Search Results (51)

Only about 5% of colorectal cancers are hereditary, which is due to the low carrier rate of pathogenic gene mutations. The typical pattern of these cases is intergenerational aggregation within families and early onset. But public awareness of early diagnosis and intervention of HCRC is insufficient, resulting in most patients being diagnosed only after developing cancer, thereby missing the optimal window for treatment. This article reviews the latest developments in precision screening, treatment, evaluation and prevention strategies for HCRC, including innovative uses of artificial intelligence (AI) in molecular diagnostics, imaging technology advances, and potential application prospects. Regarding precision screening, tests of genomics, transcriptomics, microbiome, etc., combined with personalised risk stratification, can, respectively, effectively detect pathogenic mutations and “cancer-promoting” intestinal environments in the preclinical stage. AI combined with endoscopic and imaging tools has improved the accuracy of polyp detection and tumor profiling. Liquid biopsy and molecular marker detection provide new non-invasive monitoring solutions. In precision treatment, beyond traditional approaches like surgery and chemotherapy, immunotherapy with checkpoint inhibitors may be considered for HCRC patients with mismatch repair deficiency (dMMR). For patients harboring somatic mutations such as KRAS or BRAF V600E, targeted therapy can be guided by these specific mutations. Regarding precision assessment, AI incorporates microsatellite instability (MSI) detection and imaging diagnostic techniques, crucial for integrating genetic, environmental, and lifestyle data in follow-up. This helps assess the risk of recurrence and adjust the long-term medication regimens, as well as provide effective nutritional support and psychological counselling. In summary, the rapid development of precision medicine is driving the clinical management of HCRC into the era of tailored care, aiming to optimise patient outcomes. Full article

Treatment-induced ovarian function loss is a significant concern for many young patients with breast cancer. Accurately predicting this risk is crucial for counselling young patients and informing their fertility-related decision-making. However, current risk prediction models for treatment-related ovarian function loss have limitations. To provide a broader representation of patient cohorts and improve feature selection, we combined retrospective data from six datasets within the FoRECAsT (Infertility after Cancer Predictor) databank, including 2679 pre-menopausal women diagnosed with breast cancer. This combined dataset presented notable missingness, prompting us to employ cross imputation using the k-nearest neighbours (KNN) machine learning (ML) algorithm. Employing Lasso regression, we developed an ML model to forecast the risk of treatment-related amenorrhea as a surrogate marker of ovarian function loss at 12 months after starting chemotherapy. Our model identified 20 variables significantly associated with risk of developing amenorrhea. Internal validation resulted in an area under the receiver operating characteristic curve (AUC) of 0.820 (95% CI: 0.817–0.823), while external validation with another dataset demonstrated an AUC of 0.743 (95% CI: 0.666–0.818). A cutoff of 0.20 was chosen to achieve higher sensitivity in validation, as false negatives—patients incorrectly classified as likely to regain menses—could miss timely opportunities for fertility preservation if desired. At this threshold, internal validation yielded sensitivity and precision rates of 91.3% and 61.7%, respectively, while external validation showed 92.9% and 60.0%. Leveraging ML methodologies, we not only devised a model for personalised risk prediction of amenorrhea, demonstrating substantial enhancements over existing models but also showcased a robust framework for maximally harnessing available data sources. Full article

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour that can metastasise early, may show resistance to systemic treatment, and has a poor prognosis. The use of tobacco products is closely related to the duration of their use, and approximately 95% of those diagnosed have a history of smoking. No satisfactory progress has been made in the prognosis with current treatment methods up to the present day. The treatment approach has traditionally involved long-term chemotherapy (CT) and radiotherapy (RT), and recent literature has focused on immunotherapy and genetic advancements. Surgery can only be performed in cases detected at an early stage. Although both chemotherapy and radiotherapy are indispensable options for most patients, their impact on prognosis and survival is limited. Although promising developments are expected in immunotherapy, its impact on survival is still very limited, lasting only about 2 months. In patients undergoing surgical resection as part of their treatment, overall survival (OS) ranges from 34 to 69 months. OS for 1 year is 84.8–93.8%, for 3 years is 60–71.2%, and for 5 years is 51.1–63.8%. The five-year survival rates are reported as follows: stage I 31–63.8%, stage II 25–65.5%, stage III 15–27.8%, and stage IV 0%. In this study, the prognosis and factors affecting prognosis in SCLC were investigated in light of current literature from a surgical perspective, and predictions were attempted to be made to lay the groundwork for personalised treatment approaches. Compared to non-small-cell lung cancer, the number of studies is quite limited. Most of the surgical case series were conducted in the past, retrospectively, and involved a small number of patients. Advances in immunotherapy are promising. In the early stages, resection and subsequent chemotherapy may be the main treatment. Full article

