Pub Date : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104600
Kamil Malshy , Borivoj Golijanin , Sari Khaleel , Katherine Danaher , Jilienne Widener , Stephen Schmit , Galina Lagos , Benedito Carneiro , Ali Amin , Liang Cheng , Gyan Pareek , Anthony Mega , Dragan Golijanin , Elias Hyams
Prostate cancer (PCa) is highly prevalent among aging men and a significant contributor to global mortality. Balancing early detection and treatment of “clinically significant” disease with avoiding over-detection and overtreatment of slow-growing tumors is challenging, especially for elderly patients with competing health risks and potentially aggressive disease phenotypes. This review emphasizes the importance of individualized approaches for diagnosing and treating PCa in geriatric patients. Active surveillance and watchful waiting are common strategies, while surgical interventions are less frequent but considered based on comorbidities, disease risk, and patient preferences. Radiotherapy, often combined with androgen deprivation therapy, is typical for higher-risk cases, and focal therapy is emerging to reduce morbidity. An inclusive approach combining advanced diagnostics, life expectancy considerations, and minimally invasive interventions can improve decision-making. Integrating multidisciplinary strategies with better risk stratification and less invasive options can significantly enhance care and outcomes for elderly patients with significant PCa.
{"title":"Navigating management of localized prostate cancer in the geriatric population","authors":"Kamil Malshy , Borivoj Golijanin , Sari Khaleel , Katherine Danaher , Jilienne Widener , Stephen Schmit , Galina Lagos , Benedito Carneiro , Ali Amin , Liang Cheng , Gyan Pareek , Anthony Mega , Dragan Golijanin , Elias Hyams","doi":"10.1016/j.critrevonc.2024.104600","DOIUrl":"10.1016/j.critrevonc.2024.104600","url":null,"abstract":"<div><div>Prostate cancer (PCa) is highly prevalent among aging men and a significant contributor to global mortality. Balancing early detection and treatment of “clinically significant” disease with avoiding over-detection and overtreatment of slow-growing tumors is challenging, especially for elderly patients with competing health risks and potentially aggressive disease phenotypes. This review emphasizes the importance of individualized approaches for diagnosing and treating PCa in geriatric patients. Active surveillance and watchful waiting are common strategies, while surgical interventions are less frequent but considered based on comorbidities, disease risk, and patient preferences. Radiotherapy, often combined with androgen deprivation therapy, is typical for higher-risk cases, and focal therapy is emerging to reduce morbidity. An inclusive approach combining advanced diagnostics, life expectancy considerations, and minimally invasive interventions can improve decision-making. Integrating multidisciplinary strategies with better risk stratification and less invasive options can significantly enhance care and outcomes for elderly patients with significant PCa.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104600"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873638","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2025.104643
Guanjie Lin , Ahmed Elkashif , Chayanika Saha , Jonathan A. Coulter , Nicholas J. Dunne , Helen O. McCarthy
Prostate cancer has the second highest cancer mortality rate in the UK in males. Early prostate cancer is typically asymptomatic, with diagnosis at a locally advanced or metastatic stage. In addition, the inherent heterogeneity of prostate cancer tumours differs significantly in terms of genetic, molecular, and histological features. The successful treatment of prostate cancer is therefore exceedingly challenging. Immunotherapies, particularly therapeutic vaccines, have been widely used in preclinical and clinical studies to treat various cancers. Sipuleucel-T was the first cancer vaccine approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), ushering in a new era of immunotherapy. In this review, the latest immunotherapy strategies for prostate cancer are considered with key tumour-associated antigens (TAA) and tumour-specific antigens (TSA) highlighted. The key components of mRNA vaccines include in vitro transcription, stability, and immunogenicity. Finally, strategies to circumvent in vivo mRNA degradation and approaches to optimise in vitro transcription (IVT) process are also discussed.
