Maria Riedmeier, Lester D R Thompson, Carlos Augusto Fernandes Molina, Boris Decarolis, Christoph Härtel, Paul-G Schlegel, Martin Fassnacht, Verena Wiegering
Histopathological differentiation in pediatric adrenocortical carcinoma (pACC) is difficult and clinical prediction and stratification scores are not evaluated yet. Therefore, this review aims to summarize current evidence on the value and accuracy of the two commonly used scoring systems (Weiss/Armed Forces Institute of Pathology (AFIP)) pACC. On this base, one might be able to evaluate if patients may benefit from a unique scoring system. For this, we performed a systematic review of the published literature and included 128 patients in our analysis. The majority (72%) of the pACCs had a good clinical course. The follow-up time ranged from 0 to 420 months with a mean age of 5.6 years at diagnosis. Patients with a good clinical course were younger (mean 4.8 years) than patients with a poor outcome (mean 7.6 years). Comparing the two scoring systems, the specificity of the Weiss score was very low (25%), whereas the sensitivity was 100%. According to the AFIP score, specificity (77%) was higher than the Weiss score, whereas the sensitivity of the AFIP score was minimal lower with 92%. Age differences were recognizable as the specificity was lower in infants <4 years (20%) than in older children (32%). In contrast, the specificity of the AFIP score was higher in infants <4 years (82%) than in older age groups (76%). Summarizing our results, we could show that the Weiss score is not a suitable tool for the prediction of malignancy in pACC in comparison with the AFIP score, but further efforts may seek to ensure early and accurate stratification through augmented scoring.
小儿肾上腺皮质癌(pACC)的组织病理学鉴别是困难的,临床预测和分层评分尚未评估。因此,本综述旨在总结目前两种常用评分系统(Weiss/Armed Forces Institute of Pathology (AFIP)) pACC的价值和准确性。在此基础上,人们可以评估患者是否可以从一个独特的评分系统中受益。为此,我们对已发表的文献进行了系统回顾,并将128例患者纳入我们的分析。大多数(72%)的pACCs具有良好的临床病程。随访时间为0 ~ 420个月,诊断时平均年龄5.6岁。临床病程较好的患者(平均4.8岁)比预后较差的患者(平均7.6岁)年轻。比较两种评分系统,Weiss评分的特异性很低(25%),而敏感性为100%。根据AFIP评分,特异性(77%)高于Weiss评分,而AFIP评分的敏感性最低,为92%。由于特异性在婴儿中较低,因此可以识别年龄差异
{"title":"Prognostic value of the Weiss and Wieneke (AFIP) scoring systems in pediatric ACC - a mini review.","authors":"Maria Riedmeier, Lester D R Thompson, Carlos Augusto Fernandes Molina, Boris Decarolis, Christoph Härtel, Paul-G Schlegel, Martin Fassnacht, Verena Wiegering","doi":"10.1530/ERC-22-0259","DOIUrl":"https://doi.org/10.1530/ERC-22-0259","url":null,"abstract":"<p><p>Histopathological differentiation in pediatric adrenocortical carcinoma (pACC) is difficult and clinical prediction and stratification scores are not evaluated yet. Therefore, this review aims to summarize current evidence on the value and accuracy of the two commonly used scoring systems (Weiss/Armed Forces Institute of Pathology (AFIP)) pACC. On this base, one might be able to evaluate if patients may benefit from a unique scoring system. For this, we performed a systematic review of the published literature and included 128 patients in our analysis. The majority (72%) of the pACCs had a good clinical course. The follow-up time ranged from 0 to 420 months with a mean age of 5.6 years at diagnosis. Patients with a good clinical course were younger (mean 4.8 years) than patients with a poor outcome (mean 7.6 years). Comparing the two scoring systems, the specificity of the Weiss score was very low (25%), whereas the sensitivity was 100%. According to the AFIP score, specificity (77%) was higher than the Weiss score, whereas the sensitivity of the AFIP score was minimal lower with 92%. Age differences were recognizable as the specificity was lower in infants <4 years (20%) than in older children (32%). In contrast, the specificity of the AFIP score was higher in infants <4 years (82%) than in older age groups (76%). Summarizing our results, we could show that the Weiss score is not a suitable tool for the prediction of malignancy in pACC in comparison with the AFIP score, but further efforts may seek to ensure early and accurate stratification through augmented scoring.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9148299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The purpose of this work was toinvestigate the clinicopathological characteristics at the initial diagnosis of the pituitary tumor and at pituitary carcinoma (PC) diagnosis, alongside with the management and outcomes of PCs, and identify potential prognostic factors and therapeutic strategies associated with the clinical outcome.
