Tasong J, Sheldon R, Clements A
… +2 more, Abid MT, Gan A
Cancer Treat Rev
· 2025 Dec · PMID 41192027
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BACKGROUND: Thyroid cancer incidence has risen in recent years, with high mortality rates in aggressive subtypes. Clinical trials of immune checkpoint inhibitors (ICIs), indicate efficacy against a range of solid tumours...BACKGROUND: Thyroid cancer incidence has risen in recent years, with high mortality rates in aggressive subtypes. Clinical trials of immune checkpoint inhibitors (ICIs), indicate efficacy against a range of solid tumours. However, their role in the thyroid remains to be established. This systematic review (PROSPERO: CRD420250634944) assesses the effectiveness and safety of ICIs in thyroid cancer, reported following PRISMA guidelines. METHODS: Searches were performed in 6 databases (EMBASE, PubMed, CENTRAL, Scopus, Web of Science and Clinicaltrials.gov) from inception to 10th January 2025. All studies reporting efficacy outcomes for ICIs in thyroid cancer were included. Clinical trials databases were searched for the most recent results and ongoing trials. Study quality was assessed using the CASP checklist. RESULTS: Of 1,207 studies retrieved, 33 met the inclusion criteria. Of these trials, 14 investigated ICI plus tyrosine kinase inhibitors, and 5 studies each evaluated dual ICI combinations, ICI monotherapy, or ICIs plus chemotherapy or radiotherapy. Included studies reported variable efficacy and safety. Studies in anaplastic thyroid cancer (ATC) using biomarker-stratified ICI combinations demonstrated the greatest effectiveness. The safety profiles were generally manageable, with common adverse events including fatigue, anorexia, and increased lipase levels. CONCLUSIONS: ICIs show promising responses in thyroid cancer, particularly in ATC. However, the current evidence is limited to non-randomised phase I-II studies, and no phase III trials have been conducted to date. Further investigation in larger, placebo-controlled trials is required to assess efficacy in clinical practice. Predictive biomarkers can help identify patients who may experience the greatest clinical benefit, maximising cost-effectiveness.
Zhao X, Hao Q, Alsina M
… +13 more, Acosta D, Castet F, Terán E, Cano KV, Saurí T, Macías I, Yoshikawa T, Castro S, Shoji H, Lordick F, Shen Z, Tian TV, Macarulla T
Cancer Treat Rev
· 2025 Dec · PMID 41187568
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Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements...Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements in the field. However, notable differences have historically existed between these regions in the treatment of resectable GC. In recent years, increasing convergence between Asian and Western approaches has emerged, driven by the growth of global collaborative studies. New definitive evidence suggests that the therapeutic landscape for resectable GC may undergo a significant transformation. In this review, we comprehensively examine the evolution of surgical approaches and perioperative chemotherapy strategies in Asia and the West. We summarize key clinical trials, highlight persistent survival disparities, and provide insight into current trends in perioperative management, including the recent advances in molecularly driven perioperative treatments. Finally, we outline key considerations for future multicenter perioperative trials to further guide global clinical practice.
