s1470-2045(24)00640-5
Logine Negm, Jiil Chung, Liana Nobre, Julie Bennett, Nicholas R Fernandez, Nuno Miguel Nunes, Zhihui Amy Liu, Martin Komosa, Melyssa Aronson, Cindy Zhang, Lucie Stengs, Vanessa Bianchi, Melissa Edwards, Sheradan Doherty, Ayse Bahar Ercan, Maria F Cardenas, Michael Macias, Matthew R Lueder, Michelle Ku, Monique Johnson, Uri Tabori
<h3>Background</h3>Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0–40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.<h3>Methods</h3>Clinical and molecular data were collected from a population-based cohort of children, adolescents, and young adults with gliomas from Toronto (TOR-Ped, age 0–18 years, collected Jan 1, 2000, to Dec 31, 2021; and TOR-AYA, age 18–40 years, collected Jan 1, 2000, to June 30, 2019). Additional validation paediatric cohorts from St Jude Children's Research Hospital (0–18 years, 2015–21) and the Children's Brain Tumor Network (0–18 years, 1981–2021) were used. Functional genomic tools were applied with the primary aim of assessing primary MMRD prevalence among glioma subgroups and germline impact. To evaluate the effect of primary MMRD on therapy and overall survival, Kaplan–Meier estimates were used on an additional cohort of patients with primary MMRD gliomas treated with immunotherapy.<h3>Findings</h3>1389 gliomas were included in the study. The prevalence of primary MMRD ranged between 3·7% and 12·4% in high-grade gliomas (overall 30 of 483; 6·2%, 95% CI 4·2–8·7) and less than 1% in low-grade gliomas (four of 899; 0·4%, 0·1–1·1; p<0·0001 by χ<sup>2</sup> test). Specific molecular analysis for all gliomas showed that primary MMRD was absent among oligodendrogliomas (none of 67) and uncommon in <em>BRAF</em><sup>V600E</sup> gliomas (one of 110) and histone mutant-driven gliomas (one of 150). In the paediatric age group (<18 years), primary MMRD was common in <em>IDH</em><sup>WT</sup> and <em>H3</em><sup>WT</sup> gliomas harbouring pathogenic <em>TP53</em> variants (21 of 61; 34·4%, 22·7–47·7) and in malignant <em>IDH</em><sup>mut</sup> gliomas (five of eight; 62·5%, 24·5–91·5). Germline aetiology accounted for 33 (94·3%) of 35 primary MMRD gliomas, including children, adolescents, and young adults with previously unrecognised Lynch syndrome. Survival was poor for patients with primary MMRD gliomas. Particularly poor survival was observed for those with <em>IDH</em><sup>mut</sup> astrocytomas with primary MMRD when compared with those with mismatch repair-proficient gliomas (HR 12·6, 95% CI 2·8–57·5; p=0·0011 by multivariable Cox regression). Immune checkpoint blockade was associated with improved survival for patients with primary MMRD gliomas compared with conventional chemoradiotherapy regimens (HR 0·4, 0·3–0·7; p=0·0017 by multivariable Cox regression), regardless of age or germline status.<h3>Interpretation</h3>Primary MMRD is more common than previously reported in gliomas in children, adolescents, and young adults, is enriched in specific molecular subgroups, and is associated with poor outcomes. Accurate detection, genetic testing, early diagnosis through sur
{"title":"The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study","authors":"Logine Negm, Jiil Chung, Liana Nobre, Julie Bennett, Nicholas R Fernandez, Nuno Miguel Nunes, Zhihui Amy Liu, Martin Komosa, Melyssa Aronson, Cindy Zhang, Lucie Stengs, Vanessa Bianchi, Melissa Edwards, Sheradan Doherty, Ayse Bahar Ercan, Maria F Cardenas, Michael Macias, Matthew R Lueder, Michelle Ku, Monique Johnson, Uri Tabori","doi":"10.1016/s1470-2045(24)00640-5","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00640-5","url":null,"abstract":"<h3>Background</h3>Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0–40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.