The 50 most-cited articles in Cancer, 2021

The relative importance of cardiovascular disease (CVD) and cancer as leading causes of premature death are examined in this communication. CVD and cancer are now the leading causes in 127 countries, with CVD leading in 70 countries (including Brazil and India) and cancer leading in 57 countries (including China). Such observations can be seen as part of a late phase of an epidemiologic transition, taking place in the second half of the 20th century and the first half of the present one, in which the dominance of infectious diseases is progressively superseded by noncommunicable diseases. According to present ranks and recent trends, cancer may surpass CVD as the leading cause of premature death in most countries over the course of this century. Clearly, governments must factor in these transitions in developing cancer policies for the local disease profile.

The 2016 revised fourth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporated molecular features with histologic grading, revolutionizing how oncologists conceptualize primary brain and spinal cord tumors as well as providing new insights into their management and prognosis. The 2021 revised fifth edition of the WHO classification further integrates molecular alterations for CNS tumor categorization, updating current understanding of the pathophysiology of many of these disease entities. Here, the authors review changes in the new classification for the most common primary adult tumors-gliomas (including astrocytomas, oligodendrogliomas, and ependymomas) and meningiomas-highlighting the key genomic alterations for each group classification to help clinicians interpret them as they consider therapeutic options-including clinical trials and targeted therapies-and discuss the prognosis of these tumors with their patients. The revised, updated 2021 WHO classification also further integrates molecular alterations in the…

BACKGROUND: Several important treatment and supportive care strategies have been implemented over the past 4 decades in the management of acute myeloid leukemia (AML). METHODS: The authors identified 29,107 patients who were diagnosed with de novo AML between 1980 and 2017 in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Patients were categorized into 5 age groups (ages birth to 14, 15-39, 40-59, 60-69, and ≥70 years) and 4 calendar periods (1980-1989, 1990-1999, 2000-2009, and 2010-2017). The outcomes of patients who had AML within these categories were analyzed. RESULTS: The overall 5-year survival rates in patients with AML were 9%, 15%, 22%, and 28% in the decades 1980 to 1989, 1990 to 1999, 2000 to 2009, and 2010 to 2017, respectively. Among patients aged 15 to 39 years, the 5-year survival rates were 24%, 41%, 52%, and 63%, respectively; among those aged ≥70 years, the 5-year survival rates were 1%, 2%, 3%, and 5%, respectively. Four-week mortality was surprising high among adults and older patients (range, 20%-45%), even in modern…

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan.…

BACKGROUND: Cervical cancer is 1 of the most common cancers in females worldwide. Understanding the most recent global patterns and temporal trends of cervical cancer burden might be helpful for its prevention and control. METHODS: Data on cervical cancer (International Classification of Diseases, Tenth Revision, code C53) incidence and mortality in 2018 were extracted from the GLOBOCAN 2018 database and further analyzed for their correlations with the Human Development Index. Temporal trends were analyzed using the annual percent change with joinpoint analysis among 31 countries with highly qualified data from the Cancer Incidence in Five Continents Plus and World Health Organization mortality databases. Future trends for the next 15 years were predicted using an open-source age-period-cohort model. RESULTS: Cervical cancer incidence and mortality rates were both negatively correlated with the Human Development Index (r = -0.56 for incidence, r = -0.69 for mortality; P < .001) in cross-sectional analysis, and both remained stable in 12 countries or even decreased in 14 and 18…

The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. The notable subsets of AML include acute promyelocytic leukemia (APL), core-binding factor AML (CBF-AML), AML in younger patients fit for intensive chemotherapy, and AML in older/unfit patients (usually at the age cutoff of 60-70 years). We also consider within each subset whether the AML is primary or secondary (therapy-related, evolving from untreated or treated myelodysplastic syndrome or myeloproliferative neoplasm). In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80%. Treatment of CBF-AML with fludarabine,…

BACKGROUND: Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment. METHODS: A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one-stage meta-analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC). RESULTS: Three hundred fifty-nine women with…

