e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline characteristics and treatment outcomes in African-Americans (AA) and Hispanic patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Caucasians, AA and Hispanics with mRCC treated with 1 st line VEGF-TT were identified from the IMDC. We created 2 matched cohorts: 1) AA vs. Caucasians and 2) Hispanics vs. Caucasians, both matched for age (<50; 50-59; 60-69; <70-year-old), gender, years of treatment (2003-07; 2008-12; 2013-16) and geography (Canada, USA, Europe). Weighted Cox and logistic regressions were used to compare OS, time-to-treatment failure (TTF) and best response, adjusted for nephrectomy status, IMDC risk groups, number of metastatic sites (1 v. >1) and histology (clear-cell vs. else). Results: 73 AA and 71 Hispanics met eligibility criteria and were matched with 1236 and 901 eligible Caucasians, respectively. AA had more non-clear cell histology (26% v. 11%), time from diagnosis to therapy<1 year (67% v. 55%) and anemia (75% v. 54%) vs. Caucasians. Differences were not significant for Hispanics. Clinical outcomes are presented in Table. Conclusions: Adjusted for clinical prognostic factors, Hispanics with mRCC have statistically shorter TTF and survival than Caucasians. AA had a trend toward shorter TTF (not significant) but similar survival than Caucasians. Underlying genetic/biological differences, along with potential cultural variations, may impact survival in Hispanic mRCC patients. [Table: see text]
Abstract Circulating tumor DNA (ctDNA) has emerged as a noninvasive diagnostic and prognostic tool for colorectal cancer. Here, we discuss studies that evaluate the ability of plasma-only ctDNA assays to detect minimal residual disease and the potential benefit of integration of methylation into ctDNA assays. See related articles by Parikh et al., p. 5586 and Taieb et al., p. 5638
3522 Background: Observational cohorts have shown that detection of circulating tumor DNA (ctDNA)-defined minimal residual disease (MRD) following curative intent therapy has very high specificity and positive predictive value for future radiographic recurrence with a lead time of over 9 months. However, such data have not incorporated rigorous clinical evaluation for concomitant recurrence, nor have they established the clinical utility of MRD monitoring after completion of curative intent therapy. Methods: Pts with stages II-IV CRC (6/1/19 - 12/31/22, data cutoff) treated with curative intent at MD Anderson Cancer Center were evaluated with a tumor-informed MRD assay (Signatera, Natera), as part of the institutional INTERCEPT program that aims to integrate MRD-based testing into CRC clinical care. Surveillance visits including scans and tumor markers were performed per established guidelines. ctDNA was recommended post-operatively and q3m with each surveillance visit. Pts and providers were informed of the results and subsequent clinical courses including additional radiologic testing for ctDNA+ MRD tests were tracked. Results: 1259 pts were included in the INTERCEPT program (median 57y, [21-93]; 55% male; stage% I-III/IV 69/31; colon/rectum% 61/39), with 1049 pts tested after curative intent surgery. Of these, 159/1049 pts (15%) had ctDNA+; distribution of pts, % (+ve/total) from time of such surgery in m was: 0 - 3 (54.6/43.8); 3-6 (21.3/30); 6-12 (24/33.2). Of the pts with ctDNA+ after surgery, 49 pts (32%) were ctDNA+ prior to or during adjuvant therapy and 86 (57%) during surveillance. Of the 86 pts who were ctDNA+ during surveillance, imaging revealed concomitant new metastases in 46 (53%); i.e. only 40 (47%) were true MRD+. A total of 191 imaging studies were done (range 1-4) within 90d of the initial ctDNA+ including 99 as routine surveillance concurrent with ctDNA testing and 92 as additional follow up based on results. Of 40 pts with true MRD, majority (27 pts, 67.5%) were enrolled onto ongoing MRD trials ( https://crcmrd.com/ ). Conclusions: Our experience provides support for the feasibility of incorporation of MRD testing as part of routine surveillance. ctDNA+ results trigger a high rate of reflex imaging and, as a result, 53% of ctDNA+ patients have concomitant new radiographic findings. While clinical trials are feasible in true MRD+ pts, eligibility criteria for these trials need to be carefully specified about adequate radiographic evaluation.
