Modeling precision genomic-based radiation dose response in rectal cancer

Aim: Genomic-based risk stratification to personalize radiation dose in rectal cancer. Patients & methods: We modeled genomic-based radiation dose response using the previously validated radiosensitivity index (RSI) and the clinically actionable genomic-adjusted radiation dose. Results: RSI of rectal cancer ranged from 0.19 to 0.81 in a bimodal distribution. A pathologic complete response rate of 21% was achieved in tumors with an RSI <0.31 at a minimal genomic-adjusted radiation dose of 29.76 when modeling RxRSI to the commonly prescribed physical dose of 50 Gy. RxRSI-based dose escalation to 55 Gy in tumors with an RSI of 0.31–0.34 could increase pathologic complete response by 10%. Conclusion: This study provides a theoretical platform for development of an RxRSI-based prospective trial in rectal cancer.

Impact of dual anti-HER2 therapy on pathologic complete response rate in breast cancer in a minority-enriched population.

e18111 Background: The addition of pertuzumab (P) to a neoadjuvant trastuzumab (H) plus chemotherapy combination has been shown to significantly improve the pathologic complete response rate (pCR) in localized HER2+ breast cancer; however, minorities have been under-represented in these trials. Racial/ethnic disparities have also been shown to affect outcomes of cancer treatment. This study is aimed to assess the impact of neoadjuvant dual HER2-blockade in an unselected minority-enriched population. Methods: A retrospective chart review was conducted of women with stage I to III HER2+ breast cancer who received neoadjuvant treatment between 2007 and 2017 at an academic institution and its affiliated safety net health system. Data on stage, chemotherapy, race/ethnicity, site of therapy (academic vs safety net hospital), and hormone receptor status were collected. All patients underwent surgery after completion of neoadjuvant chemotherapy. pCR was defined as ypT0/is, ypN0. Chi-squared test and univariate/multivariate logistic regression were used for statistical analysis. Results: The study population included 261 women with the following race/ethnic distribution: 37.7% Non-Hispanic Whites, 34.6% Hispanics, 20.6% Blacks, and 7% other racial/ethnic origin. Ninety-five patients (36%) received chemotherapy-H vs 166 patients (64%) received chemotherapy-HP. Patients at the safety net health system had higher stage at diagnosis compared to the academic site. Site of care and race/ethnicity did not impact the choice of neoadjuvant treatment. The pCR rate was significantly higher for the chemotherapy-HP group (55.4%) compared to the chemotherapy-H group (34.7%) (p = 0.001). There was no association between race/ethnicity, or site of treatment (academic vs safety net), and the probability of achieving pCR. Multivariate analysis showed only dual anti-HER2 therapy (OR: 2.67, CI: 1.55-4.59, p = 0.0004) and hormone-receptor negative status (OR: 2.18, CI: 1.30-3.67, p = 0.0031) to correlate with pCR. Conclusions: Neoadjuvant dual anti-HER2 therapy was more likely to result in a pCR in our minority enriched population. Our data also suggests the combination of chemotherapy-HP confers similar benefit irrespective of race/ethnicity or site of care.