Methods: PubMed was searched in May 2021 for articles in English and French reporting PCs, the diagnosis of which was made on the presence of metastases. The cases without histological proof and with either another cancer present or an atypical history for a pituitary tumor were excluded.
Results: One hundred and eighty-one articles reporting 207 cases were included, which included 38% corticotroph and 29% lactotroph carcinomas. An initial Ki67 index ≥10% was associated with shorter survival after the initial diagnosis (P = 0.01). Cases with early metastases were associated with both higher initial Ki67 index (P = 0.01) and shorter survival after PC diagnosis (P = 0.001). Interestingly, cases with short survival after PC diagnosis were associated with shorter time between the initial diagnosis and PC diagnosis (P = 0.0006) and had both higher initial Ki67 index (P = 0.003) and higher Ki67 index of the metastasis (P = 0.03). In addition, cases with long survival after PC diagnosis had received more frequently both systemic treatment after PC diagnosis (P = 0.0005) and local treatment for metastases (P < 0.0001).
Conclusions: An initial Ki67 index ≥10% is associated with worse outcome and appears as a promising early marker of future metastasis. Its presence should lead to an intensified surveillance and to a more timely management. Clinicians should not hesitate to use local treatment, independent of whether systemic treatment is used.
{"title":"Outcome and prognostic factors for pituitary carcinomas: lessons from a systematic review.","authors":"Perrine Raymond, Gerald Raverot, Mirela-Diana Ilie","doi":"10.1530/ERC-22-0338","DOIUrl":"10.1530/ERC-22-0338","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this work was toinvestigate the clinicopathological characteristics at the initial diagnosis of the pituitary tumor and at pituitary carcinoma (PC) diagnosis, alongside with the management and outcomes of PCs, and identify potential prognostic factors and therapeutic strategies associated with the clinical outcome.</p><p><strong>Methods: </strong>PubMed was searched in May 2021 for articles in English and French reporting PCs, the diagnosis of which was made on the presence of metastases. The cases without histological proof and with either another cancer present or an atypical history for a pituitary tumor were excluded.</p><p><strong>Results: </strong>One hundred and eighty-one articles reporting 207 cases were included, which included 38% corticotroph and 29% lactotroph carcinomas. An initial Ki67 index ≥10% was associated with shorter survival after the initial diagnosis (P = 0.01). Cases with early metastases were associated with both higher initial Ki67 index (P = 0.01) and shorter survival after PC diagnosis (P = 0.001). Interestingly, cases with short survival after PC diagnosis were associated with shorter time between the initial diagnosis and PC diagnosis (P = 0.0006) and had both higher initial Ki67 index (P = 0.003) and higher Ki67 index of the metastasis (P = 0.03). In addition, cases with long survival after PC diagnosis had received more frequently both systemic treatment after PC diagnosis (P = 0.0005) and local treatment for metastases (P < 0.0001).</p><p><strong>Conclusions: </strong>An initial Ki67 index ≥10% is associated with worse outcome and appears as a promising early marker of future metastasis. Its presence should lead to an intensified surveillance and to a more timely management. Clinicians should not hesitate to use local treatment, independent of whether systemic treatment is used.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9261559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-29Print Date: 2023-05-01DOI: 10.1530/ERC-22-0403
Paul C Marker, Christopher J Unterberger, Steven M Swanson
Interest in investigating the role of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis in the initiation and progression of experimentally induced carcinomas has arisen due to several observations in the human population. First, subjects with Laron syndrome who lack GH signaling have significantly lower rates of cancer than people who have normal GH signaling. Second, epidemiologic studies have found strong associations between elevated circulating IGF-1 and the incidence of several common cancers. Third, women who bear children early in life have a dramatically reduced risk of developing breast cancer, which may be due to differences in hormone levels including GH. These observations have motivated multiple studies that have experimentally altered activity of the GH/IGF-1 axis in the context of experimental carcinoma models in mice and rats. Most of these studies have utilized carcinoma models for four organ systems that are also frequent sites of carcinomas in humans: the mammary gland, prostate gland, liver, and colon. This review focuses on these studies and describes some of the most common genetic models used to alter the activity of the GH/IGF-1 axis in experimentally induced carcinomas. A recurring theme that emerges from these studies is that manipulations that reduce the activity of GH or mediators of GH action also inhibit carcinogenesis in multiple model systems.
