Splenic irradiation for splenomegaly: A systematic review

Abstract

Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r² all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.

Keywords: Cancer; Leukemia; Lymphoma; Meta-analysis; Myelofibrosis; Palliation; Radiation oncology; Radiotherapy; Splenomegaly; Toxicity.

Figure 1.. Partial response rates of SI in different diseases

Legend: Partial response rates of SI in different cancers. Legend: The rate of partial or complete response from each study is plotted vs. indicated disease (e.g. CLL/CML; PLL, HCL, MPD; or studies that included multiple cancers). The size of the circle corresponds to the number of patients included (inset). There was no apparent outlier hematologic malignancy that markedly different response rates to SI vs. other malignancies. The response is determined by directly reporting from paper abstracts or calculating a response rate based on data provided in the paper. For papers that reported separate outcomes for splenomegaly, pain, and CBC responses, a weighted average was calculated based on the number of courses.

Figure 2.. Efficacy and toxicity vs. BED

Legend: Efficacy and toxicity vs. BED for all cancers. Legend: The efficacy and toxicity are plotted vs. dose of radiation among all studies. All cancers from Fig. 1 are included. The dose of radiation is calculated by using BED = (nd[1 + d/(a/b)]), n is the number of radiation fractions and d is the fraction size, and a/b is 10. (A) The response rate (with PR or CR) for any symptom alleviation vs. BED is plotted; there is no improvement in symptoms with increasing dose. The most common fractionation regimen was 1 Gy per fraction, to a total of 10 Gy, which corresponds to a BED10 of 11 Gy (vertical line coplotted). (B) The response rate (with PR or CR) for individual symptom alleviation vs. BED is plotted. With respect to outcomes, 65–100% of patients experienced pain relief, 60–100% had a reduction in spleen size, while the number with CBC improvement was variable. The median response duration was 11 months (range 2–216). There is no improvement in symptoms with increasing dose (r2 = 0.01 0.05). The size of the circle corresponds to the number of patients included (inset). (C) The toxicity rate (grade 3–5) vs. BED is plotted. The rate of any toxicity was between 5 and 60% among most studies. There is no association in symptoms with increasing dose (r2 = 0.02 0.34). The size of the circle corresponds to the number of patients included (inset).