Pub Date : 2025-09-05DOI: 10.1016/j.ctrv.2025.103019
Lucia Musacchio , Domenica Lorusso , Giulia Sabetta , Alessandra Giustozzi , Elena Giudice , Maria Chiara Cannizzaro , Maria Teresa Perri , Anna Fagotti , Vanda Salutari
Low-grade serous ovarian carcinoma (LGSOC) represents a unique therapeutic challenge in gynecologic oncology. While it accounts for a minority of epithelial ovarian cancers (EOC), its distinct molecular landscape and limited sensitivity to conventional chemotherapy underscore the urgent need for alternative treatment paradigms. Over the past decade, advances in genomic profiling have led to a deeper understanding of its biology, revealing recurrent alterations in key signaling pathways such as (mitogen-activated protein kinase) MAPK, PI3K, and cell cycle regulators. These insights have catalyzed a shift toward precision medicine, with targeted agents and endocrine strategies emerging as promising avenues. However, despite encouraging signals from clinical trials, the rarity of LGSOC continues to hinder the development of robust, evidence-based standards. In this review, we critically examine the current treatment landscape and explore evolving therapeutic strategies, including ongoing efforts to integrate molecular biomarkers into clinical decision-making. By synthesizing recent evidence and highlighting key areas of unmet need, this review aims to provide a forward-looking perspective on the treatment of LGSOC. Future progress will depend on collaborative research, biomarker-driven clinical trial design, and a commitment to tailoring therapy based on the unique biology of this rare tumor type.
{"title":"Advances in treatment strategies for low-grade serous ovarian cancer","authors":"Lucia Musacchio , Domenica Lorusso , Giulia Sabetta , Alessandra Giustozzi , Elena Giudice , Maria Chiara Cannizzaro , Maria Teresa Perri , Anna Fagotti , Vanda Salutari","doi":"10.1016/j.ctrv.2025.103019","DOIUrl":"10.1016/j.ctrv.2025.103019","url":null,"abstract":"<div><div>Low-grade serous ovarian carcinoma (LGSOC) represents a unique therapeutic challenge in gynecologic oncology. While it accounts for a minority of epithelial ovarian cancers (EOC), its distinct molecular landscape and limited sensitivity to conventional chemotherapy underscore the urgent need for alternative treatment paradigms. Over the past decade, advances in genomic profiling have led to a deeper understanding of its biology, revealing recurrent alterations in key signaling pathways such as (mitogen-activated protein kinase) MAPK, PI3K, and cell cycle regulators. These insights have catalyzed a shift toward precision medicine, with targeted agents and endocrine strategies emerging as promising avenues. However, despite encouraging signals from clinical trials, the rarity of LGSOC continues to hinder the development of robust, evidence-based standards. In this review, we critically examine the current treatment landscape and explore evolving therapeutic strategies, including ongoing efforts to integrate molecular biomarkers into clinical decision-making. By synthesizing recent evidence and highlighting key areas of unmet need, this review aims to provide a forward-looking perspective on the treatment of LGSOC. Future progress will depend on collaborative research, biomarker-driven clinical trial design, and a commitment to tailoring therapy based on the unique biology of this rare tumor type.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103019"},"PeriodicalIF":10.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026391","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}
To critically review the emerging evidence from two randomised trials—KEYNOTE-689 and NIVOPOSTOP—on perioperative immune checkpoint inhibition in resectable, locally advanced head and neck squamous cell carcinoma, and to elucidate how these positive results may redefine the current and future treatment paradigms.
Methods
We conducted a narrative review comparing the design, patient populations, treatment protocols, and outcomes of KEYNOTE-689 and NIVOPOSTOP. Data sources included ClinicalTrials.gov, presentations at major international oncology meetings, and peer-reviewed publications.
Results
KEYNOTE-689 adopted a broad perioperative strategy using pembrolizumab both pre- and postoperatively, with (chemo)radiotherapy administered based on pathological risk. NIVOPOSTOP employed a focused adjuvant approach, using nivolumab alongside postoperative chemoradiotherapy only in high-risk patients. Despite distinct strategies, both trials demonstrated significant improvements in event-free survival (KEYNOTE-689; hazard ratio 0.73; 95% confidence interval, 0.58–0.92) and disease-free survival (NIVOPOSTOP; hazard ratio 0.76; 95% confidence interval, 0.60–0.98). KEYNOTE-689 reduced distant recurrence, while NIVOPOSTOP improved loco-regional control. Although overall survival data remain immature, both show favourable trends. Treatment adherence and treatment-related serious adverse events were lower in KEYNOTE-689.