Ricco G, Gallio C, Benhima N
… +3 more, Assaf I, Laethem JV, Sclafani F
Cancer Treat Rev
· 2025 Dec · PMID 41166896
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Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H) is an established biomarker in early-stage colon cancer and metastatic colorectal cancer. However, its prognostic significance in early-stage rectal c...Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H) is an established biomarker in early-stage colon cancer and metastatic colorectal cancer. However, its prognostic significance in early-stage rectal cancer patients treated with neoadjuvant therapy remains uncertain. We aimed to fill this gap by conducting a systematic review and meta-analysis of the available evidence. PubMed, Embase and Scopus were systematically searched from inception to 11/03/2025 for studies comparing the outcome of dMMR/MSI-H and MMR proficient/microsatellite stable (pMMR/MSS) rectal cancer patients treated with neoadjuvant therapy. Studies of immune checkpoint inhibitors were excluded. Data on pathologic complete response (pCR), pathologic tumor regression grade (pTRG), disease-free survival (DFS) and overall survival (OS) were extracted. Pooled odds ratios (ORs) and hazard ratios (HRs) with their 95 % confidence interval (95 % CI) were calculated using a random effects model. After screening 705 records, 26 retrospective studies were included, the majority of patients being treated with long-course chemoradiotherapy. There was a significant association between dMMR/MSI-H status and pCR (OR 1.50 [95 % CI: 1.04-2.14]; p = 0.03), while no association was found for pTRG (OR 0.77 [95 % CI: 0.44-1.34]; p = 0.326), DFS (HR 1.00 [95 % CI: 0.50-2.01]; p = 0.998) and OS (HR 1.42 [95 % CI: 1.00-2.01]; p = 0.051). Despite the limited data, subgroup analyses did not appear to reveal any significant difference by type of neoadjuvant treatment. In conclusion, patients with dMMR/MSI-H rectal cancer treated with standard neoadjuvant therapy are more likely to achieve a pCR than those with pMMR/MSS tumors.
Migliore C, Fenocchio E, Giordano S
… +1 more, Corso S
Cancer Treat Rev
· 2025 Dec · PMID 41138549
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Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and is associated with a very poor prognosis, largely due to its aggressive nature and, typically, late-stage diagnosis. Molecular cla...Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and is associated with a very poor prognosis, largely due to its aggressive nature and, typically, late-stage diagnosis. Molecular classifications proposed one decade ago have provided valuable insights into the disease's heterogeneity and paved the way for clinical trials of tailored treatments. However, most of these trials have failed, often due to inadequate patient selection, lack of reliable biomarkers of response/resistance, or for the high level of inter- and intra-tumor heterogeneity characterizing this disease. This Review provides an in-depth and up-to-date overview of the preclinical models of GC developed in recent years. These include patient-derived xenografts (PDXs), organoids (PDOs), and genetically engineered mouse models (GEMMs), which are valuable tools for elucidating disease mechanisms and for preclinical drug testing. We also highlight emerging molecular targets and innovative therapeutic strategies-such as immunotherapies, antibody-drug conjugates, and synthetic lethality approaches-designed to overcome the mechanisms of resistance that limit current treatment efficacy. Together, these improvements offer renewed hope for more effective and durable treatment options in GC, ultimately aiming to improve patient outcomes through a more tailored approach.
Emile SH, Wignakumar A, Syed A
… +4 more, Horesh N, Barsom SH, Garoufalia Z, Wexner SD
Cancer Treat Rev
· 2025 Dec · PMID 41135267
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BACKGROUND: This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC). METHODS: A PRISMA-compliant umb...BACKGROUND: This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC). METHODS: A PRISMA-compliant umbrella overview of systematic reviews was conducted. PubMed and Scopus were searched through October 2024 for systematic reviews that assessed the diagnostic and prognostic utility of ctDNA and microRNA in CRC. The diagnostic accuracy of ctDNA and microRNA in the detection of CRC and associated genetic mutations, and the association between ctDNA and disease recurrence and survival were assessed. RESULTS: 26 systematic reviews were included. ctDNA had pooled sensitivity and specificity in detecting KRAS mutations of 75-83 % and 91-98 %, respectively. MicroRNA had a 59-76 % pooled sensitivity and 64-89 % pooled specificity in the detection of CRC. The detection of ctDNA after surgery for CRC was associated with increased recurrence, and the risk was higher when detection followed adjuvant chemotherapy. The detection of ctDNA was associated with an increased recurrence of colorectal metastases and worse overall survival. ctDNA was associated with an increased risk of rectal cancer recurrence and reduced odds of pathologic complete response when detected after neoadjuvant therapy and after surgery. The increased risk of recurrence associated with ctDNA was proportional to the disease stage; however, evidence on this observation is limited to one meta-analysis. CONCLUSIONS: Detection of ctDNA before or after treatment of CRC, regardless of the stage, was associated with both increased recurrence and decreased survival. This negative impact was more notable when ctDNA was detected after locoregional treatment.
