Pub Date : 2025-08-14DOI: 10.1016/j.ctrv.2025.103013
Winette T.A. van der Graaf , Nina S. Heiss , Carolyn L. Hynes , Simone P. Keller , Ariane Weinman , Jean-Yves Blay , Pedro Franco , Rachel H. Giles , Denis Lacombe , Philipp Schlatter , David M. Thomas , Sahar Barjesteh van Waalwijk van Doorn-Khosrovani , Max Williamson , Ruth Plummer
Rare cancers account for a quarter of cancer diagnoses in Europe yet clinical research, diagnosis, treatment access, and survival outcomes lag significantly behind common cancers. Despite the potential of precision oncology, the consistent implementation of comprehensive genomic profiling in routine clinical practice and robust evidence-generation remains a challenge in this population, compounded by regulatory hurdles and a lack of investment in drug development. A concerted effort across all stakeholders is required to optimise diagnostics, including access to molecular profiling, to expedite clinical trials and treatment access, and to gather high-quality data, including patient-reported outcomes, in rare cancers. Some initiatives are already showing promise including the establishment of national expert reference centres and European Reference Networks such as EURACAN. However, further collaboration is required to speed up the diagnostic trajectory so that rare cancer patients present with less late-stage disease, and to facilitate clinical trials leading to wider access to precision oncology drugs shown to be safe and effective. In the context of so many hurdles (diagnosis, treatment, research, development and regulatory), there is an even greater role for patient and clinical trial organisations and funders to help fill the aforementioned gaps. Innovative solutions are urgently required to address the high unmet medical need for patients with rare cancers.
{"title":"Overcoming the barriers to treatment of rare cancer patients in the era of precision oncology: A call to action","authors":"Winette T.A. van der Graaf , Nina S. Heiss , Carolyn L. Hynes , Simone P. Keller , Ariane Weinman , Jean-Yves Blay , Pedro Franco , Rachel H. Giles , Denis Lacombe , Philipp Schlatter , David M. Thomas , Sahar Barjesteh van Waalwijk van Doorn-Khosrovani , Max Williamson , Ruth Plummer","doi":"10.1016/j.ctrv.2025.103013","DOIUrl":"10.1016/j.ctrv.2025.103013","url":null,"abstract":"<div><div>Rare cancers account for a quarter of cancer diagnoses in Europe yet clinical research, diagnosis, treatment access, and survival outcomes lag significantly behind common cancers. Despite the potential of precision oncology, the consistent implementation of comprehensive genomic profiling in routine clinical practice and robust evidence-generation remains a challenge in this population, compounded by regulatory hurdles and a lack of investment in drug development. A concerted effort across all stakeholders is required to optimise diagnostics, including access to molecular profiling, to expedite clinical trials and treatment access, and to gather high-quality data, including patient-reported outcomes, in rare cancers. Some initiatives are already showing promise including the establishment of national expert reference centres and European Reference Networks such as EURACAN. However, further collaboration is required to speed up the diagnostic trajectory so that rare cancer patients present with less late-stage disease, and to facilitate clinical trials leading to wider access to precision oncology drugs shown to be safe and effective. In the context of so many hurdles (diagnosis, treatment, research, development and regulatory), there is an even greater role for patient and clinical trial organisations and funders to help fill the aforementioned gaps. Innovative solutions are urgently required to address the high unmet medical need for patients with rare cancers.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103013"},"PeriodicalIF":10.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-11DOI: 10.1016/j.ctrv.2025.103012
Xiaoxiao Xu , Tong Yu , Zhenxing Wang
The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibodies, triggering direct cytotoxicity and immunomodulatory effects such as immunogenic cell death (ICD), antibody-dependent cellular cytotoxicity (ADCC), and dendritic cell activation. Preclinical and clinical studies highlight the synergistic effect of combining ADCs with ICIs: ADCs enhance tumor immunogenicity by releasing neoantigens, while ICIs reinvigorate T-cell-mediated antitumor responses by blocking the PD-1/PD-L1 or CTLA-4 pathways. This review explores the synergistic potential of combining ADCs and ICIs in the treatment of breast cancer, with an emphasis on mechanistic synergy and clinical outcomes. Notably, overlapping toxicities require careful monitoring. Additionally, novel immune checkpoint-targeted drug conjugates (IDCs) exhibit potential through dual-targeting and immunomodulatory mechanisms. Future efforts should focus on optimizing patient selection and developing next-generation conjugates to maximize efficacy while minimizing adverse effects.