{"title":"Key considerations for a prostate cancer mRNA vaccine","authors":"Guanjie Lin , Ahmed Elkashif , Chayanika Saha , Jonathan A. Coulter , Nicholas J. Dunne , Helen O. McCarthy","doi":"10.1016/j.critrevonc.2025.104643","DOIUrl":"10.1016/j.critrevonc.2025.104643","url":null,"abstract":"<div><div>Prostate cancer has the second highest cancer mortality rate in the UK in males. Early prostate cancer is typically asymptomatic, with diagnosis at a locally advanced or metastatic stage. In addition, the inherent heterogeneity of prostate cancer tumours differs significantly in terms of genetic, molecular, and histological features. The successful treatment of prostate cancer is therefore exceedingly challenging. Immunotherapies, particularly therapeutic vaccines, have been widely used in preclinical and clinical studies to treat various cancers. Sipuleucel-T was the first cancer vaccine approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), ushering in a new era of immunotherapy. In this review, the latest immunotherapy strategies for prostate cancer are considered with key tumour-associated antigens (TAA) and tumour-specific antigens (TSA) highlighted. The key components of mRNA vaccines include <em>in vitro</em> transcription, stability, and immunogenicity. Finally, strategies to circumvent <em>in vivo</em> mRNA degradation and approaches to optimise <em>in vitro</em> transcription (IVT) process are also discussed.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104643"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124164","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104590
Muhammad Sajjad Hassan , Hafiz Muhammad Irfan , Alamgeer , Muavia Sarwar , Zeeshan Jabbar , Shoaib Nawaz
Current therapeutic strategies for benign prostatic hyperplasia (BPH) and prostate cancer focus mainly on androgen receptors (AR) and 5-alpha reductase inhibition to suppress androgen-driven prostate growth. However, these methods often result in side effects and resistance. Recent research identifies novel targets like integrin and cadherin inhibitors, gene regulation, microRNAs, cellular senescence, and metabolomics pathways to overcome these limitations. These innovations offer more personalized approaches with potentially fewer adverse effects and reduced resistance compared to traditional androgen-focused therapies. Novel target sites and pathways, either suppressed or overexpressed, offer control points for modulating signaling in prostate diseases, suggesting future potential for treatment through innovative exogenous substances. Data was compiled from Google Scholar, PubMed, and Google to highlight the comparative potential of these emerging methods in enhancing treatment efficacy for prostate health.
{"title":"Emerging therapeutic frontiers in prostate health: Novel molecular targets and classical pathways in comparison with BPH and prostate cancer","authors":"Muhammad Sajjad Hassan , Hafiz Muhammad Irfan , Alamgeer , Muavia Sarwar , Zeeshan Jabbar , Shoaib Nawaz","doi":"10.1016/j.critrevonc.2024.104590","DOIUrl":"10.1016/j.critrevonc.2024.104590","url":null,"abstract":"<div><div>Current therapeutic strategies for benign prostatic hyperplasia (BPH) and prostate cancer focus mainly on androgen receptors (AR) and 5-alpha reductase inhibition to suppress androgen-driven prostate growth. However, these methods often result in side effects and resistance. Recent research identifies novel targets like integrin and cadherin inhibitors, gene regulation, microRNAs, cellular senescence, and metabolomics pathways to overcome these limitations. These innovations offer more personalized approaches with potentially fewer adverse effects and reduced resistance compared to traditional androgen-focused therapies. Novel target sites and pathways, either suppressed or overexpressed, offer control points for modulating signaling in prostate diseases, suggesting future potential for treatment through innovative exogenous substances. Data was compiled from Google Scholar, PubMed, and Google to highlight the comparative potential of these emerging methods in enhancing treatment efficacy for prostate health.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104590"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796674","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104572
Michael Renteln
Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase small molecule glues, but developing new small molecule drugs for each patient is not feasible currently. Certain companies are using immunotherapies to target clonal mutations. I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.
{"title":"Targeting clonal mutations with synthetic microbes","authors":"Michael Renteln","doi":"10.1016/j.critrevonc.2024.104572","DOIUrl":"10.1016/j.critrevonc.2024.104572","url":null,"abstract":"<div><div>Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal\" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase small molecule glues, but developing new small molecule drugs for each patient is not feasible currently. Certain companies are using immunotherapies to target clonal mutations. I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104572"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755378","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2025.104633
Chiara Catania , Claudia Proto , Chiara Bennati , Salvatore Grisanti , Ida Colantonio , Francesco Petrella , Andrea Riccardo Filippi , Carlo Genova , Gaia Piperno , Nazario Teodorani , Carlo Greco , Claudia Sangalli , Vieri Scotti , Francesco Agustoni , Emanuela Olmetto , Marco Russano , Vincenzo Agbaje , Angelo Platania , Marzia Di Pietro Paolo , Paolo Borghetti , Alessandro Russo
Introduction
During the recent INTERACTION group congress held on February 16–17, 2024, in Milan, Italy, many aspects of early-stage lung cancer treatment were explored. This review delves into perioperative treatment, a rapidly evolving field with an expanding therapeutic arsenal that includes chemotherapy, target therapy, and immunotherapy. The challenge remains in tailoring treatment strategies to individual patients, identifying patients best suited for surgery versus those necessitating trimodal treatment, particularly in distinguishing surgical candidates from those requiring multimodal approaches and not suitable for surgical approach.