Conclusions
Perioperative immune checkpoint inhibition is emerging as the first new standard in two decades for resectable locally advanced head and neck squamous cell carcinoma. KEYNOTE-689 highlights early immune priming, whereas NIVOPOSTOP offers a pragmatic, high-risk–targeted model with high compliance. Treatment selection should be tailored by recurrence risk, programmed death-ligand 1 expression, and multidisciplinary evaluation. Future priorities include refining patient selection and immune checkpoint blockade schedule, optimizing neoadjuvant regimens, implementing response-adapted de-escalation, and assessing cost-effectiveness.
{"title":"Comparative review of KEYNOTE-689 and NIVOPOSTOP trials and their impact on perioperative immunotherapy in locally advanced head and neck cancer","authors":"Yoshinori Imamura , Masafumi Kanno , Shigeharu Fujieda","doi":"10.1016/j.ctrv.2025.103018","DOIUrl":"10.1016/j.ctrv.2025.103018","url":null,"abstract":"<div><h3>Aim</h3><div>To critically review the emerging evidence from two randomised trials—KEYNOTE-689 and NIVOPOSTOP—on perioperative immune checkpoint inhibition in resectable, locally advanced head and neck squamous cell carcinoma, and to elucidate how these positive results may redefine the current and future treatment paradigms.</div></div><div><h3>Methods</h3><div>We conducted a narrative review comparing the design, patient populations, treatment protocols, and outcomes of KEYNOTE-689 and NIVOPOSTOP. Data sources included <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, presentations at major international oncology meetings, and peer-reviewed publications.</div></div><div><h3>Results</h3><div>KEYNOTE-689 adopted a broad perioperative strategy using pembrolizumab both pre- and postoperatively, with (chemo)radiotherapy administered based on pathological risk. NIVOPOSTOP employed a focused adjuvant approach, using nivolumab alongside postoperative chemoradiotherapy only in high-risk patients. Despite distinct strategies, both trials demonstrated significant improvements in event-free survival (KEYNOTE-689; hazard ratio 0.73; 95% confidence interval, 0.58–0.92) and disease-free survival (NIVOPOSTOP; hazard ratio 0.76; 95% confidence interval, 0.60–0.98). KEYNOTE-689 reduced distant recurrence, while NIVOPOSTOP improved loco-regional control. Although overall survival data remain immature, both show favourable trends. Treatment adherence and treatment-related serious adverse events were lower in KEYNOTE-689.</div></div><div><h3>Conclusions</h3><div>Perioperative immune checkpoint inhibition is emerging as the first new standard in two decades for resectable locally advanced head and neck squamous cell carcinoma. KEYNOTE-689 highlights early immune priming, whereas NIVOPOSTOP offers a pragmatic, high-risk–targeted model with high compliance. Treatment selection should be tailored by recurrence risk, programmed death-ligand 1 expression, and multidisciplinary evaluation. Future priorities include refining patient selection and immune checkpoint blockade schedule, optimizing neoadjuvant regimens, implementing response-adapted de-escalation, and assessing cost-effectiveness.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103018"},"PeriodicalIF":10.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932627","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 : 2025-08-27DOI: 10.1016/j.ctrv.2025.103017
Danny Lavigne , Yungan Tao , Cecile Le Péchoux , Angela Botticella , France Nguyen , Roger Sun , Pierre Blanchard , Jordi Remon , Eric Deutsch , Antonin Levy
Immunotherapy has become standard of care for numerous cancer types in the past decade. Combining radiotherapy and immunotherapy has the potential to further improve outcomes by taking advantage of their theoretical synergy on antitumoral immune response. Despite promising preclinical and early clinical studies, along with significant improvements reported in specific settings, results from larger trials attempting to expand radioimmunotherapy to diverse clinical scenarios are markedly inconsistent. This review examines published and ongoing clinical trials evaluating this treatment strategy in patients with lung and head and neck cancers, where various sequencing strategies and settings were explored, including the consolidation, concurrent, induction, resectable, and metastatic settings. We highlight similarities and differences between these two tumor sites, discussing factors contributing to the variable efficacy of this therapeutic approach across diverse clinical settings.
