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Background: 5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus. The purpose of this study was to determine whether omission of the 5-FU bolus was associated with a difference in survival and toxicity. Methods: A real-world database from Flatiron Health was queried for patients with advanced colorectal, gastroesophageal, and pancreatic cancers who received first-line FOLFOX, FOLFIRI, and FOLFIRINOX regimens. Cox proportional hazards and Kaplan-Meier analyses were performed to compare survival outcomes between patients who received the 5-FU bolus and those who did not. Inverse probability of treatment weighted (IPTW) analysis was performed to adjust for treatment selection bias. Results: This study included 11,765 patients with advanced colorectal (n=8,670), gastroesophageal (n=1,481), and pancreatic (n=1,614) cancers. Among all first-line 5-FU multidrug regimens, 10,148 (86.3%) patients received a 5-FU bolus and 1,617 (13.7%) did not. After IPTW analysis, we found that omitting the bolus was not associated with a decrease in overall survival (hazard ratio, 0.99; 95% CI, 0.91–1.07; P=.74). However, omitting the bolus was associated with reductions in neutropenia (10.7% vs 22.7%; P<.01), thrombocytopenia (11.2% vs 16.1%; P<.01), and use of granulocyte colony-stimulating factors after treatment (19.6% vs 29.1%; P<.01). Conclusions: After adjusting for baseline clinical factors, we found that omission of the 5-FU bolus from FOLFOX, FOLFIRI, and FOLFIRINOX regimens was not associated with decreased survival, but resulted in decreased toxicity and possible health care savings

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

Waldenström macroglobulinemia (WM) is a B-cell lymphoma characterized by the presence of bone marrow lymphoplasmacytic infiltration and circulating monoclonal immunoglobulin M protein. The clinical presentation of WM is variable, ranging from gradually progressive cytopenias, organomegaly, fatigue, B symptoms, and peripheral neuropathy to the more emergent presentation with symptomatic hyperviscosity, cryoglobulinemia, hemolytic anemia–associated symptoms, acquired von Willebrand disease or acquired hemophilia–associated bleeding. Approximately 1 in 5 patients with WM are asymptomatic at diagnosis and classified as having smoldering WM, not requiring WM-directed therapy. Although WM typically has an indolent, relapsing-remitting course, the outcomes are heterogeneous. The prognosis of patients with WM is known to be impacted by certain clinical and laboratory features at initial presentation, with advanced age, elevated serum lactate dehydrogenase, and low serum albumin unfavorably affecting the outcome. Although complications such as histologic transformation or light and/or heavy chain (AL/ALH) amyloidosis are infrequent, their occurrence adversely influences the disease course. The International Prognostic Staging System for WM (IPSS-WM) is a validated model, often used in clinical practice, but needs to be reexamined in the current era. The discovery of the recurrent MYD88^L265P gain-of-function point mutation and the subclonal CXCR4 mutations has helped improve our understanding of the WM biology, and the prognostic impact of these mutations is under evaluation, with somewhat inconsistent findings thus far across studies. This review discusses the clinical presentation, diagnostic criteria, and prognostic markers of WM.

Background: Adolescent and young adult (AYA) patients with cancer have historically been understudied. Few studies have examined survival disparities associated with racial/ethnic and socioeconomic status (SES) and do not account for the influence of insurance status and access to care. We evaluated the association of SES and race/ethnicity with overall mortality for AYA patients who were members of an integrated health system with relatively equal access to care. Methods: AYA patients diagnosed with the 15 most common cancer types during 2010 through 2018 at Kaiser Permanente Southern California were included. Neighborhood Deprivation Index (NDI) quartile (Q1: least deprived; Q4: most deprived) was used as a measure of SES. Mortality rate per 1,000 person-years was calculated for each racial/ethnic and NDI subgroup. Multivariable Cox model was used to estimate hazard ratios (HRs) for all-cause mortality adjusting for sex, age and stage at diagnosis, cancer type, race/ethnicity, and NDI. Results: Data for 6,379 patients were tracked for a maximum of 10 years. Crude mortality rates were higher among non-White racial/ethnic patients compared with non-Hispanic (NH)–White patients. In the Cox model, Hispanic (HR, 1.31; P=.004) and NH-Black (HR, 1.34; P=.05) patients experienced significantly higher all-cause mortality risk compared with NH-White patients. Patients from more deprived neighborhoods had higher mortality risk. In the Cox model, there was no significant difference in all-cause mortality between Q1 and Q2 through Q4 (Q2: HR, 0.88; P=.26, Q3: HR, 0.94; P=.56, and Q4: HR, 0.95; P=.70). Conclusions: For AYAs with cancer with similar access to care, Hispanic and NH-Black patients have higher risk of all-cause mortality than NH-White patients, whereas no significant SES-associated survival disparities were observed. These findings warrant further investigation, awareness, and intervention to address inequities in cancer care among vulnerable populations.