Importance Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared

Importance In spite of the effectiveness of endocrine therapy plus cyclin-dependent kinase (CDK) 4/6 inhibitors as the first-line treatment for estrogen receptor (ER)-positive, erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2/neu])-negative (ER+/ERBB2-) metastatic breast cancer (MBC), patients eventually develop resistance, and eventually most will receive chemotherapy. The METEORA-II trial

Importance Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs. Objective To assess the addition of radiotherapy to ICIs compared with ICI monotherapy

Importance Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments. Objective To investigate how often patients with low-recurrence score breast cancer

Importance Advances in cancer research and treatment access have led to decreasing cancer mortality in the US; however, cancer remains the leading cause of death among Hispanic individuals. Objective To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Hispanic individuals by demographic characteristics and to compare age-adjusted cancer death rates between the Hispanic population

Importance Combination therapy with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i: palbociclib, ribociclib, abemaciclib) and endocrine therapy (ET) has been a major advance for the treatment of hormone receptor-positive (HR+), ERBB2 (formerly HER2)-negative (ERBB2-) advanced or metastatic breast cancer. Observations Randomized phase 3 studies demonstrated that the addition of CDK4/6i reduced

Importance In the era of immuno-oncology, imaging alone seems to be insufficient to capture treatment responses, as patients with stable disease treated with immunotherapy have a wide range of clinical outcomes. There is an unmet need for complementary (ideally cost-efficient) markers that enable assessment of therapy response and outcomes in conjunction with imaging. Objectives To examine whether

Importance Patient withdrawal of consent from a cancer clinical trial is defined as a patient's volitional cessation of participation in all matters related to a trial. It can undermine the trial's purpose, make the original sample size and power calculations irrelevant, introduce bias between trial arms, and prolong the time to trial completion. Objective To report rates of and baseline factors associated

Importance Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking. Objective To evaluate preoperative SRS outcomes and prognostic factors from a large international

Importance Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second

Importance Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval

Importance MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches. Objective To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with

Importance Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. Objective To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. Design, Setting, and Participants This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75

Importance Acral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking. Objective To investigate the activity and safety of camrelizumab (an anti-programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma. Design

Importance Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need. Objective To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC. Design, Setting, and

Importance The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed. Objective To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association

Importance O6-methylguanine-DNA methyltransferase (MGMT [OMIM 156569]) promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy for glioblastomas and is routinely used to guide treatment decisions. However, the utility of MGMT promoter status for low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets. Objective

Importance Current third-line therapies for patients with metastatic colorectal cancer (MCRC) have limited efficacy. Rechallenge with epidermal growth factor receptor (EGFR) inhibitors for RAS wild-type (WT) MCRC may be valuable for these patients. Objective To compare the anti-EGFR monoclonal antibody panitumumab plus standard-of-care trifluridine-tipiracil with trifluridine-tipiracil alone as third-line

Importance Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed. Objective To quantify the

Importance Thymic carcinoma is rare, and its oncologic management is controversial due to a paucity of prospective data. For this reason, multidisciplinary consensus guidelines are crucial to guide oncologic management. Objective To develop expert multidisciplinary consensus guidelines on the management of common presentations of thymic carcinoma. Evidence Review Case variants spanning the spectrum

Importance Combination of chemotherapy with (dual) ERBB2 blockade is considered standard in hormone receptor (HR)-positive/ERBB2-positive early breast cancer (EBC). Despite some promising data on endocrine therapy (ET) combination with dual ERBB2 blockade in HR-positive/ERBB2-positive BC, to our knowledge, no prospective comparison of neoadjuvant chemotherapy vs ET plus ERBB2 blockade in particular

Importance Little is known about the risk of post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) in the setting of childhood cancer. Objective To evaluate factors associated with MIS-C and describe the clinical course of COVID-19 in the setting of MIS-C. Design, Setting, and Participants Multisite observational cohort study of a registry representing more than 100 US pediatric oncology

Importance Obesity-related cancers account for 40% of all cancers in the US. Healthy food consumption is a modifiable factor shown to reduce obesity-related cancer mortality, but residing in areas with less access to grocery stores (food deserts) or higher access to fast food (food swamps) reduces healthy food access and has been understudied. Objective To analyze the association of food deserts and

Importance Pathogenesis of acute radiation dermatitis (ARD) is not completely understood. Pro-inflammatory cutaneous bacteria may contribute to cutaneous inflammation after radiation therapy. Objective To evaluate whether nasal colonization with Staphylococcus aureus (SA) before radiation therapy is associated with ARD severity in patients with breast or head and neck cancer. Design, Setting, and Participants

Importance Evidence-based approaches for the prevention of acute radiation dermatitis (ARD) are limited, and additional strategies are necessary to optimize care. Objective To determine the efficacy of bacterial decolonization (BD) to reduce ARD severity compared with standard of care. Design, Setting, and Participants This phase 2/3 randomized clinical trial was conducted from June 2019 to August

Importance Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed. Objective To determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy

Importance Patients with early-stage ERBB2 (formerly HER2)-positive breast cancer (ERBB2+ BC) who experience a pathologic complete response (pCR) after receiving neoadjuvant therapy have favorable survival outcomes. Predicting the likelihood of pCR may help optimize neoadjuvant therapy. Objective To test the ability of the HER2DX assay to predict the likelihood of pCR in patients with early-stage ERBB2+

Importance Although breast density is an established risk factor for breast cancer, longitudinal changes in breast density have not been extensively studied to determine whether this factor is associated with breast cancer risk. Objective To prospectively evaluate the association between change in mammographic density in each breast over time and risk of subsequent breast cancer. Design, Setting, and

Importance While the characteristics of COVID-19 infection and mortality among patients with a malignant neoplasm have previously been examined, little data are available for gender-specific COVID-19 mortality. Objective To examine the gender-specific COVID-19 case fatality risks among patients with a malignant neoplasm. Design, Setting, and Participants In this cohort study using the Healthcare Cost