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Radiation therapy of eye for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Malignant lymphomas in the eye originate from the eyelid, lacrimal gland, conjunctiva, or retroorbital structures. Histologically, these are often MALT lymphomas with histologies resembling marginal zone lymphoma. 

Indications

Curative radiotherapy

  • Marginal zone lymphomas are often localized lymphomas in stage PeI, and are candidates for curative radiation therapy alone.  
  • Aggressive lymphomas (DLBCL, Burkitt's lymphoma, NK/T cell lymphoma) occur usually as more advanved disease in the ENT area with invasion into the eye. For these types, consolidative radiation therapy after chemotherapy is often given. Depending on the degree that bone structures are involved, tumor volume before chemotherapy may be decisive for field modeling.
  • Intraocular lymphomas are usually histologically DLBCL, occuring as part of PCNSL and treated as such. If radiotherapy is given as part of multimodal therapy, the eye should be included and usually bilaterally. 

Palliative radiotherapy

  • For palliative radiotherapy, the method will follow guidelines for curative radiotherapy with individual modifications. 

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

  • Isolated fields toward the eye normally to not involve the teeth in the upper jaw. If treatment becomes expanded at some point, and the teeth in the upper jaw are infiltrated, dental treatment must be finished before immobilization and treatment start. 
  • If there is relevant eye disease limiting the dose to one or both eyes, the patient should be evaluated by an opthomologist. 
  • The patient is immobilized in a mask.

Implementation

Conventional simulation

With isolated skin involvement on the eyelid, local irradiation with electrons or X-rays is considered. An eye shield inside the eyelid is used to spare the lense and retina. 

CT-based simulation

  • For deep-lying lesions, CT dose-planned treatment with photons is used.  
  • For marginal zone lymphoma in stage PeI, the entire eye within the ocular cavity is considered CTV and ITV. This is to avoid recurrence and the need to retreat in the same area. For stage PeI, local node stations are not drawn in as CTV. Bolus is considered for lesions near the skin surface. 
  • For consolidative treatment after chemotherapy for aggressive lymphomas, the initial tumor volume with areas for bone involvment is usually the appropriate GTV, and CTV is generated with 1 cm margin. 
  • Avoid hotspots in surrounding organs at risk such as the optic chiasma and pituitary gland. 
  • For marginal zone lymphomas in paired organs, recurrence or new lymphoma sometimes occurs in the contralateral organ. This is particularly the case with marginal zone lymphoma of the eye. This should be considered when choosing field set-up, and dosing to healthy tissue on the contralateral side of the head should be avoided. Two diagonal wedge fields from the front are normally adequate. 

CT dose plan, eye

Fractionation

Standard fractionation and total dose for curative therapy is given below. These are also guidelines for palliative treatment, but should be modified individually. 

  • For curative treatment of indolent NHL: 2 Gy x 15
  • For aggressive NHL: 2 Gy x 20

Follow-up

Organs at risk 

Optim chiasma and pituitary gland

The radiation doses for lymphoma treatment is under the tolerance limit for these structures, but hot areas should be avoided in these organs. 

Eyes and lenses

Cataract in the irradiated eye should be expected within years after treatment if the lense cannot be shielded. The radiation dose for lymphoma treatment is under the tolerance limit for the retina and optic nerve. The contralateral eye should be shielded as much as possible.

Salivary glands

The parotid gland is, in most cases, not included in the high-dose area, even on the side of the irradiated eye. The contralateral parotid gland should be spared as much as possible to avoid dry mouth. 


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