Search Results (1,647)

Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative ultrasound (QUS) can detect early microstructural changes in tumours and may enable timely identification of non-responders during NAC, allowing for earlier treatment intensification. In our previous prospective observational study, 100 breast cancer patients underwent QUS imaging before and four times during NAC. Machine learning algorithms based on QUS texture features acquired in the first week of treatment were developed and achieved 78% accuracy in predicting treatment response. In the current study, we aimed to validate these algorithms in an independent prospective cohort to assess reproducibility and confirm their clinical utility. Methods: We included breast cancer patients eligible for NAC per standard of care, with tumours larger than 1.5 cm. QUS imaging was acquired at baseline and during the first week of treatment. Tumour response was defined as a ≥30% reduction in target lesion size on the resection specimen compared to baseline imaging. Results: A total of 51 patients treated between 2018 and 2021 were included (median age 49 years; median tumour size 3.6 cm). Most were estrogen receptor–positive (65%) or HER2-positive (33%), and the majority received dose-dense AC-T (n = 34, 67%) or FEC-D (n = 15, 29%) chemotherapy, with or without trastuzumab. The support vector machine algorithm achieved an area under the curve of 0.71, with 86% accuracy, 91% specificity, 50% sensitivity, 93% negative predictive value, and 43% positive predictive value for predicting treatment response. Misclassifications were primarily associated with poorly defined tumours and difficulties in accurately identifying the region of interest. Conclusions: Our findings validate QUS-based machine learning models for early prediction of chemotherapy response and support their potential as non-invasive tools for treatment personalization and clinical trial development focused on early treatment intensification. Full article

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article

Prostate cancer is among the most prevalent malignancies in men worldwide, underscoring the need for early and accurate diagnostic tools. This study presents a proof-of-concept and pilot clinical validation of a novel bioelectric impedance-based biosensor for the detection of prostate-specific antigen (PSA) in human serum. The system integrates Molecular Identification through Membrane Engineering (MIME) with the xCELLigence real-time cell analysis platform, employing Vero cells electroinserted with anti-PSA antibodies. Optimization experiments identified 15,000 cells/well as the optimal configuration for impedance response. The biosensor exhibited specific, concentration-dependent changes in impedance upon exposure to PSA standard solutions and demonstrated significant differentiation between PSA-positive and PSA-negative human serum samples relative to the clinical threshold of 4 ng/mL. The biosensor offered rapid results within one minute, unlike standard immunoradiometric assay (IRMA), while showing strong diagnostic agreement. The system’s specificity, sensitivity, and reproducibility support its potential for integration into point-of-care screening workflows. This bioelectric assay represents one of the fastest PSA detection approaches reported to date and offers a promising solution for reducing overdiagnosis while improving clinical decision-making and patient outcomes. Full article

Background: Chemotherapy-induced peripheral neuropathy is a common and debilitating side effect of cancer treatment. While exercise has shown promise in alleviating this burden, it remains underutilised in clinical practice due to the lack of accessible, clinician-friendly guidance. Aim: This review aimed to synthesise current evidence on exercise interventions for managing chemotherapy-induced peripheral neuropathy and provide practical insights to support clinicians in integrating these approaches into patient care. Methods: A search was conducted across MEDLINE, CINAHL, and SPORTDiscus using keywords related to exercise and CIPN. Studies were included if they involved adults receiving neurotoxic chemotherapy and exercise-based interventions. Two authors independently screened studies and resolved conflicts with a third author. Study quality was assessed using the JBI Critical Appraisal Tools, and only studies meeting a minimum quality standard were included. A balanced sampling approach was employed. Data on study design, participant characteristics, interventions, and outcomes were extracted. Results: Eleven studies were included, covering various exercise modalities: multimodal (n = 5), yoga (n = 2), aerobic (n = 1), resistance (n = 1), balance (n = 1), and sensorimotor (n = 1). Exercise interventions, particularly multimodal exercise, significantly improved symptom severity, functionality, and quality of life (p < 0.05). The studies had high methodological quality, with randomised controlled trials scoring between 9/13 and 11/13, and quasi-experimental studies scoring 8/9 on JBI tools. Conclusions: This review highlights the significant benefits of exercise, especially multimodal exercise, for managing CIPN and provides guidance for integrating these strategies into clinical practice. Future research is needed to refine exercise prescriptions and develop standardised guidelines. Full article