{"title":"Combining antibody-drug conjugates with immune checkpoint inhibitors: A new paradigm for breast cancer therapy","authors":"Xiaoxiao Xu , Tong Yu , Zhenxing Wang","doi":"10.1016/j.ctrv.2025.103012","DOIUrl":"10.1016/j.ctrv.2025.103012","url":null,"abstract":"<div><div>The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibodies, triggering direct cytotoxicity and immunomodulatory effects such as immunogenic cell death (ICD), antibody-dependent cellular cytotoxicity (ADCC), and dendritic cell activation. Preclinical and clinical studies highlight the synergistic effect of combining ADCs with ICIs: ADCs enhance tumor immunogenicity by releasing neoantigens, while ICIs reinvigorate T-cell-mediated antitumor responses by blocking the PD-1/PD-L1 or CTLA-4 pathways. This review explores the synergistic potential of combining ADCs and ICIs in the treatment of breast cancer, with an emphasis on mechanistic synergy and clinical outcomes. Notably, overlapping toxicities require careful monitoring. Additionally, novel immune checkpoint-targeted drug conjugates (IDCs) exhibit potential through dual-targeting and immunomodulatory mechanisms. Future efforts should focus on optimizing patient selection and developing next-generation conjugates to maximize efficacy while minimizing adverse effects.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103012"},"PeriodicalIF":10.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune checkpoint inhibitors (ICIs) have improved outcomes for various malignancies. However, serious immune-related adverse events (irAEs), including neurologic complications (NAEs), may occur. The aim of this study was to examine the incidence and spectrum of NAEs and evaluate management strategies for reducing their impact.
Methods
Two studies were conducted: 1) A meta-analysis of phase I-IV clinical trials involving adults with malignancies treated with ICIs, either as monotherapy, in combination with other ICIs, or with chemotherapy. The primary outcome was the incidence of (ir)NAEs, summarized using a meta-analysis with a random-effects model. 2) A systematic review of the literature addressing the clinical manifestations and treatment of irNAEs.
Results
The meta-analysis included 657 unique trials with 91,340 participants. For all ICIs, the incidence of all-grade NAEs was 0.24% (95% CI, 0.15–0.32%). Cerebral events, cerebrovascular accidents, were increased post-treatment and accounted for 54% of all grade-5 events in clinical trials. Among 991 reported irNAE cases, 77% of patients improved with treatment; however, 42% experienced unresolved sequelae and the overall mortality rate was 17.1%. Among patients with overlapping myasthenia gravis, myositis, and myocarditis (“Triple M”), the mortality reached 38%; primarily due respiratory failure (50%) or cardiotoxicity (41%).
Conclusions
Although the incidence of ICI-related NAEs is low such side effects may lead to severe morbidity and mortality. In patients with Triple M syndrome intensive respiratory function monitoring and support are essential parameters to improve the outcome. PROSPERO Protocol # CRD42023463750.
{"title":"Immune checkpoint inhibitor-related neurotoxicity: Incidence and management. A systematic review and meta-analysis","authors":"Dorte Lisbet Nielsen , Carsten Bogh Juhl , Inna Markovna Chen , Yinghong Wang , Ole Haagen Nielsen , Bianca Denise Santomasso","doi":"10.1016/j.ctrv.2025.103011","DOIUrl":"10.1016/j.ctrv.2025.103011","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) have improved outcomes for various malignancies. However, serious immune-related adverse events (irAEs), including neurologic complications (NAEs), may occur. The aim of this study was to examine the incidence and spectrum of NAEs and evaluate management strategies for reducing their impact.</div></div><div><h3>Methods</h3><div>Two studies were conducted: 1) A <em>meta</em>-analysis of phase I-IV clinical trials involving adults with malignancies treated with ICIs, either as monotherapy, in combination with other ICIs, or with chemotherapy. The primary outcome was the incidence of (ir)NAEs, summarized using a <em>meta</em>-analysis with a random-effects model. 2) A systematic review of the literature addressing the clinical manifestations and treatment of irNAEs.</div></div><div><h3>Results</h3><div>The <em>meta</em>-analysis included 657 unique trials with 91,340 participants. For all ICIs, the incidence of all-grade NAEs was 0.24% (95% CI, 0.15–0.32%). Cerebral events, cerebrovascular accidents, were increased post-treatment and accounted for 54% of all grade-5 events in clinical trials. Among 991 reported irNAE cases, 77% of patients improved with treatment; however, 42% experienced unresolved sequelae and the overall mortality rate was 17.1%. Among patients with overlapping myasthenia gravis, myositis, and myocarditis (“Triple M”), the mortality reached 38%; primarily due respiratory failure (50%) or cardiotoxicity (41%).