Materials and methods
We conducted a literature review of phase III trials on immunotherapy and target therapy in early-stage non-small cell lung cancer (NSCLC), searching in MEDLINE, EMBASE and LILACS, adding the latest data from the European Society of Medical Oncology (ESMO) 2023 and 2024, American Society of Clinical Oncology (ASCO) 2024, and the World Conference on Lung Cancer (WCLC) 2024 conferences. A guidance on unresolved and controversial issues from the panel has been reported, also highlighting the remaining limitations that warrant further investigation and refinement in this field.
Results
Most recent data on early-stage NSCLC have been critically reviewed. The panel emphasized the importance of distinguishing, from the outset in a multidisciplinary setting, patients who are suitable for surgical treatment from those who are not. In this context, the importance of accurate staging at the time of diagnosis was highlighted. A paradigm shifts regarding the timing of molecular NGS DNA and RNA testing is strongly recommended.
Conclusion
Decisions regarding perioperative treatment in early-stage lung cancer demand early consideration, involving a multidisciplinary team and require an upfront NGS analysis. Such an approach ensures personalized care aligned with each patient's unique characteristics, optimizing treatment efficacy and overall well-being.
{"title":"Navigating chemotherapy and immunotherapy in early-stage lung cancer. A critical review and statements from INTERACTION group","authors":"Chiara Catania , Claudia Proto , Chiara Bennati , Salvatore Grisanti , Ida Colantonio , Francesco Petrella , Andrea Riccardo Filippi , Carlo Genova , Gaia Piperno , Nazario Teodorani , Carlo Greco , Claudia Sangalli , Vieri Scotti , Francesco Agustoni , Emanuela Olmetto , Marco Russano , Vincenzo Agbaje , Angelo Platania , Marzia Di Pietro Paolo , Paolo Borghetti , Alessandro Russo","doi":"10.1016/j.critrevonc.2025.104633","DOIUrl":"10.1016/j.critrevonc.2025.104633","url":null,"abstract":"<div><h3>Introduction</h3><div>During the recent INTERACTION group congress held on February 16–17, 2024, in Milan, Italy, many aspects of early-stage lung cancer treatment were explored. This review delves into perioperative treatment, a rapidly evolving field with an expanding therapeutic arsenal that includes chemotherapy, target therapy, and immunotherapy. The challenge remains in tailoring treatment strategies to individual patients, identifying patients best suited for surgery versus those necessitating trimodal treatment, particularly in distinguishing surgical candidates from those requiring multimodal approaches and not suitable for surgical approach.</div></div><div><h3>Materials and methods</h3><div>We conducted a literature review of phase III trials on immunotherapy and target therapy in early-stage non-small cell lung cancer (NSCLC), searching in MEDLINE, EMBASE and LILACS, adding the latest data from the European Society of Medical Oncology (ESMO) 2023 and 2024, American Society of Clinical Oncology (ASCO) 2024, and the World Conference on Lung Cancer (WCLC) 2024 conferences. A guidance on unresolved and controversial issues from the panel has been reported, also highlighting the remaining limitations that warrant further investigation and refinement in this field.</div></div><div><h3>Results</h3><div>Most recent data on early-stage NSCLC have been critically reviewed. The panel emphasized the importance of distinguishing, from the outset in a multidisciplinary setting, patients who are suitable for surgical treatment from those who are not. In this context, the importance of accurate staging at the time of diagnosis was highlighted. A paradigm shifts regarding the timing of molecular NGS DNA and RNA testing is strongly recommended.</div></div><div><h3>Conclusion</h3><div>Decisions regarding perioperative treatment in early-stage lung cancer demand early consideration, involving a multidisciplinary team and require an upfront NGS analysis. Such an approach ensures personalized care aligned with each patient's unique characteristics, optimizing treatment efficacy and overall well-being.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104633"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124166","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104571
