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Radiation therapy of the infraclavicular region for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

The infraclavicular region is a specific region in the Ann Arbor classification, but is rarely involved alone. The region is almost never treated alone with radiation; it is usually treated together with the axillary and supraclavicular region.

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.

     

     

     

     


    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

    Since the infraclavicular region is often treated together with the axilla and supraclavicular region, the method is usually similar to the axillary field.

    • For direct alignment on the simulator, the axillary field is aligned with the overarm abduced to 90º.
    • For CT dosage-planned treatment, the arms are immobilized over the head in a wing board or slightly along the upper body. The reproduceability of the position may be a problem with slightly abduced arms. A 5-point mask with immobilization of the shoulder area may improve stability. With skin folds, skin reactions may be more problematic with doses up to 40 Gy. A side field cannot be given toward the neck if the arms are immobilized over the head with a wing board, and contouring ofthe infraclavicular region may be more uncertain since the claviclel and soft tissue will change the position.
    • In women, the breasts should be moved out of the field. 
    • Palpable findings and possible scarring or skin changes are marked with marking thread.

      


    Implementation

    Conventional simulation

    Since the infraclavicular region is usually treated together with the axilla and supraclavicular region, the same method applies.

    For direct simulation, the field to the infraclavicular region together with the axilla and supraclavicular area runs cranially below the neck and medially at the pedicles on the same side of the spine. 

    • To include lymph nodes on the thoracic wall, the thoracic wall is included medially and an edge of the lung of 1 cm. This line follows the lower edge of the fourth rib in toward the medial border. 
    • Laterally, the border runs from the humerus and includes the lateral parts of the axilla.
    • Caudally, the border runs by the breast, depending on the location of the tumor and the patient's anatomy.  
    • Cranially and laterally, the head of the humerus is blocked out as in the mantle field.
    • The field limits are modified to have an adequate margin to the tumor. The field border should have a 3–4 cm margin to the initial tumor volume in the direction of lymph drainage (for curative treatment of localized indolent lymphomas or after limited chemotherapy for early stages of HL and aggressive NHL) or 2 cm margin to residual tumor after full chemotherapy for advanced disease. In the transversal plane, there should always be a 2 cm minimum to the field border, but the region is usually included in full standard width in the levels included in the field.  
    • Parts of the mediastinum, for example the upper mediastinum, are sometimes included.

    CT dose plan, neck region and supraclavicular fossa

    CT dose plan, axillary region

    CT-based simulation

    • For contouring of the axilla with CT, it is important to be aware that standard immobilization does not allow 90º abduction of the shoulder. Therefore, the best method for immobilization in relation to the planned target volume should be determined prior (see under preparation). 
    • Contouring of target volume in the axilla is difficult since a strictly anatomical model using CT slices often gives disproportionately large fields of both the lungs and sometimes breasts.
    • A possible solution to this problem is to first identify the desired field borders in the coronal slive with the CT dosage planning program in relation to the guidelines that apply for direct simulation and which are based on modeling of the mantle field.  An ITV can then be generated by subtracting the margin from the set-up variation and penumbra (1–1.2 cm). If necessary, this ITV can be modified for the situation. 
    • Further, it is often difficult to achieve a completely optimal dose distribution in the medial parts of the axilla due to large variations of cross measurements in the axilla and due to the percent of lung in the field. The benefit of optimal dosing in the ITV must be assessed against possible warm areas in, for example, the breast. 
     

    Fractionation  

    Standard fractionation and total dosage for curative treatment is described below. These are also normative for palliative treatment, but must be modified for each patient.  

    • For Hodgkin's lymphoma stage I-IIA without risk factors: 2 Gy x 10
    • Hodgkin's lymphoma: 1.75 Gy x 17.
    • For curative treatment of indolent non-Hodgkin lymphoma: 2 Gy x 15
    • For aggressive non-Hodgkin lymphoma: 2 Gy x 20.

    Follow-up

    Risk organs

    Skin 

    • Soreness in the skin folds of the axilla may occur. 

    Lungs

    • Subacute radiation pneumonitis during the first months after treatment may occur. Irradiated areas of the the lungs will often develop fibrosis over time. 

    Secondary cancer

    For patients receiving mantle field irradiation for Hodgkin's lymphoma, there risk for secondary cancer increases significantly, especially for organs given full therapeutic doses. Breast cancer, lung cancer, thyroid cancer, sarcomas, skin cancer, and melanoma are some of the most common. 

    Secondary cancer represents the most significant cause for increased mortality of patients cured of Hodgkin's lymphoma by radiation therapy. For younger women with mantle field irradiation under 35 years, a yearly mammogram is recommended starting about 8 years after irradiation. 

    For patients with other lymphoma entities, there are no set follow-up routines for smaller radiation fields and early diagnosis of other cancer forms. 

    The patient should be discouraged from smoking.


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