CA: A Cancer Journal for Clinicians最新文献

A 36-year-old woman presented to an outside hospital with abdominal pain in July of 2021. A computerized tomography (CT) scan of the abdomen and pelvis showed multiple, hypodense lesions within the left hepatic lobe that were concerning for metastatic disease. The largest liver lesion (3.1 × 2.2 cm) was biopsied, and pathology was consistent with metastatic, moderately differentiated adenocarcinoma. Immunohistochemistry (IHC) stains performed for further characterization of the tumor were positive for cytokeratin 7 (CK7) and CDX2 and negative for CK20, HepPar-1, Napsin A, and GATA-3, consistent with adenocarcinoma. The differential diagnosis included primary cholangiocarcinoma versus metastatic carcinoma of upper gastroesophageal or pancreaticobiliary origin. Of note, it was also suspected that the patient had amoebiasis, and she was on treatment with antibiotics. She later transferred her care to our university hospital. A follow-up CT scan of the abdomen and pelvis performed a few weeks after the initial presentation demonstrated hypodense liver lesions involving the right and left lobes as well as peripancreatic and gastrohepatic lymph nodes, which were suspicious for malignancy. Because the liver biopsy could not identify the primary tumor conclusively, subsequent endoscopic ultrasound and fine-needle aspiration of the peripancreatic lymph node were performed almost a month after the initial presentation.

The treatment paradigm of advanced CUP has remained the same for several years now. Patients with CUP are offered platinum-based and/or paclitaxel-based cytotoxic therapies at most oncology centers in a frontline setting, but the median survival remains 6–15 months.¹⁹ Attempts to treat based on tissue-of-origin identification in general have not yielded a survival advantage compared with empiric chemotherapy.⁵³

CUP is almost an ideal tumor for the incorporation of NGS-based therapeutic matching. With this strategy, genomics is the diagnosis.⁵⁴ Importantly, prior studies have shown that tailored combinations of drugs matched to a majority of the patients' genomic, transcriptomic, and immunomic alterations can be given safely (generally by using initial dose reductions and titrating the doses to tolerance) and that enhanced degrees of matching correlate with improvements in all outcome parameters across multiple tumor types, including CUP.^{3, 5, 6} Even patients, such as ours, in whom tissue is not available for NGS can have their cancer's genomic status interrogated by evaluating NGS on ctDNA derived from a small vial of blood. Indeed, the incorporation of blood-based NGS has further transformed this field and opened doors to more accessible and less time-consuming diagnostic tools that were almost unimaginable a decade ago

Overall, CUP is a heterogenous group of cancers that harbor distinct, characterizable molecular alterations

Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy—specifically hyperthermic intraperitoneal chemotherapy—with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.

Human papillomavirus (HPV) is currently linked to almost 35,000 new cases of cancer in women and men each year in the United States. Gardasil-9 (Merck & Company), the only HPV vaccine now available in the United States, is nearly 100% effective at preventing precancers caused by oncogenic HPV types. In the United States, however, only about one half of adolescents are up to date with HPV vaccination. It is well known that health care clinicians’ recommendations play a significant role in parents’ decisions regarding HPV vaccination. A growing body of literature examines specific communication strategies for promoting uptake of the HPV vaccine. A comprehensive review of the evidence for each of these strategies is needed. The authors searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Complete databases for original articles with a defined clinician communication strategy and an outcome of HPV vaccine uptake or intention to vaccinate (PROSPERO registry no. CRD42020107602). In total, 46 studies were included. The authors identified two main strategies with strong evidence supporting their positive impact on vaccine uptake: strong recommendation and presumptive recommendation. Determinations about a causal relationship were limited by the small numbers of randomized controlled trials. There is also opportunity for more research to determine the effects of motivational interviewing and cancer-prevention messaging.

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5–1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract—primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.

