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Radiation therapy of the neck region and supraclavicular fossa for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

In the Ann Arbor classification system, the neck with the ipsilateral and supraclavicular fossae are one region. In radiation therapy, it is in many cases natural to separate the upper neck region, lower neck region, and supraclavicular fossa on each side from each other. Thus, for example, when treating Waldeyers ring and no involved lymph nodes, it is correct to include the upper neck region with submental, submandibular, and occipital nodes to have an adequate margin in the caudal direction.  When treating the mediastinum, it is important to include the supraclavicular fossa bilaterally to have adequate margins to the tumor to be irradiated. Also, sometimes the supraclavicular fossa and infraclavicular fossa on the same side must be included when the axilla is irradiated. 

Curative radiation therapy

  • For localized stages of classical Hodgkin's lymphoma (stage IA/IIA), radiation therapy is given to the original area involved with margin (involved field) after chemotherapy (ABVD or equivalent).
  • For localized stages of nodular lymphocyte-rich Hodgkin's lymphoma (stage IA/IIA) without risk factors, radiation therapy alone is given to the involved area with margin (involved field) without previous chemotherapy.
  • Special guidelines apply for children and adolescents up to 18 years with Hodgkin's lymphoma. 
  • For residual tumor of Hodgkin's lymphoma after full chemotherapy for advanced Hodgkin's lymphoma (6-8 ABVD, 8 BEACOPP or equivalent), consolidative radiation therapy to the residual tumor with margin is considered.  
  • For localized stages of aggressive lymphomas (stage I-II1), consolidative radiation therapy after chemotherapy (CHOP-based or equivalent) to the original tumor-involved area with margin (involved field) is given.
  • With residual tumor of aggressive lymphomas after full chemotherapy (6-8 CHOP-based cycles or equivalent), consolidative radiotherapy to the residual tumor with margin is considered. 
  • For indolent lymphomas with localized disease (stadium I-II1), radiation therapy alone is given to the involved area with margin (involved field).

Palliative radiation therapy

As palliative radiation therapy, the method is based on guidelines for curative treatment with individual modifications.

     

     

     


    Kapitteloverskrift mangler!

    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

    For radiation therapy to the upper parts of the neck where the upper and/or lower jaw is involved, the patient must be evaluated by a dentist. Any dental treatment must be finished before immobilization and treatment start.

    Patients are immobilized with a mask (3-pint or 5-point mask) with the jaw adequately extended. A slight extension of the neck as for a mantle field is normally sufficient.


    Implementation

    Conventional simulation

    For direct simulation, the neck field can be considered a slice of an earlier mantle field.  

    • The standard upper and lower limit for a full neck field is 1–2 cm cranially for the mandibular angle (with adequate extension of the jaw, also covers submental, submandibular, and occipital nodes) and 1 cm below and along the clavicle. Craniocaudally, the field limit should be modified to have a 3–4 cm margin to the initial tumor volume (for curative treatment of localized indolent lymphomas or after limited chemotherapy for early stages of HL and aggressive NHL) or 2 cm to residual tumor after full chemotherapy for advanced disease. Thus, it is often unnecessary to irradiate the full length of the neck. 
    • If it is necessary to reach higher up on the neck, for example to cover enlarged lymph nodes in the mandibular angle, large parts of the oral cavity and back of the head will be included. In such cases, a connection to the side field by isocentric technique and half-beam block is considered.  
    • If there is involvement of the supraclavicular fossa, an adequate margin in the caudal direction is necessary to include the upper mediastinum and/or infraclavicular fossa. 
    • The lateral limit is in the air (for upper and lower neck field) or 0.5 cm medial to the acromioclavicular joint, which covers the entire supraclavicular fossa.
    • The medial border should be at least 2 cm from the tumor and should cover the entire neck region on the side to be irradiated. For unilateral irradiation, the field limit should not involve the spinal cord, to simplify later junction of new fields. If there is disease near the midline, the field limit should have pedicles on the contralateral side of the spinal column.  
    • For localized indolent lymphomas in stage I-II1, the nearest uninvolved area should be considered to be included, and thus extending the margin to the field limit beyond the 3-4 cm stated above.

    CT-based simulation

    • For CT dose-planned treatment of localized lymphomas, GTV is defined as visible tumor (or original tumor before chemotherapy).   
    • In the craniocaudal direction, there should be a 2 cm margin from the visible/original tumor to CTV (for curative treatment of localized indolent lymphomas or limited chemotherapy for early stages of HL and aggressive NHL). For residual tumor after full chemotherapy for advanved disease, there should be at least a 1 cm margin to CTV craniocaudally. 
    • There should be a 1 cm margin to CTV in the transversal plan, and CTV should normally include the entire involved lymph node region in the transversal plane.
    • Inclusion of the nearest uninvolved nodal area can be considered for indolent lymphomas in stage I-II1. This must then be contoured in the CTV.  
    • For CT dosage-planned treatment, in may be helpful to look at Dahanca's web information for contouring of neck lymph nodes. These suggestions for contouring should only be used as guidance, since it appears that the occipital and nuchal regions are somewhat poorly defined. An additional limitation is the fact that lymphomas do not follow metastatic patterns for carcinomas in the ENT area and that for lymphomas, all neck lymph nodes are irradiated either unilaterally or bilaterally at a given slice level. Since doses rarely surpass 40 Gy, risk organs such as the spine do not pose as a large limitation on treatment. A practical and more simple alternative is to draw the neck on one or both sides as one CTV including all anatomical structures.
    • An alternative is to first define the desired field limits in the coronal slice on the CT dose planning program according to guidelines that apply for direct simulation. An ITV can then be generated by subtracting the margin for set-up variation and penumbra (1-1.2 cm). This ITV can, if necessary, be modified for individual circumstances.  
    • Contouring should be done such that field limits follow geometric shapes as mentioned under conventional simulations, and should not lie in the spinal cord especially. A field is given with anteroposterior direction possibly with segments. To treat higher up on the neck, a side field or possibly diagonal wedge field can be considered. Isocentric technique with half-beam block usually causes junctioning issues.   

    CT dose plan, neck region and supraclavicular fossa

    CT dose plan, axilla region

    Fractionation

    Standard fractionation and total dose for curative treatment is given below. These are also normative for palliative treatment, but should be modified on an individual basis. 

    • For Hodgkin's lymphoma stage I-IIA without risk factors: 2 Gy x 10
    • Otherwise for Hodgkin's lymphoma: 1,75 Gy x 17.
    • Curative treatment of indolent NHL: 2 Gy x 15
    • Aggressive NHL: 2 Gy x 20.  

    Follow-up

    Risk organs

    Skin

    A certain degree of acute dermatitis may occur, and temporary hair loss (facial and neck hair) can be expected.

    Mucosa

    Varying degrees of acute mucositis can be expected. Even at doses of 30 Gy, some patients will develop significant yet temporary problems. 

    Teeth

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

    Blood vessels on the neck

    Reports show there is an increase in risk for later cerebrovascular disease after irradiation of the neck.

    Thyroid gland

    About half of patients irradiated to the entire thyroid gland develop hypothyroidism within years. Annual follow-up is necessary. Thyroid cancer may occur years after irradiation.

    Spinal cord 

    Normal radiation doses for lymphoma are under the tolerance level for serious spinal injury. Unintended warm areas of the spine must be avoided.  


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