<h3>Methods</h3>Clinical and molecular data were collected from a population-based cohort of children, adolescents, and young adults with gliomas from Toronto (TOR-Ped, age 0–18 years, collected Jan 1, 2000, to Dec 31, 2021; and TOR-AYA, age 18–40 years, collected Jan 1, 2000, to June 30, 2019). Additional validation paediatric cohorts from St Jude Children's Research Hospital (0–18 years, 2015–21) and the Children's Brain Tumor Network (0–18 years, 1981–2021) were used. Functional genomic tools were applied with the primary aim of assessing primary MMRD prevalence among glioma subgroups and germline impact. To evaluate the effect of primary MMRD on therapy and overall survival, Kaplan–Meier estimates were used on an additional cohort of patients with primary MMRD gliomas treated with immunotherapy.<h3>Findings</h3>1389 gliomas were included in the study. The prevalence of primary MMRD ranged between 3·7% and 12·4% in high-grade gliomas (overall 30 of 483; 6·2%, 95% CI 4·2–8·7) and less than 1% in low-grade gliomas (four of 899; 0·4%, 0·1–1·1; p<0·0001 by χ<sup>2</sup> test). Specific molecular analysis for all gliomas showed that primary MMRD was absent among oligodendrogliomas (none of 67) and uncommon in <em>BRAF</em><sup>V600E</sup> gliomas (one of 110) and histone mutant-driven gliomas (one of 150). In the paediatric age group (<18 years), primary MMRD was common in <em>IDH</em><sup>WT</sup> and <em>H3</em><sup>WT</sup> gliomas harbouring pathogenic <em>TP53</em> variants (21 of 61; 34·4%, 22·7–47·7) and in malignant <em>IDH</em><sup>mut</sup> gliomas (five of eight; 62·5%, 24·5–91·5). Germline aetiology accounted for 33 (94·3%) of 35 primary MMRD gliomas, including children, adolescents, and young adults with previously unrecognised Lynch syndrome. Survival was poor for patients with primary MMRD gliomas. Particularly poor survival was observed for those with <em>IDH</em><sup>mut</sup> astrocytomas with primary MMRD when compared with those with mismatch repair-proficient gliomas (HR 12·6, 95% CI 2·8–57·5; p=0·0011 by multivariable Cox regression). Immune checkpoint blockade was associated with improved survival for patients with primary MMRD gliomas compared with conventional chemoradiotherapy regimens (HR 0·4, 0·3–0·7; p=0·0017 by multivariable Cox regression), regardless of age or germline status.<h3>Interpretation</h3>Primary MMRD is more common than previously reported in gliomas in children, adolescents, and young adults, is enriched in specific molecular subgroups, and is associated with poor outcomes. Accurate detection, genetic testing, early diagnosis through sur","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/s1470-2045(24)00598-9
Anna Santarsieri, Emily Mitchell, My H Pham, Rashesh Sanghvi, Janina Jablonski, Henry Lee-Six, Katherine Sturgess, Pauline Brice, Tobias F Menne, Wendy Osborne, Thomas Creasey, Kirit M Ardeshna, Joanna Baxter, Sarah Behan, Kaljit Bhuller, Stephen Booth, Nikesh D Chavda, Graham P Collins, Dominic J Culligan, Kate Cwynarski, George A Follows
<h3>Background</h3>Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin–etoposide–doxorubicin–cyclophosphamide–vincristine–procarbazine–prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.<h3>Methods</h3>In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin–bleomycin–vinblastine–dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil–vinblastine–procarbazine–prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part).<h3>Findings</h3>In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934–1366] <em>vs</em> 290 [241–339] <em>vs</em> 186 [116–254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either AB
