American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting最新文献

Clinical trials cooperation is not a luxury; it is a necessity, now more than ever, first in light of the segmentation of tumors according to their molecular targets-which are being matched to an increasing number of competitive drugs-and second because it is the only chance to maintain academic research centered on addressing patients' needs. In its 21 years of existence, the Breast International Group, an umbrella organization supporting the activities of 54 member groups across six continents, has been confronted with challenges that include (1) keeping trust and motivation within the network; (2) improving the interface between academia and industry; (3) improving patient involvement and trust in clinical trials; and (4) fundraising for noncommercial research. We describe how these challenges have been addressed so far, with the hope of empowering the next generation of clinical investigators.

It is widely recognized that subspecialized multidisciplinary care improves neuro-oncology outcomes. Optimizing patient outcomes relies on the expertise of the treating physicians, neuroradiology and neuropathology, and supportive services familiar with common neurologic syndromes that occur after brain tumor diagnosis and treatment. Despite an increasing number of providers, patient access to specialized multidisciplinary care and clinical trials remains limited. Barriers to equitable health care exist across the United States, with marginalized communities being impacted disproportionately. Such disparity causes increased morbidity and mortality for patients from backgrounds with various elements of diversity. Limited attention to this inequity has resulted in an incomplete understanding of the spectrum of experiences that patients with neuro-oncologic diseases encounter. Clinical trials represent the highest standard and quality of care in medicine, but inclusion of under-represented and underserved groups consistently lags behind counterpart participants from majority racial and ethnic groups. Through provider education as it pertains to issues from bias and health literacy to increasing clinical trial enrollment and offering opportunities through telemedicine, opportunities for improving access to high-quality neuro-oncologic care are explored.

Colorectal cancer mortality has decreased considerably following the adoption of national screening programs, yet, within at-risk subgroups, there continue to be measurable differences in clinical outcomes from variations in screening, receipt of chemotherapy, radiation or surgery, access to clinical trials, research participation, and survivorship. These disparities are well-described and some have worsened over time. Disparities identified have included race and ethnicity, age (specifically young adults), socioeconomic status, insurance access, geography, and environmental exposures. In the context of the COVID-19 pandemic, colorectal cancer care has necessarily shifted dramatically, with broad, immediate uptake of telemedicine, transition to oral medications when feasible, and considerations for sequence of treatment. However, it has additionally marginalized patients with colorectal cancer with historically disparate cancer-specific outcomes; among them, uninsured, low-income, immigrant, and ethnic-minority patients-all of whom are more likely to become infected, be hospitalized, and die of either COVID-19 or colorectal cancer. Herein, we outline measurable disparities, review implemented solutions, and define strategies toward ensuring that all have a fair and just opportunity to be as healthy as possible.

Performing germline and somatic sequencing in locally advanced and metastatic pancreatic cancer can identify potentially targetable genomic aberrations that impact current standard treatment options or eligibility for biomarker-targeted clinical trials. Testing for deleterious germline mutations in BRCA1/2 impacts patient selection for platinum-based chemotherapy regimens and selection of patients who are candidates to receive maintenance therapy with olaparib. Additional germline mutations also similarly introduce potential vulnerabilities to the cancers that arise and may be targeted by clinical trials. Somatic mutation testing also provides opportunities for optimal selection of patients for biomarker-driven clinical trials. Although KRAS mutations are found in 90% to 93% of pancreatic cancers, there are increasing opportunities for therapies against particular mutant KRAS isoforms, especially with the advent of KRAS G12C-specific small molecule inhibitors, and KRAS targeting trials will increasingly require identification of the specific KRAS mutation present. There are also a range of tumor site-agnostic molecular features, such as microsatellite instability and NTRK fusions that, although rarely found in pancreatic cancers, impact selection of patients who have the potential for dramatic benefit with immune checkpoint inhibitors such as pembrolizumab or TRK inhibitors such as larotrectinib or entrectinib, respectively, and thus motivate broader somatic mutation and fusion testing for patients with locally advanced and metastatic pancreatic cancers. Multiple other rare actionable aberrations, particularly gene fusions in the 8% to 10% of KRAS wild-type pancreatic cancers, are also known, and enrollment in basket trials for these rare patient cohorts is highly encouraged.

