HIGHER RANGE OF STANDARD NEOADJUVANT RADIATION FOR RECTAL CANCER IMPROVES OUTCOMES
Asya Ofshteyn*, Katherine Bingmer, David Dietz, Ronald Charles, Emily Steinhagen, Sharon L. Stein
University Hospitals Cleveland Medical Center/Case Western Reserve University, Cleveland, OH
Pathologic tumor response is an important prognostic factor for long-term survival in patients with rectal cancer. Standard neoadjuvant radiation dosing for locally advanced rectal cancer ranges from 4,500 to 5,040 centigray (cGy), but it is unknown if tumor regression differs as a consequence of variation within that range. The purpose of this study was to evaluate the impact of dose variation on tumor response, as measured by pathologic tumor regression grade (TRG), in rectal patients receiving standard neoadjuvant radiation.
The National Cancer Database (NCDB) was used to identify patients 18 years of age and older with clinical stage II and III rectal cancer who received pelvic neoadjuvant radiation dosed between 4,500 and 5,040 cGy prior to surgery between 2006 and 2014. Within the standard range, lower standard dose (LSD) and higher standard dose (HSD) were defined respectively as 4,500-4,770 and 4,771-5,040 cGy. Pathologic complete response (pCR) was defined as TRG of zero. A multivariate logistic regression was performed to evaluate association between radiation dosing and pCR adjusting for demographic, hospital, and clinical factors including stage and timing of surgery after completion of neoadjuvant radiation. Bivariate testing informed our multivariate analysis.
The study cohort was 9,083 patients with complete data; 7,175 (79.0%) received LSD, while 1,908 (21.0%) received HSD. pCR was achieved in 2,852 of all patients (31.4%). On multivariate logistic regression analysis, patients who received LSD were significantly less likely to have complete tumor response (OR 0.87, 95% CI 0.78-0.97, p=0.013), see Table 1. Other factors significant and associated with pCR included age over 55 (OR 1.12), other race (OR 1.15 compared to white race), Stage II disease at diagnosis (OR 1.29) and adenocarcinoma histotype (OR 2.45). Surgery performed more than 8 weeks after completion of neoadjuvant radiation was associated with higher likelihood of pCR (OR 1.16). Gender, academic hospital setting and concurrent neoadjuvant chemotherapy were not significantly associate with pCR.
This is the first investigation demonstrating that LSD neoadjuvant radiation for rectal cancer was associated with lower likelihood of pCR compared to HSD. Patient survival is strongly correlated with pCR in past studies of rectal cancer. Prospective trials should focus on examining neoadjuvant radiation dosing within the commonly prescribed range to evaluate if HSD improves outcomes.
Table 1: Multivariate logistic regression demonstrating associations with pathologic complete response (pCR).
| Odds Ratio | 95% Confidence Interval | P Value | |
| Neoadjuvant radiation HSD 4,771-5,040 cGy (reference) | - | - | - |
| LSD 4,500-4,770 cGy | 0.87 | 0.78-0.97 | 0.013 |
| Female gender | 1.02 | 0.93-1.12 | 0.721 |
| Age over 55 years old | 1.12 | 1.01-1.24 | 0.031 |
| Race | |||
| White (reference) | - | - | - |
| Black or African-American | 0.96 | 0.81-1.15 | 0.668 |
| Other | 1.15 | 1.01-1.31 | 0.041 |
| Insurance | |||
| Uninsured (reference) | - | - | - |
| Private | 1.24 | 0.99-1.56 | 0.059 |
| Government* | 1.11 | 0.99-1.24 | 0.076 |
| Unknown | 1.02 | 0.86-1.21 | 0.843 |
| Income (quartiles) | 1.00 | 0.96-1.04 | 0.888 |
| Academic setting | 0.92 | 0.84-1.01 | 0.089 |
| Clinical stage II (III as reference) | 1.29 | 1.18-1.41 | <0.001 |
| Adenocarcinoma histotype | 2.45 | 1.91-3.15 | <0.001 |
| Neoadjuvant chemotherapy | 1.16 | 0.9-1.51 | 0.249 |
| Surgery within 42-56 days after neoadjuvant radiation (reference) | - | - | - |
| Surgery less than 42 days after neoadjuvant radiation | 0.96 | 0.83-1.12 | 0.629 |
| Surgery more than 56 days after neoadjuvant radiation | 1.16 | 1.05-1.28 | 0.003 |
*Medicare, Medicaid and other government-provided insurance.
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