背景：含丙卡嗪的化疗方案与细胞减少和不孕有关，提示干细胞毒性。在治疗霍奇金淋巴瘤时，增加剂量的博莱霉素-依托泊苷-阿霉素-环磷酰胺-长春新碱-丙卡嗪-强的松龙（eBEACOPP）越来越多地被达卡巴嗪（eBEACOPDac）取代，以降低毒性。我们的目的是研究这种药物替代对干细胞突变负担、患者生存和毒性的影响。方法：在这项两部分的回顾性观察性研究中，我们首先比较了接受eBEACOPDac （eBEACOPDac队列）、eBEACOPP（现实世界eBEACOPP队列）或阿霉素-博莱霉素- vinblastine - dacarbazine （ABVD）治疗的缓解期至少6个月的晚期霍奇金淋巴瘤患者造血干细胞和祖细胞（HSPCs）的突变情况；一名女性经典霍奇金淋巴瘤患者在怀孕前接受eBEACOPP治疗的五个孩子的口腔DNA；接受eBEACOPP治疗的轻度少精症患者的精子DNA；在用氯苯布西-长春碱-丙卡巴齐-强的松龙治疗的霍奇金淋巴瘤幸存者的盲肠腺癌和健康结肠组织中。在第二部分，我们分析了来自英国、爱尔兰和法国25个中心接受一线eBEACOPDac （eBEACOPDac队列）治疗的成年患者（16岁）的疗效和毒性数据；将疗效与德国HD18 eBEACOPP试验数据进行比较，并将毒性与英国真实数据集进行比较。德国HD18和英国真实世界数据集的参与者是先前未经治疗的霍奇金淋巴瘤的成年人（年龄16岁），接受一线eBEACOPP治疗。我们有两个共同的主要目标：定义使用或不使用含丙卡嗪的化疗治疗后的干细胞突变负担和突变特征（第一部分研究）；以及确定接受eBEACOPP或eBEACOPDac治疗的霍奇金淋巴瘤患者的无进展生存期（第二项研究）。次要目标包括总体生存，并探讨特定毒性结果的差异，包括输血要求和生殖健康措施（研究第二部分）。在研究的第一部分（突变分析）中，与接受eBEACOPDac （n=4）或ABVD （n=3）治疗的患者相比，接受eBEACOPP治疗的患者（n=5）表现出更高的HSPCs点突变负担；过量突变1150 [95% CI 934-1366] vs 290 [241-339] vs 186[116-254])。两种新的突变特征，SBSA （sbs25样）和SBSB，在HSPCs和接受含丙卡嗪化疗的患者的单个肿瘤和健康结肠样本中被鉴定出来。在接受eBEACOPP治疗的三名儿童的种系DNA和一名接受eBEACOPP治疗的男性患者的精子中也发现了SBSB。在接受ABVD或eBEACOPDac治疗的患者中检测到SBSC。在研究的第二部分（疗效和毒性分析）中，达卡巴嗪替代似乎没有损害疗效或安全性。312例患者接受eBEACOPDac治疗(eBEACOPDac队列；在德国HD18 eBEACOPP试验中，1945例患者的3年无进展生存率为93% （95% CI为903 - 94.6)（2008 - 2014年，1183例（61%）男性，中位随访57.5个月（35.4 - 64.7）），其中男性患者186例（60%），中位随访36.0个月（IQR 25.2 - 50.1））。接受eBEACOPDac治疗的患者输血量减少（平均1.70单位[SD 2.77] vs 3.69单位[SD 3.89]）；p< 0.0001)，化疗后精子浓度较高(中位数为2340万/ mL [IQR为11.0 - 63.2]vs 0.0万/ mL [IQR为0.0 - 0.001]；p= 0.0040)，且月经恢复较早(平均5.04个月[SD 3.07] vs . 8.77个月[5.57]；p= 0.0036)，与英国真实数据集中接受eBEACOPP治疗的73例患者进行比较。procarbazine在接受eBEACOPP治疗的霍奇金淋巴瘤患者及其种系DNA中诱导更高的突变负担和新的突变特征，引起了对霍奇金淋巴瘤幸存者基因组健康及其后代遗传后果的关注。然而，用达卡巴嗪代替丙卡巴嗪似乎可以减轻性腺和干细胞毒性，同时保持相似的临床疗效。资助阿登布鲁克慈善信托基金和惠康信托基金。
{"title":"The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study","authors":"Anna Santarsieri, Emily Mitchell, My H Pham, Rashesh Sanghvi, Janina Jablonski, Henry Lee-Six, Katherine Sturgess, Pauline Brice, Tobias F Menne, Wendy Osborne, Thomas Creasey, Kirit M Ardeshna, Joanna Baxter, Sarah Behan, Kaljit Bhuller, Stephen Booth, Nikesh D Chavda, Graham P Collins, Dominic J Culligan, Kate Cwynarski, George A Follows","doi":"10.1016/s1470-2045(24)00598-9","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00598-9","url":null,"abstract":"<h3>Background</h3>Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin–etoposide–doxorubicin–cyclophosphamide–vincristine–procarbazine–prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.<h3>Methods</h3>In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin–bleomycin–vinblastine–dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil–vinblastine–procarbazine–prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part).<h3>Findings</h3>In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934–1366] <em>vs</em> 290 [241–339] <em>vs</em> 186 [116–254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either AB","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<h3>Background</h3>Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged <50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.<h3>Methods</h3>Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO–International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database. The Human Development Index 2022 was retrieved from the United Nations Development Programme and grouped into very high (>0·80), high (0·70–0·79), medium (0·55–0·69), and low (<0·55) categories. Age-standardised incidence rates (ASR) per 100 000 person-years of early-onset (diagnosed between ages 25 to 49 years) and late-onset (diagnosed between ages 50 to 74 years) colorectal cancer (ICD 10th revision, C18–20), diagnosed between 1943–2003 and 2015–17, were calculated using the direct method and Segi–Doll world standard population). The primary study objective was to examine contemporary colorectal cancer incidence trends in younger adults versus older adults using data until 2017 from 50 countries and territories. Temporal trends were visualised and quantified with joinpoint regression, stratified by age at diagnosis (25–49 years or 50–74 years). Average annual percentage changes (AAPC) were estimated.