{"title":"GH-dependent growth of experimentally induced carcinomas in vivo.","authors":"Paul C Marker, Christopher J Unterberger, Steven M Swanson","doi":"10.1530/ERC-22-0403","DOIUrl":"10.1530/ERC-22-0403","url":null,"abstract":"<p><p>Interest in investigating the role of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis in the initiation and progression of experimentally induced carcinomas has arisen due to several observations in the human population. First, subjects with Laron syndrome who lack GH signaling have significantly lower rates of cancer than people who have normal GH signaling. Second, epidemiologic studies have found strong associations between elevated circulating IGF-1 and the incidence of several common cancers. Third, women who bear children early in life have a dramatically reduced risk of developing breast cancer, which may be due to differences in hormone levels including GH. These observations have motivated multiple studies that have experimentally altered activity of the GH/IGF-1 axis in the context of experimental carcinoma models in mice and rats. Most of these studies have utilized carcinoma models for four organ systems that are also frequent sites of carcinomas in humans: the mammary gland, prostate gland, liver, and colon. This review focuses on these studies and describes some of the most common genetic models used to alter the activity of the GH/IGF-1 axis in experimentally induced carcinomas. A recurring theme that emerges from these studies is that manipulations that reduce the activity of GH or mediators of GH action also inhibit carcinogenesis in multiple model systems.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140676/pdf/nihms-1890073.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9381781","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}
Pub Date : 2023-03-27Print Date: 2023-05-01DOI: 10.1530/ERC-22-0321
Wenzel M Hackeng, Lodewijk A A Brosens, Koen M A Dreijerink
Insulinomas are rare functional pancreatic neuroendocrine tumors. While most insulinomas are indolent and cured after surgery, 10-15% of cases show aggressive or malignant tumor behavior and metastasize locally or to distant organs. Patients with metastatic insulinoma survive significantly shorter. Recognizing aggressive insulinomas can help to predict prognosis, guide therapy and determine follow-up intensity after surgery. This review offers a summary of the literature on the significant clinical, pathological, genetic and epigenetic differences between indolent and aggressive insulinomas. Aggressive insulinomas are characterized by rapid onset of symptoms, larger size, expression of ARX and alpha-1-antitrypsin and decreased or absent immunohistochemical expression of insulin, PDX1 and GLP-1R. Moreover, aggressive insulinomas often harbor ATRX or DAXX mutations, the alternative lengthening of telomeres phenotype and chromosomal instability. Tumor grade and MEN1 and YY1 mutations are less useful for predicting behavior. Aggressive insulinomas have similarities to normal alpha-cells and non-functional pancreatic neuroendocrine tumors, while indolent insulinomas remain closely related to normal beta-cells. In conclusion, indolent and aggressive insulinoma are different entities, and distinguishing these will have future clinical value in determining prognosis and treatment.