Background/Objectives: To evaluate the clinicopathological features, treatment, and survival outcomes and to identify independent prognosticators for recurrence and mortality in patients with endometrioid ovarian cancer. Methods: The medical records of patients diagnosed with endometrioid ovarian carcinoma between January 2010 and December 2022 were reviewed retrospectively. Demographic and disease-related data were evaluated. Kaplan–Meier survival analysis using log rank test and Cox regression was performed. Results: Seventy-six patients were included in the study. The median age at diagnosis was 54 years (range 31–86). A total of 85.5% of the patients were diagnosed with early-stage disease and 88.1% of the tumours represented low-grade carcinomas. Synchronous endometrioid endometrial cancer was confirmed in 19.7% of the cases. All patients underwent surgical management and 65.8% received adjuvant chemotherapy. Median follow-up time was 67.5 months. The 5-year disease-free survival and overall survival were 92.1% and 93.4%, respectively. The risk of cancer-related death was higher in advanced stages (HR = 13.86; 95% CI 2.16–57.17; p < 0.001) and in the presence of residual disease (HR = 15.18; 95% CI 2.36–87.17; p < 0.002). Residual disease and advanced stages were also identified as independent risk factors for disease relapse with HR = 16.04 (95% CI 2.61–93.7; p < 0.002) and HR = 11.73 (95% CI 1.92–41.6; p < 0.001), respectively. Conclusions: Endometrioid ovarian carcinoma usually affects younger patients with the majority of the cases representing low-grade carcinomas diagnosed at early stages. Residual disease and advanced stages are independently associated with inferior survival outcomes. There was no significance of lymph node dissection and adjuvant chemotherapy in the overall and recurrence-free survival rates. Further research focusing on molecular profiling should aim to define the prevalence and the prognostic value of major molecular alterations and develop precise stratification models to plan personalised treatment for optimal care. Full article

We propose a life-expectancy pay-off function (LEP) for determining optimal cancer treatment within a control theory framework. The LEP averages life expectancy over all future outcomes, outcomes that are determined by key events during therapy such as tumour elimination (cure) and patient death (including treatment related mortality). We analyse this optimisation problem for tumours treated with chemotherapy using tumour growth models based on ordinary differential equations. To incorporate tumour elimination we draw on branching processes to compute the probability distribution of tumour population extinction. To demonstrate the approach, we apply the LEP framework to simplified one-compartment models of tumour growth that include three possible outcomes: cure, relapse, or death during treatment. Using Pontryagin’s maximum principle (PMP) we show that the best treatment strategies fall into three categories: (i) continuous treatment at the maximum tolerated dose (MTD), (ii) no treatment, or (iii) treat-and-stop therapy, where the drug is given at the MTD and then halted before the treatment (time) horizon. Optimal treatment strategies are independent of the time horizon unless the time horizon is too short to accommodate the most effective (treat-and-stop) therapy. For sufficiently long horizons, the optimal solution is either no treatment (when treatment yields no benefit) or treat-and-stop. Patients, thus, split into an untreatable class and a treatable class, with patient demographics, tumour size, tumour response, and drug toxicity determining whether a patient benefits from treatment. The LEP is in principle parametrisable from data, requiring estimation of the rates of each event and the associated life expectancy under that event. This makes the approach suitable for personalising cancer therapy based on tumour characteristics and patient-specific risk profiles. Full article