<h3>Findings</h3>In the most recent 5 years (2013–17 for all countries analysed, except for Japan [2011–15], Spain [2012–16], and Costa Rica [2012–16]), the incidence rate of early-onset colorectal cancer was highest in Australia (ASR 16·5 [95% CI 16·1–16·9]), the USA (Puerto Rico; 15·2 [14·2–16·2]), New Zealand (14·8 [14·0–15·6]), the USA (14·8 [14·7–14·9]), and South Korea (14·3 [14·0–14·5]) and lowest in Uganda (4·4 [3·6–5·2]) and India (3·5 [3·3–3·7]). The highest incidence rates among older adults were found in the Netherlands (168·4 [166·9–170·0]) and Denmark (158·3 [155·8–160·9]) and the lowest were in Uganda (45·9 [38·5–51·4]) and India (23·5 [22·8–24·3]). In terms of AAPC, in the most recent 10 years, incidence rates of early-onset colorectal cancer were stable in 23 countries, but increased in 27 countries with the greatest annual increases in New Zealand (AAPC 3·97% [95% CI 2·44–5·52]), Chile (3·96% [1·26–6·74]), Puerto Rico (3·81% [2·68–4·96]), and England (3·59% [3·12–4·06]). 14 of the 27 countries and territories showed either stable (Argentina, France, Ireland, Norway, and Puerto Rico) or decreasing (Australia, Canada, Germany, Israel, New Zealand, Slovenia, England, Scotland, and the USA) trends in older adults. For the 13 countries with increasing trends in both age groups, the average annual percentage increase in younger compared to older adults was higher in Chile, Japan, Sweden, t
{"title":"Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data","authors":"Hyuna Sung, Rebecca L Siegel, Mathieu Laversanne, Chenxi Jiang, Eileen Morgan, Mariam Zahwe, Yin Cao, Freddie Bray, Ahmedin Jemal","doi":"10.1016/s1470-2045(24)00600-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00600-4","url":null,"abstract":"<h3>Background</h3>Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged <50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.<h3>Methods</h3>Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO–International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database. The Human Development Index 2022 was retrieved from the United Nations Development Programme and grouped into very high (>0·80), high (0·70–0·79), medium (0·55–0·69), and low (<0·55) categories. Age-standardised incidence rates (ASR) per 100 000 person-years of early-onset (diagnosed between ages 25 to 49 years) and late-onset (diagnosed between ages 50 to 74 years) colorectal cancer (ICD 10th revision, C18–20), diagnosed between 1943–2003 and 2015–17, were calculated using the direct method and Segi–Doll world standard population). The primary study objective was to examine contemporary colorectal cancer incidence trends in younger adults versus older adults using data until 2017 from 50 countries and territories. Temporal trends were visualised and quantified with joinpoint regression, stratified by age at diagnosis (25–49 years or 50–74 years). Average annual percentage changes (AAPC) were estimated.<h3>Findings</h3>In the most recent 5 years (2013–17 for all countries analysed, except for Japan [2011–15], Spain [2012–16], and Costa Rica [2012–16]), the incidence rate of early-onset colorectal cancer was highest in Australia (ASR 16·5 [95% CI 16·1–16·9]), the USA (Puerto Rico; 15·2 [14·2–16·2]), New Zealand (14·8 [14·0–15·6]), the USA (14·8 [14·7–14·9]), and South Korea (14·3 [14·0–14·5]) and lowest in Uganda (4·4 [3·6–5·2]) and India (3·5 [3·3–3·7]). The highest incidence rates among older adults were found in the Netherlands (168·4 [166·9–170·0]) and Denmark (158·3 [155·8–160·9]) and the lowest were in Uganda (45·9 [38·5–51·4]) and India (23·5 [22·8–24·3]). In terms of AAPC, in the most recent 10 years, incidence rates of early-onset colorectal cancer were stable in 23 countries, but increased in 27 countries with the greatest annual increases in New Zealand (AAPC 3·97% [95% CI 2·44–5·52]), Chile (3·96% [1·26–6·74]), Puerto Rico (3·81% [2·68–4·96]), and England (3·59% [3·12–4·06]). 