</div></div><div><h3>Conclusions</h3><div>Although the incidence of ICI-related NAEs is low such side effects may lead to severe morbidity and mortality. In patients with Triple M syndrome intensive respiratory function monitoring and support are essential parameters to improve the outcome. PROSPERO Protocol # CRD42023463750.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103011"},"PeriodicalIF":10.5,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07DOI: 10.1016/j.ctrv.2025.103001
Giovanni Corso , Sherry Shen , Carmen Criscitiello , Rita Mukhtar , Lauren Gamble , Elena Guerini Rocco , Filippo Pesapane , Luca Nicosia , Komal Jhaveri , Beatrice Taurelli Salimbeni , Giulia Massari , Eleonora Meduri , Alessandra Margherita De Scalzi , Alberto Concardi , Francesca Magnoni , Anita Mamtani , Fresia Pareja , Maria Cristina Leonardi , Virgilio Sacchini , Giorgio Bogani , Mark E. Robson
Invasive lobular carcinoma (ILC) represents approximately 10–15% of all breast cancers and is defined by a unique discohesive morphology due to loss of E-cadherin. Despite its prevalence, ILC has been historically underrepresented in clinical and translational research, contributing to diagnostic, therapeutic, and prognostic uncertainties. This narrative review, conducted by the Invasive Lobular Carcinoma Research Group, synthesizes current evidence on ILC with expert perspectives to inform future research and clinical strategies.
We highlight the distinct biology of ILC, including characteristic genomic alterations (e.g., CDH1, PIK3CA, ERBB2 mutations) and its relationship with endocrine sensitivity and limited immune infiltration. Diagnostic challenges are underscored by ILC’s subtle imaging presentation and underestimation of tumor extent on mammography and ultrasound, with MRI and contrast-enhanced mammography offering improved accuracy. The review discusses evolving surgical approaches, axillary staging considerations, and radiotherapy strategies, with an emphasis on adapting techniques to ILC’s infiltrative growth.
Endocrine therapy remains central for hormone receptor–positive ILC, with emerging evidence supporting CDK4/6 inhibitors and extended endocrine therapy in high-risk cases. Investigational therapies targeting ILC-enriched mutations and synthetic lethality mechanisms (e.g., ROS1 inhibition in CDH1-deficient tumors) hold promise for personalized treatment.
This comprehensive review identifies knowledge gaps and advocates for histology-specific clinical trials, biomarker-driven treatment strategies, and tailored imaging and surgical techniques to improve outcomes for patients with ILC.
{"title":"Invasive lobular carcinoma: Strategies and perspectives from the lobular breast cancer research group","authors":"Giovanni Corso , Sherry Shen , Carmen Criscitiello , Rita Mukhtar , Lauren Gamble , Elena Guerini Rocco , Filippo Pesapane , Luca Nicosia , Komal Jhaveri , Beatrice Taurelli Salimbeni , Giulia Massari , Eleonora Meduri , Alessandra Margherita De Scalzi , Alberto Concardi , Francesca Magnoni , Anita Mamtani , Fresia Pareja , Maria Cristina Leonardi , Virgilio Sacchini , Giorgio Bogani , Mark E. Robson","doi":"10.1016/j.ctrv.2025.103001","DOIUrl":"10.1016/j.ctrv.2025.103001","url":null,"abstract":"<div><div>Invasive lobular carcinoma (ILC) represents approximately 10–15% of all breast cancers and is defined by a unique discohesive morphology due to loss of E-cadherin. Despite its prevalence, ILC has been historically underrepresented in clinical and translational research, contributing to diagnostic, therapeutic, and prognostic uncertainties. This narrative review, conducted by the Invasive Lobular Carcinoma Research Group, synthesizes current evidence on ILC with expert perspectives to inform future research and clinical strategies.</div><div>We highlight the distinct biology of ILC, including characteristic genomic alterations (e.g., <em>CDH1</em>, <em>PIK3CA</em>, <em>ERBB2</em> mutations) and its relationship with endocrine sensitivity and limited immune infiltration. Diagnostic challenges are underscored by ILC’s subtle imaging presentation and underestimation of tumor extent on mammography and ultrasound, with MRI and contrast-enhanced mammography offering improved accuracy. The review discusses evolving surgical approaches, axillary staging considerations, and radiotherapy strategies, with an emphasis on adapting techniques to ILC’s infiltrative growth.