Seminars in oncology最新文献

Lung cancer (both adenocarcinoma and squamous cell) progress through a series of pre-malignant histologic changes before the development of invasive disease. Each of these carcinogenic cascades is defined by genetic and epigenetic alterations in pulmonary epithelial cells. Additionally, alterations in the immune response, progenitor cell function, mutational burden, and microenvironmental mediated survival of mutated clones contribute to the risk of pre-malignant lesions progressing to cancer. Medical preventions studies have been completed and current and future trials are informed by the improved understanding of pre-malignancy. This will lead to precision chemoprevention trials based on lesional biology and histologic characteristics.

Two randomized trials have shown that lung cancer screening (LCS) with low dose computed tomography (LDCT) reduces lung cancer mortality in patients at high-risk for lung malignancy by identifying early-stage cancers, when local cure and control is achievable. The implementation of LCS in the United States has revealed multiple barriers to preventive cancer care. Rates of LCS are disappointingly low with estimates between 5%–18% of eligible patients screened. Equally concerning, follow-up after baseline screening is far lower than that of clinical trials (44-66% v >90%). To optimize the benefits of LCS, programs must identify and address factors related to LCS participation and follow-up while concurrently recognizing and mitigating barriers. As a relatively new screening test, the most effective processes for LCS are uncertain. Therefore, LCS programs have adopted a wide range of approaches without clearly established best practices to guide them, particularly in rural and resource-limited settings. In this narrative review, we identify barriers and facilitators to LCS, focusing on those studies in non-clinical trial settings — reflecting “real world” challenges. Our goal is to identify effective and scalable LCS practices that will increase LCS participation, improve adherence to follow-up, inform strategies for quality improvement, and support new research approaches.

Lung cancer is responsible for more deaths annually in the United States than breast, prostate and colon cancers combined. Lung cancer screening with annual low-dose computed tomography reduces lung cancer mortality in high-risk patients through early detection. The incidence of lung cancer is higher in the veteran population compared to the general population due, in part, to the prevalence of tobacco use. Early detection of lung cancer is therefore an important goal of the Veterans Health Administration (VHA), the largest integrated health care system in the United States. The following will review previous and current initiatives undertaken by the VHA to implement and expand access to lung cancer screening and will highlight target areas of interest to improve uptake and quality of lung cancer screening. Through these initiatives and programs, the VHA aims to provide high quality and equitable access to lung cancer screening for all Veterans that incorporates research that will improve outcomes and potentially inform and optimize the practice of Lung cancer screening across the United States.

The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past several decades, as a means of reducing lung cancer mortality, to identify asymptomatic disease when it is potentially curable. The National Lung Screening Trial (NLST) established that low-dose computed tomography (LDCT) scans of the chest can be instrumental in reducing lung cancer mortality but the criteria for screening implemented in this trial may not be equitably sensitive across racial and sex subpopulations. Furthermore, the high false detection rate reported in this trial has raised concerns regarding overdiagnosis with LDCT alone. The aim of this review is to summarize the history of lung cancer screening trials, limitations of lung cancer screening, the impact of alternative risk prediction models in reducing disparities, and the use of biomarkers in conjunction with imaging to improve diagnostic authenticity.

Unleashing the immune system to fight cancer has been a major breakthrough in cancer therapeutics since 2014 when anti-PD-1 antibodies (pembrolizumab and nivolumab) were approved for patients with metastatic melanoma. Therapeutic indications have rapidly expanded for many types of advanced cancer, including lung cancer. A variety of antibodies targeting the PD-1/PD-L1 checkpoint are contributing to this paradigm shift. The field now confronts two salient challenges: first, to improve the therapeutic outcome given the low response rate across the histologies; second, to identify biomarkers for improved patient selection. Pre-clinical and clinical studies are underway to evaluate combinatorial treatments to improve the therapeutic outcome paired with correlative studies to identify the factors associated with response and resistance. One of the emerging strategies is to combine epigenetic modifiers with immune checkpoint blockade (ICB) based on the evidence that targeting epigenetic elements can enhance anti-tumor immunity by reshaping the tumor microenvironment (TME). We will briefly review pleotropic biological functions of enhancer of zeste homolog 2 (EZH2), the enzymatic subunit of polycomb repressive complex 2 (PRC2), clinical developments of oral EZH2 inhibitors, and potentially promising approaches to combine EZH2 inhibitors and PD-1 blockade for patients with advanced solid tumors, focusing on lung cancer.

