Abstract PD5-04: Risk factors for long-term adjuvant chemotherapy toxicity using pre-treatment host factors and self-rated treatment bother (GP5) in a clinical trial population
Authors: Henry N. Lynn , Kim Sungjin , Hays Ron D. , Diniz Marcio A. , Luu Michael , Tighiouart Mourad , Cecchini Reena S. , Yothers Greg , Rogatko Andre , Ganz Patricia A. 
Published: March 2022

Abstract
Background: Chemotherapy-induced toxicities are prevalent in patients treated with adjuvant chemotherapy and often impact on activities of daily living and other aspects of function and well-being. Understanding which patients are more likely to experience long-term chemotherapy-induced peripheral neuropathy (CIPN) and hot flashes may help tailor treatment recommendations. Methods: Patients enrolled in the NRG Oncology/NSABP B-30 clinical trial were randomized to doxorubicin and docetaxel (AT), doxorubicin, docetaxel, and cyclophosphamide (ATC), or doxorubicin and cyclophosphamide followed by docetaxel (AC-T) (with increasing docetaxel doses across regimens). 1840 patients completed patient-reported outcomes (PRO) questionnaires including a symptom checklist asking about bother due to “numbness or tingling in hands or feet” and “hot flashes” as well as the FACT-General question 5 (GP5; “I am bothered by side effects of treatment”), assessed using a 5 category response scale. We examined the impact of pre-treatment host factors (demographic and clinical) on development and persistence of CIPN and hot flashes in NSABP B-30 patients. Analyses were performed using the Toxicity Index (TI), which summarizes the severity and frequency of toxicities over time. Univariate and multivariable probabilistic index models, a rank-based method that is a more general version of the Kruskal-Wallis test, for the cumulative TI of toxicity in the acute period (cycle 4 day 1 through 12 months post-randomization) and long-term follow-up (18 and 24 months post-randomization) were performed, and included baseline demographic, clinical, and PRO data. Results: Multivariable analysis revealed a higher probability of CIPN in the acute period for patients randomized to the AC-T treatment regimen and those with pre-existing numbness, higher GP5 at baseline, Black race, and obesity. In the long-term follow-up period, all the above factors except race were statistically significant. Older age at surgery and mastectomy were also associated with persistence of CIPN. GP5 at 12 months was significantly associated with the probability of CIPN in the longer-term period (0.577, p&lt;.001). Multivariable analysis revealed a higher probability of hot flashes in the acute period for patients treated randomized to the ATC treatment regimen and those with pre-existing hot flashes, greater GP5 at baseline, younger age, and obesity. In the longer-term period, all the above factors except baseline GP5 and obesity remained statistically significant. Endocrine therapy was also significantly associated with long-term hot flashes. GP5 at 12 months was statistically significantly associated with the probability of hot flashes in the longer-term period (0.561, p&lt;.001). Conclusions: Most pre-treatment patient characteristics that influence early development of CIPN and hot flashes are also associated with persistence of toxicity beyond 1 year. Persistent bother from side effects of treatment at 12 months (GP5) predicts continued toxicity during the subsequent year. Support: U10CA180868; U10CA180822.
Multivariable probabilistic index models for cumulative TIsVariableComparison A&lt;BProbability CIPN - AcuteP valueProbability CIPN - Long-termP valueProbability Hot Flashes - AcuteP valueProbability Hot Flashes - Long-termP valueTreatmentAT &lt; ATC0.537&lt;.0010.519.2450.567&lt;.0010.577&lt;.001AT &lt; AC-T0.688&lt;.0010.591&lt;.0010.502.9050.542.058ATC &lt; AC-T0.655&lt;.0010.573&lt;.0010.435&lt;.0010.465.167Numbness at baselinePer 1-unit increment0.597&lt;.0010.595&lt;.001NANANANAHot flashes at baselinePer 1-unit incrementNANANANA0.601&lt;.0010.592&lt;.001GP5 at baselinePer 1-unit increment0.516.0330.523.0040.521.0040.509.289Age at surgeryPer 1-year increment0.501.0880.503.0010.492&lt;.0010.498.016BMIObesity &lt; Normal0.453.0010.411&lt;.0010.516.3760.510.582Obesity &lt; Overweight0.475.1470.470.0870.536.0420.532.087RaceWhite &lt; Black0.587.0010.523.3630.499.9710.518.547Breast surgeryLumpectomy &lt; Mastectomy0.515.2500.548&lt;.0010.503.8290.507.629Endocrine therapyNo &lt; YesNANA0.490.576NANA0.655&lt;.001
Citation Format: N. Lynn Henry, Sungjin Kim, Ron D. Hays, Marcio A. Diniz, Michael Luu, Mourad Tighiouart, Reena S. Cecchini, Greg Yothers, Andre Rogatko, Patricia A. Ganz. Risk factors for long-term adjuvant chemotherapy toxicity using pre-treatment host factors and self-rated treatment bother (GP5) in a clinical trial population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-04.