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Radiation therapy for the spleen for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

The spleen and lymph nodes along the splenic vessels and by the hilum of the spleen are considered one lymphatic region in the Ann Arbor system. Lymph node involvement in the spleen usually occurs as part of the general disease. With local treatment for lymphoma in the spleen, a splenectomy is an alternative that must be considered on an individual basis.    

Curative radiation therapy

  • Residual tumor in the speen after full chemotherapy for advanced Hodgkin's lymphoma (6-8 ABVD, 8 BEACOPP or equivalent) or aggressive lymphomas (6–8 CHOP-based cycles or equivalent) may be a circumstance for consolidative radiation therapy to the whole spleen. Alternatives may be a splenectomy, or with a negative biopsy, observation only. 
  • Special guidelines apply for children and adolescents up to 18 years with Hodgkin's lymphoma.
  • Localized stages of Hodgkin's lymphoma (stage IA/IIA) with spleen involvement, based on severity, are considered for consolidative radiation therapy to the involved field after 2–4 ABVD cycles or equivalent. Chemotherapy as for advanced disease may be considered an alternative, but radiation therapy is given only to residual lesions after a splenectomy. 
  • Localized stages of aggressive lymphomas (stage I/PeI-II1/PeII1), based on severity, are given consolidative radiation therapy after CHOP-based chemotherapy or equivalent to the initial tumor volume before chemotherapy. In both of these cases, the lymph nodes along the splenic vessels are included, and if necessary, the upper retroperitoneal lymph nodes as well to achieve adequate margins to the primary tumor area.  
  • Indolent lymphomas with localized spleen involvement almost never occur, and are primarily evaluated for splenectomy. 

Palliative radiation therapy

  • Palliative radiation therapy to the spleen for lymphoma or myeloproliferative disease is an alternative. The indications for this may be, for example, splenomegaly with abdominal discomfort or hypersplenism. Radiation therapy may also be an alternative for patients not expected to tolerate a splenectomy. 
  • It is important to evaluate the degree of extramedullary hematopoiesis in the spleen in these patients, since radiation therapy in many cases can lead to serious pancytopenia, especially if the spleen contributes signficantly to the hematopoiesis. 

Definitions

Target Volume

 

Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)

GTV (= Gross Tumor Volume)

Tumor volume

Palpable or visible/identifiable area of malignant growth.

CTV (= Clinical Target Volume)

Clinical target volume

Tissue volume containing GTV and subclinical microscopic malignant disease.

ITV (= Internal Target Volume)

Target volume

Volume containing CTV and an internal margin taking into account internal movements and changes in CTV. This is the volume that should receive an optimal dose.

PTV (= Planning Target Volume)

Planning volume

Geometric volume containing ITV and one Setup margin taking into account assumed variation in patient movements, patient positioning, and field alignment.

Planning contour: Beams-Eye-View projection of PTV.

IM (= Inner margin) and SM (= Setup margin)

IM and SM cannot be summed linearly. Total margin must be given specifically for different tumor localizations.

Field limit

The field limit is defined as the area that 50% of the isodose curve outside the target volume must have to give a therapeutic isodose (90% isodose) which encircles the target volume to be treated. The distance from 90-50% of the isodose (penumbra) depends on multiple conditions and is typically 5-7 mm.

Definition of margins

The table below summarizes standards for use of the term GTV, for margins to CTV and ITV, as well as formulation of field limits for radiation therapy of malignant lymphomas.

Target volume for radiotherapy

GTV Tumor in indolent NHL stage I/II1, original tumor (before chemotherapy minus balloon effect) in aggressive NHL stage I/II1 and HL stage I/IIA

Residual tumor in aggressive NHL stage II2/IV and HL stage IIB/IV

CTV GTV + 2 cm craniocaudal to confined disease/short chemotherapy

GTV + 1 cm craniocaudal to residual tumor from advanced disease after full chemotherapy

GTV + 1 cm in the transversal plane

CTV should always include the entire lymph node region in the levels to be irradiated (limited in the lungs and bone, unless there is suspicion of infiltration).

CTV may for indolent NHL stage I/II1 include the nearest non-infiltrated lymph node region or parts of it.

ITV CTV if internal movement is negligent (CNS, ENH and others)

CTV + up to 1 cm craniocaudal and up to 0.5 cm transversal in the mediastinum

CTV + 2–3 cm in mesentary and stomach

CTV + up to 0.5 cm transversal retroperitoneally

PTV

Not routinely defined

Field limits

Are set to 1 cm outside ITV for set-up margin and penumbra

Field limits should be arranged so that later junctions are as simple as possible (for example on one side of the spine, in invertebral discs)

Involved node

The field of radiation surrounding macroscopically involved lymph nodes alone with margin. This definition is currently not widely used in Norway, but is emerging in international studies.

Involved field

The involved field is the field of radiation surrounding the macroscopically involved lymph node region or organ with margin. After limited chemotherapy of localized lymphomas, the original macroscopically involved area is used as the foundation for field contouring (with the exception of the balloon effect). For residual lesions after full chemotherapy for advanced stages, the residual tumor is usually used as the foundation (with some exceptions). What determines an adequatemargin from the macrotumor to the field limit depends on multiple factors. For early stages of NHL and HL without previous chemotherapy or after chemotherapy (3–6 CHOP-based cycles, 2–4 ABVD or equivalent), the margins from the initial tumor to the field limit should be 3-4 cmin the direction of lymph drainage lengthwise from initial extent and 2 cm in the transversal plan (exception for balloon effect). With residual lesion have full chemotherapy for advanced NHL and HL and relatively little internal movement, then 2 cm from residualtumor to the field limit is used. Larger margins may be considered in areas for greater internal movement (abdomen, structures near diaphragm). As a general rule with nodal involvement, the target volume includes the entire lymph node region in the transversal plane for the levels included in the field.