</div><div>Endocrine therapy remains central for hormone receptor–positive ILC, with emerging evidence supporting CDK4/6 inhibitors and extended endocrine therapy in high-risk cases. Investigational therapies targeting ILC-enriched mutations and synthetic lethality mechanisms (e.g., ROS1 inhibition in <em>CDH1</em>-deficient tumors) hold promise for personalized treatment.</div><div>This comprehensive review identifies knowledge gaps and advocates for histology-specific clinical trials, biomarker-driven treatment strategies, and tailored imaging and surgical techniques to improve outcomes for patients with ILC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103001"},"PeriodicalIF":10.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-06DOI: 10.1016/j.ctrv.2025.103003
Silvia Stacchiotti , Pan Pantziarka , Hugh Leonard , Caroline Voltz , Laura Abatedaga , Gauthier Bouche , Christelle Bouygues , Judith V.M.G. Bovee , Winette T.A. Van der Graaf , Teresa De Rojas , Lorenzo D’Ambrosio , Martha Donoghue , Harald Enzmann , Gerry Feeney , Paolo Foggi , Anna Maria Frezza , Ralf Herold , Robin L. Jones , Bernd Kasper , Kit Roes , Pierre Demolis
Ultra-rare sarcomas (URS) and ultra-rare cancers (URC) represent a unique challenge in oncology due to their rarity, heterogeneity, and the severe unmet clinical needs of affected patients. In 2024, the European Medicines Agency (EMA) and the European Organisation for Research and Treatment of Cancer (EORTC) convened two multi-stakeholder workshops, bringing together regulators, clinicians, researchers, and patient advocates. These workshops aimed to explore innovative strategies for treatment development and establish a framework for future collaboration.
Key issues were discussed, including the scarcity of biological and clinical data, major barriers in conducting randomized trials, and limited pharmaceutical investment. A key outcome was the unanimous commitment of all stakeholders, including regulatory agencies such as EMA and the U.S. FDA, to work together towards pragmatic solutions. Participants recognized the necessity of flexible regulatory approaches, alternative trial designs, and meaningful endpoints tailored to ultra-rare conditions. The workshops also highlighted the importance of global collaboration, early regulatory engagement, and leveraging existing mechanisms like orphan drug designation and conditional approvals.
The discussions emphasized that while scientific rigor must be upheld, regulatory frameworks must adapt to the specific challenges posed by URS. Stakeholders pledged to maintain open dialogue, share expertise, and develop innovative infrastructures to accelerate progress.
This collaborative commitment marks a critical step forward in addressing the high unmet needs of URS. By fostering a unified effort among diverse stakeholders, the workshops established a model for advancing treatments in other URC, prioritizing patient outcomes while navigating the complexities of drug development for these challenging diseases.
{"title":"How to foster new treatment development in ultra-rare tumours? Joint EMA-EORTC multi-stakeholder workshops on ultra-rare sarcomas as a model for rare cancers","authors":"Silvia Stacchiotti , Pan Pantziarka , Hugh Leonard , Caroline Voltz , Laura Abatedaga , Gauthier Bouche , Christelle Bouygues , Judith V.M.G. Bovee , Winette T.A. Van der Graaf , Teresa De Rojas , Lorenzo D’Ambrosio , Martha Donoghue , Harald Enzmann , Gerry Feeney , Paolo Foggi , Anna Maria Frezza , Ralf Herold , Robin L. Jones , Bernd Kasper , Kit Roes , Pierre Demolis","doi":"10.1016/j.ctrv.2025.103003","DOIUrl":"10.1016/j.ctrv.2025.103003","url":null,"abstract":"<div><div>Ultra-rare sarcomas (URS) and ultra-rare cancers (URC) represent a unique challenge in oncology due to their rarity, heterogeneity, and the severe unmet clinical needs of affected patients. In 2024, the European Medicines Agency (EMA) and the European Organisation for Research and Treatment of Cancer (EORTC) convened two multi-stakeholder workshops, bringing together regulators, clinicians, researchers, and patient advocates. These workshops aimed to explore innovative strategies for treatment development and establish a framework for future collaboration.</div><div>Key issues were discussed, including the scarcity of biological and clinical data, major barriers in conducting randomized trials, and limited pharmaceutical investment. A key outcome was the unanimous commitment of all stakeholders, including regulatory agencies such as EMA and the U.S. FDA, to work together towards pragmatic solutions. Participants recognized the necessity of flexible regulatory approaches, alternative trial designs, and meaningful endpoints tailored to ultra-rare conditions. The workshops also highlighted the importance of global collaboration, early regulatory engagement, and leveraging existing mechanisms like orphan drug designation and conditional approvals.