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spleen_adam.jpg (9660 bytes) Radiation to the Spleen

It is uncommon for cancer to arise in the spleen or metastasize to the spleen.  Patients with hematological disorders may have an enlarged spleen (splenomegaly) that is destroying blood cells or causing pain... and low dose radiation to the spleen may be useful as noted below. Moss recommends a dose of 50cGy  2 or 3 times a week up to 300 - 900cGy.

see review here

Splenic Irradiation
 
Massive splenomegaly may be seen with CML, CLL, hairy cell leukemia, and splenic marginal zone lymphomas, where the spleen can extend into the pelvis. Significant splenomegaly may also occur with prolymphocytic leukemia, myeloproliferative disorders such as polycythemia vera or essential thrombocytosis, or myelofibrosis. One type of myelofibrosis called agnogenic myeloid metaplasia is characterized by progressive bone marrow failure, splenomegaly, and extramedullary hematopoiesis. It is therapeutically important to recognize which conditions of splenomegaly are due to extramedullary hematopoiesis rather than leukemic infiltration as whole spleen radiotherapy with modest radiation doses can result in severe, long-lasting pancytopenia when the spleen is the primary hematopoiesis site. Splenic hematopoiesis can also occur with late stages of CML, myeloproliferative disorders, and hairy cell leukemia.
 
Historically, splenic radiotherapy was commonly employed for palliation, but it is now uncommon, as more effective systemic treatments have been developed. Nevertheless, the radiation oncologist is called on to assist with the management of symptomatic splenomegaly from these hematologic disorders from time to time, often with excellent results. Leukemic infiltration of the spleen responds to relatively low doses of radiation. Particularly in an elderly patient with other comorbidities, palliative splenic radiotherapy can offer significantly less risk than splenectomy.

 

Anterior and posterior opposed portals for photon treatments are generally employed. In cases of leukemic infiltration, standard practice is to treat the whole spleen in 0.5 to 1.0 Gy fractions either daily or two to three times a week with doses titrated to response and hematologic tolerance. As the spleen responds, one may progressively shrink the treatment fields accordingly. Generally, it is prudent to start treatment very conservatively. Blood counts may need to be monitored several times a week. Total radiation dose delivered is determined clinically by when palliation is achieved. Total doses are typically in the range of 4 to 10 Gy with usually no more than 20 Gy required. Occasionally, a large spleen that is extensively fibrotic will not respond to radiotherapy. CLL and prolymphocytic leukemia are particularly radiosensitive, with occasional abscopal effects seen with splenic irradiation.

 

In patients with extramedullary hematopoiesis, the potential for severe neutropenia or thrombocytopenia is very high with even modest radiation doses. Dose per fraction may need to be as low as 0.1 to 0.5 Gy treating several times a week to avoid severe and protracted myelosuppression. Another strategy in this situation is to treat only half of the spleen. For myelodysplastic conditions or extramedullary/intrasplenic hematopoiesis, total doses of 1 to 9 Gy are usually adequate. With splenic irradiation, nausea is uncommon with these low-dose fractions, but can be readily managed with antiemetics if necessary. As there can be rapid cell lysis, allopurinol to prevent uric acid nephropathy is advised. Cumulative dose to the left kidney should be monitored, especially as retreatment in the future may be required; but it is rare for doses beyond 20 Gy to be required.

Splenic irradiation in treatment of primary myelofibrosis Splenic irradiation (SI) usually provides a transient (three to six months) benefit and can be appropriate for patients who are poor surgical candidates. In our series of 23 patients with MMM, 8 of whom received multiple courses of SI, 94 percent of courses resulted in an objective reduction in splenic size and symptomatic relief; the median duration of response was six months. The median dose of SI per course was 2.8 Gy, administered in a median of 7.5 fractions. Significant cytopenia occurred in 32 percent of courses, and life-threatening pancytopenia after a single course of SI occurred in six patients (26 percent), resulting in fatal sepsis or hemorrhage in three. Nine patients underwent subsequent splenectomy with a perioperative mortality of 11 percent; three of these required reexploration for postoperative bleeding.

