Answer questions and earn CME/CNEOver the past few decades, a body of research has emerged confirming what many adult patients with noncentral nervous system cancer have long reported—that cancer and its treatment are frequently associated with cancer‐related cognitive impairment (CRCI). The severity of CRCI varies, and symptoms can emerge early or late in the disease course. Nonetheless, CRCI is typically mild to moderate in nature and primarily involves the domains of memory, attention, executive functioning, and processing speed. Animal models and novel neuroimaging techniques have begun to unravel the pathophysiologic mechanisms underlying CRCI, including the role of inflammatory cascades, direct neurotoxic effects, damage to progenitor cells, white matter abnormalities, and reduced functional connectivity, among others. Given the paucity of research on CRCI with other cancer populations, this review synthesizes the current literature with a deliberate focus on CRCI within the context of breast cancer. A hypothetical case‐study approach is used to illustrate how CRCI often presents clinically and how current science can inform practice. While the literature regarding intervention for CRCI is nascent, behavioral and pharmacologic approaches are discussed. CA Cancer J Clin 2015;65: 123–138. © 2014 American Cancer Society.

Various tumor characteristics have been associated with neurocognitive functioning (NCF), though the role of tumor grade has not been adequately examined. Seventy-two patients with histologically confirmed grade IV glioma (n = 37), grade III glioma (n = 20), and grade II glioma (n = 15) in the left temporal lobe completed preoperative neuropsychological assessment. Rates of impairment and mean test performances were compared by tumor grade with follow-up analysis of the influence of other tumor- and patient-related characteristics on NCF. NCF impairment was more frequent in patients with grade IV tumor compared with patients with lower-grade tumors in verbal learning, executive functioning, as well as language abilities. Mean performances significantly differed by tumor grade on measures of verbal learning, processing speed, executive functioning, and language, with the grade IV group exhibiting worse performances than patients with lower-grade tumors. Group differences in mean performances remained significant when controlling for T1-weighted and fluid attenuated inversion recovery MRI-based lesion volume. Performances did not differ by seizure status or antiepileptic and steroid use. Compared with patients with grade II or III left temporal lobe glioma, patients with grade IV tumors exhibit greater difficulty with verbal learning, processing speed, executive functioning, and language. Differences in NCF associated with glioma grade were independent of lesion volume, seizure status, and antiepileptic or steroid use, lending support to the concept of “lesion momentum” as a primary contributor to deficits in NCF of newly diagnosed patients prior to surgery.

We report the analysis involving patients treated on the initial CODEL design. Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months. TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.