</div><div>The discussions emphasized that while scientific rigor must be upheld, regulatory frameworks must adapt to the specific challenges posed by URS. Stakeholders pledged to maintain open dialogue, share expertise, and develop innovative infrastructures to accelerate progress.</div><div>This collaborative commitment marks a critical step forward in addressing the high unmet needs of URS. By fostering a unified effort among diverse stakeholders, the workshops established a model for advancing treatments in other URC, prioritizing patient outcomes while navigating the complexities of drug development for these challenging diseases.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103003"},"PeriodicalIF":10.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-25DOI: 10.1016/j.ctrv.2025.103000
Lorenzo Lobianco , Gabriele Calvanese , Debora D’Ausilio , Sabrina Rossetti , Sabrina Chiara Cecere , Jole Ventriglia , Carmela Pisano , Rosa Tambaro , Marilena Di Napoli , Anna Passarelli , Cristin Roma , Antonella De Luca , Filippo Sepe , Silvana Cozzolino , Erica Perri , Maria Rosaria Lamia , Carlo Moccia , Sandro Pignata
Prostate cancer (PC) is the second most common cancer and the fifth leading cause of cancer mortality in men, worldwide. Genomic analysis identified alterations in DNA damage repair (DDR) pathways, in up to 30% of metastatic castration-resistant prostate cancer (mCRPC). Homologous recombination repair (HRR) mutations in BRCA1/2 emerged as a relevant biomarker in PC, linked to aggressive behavior, unfavorable outcomes and notable responses to poly-ADP ribose polymerase inhibitors (PARPi). While PARPi efficacy in BRCA-mutated mCRPC is well established, their role in earlier disease stages is currently under investigation. This non-systematic narrative review aims to summarize current evidence on PARPi in PC, outlining approved indications, ongoing clinical trials, and emerging therapeutic strategies across different disease settings.
{"title":"The emerging role of PARP inhibitors in prostate cancer: A narrative review","authors":"Lorenzo Lobianco , Gabriele Calvanese , Debora D’Ausilio , Sabrina Rossetti , Sabrina Chiara Cecere , Jole Ventriglia , Carmela Pisano , Rosa Tambaro , Marilena Di Napoli , Anna Passarelli , Cristin Roma , Antonella De Luca , Filippo Sepe , Silvana Cozzolino , Erica Perri , Maria Rosaria Lamia , Carlo Moccia , Sandro Pignata","doi":"10.1016/j.ctrv.2025.103000","DOIUrl":"10.1016/j.ctrv.2025.103000","url":null,"abstract":"<div><div>Prostate cancer (PC) is the second most common cancer and the fifth leading cause of cancer mortality in men, worldwide. Genomic analysis identified alterations in DNA damage repair (DDR) pathways, in up to 30% of metastatic castration-resistant prostate cancer (mCRPC). Homologous recombination repair (HRR) mutations in <em>BRCA1/2</em> emerged as a relevant biomarker in PC, linked to aggressive behavior, unfavorable outcomes and notable responses to poly-ADP ribose polymerase inhibitors (PARPi). While PARPi efficacy in BRCA-mutated mCRPC is well established, their role in earlier disease stages is currently under investigation. This non-systematic narrative review aims to summarize current evidence on PARPi in PC, outlining approved indications, ongoing clinical trials, and emerging therapeutic strategies across different disease settings.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103000"},"PeriodicalIF":10.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-24DOI: 10.1016/j.ctrv.2025.102998
Francesco Panzuto , Simona Barbi , Annalisa Trama , Nicola Fazio
Neuroendocrine neoplasms (NENs) exemplify the challenges and opportunities inherent in managing rare cancers. Their rarity, biological heterogeneity, and diagnostic complexity necessitate a highly structured and multidisciplinary approach to patient care. In this context, education and training emerge as central pillars for improving clinical outcomes.
This review highlights how integrating multidisciplinary teams of diverse medical specialties enhances diagnostic accuracy, refines therapeutic strategies, and ensures adherence to evolving best practices. Establishing dedicated training pathways—both through traditional educational models and innovative digital platforms—is crucial to address the unique learning needs posed by NENs.