Other centers have used total SI doses as low as 0.15 Gy and as high as 65 Gy, with generally excellent results, especially if SI is started in small fractions of 0.25 to 0.50 Gy given two to three times per week, with modifications as dictated by the clinical situation and frequently obtained blood counts. The range of regimens can be illustrated by the following two reports:

  • In a retrospective study of 14 patients with MMM treated with SI for symptoms due to splenomegaly, doses ranged from 7 to 24 Gy Relief of symptoms was achieved in all patients, with 30 to 70 percent reduction in splenic size. Side effects were mild and did not require interruption of treatment, although four patients developed severe anemia.
  • In another series, 17 patients with CML or MMM were treated with SI to a total dose of 0.15 to 16 Gy, with fractions given only two to three times per week. Fourteen of 19 courses given for splenic pain produced a significant subjective relief, while 17 of 26 courses given for splenomegaly obtained at least 50 percent reduction in splenic size.

Palliative irradiation of the spleen.

McFarland JT, Kuzma C, Millard FE, Johnstone PA. Am J Clin Oncol. 2003 Apr;26(2):178-83.

Radiation Oncology, Naval Medical Center, San Diego, CA 92134, USA.

We analyzed the efficacy of splenic irradiation in a population of patients with hematologic diseases. The records of the Radiation Oncology Division, Naval Medical Center San Diego were retrospectively reviewed for all patients treated with splenic irradiation (SI) between January 1, 1990 and March 1, 2001. The charts of 17 patients were identified: 5 patients had chronic myelogenous leukemia, 4 had chronic lymphocytic leukemia, 4 had idiopathic myelofibrosis, 2 had polycythemia vera, and 1 patient each had idiopathic thrombocytopenic purpura and acute myelogenous leukemia. Patient ages ranged from 37 to 88 years. Sixteen of 17 suffered from symptomatic splenomegaly. Twenty-six courses of splenic irradiation were delivered to these 17 patients. Treatment courses generally consisted of two fractions of 50 cGy in the first week, two fractions of 75 cGy the second week, and two fractions of 100 cGy the third week. Blood counts were checked prior to each treatment. Seven of the 17 patients died 1 month or less after SI due to the terminal nature of their disease. Twenty-two of 25 treatment courses for splenomegaly resulted in decreased pain and symptoms. Five patients required two treatment courses for splenomegaly, and one patient required five treatment courses. Three of four patients treated for thrombocytopenia demonstrated improvement, but only one was evaluable for more than 2 weeks due to disease-related mortality. Three of five patients treated for leukocytosis had significant improvement. In general, patients suffered few significant complications from this palliative intervention. Splenic irradiation can effectively palliate symptomatic splenomegaly in patients for whom splenectomy is not an option. Retreatment is possible. Splenic irradiation is less effective in the treatment of thrombocytopenia or leukocytosis.

Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia.

Elliott MA,. Br J Haematol. 1998 Nov;103(2):505-11.

Division of Hematology and Internal Medicine, Mayo Clinic and Mayo Foundation,

Twenty-three patients who had myelofibrosis with myeloid metaplasia (MMM) were treated at our institution with 50 courses of splenic irradiation (SI) for symptomatic splenomegaly. The median dose of radiation per course was 277.5 cGy, administered in a median of 7.5 fractions. 8/23 patients received multiple courses of SI. Of 49 evaluable courses of SI, 46 (93.9%) resulted in an objective decrease in spleen size. The median duration of response was 6 months (range 1-41). Reduction in spleen size was associated with symptomatic relief in all patients. Overall median survival after SI was 22 months. Significant cytopenia occurred in 10 (43.5%) patients, or 16 (32%) of the 50 courses of SI. Prolonged, life-threatening pancytopenia after a single course of SI occurred in six patients (26%), resulting in fatal sepsis or haemorrhage in three (13%). Nine patients underwent subsequent splenectomy: the perioperative mortality rate was 11%. One third of patients experienced postoperative intra-abdominal haemorrhage necessitating surgical re-exploration. SI can provide symptomatic relief and a reduction in spleen size in most MMM patients. The increased risk of postoperative bleeding in patients requiring subsequent splenectomy dictates against considering SI as an alternative to splenectomy for patients who are otherwise good surgical candidates.