{"title":"Aggressive versus indolent insulinomas: new clinicopathological insights.","authors":"Wenzel M Hackeng, Lodewijk A A Brosens, Koen M A Dreijerink","doi":"10.1530/ERC-22-0321","DOIUrl":"10.1530/ERC-22-0321","url":null,"abstract":"<p><p>Insulinomas are rare functional pancreatic neuroendocrine tumors. While most insulinomas are indolent and cured after surgery, 10-15% of cases show aggressive or malignant tumor behavior and metastasize locally or to distant organs. Patients with metastatic insulinoma survive significantly shorter. Recognizing aggressive insulinomas can help to predict prognosis, guide therapy and determine follow-up intensity after surgery. This review offers a summary of the literature on the significant clinical, pathological, genetic and epigenetic differences between indolent and aggressive insulinomas. Aggressive insulinomas are characterized by rapid onset of symptoms, larger size, expression of ARX and alpha-1-antitrypsin and decreased or absent immunohistochemical expression of insulin, PDX1 and GLP-1R. Moreover, aggressive insulinomas often harbor ATRX or DAXX mutations, the alternative lengthening of telomeres phenotype and chromosomal instability. Tumor grade and MEN1 and YY1 mutations are less useful for predicting behavior. Aggressive insulinomas have similarities to normal alpha-cells and non-functional pancreatic neuroendocrine tumors, while indolent insulinomas remain closely related to normal beta-cells. In conclusion, indolent and aggressive insulinoma are different entities, and distinguishing these will have future clinical value in determining prognosis and treatment.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-22Print Date: 2023-04-01DOI: 10.1530/ERC-22-0287
Pia Roser, Bianca M Leca, Claudia Coelho, Klaus-Martin Schulte, Jackie Gilbert, Eftychia E Drakou, Christos Kosmas, Ling Ling Chuah, Husam Wassati, Alexander D Miras, James Crane, Simon J B Aylwin, Ashley B Grossman, Georgios K Dimitriadis
Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management.
甲状旁腺癌是最不常见的内分泌恶性肿瘤之一,约占所有原发性甲状旁腺功能亢进患者的1%。对2000年1月至2022年3月期间通过Medline、Embase、Cochrane Central Register of Controlled Trials、EudraCT、ClinicalTrials.gov、CINAHL和SCOPUS发表的同行评审文献进行了系统综述。如果手稿包括患有甲状旁腺癌的成年非妊娠人群的数据,则符合条件。没有对干预措施、比较标准或后续行动的持续时间施加任何限制。排除单一病例报告、综述或荟萃分析。感兴趣的结果是分子发病机制、临床表现、鉴别诊断、治疗、随访和总生存率。研究质量采用纽卡斯尔-渥太华量表进行观察性研究。这篇综述包括来自17个国家的75项研究,报告了3000多名甲状旁腺癌患者。CDC73突变已被认为在分子发病机制中起着关键作用。甲状旁腺癌通常表现为钙和甲状旁腺激素水平显著升高。最常见的症状是骨骼和肌肉疼痛或虚弱。整体切除仍然是手术方法的黄金标准。5年总生存率在60%至93%之间,抵抗性高钙血症是死亡率的重要原因。新出现的证据表明,基于分子生物标志物的靶向治疗提供了一种新的治疗选择。个人电脑的稀缺性和个性化治疗的需求保证了在个人电脑管理方面有良好记录的“卓越中心”进行多学科管理。
{"title":"Diagnosis and management of parathyroid carcinoma: a state-of-the-art review.","authors":"Pia Roser, Bianca M Leca, Claudia Coelho, Klaus-Martin Schulte, Jackie Gilbert, Eftychia E Drakou, Christos Kosmas, Ling Ling Chuah, Husam Wassati, Alexander D Miras, James Crane, Simon J B Aylwin, Ashley B Grossman, Georgios K Dimitriadis","doi":"10.1530/ERC-22-0287","DOIUrl":"10.1530/ERC-22-0287","url":null,"abstract":"<p><p>Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9320924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-15Print Date: 2023-04-01DOI: 10.1530/ERC-22-0372
Alessandra Mangone, Barbara Altieri, Mario Detomas, Alessandro Prete, Haider Abbas, Miriam Asia, Yasir S Elhassan, Giovanna Mantovani, Cristina L Ronchi
Treatment for advanced adrenocortical carcinoma (ACC) consists of mitotane alone or combined with etoposide, doxorubicin, and cisplatin (EDP). Although both therapies are widely used, markers of response are still lacking. Since inflammation-based scores have been proposed as prognostic factors in ACC, we aimed to investigate their role in predicting the response to first-line chemotherapy. We performed a retrospective analysis of patients with advanced ACC treated with mitotane monotherapy or EDP ± mitotane. Clinical parameters (tumour stage at diagnosis, resection status, Ki67, time from diagnosis to treatment start, performance status, plasma mitotane levels, time in mitotane target ≥ 80%, clinically overt cortisol hypersecretion), and pretreatment inflammation-based scores (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, derived neutrophil-to-lymphocyte ratio) were investigated. The primary endpoints were overall survival (OS) and time-to-progression (TTP) from treatment initiation, the secondary endpoint was the best objective response to treatment. We included 90 patients (59% = women, median age = 51 years) treated with mitotane monotherapy (n = 40) or EDP ± mitotane (n = 50). In the mitotane monotherapy cohort, NLR ≥ 5 and PLR ≥ 190 predicted shorter OS (hazard ratio (HR): 145.83, 95% CI: 1.87-11,323.83; HR: 165.50, 95% CI: 1.76-15,538.04, respectively), remaining significant at multivariable analysis including clinical variables. NLR was also associated with shorter TTP (HR: 2.58, 95% CI: 1.28-5.20), but only at univariable analysis. Patients with NLR ≥ 5 showed a worse treatment response than those with NLR < 5 (P = 0.040). In the EDP ± mitotane cohort, NLR ≥ 5 predicted shorter OS (HR: 2.52, 95% CI: 1.30-4.88) and TTP (HR: 1.95, 95% CI: 1.04-3.66) at univariable analysis. In conclusion, inflammation-based scores, calculated from routinely measured parameters, may help predict response to chemotherapy in advanced ACC.
{"title":"Inflammation-based scores as predictors of treatment response in advanced adrenocortical carcinoma.","authors":"Alessandra Mangone, Barbara Altieri, Mario Detomas, Alessandro Prete, Haider Abbas, Miriam Asia, Yasir S Elhassan, Giovanna Mantovani, Cristina L Ronchi","doi":"10.1530/ERC-22-0372","DOIUrl":"10.1530/ERC-22-0372","url":null,"abstract":"<p><p>Treatment for advanced adrenocortical carcinoma (ACC) consists of mitotane alone or combined with etoposide, doxorubicin, and cisplatin (EDP). Although both therapies are widely used, markers of response are still lacking. Since inflammation-based scores have been proposed as prognostic factors in ACC, we aimed to investigate their role in predicting the response to first-line chemotherapy. We performed a retrospective analysis of patients with advanced ACC treated with mitotane monotherapy or EDP ± mitotane. Clinical parameters (tumour stage at diagnosis, resection status, Ki67, time from diagnosis to treatment start, performance status, plasma mitotane levels, time in mitotane target ≥ 80%, clinically overt cortisol hypersecretion), and pretreatment inflammation-based scores (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, derived neutrophil-to-lymphocyte ratio) were investigated. The primary endpoints were overall survival (OS) and time-to-progression (TTP) from treatment initiation, the secondary endpoint was the best objective response to treatment. We included 90 patients (59% = women, median age = 51 years) treated with mitotane monotherapy (n = 40) or EDP ± mitotane (n = 50). In the mitotane monotherapy cohort, NLR ≥ 5 and PLR ≥ 190 predicted shorter OS (hazard ratio (HR): 145.83, 95% CI: 1.87-11,323.83; HR: 165.50, 95% CI: 1.76-15,538.04, respectively), remaining significant at multivariable analysis including clinical variables. NLR was also associated with shorter TTP (HR: 2.58, 95% CI: 1.28-5.20), but only at univariable analysis. Patients with NLR ≥ 5 showed a worse treatment response than those with NLR < 5 (P = 0.040). In the EDP ± mitotane cohort, NLR ≥ 5 predicted shorter OS (HR: 2.52, 95% CI: 1.30-4.88) and TTP (HR: 1.95, 95% CI: 1.04-3.66) at univariable analysis. In conclusion, inflammation-based scores, calculated from routinely measured parameters, may help predict response to chemotherapy in advanced ACC.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280408","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}
Pub Date : 2023-03-10Print Date: 2023-04-01DOI: 10.1530/ERC-22-0400
Cesar Luiz Boguszewski, Margaret Cristina da Silva Boguszewski, Wouter W de Herder
