ESTRO 2024 - Abstract Book

S2528

Clinical - Urology

ESTRO 2024

In October 2011 a pilot study was activated at San Raffaele Scientific Institute, Milan, with the aim of analyzing intestinal, hematological and urinary toxicity induced by RT including the irradiation of pelvic lymph-nodes/lymph nodal area for the treatment of clinically localized PCa. In September 2012, the observational prospective cohort study IHU WPRT-TOX (ClinicalTrial.gov registered study) was started for sharing the same objective in a multi institute frame. Full details on recruited patients’ health, comorbidities, smoking habits were gathered at baseline. Blood samples were collected at baseline, RT mid-point and end, 3 and 6 months after RT end, and thereafter every 6 months up to 5 years. Absolute counts of white blood cells (WBC), lymphocytes (ALC), neutrophils (ANC), platelets (PLT), red blood cells (RBC) and hemoglobin levels (Hb) were monitored for early and late HT. Details relative to RT technique and intent, surgery, fractionation, ADT type and duration, prescribed dose to lymph-node planning treatment volume (PTVLN) and prostate/prostatic bed were also collected and described elsewhere [1]. With the purpose of thoroughly investigating the possible effects of irradiation on pelvic hematopoietic bone marrow (BM), computational procedures were developed to extract the PTVLN volume (cc) along with its craniocaudal extent (mm) from the L5 vertebrae lower edge (arbitrarily set reference level) to the PTVLN upper extremity. Lymphopenia was defined based on CTCAE v4.03 criteria. For current analysis, acute Grade≥3 (G3+) and late Grade≥2 (G2+) lymphopenia were established as endpoints, being ALC<500/μL at RT mid -point or end and ALC<800/μL at 2 years or 30 months after RT -end, respectively. Only patients with complete blood tests at baseline, RT mid-point and/or end, 3 or 6 months, 12 or 18 months, 24 or 30 months were included in the present study (n=499). The primary endpoint was the occurrence of late G2+ lymphopenia; acute G3+ lymphopenia was separately considered among its potential predictors. Eighteen other variables were considered: WBC, ALC, ANC and age at baseline, BMI, smoking, diabetes, hypertension, ADT type and duration, neoadjuvant ADT duration, craniocaudal extent and PTVLN volume, hypofractionation, previous prostatectomy, RT technique and 2-Gy equivalent total doses (for a/b=3Gy, EQD2) to prostate/prostatic bed PTV and PTVLN. First, data from the 499 patients underwent preprocessing where the effect of each covariate on the binary outcome was assessed using univariate logistic regression. A significance level of p<0.3 was set for the variables to progress to pairwise Spearman correlation test of the association between variables. In case of high-level correlation (ρ>0.7) between two variables with p -value<0.3 at univariable, the one with the lowest p-value was considered. In the training phase, a backward stepwise multiple logistic regression was fitted, retaining variables with p-value<0.05. During internal validation, 1000 bootstrap replicates of the original dataset were generated to evaluate the robustness of the model. Median coefficients, p-values, odds ratios, average precision, F1 score, ROC curve AUC, McFadden’s pseudo -R-squared and LLRp-value across replicates were computed.

Results:

Late G2+ lymphopenia was experienced by 9.2% of patients.

The variables retained for late toxicity by multivariate prediction were: ALC at baseline (μL -1 ) [HR=0.997, 95%CI 0.996-0.998, p<10 -3 ], smoke (yes/no) [HR=2.744, 95%CI 1.21-6.22, p=0.016] and craniocaudal extent (mm) [HR=1.016, 95%CI 1.004-1.027, p=0.01]. Median and standard errors of internal validation performance statistics (average precision: 0.43, 0.06; F1 score: 0.4, 0.04; ROC curve AUC: 0.87, 0.02; McFadden’s pseudo -R-squared: 0.26, 0.05) were evaluated grouping over the replicates for which each single covariate and overall model LLRp-values were<0.05.