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Total neoadjuvant therapy (TNT) in early-onset (EO) vs average-onset (AO) locally advanced rectal cancer (LARC): Patient characteristics and tolerance
Background
TNT increases the rate of clinical complete response (cCR), which may allow more patients to proceed with watch-and-wait (WW) surveillance. Patients with EO (< 50 years of age) colorectal cancer (CRC) have been shown to have significantly more nausea and vomiting with adjuvant fluoropyrimidine and oxaliplatin compared to patients with AO (≥50 years) CRC. Despite the rising incidence of EO rectal cancer (RC) and increasing use of TNT, there are limited data regarding tolerance of TNT for patients with EORC.
Methods
Data from January 1, 2015 through April 28, 2021 were abstracted from our institution’s IRB-approved RC database. TNT typically consisted of induction chemoradiation (50-50.4 Gy in 25-28 fractions with fluoropyrimidine) followed by tumor assessment 5 weeks later, followed by 4 months of consolidation chemotherapy (FOLFOX or CAPOX). The following characteristics were compared between EO and AO patients in this retrospective analysis: demographic features, toxicities, and treatment delivery. A Pearson’s Chi-squared test and Fisher’s exact test were used to compare the EO with AO patients.
Results
A total of 1,263 patients with rectal cancer were treated during the study period. Of these, 118 with LARC (clinical stage II or III) received TNT at our institution and are included in this study. There were 39 EO patients and 79 AO patients. The mean age of the EO patients and AO patients was 43 years and 62 years, respectively. Females comprised 51% of the EO patients and 33% of the AO patients (p=0.054). There were no racial or ethnic differences between the EO and AO patients. Of the 92 cancers tested for mismatch repair, only 3 were deficient (3%). Among the EO patients, 15% had an identified germline pathogenic variant. Between the EO and AO patients, there was no difference in the distribution of clinical T, N, and overall stage. There was no difference in concurrent chemotherapy or consolidation chemotherapy regimens. EO patients experienced more nausea of any grade (51% vs 29%, p =0.019) than AO patients. There was no difference in other toxicities. Dose reduction for toxicity occurred in 41% of EO patients and 61% of AO patients (p = 0.043).
Conclusions
Our retrospective analysis of TNT tolerance suggests that younger patients have higher rates of nausea but are less likely to require a dose reduction. These findings are consistent with adjuvant chemotherapy outcomes in EOCRC. Further data will be presented on the timing of nausea in order to optimize treatment for patients with EORC.
Legal entity responsible for the study
Cleveland Clinic.
Funding
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH.
Disclosures
E. Gorgun: Honoraria (Institution): Boston scientific, Olympus, Dilumen. S. Kamath: Advisory / Consultancy: Exelixis, Tempus, Guardant Health. A. Khorana: Honoraria (self): Bayer, BMS, Pfizer; Advisory / Consultancy: BMS, Anthos, Bayer. All other authors have declared no conflicts of interest.