14 of the 27 countries and territories showed either stable (Argentina, France, Ireland, Norway, and Puerto Rico) or decreasing (Australia, Canada, Germany, Israel, New Zealand, Slovenia, England, Scotland, and the USA) trends in older adults. For the 13 countries with increasing trends in both age groups, the average annual percentage increase in younger compared to older adults was higher in Chile, Japan, Sweden, t","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"232 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/s1470-2045(24)00718-6
Sharmila Devi
No Abstract
没有抽象的
{"title":"Pharmacy closures in the USA and Europe","authors":"Sharmila Devi","doi":"10.1016/s1470-2045(24)00718-6","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00718-6","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/s1470-2045(24)00719-8
Karl Gruber
No Abstract
无摘要
{"title":"Prior authorisation is can harm patients with cancer in the USA","authors":"Karl Gruber","doi":"10.1016/s1470-2045(24)00719-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00719-8","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/s1470-2045(24)00661-2
Icro Meattini, Maria Carmen De Santis, Luca Visani, Marta Scorsetti, Alessandra Fozza, Bruno Meduri, Fiorenza De Rose, Elisabetta Bonzano, Agnese Prisco, Valeria Masiello, Eliana La Rocca, Ruggero Spoto, Carlotta Becherini, Gladys Blandino, Luca Moscetti, Riccardo Ray Colciago, Riccardo A Audisio, Etienne Brain, Saverio Caini, Marije Hamaker, Jure Verbancic
<h3>Background</h3>Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.<h3>Methods</h3>This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5–10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5–15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT04134598</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and is ongoing and actively recruiting.<h3>Findings</h3>Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9–24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0–80·0) in the radiotherapy group and 74·0 years (72·0–80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9
{"title":"Single-modality endocrine therapy versus radiotherapy after breast-conserving surgery in women aged 70 years and older with luminal A-like early breast cancer (EUROPA): a preplanned interim analysis of a phase 3, non-inferiority, randomised trial","authors":"Icro Meattini, Maria Carmen De Santis, Luca Visani, Marta Scorsetti, Alessandra Fozza, Bruno Meduri, Fiorenza De Rose, Elisabetta Bonzano, Agnese Prisco, Valeria Masiello, Eliana La Rocca, Ruggero Spoto, Carlotta Becherini, Gladys Blandino, Luca Moscetti, Riccardo Ray Colciago, Riccardo A Audisio, Etienne Brain, Saverio Caini, Marije Hamaker, Jure Verbancic","doi":"10.1016/s1470-2045(24)00661-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00661-2","url":null,"abstract":"<h3>Background</h3>Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.<h3>Methods</h3>This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5–10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5–15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT04134598</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is ongoing and actively recruiting.<h3>Findings</h3>Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9–24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0–80·0) in the radiotherapy group and 74·0 years (72·0–80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 ","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/s1470-2045(24)00707-1