Traditionally, the entire inolved lymph node area has been included completely in the craniocaudal direction (direction of lymph drainage). This provides a recognizeable geometric field (parts of mantle or inverted Y field) which is advantageous for standardization, reproduciblity, later junctioning etc. The lymph node regions as defined in the Ann Arbor classification then do not represent any biologically functional entitites and are not considered a base for radiation therapy. Thus, it is natural to see the regions coherently length-wise inthe direction of lymph drainage and use margins to involved lymph nodes to avoid irradiation of entire regions (for example in the neck, supreclavicular region, mediastinum, and retroperitoneum). Parts of neighboring organs are included to satisfy the minimum margins given above. Field modeling should still be geometric shapes as much as possible to make later joining of fields easier and to avoid border recurrences in areas difficult to irradiate again.

For extranodal lymfomas/organ manifestations, it is sometimes natural to include the entire organ (thyroid gland, stomach, brain, spinal cord). In such cases, it is also necessary to take internal movement into consideration, for example, stomach movement and movement of lung borders etc. With multiple organ localizations, it is not possible to give full doses to the entire organ due to the tolerance for ionizing radiation (lungs, liver, kidneys) and the fields and doses must be adapted accordingly.

Extended field

This type of field includes macroscopically involved regions/organs and lymph node regions that are assumed to have diseased cells. This may be the nearest macroscopically normal region or multiple, more distant areas. This technique was developed for Hodgkin's lymphoma when radiation therapy was used as the only treatment modality and was given to large areas with assumed microscopic disease on one or both sides of the diaphragm (mantle field, paraaortal field, inverted Y-field). In today's practice, the term 'extended field' is not widely used. For localized stages of low-grade NHL, where radiotherapy is given alone to cure the disease, we have chosen to include the nearest uninvolved regions in the field of radiation, a type of "minimally extended field". This is not, however, practiced by all radiation therapy centers in Norway.


Preparation

  • The patient should be given a pneumococcal vaccine at least 2 weeks before starting radiation therapy for the spleen, which is the same as for a splenectomy. 
  • The left kidney will always be partly or comletely involved in treatment and evaluation of kidney function (total and each side) and kidney position is done before simulation/dose planning, especially if the dose is over 20 Gy. 
  • Ultrasound before direct simulation to mark the position of the spleen on the abdominal wall during normal inspiration and expiration is advantageous. 
  • The patient lies supine.

Implementation

Conventional simulation

  • For conventional simulation, it is sometimes possible to use palpation findings as a guideline for field modeling, or view the spleen as a soft tissue shadow on X-ray images. 

  • Ultrasound to mark the position of the spleen on the abdominal wall during normal inspiration and expiration may be advantageous. 

  • The spleen lies under the left diaphragmatic arch and follows this cranially and laterally. The medial and caudal borders of the spleen may vary. Craniocaudally, consideration for movement of the diaphragm should be taken, and the field border should therefore be up to 2 cm above the diaphragm in the lung. 

    The movement of the diaphragm is checked by X-ray. 

  • Lymph nodes of the hilum of the spleen and along the splenic vessels are often included. 

  • The stem of the spleen with vessels often project over the upper third of the left kidney and in toward the upper paraaortal region.  

  • The field border should have a minimum 2 cm margin to the spleen contour. With involvement of the hilum of the spleen, a there must also be a margin along this in toward the upper paraaortal region. 

CT-based simulation

  • Visible tumor in the spleen is defined as GTV together with any visible changes in the hilum of the spleen and along the splenic vessels. 

  • CTV is generated with a 1 cm margin. The entire spleen is always included in CTV. The hilum of the spleen and lymph nodes along the splenic vessels and in toward the upper paraaortal region are aslo included if this indicated.  

  • There should be a margin of 1 cm (minimum) in the craniocaudal direction to ITV (diaphragm movement) and 0.5–1 cm in the transversal plane.

  • The pasient should be viewed on the simulator to check that the field borders are sufficient, and especially that the cranial borders are over the diaphragm with adequate margins in all phases of respiration.  

CT dose plan, spleen

Fractionation

Standard fractionation and total dose for curative treatment is given below.

  • For Hodgkin's lymphoma stage I-IIA without risk factors: 2 Gy x 10
  • Otherwise for Hodgkin's lymphoma: 1.75 Gy x 17
  • For curative treatment of indolent non-Hodgkin lymphoma: 2 Gy x 15
  • For aggressive NHL: 2 Gy x 20.
For palliative therapy, the fractioned dose and dose and total dose should be individualized. 
  • Many patients without extramedullary hepatopoiesis in the spleen will tolerate fractions of 1.2–1.5 Gy given 4-5 times per week up to 20–30 Gy. Field reduction may be possible as the spleen reduces in size. 
  • If there is suspicion of extramedullary hematopoiesis in the spleen, fractioned doses of 0.2–0.5 Gy given 3 times per week may be advantageous, at least initially. The patient's general status and counts are evaluated regularly during treatment. The total dose and field reduction is evaluated during treatment, and total doses of 1–10 Gy may be adequate treatment for most. 

Follow-up

Organs at risk 

Stomach and intestines

Nausea can be expected in most patients undergoing this treatment. Nausea prophylaxis should be started before the first fraction. Dyspepsia, diarrhea, and pain may be a sign of mucositis in the stomach and intestines. Ulcerations and perforation can also occur.

Bone marrow 

Depending on bone marrow function, a fall in counts may occur and should be measured in patients during and shortly after treatment. Regular follow-up may be necessary during this time.

Kidney 

Depending on the dose received by the kidneys, a reduction in kidney function and renal hypertonia may occur in the long run.


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