Nicola Silvestris , Giuseppe Aprile , Dalila Tessitore , Giulia Mentrasti , Maria Cristina Petrella , Desirèe Speranza , Amanda Casirati , Riccardo Caccialanza , Saverio Cinieri , Paolo Pedrazzoli , on behalf of the Italian Intersociety Working Group for Nutritional Support in Cancer Patients
Cancer is currently one of the biggest public health challenges worldwide, ranking as the second leading cause of death globally. To date, strong epidemiological associations have been demonstrated between unhealthy lifestyles and eating habits, i.e. obesity, and an increased risk of developing cancer. However, there is limited evidence regarding the impact of specific dietary regimes on cancer outcomes during conventional cancer treatments. This paper systematically reviews and evaluates preclinical and clinical evidence regarding the effects of fasting, fast-mimicking diet, ketogenic diet, vegan diet, alkaline diet, paleolithic diet, the Gerson regimen, and macrobiotic diet in the context of cancer treatments. Clinical trials on dietary regimes as complementary cancer therapy are limited by significant differences in trial design, patient characteristics, and cancer type, making it difficult to draw conclusions. In the future, more uniformly controlled clinical trials should help to better define the role of diets in cancer management.
{"title":"Harnessing tumor metabolism during cancer treatment: A narrative review of emerging dietary approaches","authors":"Nicola Silvestris , Giuseppe Aprile , Dalila Tessitore , Giulia Mentrasti , Maria Cristina Petrella , Desirèe Speranza , Amanda Casirati , Riccardo Caccialanza , Saverio Cinieri , Paolo Pedrazzoli , on behalf of the Italian Intersociety Working Group for Nutritional Support in Cancer Patients","doi":"10.1016/j.critrevonc.2024.104571","DOIUrl":"10.1016/j.critrevonc.2024.104571","url":null,"abstract":"<div><div>Cancer is currently one of the biggest public health challenges worldwide, ranking as the second leading cause of death globally. To date, strong epidemiological associations have been demonstrated between unhealthy lifestyles and eating habits, i.e. obesity, and an increased risk of developing cancer. However, there is limited evidence regarding the impact of specific dietary regimes on cancer outcomes during conventional cancer treatments. This paper systematically reviews and evaluates preclinical and clinical evidence regarding the effects of fasting, fast-mimicking diet, ketogenic diet, vegan diet, alkaline diet, paleolithic diet, the Gerson regimen, and macrobiotic diet in the context of cancer treatments. Clinical trials on dietary regimes as complementary cancer therapy are limited by significant differences in trial design, patient characteristics, and cancer type, making it difficult to draw conclusions. In the future, more uniformly controlled clinical trials should help to better define the role of diets in cancer management.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104571"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712202","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}
The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management. Indeed, the therapeutic options are sometimes unfamiliar and may be further complicated by the lack of recommendations in the event of failure of a well-managed first-line treatment. Finally, the attribution of ICIs to certain CNS disorders is controversial and may lead to an incorrect decision to discontinue or contraindicate treatment, resulting in an irremediable loss of opportunity for the patient. Therefore, the aim of this review is to present known/suspected CNS nirAEs induced by ICI, their diagnostic approach and management through therapeutic advices for optimal treatment and rechallenge opportunities.
