Current Treatment Options in Oncology最新文献

The internal tandem duplication (ITD) mutation of the FMS-like receptor tyrosine kinase 3 (FLT3-ITD) is the most common mutation observed in approximately 30% of acute myeloid leukemia (AML) patients. It represents poor prognosis due to continuous activation of downstream growth-promoting signaling pathways such as STAT5 and PI3K/AKT. Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. However, patients possess generally poor remission rates and acquired resistance when FLT3I used alone. Various factors in patients could cause these adverse effects including altered epigenetic regulation, causing mainly abnormal gene expression patterns. Epigenetic modifications are required for hematopoietic stem cell (HSC) self-renewal and differentiation; however, critical driver mutations have been identified in genes controlling DNA methylation (such as DNMT3A, TET2, IDH1/2). These regulators cause leukemia pathogenesis and affect disease diagnosis and prognosis when they co-occur with FLT3-ITD mutation. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I’s activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients’ mutational status in terms of FLT3 and DNA methlome regulators.

Dysphagia, difficulty in eating and drinking, remains the most common side effect of radiotherapy treatment for head and neck cancer (HNC) with devastating consequences for function and quality of life (QOL). Over the past decade, 5-year survival has improved due to multiple factors including treatment advances, reduction in smoking, introduction of the human papillomavirus (HPV) vaccine and more favourable prognosis of HPV-related cancers. Increased prevalence of HPV-positive disease, which tends to affect younger individuals, has led to an elevated number of people living for longer with the sequelae of cancer and its treatment. Symptoms are compounded by late effects of radiotherapy which may lead to worsening of dysphagia for some long-term survivors or new-onset dysphagia for others. Speech-language pathology (SLP) input remains core to the assessment and management of dysphagia following HNC treatment. In this article, we present current SLP management of dysphagia post-radiotherapy. We discuss conventional treatment approaches, the emergence of therapy adjuncts and current service delivery models. The impact of adherence on therapy outcomes is highlighted. Despite treatment advancements, patients continue to present with dysphagia which is resistant to existing intervention approaches. There is wide variation in treatment programmes, with a paucity of evidence to support optimal type, timing and intensity of treatment. We discuss the need for further research, including exploration of the impact of radiotherapy on the central nervous system (CNS), the link between sarcopenia and radiotherapy-induced dysphagia and the benefits of visual biofeedback in rehabilitation.

Opinion statement: Targeted treatment strategies are available for human epidermal growth factor receptor 2 (HER2)-positive (amplified and/or overexpressed) metastatic colorectal cancer (mCRC), and HER2 testing is indicated in patients with mCRC. At present, standard of care first-line treatment for those with HER2-positive mCRC remains chemotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors or bevacizumab, depending on RAS/BRAF mutational status and tumor sidedness. HER2-targeted agents should be considered for those with RAS/BRAF wild-type disease in subsequent-line treatment and in first-line treatment for patients not appropriate for intensive therapy. While the choice of anti-HER2 therapy is empiric given lack of head-to-head comparisons, the combination of trastuzumab plus tucatinib has received FDA accelerated approval for use in this setting and is generally the authors' preference. Trastuzumab plus lapatinib, trastuzumab plus pertuzumab, and trastuzumab deruxtecan (T-DXd) also have evidence of efficacy in this setting. As T-DXd has demonstrated activity following treatment with other HER2-targeted regimens and carries an increased risk of high-grade toxicities, the authors favor reserving it for use after progression on prior anti-HER2 therapy. HER2-targeted therapies that inhibit signal transduction appear to have limited activity in those with RAS mutations, including trastuzumab-containing regimens. However, the antibody drug conjugate T-DXd has some data showing efficacy in this setting, and the authors would consider T-DXd in subsequent-line therapy for HER2-positive, RAS-mutated mCRC. Several areas of uncertainty remain regarding how to best utilize HER2-targeted therapies in mCRC. These include the optimal sequence of anti-HER2 therapies with chemotherapy and anti-EGFR therapies, the optimal combination partners for anti-HER2 therapies, and the incorporation of predictive biomarkers to guide use of anti-HER2 therapies. Results of ongoing studies may thus alter the treatment paradigm above in the coming years.

Cardio-oncology is an emerging interdisciplinary field dedicated to the early detection and treatment of adverse cardiovascular events associated with anticancer treatment, and current clinical management of anticancer-treatment-related cardiovascular toxicity (CTR-CVT) remains limited by a lack of detailed phenotypic data. However, the promise of diagnosing CTR-CVT using deep phenotyping has emerged with the development of precision medicine, particularly the use of omics-based methodologies to discover sensitive biomarkers of the disease. In the future, combining information produced by a variety of omics methodologies could expand the clinical practice of cardio-oncology. In this review, we demonstrate how omics approaches can improve our comprehension of CTR-CVT deep phenotyping, discuss the positive and negative aspects of available omics approaches for CTR-CVT diagnosis, and outline how to integrate multiple sets of omics data into individualized monitoring and treatment. This will offer a reliable technical route for lowering cardiovascular morbidity and mortality in cancer patients and survivors.

Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen’s disease (BD) and extramammary Paget’s disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration.

The treatment of oligometastatic genitourinary cancers is a rapidly advancing field with ablative radiotherapy as one of the critical treatment components. The oligometastatic disease state, which can be defined as 1–5 metastatic sites with a controlled primary, represents a distinct clinical state where comprehensive ablative local therapies may provide improved outcomes. Enhanced imaging has increased the number of patients identified with oligometastatic disease. Evidence for improved outcomes with metastasis-directed therapy (MDT) in oligometastatic genitourinary cancers is increasing, and previously published outcome data continues to mature with an increasing body of prospective data to inform the role of MDT in histology-specific settings or in the context of systemic therapy. In select patients, MDT can offer benefits beyond improved local control and allow for time off of systemic therapy, prolonged time until next therapy, or even the hope of cure. However, treatment decisions for locally ablative therapy must be balanced with consideration towards safety. There are exciting advances in technologies to target and adapt treatment in real-time which have expanded options for safer delivery and dose escalation to metastatic targets near critical organs at risk. The role of systemic therapies in conjunction with MDT and incorporation of tumor genetic information to further refine prognostication and treatment decision-making in the oligometastatic setting is actively being investigated. These developments highlight the evolving field of treatment of oligometastatic disease. Future prospective studies combining MDT with enhanced imaging and integrating MDT with evolving systemic therapies will enable the optimal selection of patients most likely to benefit from this “all-or-none” approach and reveal settings in which a combination of therapies could result in synergistic outcomes.

Opinion statement: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.

Opinion statement: This paper shines a light on the exciting progress being made in using immunotherapy to treat advanced gastroesophageal cancers. The positive results from trials using drugs like Pembrolizumab and Nivolumab are certainly encouraging and open new possibilities for treating this challenging disease. However, it is clear that we still have a lot to learn about how to predict which patients will benefit most from these treatments. The exploration of combining therapies and using machine learning to guide treatment shows promise. Moving forward, it is crucial that researchers and healthcare professionals continue to work together, sharing knowledge and findings to continue the advancements in this important area.

Opinion statement: Treatment guidelines for colorectal cancer (CRC) are primarily based on the results of randomized clinical trials (RCTs), the gold standard methodology to evaluate safety and efficacy of oncological treatments. However, generalizability of trial results is often limited due to stringent eligibility criteria, underrepresentation of specific populations, and more heterogeneity in clinical practice. This may result in an efficacy-effectiveness gap and uncertainty regarding meaningful benefit versus treatment harm. Meanwhile, conduct of traditional RCTs has become increasingly challenging due to identification of a growing number of (small) molecular subtypes. These challenges-combined with the digitalization of health records-have led to growing interest in use of real-world data (RWD) to complement evidence from RCTs. RWD is used to evaluate epidemiological trends, quality of care, treatment effectiveness, long-term (rare) safety, and quality of life (QoL) measures. In addition, RWD is increasingly considered in decision-making by clinicians, regulators, and payers. In this narrative review, we elaborate on these applications in CRC, and provide illustrative examples. As long as the quality of RWD is safeguarded, ongoing developments, such as common data models, federated learning, and predictive modelling, will further unfold its potential. First, whenever possible, we recommend conducting pragmatic trials, such as registry-based RCTs, to optimize generalizability and answer clinical questions that are not addressed in registrational trials. Second, we argue that marketing approval should be conditional for patients who would have been ineligible for the registrational trial, awaiting planned (non) randomized evaluation of outcomes in the real world. Third, high-quality effectiveness results should be incorporated in treatment guidelines to aid in patient counseling. We believe that a coordinated effort from all stakeholders is essential to improve the quality of RWD, create a learning healthcare system with optimal use of trials and real-world evidence (RWE), and ultimately ensure personalized care for every CRC patient.

Opinion statement: Despite targeted therapy and immunotherapy being recognized as established frontline treatments for advanced non-small cell lung cancer (NSCLC), the unavoidable development of resistance and disease progression poses ongoing challenges. Antibody-drug conjugates (ADCs) offer a potent treatment option for NSCLC through the specific delivery of cytotoxic agents to tumor cells that display distinct antigens. This review delves into the latest evidence regarding promising ADC agents for NSCLC, focusing on their targets, effectiveness, and safety assessments. Additionally, our study provides insights into managing toxicities, identifying biomarkers, devising methods to counter resistance mechanisms, tackling prevailing challenges, and outlining prospects for the clinical implementation of these innovative ADCs and combination regimens in NSCLC.