Scientific societies play a pivotal role by producing guidelines and fostering continuous professional development, although notable variability across international recommendations emphasizes the need for clinicians to harmonize and interpret critically. Patient advocacy groups, meanwhile, have become essential actors in the educational ecosystem, bridging informational gaps and advocating for patient-centered research and policy initiatives.
Emerging technologies, particularly artificial intelligence, offer promising tools to support clinical education and decision-making, provided that their implementation is cautious, validated, and integrated under healthcare professionals’ guidance.
By analyzing the NEN model, this review underscores that the future of rare cancer management relies on building strong collaborative networks, promoting standardized yet flexible educational programs, and embracing technological innovation, always focusing on quality, safety, and patient-centered care.
{"title":"The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management","authors":"Francesco Panzuto , Simona Barbi , Annalisa Trama , Nicola Fazio","doi":"10.1016/j.ctrv.2025.102998","DOIUrl":"10.1016/j.ctrv.2025.102998","url":null,"abstract":"<div><div>Neuroendocrine neoplasms (NENs) exemplify the challenges and opportunities inherent in managing rare cancers. Their rarity, biological heterogeneity, and diagnostic complexity necessitate a highly structured and multidisciplinary approach to patient care. In this context, education and training emerge as central pillars for improving clinical outcomes.</div><div>This review highlights how integrating multidisciplinary teams of diverse medical specialties enhances diagnostic accuracy, refines therapeutic strategies, and ensures adherence to evolving best practices. Establishing dedicated training pathways—both through traditional educational models and innovative digital platforms—is crucial to address the unique learning needs posed by NENs.</div><div>Scientific societies play a pivotal role by producing guidelines and fostering continuous professional development, although notable variability across international recommendations emphasizes the need for clinicians to harmonize and interpret critically. Patient advocacy groups, meanwhile, have become essential actors in the educational ecosystem, bridging informational gaps and advocating for patient-centered research and policy initiatives.</div><div>Emerging technologies, particularly artificial intelligence, offer promising tools to support clinical education and decision-making, provided that their implementation is cautious, validated, and integrated under healthcare professionals’ guidance.</div><div>By analyzing the NEN model, this review underscores that the future of rare cancer management relies on building strong collaborative networks, promoting standardized yet flexible educational programs, and embracing technological innovation, always focusing on quality, safety, and patient-centered care.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102998"},"PeriodicalIF":9.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-24DOI: 10.1016/j.ctrv.2025.102999
Anja Holz , Bidisha Paul , Antonia Zapf , Klaus Pantel , Simon A. Joosse
Background
The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the prognostic value of sequential liquid biopsies in patients with metastatic colorectal cancer treated with systemic therapy.
Methods
Randomized, non-randomized, and prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included.
Results
Fifty-six studies involving 3735 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was strongly associated with progression-free survival (HR: 2.44, 95% CI: 2.02–2.95) and overall survival (HR: 2.53, 95% CI: 2.01–3.18), which were reported in 39 and 33 studies, respectively.
Conclusion
Our analyses underscore the strong prognostic value of longitudinal plasma-based ctDNA analysis through liquid biopsy in mCRC patients. Subsequent research should evaluate the role of ctDNA in guiding therapy decisions, particularly in identifying patients likely to benefit from continuation or change of systemic therapy. While further standardization of ctDNA testing remains necessary, current evidence supports integrating serial ctDNA monitoring into upcoming clinical mCRC intervention trials, to lay the groundwork for its inclusion into future RECIST versions.
Protocol registration
The protocol for this review was registered on PROSPERO (CRD42023420012).
