Muscle mass at the time of diagnosis of nonmetastatic colon cancer and early discontinuation of chemotherapy, delays, and dose reductions on adjuvant FOLFOX: The C‐SCANS study

Abstract

Background For many chemotherapy regimens dosed on body surface area (BSA), patients are dose-reduced, delayed, or discontinue treatment, reducing survival. Consideration of body composition may be useful in individualizing chemotherapy dosing, but few studies examine the association of body composition with chemotherapy tolerance in colon cancer. Methods We identified non-metastatic colon cancer patients diagnosed from 2006–2011 at Kaiser Permanente who received FOLFOX as initial adjuvant chemotherapy (n=533). We quantified patients’ muscle mass using clinically-acquired computed tomography (CT) scans and quantified chemotherapy doses, treatment dates, and related toxicities using the electronic medical record. In logistic regression models adjusting for age, sex, and stage, we examined associations of muscle tertiles with early discontinuation (<6 cycles), treatment delay (≥3 days off-schedule ≥3 times), and/or dose reduction (relative dose intensity≤0.70, based on planned treatment). Results Average age at diagnosis was 58.7 years, body surface area (BSA) was 1.9 m2, and body mass index was 28.7 kg/m2. Compared to the highest sex-specific tertile of muscle, patients in the lowest tertile were more likely to experience toxicities had twice the risk of adverse outcomes on FOLFOX: odds ratios (OR) and 95% Confidence Intervals (95%CI) were OR=2.34 (95%CI: 1.04, 5.24; p-trend=0.03) for early discontinuation, OR=2.24 (95%CI: 1.37, 3.66; p-trend=0.002) for treatment delay and OR=2.28 (95%CI: 1.19, 4.36; p-trend=0.01) for dose reduction. Conclusions Lower muscle mass is associated with greater toxicity and poor chemotherapy adherence on FOLFOX. Many chemotherapy drugs are dosed on BSA: treatment may be better individualized if muscle mass is considered.

Computed Tomography-Based Body Composition Is Not Consistently Associated with Outcome in Older Patients with Colorectal Cancer

“…The current body of evidence shows inconsistent associations between body composition measures and adverse outcomes in patients with CRC. Low SM has been shown to be associated with severe postoperative complications , LOS , dose‐limiting toxicity , and long‐term survival . However, other studies did not show associations between low SM and overall or severe postoperative complications , readmission , and long‐term survival .…”

Clinical implications of low skeletal muscle mass in early-stage breast and colorectal cancer

“…25–29 Furthermore, another study found that among 533 non-metastatic colon cancer patients receiving FOLFOX chemotherapy, those in the lowest tertile of muscle mass were more likely to be dose-reduced (OR=2.28; 95% CI=1.19–4.36), dose-delayed (OR= 2.24; 95% CI=1.37–3.66), and to discontinue chemotherapy prematurely (OR= 2.34; 95% CI=1.04–5.24), than those in the highest tertile. 30 …”

Prognostic factors of adjuvant chemotherapy discontinuation among stage III colon cancer patients: A survey of medical oncologists and a systematic review and meta‐analysis

“…With respect to multivariable adjustment, only one study used backwards elimination with a liberal p‐value to select which subset of covariates to include in the multivariable model (Table ). The other investigations that reported a multivariable‐adjusted analysis included all covariates that were examined with the exception of Cespedes Feliciano et al (2017) which adjusted for three variables based upon their expert opinion (Table ) . All of the observational cohort studies collected data retrospectively using medical records and/or routinely collected administrative data (eg hospital or pharmacy dispensary records).…”

“…There were reports from individual studies of a higher odds of discontinuation among individuals who were white vs black (OR: 1.48; 95% CI: 1.12‐1.95), unmarried vs married (OR: 1.55; 95% CI: 1.21‐1.97), and in lower vs upper tertiles of muscle mass (OR: 2.34, 95% CI: 1.04‐5.24) . Hu et al (2011) found that living in a rural location was not associated with chemotherapy discontinuation (OR rural vs big metro : 1.25; 95% CI: 0.80‐1.95) .…”