Objective: This multicentre study investigates unmet supportive care needs (SCNs) among cancer survivors in Spain and analyses sociodemographic and cancer-related risk factors. Methods: A cross-sectional design was used with 1862 cancer survivors aged 18–92 years who had completed primary treatment with curative intent and were disease-free. Participants responded to the Cancer Survivors’ Unmet Needs (CaSUN) questionnaire. Descriptive and multivariate analyses explored SCNs in the total sample and subgroups, as well as differences according to sociodemographic and cancer-related variables. Results: At least 20% of participants reported 18 needs out of a total of 35 identified by the CaSUN questionnaire. One-third to half reported needs in the comprehensive care and information domain. Risk factors for reporting more needs included younger age; female sex; not having a partner; being on sick leave or unemployed; having a diagnosis of haematological, breast or gynaecological cancer; receiving systemic treatment (chemotherapy and/or hormone therapy); and being at an earlier stage of survival. Conclusions: The study highlights significant unmet care needs among cancer survivors in Spain and the urgency of improving management of the physical and psychosocial effects of cancer and its treatment. Special attention should be given to those at greatest risk through personalised and comprehensive care strategies integrated into survivorship programs. Full article

Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments—including chemotherapy, radiotherapy, immunotherapy, and surgery—are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In contrast, peptide-based therapeutics offer a paradigm shift, combining high tumour-targeting precision with minimal off-target effects. Their low immunogenicity, multi-pathway modulation capabilities, and adaptability for diagnostics and therapy make them ideal candidates for advancing oncology care. Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., ¹⁸F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and ¹⁷⁷Lu-FAP-2286 integrating imaging and radiotherapy). Despite their promise, peptides face challenges like metabolic instability and short half-lives. Recent advances in structural engineering (e.g., cyclization and D-amino acid incorporation) and delivery systems (e.g., nanoparticles and PEGylation) have significantly enhanced their clinical potential. This review highlights peptide-based agents in development, showcasing their ability to improve early cancer detection, reduce metastasis, and enhance therapeutic efficacy with fewer adverse effects. Examples like CLP002 underscore their role in personalised medicine. By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology. Full article

Background/objectives: Pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a solid indicator of favourable prognosis, potentially also being useful for more conservative patient management. We aim to explore the potential of [¹⁸F]FDG PET/CT as a non-invasive method to predict response to NAC. Methods: In this prospective, observational cohort study, we enrolled BC patient candidates for NAC who underwent baseline and preoperative [¹⁸F]FDG PET/CT. NAC response was determined using final histopathology. PET images were assessed qualitatively and semi-quantitatively, and the findings correlated with NAC response. Results: In total, 133 BC patients were included. The visual analysis of preoperative PET/CT detected residual disease (RD) with high specificity (>93%) and moderate sensitivity, based on pCR/RD classification and RCB index. Semiquantitative measures (SUVmax, TBR) were significantly higher in non-responders across the classification methods (p < 0.001 for all). Conclusions: These findings highlight the potential of preoperative [¹⁸F]FDG PET/CT as a complementary tool for identifying excellent responders to NAC across BC subtypes or response criteria. This could inform personalised treatment and potentially allow for surgery to be omitted in selected patients. Full article

The emergence of nanotechnology in medicine, particularly using iron oxide nanoparticles (IONPs), may impact cancer treatment strategies. IONPs exhibit unique properties, such as superparamagnetism, biocompatibility, and ease of surface modification, making them ideal candidates for imaging, and therapeutic interventions. Their application in targeted drug delivery, especially with traditional chemotherapeutic agents like cisplatin, has shown potential in overcoming limitations such as low bioavailability and systemic toxicity of chemotherapies. Moreover, IONPs, by releasing iron ions, can induce ferroptosis, a form of iron-dependent cell death, which offers a promising pathway to reverse radio- and chemoresistance in cancer therapy. In particular, IONPs demonstrate significant potential as radiosensitisers, enhancing the effects of radiotherapy by promoting reactive oxygen species (ROS) generation, lipid peroxidation, and modulating the tumour microenvironment to stimulate antitumour immune responses. This review explores the multifunctional roles of IONPs in radiosensitisation through ferroptosis induction, highlighting their promise in advancing treatment for head and neck cancers. Additional research is crucial to fully addressing their potential in clinical settings, offering a novel approach to personalised cancer treatment. Full article