N Lynn Henry
No Abstract
没有抽象的
{"title":"Optimising therapy and avoiding overtreatment in breast cancer","authors":"N Lynn Henry","doi":"10.1016/s1470-2045(24)00707-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00707-1","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-06DOI: 10.1016/s1470-2045(24)00711-3
Munyaradzi Makoni
No Abstract
没有抽象的
{"title":"Africa renews commitment to an accelerated plan to end cervical cancer by 2030","authors":"Munyaradzi Makoni","doi":"10.1016/s1470-2045(24)00711-3","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00711-3","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-06DOI: 10.1016/s1470-2045(24)00599-0
Yu Zhao, Shan Xiong, Qin Ren, Jun Wang, Min Li, Lin Yang, Di Wu, Kejing Tang, Xiaojie Pan, Fengxia Chen, Wenxiang Wang, Shi Jin, Xianling Liu, Gen Lin, Wenxiu Yao, Linbo Cai, Yi Yang, Jixian Liu, Jingxun Wu, Wenfan Fu, Wenhua Liang
<h3>Background</h3>Accurate detection of driver gene mutations is crucial for treatment planning and predicting prognosis for patients with lung cancer. Conventional genomic testing requires high-quality tissue samples and is time-consuming and resource-consuming, and as a result, is not available for most patients, especially those in low-resource settings. We aimed to develop an annotation-free Deep learning-enabled artificial intelligence method to predict GEne Mutations (DeepGEM) from routinely acquired histological slides.<h3>Methods</h3>In this multicentre retrospective study, we collected data for patients with lung cancer who had a biopsy and multigene next-generation sequencing done at 16 hospitals in China (with no restrictions on age, sex, or histology type), to form a large multicentre dataset comprising paired pathological image and multiple gene mutation information. We also included patients from The Cancer Genome Atlas (TCGA) publicly available dataset. Our developed model is an instance-level and bag-level co-supervised multiple instance learning method with label disambiguation design. We trained and initially tested the DeepGEM model on the internal dataset (patients from the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China), and further evaluated it on the external dataset (patients from the remaining 15 centres) and the public TCGA dataset. Additionally, a dataset of patients from the same medical centre as the internal dataset, but without overlap, was used to evaluate the model's generalisation ability to biopsy samples from lymph node metastases. The primary objective was the performance of the DeepGEM model in predicting gene mutations (area under the curve [AUC] and accuracy) in the four prespecified groups (ie, the hold-out internal test set, multicentre external test set, TCGA set, and lymph node metastases set).<h3>Findings</h3>Assessable pathological images and multigene testing information were available for 3697 patients who had biopsy and multigene next-generation sequencing done between Jan 1, 2018, and March 31, 2022, at the 16 centres. We excluded 60 patients with low-quality images. We included 3767 images from 3637 consecutive patients (1978 [54·4%] men, 1514 [41·6%] women, 145 [4·0%] unknown; median age 60 years [IQR 52–67]), with 1716 patients in the internal dataset, 1718 patients in the external dataset, and 203 patients in the lymph node metastases dataset. The DeepGEM model showed robust performance in the internal dataset: for excisional biopsy samples, AUC values for gene mutation prediction ranged from 0·90 (95% CI 0·77–1·00) to 0·97 (0·93–1·00) and accuracy values ranged from 0·91 (0·85–0·98) to 0·97 (0·93–1·00); for aspiration biopsy samples, AUC values ranged from 0·85 (0·80–0·91) to 0·95 (0·86–1·00) and accuracy values ranged from 0·79 (0·74–0·85) to 0·99 (0·98–1·00). In the multicentre external dataset, for excisional biopsy samples, AUC values ranged from 0·80 (95% CI