{"title":"Circulating tumor DNA as prognostic marker in patients with metastatic colorectal cancer undergoing systemic therapy: A systematic review and meta-analysis","authors":"Anja Holz , Bidisha Paul , Antonia Zapf , Klaus Pantel , Simon A. Joosse","doi":"10.1016/j.ctrv.2025.102999","DOIUrl":"10.1016/j.ctrv.2025.102999","url":null,"abstract":"<div><h3>Background</h3><div>The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the prognostic value of sequential liquid biopsies in patients with metastatic colorectal cancer treated with systemic therapy.</div></div><div><h3>Methods</h3><div>Randomized, non-randomized, and prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included.</div></div><div><h3>Results</h3><div>Fifty-six studies involving 3735 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was strongly associated with progression-free survival (HR: 2.44, 95% CI: 2.02–2.95) and overall survival (HR: 2.53, 95% CI: 2.01–3.18), which were reported in 39 and 33 studies, respectively.</div></div><div><h3>Conclusion</h3><div>Our analyses underscore the strong prognostic value of longitudinal plasma-based ctDNA analysis through liquid biopsy in mCRC patients. Subsequent research should evaluate the role of ctDNA in guiding therapy decisions, particularly in identifying patients likely to benefit from continuation or change of systemic therapy. While further standardization of ctDNA testing remains necessary, current evidence supports integrating serial ctDNA monitoring into upcoming clinical mCRC intervention trials, to lay the groundwork for its inclusion into future RECIST versions.</div></div><div><h3>Protocol registration</h3><div>The protocol for this review was registered on PROSPERO (CRD42023420012).</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102999"},"PeriodicalIF":10.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-23DOI: 10.1016/j.ctrv.2025.102997
Gabrielle J. Williams , John F. Thompson
Objective
Multidisciplinary team (MDT) review of cancer patients has become routine in many institutions worldwide. The process seeks to ensure correct diagnosis and staging, optimise treatment decisions and improve outcomes. The aim of this study was to measure any differences in management and survival of cancer patients reviewed at an MDT meeting compared to patients not reviewed or with management plans made prior to MDT review.
Methods and Analysis
A PRISMA-compliant systematic review was undertaken with searches of Medline, Embase and the Cochrane Trials Register to 7 June 2024, with no restrictions on language or era.
Results
From 2832 titles, 179 comparative studies were identified. Hazard ratios (HRs) for death, generated from multivariable analyses, were reported in 37 studies that included 56,187 patients but estimates were highly variable (I2 87 %), ranging from HR 0.1 to 0.96. While the magnitude of the benefit for patients after MDT review was variable, all 37 studies reported a reduced risk of death for MDT-reviewed patients compared to non-reviewed patients. Sub-group analyses based on the patient’s cancer type reduced heterogeneity in patients with breast and hepatocellular carcinomas and suggested a reduced risk of death in MDT-reviewed patients compared to those not reviewed (HR 0.86, 95 %CI 0.79–0.93, I2 56 %, p = 0.0001 and HR 0.82, 95 %CI 0.76–0.88, I2 36 %, p < 0.00001, respectively).
Conclusion
Extensive evidence shows a survival benefit for cancer patients discussed at an MDT meeting but there is considerable variation in the reported magnitude of that benefit, ranging from a 4% to a 90% reduction in the risk of death.
目的：多学科小组（MDT）对癌症患者的复查已成为世界范围内许多机构的常规工作。该过程旨在确保正确的诊断和分期，优化治疗决策并改善结果。本研究的目的是衡量在MDT会议上接受审查的癌症患者与未接受审查的患者或在MDT审查之前制定了管理计划的患者相比，在管理和生存方面的任何差异。方法和分析采用符合prisma标准的系统评价，检索Medline、Embase和Cochrane Trials Register至2024年6月7日，无语言和时代限制。结果从2832篇文献中筛选出179篇比较研究。由多变量分析得出的死亡风险比（HRs）在37项研究中报告，其中包括56,187例患者，但估计值变化很大（i287%），风险比范围为0.1至0.96。虽然MDT审查后患者获益的幅度是可变的，但所有37项研究都报告了MDT审查的患者与未审查的患者相比死亡风险降低。基于患者癌症类型的亚组分析降低了乳腺癌和肝细胞癌患者的异质性，并表明与未接受mdt审查的患者相比，接受mdt审查的患者的死亡风险降低(HR 0.86, 95% CI 0.79-0.93, I2 56%, p = 0.0001; HR 0.82, 95% CI 0.76-0.88, I2 36%, p <；分别为0.00001)。结论：广泛的证据表明，在MDT会议上讨论了癌症患者的生存获益，但报告的获益幅度差异很大，从4%到90%的死亡风险降低不等。
{"title":"Management changes and survival outcomes for cancer patients after multidisciplinary team discussion; a systematic review and meta-analysis","authors":"Gabrielle J. Williams , John F. Thompson","doi":"10.1016/j.ctrv.2025.102997","DOIUrl":"10.1016/j.ctrv.2025.102997","url":null,"abstract":"<div><h3>Objective</h3><div>Multidisciplinary team (MDT) review of cancer patients has become routine in many institutions worldwide. The process seeks to ensure correct diagnosis and staging, optimise treatment decisions and improve outcomes. The aim of this study was to measure any differences in management and survival of cancer patients reviewed at an MDT meeting compared to patients not reviewed or with management plans made prior to MDT review.