BACKGROUND: The global burden of gallbladder and biliary tract cancer (GBTC) is increasing. A comprehensive evaluation of the burden is crucial to improve strategies for GBTC prevention and treatment. METHODS: The incidence rates, mortality, and disability-adjusted life years (DALYs) of GBTC from 1990 to 2017 were extracted from the Global Burden of Diseases Study (GBD) 2017. Estimated annual percent changes (EAPCs) were calculated to quantify GBTC trends during the study period. RESULTS: Globally, there were 210,878 new cases, 173,974 deaths, and 3,483,046 DALYs because of GBTC in 2017. GBTC incidence increased by 76%, mortality increased by 65%, and DALYs increased by 52% from 1990 to 2017. In addition, relatively higher Socio-Demographic Index regions had greater incidence and death rates but greatly decreased age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). At the national level, Chile had the highest ASIR (10.38 per 100,000 population) and the highest ASDR (10.43 per 100,000 population) in 2017. The largest increases in ASIR (EAPC, 3.38) and ASDR…

Background TP53 mutation (TP53mut) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53mut confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53mut AML who were treated with a 10‐day decitabine and venetoclax (DEC10‐VEN) (ClinicalTrials.gov identifier NCT03404193). Methods Patients with newly diagnosed AML received decitabine 20 mg/m2 for 10 days every 4 to 6 weeks for induction, followed by decitabine for 5 days after response. The venetoclax dose was 400 mg daily. TP53mut was identified in bone marrow samples using next‐generation sequencing, with sensitivity of 5%. Outcomes were analyzed according to European LeukemiaNet 2017 guidelines. Results Among 118 patients (median age, 72 years; age range, 49‐89 years), 63 (53%) had secondary AML, 39 (33%) had AML with complex karyotype, and 35 (30%) had TP53mut AML. The median TP53 variant allele frequency was 32% (interquartile range, 16%‐65%), 8 patients (23%) had…

BACKGROUND: On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg. METHODS: DREAMM-2 is an ongoing, phase 2, open-label, 2-arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti-CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee. RESULTS: As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty-one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%-43.6%) achieved an overall response, and 18 responders achieved a very…

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of…

BACKGROUND: Fear of cancer recurrence (FCR) is more intense in younger women. Because FCR is a powerful determinant of quality of life, identifying those at risk for persistently elevated FCR can inform timing of interventions. METHODS: A total of 965 women with stage 0 to stage III breast cancer enrolled in the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with breast cancer at age ≤40 years, completed the 3-item Lasry Fear of Recurrence Index. Group-based trajectory modeling was used to classify distinct FCR patterns from baseline through 5 years post-diagnosis. Multinomial logistic regression was used to identify patient, disease, and treatment characteristics associated with each trajectory. RESULTS: Five FCR trajectories were identified with the majority of participants having moderate (33.1%) or high FCR (27.6%) that improved over time. A total of 6.9% participants had moderate FCR that worsened, whereas 21.7% had high FCR at baseline that remained high throughout. In the fully adjusted multinomial model, stages II and III (vs stage I) were…

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) data from 1973-2010 have been used to show that minority women have disproportionately higher percentages of breast cancers diagnosed at younger ages in comparison with White women. METHODS: The authors analyzed SEER 21 invasive breast cancer incidence data for 2014-2017 and National Center for Health Statistics mortality data for 2014-2018 and compared invasive incidence and mortality by age in non-Hispanic Black (NH-Black), Asian American/Pacific Islander (AAPI), Native American, and Hispanic women with those in non-Hispanic White (NH-White) women. They evaluated incidence rates and percentages of invasive breast cancer cases and breast cancer deaths occurring before the age of 50 years along with advanced-stage incidence rates and percentages in minority women versus NH-White women. RESULTS: Recent SEER data showed that invasive breast cancers were diagnosed at significantly younger ages in minority women versus NH-White women. Among women diagnosed with invasive breast cancer, compared with NH-White women, minority…

