CA: A Cancer Journal for Clinicians最新文献

Early results from the first study comparing active monitoring to surgery for patients with low-risk ductal carcinoma in situ (DCIS) support the short-term safety of active monitoring.

Researchers released the 2-year findings from a prospective, randomized clinical trial known as the Comparing an Operation to Monitoring With or Without Endocrine Therapy (COMET) study. Results showed that the rate of invasive cancer in both groups was low, but patients who had surgery (or guideline-concordant care) for DCIS had a slightly higher rate of invasive cancer than the group that underwent active monitoring. Although the study is a preliminary analysis, investigators are encouraged by the findings.

“I don’t think we have enough long-term data yet to offer active monitoring to DCIS patients, because two years is pretty short, but if these results are supported and durable at five years, we may be able to start offering it as a possible option,” says coprincipal investigator Shelley Hwang, MD, MPH, who is the vice-chair of research in the Department of Surgery at the Duke Cancer Institute in Durham, North Carolina. “The results are very provocative in terms of turning the assumption that we’ve always had on its head, and that’s why it’s such an important study—because it challenges dogma.”

Dr Hwang and her colleagues presented the COMET study results in December 2024 at the San Antonio Breast Cancer Symposium. Findings were concurrently published in the Journal of the American Medical Association (doi:10.1001/jama.2024.26698).

The trial enrolled 995 women aged 40 years or older with a new diagnosis of hormone receptor–positive grade 1 or 2 DCIS without invasive cancer. Participants were enrolled at 100 US Alliance Cooperative Group clinical trial sites from 2017 to 2023. They were randomized, with 484 participants assigned to active monitoring and 473 assigned to receive surgery. Participants will be followed for 10 years.

The main purpose is to determine if DCIS, which is also called stage 0 breast cancer, needs to be treated with surgery in every patient.

“We’ve never really put our treatments to that sort of test because everyone has been really fearful of doing anything less,” Dr Hwang says.

The study excluded patients who were hormone receptor–negative as well as those who had a physical finding such as a lump, bloody discharge, or changes in the skin. Patients were allowed to enter the study regardless of the size of their DCIS.

Active monitoring, with or without endocrine therapy, included follow-up breast imaging along with a physical examination every 6 months. Although endocrine therapy was not mandatory, more than 70% chose to receive it. Guidance-concordant care was surgery with or without radiation therapy and with or without endocrine therapy. This group also had 6-month follow-ups.

The primary outcome of the preliminary analysis was the 2-year cumulative risk of an invasive breas

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of all ovarian cancer cases and contributing significantly to the high mortality rates associated with this disease. Because of the asymptomatic nature of early stage disease, most patients are diagnosed at advanced stages when the cancer has already spread into the abdominal cavity, requiring complex and intensive surgical and chemotherapeutic interventions followed by maintenance therapies. Although a minority of cases are associated with well defined genetic syndromes, specific risk factors and a clear etiology in many cases remain elusive. HGSOC tumors are characterized by a high frequency of somatic gene copy number alterations, often associated with defects in homologous recombination repair of DNA. All attempts to introduce an effective screening for HGSOC to date have been unsuccessful. This review elucidates the complexities surrounding HGSOC and encompasses its etiology, epidemiology, classification, pathogenesis, and the current array of treatment strategies. Understanding molecular underpinnings is crucial for the development of targeted therapies and personalized multimodal treatment approaches in centralized therapeutic structures. This review also examines the importance of the tumor microenvironment. In addition, the authors' objective is to underscore the critical importance of placing the patient's perspective and diversity at the forefront of therapeutic strategies, thereby fostering a genuinely participatory decision-making process and ultimately improving patient quality of life.

The peripheral T-cell lymphomas (PTCL) are the only disease for which four histone deacetylase (HDAC) inhibitors have been approved globally as single agents. Although it is not clear why the PTCL exhibit such a vulnerability to these drugs, understanding the biological basis for this activity is essential. Many lines of data have established that the PTCL exhibit marked sensitivity to other epigenetically targeted drugs, including EZH2 and DNMT3 (DNA-methyltransferase 3) inhibitors. Even more compelling is the finding that combinations of drugs targeting the epigenetic biology of PTCL are beginning to produce provocative data, leading some to wonder if these agents can replace historical chemotherapy regimens routinely used for patients with the disease. Simultaneously, the field has identified a spectrum of mutations in genes governing epigenetic biology in many subtypes of PTCL, although the T follicular helper lymphomas, including angioimmunoblastic T-cell lymphoma, appear to be particularly enriched for these genetic features. While the direct relationship between the presence of any one of these mutations and responsiveness to a particular epigenetic drug has yet to be established, it is increasingly accepted that the PTCL may be the prototypical epigenetic disease as no other form of cancer has exhibited such a vulnerability to this diversity of epigenetically targeted agents. Herein, we comprehensively review this esoteric and rapidly evolving field to identify themes and lessons from these experiences that may guide efforts to improve outcomes of patients with T-cell neoplasms. Furthermore, we will discuss how these concepts might be applied to the broader field of cancer medicine.

