Patient-Reported Functional Outcome of Patients with Rectal Cancer Undergoing Watch-and-Wait vs. Surgery after Chemoradiotherapy

Abstract

algorithms with false discovery rate (FDR) correction. These genomic findings were correlated with clinical data. Results: Of 341 pts in the MMC arm, 64 had tumor DNA available and 62 underwent successful WES. WES of the cisplatin arm is ongoing. Baseline characteristics and clinical outcomes did not differ significantly between MMC cases that did vs. did not undergo WES. Known cancer genes significantly mutated in the MMC arm included the PI3 kinase (PI3K) pathway members PIK3CA (29%, FDR qZ0.001) and PTEN (6.5%, qZ0.038); EP400 (18%, qZ0.020), a chromatin remodeling protein previously implicated in modulation of HPV oncogenicity; and FBXW7 (15%, qZ0.026), a ubiquitin ligase tumor suppressor also mutated in other squamous cell carcinomas. Median tumor mutational burden was 5.8 nonsynonymous mutations per megabase (min-max: 2.9-22.9). Chromosome 3q29 (harboring PIK3CA) was amplified in 50% of samples (q<0.001). EP400 mutations were associated with younger age at diagnosis (mean 45.5 y AE 4.8 vs. 58.6 y AE 10.6, pZ0.002); no recurrently mutated cancer genes were associated with T stage, N stage, or sex. On Cox multivariable analysis with T stage, N stage, and sex, FBXW7 mutations were associated with significantly inferior DFS (HR 2.47 [1.02-5.96], pZ0.045) and a trend towards inferior OS (HR 2.61 [0.97-7.04], pZ0.058). Conclusion: These results represent the most comprehensive genomic characterization of AC to date and, uniquely, are contextualized with clinical data from a phase III trial. Clinical-genomic analysis of the MMC arm of NRG/RTOG 98-11 revealed frequent alterations in the PI3K pathway and an association between EP400 mutations and younger age; moreover, FBXW7 mutations were associated with inferior outcomes. WES of the cisplatin arm is ongoing and will provide additional power to detect genomic events and clinical associations. These hypothesis-generating results suggest that profiling clinical trial specimens with modern sequencing-based approaches may help advance genomically-informed, precision oncology approaches for pts treated with CRT.

The Longitudinal Course of Low-anterior Resection Syndrome

“…Overall, individual patientlevel data were available and provided from 8 studies. These encompassed 5 prospective cohort studies, 9,17,[20][21][22] 1 randomized controlled trial (RCT), 23 and 2 prospective LARS score assessments of previously operated cohorts. 24,25 A summary of included studies is presented in Supplemental Digital Content Table S1, http://links.lww.com/SLA/ D711.…”

Gross morphologic features of surgical specimen in rectal cancer patients with pathological complete response following neoadjuvant chemoradiotherapy: A cross‐sectional study

“…In other words, they might have theoretically benefited from the watch-and-wait approach rather than total mesorectal excision (TME) in terms of higher quality of life, better function-related outcomes, reduced overall costs, and a comparable cancer-specific survival. [17][18][19][20] According to the definition, surgical specimen evaluation is crucial for pCR confirmation, which is unavailable in the preoperative period. Therefore, data regarding the presence of pCR cannot play a direct role in preoperative decision-making regarding whether or not surgical resection is required.…”

“…Due to the lower odds of local and distant tumor spread and higher disease‐free and overall survival in this subset of patients, 9,10 it has been postulated that patients with a pCR could have avoided radical surgery. In other words, they might have theoretically benefited from the watch‐and‐wait approach rather than total mesorectal excision (TME) in terms of higher quality of life, better function‐related outcomes, reduced overall costs, and a comparable cancer‐specific survival 17–20 …”