Kim S, Sheth K, Yu X
… +2 more, Porterfield L, Vaughan EM
Cancer Treat Rev
· 2025 Dec · PMID 41135266
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BACKGROUND: Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for < 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast...BACKGROUND: Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for < 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy-though supporting evidence remains limited. AIM: To assess clinical characteristics and treatment outcomes of SBACC of the breast. METHODS: This study presents a case of breast SBACC and a systematic review of five databases (inception-September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO. RESULTS: Nineteen studies and one new case (134 patients, aged 19-89) were included. Except for three patients who had with metastatic disease at diagnosis, the rest (97 %) were treated with surgery; 55.6 % received chemotherapy. Among nine patients given neoadjuvant chemotherapy and/or immunotherapy, none achieved complete pathological response, and most had poor outcomes. In non-metastatic cases with reported treatment (n = 99), younger age predicted recurrence (p = 0.032) but not chemotherapy receipt (p = 0.082). Chemotherapy did not reduce recurrence risk (p = 0.819). Mastectomy versus breast-conserving surgery with radiation had similar outcomes (p = 0.197). CONCLUSIONS: Although limited data are available for this rare cancer, evidence for the efficacy of chemotherapy and immunotherapy for SBACC treatment is lacking. Treatment plans should be individualized to reduce the physical, psychological, and financial burdens on both patients and healthcare systems.
Cancer Treat Rev
· 2025 Dec · PMID 41110184
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BACKGROUND: Radiotherapy is associated with pulmonary fibrosis in 5-15% of cases, potentially impacting lung function and thus the quality of life of patients with breast cancer. This study aimed to assess short, middle,...BACKGROUND: Radiotherapy is associated with pulmonary fibrosis in 5-15% of cases, potentially impacting lung function and thus the quality of life of patients with breast cancer. This study aimed to assess short, middle, and long-term effects of radiotherapy on lung function in women treated for breast cancer. MATERIALS AND METHODS: A thorough literature search of databases (Medline, Web of Science, Scopus, and CENTRAL) up to October 2024 was conducted. Included were observational, experimental, and quasi-experimental studies assessing radiotherapy effects on lung function in women treated for breast cancer. A meta-analysis summarised findings, and risk of bias (Cochrane ROBINS-E) and quality of evidence (GRADE framework) were assessed. RESULTS: Twenty-two studies totalled 1042 women, of median age 51 years [range 44-56]. Radiotherapy administered conventionally (46-58 Gy, 1.8-2.2 Gy/fraction, 23-28 sessions, 5 days/week, 5 weeks) or hypo-fractionated (40-43.2 Gy, 2.7-2.8 Gy/fraction, 15-16 sessions, 5 days/week, 3 weeks), resulted in significant declines in FEV%predicted, FVC%predicted, and DLCO%predicted at one-, three-, six-, and 12-months post-radiotherapy. Clinically relevant reductions (≥5%) were noted for FEV%predicted at one and 12 months (MD[95 %CI) = -7.94[-13.94; -1.93], -5.10[-8.81; -1.39], respectively), FVC%predicted at one, six, and 12 months (-5.98[-11.78; -0.17], -5.90[-9.01; -2.79], -5.58[-9.32;-1.83], respectively), and DLCO%predicted at one, three, and 12 months (-8.00[-15.66; -0.34], -5.51[-7.91; -3.11], -6.76 [-10.27; -3.25], respectively). Risk of bias was low in 64 %, moderate in 14 %, and high in 23 % of studies. GRADE assessment indicated moderate level of evidence. CONCLUSIONS: Radiotherapy may affect lung function in women treated for breast cancer, especially in the absence of lung-sparing techniques, resulting in declines persisting up to 12 months post-radiation. However, heterogeneity in patient characteristics and treatment protocols among studies warrants cautious interpretation of these findings. This highlights the need for enhanced monitoring and supportive pharmacological and non-pharmacological interventions in this patient group.