</div></div><div><h3>Methods and Analysis</h3><div>A PRISMA-compliant systematic review was undertaken with searches of Medline, Embase and the Cochrane Trials Register to 7 June 2024, with no restrictions on language or era.</div></div><div><h3>Results</h3><div>From 2832 titles, 179 comparative studies were identified. Hazard ratios (HRs) for death, generated from multivariable analyses, were reported in 37 studies that included 56,187 patients but estimates were highly variable (I<sup>2</sup> 87 %), ranging from HR 0.1 to 0.96. While the magnitude of the benefit for patients after MDT review was variable, all 37 studies reported a reduced risk of death for MDT-reviewed patients compared to non-reviewed patients. Sub-group analyses based on the patient’s cancer type reduced heterogeneity in patients with breast and hepatocellular carcinomas and suggested a reduced risk of death in MDT-reviewed patients compared to those not reviewed (HR 0.86, 95 %CI 0.79–0.93, I<sup>2</sup> 56 %, p = 0.0001 and HR 0.82, 95 %CI 0.76–0.88, I<sup>2</sup> 36 %, p < 0.00001, respectively).</div></div><div><h3>Conclusion</h3><div>Extensive evidence shows a survival benefit for cancer patients discussed at an MDT meeting but there is considerable variation in the reported magnitude of that benefit, ranging from a 4% to a 90% reduction in the risk of death.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102997"},"PeriodicalIF":9.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1016/j.ctrv.2025.102996
F. Javier Muñoz-Carrillo , Marta Garcia de Herreros , David Carrillo , Olenka Peralta , Caterina Aversa , Laia Fernández-Mañas , Laura Ferrer-Mileo , Mariana Altamirano , Òscar Reig Torras , Natalia Jimenez , Begoña Mellado
Prostate cancer (PC) is one of the most prevalent malignancies worldwide. Metastatic PC remains an incurable disease, with the androgen receptor (AR) pathway being the primary driver of tumor progression and the main target for therapeutic strategies. Thus, patients usually undergo long-term treatments, particularly androgen deprivation therapy (ADT), which can worsen the intrinsic deterioration in quality of life (QoL) caused by the disease burden. Increasing evidence supports the use of physical activity (PA) and structured exercise (EX) as complementary measures to mitigate treatment-related adverse effects and improve clinical outcomes across tumor types. EX has shown benefits across multiple systems and plays a significant role in modulating tumor progression through several cellular pathways. Furthermore, it has confirmed potential to alleviate cancer-related symptoms while enhancing functional capacity and tolerability of treatment. This review gathers the current evidence regarding the impact of PA and EX on patients with metastatic PC, integrating both epidemiological and interventional studies. Despite promising findings, most of the available evidence is documented on non-metastatic populations, highlighting the need for directed studies in advanced disease settings. Future research is needed in metastatic PC patients, in order to assess long-term impacts of EX in this population.
{"title":"Exercise in patients with metastatic prostate cancer: A comprehensive review","authors":"F. Javier Muñoz-Carrillo , Marta Garcia de Herreros , David Carrillo , Olenka Peralta , Caterina Aversa , Laia Fernández-Mañas , Laura Ferrer-Mileo , Mariana Altamirano , Òscar Reig Torras , Natalia Jimenez , Begoña Mellado","doi":"10.1016/j.ctrv.2025.102996","DOIUrl":"10.1016/j.ctrv.2025.102996","url":null,"abstract":"<div><div>Prostate cancer (PC) is one of the most prevalent malignancies worldwide. Metastatic PC remains an incurable disease, with the androgen receptor (AR) pathway being the primary driver of tumor progression and the main target for therapeutic strategies. Thus, patients usually undergo long-term treatments, particularly androgen deprivation therapy (ADT), which can worsen the intrinsic deterioration in quality of life (QoL) caused by the disease burden. Increasing evidence supports the use of physical activity (PA) and structured exercise (EX) as complementary measures to mitigate treatment-related adverse effects and improve clinical outcomes across tumor types. EX has shown benefits across multiple systems and plays a significant role in modulating tumor progression through several cellular pathways. Furthermore, it has confirmed potential to alleviate cancer-related symptoms while enhancing functional capacity and tolerability of treatment. This review gathers the current evidence regarding the impact of PA and EX on patients with metastatic PC, integrating both epidemiological and interventional studies. Despite promising findings, most of the available evidence is documented on non-metastatic populations, highlighting the need for directed studies in advanced disease settings. Future research is needed in metastatic PC patients, in order to assess long-term impacts of EX in this population.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102996"},"PeriodicalIF":9.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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