According to the literature, skin metastases affect 0.7%–10.4% of patients with malignant neoplasms of internal organs and may be 1 presentation of systemic spread of the cancer. Skin metastases may be the first sign of relapse after treatment and about 30% of cases of skin metastases are diagnosed before the diagnosis of internal organ cancer. Cutaneous metastases most often come from breast cancer and melanoma. They can present synchronous or metachronous. Adequate vigilance, combined with knowledge of the clinical picture and epidemiology, can contribute to accurate diagnosis and treatment. Clinically, skin metastases occur in the form of atypical solitary, painless nodules, or tumors. Lumps or infiltrating foci do not show clinical features that help in making a diagnosis. Skin changes are more accessible during physical examination, and it is easier to do a biopsy and provide histological assessment. Dermoscopy, a useful initial tool for the assessment of skin metastases, can lead to a rapid accurate diagnosis and treatment. Ultimately, the diagnosis of a metastatic malignancy is confirmed by histopathological examination.

Equity in oncology clinical trial participation has been declared a global priority. Australia is a key stakeholder in the global clinical trials sphere and managed to maintain high clinical trial activity during the COVID pandemic. Despite these successes, there is paucity of understanding about what influences clinical trial participation in Australia. In the international context, systematic reviews have highlighted that sociodemographic barriers, access to health care, clinical trial inclusion criteria, and attitudes of physicians and patients are factors which influence oncology trial participation. Exploring the factors in Australian health services which influence trial participation is now of significant importance. The lack of clear evidence directly highlights a need to assess the factors that influence oncology trial participation in Australia. We call for review of existing data to identify future directions in Australia which will potentially give deeper insights for the international clinical trial community.

Individuals with germline E-cadherin (CDH1) mutations are at high risk of developing diffuse gastric cancer (GC) and prophylactic total gastrectomy (PTG) represents the only life-saving treatment. We reviewed all PTGs reported in literature associated with CDH1 germline mutations. A total of 224 PTGs were reported. The majority were described in the United States of America (50%), the Netherlands (17.8%), and Canada (12.5%). GC was identified in 85.4% of cases after PTG, with a high rate of “no cancer” at histopathology identified in the United States of America (19.6%). Considering the mutation type, a total of 61 different germline mutations was reported, primarily non-missense versus missense alterations (86.9% v 13.1%). Twenty-one PTGs were performed in individuals with no family history of GC, and tumor was detected in 33.3% of investigated cases; regarding individuals with a family history of GC, tumor was identified in 85% of cases. PTG remains the best treatment for individuals harboring germline CDH1 mutations and fulfilling specific clinical criteria; in other CDH1-associated conditions, PTG should be suggested, but not strongly recommended. Additional studies are required to assess the cancer risk in those conditions.

Drug-drug interactions (DDIs) with anticancer drugs are common and can significantly affect efficacy and toxicity of treatment. Therefore, a Dutch Multidisciplinary Expert group is assessing the clinical significance of DDIs in oncology and provides recommendations for the management of these DDIs. We present an overview of methodology and outcome of an evidence- and consensus-based assessment of DDIs between anticancer drugs and non-anticancer drugs.

A literature search was performed through PubMed and EMA and FDA assessment reports, to identify potential DDI's involving anticancer drugs. For each potential DDI a concept report for risk analysis and practical advice for management was created. Subsequently, this risk analysis and the corresponding advice were assessed and weighed.

A total of 290 potential DDIs have been identified in the literature thus far. Of these 290 potential DDIs, the Expert Group has identified 94 (32%) DDIs as clinically relevant, with a need for an automated alert and a suggested intervention. Furthermore, 110 DDIs have been identified as clinically not relevant. For 86 potential DDIs evidence supporting a relevant DDI was insufficient and in these cases neither an alert nor advice regarding a suggested intervention were formulated.

A transparent risk analysis is presented for identification of clinically relevant DDIs with anticancer drugs. Integration of DDI guidelines into the national electronic prescribing system is essential to achieve optimal efficacy and minimal toxicity in patients receiving anticancer therapy. A clear overview of clinically relevant DDIs with anticancer therapy provides clinicians with a structured, evidence-based and consensus-built tool for anticancer therapy surveillance.