Wekking D, Ende TVD, Bijlsma MF
… +3 more, Vidal-Itriago A, Nieuwdorp M, van Laarhoven HWM
Cancer Treat Rev
· 2025 Nov · PMID 41061376
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BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes...BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action. METHODS: A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen. RESULTS: 45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration. CONCLUSION: Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.
Canha-Borges A, Nunes B, Quintas ST
… +6 more, Paredes J, Meziani L, Mondini M, Oliveira MJ, Deutsch E, Castro F
Cancer Treat Rev
· 2025 Nov · PMID 41046712
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Breast cancer is the most common and deadliest cancer in women worldwide. Among the distinct subtypes, triple negative breast cancer (TNBC) stands out as the most aggressive one, showing high resistance to treatments, in...Breast cancer is the most common and deadliest cancer in women worldwide. Among the distinct subtypes, triple negative breast cancer (TNBC) stands out as the most aggressive one, showing high resistance to treatments, including chemotherapy, radiotherapy, and immunotherapy. Radiotherapy remains a standard treatment for TNBC, offering significant benefits in reducing local relapse. However, resistance to radiotherapy remains a major challenge, limiting its effectiveness and narrowing treatment options. Radioresistance in TNBC is driven by both tumor cell-intrinsic mechanisms and tumor immune microenvironment (TIME)-related processes. Intrinsically, TNBC cells employ strategies such as enhanced DNA damage repair mechanisms, tumor hypoxia adaptation, activation of survival pathways, and the contribution of cancer stem cells and extracellular vesicles. Extrinsically, the TIME can further fuel resistance by recruiting immunosuppressive cells (myeloid-derived suppressor cells, macrophages, neutrophils and regulatory T cells) and by releasing factors that impair the antitumor immune response mediated by T cells and natural killer cells. This review explores the dual contribution of cancer cell-specific mechanisms and TIME dynamics in TNBC radioresistance. We further discuss the paradoxical role of the immune system in radioresponse, highlighting emerging combination therapies, and address the challenges of translating these strategies into clinical applications. Ongoing clinical trials targeting radioresistance are also summarized, reflecting the latest efforts to enhance therapeutic outcomes for TNBC patients.
Charnley N, Fife K, Heng DYC
… +9 more, Larkin J, McGrane J, Négrier S, Vasudev N, Venugopal B, Chisholm A, Ogareva A, Prendergast Á, Albiges L
Cancer Treat Rev
· 2025 Nov · PMID 41014863
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INTRODUCTION: Brain metastases (BrM) are a negative prognostic factor in renal cell carcinoma (RCC) populations. Patients with RCC and BrM (RCC BrM + ) may receive systemic therapy and/or brain-targeted (local) treatment...INTRODUCTION: Brain metastases (BrM) are a negative prognostic factor in renal cell carcinoma (RCC) populations. Patients with RCC and BrM (RCC BrM + ) may receive systemic therapy and/or brain-targeted (local) treatment. We performed a systematic literature review to identify clinical trials and non-interventional studies reporting data on BrM impact on systemic treatment outcomes in patients with RCC. METHODS: We systematically searched the MEDLINE and Embase databases in January 2024 for publications reporting efficacy/effectiveness and/or safety/tolerability outcomes by BrM status from phase 2 and phase 3 clinical trials and non-interventional studies of systemic RCC therapies. Data were extracted from publications meeting predefined criteria (PROSPERO registration, CRD42023494896) and reported in accordance with PRISMA guidelines. RESULTS: Sixty-two publications (of 651 screened) were eligible (4 from prospective trials) and included 4,637 patients with RCC BrM + treated with systemic therapy. The most evaluated systemic therapies were sunitinib, nivolumab, ipilimumab + nivolumab, cabozantinib and sorafenib. Tolerability was generally consistent with known safety profiles in RCC trial populations. In the clinical trials, systemic treatment benefits for patients with RCC BrM + were equivocal. In non-interventional studies, survival was generally poorer in patients with RCC BrM + than reference groups (overall/BrM-). Survival and intracranial control benefits in patients with RCC BrM + were reported for some multimodal (systemic plus local) treatment strategies. There were no robust comparative data to guide systemic treatment selection. CONCLUSION: We identified a need for robust data on intracranial and extracranial responses to systemic therapy in patients with RCC BrM+, taking into account prior local therapy exposure.
