Intensity of chemotherapy regimens for patients with Lynch syndrome and colorectal cancer.

Abstract

10608 Background: Lynch syndrome (LS), associated with inherited pathogenic variants (PVs) in MLH1, MSH2, MSH6, PMS2 or EPCAM , is the most common inherited colorectal cancer (CRC) syndrome. Nearly all LS-associated CRCs are mismatch repair-deficient and microsatellite instability-high (dMMR/MSI-H), a phenotype associated with low recurrence risk and limited benefit from single-agent chemotherapy. Guidelines recommend no adjuvant chemotherapy for most dMMR/MSI-H stage II CRC. A fluoropyrimidine + oxaliplatin is recommended for all dMMR/MSI-H stage III CRC. Methods: We linked SEER registry records from Georgia and Los Angeles to germline genetic testing results from 4 labs. We included patients with resected stage II or III CRC diagnosed 2013-19 who linked to genetic test results. Chemotherapy details were extracted from SEER text fields completed by registrars. Regimens were classified as 1) No adjuvant chemotherapy; 2) Less intensive (5-FU or capecitabine); 3) More intensive (5-FU or capecitabine + oxaliplatin). We examined associations between genetic testing results and intensity of adjuvant chemotherapy. Covariates included age, sex, race, ethnicity, rurality. Results: Among 2770 patients, 1176 had stage II and 1594 had stage III CRC; 271 had a LS gene PV. The table shows results of multivariable analysis stratified by stage. Adjuvant chemotherapy intensity did not vary between patients with LS versus negative genetic test results. Older age was associated with receipt of no or less intensive chemotherapy in stage II and III CRC. Hispanic patients with Stage III CRC were more likely to receive no chemotherapy compared to non-Hispanic White patients. Conclusions: In this population-based cohort of CRC patients from two states, adjuvant chemotherapy regimen intensity did not vary with germline genetic test results. These findings suggest that patients with LS and stage II CRC are being overtreated. Clinicians may require education about optimizing CRC therapy for patients with LS. Stage II No Chemo (OR, 95% CI) Stage II Less Intensive (OR, 95% CI) Stage III No Chemo (OR, 95% CI) Stage III Less Intensive (OR, 95% CI) Genetic Test Result Negative (Ref)  Lynch PV 1.39 (0.86-2.24) 0.60 (0.29-1.26) 0.94 (0.42-2.11) 1.06 (0.50-2.26)  Other PV 0.80 (0.39-1.65) 1.03 (0.42-2.54) 0.58 (0.23-1.41) 1.29 (0.67-2.51)  VUS only 0.89 (0.61-1.30) 0.57 (0.35-0.94) 0.99 (0.65-1.50) 0.81 (0.53-1.25)  Age (years) 1.05 (1.04-1.07) 1.02 (1.00-1.03) 1.07 (1.05-1.08) 1.05 (1.03-1.06)  Female (vs. male) 0.96 (0.68-1.29) 0.89 (0.59-1.34) 1.00 (0.69-1.46) 1.15 (0.80-1.64) Race/Ethnicity Non-Hispanic White (ref)  Asian 0.75 (0.42-1.32) 1.21 (0.60-2.43) 1.24 (0.60-2.57) 1.22 (0.67-2.24)  Black 1.11 (0.67-1.84) 1.06 (0.56-1.98) 1.30 (0.75-2.25) 0.93 (0.52-1.66)  Hispanic 1.05 (0.66-1.67) 0.60 (0.30-1.18) 1.71 (1.02-2.87) 1.31 (0.77-2.24)  Rural (vs. urban) 1.14 (0.64-2.02) 1.31 (0.63-2.75) 1.08 (0.57-2.03) 1.26 (0.69-2.28)