Cancer molecular imaging is the noninvasive visualization of a process unique to or altered in neoplasia, such as proliferation, glucose metabolism, and receptor expression, which is relevant to patient management. Several molecular imaging modalities are now available, including magnetic resonance, optical, and nuclear imaging. Nuclear imaging, particularly using fluorine-18–fluorodeoxyglucose positron emission tomography, is widely used in the staging and response assessment of multiple cancer types. However, at this writing, new nuclear medicine probes, especially positron emission tomography tracers, are increasingly used or are being investigated for cancer evaluation. This review focuses on these probes, their biologic targets, and the applications or potential applications for their use in the assessment of various neoplasms, including both probes available for commercial use—such as somatostatin receptor ligands in neuroendocrine tumors, prostate-specific membrane antigen ligands in prostate cancer, norepinephrine analogs in neural crest tumors like neuroblastoma, and estrogen analogs in breast cancer—and others in clinical development, such as fibroblast-activating protein inhibitors, C-X-C chemokine receptor type 4 ligands, and monoclonal antibodies targeting receptor tyrosine kinases, CD4-positive or CD8-positive tumor-infiltrating lymphocytes, tumor-associated macrophages, and cancer stem cell biomarkers. These developments represent a major step toward the integration of molecular imaging as a powerful tool in precision medicine, with an expectedly significant impact on patient management and outcome.

Individuals from rural areas in the United States suffer higher rates of morbidity and mortality from cancer than their urban counterparts. This review is based on the idea that equity—the elimination of unnecessary and preventable differences between groups of individuals—should underlie access to cancer care resources for patients from rural areas. Access to cancer clinical trials serves as the framework for identifying and understanding barriers in access to quality oncologic care. The authors discuss the interplay between rural living, socioeconomic status, culture, and health; and they highlight how economic considerations in rural areas often limit access to clinical trials and oncologic care because economies of scale do not apply in these regions given the requirement for high-quality oncology care even with lower patient volumes. The authors propose solutions to enhance access to clinical trials and improve the quality of oncologic care in rural areas, viewing these aims as ethical and moral imperatives.

Patients living in rural communities who have chronic diseases, including cancer, have inferior survival compared to those living in urban areas. In this issue, Unger et al. provide an excellent overview of factors that challenge rural patients while highlighting how clinical trial availability can improve rural outcomes.¹ They discuss delayed diagnosis, underinsurance, provider shortages, the higher incidence of comorbid illness and poverty, and other factors. All of these are commonly recognized factors that contribute to inferior outcomes for patients with cancer in rural communities. However, there are less well known challenges facing both patients and providers in rural areas that may result in persistent and poorer outcomes, even when more well known factors may be overcome. These factors are important not only because they contribute to cancer care decisions and outcomes but because they also compound the reluctance of patients living in rural areas to participate in clinical trials.

Rural practices exist in densely populated states like New York, Washington, and Pennsylvania and in large, underpopulated states like Wyoming, Alaska, and the Dakotas. Patients from these latter locations face chronic provider shortages as well as the challenge of long drives for routine care. Both of these result in patients tending to ignore early signs and symptoms that may appear minor but contribute to delayed diagnosis.¹ What is under-recognized is the lack of public transportation in these rural states to help patients get to and from chemotherapy appointments, whether in outlying communities or in rural towns. Finding rides for treatment, especially because of post-treatment malaise, fatigue, or nausea (which can make driving home unsafe), is a challenge that leads many to abandon cancer care. The long drives often required in rural areas go beyond a barrier for patient access. There exists an increased risk of road closure because of wind, snow, poor visibility, or accidents, leading to more frequently interrupted care. Closed roads affect the ability of courier and mail services to deliver necessary chemotherapy drugs to patients or even to the hospital. The lack of neighboring hospitals means one cannot tap another facility for a loan (a cup of chemo, as it were) to tide a patient over. This also results in delayed and often repeated cycles of interrupted chemotherapy. The effect on clinical trials is felt in the delayed delivery of trial drugs, delayed visits for time-sensitive clinical trial toxicity assessments, and even on-study required blood draws.

Local free housing close to treatment areas is offered in some rural sites, but this housing may not allow relatives or pets and results in a sense of isolation of patients from their sources of emotional support. Thus, even when available, free local housing is underused.

Although a hub-and-spoke model of decentralized ca

Lung cancer mortality rates in the United States have declined steeply in recent decades, largely because of substantial reductions in smoking prevalence, as approximately 85% of lung cancer deaths are attributable to cigarette smoking. In this study, the authors estimate the number of averted lung cancer deaths and corresponding person-years of life gained during 1970–2022 as a measure of progress in cancer prevention through tobacco control. By using the 1970–2022 National Center for Health Statistics mortality data (with national coverage), the authors calculated the expected number of deaths for each year, age, sex, race, and age group based on the expected lung cancer death rate multiplied by the population at risk in that group. The number of averted lung cancer deaths were calculated by subtracting the observed number of deaths from the expected number in each group. Person-years of life gained were estimated as a measure of avoided premature mortality based on the average additional years a person would have lived if they had not died from lung cancer. The authors estimated that 3,856,240 lung cancer deaths (2,246,610 in men, 1,609,630 in women) were averted, and 76,275,550 person-years of life (40,277,690 in men, 35,997,860 in women) were gained during 1970–2022, with an average of 19.8 person-years of life gained (17.9 in men, 22.4 in women) per averted death. The number of averted lung cancer deaths accounted for 51.4% of the estimated declines in overall cancer deaths and was substantially greater in men (60.1%) than in women (42.7%). By race, this proportion was 53.6% in the White population (62.8% in men, 44.6% in women) and 40.0% in the Black population (44.4% in men, 34.7% in women). The substantial estimated numbers of averted lung cancer deaths and person-years of life gained highlight the remarkable effect of progress against smoking on reducing premature mortality from lung cancer.