van Putten J, Lankhorst LH, de Langen AJ
… +11 more, van der Wekken AJ, Roodhart J, Bolhuis K, Oosting SF, van Dongen M, Kok M, Geurts M, Koekkoek JAF, Cuppen E, Nienhuis HH, van der Graaf WTA
Cancer Treat Rev
· 2025 Nov · PMID 41014862
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Cancer in Adolescents and Young Adults (AYAs) represents a unique biological intersection, encompassing malignancies typical of both paediatric and older adults, as well as age-specific cancers. Yet, diagnostic and treat...Cancer in Adolescents and Young Adults (AYAs) represents a unique biological intersection, encompassing malignancies typical of both paediatric and older adults, as well as age-specific cancers. Yet, diagnostic and treatment approaches are not tailored to AYAs, potentially overlooking age-specific molecular characteristics. This review examines genomic differences between AYAs and paediatric and older patients, emphasising trends in cancer driver genes and identifying knowledge gaps that limit our understanding of AYA cancer biology. Across studies and cancer types, the AYA age range varies but is typically defined as 15-39 years. Remarkably, for nearly half of cancers diagnosed in AYAs, little or no literature exists on genomic differences or similarities compared to other age groups. Common cancers like testicular cancer and gynaecological cancer are underrepresented, while other typical AYA cancers such as thyroid cancer entirely lack comparative literature. In contrast, less common AYA cancers such as lung cancer and colorectal cancer are investigated extensively. Although genomic differences are reported across cancer types and in pan-cancer analyses, findings are often not generalisable to relevant subtypes or inconsistent, and insights gained are limited by the use of single-gene assays or small gene panels. This review reveals an imbalance between the global incidence of AYA cancers and the scope of comparative genomic studies, as well as a lack of broader comprehensive molecular profiling. Addressing these gaps through broader genomic research, particularly in underexplored cancers, is essential to determine whether AYA tumour biology is indeed distinctive, and how age-appropriate, genomics-driven precision oncology should be delivered.
Di Lauro V, Rizzo A, Tafuro M
… +8 more, Fina E, Martinelli C, Calderaio C, Di Rienzo R, Pirolo M, Fanizzi A, Massafra R, De Laurentiis M
Cancer Treat Rev
· 2025 Nov · PMID 40987130
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Antibody-drug conjugates have recently revolutionized the treatment scenario of several tumors, including breast cancer. Among these, Datopotamab deruxtecan (Dato-DXd) is an ADC composed of a humanized anti-TROP2 monoclo...Antibody-drug conjugates have recently revolutionized the treatment scenario of several tumors, including breast cancer. Among these, Datopotamab deruxtecan (Dato-DXd) is an ADC composed of a humanized anti-TROP2 monoclonal antibody linked to a potent exatecan-derived topoisomerase I inhibitor payload, deruxtecan (DXd), via a plasma-stable, selectively cleavable linker. Dato-DXd has shown notable efficacy and an overall tolerable safety profile, according to available evidence. Herein, we provide an overview of the pharmacological features, mechanisms of action, clinical efficacy, and adverse events of Dato-DXd in breast cancer. Furthermore, the current review proposes strategies to optimize patient management and accelerate the clinical development of Dato-DXd in this setting.
