Current Treatment Options in Oncology最新文献

Opinion statement: Clinical management of melanoma brain metastases is complex and requires multidisciplinary approach. With close collaboration between neurosurgeons, radiation oncologists and medical oncologists, melanoma patients with brain are offered different treatment modalities: surgery, radiation therapy, systemic therapy or combined treatments. Radiation therapy (whole brain radiotherapy- WBRT and stereotactic radiosurgery- SRS) is an integral part of treating melanoma brain metastases. Use of immunotherapy (checkpoint inhibitors) and targeted therapy (BRAF/MEK inhibitors) significantly changed the outcome in patients with melanoma metastases. Currently, ipilimumab and nivolumab (COMBO) is the preferred first-line systemic therapy for all patients with asymptomatic brain metastases, regardless of BRAF status (BRAF wild-type and BRAF-mutated). Although at the moment there is no consensus on the concomitant use of SRS and COMBO, results from clinical trials suggest that this combined treatment modality should be considered the standard of care for melanoma patients with brain metastases. However, further clinical research is required to define optimal treatment modalities for routine management of melanoma brain lesions.

Opinion statement: Breast cancer metastasizing to the central nervous system (CNS) encompasses two distinct entities: brain metastases involving the cerebral parenchyma and infiltration of the leptomeningeal space, i.e., leptomeningeal disease. CNS metastases affect 10-15% of patients with hormone receptor-positive-status and nearly one-half of those with HER2-positive and triple-negative breast cancer with distant metastatic disease. Significant clinical morbidity and heterogeneous penetration of the blood-brain barrier by systemic therapies contribute to the poor prognosis associated with brain metastases. Recent advances in radiotherapy, including stereotactic approaches and morbidity-reducing strategies such as the use of memantine and hippocampal avoidance in whole brain radiation, coupled with the development of more effective CNS-penetrant systemic therapies, including small molecules and antibody-drug conjugates, have significantly improved patient outcomes. Consequently, patients with breast cancer CNS metastases have improved survival compared to prior decades, and longitudinal care has become increasingly complex, necessitating a multidisciplinary approach to achieve optimal outcomes for patients.

Opinion statement: The vast majority of neuroendocrine 'neoplasms (NENs) are sporadic, although recent evidence has indicated that a subset of these cancers may also originate as a result of genetic germline mutations. To date, 10% of these cancers can be linked to an inherited genetic syndrome. Genetic diagnosis is crucial for patients with a suspected hereditary NEN syndrome, as it recognizes patients carrying germline mutations and allows for personalized clinical follow-up, considering the higher risk of developing other tumours. The potential for early genetic detection has significant implications for the treatment of patients with hereditary NEN syndrome, as it may facilitate the delivery of precision therapy that differs from that typically provided to other patients. Thus, the integration of genotypic and phenotypic diagnostic methods help clinicians to provide more informed treatment and to extend appropriate prevention to family members.

Opinion statement: Lung cancer is the leading cause of cancer-related deaths worldwide, with about 85% of patients being diagnosed as non-small cell lung cancer (NSCLC); and most presenting with stage IV disease initially. With the continuous advancement of treatment strategies of oncology, immunotherapy with/without chemo-immunotherapy has become the first-line treatment for patients with stage IV NSCLC. However, a proportion of patients still develop resistance to the treatment regimen and experience local progression, and primary lung lesion progression is the main progression pattern of stage IV NSCLC. Preclinical and clinical studies have demonstrated the potential of radiotherapy in anti-tumor treatment and suggest that administering local radiotherapy prior to cancer progression can prolong survival. Therefore, we consider whether adding local radiotherapy before the progression of a pulmonary lesion in stage IV NSCLC patients receiving chemo-immunotherapy would be beneficial. The present review aims to explore the efficacy and safety of combining radiotherapy with immunotherapy in the treatment of stage IV NSCLC, delving into the intricacies of their underlying mechanism.

Opinion statement: The biological heterogeneity of colorectal cancer makes its molecular characteristics essential for therapeutic decision-making and prognostic evaluation. Recent advancements in consensus molecular subtyping, based on gene expression profiling, have provided deeper insights into the heterogeneity of CRC. CMS1, known as the immune subtype, is characterized by robust immune activity and microsatellite instability. CMS2, the canonical subtype, exhibits significant activation of the WNT and MYC signaling pathways. CMS3, the metabolic subtype, features unique metabolic dysregulations. CMS4, the mesenchymal subtype, is recognized for its stromal invasion and angiogenesis, which are associated with a poorer prognosis. This review delivers a thorough analysis of the biological and clinical responses of each CMS subtype in colorectal cancer, highlighting their therapeutic vulnerabilities. It integrates data and clinical trial results to suggest potential new therapies for each subtype. The goal is to improve therapeutic efficacy, minimize treatment disparities, and offer CRC patients more precise treatment options.