{"title":"Central nervous system complications of immune checkpoint inhibitors: A comprehensive review","authors":"Sébastien Lopes , Lucile Pabst , Thibault Bahougne , Philippe Barthélémy , Romain Guitton , Kevin Didier , Lionnel Geoffrois , Florence Granel-Brocard , Bertrand Mennecier , Céline Mascaux , Stéphane Kremer , Nicolas Collongues","doi":"10.1016/j.critrevonc.2024.104595","DOIUrl":"10.1016/j.critrevonc.2024.104595","url":null,"abstract":"<div><div>The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management. Indeed, the therapeutic options are sometimes unfamiliar and may be further complicated by the lack of recommendations in the event of failure of a well-managed first-line treatment. Finally, the attribution of ICIs to certain CNS disorders is controversial and may lead to an incorrect decision to discontinue or contraindicate treatment, resulting in an irremediable loss of opportunity for the patient. Therefore, the aim of this review is to present known/suspected CNS nirAEs induced by ICI, their diagnostic approach and management through therapeutic advices for optimal treatment and rechallenge opportunities.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104595"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite the impressive improvements achieved by endocrine therapy and CDK4/6 inhibitors (CDK4/6i) and the forthcoming availability of alternative endocrine manipulations and targeted therapies, hormone-receptor positive/HER2 negative (HR+/HER2-) advanced breast cancer (ABC) is almost inevitably destined to become endocrine- refractory. At this time chemotherapy has been recently challenged and partly replaced by new targeted options as antibody-drug conjugated (ADCs). Trastuzumab-deruxtecan has been proven meaningfully superior to chemotherapy either in 1st and later lines after progression to CDK4/6i in HER2-low ABC and results with other ADCs as Sacituzumab Govitecan and Datopotamab-deruxtecan are promising, but the definition of cross-resistance between these drugs sharing either antibody or payload is crucial before implementing them in a useful sequence. While PARP inhibitors are the standard 2nd line in patients with gBRCA mutation, it is not still known whether patients with mutations of PALB2 or of other homologous recombinant defect (HRD)-related genes will benefit of the same treatment. On the other hand, the results obtained with immune checkpoint inhibitors (ICIs) in HR+ /HER2-ABC contrarily to the early setting are disappointing up to now, but investigations of ICIs in combination with other targeted drugs which may increase immune response and the search for better markers of activity are under way. Moreover the anticipation in upfront treatment of ADCs or PARPi in patients with features of putative endocrine resistance and/or of less sensitiviy to CDK4/6i and the choice of therapy in patients recurring during or soon after adjuvant CDK4/6i and olaparib represent further challenges for the future.
{"title":"Beyond failure of endocrine-based therapies in HR+/HER2 negative advanced breast cancer: What before chemotherapy? A glimpse into the future","authors":"Rosalba Torrisi , Riccardo Gerosa , Chiara Miggiano , Giuseppe Saltalamacchia , Chiara Benvenuti , Armando Santoro","doi":"10.1016/j.critrevonc.2025.104634","DOIUrl":"10.1016/j.critrevonc.2025.104634","url":null,"abstract":"<div><div>Despite the impressive improvements achieved by endocrine therapy and CDK4/6 inhibitors (CDK4/6i) and the forthcoming availability of alternative endocrine manipulations and targeted therapies, hormone-receptor positive/HER2 negative (HR+/HER2-) advanced breast cancer (ABC) is almost inevitably destined to become endocrine- refractory. At this time chemotherapy has been recently challenged and partly replaced by new targeted options as antibody-drug conjugated (ADCs). Trastuzumab-deruxtecan has been proven meaningfully superior to chemotherapy either in 1st and later lines after progression to CDK4/6i in HER2-low ABC and results with other ADCs as Sacituzumab Govitecan and Datopotamab-deruxtecan are promising, but the definition of cross-resistance between these drugs sharing either antibody or payload is crucial before implementing them in a useful sequence. While PARP inhibitors are the standard 2nd line in patients with g<em>BRCA</em> mutation, it is not still known whether patients with mutations of <em>PALB2</em> or of other homologous recombinant defect (HRD)-related genes will benefit of the same treatment. On the other hand, the results obtained with immune checkpoint inhibitors (ICIs) in HR+ /HER2-ABC contrarily to the early setting are disappointing up to now, but investigations of ICIs in combination with other targeted drugs which may increase immune response and the search for better markers of activity are under way. Moreover the anticipation in upfront treatment of ADCs or PARPi in patients with features of putative endocrine resistance and/or of less sensitiviy to CDK4/6i and the choice of therapy in patients recurring during or soon after adjuvant CDK4/6i and olaparib represent further challenges for the future.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104634"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124114","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104578
Mehrsa Mennati , Aysan Moeinafshar , Nima Rezaei
Breast cancer is one of the most common types of cancer among women in Western countries. Historically treated with radical and modified radical surgeries, breast cancer is now primarily managed with breast-conserving surgery combined with postsurgical radiotherapy. Oncoplastic breast surgery, a technique that integrates aesthetic breast reduction methods with cancer surgery, has been developed as a tumor-specific approach to facilitate breast conservation while removing the tumor. This method allows for higher excision volumes with minimal aesthetic compromise. The main components of oncoplastic surgery are volume displacement and volume replacement techniques. This review discusses the essential role of oncoplastic techniques in breast-conserving surgery (BCS), which has evolved into the standard of care for early-stage breast cancer. Understanding these techniques is critical for all breast surgeons to optimize both aesthetic and oncologic outcomes.