BACKGROUND: The authors previously reported the results of the nonpancreatic neuroendocrine neoplasm cohort of the SWOG S1609 DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial, which permitted all histologic grades and had a 44% overall response rate (ORR) among patients with high-grade disease. Here they sought to validate their findings in a dedicated prospective cohort of high-grade neuroendocrine neoplasms within S1609. METHODS: A prospective, open-label, multicenter, phase 2 clinical trial of ipilimumab plus nivolumab was conducted across multiple rare tumor cohorts. The dedicated, high-grade neuroendocrine neoplasm cohort was examined here. The primary end point was the ORR according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Nineteen patients with high-grade neuroendocrine neoplasms (defined by local pathology review) were enrolled in this cohort of S1609. The most common primary sites were unknown primaries (21%), which were…

BACKGROUND: Current treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of the anti-programmed death 1 (anti-PD-1) immunotherapy, pembrolizumab, in programmed death ligand 1 (PD-L1)-positive, recurrent glioblastoma. METHODS: Adult patients with PD-L1-positive tumors were enrolled in the recurrent glioblastoma cohort of the multicohort, phase 1b KEYNOTE-028 study (ClinicalTrials.gov identifier, NCT02054806) and received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years. The primary endpoint was investigator-assessed overall response rate according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Archival tumor samples were assessed for PD-L1 expression levels (prospectively) and T-cell-inflamed gene expression profile score (retrospectively). RESULTS: After a median follow-up of 14 months (range, 2-55 months) among the 26 enrolled patients, the overall response rate was 8% (95% CI, 1%-26%). Two partial responses, lasting 8.3 and 22.8 months, occurred. Progression-free survival (median, 2.8 months; 95%…

BACKGROUND: Social determinants of health (SDOHs) cluster together and can have deleterious impacts on health outcomes. Individually, SDOHs increase the risk of cancer mortality, but their cumulative burden is not well understood. The authors sought to determine the combined effect of SDOH on cancer mortality. METHODS: Using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, the authors studied 29,766 participants aged 45+ years and followed them 10+ years. Eight potential SDOHs were considered, and retained SDOHs that were associated with cancer mortality (P < .10) were retained to create a count (0, 1, 2, 3+). Cox proportional hazard models estimated associations between the SDOH count and cancer mortality through December 31, 2017, adjusting for confounders. Models were age-stratified (45-64 vs 65+ years). RESULTS: Participants were followed for a median of 10.6 years (interquartile range [IQR], 6.5, 12.7 years). Low education, low income, zip code poverty, poor public health infrastructure, lack of health insurance, and social isolation were…

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions in treatment for cancer. Less is known about its impact on new cancer diagnoses, where delays could cause worsening long-term outcomes. This study quantifies decreases in encounters related to prostate, lung, bladder and colorectal cancers, procedures that facilitate their diagnosis, and new diagnoses of those cancers in the COVID era compared to pre-COVID era. METHODS: All encounters at Veterans' Affairs facilities nationwide from 2016 through 2020 were reviewed. The authors quantified trends in new diagnoses of cancer and in procedures facilitating their diagnosis, from January 1, 2018 onward. Using 2018 to 2019 as baseline, reductions in procedures and new cancer diagnoses in 2020 were estimated. Calculated absolute and percentage differences in annual volume and observed-to-expected volume ratios were calculated. Heat maps and funnel plots of volume changes were generated. RESULTS: From 2018 through 2020, there were 4.1 million cancer-related encounters, 3.9 million relevant procedures, and 251,647…

BACKGROUND: The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. METHODS: This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%). RESULTS: The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In…

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited. METHODS: This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years. RESULTS: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS…