The overwhelming majority of head and neck cancers and related deaths occur in low- and middle-income countries, which have challenges related to burden of disease versus access to care. Yet the additional health care burden of the COVID-19 pandemic has also impacted access to care for patients with head and neck cancer in the United States. This article focuses on challenges and innovation in prioritizing head and neck cancer care in Sub-Saharan Africa, the Indian experience of value-added head and neck cancer care in busy and densely populated regions, and strategies to optimize the management of head and neck cancer in the United States during the COVID-19 pandemic.

Oropharyngeal, cervical, vulvar, and anal cancers share a common risk factor of HPV infection. HPV vaccination is currently recommended at age 11 or 12 to prevent new HPV infections for all genders with catch-up vaccination recommened up to age 26. Despite the known effectiveness of HPV vaccination to prevent HPV-related cancer, there is continued low uptake in the United States; only 40% of eligible persons were vaccinated in 2018, though rates are 70% among teenagers. Current American Cancer Society cancer screening guidelines recommend cervical cancer screening, but do not have specific recommendations for screening for other HPV-related cancers. Oropharyngeal cancer precursors have yet to be identified, and there are currently no routine screening tests for oropharyngeal cancer recommended by the U.S. Preventive Services Task Force. The U.S. Preventive Services Task Force and American Cancer Society recommend cervical cancer screening for women at average risk up to age 65, and screening guidelines do not currently differ by HPV vaccination status. Primary HPV DNA testing was first approved for cervical cancer screening in 2016 and was shown to be superior for cervical cancer prevention. Vulvar and anal cancer precursors have been identified, but optimal screening remains unclear. Examination of the anal canal and perianus is best performed by trained clinicians using high-resolution anoscopy, and effectiveness of using high-resolution anoscopy to detect and treat anal high-grade squamous intraepithelial lesions to prevent cancer is actively being researched. Current multistep approaches to control HPV-related malignancies include HPV vaccination coupled with cervical cancer screening or surveillance for oropharyngeal, vulvar, and anal cancers.

Approximately 185,840 individuals will be diagnosed with hematologic malignancies in the United States in 2020. Disparities in disease incidence, prevalence, burden, mortality, and survivorship have been identified among this patient population. Contributing factors include genetic ancestry, race/ethnicity, sex, socioeconomic status, and geographic region. Historically, these inequities have been understudied. Addressing these disparities requires a systems-level approach, improving access to care and reducing biases in the clinical setting. Additional research is needed to construct comprehensive, multilevel models to explore systematic observational studies and perform strategic intervention trials to overcome these disparities.

The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported. In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children's Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.

The term "undruggable" is used to describe a protein that is not pharmacologically capable of being targeted; recently, however, substantial efforts have been made to turn these proteins into "druggable" targets. Thus, "difficult to drug" or "yet to be drugged" are perhaps more appropriate terms. In cancer, a number of elusive targets fall into this category, including transcription factors such as STAT3, TP53, and MYC. Pharmacologically targeting these intractable proteins is now a key challenge of modern drug development, requiring innovation and the development of new technologies. In this article, we discuss some of the recent technologic and pharmacologic advances that have underpinned the erosion of the concept of undruggability. We describe recent successes in drugging the undruggable RAS (KRAS G12C and HRAS), and discuss the advances that have led to the validation of further targets previously believed to be undruggable, such as HIF-2α, BCL-2, MDM2, and MLL. Finally, we look to the future and describe important advances that are likely to have a major impact on targeting undruggable targets, such as the advent of proteolysis-targeting chimeras and protein-protein modulators, which are leading to considerable excitement surrounding the development of cancer targets.

This review aims to provide an overview of nonsurgical treatment strategies for central nervous system metastases in melanoma as well as discuss treatment challenges and future directions. Recent strategies for melanoma brain metastases have involved proving the intracranial activity of approved therapies as well as identifying novel drug targets. BRAF/MEK combination therapy has intracranial activity in those with BRAF V600 mutations, though disease control is shorter for intracranial than extracranial metastases. Immunotherapy and combination immunotherapies have emerged as providing durable responses in melanoma, and newer studies combining immunotherapy with targeted therapies are emerging. Continued challenges include penetration through the blood-brain barrier and development of resistance mechanisms. Novel therapeutic targets and methods to improve central nervous system penetrance are being identified through the application of deep DNA- and RNA-sequencing analyses. Radiation therapy approaches, especially stereotactic radiosurgery in combination or in sequence with systemic therapies, are also being investigated. Both targeted therapies and immunotherapies have revolutionized the field of melanoma treatment. Multimodality approaches with multidisciplinary teams will pave the way for the future of central nervous system disease treatment in melanoma.