Background: The advances in cancer diagnosis and treatment have significantly improved survival rates in pediatric patients, with five-year survival now exceeding 80% in many high-income countries. However, these life-saving therapies often carry long-term consequences, including impaired fertility. The reproductive health of childhood cancer survivors has emerged as a key issue in survivorship care. Objective: This narrative review aims to examine the gonadotoxic effects of cancer treatments on pediatric patients, evaluate fertility preservation strategies in both males and females, and provide guidance on the long-term monitoring of reproductive function post treatment. Methods: A comprehensive literature review was conducted using PubMed, including randomized trials, cohort studies, and clinical guidelines published up to March 2024. The keywords focused on pediatric oncology, fertility, and reproductive endocrinology. Studies were selected based on relevance to treatment-related gonadotoxicity, fertility preservation options, and follow-up care. Results: Radiotherapy and alkylating agents pose the highest risk to fertility. Postpubertal patients have access to standardized preservation techniques, while prepubertal options remain experimental. Long-term effects include premature ovarian insufficiency, azoospermia, hypogonadism, and uterine dysfunction. The psychosocial impacts, especially in female survivors, are profound and often overlooked. Conclusions: Fertility preservation should be discussed at diagnosis and integrated into treatment planning in pediatric patients with cancer. While options for postpubertal patients are established, more research is needed to validate safe and effective strategies for younger populations. A multidisciplinary approach and long-term surveillance are essential for safeguarding future reproductive potential in childhood cancer survivors. Full article

Background/Objectives: Since breast cancer (BC) survival rates have increased to 91% at 5 years and 80% at 15 years postdiagnosis, there is a growing awareness of the importance of addressing the long-term well-being of patients. Consequently, integrative oncology, which combines standard therapies with complementary approaches (nutrition, mind–body practices, and lifestyle modifications), has emerged as a patient-centred model aimed at improving symptom management, treatment adherence, and overall quality of life (QoL). This study aims to demonstrate how integrative therapies can benefit body composition, phase angle, and fluid and electrolyte balance through bioelectrical impedance analysis (BIA). Methods: This study considers a patient who underwent BC surgery and was enrolled in the AMICO clinic for anamnesis, as well as their oncological pathology data, assessment of QoL, and BIA. The breast surgeon specialising in integrative oncology therapies prescribed the patient curcumin and polydatin, moderate physical activity, a balanced diet, and Qigong sessions. The patient underwent monitoring through haematochemical analysis, BIA, and a QoL questionnaire, with follow-up every four months. Results: Between 4 and 12 months, fat mass (FM) and body mass index (BMI) markedly decreased, whereas fat-free mass (FFM), total body water (TBW), and skeletal muscle mass (SMM) increased progressively. Moreover, the improvements in the Na/K ratio and phase angle (PhA) suggest a shift toward better electrolyte and fluid balance and enhanced cellular integrity and membrane function. Equally outstanding were her psychological benefits in terms of mood, sleep, anxiety, and melancholy. Conclusions: Patient progress in body composition, metabolic function, pain management, and psychological status measured during the 12-month follow-up demonstrates the potential benefits of an integrative approach to supportive cancer care. Full article

Background: Consolidation therapy with durvalumab after definitive chemoradiotherapy (CRT) has become the standard care for patients with stage III non-small-cell lung cancer (NSCLC) following the PACIFIC trial. However, real-world data evaluating outcomes under routine clinical conditions remain limited, particularly in European cohorts. Methods: In this retrospective single-center study, we analyzed clinical data from 72 patients with stage III NSCLC treated with definitive CRT between 2017 and 2022. The patients were stratified by receipt of durvalumab consolidation. Univariable and multivariable Cox regression models were used to assess overall survival (OS) and progression-free survival (PFS). Stepwise variable selection based on the Akaike Information Criterion (AIC) was used to construct an optimized multivariable model. A sensitivity analysis with adjustment for treatment period (2017–2018 vs. 2019–2022) was conducted to account for the introduction of durvalumab into routine clinical practice. Results: Among 72 patients, 35 received durvalumab and 37 did not. The median OS was 2.08 years; the 3- and 5-year OS rates were 38.6% and 30.3%, respectively. Multivariable regression revealed significantly improved OS associated with Karnofsky performance status (KPS) > 80% (HR 0.29, p = 0.003), Charlson Comorbidity Index (CCI) ≤ 2 (HR 0.39, p = 0.009), and durvalumab treatment (HR 3.99, p = 0.008). PD-L1 expression ≥ 1% showed a trend toward improved OS (HR 3.72, p = 0.063). The median progression-free survival (PFS) for the total cohort was 1.17 years. The estimated 3- and 5-year PFS rates were 31.1% and 26.3%, respectively. Patients treated with durvalumab had a longer median PFS (20.5 months) compared to those without durvalumab (12.0 months). In the multivariable analysis, KPS > 80% (HR 0.29, p < 0.001), CCI ≤ 2 (HR 0.53, p = 0.048), and durvalumab treatment (HR 2.81, p = 0.023) were significantly associated with improved PFS. A sensitivity analysis adjusting for treatment period—reflecting the introduction of durvalumab into routine clinical practice from 2019—confirmed the robustness of these findings. Conclusions: Our findings support the clinical benefit of durvalumab consolidation following CRT in a real-world population, especially in patients with good performance status and low comorbidity burden. These results confirm and extend the PACIFIC trial findings into routine clinical practice, highlighting the prognostic value of functional status and comorbidity alongside PD-L1 expression. Full article

Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer. Full article

Anal cancer is a rare malignancy with rising incidence. Definitive treatment with radiation and concurrent chemotherapy represent the standard of care for patients with non-metastatic disease. Advances in radiation delivery through the use of intensity-modulated radiotherapy have significantly reduced the toxic effects of treatment. Adaptive radiotherapy (ART) has emerged as a strategy to further enhance treatment precision and individualize therapy in response to patient-specific changes during the course of chemoradiotherapy. The rationale for ART in anal cancer stems from the recognition that significant anatomic and tumor changes can occur throughout the 5–6-week treatment course, including tumor shrinkage, weight loss, and variable rectal/bladder filling. This review discusses the role of ART in contemporary anal cancer management. We overview the principles of ART, delineate the technical workflows (including both computed tomography (CT) and MR-guided approaches), and examine how adaptive techniques are applied in treatment planning and delivery. We also review the clinical evidence to date, including dosimetric studies and emerging clinical trial data on ART in anal cancer, particularly its impact on outcomes and toxicity. Full article

The concept of “more is better” has long dominated cancer treatment, emphasizing aggressive therapies despite their toxicity. However, the rise of personalized medicine has fostered treatment de-escalation strategies aimed at minimizing toxicity, improving quality of life, and reducing costs. This position paper highlights key applications of de-escalation in medical oncology, with a primary focus on breast cancer and notable examples in colorectal, head and neck, ovarian, lung, and prostate cancers. Various approaches, including dose reduction, treatment duration shortening, and regimen optimization, have demonstrated efficacy without compromising clinical outcomes. Advances in molecular diagnostics, such as Oncotype Dx in breast cancer and circulating tumor DNA (ctDNA) analysis in colorectal cancer, have facilitated patient selection for de-escalation. While these strategies present promising results, challenges remain, particularly in balancing treatment intensity with oncologic control. The review underscores the need for further prospective trials to refine de-escalation approaches and ensure their safe integration into standard oncologic care. Full article

Background and Objectives: The COVID-19 pandemic disrupted cancer care, prompting adaptations to reduce patient exposure while preserving treatment efficacy. This retrospective observational study compared a weekly cisplatin and 5-fluorouracil (5-FU) regimen to the standard monthly regimen for neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Materials and Methods: This single-center retrospective study included 91 patients, divided into two cohorts: weekly chemotherapy (n = 30) and standard chemotherapy (n = 61). Treatment assignment was based on hospital policy changes during the pandemic, with weekly outpatient chemotherapy implemented after November 2022 to conserve inpatient resources. All patients received radiotherapy at 50 Gy in 25 fractions. The weekly regimen consisted of cisplatin 20 mg/m² and 5-FU 800 mg/m², administered over 1–2 h weekly, while the standard regimen administered the same doses over four consecutive days on weeks 1 and 5. Primary endpoints were pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: The response rates were similar between groups (weekly: 86.7% vs. standard: 90.2%; p = 0.724). The weekly regimen group showed a higher pCR (40.0% vs. 26.2%; p = 0.181) and significantly lower recurrence (26.7% vs. 52.5%; p = 0.020). Mortality was also reduced in the weekly group (6.7% vs. 34.4%; p = 0.004), though the follow-up duration was shorter (10.6 vs. 22.8 months; p < 0.001). Conclusions: In this retrospective observational study, weekly cisplatin and 5-FU demonstrated comparable efficacy to the standard regimen, with potential advantages in reducing recurrence and mortality. This modified approach may be a viable alternative for maintaining oncologic outcomes while minimizing the burden on healthcare systems during pandemic conditions, although prospective validation is needed. Full article

Background/Objectives: Next-generation-sequencing-based genomic profiling (GP) of advanced breast cancer (BC) has been increasingly integrated into clinical practice. The growing number of biomarker-based therapies in BC increasingly complicates treatment decisions. As a result, molecular tumor boards (MTBs) have become pivotal. However, real-world data on the utility of MTBs in advanced BC remain limited. This study evaluates the translation of molecular findings in BC patients into MTB recommendations and examines their implementation and outcomes in real-world clinical practice. Methods: This retrospective, single-center study included 103 BC patients who received GP between January 2018 and December 2023. Patients were discussed at the weekly multidisciplinary MTB of our institution. Data retrieved included patient characteristics, GP results, and MTB recommendations, which were consecutively matched with treatment outcomes, namely the proportion of patients receiving an MTB treatment recommendation, proportion of patients receiving molecularly matched targeted therapy (MTT), and best treatment response. Results: The MTB reviewed 94 patients and provided 155 recommendations to 68 patients (72.3%), including systemic anti-cancer treatment (n = 123), clinical study participation (n = 4), genetic counseling (n = 12), and additional molecular testing (n = 16) recommendations. Treatment recommendations were provided to 63 patients (67%), of whom 38 (60.3%) received MTT. Of the 35 patients eligible for response assessment, 16 (45.7%) demonstrated clinical benefit: three achieved a complete response, six a partial response, and ten a stable disease > 6 months. Conclusions: GP and MTBs expand biomarker-matched treatment options to BC patients beyond the standard of care. Around half of the patients who receive MTT experience a clinical benefit. The standardization of procedures, the development of multi-biomarker-based prediction, and the enhancement in MTT delivery to patients are key challenges, which should be addressed in future initiatives. Full article