Predictors of acute lymphopenia after radiotherapy for prostate cancer including pelvic node irradiation: results of a real-world prospective multi-centric study

Background: Acute lymphopenia (AL) is a clinically relevant concern in patients undergoing pelvic lymph-node irradiation (PNI) for prostate cancer (PCa) and reliable predictive models are not available. The purpose of the current analysis was to develop a predictive model of AL after PNI for PCa combining dosimetric and clinical information in a large, prospectively followed cohort. Materials and methods: Clinical/dosimetry/blood test data from a multi-centric prospective study were available, including absolute lymphocyte count (ALC) at baseline, mid-point and radiotherapy (RT) end. Dose-volume histograms (DVHs) of the body and of pelvic bones were extracted, as well as the integral dose (ID) to the body. Lymph-nodal planning target volume (LN-PTV) and its cranial limit were also recovered. The current analysis focused on acute CTCAEv4.03 grade ≥ 3 (G3+) lymphopenia (ALC < 500/μl), defined as the lowest count between baseline and mid-point or RT end. The patient population was split into training and validation cohorts, and a multivariable logistic regression model combining DVHs and clinical information was trained and validated. Results: 700/887 patients with full 3D planning data and available baseline, mid-point and RT end counts were considered. 290 patients (41.4%) experienced acute G3+ lymphopenia. Both ID and pelvic bone DVH parameters were significantly associated with the endpoint. The two best resulting models included baseline ALC (OR = 0.999, P < 0.001) and ID (Gy∗l) (OR = 1.003, P = 0.012) or baseline ALC, cranial LN-PTV limit (OR = 1.019, P < 0.001) and EQD2 to LN-PTV (OR = 1.095, P = 0.002), when replacing ID with the cranial LN-PTV limit. Conclusions: Severe AL after PNI for PCa is largely modulated by baseline ALC, with an independent role of the LN-PTV cranial limit or, alternatively, of ID, with the risk increasing by 5%-10% per 102 Gy∗l.