Cancer journal最新文献

Abstract: Immune checkpoint inhibition and targeted therapies have revolutionized the treatment of melanoma. However, chemotherapy and interleukin 2 (IL-2) therapy may still have a role in the later-line treatment of patients who do not have durable responses to other treatments. Chemotherapy can work transiently in patients whose disease has progressed on immune checkpoint inhibitors and for whom there are no appropriate targeted therapy options. High-dose IL-2 therapy can still be effective for a very small number of patients following progression on other therapies. In addition, modified IL-2 agents and IL-2 in combination with tumor-infiltrating lymphocyte therapy may play a role in future treatments for melanoma.

Abstract: Traditional chemotherapy has been ineffective in the treatment of metastatic melanoma. Until the use of checkpoint inhibitors, patients had very limited survival. Since the original US Food and Drug Administration approval of ipilimumab over a decade ago, the armamentarium of immunotherapeutic agents has expanded to include programmed cell death protein 1 and lymphocyte activation gene 3 antibodies, requiring a nuanced approach to the selection of frontline treatments, managing patients through recurrence and progression, and determining length of therapy. Herein, we review the existing evidence supporting current standard immunotherapy regimens and discuss the clinical decision-making involved in treating patients with metastatic melanoma with checkpoint inhibitors.

Abstract: Uveal melanoma (UM), arising from intraocular melanocytes, poses a complex clinical challenge with a substantial risk of distant metastasis, often to the liver. Molecular profiling, encompassing genetic, cytogenetic, gene expression, and immunological subsets, plays a pivotal role in determining prognoses. The evolving landscape includes promising systemic treatments, such as tebentafusp, a novel immune-modulating bispecific fusion protein, and targeted therapies. Combined regional and systemic approaches, including immune checkpoint inhibitors and innovative liver-directed therapy, are also under investigation. Although recent progress has improved outcomes, ongoing research aims to address the unique challenges of UM and develop effective therapies, particularly for HLA-A*02:01-negative patients who represent a significant unmet medical need. This review comprehensively discusses the molecular characteristics of UM, risk stratification methods, and the current and future spectrum of regional and systemic therapeutic modalities.

Abstract: Patients with stage III resectable melanoma carry a high risk of melanoma recurrence that ranges from approximately 40% to 90% at 5 years following surgical management alone. Postoperative systemic adjuvant therapy targets residual micrometastatic disease that could be the source of future recurrence and death from melanoma. Randomized phase III adjuvant trials reported significant improvements in overall survival with high-dose interferon α in 2 of 3 studies (compared with observation and GMK ganglioside vaccine) and with anti-cytotoxic T-lymphocyte antigen 4 ipilimumab at 10 mg/kg compared with placebo and ipilimumab 3 mg/kg compared with high-dose interferon α. In the modern era, more recent phase III trials demonstrated significant recurrence-free survival improvements with anti-programmed cell death protein 1, pembrolizumab, and BRAF-MEK inhibitor combination dabrafenib-trametinib (for BRAF mutant melanoma) versus placebo. Furthermore, anti-programmed cell death protein 1, nivolumab and pembrolizumab have both been shown to significantly improve recurrence-free survival as compared with ipilimumab 10 mg/kg. For melanoma patients with clinically or radiologically detectable locoregionally advanced disease, emerging data support an important role for preoperative systemic neoadjuvant therapy. Importantly, a recent cooperative group trial (S1801) reported superior event-free survival rates with neoadjuvant versus adjuvant therapy. Collectively, current data from neoadjuvant immunotherapy and targeted therapy trials support a future change in clinical practice in favor of neoadjuvant therapy for eligible melanoma patients.