{"title":"Deep learning using histological images for gene mutation prediction in lung cancer: a multicentre retrospective study","authors":"Yu Zhao, Shan Xiong, Qin Ren, Jun Wang, Min Li, Lin Yang, Di Wu, Kejing Tang, Xiaojie Pan, Fengxia Chen, Wenxiang Wang, Shi Jin, Xianling Liu, Gen Lin, Wenxiu Yao, Linbo Cai, Yi Yang, Jixian Liu, Jingxun Wu, Wenfan Fu, Wenhua Liang","doi":"10.1016/s1470-2045(24)00599-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00599-0","url":null,"abstract":"<h3>Background</h3>Accurate detection of driver gene mutations is crucial for treatment planning and predicting prognosis for patients with lung cancer. Conventional genomic testing requires high-quality tissue samples and is time-consuming and resource-consuming, and as a result, is not available for most patients, especially those in low-resource settings. We aimed to develop an annotation-free Deep learning-enabled artificial intelligence method to predict GEne Mutations (DeepGEM) from routinely acquired histological slides.<h3>Methods</h3>In this multicentre retrospective study, we collected data for patients with lung cancer who had a biopsy and multigene next-generation sequencing done at 16 hospitals in China (with no restrictions on age, sex, or histology type), to form a large multicentre dataset comprising paired pathological image and multiple gene mutation information. We also included patients from The Cancer Genome Atlas (TCGA) publicly available dataset. Our developed model is an instance-level and bag-level co-supervised multiple instance learning method with label disambiguation design. We trained and initially tested the DeepGEM model on the internal dataset (patients from the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China), and further evaluated it on the external dataset (patients from the remaining 15 centres) and the public TCGA dataset. Additionally, a dataset of patients from the same medical centre as the internal dataset, but without overlap, was used to evaluate the model's generalisation ability to biopsy samples from lymph node metastases. The primary objective was the performance of the DeepGEM model in predicting gene mutations (area under the curve [AUC] and accuracy) in the four prespecified groups (ie, the hold-out internal test set, multicentre external test set, TCGA set, and lymph node metastases set).<h3>Findings</h3>Assessable pathological images and multigene testing information were available for 3697 patients who had biopsy and multigene next-generation sequencing done between Jan 1, 2018, and March 31, 2022, at the 16 centres. We excluded 60 patients with low-quality images. We included 3767 images from 3637 consecutive patients (1978 [54·4%] men, 1514 [41·6%] women, 145 [4·0%] unknown; median age 60 years [IQR 52–67]), with 1716 patients in the internal dataset, 1718 patients in the external dataset, and 203 patients in the lymph node metastases dataset. The DeepGEM model showed robust performance in the internal dataset: for excisional biopsy samples, AUC values for gene mutation prediction ranged from 0·90 (95% CI 0·77–1·00) to 0·97 (0·93–1·00) and accuracy values ranged from 0·91 (0·85–0·98) to 0·97 (0·93–1·00); for aspiration biopsy samples, AUC values ranged from 0·85 (0·80–0·91) to 0·95 (0·86–1·00) and accuracy values ranged from 0·79 (0·74–0·85) to 0·99 (0·98–1·00). In the multicentre external dataset, for excisional biopsy samples, AUC values ranged from 0·80 (95% CI","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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