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

Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision. Beyond statistical simulations, there are little data to refute the supposed shortcomings ascribed to the 3+3 method. Even so, to address the unique nuances of gene- and immune-targeted compounds, a variety of inventive phase 1 trial designs have been suggested. Strategies for developing these therapies have launched first-in-human studies devised to acquire a breadth of patient data that far exceed the size of a typical phase I design and blur the distinction between dose selection and efficacy evaluation. Recent phase I trials of promising cancer therapies assessed objective tumor response and durability at various doses and schedules as well as incorporated multiple expansion cohorts spanning a variety of histology or biomarker-defined tumor subtypes, sometimes resulting in U.S. Food and Drug Administration approval after phase I. This article reviews recent innovations in phase I design from the perspective of multiple stakeholders and provides recommendations for future trials.

Targeting the androgen receptor by depriving testosterone with gonadotropin-releasing hormone agonists or antagonists, or surgical castration, has been the backbone of metastatic prostate cancer treatment. Although most prostate cancers initially respond to androgen deprivation, metastatic castration-resistant prostate cancer evolves into a heterogeneous disease with diverse drivers of progression and mechanisms of therapeutic resistance. Development of castrate resistance phenotype is associated with lethality despite the recent noteworthy strides gained via increase in therapeutic options. Identification of novel therapeutics to further improve survival and achieve durable responses in metastatic castration-resistant prostate cancer is a clinical necessity. In this review, we outline the existing avengers for treatment of metastatic castration-resistant prostate cancer by clinical presentation, placing into context the clinical state of the patient, such as burden of disease and symptoms. Doing so might aid in the ability to optimize the sequence of agents and allow for maximal exposure to life-prolonging therapeutics. Realizing the limitations of the androgen signaling inhibition, we explore the androgen-indifferent prostate cancer: the mutants. Classically, these subtypes have been associated with variant histology, but androgen-indifferent prostate cancer features are now frequently observed in association with heterogeneous morphologies, including double-negative prostate cancers, lacking both androgen receptor and neuroendocrine features, or clinicopathologic criteria, such as the aggressive variant prostate cancer criteria. The framework of new avengers against metastatic castration-resistant prostate cancer based on mechanism, including DNA repair, immune checkpoint inhibition, PTEN/PI3K/AKT pathway, prostate-specific membrane antigen targets, bispecific T-cell engagers, and radionuclide therapies, is summarized in this review.

Optimizing the well-being of the oncology clinician has never been more important. Well-being is a critical priority for the cancer organization because burnout adversely impacts the quality of care, patient satisfaction, the workforce, and overall practice success. To date, 45% of U.S. ASCO member medical oncologists report experiencing burnout symptoms of emotional exhaustion and depersonalization. As the COVID-19 pandemic remains widespread with periods of outbreaks, recovery, and response with substantial personal and professional consequences for the clinician, it is imperative that the oncologist, team, and organization gain direct access to resources addressing burnout. In response, the Clinician Well-Being Task Force was created to improve the quality, safety, and value of cancer care by enhancing oncology clinician well-being and practice sustainability. Well-being is an integrative concept that characterizes quality of life and encompasses an individual's work- and personal health-related environmental, organizational, and psychosocial factors. These resources can be useful for the cancer organization to develop a well-being blueprint: a detailed start plan with recognized strategies and interventions targeting all oncology stakeholders to support a culture of community in oncology.

Adult cancer disparities have been documented for decades and continue to persist despite clinical advancements in cancer prevention, detection, and treatment. Pediatric cancer survival has improved significantly in the United States for the past 5 decades to over 80%; however, disparate outcomes among children and adolescents with cancer still affect many populations in the United States and globally, including racial and ethnic minorities, populations with low socioeconomic status, and residents of underserved areas. To achieve equitable outcomes for all children and adolescents with cancer, it is imperative that concerted multilevel approaches be carried out to understand and address health disparities and to ensure access to high-quality cancer care. Addressing social determinants of health, such as removing barriers to health care access and ensuring access to social supports, can reduce pediatric cancer disparities. Nevertheless, public health policy, health system interventions, and innovative delivery of evidence-based services are critically needed. Partnerships among patients, caregivers, and health care providers, and among health care, academic, and governmental institutions, have a pivotal role in reducing cancer disparities and improving outcomes in the 21st century.

Despite recent treatment advances, kidney and bladder cancer cases have continued to rise in both incidence and mortality over the last few decades. Not every demographic subgroup of patients diagnosed with these cancers has an equivalent outcome. Women diagnosed with bladder cancer have worse overall survival than men diagnosed with bladder cancer. Older adults with muscle-invasive bladder cancer have worse cancer-specific outcomes than do younger patients. Black patients diagnosed with kidney and bladder cancers appear to have worse overall survival than White patients diagnosed with these cancers. Although these differences in outcomes are likely multifactorial, in many cases they may be based on modifiable approaches to screening, diagnosing, and treating patients. We explore various causes of these differences in outcomes between patients and address patient engagement strategies and avenues to effect change. In 2021, equity in cancer and cancer care delivery has a more prominent place in the hierarchy of the continuum of medicine. Continued focus on this topic is critical, with clear accountabilities established and barriers to best care for patients eliminated.

