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Radiation therapy for the nose and sinuses for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

Lymphomas in this area are often aggressive lymphomas such as DLBCL, NK/T cell lymphomas, and Burkitt's lymphoma. NK/T cell lymphomas as a group are rare, but have a predilection for this localization. Tumors often have a locally aggressive growth pattern with infiltration of bone in surrounding structures (eye, skull with possible intracranial growth, oral cavity, skin). As for aggressive lymphomas in general, they are normally treated with chemotherapy initially according to histology, stage, and risk profile. Aggressive lymphomas in this localization lead to a higher risk for CNS manifestations and CNS-directed treatment/prophylaxis is often indicated. 

Curative radiation therapy

  • Radiation therapy is given as consolidative after chemotherapy regardless of histology and should always be considered if there is involvement of bone and/or there is residual tumor after chemotherapy.

Palliative radiation therapy

  • As palliative radiation therapy, the method is based on guidelines for curative treatment 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

  • The patient must be evaluated by a dentist and any dental treatment must be finished before treatment is started.
  • If one or both eyes are involved, it must be evaluated whether there is disease that may limit the dose to one or both eyes.
  • The patient must be immobilized with a mask.

Implementation

CT-based simulation

The treatment is planned using CT.

  • Visible tumor is defined as GTV. If initially there is locally advanved growth, with bone destruction, the initial tumor volume before chemotherapy is used in areas with bone involvement.
  • CTV is generated with 1 cm margin to GTV.
  • Avoid hot areas in organs at risk such as the eyes, optic chiasma, or pituitary with complicated field layout.

CT dose plan, nose and sinuses

Fractionation

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

  • For Hodgkin's lymphoma: 1.75 Gy x 17
  • For aggressive Non-Hodgkins lymphoma: 2 Gy x 20

Follow-up

Organs at risk

Mucosa 

Acute mucosal toxicity such as mucositis in the nose, mouth, and larynx during treatment and shortly after occurs in most patients, some are considerably affected.

Skin and hair

Reversible alopecia in irradiated areas of the head and jaw (beard growth) should be expected. 

Lense, eyes, optic chiasma, pituitary gland

Fields to the ear-nose-throat region will contribute a small dose that normally lies under the tolerance dose for these organs. It is important to avoid unintended hot spots in these organs.

Teeth

Defects should be repaired before treatment start to prevent later osteoradionecrosis. Caution should be used with dental treatment after irradiation. 

Salivary glands

Lasting dry mouth should be expected if the field includes both parotid glands. If this can be avoided, problems are often reduced moderately.

Blood vessels in the neck 

After irradiating blood vessels in the neck, there is a small increased risk for cerebrovascular complications.


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