The association between growth hormone (GH) and carcinogenesis has long been postulated. The rationale for this association is that several components of the GH axis play an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis and have been tested as targets for cancer therapy. Epidemiological and clinical studies have examined the association between height, growth patterns, and insulin-like growth factor 1 (IGF1) levels with the most common types of malignancies, while genome-wide association studies have revealed several height-associated genes linked to cancer and/or metastasis-driving pathways. In this context, a permissive role of the GH-IGF signaling system in the link between height and cancer risk has also been investigated. In animal and human models, genetic defects associated with GH deficiency or resistance are associated with protection from tumor development, while the risk of malignancies in acromegaly or in patients exposed to recombinant GH therapy has long been a matter of concern and scrutiny. In this review, we present a narrative and historical review covering the potential relations among height, growth patterns, GH axis, and cancer.
{"title":"The science behind the relations among cancer, height, growth patterns, and growth hormone axis.","authors":"Cesar Luiz Boguszewski, Margaret Cristina da Silva Boguszewski, Wouter W de Herder","doi":"10.1530/ERC-22-0400","DOIUrl":"10.1530/ERC-22-0400","url":null,"abstract":"<p><p>The association between growth hormone (GH) and carcinogenesis has long been postulated. The rationale for this association is that several components of the GH axis play an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis and have been tested as targets for cancer therapy. Epidemiological and clinical studies have examined the association between height, growth patterns, and insulin-like growth factor 1 (IGF1) levels with the most common types of malignancies, while genome-wide association studies have revealed several height-associated genes linked to cancer and/or metastasis-driving pathways. In this context, a permissive role of the GH-IGF signaling system in the link between height and cancer risk has also been investigated. In animal and human models, genetic defects associated with GH deficiency or resistance are associated with protection from tumor development, while the risk of malignancies in acromegaly or in patients exposed to recombinant GH therapy has long been a matter of concern and scrutiny. In this review, we present a narrative and historical review covering the potential relations among height, growth patterns, GH axis, and cancer.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9148328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-10Print Date: 2023-04-01DOI: 10.1530/ERC-22-0184
Su Yon Jung, Jeanette C Papp, Eric M Sobel, Matteo Pellegrini, Herbert Yu
Insulin resistance (IR) is a well-established risk factor for breast cancer (BC) development in African American (AA) postmenopausal women. While obesity and IR are more prevalent in AA than in white women, they are under-represented in genome-wide studies for systemic regulation of IR. By examining 780 genome-wide IR single-nucleotide polymorphisms (SNPs) available in our data, we tested 4689 AA women in a Random Survival Forest framework. With 37 BC-associated lifestyle factors, we conducted a gene-environment interaction analysis to estimate risk prediction for BC with the most influential genetic and behavioral factors and evaluated their combined and joint effects on BC risk. By accounting for variations of individual SNPs in BC in the prediction model, we detected four fasting glucose-associated SNPs in PCSK1, SPC25, ADCY5, and MTNR1B and three lifestyle factors (smoking, oral contraceptive use, and age at menopause) as the most predictive markers for BC risk. Our joint analysis of risk genotypes and lifestyle with smoking revealed a synergistic effect on the increased risk of BC, particularly estrogen/progesterone positive (ER/PR+) BC, in a gene-lifestyle dose-dependent manner. The joint effect of smoking was more substantial in women with prolonged exposure to cigarette smoking and female hormones. The top genome-wide association-SNPs associated with metabolic biomarkers in combination with lifestyles synergistically increase the predictability of invasive ER/PR+ BC risk among AA women. Our findings highlight generically targeted preventive interventions for women who carry particular risk genotypes and lifestyles.
