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Hematological Toxicity and Bone Marrow Dose-Volume Effects in Chemotherapy-Naïve Patients Treated With Whole Pelvic
Julie den Hartog1, Gert De Meerleer1, Annouschka Laenen2
1Department of Radiation Oncology, University Hospitals Leuven, Belgium.
Purpose:
Whole pelvic radiation therapy combined with androgen-deprivation therapy improves prostate cancer-specific survival in pathologic pelvic lymph node-positive prostate cancer. Elective para-aortic radiation therapy may further improve clinical outcomes and is under investigation in the Para-Aortic Radiotherapy (PART) study (NCT03079323). This study investigated the effect of whole pelvic radiation therapy plus PART on hematological toxicity (HemT).
Methods And Materials:
HemT and bone marrow (BM) dose-volume relationships were analyzed in the first 75 PART patients enrolled in the University Hospitals Leuven, all receiving 24 months of androgen-deprivation therapy or antiandrogen therapy. Hematological changes were assessed longitudinally. Associations were analyzed using linear models for repeated measures, with false discovery rate correction.
Results:
At 57-months median follow-up (median age, 66 years), no HemT caused treatment interruption. All blood parameters declined significantly after radiation therapy (all P < .01 at 1, 3, 6, and 24 months). Grade 4 toxicity was limited to lymphopenia (acute 7%, late 1%), grade 3 leukopenia occurred in 1% acutely and late. No grade 3-4 anemia or grade 2-4 thrombocytopenia was seen. BM dosimetric analysis showed that larger low-dose volumes (V3, V5, and V10) in the lower pelvis, whole pelvis, and whole pelvis plus retroperitoneal region were significant associated with greater late absolute lymphocyte count (ALC) decline. Every 100 cm3 increase in absolute volume correlated with a late ALC decrease of -0.04 to -0.08 × 109 /L (all false discovery rates; P ≤ .01).
Conclusions:
Extended-field radiation therapy is clinically well tolerated in chemotherapy-naïve pathologic pelvic lymph node-positive prostate cancer patients, with no toxicity-related treatment interruptions. However, persistent lymphopenia was observed. Dose-dependent association between low-dose BM irradiation (V3-V10) and late ALC decline supports further research into BM-sparing techniques to reduce long-term toxicity.
