The absolute volume of PET-defined, active bone marrow spared predicts for high grade hematologic toxicity in cervical cancer patients undergoing chemoradiation.

Abstract

Hematologic toxicity (HT) in cervical cancer patients can cause treatment delays and reduction in chemotherapy, especially in high risk patients. Dose to PET-defined regions of active bone marrow (ABM) has been shown to correlate with cytopenias. An absolute volume of ABM spared may accurately represent hematopoietic reserve and risk of HT. This analysis evaluates whether the volume of ABM spared can more accurately predict HT compared to conventional dosimetric parameters. Thirty-one patients treated for cervical cancer with chemoradiation from 9/2011 to 8/2016 were retrospectively reviewed. Receiver operating characteristic (ROC) curve were used to assess optimal cutpoint criterions for grade 3+HT based on the CTCAEv4. Conventional dosimetric parameters to PBM and ABM (mean dose, V10, V20, V40) were assessed as well as the absolute volume (cc) of PBM and ABM spared 10, 20, and 40Gy. The absolute volume of PBM spared 10Gy (<230cc; AUC 0.732, p=0.03) as well as volume of ABM spared 10Gy (<179cc; AUC 0.815, p=0.0002), spared 20Gy (<186cc; AUC 0.774, p=0.0015), and spared 40Gy (<738cc; AUC 0.887, p<0.0001) all predicted grade 3+HT. In patients with <738cc of ABM spared 40Gy, 18/18 (100%) had grade 3+toxicity compared to 6/13 (46%) of patients with >738cc of ABM spared 40Gy (p<0.0001). The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40Gy (>738cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use.