胰岛素抵抗(IR)是非裔美国人(AA)绝经后妇女罹患乳腺癌(BC)的公认风险因素。虽然肥胖和胰岛素抵抗在非裔美国人中的发病率高于白人妇女,但在有关胰岛素抵抗系统调控的全基因组研究中,非裔美国人的代表性却不足。通过研究数据中可用的 780 个全基因组 IR 单核苷酸多态性(SNPs),我们在随机生存森林框架中对 4689 名 AA 妇女进行了测试。通过 37 种与 BC 相关的生活方式因素,我们进行了基因与环境交互作用分析,以估算出最有影响力的遗传和行为因素对 BC 的风险预测,并评估了它们对 BC 风险的联合影响。通过在预测模型中考虑 BC 中单个 SNP 的变化,我们发现 PCSK1、SPC25、ADCY5 和 MTNR1B 中的四个空腹血糖相关 SNP 和三个生活方式因素(吸烟、口服避孕药和绝经年龄)是对 BC 风险最具预测性的标记。我们对风险基因型和生活方式与吸烟的联合分析表明,基因-生活方式剂量依赖性对增加 BC(尤其是雌激素/孕激素阳性(ER/PR+)BC)风险有协同作用。在长期吸烟和接触女性荷尔蒙的女性中,吸烟的联合效应更为显著。与代谢生物标志物相关的顶级全基因组关联-SNPs与生活方式相结合,协同提高了AA妇女中侵袭性ER/PR+ BC风险的可预测性。我们的研究结果突显了针对携带特定风险基因型和生活方式的女性的通用性针对性预防干预措施。
{"title":"Genetic variants of glucose metabolism and exposure to smoking in African American breast cancer.","authors":"Su Yon Jung, Jeanette C Papp, Eric M Sobel, Matteo Pellegrini, Herbert Yu","doi":"10.1530/ERC-22-0184","DOIUrl":"10.1530/ERC-22-0184","url":null,"abstract":"<p><p>Insulin resistance (IR) is a well-established risk factor for breast cancer (BC) development in African American (AA) postmenopausal women. While obesity and IR are more prevalent in AA than in white women, they are under-represented in genome-wide studies for systemic regulation of IR. By examining 780 genome-wide IR single-nucleotide polymorphisms (SNPs) available in our data, we tested 4689 AA women in a Random Survival Forest framework. With 37 BC-associated lifestyle factors, we conducted a gene-environment interaction analysis to estimate risk prediction for BC with the most influential genetic and behavioral factors and evaluated their combined and joint effects on BC risk. By accounting for variations of individual SNPs in BC in the prediction model, we detected four fasting glucose-associated SNPs in PCSK1, SPC25, ADCY5, and MTNR1B and three lifestyle factors (smoking, oral contraceptive use, and age at menopause) as the most predictive markers for BC risk. Our joint analysis of risk genotypes and lifestyle with smoking revealed a synergistic effect on the increased risk of BC, particularly estrogen/progesterone positive (ER/PR+) BC, in a gene-lifestyle dose-dependent manner. The joint effect of smoking was more substantial in women with prolonged exposure to cigarette smoking and female hormones. The top genome-wide association-SNPs associated with metabolic biomarkers in combination with lifestyles synergistically increase the predictability of invasive ER/PR+ BC risk among AA women. Our findings highlight generically targeted preventive interventions for women who carry particular risk genotypes and lifestyles.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095926/pdf/nihms-1878594.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9366635","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}
Pub Date : 2023-03-08Print Date: 2023-04-01DOI: 10.1530/ERC-22-0373
Anne-Paule Gimenez-Roqueplo, Mercedes Robledo, Patricia L M Dahia
Paragangliomas (PGL) of the adrenal (also known as pheochromocytomas) or extra-adrenal neural crest-derived cells are highly heritable tumors, usually driven by single pathogenic variants that occur mutually exclusively in genes involved in multiple cellular processes, including the response to hypoxia, MAPK/ERK signaling, and WNT signaling. The discovery of driver mutations has led to active clinical surveillance with outcome implications in familial PGL. The spectrum of mutations continues to grow and reveal unique mechanisms of tumorigenesis that inform tumor biology and provide the rationale for targeted therapy. Here we review recent progress in the genetics and molecular pathogenesis of PGLs and discuss new prospects for advancing research with new disease models and ongoing clinical trials presented at the recent International Symposium of Pheochromocytomas and Paragangliomas (ISP2022) held in October 2022 in Prague.