A study of splenic irradiation in chronic lymphocytic leukemia.

Guiney MJ, L   Int J Radiat Oncol Biol Phys. 1989 Jan;16(1):225-9.

Department of Haematology and Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia.

A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemaglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

Splenic irradiation in the palliation of patients with lymphoproliferative and myeloproliferative disorders.

Paulino AC, Reddy SP. Am J Hosp Palliat Care. 1996 Nov-Dec;13(6):32-5.

INTRODUCTION: Splenic irradiation is an accepted mode of treatment for palliation of hypersplenism and splenic pain for patients with lymphoproliferative or myeloproliferative disorders. However, results are conflicting regarding the duration of palliation and the toxicity associated with this treatment. METHODS: Twenty-five patients with lymphoproliferative or myeloproliferative disorders were treated with splenic irradiation for palliation of splenomegaly and pain. The spleen was measured and pain and toxicity were assessed during radiation therapy. RESULTS: Splenomegaly and splenic pain decreased in 60 percent and 91 percent of patients, respectively. Radiation doses higher than 500 cGy appeared to be more effective than lower doses in reducing the spleen size in patients with chronic lymphocytic leukemia. Regression of splenomegaly and pain relief were maintained for less than one year and more than six months, respectively. Acute radiation toxicity resulted in the cessation of radiotherapy in two patients. CONCLUSION: Splenic irradiation is effective in the short-term palliation of splenomegaly and pain and may be most useful in the subset of patients with a life expectancy of less than one year. Terminally ill patients with splenomegaly secondary to lymphoproliferative or myeloproliferative disorders may benefit from splenic irradiation to minimize pain and pressure symptoms in addition to possible reduction of narcotic use.

Short-time splenic irradiation for splenomegaly.

Schratter-Sehn AU, . Onkologie. 2003 Feb;26(1):21-4.

Institute of Radio-Oncology, Kaiser-Franz-Josef Hospital, Vienna, Austria.

BACKGROUND: Splenic irradiation is routinely used in the supportive treatment of lymphoepithelial and hemopoietic diseases associated with splenomegaly. A new short-time irradiation schedule with conventional dosage (Group A: 2 Gy/fract.) was compared retrospectively with low-dose prolonged treatment schedules (Group B: < or = 1 Gy/fract.) to establish its tolerance and its efficacy in terms of relieving splenomegaly-associated symptoms. PATIENTS AND METHOD: Between 12/1996 and 3/2002 49 patients (6 with CLL, 14 with CML, 6 with NHL, 16 with MPD, 6 with OMF and 1 with AML) underwent 85 treatment courses (13 courses low-dose prolonged treatment and 72 courses short-time treatment). The spleens had been exposed to pretreatment doses of 3-70 Gy (mean 20.75 Gy). Splenic size was 12-35 cm (mean 22.76 cm). One treatment was done with 60Co. 9-20 MeV electron beams were used in 23 treatments and 6 MV photons in 61 treatments. Blood counts were monitored daily. Clinical improvement (pain relief, improvement of splenomegaly-associated symptoms), spleen volume reduction and effects on blood counts were evaluated and documented at the end of the treatment. RESULTS: Of the 85 treated patients, 55 (Group A: 47/72, Group B: 8/13) showed a > 10% reduction of spleen volume and 62 (Group A: 57/72, Group B: 5/13) clinical improvement. 15 of 49 patients underwent multiple irradiation (2-8 courses) without clinical or hematologic complications. The intervals between the courses were 2-19 months. Rapid response in terms of reduction in splenic size in 23 patients permitted field reduction during treatment. Significant hematologic abnormalities were absent throughout. CONCLUSION: The short-time treatment schedule ensured a rapid response with relief of pain and improvement of gastrointestinal and pulmonary symptoms at an overall treatment time shorter than that of low-dose prolonged treatment schedules. No differences in terms of hematologic abnormalities were found between single doses of 2 Gy and < or = 1 Gy. Copyright 2003 S. Karger GmbH, Freiburg

Splenic irradiation in myelofibrosis with myeloid metaplasia: a review.

Elliott MA, Tefferi A.  Blood Rev. 1999 Sep;13(3):163-70.