Introduction: Metastatic uveal melanoma (mUM) is a rare and aggressive malignancy characterised by poor responsiveness to conventional chemotherapies, posing significant treatment challenges. Immune checkpoint inhibitor (ICI) therapies, including monotherapies with Ipilimumab, pembrolizumab, and nivolumab, as well as dual ICI therapy, have emerged as potential treatments. Whilst current research favours dual therapy over single therapy, comprehensive individualised comparisons of the efficacy and safety profiles of these therapies remain limited. This meta-analysis aims to evaluate the clinical outcomes of single ICI therapies individually and compare against combination therapy to guide optimal treatment strategies for mUM. Methods: A systematic literature review was conducted to identify studies reporting objective response rates (ORR), disease control rates (DCR), median progression-free survival (MPFS), and adverse event rates (AER) for Ipilimumab, pembrolizumab, nivolumab, and dual ICI therapy. Data were aggregated using forest plots and analysed to compare the efficacy and safety of each regimen. Results: Dual ICI therapy demonstrated the highest ORR and DCR but showed no statistically significant advantage over monotherapies. Dual therapy also had a lower MPFS than both pembrolizumab and nivolumab monotherapies. Furthermore, dual therapy was associated with a much greater AER compared to any single therapy, including pembrolizumab and nivolumab. Conclusions: While dual ICI therapy offers improved ORR and DCR on aggregate analyses, monotherapies like pembrolizumab provide comparable outcomes in specific metrics, particularly MPFS, with significantly reduced toxicity. These findings underscore the need for personalised ICI regimens tailored to individual patient profiles rather than defaulting to dual therapy. Further research is essential to refine treatment guidelines and optimise outcomes for mUM patients. Full article

Acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) remain significant challenges in haematological oncology. This review examines the pathophysiology, classification, and risk stratification of these aggressive malignancies, emphasising their impact on treatment strategies and prognosis. We discuss current standard-of-care treatments, including chemotherapy regimens and targeted therapies, while addressing the associated adverse effects and hypersensitivity reactions. Delving into the metabolic characteristics and vulnerabilities of leukaemia cells, the review highlights the key differences between lymphoid and myeloid leukaemia and how metabolic insights can be utilised for therapeutic purposes, with special focus on asparaginase therapy and its potential for improvement in both ALL and AML treatment. The review conveys the importance of personalised medicine approaches based on individual metabolic profiles and the challenges posed by metabolic heterogeneity and plasticity in leukaemia cells. Combining molecular and metabolic profiling can enhance and refine treatment strategies for acute leukaemia, potentially improving patient outcomes and quality of life. However, integrating these into routine clinical practice requires overcoming various practical, technical, and logistical issues. Full article

Background/Objectives: Camptothecin (CPT) and its derivatives, irinotecan and topotecan, are integral components of cancer chemotherapy, often used in combination therapies. This meta-analysis evaluates the efficacy of CPT-based combination treatments in cancer patients. Methods: We systematically searched the literature database using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for articles published between 2000 and 2022. Published studies were retrieved through an electronic search on the Web of Science, PubMed, and Google Scholar databases. A total of 138 studies were downloaded and examined, and 71 eligible studies were selected for meta-analysis after excluding studies that did not meet the inclusion criteria. Results: Ultimately, a total of 71 studies were included in the analysis, comprising non-small cell lung cancer (NSCLC), colorectal cancer (COLRC), oesophageal/gastric cancer (O/GC), and small cell lung cancer (SCLC). For NSCLC, the objective response rate (RR) was 31.8% (95% CI: 27.3–37.1%, p = 0.025), with irinotecan plus cisplatin showing significantly higher efficacy compared to other irinotecan-based combinations. In COLRC, irinotecan and 5-fluorouracil/leucovorin plus bevacizumab demonstrated superior efficacy with a RR of 44% (95% CI: 34–58, p < 0.001) and minimal haematological toxicity. In O/GC, irinotecan-based combinations showed an average RR of 43% (95% CI: 27–70, p < 0.001) and average overall survival (OS) and progression-free survival (PFS) rates of 10.2 and 5.5 months, respectively. For SCLC, irinotecan-based combinations had a higher control response than topotecan-based ones, while the latter exhibited higher rates of stable and progressive disease. The overall RR for SCLC was 45% (95% CI: 34.3–60.2, p < 0.001). Conclusions: The existing evidence underscored the potential of CPT-based combination therapy in various cancers. Among the various combinations discussed in this analysis, irinotecan plus cisplatin demonstrated the highest objective RR in 12 trials focused on NSCLC. This study provides valuable insights into potential treatment strategies for various types of cancer, emphasising the importance of personalised and tailored approaches to maximise efficacy and minimise adverse effects. Full article

