title: Hematologic Toxicity in Patients Treated With Postprostatectomy Whole-Pelvis Irradiation With Different Intensity Modulated Radiation Therapy Techniques Is Not Negligible and Is Prolonged: Preliminary Results of a Longitudinal, Observational Study.
abstract: To address the thus-far poorly investigated severity and duration of hematologic toxicity from whole-pelvis radiation therapy (WPRT) in a cohort of chemo-naïve patients treated with postprostatectomy radiation therapy including WPRT with different intensity modulated radiation therapy (IMRT) techniques, doses, and fractionations.
  
  
  
  This analysis pertains to 125 patients (70 from a pilot study and 55 from an observational protocol) for whom 1 baseline and at least 3 subsequent blood samples (median 6), obtained at irradiation midpoint and end, and thereafter at 3, 6, and 12 months, were available. Patients were treated with adjuvant (n=73) or salvage intent; static-field IMRT (n=19); volumetric modulated arc therapy (n=60) or helical Tomotherapy (n=46); and conventional (n=39) or moderately hypofractionated (median 2.35 Gy per fraction, n=86) regimens. The median 2-Gy equivalent dose (EQD2) to the prostatic bed was 70.4 Gy with a lymph-nodal planning target volume of 50.2 Gy. Clinical and dosimetric data were collected.
  
  
  
  Both leukopenia and thrombocytopenia were significant (median nadir count 65% and 67% of baseline, respectively), with leukopenia also persisting (1-year median count 75% of baseline). Lymphopenia was the major contributor to the severity and 1-year persistence of leukopenia; all patients developed acute grade ≥1 lymphopenia (61% and 26% grade 2 and ≥3, respectively), whereas 1-year grade ≥2 lymphopenia was still present in 16%. In addition to an independent predictive role of corresponding baseline values, multivariable analyses highlighted that higher EQD2 doses to lymph nodal planning target volume increased risk of acute neutropenia and hypofractionation for acute thrombocytopenia. Of note, patients of older age were at higher risk for acute grade 2 lymphopenia, and interestingly, increased risk of grade >2 lymphopenia for those who smoked at least one year. No role for different IMRT techniques indicated.
  
  
  
  Leukopenia and lymphopenia after postprostatectomy WPRT were found to be less negligible and more prolonged than expected. A number of radiation-related and clinical factors favoring hematologic toxicity, whose awareness may be crucial when prescribing WPRT, in particular if concomitant to chemotherapy, were identified.
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy. Electronic address: cozzarini.cesare@hsr.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Cozzarini
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Noris Chiorda
authors.affiliation: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Sini
authors.affiliation: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
authors.affiliation: Department of Urology, Vita-Salute University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology, Vita-Salute University, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Di Muzio
mesh_terms: D000368:Aged; D019583:Dose Fractionation, Radiation; D006801:Humans; D007970:Leukopenia / Q000209:etiology*; D008137:Longitudinal Studies; D008231:Lymphopenia / Q000209:etiology*; D008297:Male; D010388:Pelvis / Q000528:radiation effects*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D011832:Radiation Injuries / Q000209:etiology*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*