Previous studies using data from the early 2000s demonstrated that patients who were uninsured were more likely to present with late-stage disease and had worse short-term survival after cancer diagnosis in the United States. In this report, the authors provide comprehensive data on the associations of health insurance coverage type with stage at diagnosis and long-term survival in individuals aged 18–64 years who were diagnosed between 2010 and 2013 with 19 common cancers from the National Cancer Database, with survival follow-up through December 31, 2019. Compared with privately insured patients, Medicaid-insured and uninsured patients were significantly more likely to be diagnosed with late-stage (III/IV) cancer for all stageable cancers combined and separately. For all stageable cancers combined and for six cancer sites—prostate, colorectal, non-Hodgkin lymphoma, oral cavity, liver, and esophagus—uninsured patients with Stage I disease had worse survival than privately insured patients with Stage II disease. Patients without private insurance coverage had worse short-term and long-term survival at each stage for all cancers combined; patients who were uninsured had worse stage-specific survival for 12 of 17 stageable cancers and had worse survival for leukemia and brain tumors. Expanding access to comprehensive health insurance coverage is crucial for improving access to cancer care and outcomes, including stage at diagnosis and survival.

Two new studies examine COVID-19 from the perspective of cancer survivors. One of the studies, which appears in the Journal of the National Cancer Institute (JNCI) (doi:10.1093/jnci/djab012), examines the prevalence among cancer survivors of medical factors associated with severe COVID-19 disease. The other study, published in the Journal of the National Comprehensive Cancer Network (JNCCN) (doi:10.6004/jnccn.2021.7113), compares the incidence of adverse events among cancer survivors and persons without a history of cancer after SARS-CoV-2 vaccination.

Considered together, these 2 studies should help reassure cancer survivors regarding the safety of COVID19 vaccination and should alert them to their increased risk of severe outcomes from SARS-CoV-2 infection.

For the JNCI study, researchers from the Roswell Park Comprehensive Cancer Center and the American Cancer Society used the 2016 to 2018 National Health Interview Survey to identify 6411 cancer survivors and 77,748 adults without a history of cancer in the United States. Excluded were nearly 3000 subjects with nonmelanoma skin cancer exclusively or those who were diagnosed with cancer before they turned 18 years old. The researchers noted the sociodemographic variables of the included subjects, including where they lived and their age, sex, race, ethnicity, educational level, insurance status, and personal economic levels.

The researchers found that 56.4% of the cancer survivors had 1 or more of the underlying risk factors that prior studies had shown to be associated with severe COVID-19 disease, and 22.9% had at least 2. By contrast, only 41.6% of those without a cancer history reported at least 1 and only 10.8% reported 2 or more risk factors. Obesity ranked as the most common risk factor among cancer survivors (30.8%), followed by heart diseases (25.1%), diabetes (17.0), chronic obstructive pulmonary disease (9.2%), and chronic kidney disease 5.6%.

In the JNCCN study, researchers noted that the majority of safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, despite the greater risk that these patients have to contract SARS-CoV-2 and become seriously ill. Between February 16, 2021, and May 15, 2021, they enrolled 2033 participants in a prospective, observational study conducted at the Fox Chase Cancer Center in Philadelphia, Pennsylvania. Each study participant received 2 doses of the Pfizer BNT162b2 vaccine, with the second doses administered 3 weeks after the first. There were 2 surveys given to the subjects. The first survey, asking about adverse reactions to dose 1 of the vaccine, was completed in person at the time of the second dose by 1752 patients. The second survey was completed either by telephone or online approximately 2 weeks after the second vaccine dose by 1260 participants. There were reports of COVID-19 infection before vaccination by 3.4% of all respondents. Of the 1753 patients who completed at lea

Anew study reports that breast cancer (BC) survivors are at a greater risk for diabetes, high blood pressure, and dyslipidemia than women who have never been treated for BC. Appearing in the Journal of Clinical Oncology (doi:10.1200/JCO.21.01738), the study is based on data derived from the Pathways Heart Study at Kaiser Permanente Northern California (KPNC).

The researchers accessed the electronic health records of more than 4.5 million KPNC members at 21 hospitals and over 260 outpatient clinics in Northern California to identify women who were diagnosed with invasive BC between 2005 and 2013 and who were at least aged 21 years old. They identified 14,942 BC survivors and a control group of 74,702 women without a history of BC who had a similar age, race and ethnicity.

The researchers obtained data regarding each subject’s sociodemographic characteristics, including birth year, race, ethnicity, household income, and education level. They also included data on body mass index, menopausal status, smoking status, and whether the subjects had previously been diagnosed with a cardiometabolic condition. Clinical data for BC subjects included their tumor laterality and other characteristics, and details about their diagnosis and care, including the treatments they underwent, laboratory results, pharmacy records, and survival.