Alameda-Guijarro M, Rueda-Lara A, Martin-Montalvo G
… +7 more, Higuera O, Gutiérrez-Sainz L, Jiménez-Bou D, Villamayor J, de Castro J, Custodio A, Pérez-Wert P
Cancer Treat Rev
· 2025 Nov · PMID 40976218
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Socha J, Michalski W, Glynne-Jones R
… +2 more, Glimelius B, Bujko K
Cancer Treat Rev
· 2025 Nov · PMID 40946451
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INTRODUCTION: The RAPIDO and PRODIGE-23 randomised trials of neoadjuvant versus adjuvant chemotherapy for rectal cancer showed that disease-free survival (DFS) curves diverged early, suggesting that much of the benefit f...INTRODUCTION: The RAPIDO and PRODIGE-23 randomised trials of neoadjuvant versus adjuvant chemotherapy for rectal cancer showed that disease-free survival (DFS) curves diverged early, suggesting that much of the benefit from neoadjuvant chemotherapy occurred within six months. We aimed to determine whether the DFS benefit at six months in trials evaluating neoadjuvant chemotherapy can predict the benefit at 36 months, and to compare the timing of DFS benefit in trials of neoadjuvant versus in those of adjuvant chemotherapy. MATERIAL AND METHODS: A systematic review identified ten randomised trials comparing neoadjuvant with adjuvant chemotherapy and 37 randomised trials of adjuvant chemotherapy eligible for meta-analysis in rectal or colon cancer. Absolute differences in DFS between experimental and control groups at six and 36 months were extracted from Kaplan-Meier curves. The increment in the DFS benefit between the sixth and 36th months was calculated. RESULTS: In neoadjuvant chemotherapy trials, DFS benefit at six months (3.7 %, 95 % confidence interval [CI]: 1.9 to 5.4) did not differ significantly from that at 36 months (4.1 %, 95 % CI: 2.0 to 6.3), and the pooled absolute increment in DFS benefit between the sixth and 36th months was only 0.8 % (95 % CI: -1.6 to 3.2). The DFS benefit emerged earlier in neoadjuvant than in adjuvant chemotherapy trials. CONCLUSION: In randomised trials comparing neoadjuvant with adjuvant chemotherapy, most of the DFS benefit from neoadjuvant chemotherapy manifests itself within the first six months. Therefore, assessing DFS at six months may potentially serve as an early indicator of long-term efficacy.
Musacchio L, Lorusso D, Sabetta G
… +6 more, Giustozzi A, Giudice E, Cannizzaro MC, Perri MT, Fagotti A, Salutari V
Cancer Treat Rev
· 2025 Nov · PMID 40934817
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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 lim...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.
Cancer Treat Rev
· 2025 Nov · PMID 40907366
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AIM: 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, a...AIM: 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.
van der Graaf WTA, Heiss NS, Hynes CL
… +11 more, Keller SP, Weinman A, Blay JY, Franco P, Giles RH, Lacombe D, Schlatter P, Thomas DM, van Waalwijk van Doorn-Khosrovani SB, Williamson M, Plummer R
Cancer Treat Rev
· 2025 Nov · PMID 40902364
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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 oncol...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.
Galle PR, Reck M, Pinato DJ
… +9 more, Garcia-Campelo R, Finn RS, Cousin S, Zanghi J, Bernaards CA, Swanson SJ, Morris S, Song Y, Peters S
Cancer Treat Rev
· 2025 Nov · PMID 40886486
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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 phar...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.
Lavigne D, Tao Y, Péchoux CL
… +7 more, Botticella A, Nguyen F, Sun R, Blanchard P, Remon J, Deutsch E, Levy A
Cancer Treat Rev
· 2025 Nov · PMID 40886485
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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 syne...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.