BACKGROUND: Cancer survivors develop other chronic medical conditions because of shared risk factors and delayed effects of cancer treatment. This study investigated trends in the prevalence of chronic diseases and estimated their population sizes among adult cancer survivors in the United States from 2002 to 2018. METHODS: Using 2002-2018 National Health Interview Survey data, this study calculated the age-sex-race/ethnicity-adjusted prevalences and estimated the population sizes for the following chronic conditions among cancer survivors: hypertension, diabetes, stroke, heart disease, chronic obstructive pulmonary disease (COPD)/asthma, hepatitis, arthritis, liver disease, kidney disease, and morbid obesity. This study also examined multiple chronic conditions (MCC; 3 or more health conditions). MCC trends were further examined by sociodemographic factors to identify high-risk populations. Parallel analyses were performed for participants without a cancer history to provide a reference. RESULTS: Among 30,728 cancers survivors, increasing trends were observed in the prevalence of…

BACKGROUND: Research into the clustering of symptoms may improve the understanding of the underlying mechanisms that affect survivors' symptom burden. This study applied network analyses in a balanced sample of cancer survivors to 1) explore the clustering of symptoms and 2) assess differences in symptom clustering between cancer types, treatment regimens, and short-term and long-term survivors. METHODS: This study used cross-sectional survey data, collected between 2008 and 2018, from the population-based Patient Reported Outcomes Following Initial Treatment and Long Term Evaluation of Survivorship registry, which included survivors of 7 cancer types (colorectal cancer, breast cancer, ovarian cancer, thyroid cancer, chronic lymphocytic leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma). Regularized partial correlation network analysis was used to explore and visualize the associations between self-reported symptoms (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire) and the centrality of these symptoms in the network (ie, how strongly a…

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period…

BACKGROUND: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials. METHODS: UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy. RESULTS: The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets…

BACKGROUND: To understand how health care delays may affect breast cancer detection, the authors quantified changes in breast-related preventive and diagnostic care during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Eligible women (N = 39,444) were aged ≥18 years and received a screening mammogram, diagnostic mammogram, or breast biopsy between January 1, 2019 and September 30, 2020, at 7 academic and community breast imaging facilities in North Carolina. Changes in the number of mammography or breast biopsy examinations after March 3, 2020 (the first COVID-19 diagnosis in North Carolina) were evaluated and compared with the expected numbers based on trends between January 1, 2019 and March 2, 2020. Changes in the predicted mean monthly number of examinations were estimated using interrupted time series models. Differences in patient characteristics were tested using least squares means regression. RESULTS: Fewer examinations than expected were received after the pandemic's onset. Maximum reductions occurred in March 2020 for screening mammography (-85.1%; 95% CI,…

This commentary provides a concise overview of the epidemiology of cancer survivorship and work, common functional limitations experienced by cancer survivors, and evidence‐based recommendations for interventions available to improve function. It also describes the US Social Security Administration's disability claims process, its eligibility requirements, and barriers for long‐term survivors in securing approval for disability claims, and offers insights for practicing clinicians in holistically addressing functional limitations in practice.

Background The number of patients with atrial fibrillation (AF) and cancer is rapidly increasing in clinical practice. The impact of cancer on clinical outcomes in this patient population is unclear, as is the performance of the HAS‐BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol) and CHA2DS2‐VASc (Congestive Heart Failure, Hypertension, Age ≥ 75 years, Diabetes Mellitus, Stroke or Transient Ischemic Attack, Vascular Disease, Age 65 to 74 Years, Sex Category) scores. Methods This was an observational, retrospective cohort study including 2,435,541 adults hospitalized with AF. The authors investigated the incidence rates (IRs) of all‐cause and cardiovascular mortality, ischemic stroke, major bleeding, and intracranial hemorrhage (ICH) according to the presence of cancer and cancer types. Results Overall, 399,344 (16.4%) had cancer, with the most common cancers being metastatic, prostatic, colorectal, lung, breast, and bladder. During a mean follow‐up of 2.0 years, cancer increased all‐cause mortality…

BACKGROUND: Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. METHODS: The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. RESULTS: The median follow-up was 32.6 months (range, 12.4-240…