Opinion statement: Recent advancements in the treatment of early-stage breast cancer have significantly shifted the radiotherapy landscape. Traditionally, the standard of care included lumpectomy followed by endocrine therapy and 3-5 weeks of adjuvant radiation targeting the entire unilateral breast. This review summaries modern trials, emphasizing data reported since 2019 that have changed radiation treatment paradigms. Ultra-hypofractionated treatment regimens have enabled radiation oncologists to deliver the total radiation dose in as few as 5 treatments over 1 week for select patients. Partial breast irradiation, treating only the breast tissue nearest to the lumpectomy cavity, has also emerged as an effective and well-tolerated treatment. Furthermore, a growing body of evidence supports the safety of omitting radiation completely for certain older adults with low-risk disease. Ongoing research in areas such as precision cancer care, treatment de-escalation, and toxicity prevention and management reflects a broader shift toward shared decision-making in medicine and individually tailored treatment paradigms. As research progresses, treatment options will continue to evolve. Advances in radiation oncology will give the oncology team a growing array of tools to custom treatment plans to individual patient risks and toxicity concerns. Knowledge of radiation advances should be used to facilitate shared decisions with patients about the balance of treatment efficacy, toxicity, and quality of life, with the ultimate goal of promoting high-quality, personalized, and patient-centered cancer care.

Opinion statement: Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) have revolutionized the management of hormone receptor-positive (HR +) breast cancer. However, resistance to CDK4/6i remains an unavoidable challenge, with limited evidence to guide the choice of subsequent treatments. Continuation of CDK4/6 inhibition raises as a compelling treatment option and is currently an active area of research. This approach encompasses multifaceted strategies regarding CDK4/6i sequence (same or switched agent), endocrine therapy (ET) partner and potential combination with a third drug. Continuing CDK4/6 inhibition while targeting ET resistance in tumours still dependent on ER activity (i.e., ESR1 mutation) through a ctDNA-guided approach has the potential of becoming practice-changing, pending the results of ongoing phase III studies. Conversely, the efficacy of this strategy in cases of radiological progression in a biomarker-unselected population appears to be rather unsatisfactory. While some benefit, albeit modest, has been observed from switching to a different CDK4/6i after progression (e.g. ribociclib after palbociclib in the MAINTAIN trial and abemaciclib after both palbociclib and ribociclib in the postMONARCH trial), the current evidence (mainly with palbociclib) clearly argues against maintaining the same CDK4/6i. Biomarker analyses to optimally identify patients suitable for this approach yielded inconsistent findings that do not apply to daily clinical decision making. Attractive preliminary efficacy has recently emerged from combining a third agent (immunotherapy, AKT/ PIK3CA/mTOR inhibitor, new ET agents, CDK2 inhibitors) to CDK4/6i and ET, but further validation in larger ongoing trials is required to also determine the optimal timing for incorporating these agents into the therapeutic timeline. To date, CDK4/6i after CDK4/6i progression is far from being a standard of care. However, selected patients with indolent disease, prolonged exposure to previous CDK4/6i treatment (especially palbociclib) and without actionable molecular alterations, may be suitable for suchmaintenance strategy beyond progression. In this challenging and rapidly evolving treatment landscape, ongoing studies can refine the optimal approach and identify clinical and molecular factors to select the best treatment for the right patient.

Opinion statement: Among cervical cancers, adenocarcinoma is less common than squamous cell carcinoma of the cervix; however, the incidence of these cancers is rising. The incidence has changed largely due to a shift in risk factors as well as the evolution of the diagnosis and classification of adenocarcinoma. Adenocarcinoma of the cervix is composed of a diverse group of neoplasms that can be classified by various factors. In this review article, preinvasive disease, updated classifications of adenocarcinoma, and treatment options for cervical adenocarcinoma are discussed with a focus on current and future therapies. Advances in antibody-drug conjugates (ADC) and immunotherapy have increased the treatment options available for usual-type adenocarcinoma but there is still a lack of variety of treatment options for the remaining 25% of non-usual-type adenocarcinomas.

Opinion statement: Melanoma, a highly invasive skin cancer resulting from melanocyte malignant transformation, is the third most common skin malignancy. Despite accounting for only 4% to 5% of all skin malignancies, it is responsible for 80% of skin cancer-related deaths. Targeted therapies and immune checkpoint inhibitors have improved survival rates, yet drug resistance remains a major challenge. In this review, I explore the latest research progress on melanoma drug resistance mechanisms and clinical treatment methods. This aims to provide insights for more effective treatment strategies and improve patient prognosis and quality of life. I also discuss potential strategies to overcome drug resistance based on the latest scientific findings, with a particular focus on the complex and multi-factorial drug resistance mechanisms of melanomas, including genetic mutations, epigenetic changes, and tumor microenvironment factors. Understanding these mechanisms is crucial for developing new drugs and combination therapies targeting drug-resistant tumors. Analyzing complex drug resistance pathways paves the way for personalized medical approaches, which is expected to provide enlightenment on breaking through drug resistance barriers and enhancing the effectiveness of melanoma treatment.

Opinion statement: Breast cancer represents one of the most common malignancies worldwide. In early stages a combination of treatment strategies are offered with curative intent, whereas the therapeutic aim in metastatic disease is to provide the longest possible survival with an acceptable quality of life. The term "oligometastasis", first described by Hellmann and Weichselbaum in 1995, represents an intermediate state between local and systemic disease, where radical focal treatments to all metastatic lesions might have a curative potential. Due to sufficient lack of data, the proper management of oligometastatic disease remains even until today a highly unmet need. Surgery, radiotherapy or ablation (radiofrequency or cryotherapy) are among the local eradication therapies that could offer long-term outcomes in patients with oligometastatic breast cancer (OMBC). The present review aims to bring the readers up to the latest data regarding the management of OMBC according to the different organs involved by setting a framework of current treatment paradigms. It also brings to the forefront debatable questions requiring multidisciplinary approach and highlights the concerns arising from dealing with this clinically and biologically unique entity in everyday clinical practice.