Abstract: Melanoma is the most lethal cutaneous malignancy worldwide. The last 15 years have ushered in several regulatory approvals that have dramatically altered the landscape of treatment options for patients with melanoma. Many patients with melanoma harbor activating mutations in the BRAF proto-oncogene, a key component of the mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therapies targeting BRAF have led to remarkable improvements in both response rates and survival in patients with metastatic disease. In parallel with these developments in MAPK-targeted therapy has been the clinical development of immune checkpoint inhibitors, which also have improved response rates and survival in patients with metastatic disease including randomized trials compared with MAPK-targeted therapy in patients with advanced, BRAF-mutant melanoma. Immune checkpoint inhibitors have become the preferred first-line standard-of-care treatment for patients with newly diagnosed metastatic disease in patients irrespective of BRAF mutational status. Given these developments, it is now less clear how to optimize the use of MAPK-targeted therapy regarding treatment setting and in sequence with immune checkpoint inhibitor.

Abstract: Intratumoral therapies represent a unique avenue for drug development in melanoma as patients often have accessible lesions that are particularly amenable to these approaches. In addition, a majority of intratumoral therapies have focused on stimulating antitumor immune responses, making them a particularly attractive option for use in melanoma. In this review, we describe applications for talimogene laherparepvec, a US Food and Drug Administration-approved intratumoral therapy in melanoma, as well as several classes of intratumoral therapies in development including novel oncolytic viruses, mRNA-based intratumoral injections, and cytokines and other signaling molecules.

Abstract: Despite that telehealth has been crucial to the delivery of oncology care during the COVID-19 pandemic, the impact of this care delivery mechanism on outcomes in cancer care has not been rigorously studied relative standard in-person care for patients with cancer. Patient-centered outcomes such as quality of life, patient satisfaction, and symptoms are important outcomes that have been the primary focus of many of the existing studies in this space, yet only a select few have evaluated overall survival and other objective efficacy endpoints. Studies have alluded to positive effects of telehealth on mitigating financial toxicity and enhancing cost-effective care delivery in oncology. Telehealth carries much potential for advancing care for patients with cancer, but future study should focus on additional efficacy endpoints, implementation, and ways to reduce disparities.

Abstract: Digital health tools extend well beyond telemedicine, holding great potential to advance oncological care. We survey digital health and provide recommendations across the health continuum, tailoring them to oncology, including prevention, detection and diagnosis, and treatment and monitoring. Within the prevention realm, we review wellness technologies, cancer screening, mental health solutions, and digital biomarkers. For detection and diagnosis, we describe existing and emerging solutions for remote patient monitoring and various means to capture digital biomarkers, the "digital exam," and "digital outcomes." Treatment and monitoring solutions include telemedicine, chatbots, and digital therapeutics, which are also explored. We also discuss a host of technology enablers that are required for successful implementation and sustainment of digital health-enabled care. Our recommendations pertain to health care systems as well as companies that work with these systems or provide care to patients directly.

Abstract: Telecommunications technology began to be integrated into health care delivery by the mid-1900s, with the goal of increasing access to care including access to cancer care.There have been at least 3 significant telehealth expansion periods, with the most recent related to the COVID-19 pandemic. Technology uptake increased in the 1990s as quality improved, costs came down, and usability factors were addressed. As telehealth practice transitioned to use of personal devices, the COVID-19 pandemic arose, and necessity compelled widespread telehealth uptake. Most patients and clinicians entered the pandemic with little if any telehealth experience and often no training on using personal devices to access health care. Teleoncology data reveal cancer care feasibility and acceptability with generally high levels of satisfaction for both patients and clinicians. Sustaining the progress made in telehealth uptake requires ongoing insurance coverage with parity in coverage, licensure facilitation, and ongoing development of technology that is easy to use. In addition, to tele-cancer care appointments, the technology may be used for care coordination, education, and increased access to cancer clinical trials.

Abstract: During the COVID-19 pandemic, there was an unprecedented growth in telemedicine due to the need to provide safe access to care during a global pandemic. The regulatory, compliance, and payment policy landscape favorably changed, paving the way for growth in utilization. Despite these favorable changes in the landscape, operational and technical burdens remained barriers to optimal use of telemedicine. Investments in operational processes and vendor selection can improve the patient and clinician experience in using telemedicine, so this digital tool can diminish burnout.