BACKGROUND: Historically, the prognosis for patients who have melanoma brain metastasis (MBM) has been dismal. However, breakthroughs in targeted and immunotherapies have improved long-term survival in those with advanced melanoma. Therefore, MBM presentation, prognosis, and the use of multimodality central nervous system (CNS)-directed treatment were reassessed. METHODS: In this retrospective study, the authors evaluated patients with MBM who received treatment at Memorial Sloan Kettering Cancer Center between 2010 and 2019. Kaplan-Meier methodology was used to describe overall survival (OS). Recursive partitioning analysis and time-dependent multivariable Cox modeling were used to assess prognostic variables and to associate CNS-directed treatments with OS. RESULTS: Four hundred twenty-five patients with 2488 brain metastases were included. The median OS after an MBM diagnosis was 8.9 months (95% CI, 7.9-11.3 months). Patients who were diagnosed with MBM between 2015 and 2019 experienced longer OS compared to those who were diagnosed between 2010 and 2014 (OS, 13.0 months [95% CI,…

BACKGROUND: The authors hypothesized that patients developing immune-related adverse events (irAEs) while receiving immune checkpoint inhibition (ICI) for recurrent/metastatic head and neck cancer (HNC) would have improved oncologic outcomes. METHODS: Patients with recurrent/metastatic HNC received ICI at 2 centers. Univariate and multivariate logistic regression, Kaplan-Meier methods, and Cox proportional hazards regression were used to associate the irAE status with the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in cohort 1 (n = 108). These outcomes were also analyzed in an independent cohort of patients receiving ICI (cohort 2; 47 evaluable for irAEs). RESULTS: The median follow-up was 8.4 months for patients treated in cohort 1. Sixty irAEs occurred in 49 of 108 patients with 5 grade 3 or higher irAEs (10.2%). ORR was higher for irAE+ patients (30.6%) in comparison with irAE- patients (12.3%; P = .02). The median PFS was 6.9 months for irAE+ patients and 2.1 months for irAE- patients (P = .0004), and the median OS was 12.5 and 6.8…

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had wide-ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. METHODS: The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web-based or telephone COVID-19 survey, between May 27 and September 11, 2020. Mixed-effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies-Depression [CES-D] scale) from before to during the pandemic in survivors versus controls and to test survivor-control differences in the associations between changes in loneliness and changes in mental health, including depression (CES-D, excluding the loneliness item), anxiety (the State-Trait Anxiety Inventory), and…

BACKGROUND: The achievement of a 3-month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs). METHODS: The authors reviewed 204 patients with Ph-positive ALL who were treated between January 2001 and December 2018 using the combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow-up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow-up. RESULTS: Overall, a 3-month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median…

BACKGROUND: Microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) is a biomarker for responses to immune checkpoint inhibitors (ICIs). Whether mechanisms underlying microsatellite instability alter responses to ICIs is unclear. This article reports data from a prospective phase 2 pilot study of pembrolizumab in patients with recurrent MSI-H endometrial cancer (EC) analyzed by whole exome sequencing (WES) and potential mechanisms of primary/secondary ICI resistance (NCT02899793). METHODS: Patients with measurable MSI-H/dMMR EC confirmed by polymerase chain reaction/immunohistochemistry were evaluated by WES and received 200 mg of pembrolizumab every 3 weeks for ≤2 years. The primary end point was the objective response rate (ORR). Secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-five patients (24 evaluable) were treated. Six patients (25%) harbored Lynch/Lynch-like tumors, whereas 18 (75%) had sporadic EC. The tumor mutation burden was higher in Lynch-like tumors (median, 2939 mutations/megabase [Mut/Mb];…