Two years after their cancer diagnosis, the cumulative incidence of hypertension in BC survivors was 10.9% versus 8.9% in the women without BC, although this difference was no longer present by 10 years post-diagnosis. A higher cumulative incidence of diabetes in BC survivors was evident after 2 years of follow-up (2.1% vs 1.7%) and remained so at 10 years of follow-up (9.3% vs 8.8%). The multivariable hazard ratio for diabetes in BC survivors (relative to control subjects) was 1.16 (95% CI, 1.07-1.26). Hazard ratios for diabetes were even higher in BC survivors who received chemotherapy (1.23; 95% CI, 1.11-1.38), left-sided radiation therapy (1.29; 95% CI, 1.13- 1.48), or endocrine therapy (1.23; 95% CI, 1.12-1.34). The multivariable hazard ratio for hypertension was not significantly higher in BC survivors overall (relative to control subjects), yet was significantly higher in subgroups of patients who had received left-sided radiation therapy (1.11; 95% CI, 1.02-1.21) and endocrine therapy (1.10; 95% CI, 1.03-1.16).

Although being overweight is associated with diabetes, hypertension, and postmenopausal breast cancer, even BC survivors who were not overweight at the time of their diagnosis faced a significantly higher risk of developing diabetes and high blood pressure relative to the control subjects without breast cancer.

“We believe our study builds on and contributes to the growing clinical field of cardio-oncology,” says Dr. Kwan. She notes that over the past decade, oncologists and cardiologists have begun to work closely together to meet the needs of patients with cancer who have r

The number of cancer survivors continues to increase in the United States due to the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate triennially to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries, vital statistics from the Centers for Disease Control and Prevention’s National Center for Health Statistics, and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Database are presented for the most prevalent cancer types by race, and cancer-related and treatment-related side-effects are also briefly described. More than 18 million Americans (8.3 million males and 9.7 million females) with a history of cancer were alive on January 1, 2022. The 3 most prevalent cancers are prostate (3,523,230), melanoma of the skin (760,640), and colon and rectum (726,450) among males and breast (4,055,770), uterine corpus (891,560), and thyroid (823,800) among females. More than one-half (53%) of survivors were diagnosed within the past 10 years, and two-thirds (67%) were aged 65 years or older. One of the largest racial disparities in treatment is for rectal cancer, for which 41% of Black patients with stage I disease receive proctectomy or proctocolectomy compared to 66% of White patients. Surgical receipt is also substantially lower among Black patients with non-small cell lung cancer, 49% for stages I-II and 16% for stage III versus 55% and 22% for White patients, respectively. These treatment disparities are exacerbated by the fact that Black patients continue to be less likely to be diagnosed with stage I disease than White patients for most cancers, with some of the largest disparities for female breast (53% vs 68%) and endometrial (59% vs 73%). Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based strategies and equitable access to available resources are needed to mitigate disparities for communities of color and optimize care for people with a history of cancer. CA Cancer J Clin. 2022;72:409-436.

Depression is highly prevalent in those diagnosed with cancer and is also associated with poorer prognostic outcomes. Mindfulness-based interventions are effective in reducing depressive symptoms and improving quality of life in patients with cancer. The objective of this review was to investigate whether mindfulness practices can improve survival and, if so, what mechanisms of action may contribute to these outcomes. Although no long-term studies have investigated this hypothesis, the current literature supports an inflammatory basis for depression, implicating proinflammatory cytokines and hypothalamic-pituitary-adrenal axis dysfunction as contributing factors. Markers of inflammation, such as interleukin-6, tumor necrosis factor-α, and cortisol, are all found at elevated concentrations in many depressed individuals. These exact mechanisms are associated with higher mortality in patients with cancer. Mindfulness has been studied for its effects on cytokine and cortisol levels, and there are promising data to support that the intervention can measurably decrease inflammation. Therefore, it is conceivable that mindfulness programs can affect survival in this population. There are limited data on the long-term effects of mindfulness on depression and inflammatory markers in patients with cancer, and there are potential barriers to the implementation of mindfulness-based interventions as part of a comprehensive treatment plan. Therefore, it is necessary to further explore these questions through longitudinal studies to establish a survival correlation. CA Cancer J Clin. 2022;72:490-502.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.