{"title":"Enhancing breast cancer surgery outcomes: A comprehensive review of oncoplastic techniques, surgical planning, and aesthetic considerations","authors":"Mehrsa Mennati , Aysan Moeinafshar , Nima Rezaei","doi":"10.1016/j.critrevonc.2024.104578","DOIUrl":"10.1016/j.critrevonc.2024.104578","url":null,"abstract":"<div><div>Breast cancer is one of the most common types of cancer among women in Western countries. Historically treated with radical and modified radical surgeries, breast cancer is now primarily managed with breast-conserving surgery combined with postsurgical radiotherapy. Oncoplastic breast surgery, a technique that integrates aesthetic breast reduction methods with cancer surgery, has been developed as a tumor-specific approach to facilitate breast conservation while removing the tumor. This method allows for higher excision volumes with minimal aesthetic compromise. The main components of oncoplastic surgery are volume displacement and volume replacement techniques. This review discusses the essential role of oncoplastic techniques in breast-conserving surgery (BCS), which has evolved into the standard of care for early-stage breast cancer. Understanding these techniques is critical for all breast surgeons to optimize both aesthetic and oncologic outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104578"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752601","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 : 2025-02-01DOI: 10.1016/j.critrevonc.2024.104587
Lavinia Piazza , Anna Carollo , Enrica Di Martino , Maria Eugenia Novara , Sofia Cutaia , Alessio Provenzani , Sergio Rizzo
Background and aims
The aim of this systematic review was to assess the risk of cardiac toxicity in patients undergoing approved PD-1 (nivolumab, pembrolizumab, cemiplimab, dostarlimab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab) inhibitors.
Results
Among a total of 2272 articles, 11 phase II and III clinical trials included: 5463 patients and 175 cardiac adverse events. The most common cardiac disorder was atrial fibrillation (12 %), while cardiac arrest and cardiac failure (6 %) led to death in three cases. Overall, ICI treatment increased the risk of cardiotoxicity compared with control groups (RR=1.62, 95 %-CI= 1.18–2.24, p-value=0.0033; OR=1.71, 95 %-CI= 1.20–2.42, p-value=0.0027).
Conclusions
This study proved that the recognition of frequency and severity of all grade cardiotoxicity associated with ICIs is still underestimated. Thus, a systematic cardiological screening becomes necessary, in order to intercept the potential cardiological complications beforehand and optimize the outcomes of the respective treatment with PD-1, PD-L1 and CTLA-4 inhibitors.
{"title":"Cardiotoxicity associated with immune checkpoint inhibitors: Systematic review and meta-analysis","authors":"Lavinia Piazza , Anna Carollo , Enrica Di Martino , Maria Eugenia Novara , Sofia Cutaia , Alessio Provenzani , Sergio Rizzo","doi":"10.1016/j.critrevonc.2024.104587","DOIUrl":"10.1016/j.critrevonc.2024.104587","url":null,"abstract":"<div><h3>Background and aims</h3><div>The aim of this systematic review was to assess the risk of cardiac toxicity in patients undergoing approved PD-1 (nivolumab, pembrolizumab, cemiplimab, dostarlimab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab) inhibitors.</div></div><div><h3>Results</h3><div>Among a total of 2272 articles, 11 phase II and III clinical trials included: 5463 patients and 175 cardiac adverse events. The most common cardiac disorder was atrial fibrillation (12 %), while cardiac arrest and cardiac failure (6 %) led to death in three cases. Overall, ICI treatment increased the risk of cardiotoxicity compared with control groups (RR=1.62, 95 %-CI= 1.18–2.24, p-value=0.0033; OR=1.71, 95 %-CI= 1.20–2.42, p-value=0.0027).</div></div><div><h3>Conclusions</h3><div>This study proved that the recognition of frequency and severity of all grade cardiotoxicity associated with ICIs is still underestimated. Thus, a systematic cardiological screening becomes necessary, in order to intercept the potential cardiological complications beforehand and optimize the outcomes of the respective treatment with PD-1, PD-L1 and CTLA-4 inhibitors.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104587"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820197","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}
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