Current Treatment Options in Oncology最新文献

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: Type 2 Diabetes Mellitus (T2DM) and leukemia are two major global health concerns, both contributing significantly to morbidity and mortality. Epidemiological evidence demonstrates a strong correlation between T2DM and an increased risk of leukemia, particularly driven by insulin resistance, hyperglycemia, and the resultant metabolic dysregulation. Key shared risk factors, including obesity and chronic inflammation, create a conducive environment for leukemogenesis, intensifying cancer cell proliferation and resistance to standard therapies. Insulin resistance, in particular, triggers oncogenic pathways such as PI3K/AKT and MAPK, exacerbating the aggressive phenotype seen in leukemia patients with T2DM. Additionally, clonal hematopoiesis of indeterminate potential (CHIP) is implicated in the higher leukemia risk observed in diabetic populations, especially among the elderly. Molecular mechanisms like the insulin-like growth factor (IGF) system further highlight the intricate link between these diseases, promoting survival and proliferation of leukemia cells. The coexistence of T2DM in leukemia patients is associated with poorer prognostic outcomes, including increased susceptibility to infections, reduced survival, and greater treatment resistance. Antidiabetic agents, notably metformin and pioglitazone, show promise in enhancing chemotherapy efficacy and improving patient outcomes by targeting metabolic pathways. These results highlight the need for comprehensive treatment approaches that target both metabolic abnormalities and cancer-related mechanisms in patients suffering from both T2DM and leukemia.

Opinion statement: The landscape of treatment of advanced PDAC is witnessing significant changes. This is in part due to the advent of molecular profiling, which has highlighted molecularly-distinct subsets of pts, especially those with KRAS wild-type disease. We now know that these pts harbor genomic alterations that not only serve as molecular drivers but also pose as therapeutically relevant markers. In the absence of strong evidence to support the use of targeted therapy in the front-line setting, we continue to offer chemotherapy for treatment-naïve pts. However, an argument can be made for the front-line use of targeted therapy in pts who are not fit for chemotherapy or who are not interested in it. The challenge is ensuring that molecular profiling is done in a timely fashion to prevent significant delays in therapy. In our practice, we offer molecular testing to all pts with a new diagnosis of advanced PDAC. We prefer the utility of targeted therapy in the second line and beyond for pts who have an actionable target, over the use of further chemotherapy, as targeted therapy appears to confer deep and durable responses and longer survival. For pts with MSI-H or MMRd disease, the use of immunotherapy is indicated, although it has to be noted that MSI-H/MMRd PDAC performed worse that other MSI-H/MMRd cancers treated with immunotherapy. Therefore, in the presence of MSI-H/MMRd and an additional actionable target, we prefer treating with targeted therapy and reserving immunotherapy for later lines. Pt preference has to be taken into consideration at all times though.

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.

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: Palliative care seeks to address the physical, psychosocial and spiritual concerns of patients with a life limiting illness and their caregivers. Early referral to palliative care improves symptoms and is the standard of care. This paper evaluates the evidence for different models of community palliative care and looks at the effects of homecare, hospice programs and residential aged care facility (RACF) interventions on symptom management, home death rate and acute health service utilization. It also examines the impact of COVID-19, telehealth, integration and staffing models on the efficacy of community palliative care. Evidence suggests that community palliative care increases the rate of death at home and may improve satisfaction with care, but effect on symptoms and acute health care utilization are less certain. Enrolment in a hospice program may decrease hospitalizations and improve satisfaction. RACF staff training interventions to improve the quality of palliative care provided to residents show mixed results across all indicators. COVID-19 saw a relative increase in the demand for community palliative care, as people opted out of the hospital system. Models of community palliative care that facilitate integration, support primary health providers, and promote technological innovation are worthy of further research.

Opinion statement: The therapeutic landscape for HER2-positive metastatic breast cancer has exploded in the last two decades following the initial advent of trastuzumab, a monoclonal antibody. While the first line treatment has remained a combination of dual HER2 blockade with taxane chemotherapy, we now have several exciting options in the second line and beyond. The introduction of antibody-drug conjugates, in specific trastuzumab deruxtecan, has resulted in the best progression-free survival among patients with this subtype of breast cancer. Given the excellent outcomes of these drugs, clinical trials are now evaluating the role of ADCs in the front-line setting in previously untreated patients. In addition, there are also clinical trials evaluating the role of other targets in patients with HER2-positive cancers, including PI3KCA mutations, PD-L1 and CDK4/6. Given the predilection for brain metastases in this population, there is enthusiasm to identify the optimal combination of effective treatments. Tucatinib, capecitabine, and trastuzumab combination represent one such promising strategy. With the increasing longevity of these patients, important clinical questions include optimal treatment sequencing, the role of de-escalation of treatment in excellent responders, and the associated financial toxicity. Despite the aggressive nature of this subtype of breast cancer, the outcomes continue to improve for these patients with the evolving treatments.

Opinion statement: Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Opinion statement: The renin-angiotensin-aldosterone system (RAAS) is a crucial regulator of the cardiovascular system and a target for widely used therapeutic drugs. Dysregulation of RAAS, implicated in prevalent diseases like hypertension and heart failure, has recently gained attention in oncological contexts due to its role in tumor biology and cardiovascular toxicities (CVTs). Thus, RAAS inhibitors (RAASi) may be used as potential supplementary therapies in cancer treatment and CVT prevention. Oncological treatments have evolved significantly, impacting patient survival and safety profiles. However, they pose cardiovascular risks, necessitating strategies for mitigating adverse effects. The main drug classes used in oncology include anthracyclines, anti-HER2 therapies, immune checkpoint inhibitors (ICIs), and vascular endothelial growth factor (VEGF) signaling pathway inhibitors (VSPI). While effective against cancer, these drugs induce varying CVTs. RAASi adjunctive therapy shows promise in enhancing clinical outcomes and protecting the cardiovascular system. Understanding RAAS involvement in cancer and CVT can inform personalized treatment approaches and improve patient care.

Opinion statement: Breast cancer does not wait until a woman reaches her 50's to strike. One in six cases occurs in women between the ages of 40 and 49 and breast cancer is the most prevalent cancer and the leading cause of cancer-related deaths among women under 50 in the United States (10% of breast cancer deaths), emphasizing the urgency of early detection (American Society. 2024). Duffy et al. highlight the vital role of mammography screening in younger women, showing that starting screening at 40 reduces breast cancer mortality, with a consistent absolute reduction over time (Duffy et al. Health Technol Assess. 24(55):1-24, 2020). By starting yearly mammograms at 40, we could see a remarkable 40% reduction in breast cancer deaths (Monticciolo et al. J Am Coll Radiol. 18(9):1280-8, 2021). Screening at age 40 also adds little to the burden of overdiagnosis that already arises from screening at age 50 and older. Comparing this to biennial screening between ages 50-74, yearly screening at 40 saves approximately 13,770 more lives annually according to a report by the American Cancer Society published in JAMA in 2015 (Oeffinger et al. JAMA. 314(15):1599-614, 2015). But it's not just about saving lives; it's also about preserving quality of life. Between ages 40 and 49, 12-15% of years of life lost are attributed to breast cancer, highlighting the impact on women's lives. Early detection through screening can minimize these losses, ensuring more years spent with loved ones. It's clear: starting mammograms at age 40 saves lives. We must prioritize early detection and make screening accessible to all women, regardless of age. This proactive approach can reduce the burden of breast cancer and pave the way for a healthier future for women everywhere.