Palliative splenic irradiation in primary and post PV/ET myelofibrosis: outcomes and toxicity of three radiation schedules

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Mario Federico *
Guido Pagnucco
Antonio Russo
Giovanni Cardinale
Patrizia Guerrieri
Francesco Sciumè
Catherine Evangeline Symonds
Letizia Cito
Sergio Siragusa
Nicola Gebbia
Roberto Lagalla
Massimo Midiri
Antonio Giordano
Paolo Montemaggi
(*) Corresponding Author:
Mario Federico | mfede@temple.edu

Abstract

Splenectomy and splenic irradiation (SI) are the sole treatment modalities to control drug resistant splenomegaly in patients with myelofibrosis (MF). SI has been used in poor surgical candidates but optimal total dose and fractionation are unclear. We retrospectively reviewed 14 MF patients with symptomatic splenomegaly. Patients received a median of 10 fractions in two weeks. Fraction size ranged from 0.2-1.4 Gy, and total dose varied from 2-10.8 Gy per RT course. Overall results indicate that 81.8% of radiation courses achieved a significant spleen reduction. Splenic pain relief and gastrointestinal symptoms reduction were obtained in 94% and 91% of courses, respectively. Severe cytopenias occurred in 13% of radiation courses. Furthermore patients were divided in three groups according to the radiation dose they received: 6 patients in the low-dose group (LDG) received a normalized dose of 1.67 Gy; 4 patients in the intermediate-dose group (IDG) received a normalized dose 4.37 Gy; the remaining 4 patients in the high-dose group (HDG) received a normalized dose of 9.2 Gy. Subgroup analysis showed that if no differences in terms of treatment’s efficacy were seen among dose groups, hematologic toxicity rates distributed differently. Severe cytopenias occurred in 50% of courses in the HDG, and in the 14.3% and in 0% of the IDG and LDG respectively. Spleen reduction and pain relief lasted for a median of 5.5 months in all groups. Due to the efficacy and tolerability of the low-dose irradiation 4 patients from the LDG and IDG were retreated and received on the whole 12 RT courses. Multiple retreatments did not show decremental trends in terms of rates of response to radiation nor in terms of duration of clinical response. Moreover, retreatment courses did not cause an increased rate of adverse effects and none of the retreated patients experienced severe hematologic toxicities. The average time of clinical benefit in retreated patients was much longer (21 months, range 44-10) than patients who were not retreated (5,75 months, range 3-6).

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Author Biographies

Mario Federico, University of Palermo / SHRO

Radiation Oncology dept University of Palermo 

Post Doctoral Fellow Sbarro Health Research Organization

Guido Pagnucco, U.O. Ematologia – ARNAS Civico -Dipartimento Oncologico M. Ascoli. Palermo

Chairman Hematology dept

Antonio Russo, U.O. Oncologia Medica - Università degli Studi di Palermo

Associate Professor of Medical Oncology

Giovanni Cardinale, U.O. Ematologia – ARNAS Civico -Dipartimento Oncologico M. Ascoli. Palermo

Senior attending Hematology dept

Patrizia Guerrieri, U.O. Radioterapia – ARNAS Civico - Dipartimento Oncologico M. Ascoli – Palermo

senior attending Radiation Oncology dept

Francesco Sciumè, U.O. Radioterapia – ARNAS Civico - Dipartimento Oncologico M. Ascoli – Palermo

attending radiation Oncology dept

Catherine Evangeline Symonds, SHRO

Ph.D student

Sergio Siragusa, Hematology department , University of Palermo

Associate Professor of Hematology

Nicola Gebbia, Medical Oncology dept. University of Palermo

Chairman and Director of Medical Oncology Dept

Roberto Lagalla, DiBiMeL University of Palermo

Professor of Radiology Chairman and director DiBiMeL

Massimo Midiri, DiBiMeL University of Palermo

Professor of Radiology

Antonio Giordano, SHRO - Temple University

Chairman and Director SHRO

Paolo Montemaggi, U.O. Radioterapia – ARNAS Civico - Dipartimento Oncologico M. Ascoli – Palermo

Chairman and director Radiation Oncology Dept