Division of Hematology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

Morbidity from myeloid metaplasia and myelofibrosis arises from progressive anemia and abdominal discomfort related to massive splenomegaly, which may be associated with hypercatabolic symptoms. To date, no therapy, other than allogeneic bone marrow transplantation, has been shown to cure or to prolong the survival of these patients. Thus, current management strategies are palliative and include red cell transfusional support and androgen therapy for anemia; chemotherapeutic agents for control of thrombocytosis, leukocytosis, and hypermetabolic symptoms; and splenectomy or splenic irradiation for symptomatic splenomegaly. The major indication for splenic irradiation is left upper quadrant discomfort related to massive splenomegaly, usually in patients for whom splenectomy is contraindicated or has been declined. In most patients, it provides relief from abdominal pain and a moderate reduction in splenic size. Although responses are transient, some patients may experience prolonged relief. Splenic irradiation can result in prolonged myelosuppression in certain patients. This calls for cautious dosing, because individual sensitivity is variable and cannot be predicted. The use of splenic irradiation does not preclude subsequent splenectomy; however, the increased risk of postoperative hemorrhage should discourage consideration of splenic irradiation as an alternative or a temporizing measure before splenectomy when indicated.

Splenic irradiation for chronic autoimmune thrombocytopenic purpura in patients with contra-indications to splenectomy.

Caulier MT, Darloy F, Rose C, Camier G, Morel P, Bauters F, Fenaux P.  Br J Haematol. 1995 Sep;91(1):208-11.

Service des Maladies du Sang, C.H.U. Lille, France.

We treated by splenic irradiation eight patients with chronic idiopathic thrombocytopenic purpura (ITP, seven cases) or secondary autoimmune thrombocytopenic purpura (one case) who had contra-indications to splenectomy. A total dose of 15 Gy was delivered to the spleen, with left kidney protection. One patient had a good durable response (> 1 year); two patients had a good transient response (of 3 months duration) but they responded again to a second course of irradiation; two patients had only partial response, but have required no other treatments for 2 years; the three remaining patients had no response. Side-effects were minor. Therefore splenic irradiation appears to be a therapeutic option in patients with chronic ITP who have contra-indications to splenectomy.

Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases.

Weinmann M, Becker G, Einsele H, Bamberg M.  Strahlenther Onkol. 2001 Feb;177(2):105-11.

Department of Radiation Oncology, University of Tubingen, Germany. martin.weinmann@med.uni-tuebingen.de

BACKGROUND: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. PATIENTS, MATERIALS AND METHODS: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. RESULTS: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. CONCLUSIONS: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality.

Splenic radiation for corticosteroid-resistant immune thrombocytopenia.

Calverley DC, Jones GW, Kelton JG.  Ann Intern Med. 1992 Jun 15;116(12 Pt 1):977-81.

Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada.

OBJECTIVE: To determine the role of splenic radiation as a treatment for immune thrombocytopenia. DESIGN: Retrospective analysis of an open, nonrandomized investigation. SETTING: A regional cancer center, referred care, and primary care settings. PATIENTS: Eleven older patients with idiopathic thrombocytopenic purpura (ITP) and 8 patients with secondary immune thrombocytopenia refractory to corticosteroid treatment for whom surgery would have posed a high risk. INTERVENTION: A short course (1 to 6 weeks) of radiation therapy to the spleen (total dose, 75 to 1370 cGy) with or without concurrent and postradiation corticosteroid administration. MEASUREMENTS: Efficacy was assessed by measuring any increase in the platelet count and by monitoring the duration of response and side effects. RESULTS: Of 11 patients with ITP, 8 patients responded. Three patients had a sustained (greater than 52 weeks) increase in the platelet count to safe levels after therapy was discontinued. An additional patient had a sustained response but required intermittent, low-dose corticosteroids. Four other patients had increases in their platelet counts that lasted from 8 to 25 weeks. Two of the eight patients without ITP had a positive response, whereas four did not respond, and two were not evaluable. Patients had no adverse reactions to the radiation treatment. CONCLUSION: Splenic radiation can be a safe and effective method to raise the platelet count in older patients with ITP that is refractory to corticosteroids and in whom the risks associated with splenectomy are high.