BACKGROUND: Risk stratification for patients with differentiated thyroid cancer (DTC) is based primarily on pathologic tumor characteristics. Accurate preoperative prognostication could allow for more informed initial surgical recommendations, particularly among patients at a higher risk for distant metastasis (DM). The objective of this study was to characterize the genetic profile of DTC with DM and to validate a molecular-based risk stratification. METHODS: A case-control study design was used to analyze patients who had DTC with DM (n = 62) and a propensity matched cohort of patients who had DTC without DM after at least 5 years of follow-up using the ThyroSeq version 3 targeted next-generation sequencing assay. The results were classified into high-risk, intermediate-risk, and low-risk of aggressive disease. RESULTS: Most patients who had DTC with DM (66%) had a late-hit mutation in TERT, TP53, or PIK3CA. After propensity matching by age, tumor size, and sex, the high-risk molecular profile had strong association with DM (high-risk vs intermediate-risk: odds ratio, 25.1; 95%…

Radiation therapy exerts a tumoricidal local effect as well as both local and systemic immunomodulation. Immune checkpoint blockade has become a widely used treatment modality across cancer types with a rapidly growing list of agents and US Food and Drug Administration-approved indications. Moreover, there may be synergy between radiation therapy and immune checkpoint blockade. Various strategies have been used, but the optimal sequencing of these therapies is unclear. In this review, the authors discuss the major mechanisms of available immune checkpoint inhibitors and explore the available preclinical and clinical evidence regarding treatment sequencing. They also review safety considerations and conclude with possible future directions.

BACKGROUND: Concerns have been raised about access to cancer screening and the timely receipt of cancer care for people with an intellectual disability (ID). However, knowledge about cancer mortality as a potential consequence of these disparities is still limited. This study, therefore, compared cancer-related mortality patterns between people with and without ID. METHODS: A historical cohort study (2015-2019) linked the Dutch adult population (approximately 12 million people with an ID prevalence of 1.45%) and mortality registries. Cancer-related mortality was identified by the underlying cause of death (according to the chapter on neoplasms in the International Classification of Diseases, Tenth Revision). Observed mortality and calculated age- and sex-standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were reported. RESULTS: There were 11,102 deaths in the ID population (21.7% cancer-related; n = 2408) and 730,405 deaths in the general population (31.2%; n = 228,120) available for analysis. Cancer was noted as the cause of death more often among people with…

BACKGROUND: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. METHODS: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. RESULTS: Among 464,371 participants, a positive…

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors may synergize with programmed cell death receptor-1 (PD-1) inhibitors to enhance adaptive and innate antitumor immune responses. In the phase 2 JASPER study (NCT04475939), the PARP inhibitor niraparib was evaluated in combination with the PD-1 inhibitor pembrolizumab in patients with metastatic and/or locally advanced non-small cell lung cancer (NSCLC). METHODS: Patients whose tumors had programmed cell death ligand 1 (PD-L1) tumor proportion scores (TPS) ≥50% (cohort 1) or 1%-49% (cohort 2) received first-line niraparib (200 mg once daily) plus pembrolizumab (200 mg every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. RESULTS: Thirty-eight patients were enrolled in cohorts 1 and 2. In cohort 1, ORR (95% confidence interval [CI]) was 56.3% (9 of 16 patients; 29.9%-80.2%); 2 of 16 patients had complete responses and 7 of 16 had partial…

BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous malignancy driven by genetic and epigenetic factors. Inhibition of bromodomain and extraterminal (BET) proteins, epigenetic readers that play pivotal roles in the regulation of genes relevant to cancer pathogenesis, constitutes a novel AML treatment approach. METHODS: In this first-in-human study of the pan-BET inhibitor mivebresib as monotherapy (MIV-mono) or in combination with venetoclax (MIV-Ven), the safety profile, efficacy, and pharmacodynamics of mivebresib were determined in patients with relapsed/refractory AML (ClinicalTrials.gov identifier NCT02391480). Mivebresib was administered at 3 monotherapy dose levels (1.5, 2.0, or 2.5 mg) or in combination with venetoclax (400 or 800 mg). RESULTS: Forty-four patients started treatment: of 19 who started MIV-mono, 5 went on to receive MIV-Ven combination therapy after disease progression and a washout period. Twenty-five patients started MIV-Ven, resulting in a total of 30 patients treated with the combination. The most common mivebresib-related treatment-emergent adverse…