196 Background: In patients (pts) with resected colorectal cancer (CRC), circulating tumor DNA (ctDNA) is an emerging tool for the detection of minimal residual disease (MRD) following the completion of curative intent therapy. The presence of MRD is highly prognostic, with MRD+ pts having worse disease-free survival (DFS). Prior to the advent of ctDNA, the modest negative prognostic implications of BRAF and RAS mutations (mt) on DFS were established in some studies. However, it is unclear if these previously noted prognostic effects of RAS/BRAF mts will be maintained with the information provided with ctDNA testing for MRD. Methods: As part of the INTERCEPT program, pts with Stage II-IV CRC treated with curative intent at MD Anderson Cancer Center were evaluated with a tissue-informed ctDNA assay (Signatera). This ctDNA testing was performed along with routine surveillance visits (post-operatively and Q3 months). A cohort of patients from the INTERCEPT program also had correlative analysis performed including whole exome sequencing called by GATK-Mutect2 to assess for BRAFV600E and RAS mt. Results: Within the INTERCEPT program, 265 pts had whole exome sequencing and were included for this analysis, with RAS mutations in 44% (n=116) and BRAF V600E in 3.8% (n=10). After a median follow up of 16-m, the median was DFS 7.93-m (95% CI 5.52 – 10.33-m) in ctDNA+ vs not reached in ctDNA-ve. There was no significant difference between ctDNA+ rates in RAS mt vs RAS wt pts (χ2 p=0.41); 217 pts were ctDNA-ve with a DFS HR=1.81 for RAS mut vs wt (95% CI 0.57-5.73, p=0.30). The 12-m DFS in this cohort was 95.2% in RAS mt vs 97.9% in RAS wt (OR 1.25, 95% CI 0.4-4.4, p=NS). 48 pts were ctDNA+, with no difference in DFS by RAS mt status with HR=1.42 (95% CI 0.76 – 2.64, p = NS), which was unchanged after excluding those with radiographically evident disease at or shortly after the finding of ctDNA+. In a multivariate model, after controlling for ctDNA status, there was no prognostic impact of RAS on DFS in the larger population with HR 1.51 (95% CI 0.88 – 2.60; p = NS). While the number of pts with BRAF V600E mt was low, there was no evidence of a prognostic effect after controlling for ctDNA status. Conclusions: In CRC pts treated with curative intent, positive ctDNA at any point post-operatively or during surveillance is highly predictive of disease recurrence. In these pts, RAS mt status was not associated with DFS. Moreover, RAS mt pts are not more likely to be ctDNA+ve. Thus, our data suggest that the presence of ctDNA defined MRD has greater prognostic value than the presence or absence of RAS or BRAF V600E mt.
<p>Proportion of patients with disease recurrence (<b>A</b>) and percentage of patients with disease recurrence stratified by reason for immunotherapy cessation (<b>B</b>).</p>
<p>Percentage of patients with recurrence stratified by therapy regimen (<b>A</b>), etiology of MSI-H status (<b>B</b>), timing of metastatic onset (<b>C</b>), and gender (<b>D</b>).</p>
<p>Association between disease recurrence after immunotherapy cessation and metastatic organ involvement (<b>A</b>) and mutation status (<b>B</b>).</p>
<p>Percentage of patients with recurrence stratified by therapy regimen (<b>A</b>), etiology of MSI-H status (<b>B</b>), timing of metastatic onset (<b>C</b>), and gender (<b>D</b>).</p>
Importance Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown. Objective To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer. Design, Setting, and Participants This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models. Main Outcome OS, from diagnosis date and from start of first-line chemotherapy. Results The study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P &lt;.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P &lt;.001; and 0.86; 95% CI, 0.81-0.92; P &lt;.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P &lt;.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC , KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; &lt; 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%). Conclusions This single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and the molecular pathogenesis of colorectal cancer with chemotherapy response is needed.