{"title":"Radioimmunotherapy for lung and head and neck cancers: A comparative review of clinical trial results and sequencing strategies","authors":"Danny Lavigne , Yungan Tao , Cecile Le Péchoux , Angela Botticella , France Nguyen , Roger Sun , Pierre Blanchard , Jordi Remon , Eric Deutsch , Antonin Levy","doi":"10.1016/j.ctrv.2025.103017","DOIUrl":"10.1016/j.ctrv.2025.103017","url":null,"abstract":"<div><div>Immunotherapy has become standard of care for numerous cancer types in the past decade. Combining radiotherapy and immunotherapy has the potential to further improve outcomes by taking advantage of their theoretical synergy on antitumoral immune response. Despite promising preclinical and early clinical studies, along with significant improvements reported in specific settings, results from larger trials attempting to expand radioimmunotherapy to diverse clinical scenarios are markedly inconsistent. This review examines published and ongoing clinical trials evaluating this treatment strategy in patients with lung and head and neck cancers, where various sequencing strategies and settings were explored, including the consolidation, concurrent, induction, resectable, and metastatic settings. We highlight similarities and differences between these two tumor sites, discussing factors contributing to the variable efficacy of this therapeutic approach across diverse clinical settings.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103017"},"PeriodicalIF":10.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920379","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 : 2025-08-25DOI: 10.1016/j.ctrv.2025.103016
Peter R. Galle , Martin Reck , David J. Pinato , Rosario Garcia-Campelo , Richard S. Finn , Sophie Cousin , Jim Zanghi , Coen A. Bernaards , Steven J. Swanson , Stefanie Morris , Yuan Song , Solange Peters
Immunogenicity of a therapeutic protein product may elicit an unintended immune response, and is a critical aspect evaluated in oncology clinical trials. The development of anti-drug antibodies (ADAs) can impact the pharmacokinetics, pharmacodynamics, efficacy, and safety of these therapies. We review the background and nomenclature of immunogenicity assessment in oncology studies and emphasize the complexities in ADA detection arising from assay sensitivity, drug interference, and notably, the frequency of patient sampling for ADA analysis. The applicability of common nomenclature, however, has limitations in the context of oncology. Of prime consideration for physicians is that the clinical impact of ADA is far more important than just their presence. Furthermore, the interpretation of immunogenicity data in oncology is complicated by patient-specific factors, concomitant treatments, and potential survivorship bias. Regulatory guidelines acknowledge these complexities, mandating specific statements on product labels cautioning against cross-trial comparisons of ADA incidence due to variations in assay methods and sampling schedules. Accurate interpretation of immunogenicity data, considering assay methodologies, study design, and sampling frequency, is crucial for clinicians to assess the clinical relevance of ADA findings and make informed treatment decisions for patients receiving therapeutic protein products in oncology. The focus should be on the clinical relevance of ADAs rather than simply their incidence.
{"title":"Interpreting immunogenicity in oncology clinical trials","authors":"Peter R. Galle , Martin Reck , David J. Pinato , Rosario Garcia-Campelo , Richard S. Finn , Sophie Cousin , Jim Zanghi , Coen A. Bernaards , Steven J. Swanson , Stefanie Morris , Yuan Song , Solange Peters","doi":"10.1016/j.ctrv.2025.103016","DOIUrl":"10.1016/j.ctrv.2025.103016","url":null,"abstract":"<div><div>Immunogenicity of a therapeutic protein product may elicit an unintended immune response, and is a critical aspect evaluated in oncology clinical trials. The development of anti-drug antibodies (ADAs) can impact the pharmacokinetics, pharmacodynamics, efficacy, and safety of these therapies. We review the background and nomenclature of immunogenicity assessment in oncology studies and emphasize the complexities in ADA detection arising from assay sensitivity, drug interference, and notably, the frequency of patient sampling for ADA analysis. The applicability of common nomenclature, however, has limitations in the context of oncology. Of prime consideration for physicians is that the clinical impact of ADA is far more important than just their presence. Furthermore, the interpretation of immunogenicity data in oncology is complicated by patient-specific factors, concomitant treatments, and potential survivorship bias. Regulatory guidelines acknowledge these complexities, mandating specific statements on product labels cautioning against cross-trial comparisons of ADA incidence due to variations in assay methods and sampling schedules. Accurate interpretation of immunogenicity data, considering assay methodologies, study design, and sampling frequency, is crucial for clinicians to assess the clinical relevance of ADA findings and make informed treatment decisions for patients receiving therapeutic protein products in oncology. The focus should be on the clinical relevance of ADAs rather than simply their incidence.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103016"},"PeriodicalIF":10.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920380","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 : 2025-08-22DOI: 10.1016/j.ctrv.2025.103014
Ying Yu, Yuxi Luo, Fujuan Zeng, Anwen Liu