BACKGROUND: Oncology patients and physicians value empathy because of its association with improved health outcomes. Common measures of empathy lack consistency and were developed without direct input from patients. Because of their intense engagement with health care systems, oncology patients may have unique perspectives on what behaviors signal empathy in a clinical setting. METHODS: As part of a cross-sectional study of patient perspectives on clinician empathy at an academic cancer center in the northeastern United States, the authors solicited up to 10 free-text responses to an open-ended question about what clinician behaviors define empathy. RESULTS: The authors categorized open-ended responses from 89 oncology patients into 5 categories representing 14 themes. These categories were relationship sensitivity, focus on the whole person, communication, clinician attributes, and institutional resources and care processes. Frequently represented themes, including listening, understanding, and attention to emotions and what matters most, aligned with existing measures of empathy;…

BACKGROUND: The US opioid epidemic has prompted dramatic changes in public attitudes and regulations governing opioid prescribing. Little is known about the experiences of patients with advanced cancer using opioids in the context of the epidemic. METHODS: Semistructured interviews of 26 patients with advanced cancer were conducted between May 2019 and April 2020; their experiences self-managing chronic pain with opioids were evaluated. RESULTS: Patients consistently described the negative impact of the opioid epidemic on their ability to self-manage pain. Negative media coverage and personal experiences with the epidemic promoted stigma, fear, and guilt surrounding opioid use. As a result, many patients delayed initiating opioids and often viewed their decision to take opioids as a moral failure-as "caving in." Patients frequently managed this internal conflict through opioid-restricting behaviors (eg, skipping or taking lower doses). Stigma also impeded patient-clinician communication; patients often avoided discussing opioids or purposely conveyed underusing them to avoid being…

BACKGROUND: Loneliness and social isolation are significant public health problems that are being exacerbated during the coronavirus disease 2019 pandemic. Little is known about the associations between loneliness and symptom burden in oncology patients before and during the pandemic. Study purposes include determining the prevalence of loneliness in a sample of oncology patients; evaluating for differences in demographic, clinical, and symptom characteristics between lonely and nonlonely patients; and determining which demographic, clinical, and symptom characteristics were associated with membership in the lonely group. METHODS: A convenience sample (n = 606) completed online surveys that evaluated the severity of loneliness, social isolation, and common symptoms (ie, anxiety, depression, fatigue, sleep disturbance, cognitive dysfunction, and pain) in oncology patients. Parametric and nonparametric tests were used to evaluate for differences in scores between the lonely and nonlonely groups. Logistic regression analysis was used to determine risk factors for membership in the…

BACKGROUND: More than 3.6 million men in the United States harbor a diagnosis of prostate cancer (PCa). The authors sought to provide in-depth analyses of the causes of death for contemporary survivors. METHODS: The authors performed a population-based cohort study in the United States (2000-2016) to assess causes of death for men diagnosed with PCa stratified by demographics and tumor stage. Using general population data, they calculated standardized mortality ratios (SMRs) as observed-to-expected death ratios. RESULTS: In total, 752,092 men with PCa, including 200,302 who died (27%), were assessed. A total of 29,048 men with local/regional disease (17%) died of PCa, whereas more than 4-fold men died of other causes (n = 143,719 [83%]). SMRs for death from noncancer causes (0.77; 95% confidence interval [CI], 0.77-0.78) suggested that these men were less likely than the general population to die of most other causes. The most common noncancer cause of death was cardiac-related (23%; SMR, 0.76; 95% CI, 0.75-0.77). Among men with distant PCa, 90% of deaths occurred within 5 years of…