{"title":"Update on the genetics of paragangliomas.","authors":"Anne-Paule Gimenez-Roqueplo, Mercedes Robledo, Patricia L M Dahia","doi":"10.1530/ERC-22-0373","DOIUrl":"10.1530/ERC-22-0373","url":null,"abstract":"<p><p>Paragangliomas (PGL) of the adrenal (also known as pheochromocytomas) or extra-adrenal neural crest-derived cells are highly heritable tumors, usually driven by single pathogenic variants that occur mutually exclusively in genes involved in multiple cellular processes, including the response to hypoxia, MAPK/ERK signaling, and WNT signaling. The discovery of driver mutations has led to active clinical surveillance with outcome implications in familial PGL. The spectrum of mutations continues to grow and reveal unique mechanisms of tumorigenesis that inform tumor biology and provide the rationale for targeted therapy. Here we review recent progress in the genetics and molecular pathogenesis of PGLs and discuss new prospects for advancing research with new disease models and ongoing clinical trials presented at the recent International Symposium of Pheochromocytomas and Paragangliomas (ISP2022) held in October 2022 in Prague.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280439","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}
Pub Date : 2023-02-20Print Date: 2023-04-01DOI: 10.1530/ERC-22-0375
David Taieb, Christelle Fargette, Abhishek Jha, Karel Pacak
Precision medicine (PM) aims to maximize the risk-benefit balance of medical decisions by integrating individual patient and disease characteristics. This approach is gaining increasing recognition from clinicians, healthcare systems, pharmaceutical companies, patients, and governments. Nuclear medicine plays a critical role in PM by its virtue of providing critical information at every step of disease management, digital markers, and companion diagnostics/therapeutics. It is anticipated that technological breakthroughs and new tracers will continue to position nuclear medicine among the significant players in PM.
{"title":"Nuclear medicine in pheochromocytoma and paraganglioma: at a crossroads with precision medicine.","authors":"David Taieb, Christelle Fargette, Abhishek Jha, Karel Pacak","doi":"10.1530/ERC-22-0375","DOIUrl":"10.1530/ERC-22-0375","url":null,"abstract":"<p><p>Precision medicine (PM) aims to maximize the risk-benefit balance of medical decisions by integrating individual patient and disease characteristics. This approach is gaining increasing recognition from clinicians, healthcare systems, pharmaceutical companies, patients, and governments. Nuclear medicine plays a critical role in PM by its virtue of providing critical information at every step of disease management, digital markers, and companion diagnostics/therapeutics. It is anticipated that technological breakthroughs and new tracers will continue to position nuclear medicine among the significant players in PM.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9160885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}