Brain radiotherapy (BRT) has traditionally been the mainstay of treatment for non-small cell lung cancer brain metastases (NSCLC-BM), given the low intracranial efficacy of conventional systemic therapies. In recent years, immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for advanced NSCLC without actionable driver mutations and have shown promising benefits in patients with BM. However, their intracranial efficacy remains modest, as the highest reported intracranial objective response rate and median intracranial progression-free survival in first-line populations reaching only 56.3 % and 12.7 months, respectively, which is likely explained by restricted blood-brain barrier permeability, the immunosuppressive tumor microenvironment within BM, and both primary and acquired resistance to ICIs. Preclinical evidence suggests that BRT can synergize with ICIs by enhancing antitumor immunity and overcoming immune resistance, primarily through blood-brain barrier disruption and tumor microenvironment remodeling. Consistently, encouraging clinical outcomes have been reported with the combination of BRT and ICI (BRT-ICI) in NSCLC-BM, while prospective data remain scarce. A recent phase II trial reported some of the most favorable outcomes to date with BRT-ICI plus chemotherapy, showing an intracranial objective response rate of 82.5 %, a median intracranial progression-free survival of 16.1 months, and a median overall survival of 20.9 months in treatment-naive patients with NSCLC-BM. Despite these advances, the optimal schedule of BRT-ICI remains controversial, with ongoing debates on treatment sequencing, timing, and radiation dose-fractionation. Additionally, critical challenges persist, including the risk of neurological toxicity, particularly radiation necrosis, and the absence of predictive biomarkers for patient selection. This review summarizes the current advances in ICI-based systemic therapies for NSCLC-BM, discusses the existing opportunities and progress of BRT-ICI, and reflects on challenges in optimizing this strategy in the immunotherapy era.
{"title":"Opportunities and challenges for non–small cell lung cancer brain metastases in the immunotherapy era","authors":"Ying Yu, Yuxi Luo, Fujuan Zeng, Anwen Liu","doi":"10.1016/j.ctrv.2025.103014","DOIUrl":"10.1016/j.ctrv.2025.103014","url":null,"abstract":"<div><div>Brain radiotherapy (BRT) has traditionally been the mainstay of treatment for non-small cell lung cancer brain metastases (NSCLC-BM), given the low intracranial efficacy of conventional systemic therapies. In recent years, immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for advanced NSCLC without actionable driver mutations and have shown promising benefits in patients with BM. However, their intracranial efficacy remains modest, as the highest reported intracranial objective response rate and median intracranial progression-free survival in first-line populations reaching only 56.3 % and 12.7 months, respectively, which is likely explained by restricted blood-brain barrier permeability, the immunosuppressive tumor microenvironment within BM, and both primary and acquired resistance to ICIs. Preclinical evidence suggests that BRT can synergize with ICIs by enhancing antitumor immunity and overcoming immune resistance, primarily through blood-brain barrier disruption and tumor microenvironment remodeling. Consistently, encouraging clinical outcomes have been reported with the combination of BRT and ICI (BRT-ICI) in NSCLC-BM, while prospective data remain scarce. A recent phase II trial reported some of the most favorable outcomes to date with BRT-ICI plus chemotherapy, showing an intracranial objective response rate of 82.5 %, a median intracranial progression-free survival of 16.1 months, and a median overall survival of 20.9 months in treatment-naive patients with NSCLC-BM. Despite these advances, the optimal schedule of BRT-ICI remains controversial, with ongoing debates on treatment sequencing, timing, and radiation dose-fractionation. Additionally, critical challenges persist, including the risk of neurological toxicity, particularly radiation necrosis, and the absence of predictive biomarkers for patient selection. This review summarizes the current advances in ICI-based systemic therapies for NSCLC-BM, discusses the existing opportunities and progress of BRT-ICI, and reflects on challenges in optimizing this strategy in the immunotherapy era.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103014"},"PeriodicalIF":10.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907517","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 : 2025-08-19DOI: 10.1016/j.ctrv.2025.103015
Marco Airoldi , Susana Roselló , Noelia Tarazona , Marisol Huerta , Leticia Pérez-Santiago , Tania Fleitas , Vicente Pla-Martí , Alberto Puccini , Desamparados Roda , Andrés Cervantes
The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy’s potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient’s well-being.
{"title":"Advances in the management of locally advanced rectal cancer: A shift toward a patient-centred approach to balance outcomes and quality of life","authors":"Marco Airoldi , Susana Roselló , Noelia Tarazona , Marisol Huerta , Leticia Pérez-Santiago , Tania Fleitas , Vicente Pla-Martí , Alberto Puccini , Desamparados Roda , Andrés Cervantes","doi":"10.1016/j.ctrv.2025.103015","DOIUrl":"10.1016/j.ctrv.2025.103015","url":null,"abstract":"<div><div>The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy’s potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient’s well-being.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103015"},"PeriodicalIF":10.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893040","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 : 2025-08-14DOI: 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}
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