The COVID-19 pandemic and the simultaneous increased focus on structural racism and racial/ethnic disparities across the United States have shed light on glaring inequities in U.S. health care, both in oncology and more generally. In this article, we describe how, through the lens of fundamental ethical principles, an ethical imperative exists for the oncology community to overcome these inequities in cancer care, research, and the oncology workforce. We first explain why this is an ethical imperative, centering the discussion on lessons learned during 2020. We continue by describing ongoing equity-focused efforts by ASCO and other related professional medical organizations. We end with a call to action-all members of the oncology community have an ethical responsibility to take steps to address inequities in their clinical and academic work-and with guidance to practicing oncologists looking to optimize equity in their research and clinical practice.

Cognitive symptoms occur in almost all patients with brain tumors at varying points in the disease course. Deficits in neurocognitive function may be caused by the tumor itself, treatment (surgery, radiation, or chemotherapy), or other complicating factors (e.g., seizures, fatigue, mood disturbance) and can have a profound effect on functional independence and quality of life. Assessment of neurocognitive function is an important part of comprehensive care of patients with brain tumors. In the neuro-oncology clinic, assessment may include cognitive screening tools and inquiry into subjective cognitive function. Neuropsychological assessment is an important adjunct to identify cognitive symptoms and can be used as an opportunity to intervene through transformative feedback and treatment planning. Preventative measures can be taken to reduce cognitive side effects of treatment, such as awake craniotomies with intraoperative mapping during neurosurgery or prophylactic measures during radiation therapy (e.g., hippocampal avoidance, neuroprotectant treatment with memantine). Rehabilitative therapies, including cognitive rehabilitation and computerized cognitive exercise, are options for managing cognitive problems in an individualized manner. Pharmacotherapy, including use of stimulant medications and acetylcholinesterase inhibitors, has shown benefits for patients with brain tumors when tailored to an individual's cognitive profile. Identification and management of co-occurring issues, such as sleep disturbance, fatigue, and depression, can also improve neurocognitive function. There are promising therapies under development that may provide new options for treatment in the future. Integrating careful assessment and treatment of cognition throughout the disease course for patients with brain tumors can improve functional outcomes and quality of life.

Persistent disparities in the burden of breast cancer between African Americans and White Americans have been documented over many decades. Features characterizing breast cancer in the African American community include a 40% higher mortality rate, younger age distribution, greater advanced-stage distribution, increased risk of biologically aggressive disease such as the triple-negative phenotype, and increased incidence of male breast cancer. Public health experts, genetics researchers, clinical trialists, multidisciplinary oncology teams, and advocates must collaborate to comprehensively address the multifactorial etiology of and remedies for breast cancer disparities. Efforts to achieve breast health equity through improved access to affordable, high-quality care are especially imperative in the context of the COVID-19 pandemic and its disproportionately high economic toll on African Americans.

People experiencing homelessness are particularly vulnerable when diagnosed with pancreatic cancer. Patients with lower socioeconomic status have worse outcomes from pancreatic cancer as the result of disparities in access to treatment and barriers to navigation of the health care system. Patients with lower socioeconomic status, or who are vulnerably housed, are less likely to receive surgical treatment even when it is recommended by National Comprehensive Cancer Network guidelines. This disparity in access to surgical care explains much of the gap in pancreatic cancer outcomes. There are many factors that contribute to this disparity in surgical management of pancreatic cancer in people experiencing homelessness. These include a lack of reliable transportation, feeling unwelcome in the medical setting, a lack of primary care and health insurance, and implicit biases of health care providers, including racial bias. Solutions that focus on rectifying these problems include utilizing patient navigators, addressing implicit biases of all health care providers and staff, creating an environment that caters to the needs of patients experiencing homelessness, and improving their access to insurance and regional support networks. Implementing these potential solutions all the way from the individual provider to national safety nets could improve outcomes for patients with pancreatic cancer who are experiencing homelessness.

Effective delivery of cancer care via telehealth requires a planned care system that accounts for myriad patient, provider, and practice/cancer center resources before, during, and after the care episode. Telehealth is broadly defined as a method to have virtual, bidirectional communication between patients and providers. Telehealth can include methods such as audio-only, video-consultation, and tele-monitoring, which can occur in a synchronous, asynchronous, or blended format. The purpose of this review is to present common foundational principles for providing clinical cancer care via telehealth, followed by an overview of three distinct examples of comprehensive telehealth programs that have been developed to meet the needs of patients and families across the cancer trajectory, including survivorship, rehabilitation, and palliative care phases. The programs described are exemplars that were developed and implemented prior to the coronavirus pandemic, so they reflect many years of planning and evidence. Lessons learned include the need for ongoing patient support, clinician training, and cancer health system/practice programmatic considerations such as billing, scheduling, reimbursement, software, and hardware/platform security. Although the COVID-19 pandemic produced an explosive shift in regulations and implementation, sustainability of these changes may not be long-term. Nevertheless, a permanent shift in cancer care to include telehealth is likely here to stay.