BACKGROUND: Because of the growing number of actionable biomarkers in non-small cell lung cancer (NSCLC), sufficient tissue availability for testing is becoming a greater challenge. Liquid biopsy offers a potential solution by complementing standard tissue-based methods. In this study, the authors analyzed the concordance of actionable genomic alterations sequenced from circulating tumor DNA (ctDNA; Guardant360) and tissue (Oncomine Focus Assay). METHODS: From September 2015 to May 2018, 421 paired plasma and tissue samples from patients with advanced NSCLC who had previously undergone tissue testing by standard methods were collected. Both types of samples were available for 287 patients (262 in cohort 1 [treatment-naive] and 25 in cohort 2 [treatment failure]), and only 1 sample type was available for 134 patients (50 in cohort 3 [plasma only] and 84 in cohort 4 [tissue only]). RESULTS: In cohort 1, 198 samples (77.6%) showed concordance between tissue and plasma next-generation sequencing (NGS). Among the discordant cases, plasma testing detected additional genomic alterations in…

BACKGROUND: KEYNOTE-063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second-line therapy in Asian patients with advanced programmed death ligand 1 (PD-L1)-positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer. METHODS: of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression-free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety. RESULTS: Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE-061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval [CI], 4-10 months) with pembrolizumab versus 8 months (95% CI, 5-11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63-1.54). Median PFS was 2 months (95% CI, 1-3 months) with pembrolizumab versus 4 months (95% CI, 3-6…

BACKGROUND: Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC. METHODS: HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi-square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. RESULTS: A total of 163 HPV-OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV-OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8-6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1-3.2]) and oral sex…

There is a growing need for diversity, equity, and inclusion (DEI) in cancer care, particularly with respect to equal access and accrual to clinical trials. This commentary describe steps taken to address disparities in the authors' own clinical practice and proposes actions at the patient, provider, community, and institution levels to improve DEI in clinical trials.

BACKGROUND: The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone-a lay navigator-led, early palliative care telehealth intervention for African American/Black and/or rural-dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188). METHODS: This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid-tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20-minute to 60-minute telehealth coaching sessions plus monthly follow-up for 24 weeks, reviewing skills in stress management, self-care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants'…

Background Venetoclax (VEN) combined with the hypomethylating agent (HMA) azacitidine improves survival in patients aged ≥75 years with newly diagnosed acute myeloid leukemia (AML). VEN and HMA treatment can result in prolonged and often profound neutropenia, and this warrants antifungal prophylaxis. Azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism; this results in VEN dose reductions for each concomitant antifungal. Limited clinical data exist on outcomes for patients treated with VEN, an HMA, and various azoles. Methods The time to neutrophil recovery (absolute neutrophil count [ANC] > 1000 cells/mm 3 ) and platelet (PLT) recovery (PLT count > 100,000 cells/mm 3 ) in 64 patients with newly diagnosed AML who achieved a response after course 1 of VEN plus an HMA were evaluated. HMA therapy included azacitidine (75 mg/m 2 intravenously/subcutaneously for 7 days) or decitabine (20 mg/m 2 intravenously for 5 or 10 days). Results Forty‐seven patients (73%) received an azole: posaconazole (n = 17; 27%), voriconazole (n = 9; 14%),…

BACKGROUND: Fatigue is a common and expected side effect of cancer treatment. However, the majority of studies to date have focused on average levels of fatigue, which may obscure important individual differences in the severity and course of fatigue over time. The current study was designed to identify distinct trajectories of fatigue from diagnosis into survivorship in a longitudinal study of women with early-stage breast cancer. METHODS: Women with stage 0 to stage IIIA breast cancer (270 women) were recruited before (neo)adjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy and completed assessments at baseline; posttreatment; and at 6 months, 12 months, and 18 months of follow-up. Growth mixture modeling was used to identify trajectories of fatigue, and differences among the trajectory groups with regard to demographic, medical, and psychosocial variables were examined. RESULTS: Five distinct trajectories of fatigue were identified: Stable Low (66%), with low levels of fatigue across assessments; Stable High (13%), with high fatigue across assessments;…

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%),…