Alopecia is a common adverse effect of neoadjuvant or adjuvant chemotherapy in patients with early breast cancer. While hair typically regrows over time, more than 40% of patients continue to suffer from permanent partial alopecia, significantly affecting body image, psychological well-being, and quality of life. This concern is a recognized reason why some breast cancer patients decline life-saving chemotherapy. It is critical for healthcare professionals to consider the impact of this distressing side effect and adopt supportive measures to mitigate it. Among the various strategies investigated to reduce chemotherapy-induced alopecia (CIA), scalp cooling has emerged as the most effective. This article reviews the pathophysiology of CIA and examines the efficacy of different scalp cooling methods. Scalp cooling has been shown to reduce the incidence of CIA, defined as less than 50% hair loss, by 50% in patients receiving chemotherapy. It is associated with high patient satisfaction and does not significantly increase the risk of scalp metastasis or compromise overall survival. Promising new scalp cooling technologies, such as cryogenic nitrogen oxide cryotherapy, offer the potential to achieve and maintain lower scalp temperatures, potentially enhancing therapeutic effects. Further investigation into these approaches is warranted. Research on CIA is hindered by significant heterogeneity and the lack of standardised methods for assessing hair loss. To advance the field, further interdisciplinary research is crucial to develop preclinical models of CIA, establish a uniform, internationally accepted and standardised classification system, and establish an objective, personalised prognosis monitoring system. Full article

Triple-negative breast cancer (TNBC) presents a significant medical challenge due to its highly invasive nature, high rate of metastasis, and lack of drug-targetable receptors, which together lead to poor prognosis and limited treatment options. The traditional treatment guidelines for early TNBC are based on a multimodal approach integrating chemotherapy, surgery, and radiation and are associated with low overall survival and high relapse rates. Therefore, the approach to treating early TNBC has shifted towards neoadjuvant treatment (NAC), given to the patient before surgery and which aims to reduce tumour size, reduce the risk of recurrence, and improve the pathological complete response (pCR) rate. However, recent studies have shown that NAC is associated with only 30% of patients achieving pCR. Thus, novel predictive biomarkers are essential if treatment decisions are to be optimised and chemotherapy toxicities minimised. Given the heterogeneity of TNBC, mass spectrometry-based proteomics technologies offer valuable tools for the discovery of targetable biomarkers for prognosis and prediction of toxicity. These biomarkers can serve as critical targets for therapeutic intervention. This review aims to provide a comprehensive overview of TNBC diagnosis and treatment, highlighting the need for a new approach. Specifically, it highlights how mass spectrometry-based can address key unmet clinical needs by identifying novel protein biomarkers to distinguish and early prognostication between TNBC patient groups who are being treated with NAC. By integrating proteomic insights, we anticipate enhanced treatment personalisation, improved clinical outcomes, and ultimately, increased survival rates for TNBC patients. Full article

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer in individuals under 50 years of age, has shown an alarming increase in incidence worldwide. We report a case of a twenty-four-year-old female with a strong family history of colorectal cancer (CRC) but without an identified underlying genetic predisposition syndrome. Two years after primary surgery and adjuvant chemotherapy, the patient developed new liver lesions. Extensive diagnostic imaging was conducted to investigate suspected liver metastases, ultimately leading to a diagnosis of focal nodular hyperplasia. The young age of the patient has prompted comprehensive genomic and transcriptomic profiling in order to identify potential oncogenic drivers and inform further clinical management of the patient. Besides a number of oncogenic mutations identified in the patient’s tumour sample, including KRAS G12D, TP53 R248W and TTN L28470V, we have also identified a homozygous deletion of 24.5 MB on chromosome 8. A multivariate Cox regression analysis of this patient’s mutation profile conferred a favourable prognosis when compared with the TCGA COADREAD database. Notably, the identified deletion on chromosome 8 includes the WRN gene, which could contribute to the patient’s overall positive response to chemotherapy. The complex clinical presentation, including the need for emergency surgery, early age at diagnosis, strong family history, and unexpected findings on surveillance imaging, necessitated a multidisciplinary approach involving medical, radiation, and surgical oncologists, along with psychological support and reproductive medicine specialists. Molecular profiling of the tumour strongly indicates that patients with complex mutational profile and rare genomic rearrangements require a prolonged surveillance and personalised informed interventions. Full article