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Radiation therapy for the inguinal and femoral region for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

Lymph nodes by the inguinal ligament and upper thigh are defined by the Ann Arbor classification systen as one region. Lymphoma involvement occurs in the femoral region with relative variation compared to caudal spreading. 

Radiation therapy to the inguinal/femoral region is given in many instances, often together with the iliacal region or as a dog-leg field. 

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

    Radiation therapy to the inguinal and femoral region is considered part of an inverted Y field.

    • Sperm banking for men and possibly freezing of ovarian tissue or operative elevating or fixing of the ovaries (ovariopexy) in girls/women is considered. 
    • The patient lies supine with their arms by their side.
    • In male patients, there must be adequate space between the legs for placement of a gonadal shield (scrotum cup, lead belt and/ or gonadal shield). For irradiation of the iliacal region on one side (and dog leg field or L field), a lead belt is used where the scrotum is over on the contralateral side and shielded with a lead shield. For bilateral irradiation, a scrotum cup is used in addition to a lead shield. 
    • For girls and women of fertile age, shielding of the ovaries and/or ovariopexy should be considered. Ovariopexy is the surgical relocation of the ovaries out of the small pelvis to the midline behind the uterus. Surgical clips should indicate where the ovaries are located. Only then is it possible to exclude the ovaries from the target volume. The ovaries can be shielded additionally from diffuse radiation by using a gonadal shield attached to the treatment table.
    • If there is uncertainty of kidney function and the location of the kidneys relative to the fields, GFR with renography should be performed before simulation. 
    • To localize the kidneys during simulation, intravenous urography is performed. Evaluation of the amount of kidney included in the field that will necessitate changes to the fields after, for example 18–20 Gy can then be done.
    • The need for marking the biopsy scar/palpable findings with marking thread should be considered. 
     

    Implementation

    Conventional simulation

    • A standard inguinal and femoral field has a cranial border at minimum 2 cm above the inguinal ligament. The caudal border is below the fossa ovalis, which by X-ray is almost equivalent to the lower border distal to the small trochanter.  
    • The lateral border standardly runs from the lateral border of the acetabulum. The medial border is such that the skin border medial to the thigh is spared, which is about 2-3 cm lateral to the symphysus.
    • Depending on the craniocaudal extent of the tumor, the field border should 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 margin to the residual tumor after full chemotherapy for advanced disease. 
    • The border from the tumor to the field border in the transversal plane should be 2 cm. 
    • An isolated inguinal/femoral field may possibly be irradiated from the front in one field, and electron radiation may also be considered. This may give a smaller dose to the femur head. 
    • Since the distal iliacal region is often included, the half-beam block technique can be used which allows one front field in the bottom area and through irradiation in the upper area. At Oslo University Hospital, a standard procedure for unilateral and inguinal irradiation has been created for this purpose.

    CT-based simulation

    • The actual or orginal tumor volume (for curative treatment of localized indolent lymphomas or after limited chemotherapy for early stages of HL and aggressive NHL) defines GTV.
    • CTV is generated by the margin in the craniocaudal direction 2 cm (for curative treatment of localized indolent lymphomas or after limited chemotherapy for early stages of HL and aggressive NHL) or 1 cm (residual tumor after full chemotherapy). A 1 cm margin to CTV in the transversal plane, and CTV are contoured such that the entire nodal region is included in the levels irradiated.
    • CTV is set similar to ITV.
    • An alternative is to first define the desired field borders in the coronal slice on the CT dose plan program according to the guidelines that apply for direct simulation. An ITV can then be generated by subracting the margin from the set-up variation and penumbra (1–1.2 cm). This ITV can, if necessary, be modified for the situation. 

    CT dose plan, inguinal and femoral region 

    Gonadal shielding

    • Gonads present in the primary field, but not within the target volume, must be shielded by blocks in the filter holder or by using a multileaf collimator. At Oslo University Hospital HF, lead blocks have traditionally been used rendering 10 half value layers. The standard blocks used previously for the scrotum (in men) and bladder bladder (both women and men) are no longer used. The leaves from the multileaf collimator can be enhanced by using and extra lead layer to give the same effect.   

    • For girls and women of fertile age, shielding of the ovaries and/or ovariopexy should be considered. Ovariopexy is the surgical relocation of the ovaries out of the small pelvis to the midline behind the uterus. Surgical clips should indicate where the ovaries are located. Only then is it possible to exclude the ovaries from the target volume. 

    • In addition to shielding, it is important to consider use of close shielding against diffuse radiation, which mainly occurs in the filter holder and multileaf collimator. This applies to both the gonads that lie in the primary field but are shielded with blocks or multileaf collimator and for gonads that lie outside but near the primary field. At Oslo University Hospital today, a lead belt is used to pull the scrotum away from the field for unilateral irradiation in the pelvic region, as well as a gonadal shield attached to the treatment table. For symmetric irradiation in the pelvic region, a scrotum cup is used (5 mm of lead under and on the side of the scrotum) with a 3 cm lead block on top. The ovaries are shielded from diffuse spreading if they are in the primary field or near it with a gonadal shield attached to the treatment table.    

    Fractionation

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

    • For Hodgkin's lymphoma stage I-IIA without risk factors: 2 Gy x 10 (note that iliacal involvement itself is a risk factor)
    • 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.

    Follow-up

    Risk organs

    Intestines

    In some patients, nausea, diarrhea and rectal symptoms in the form of pain and bleeding can occur.

    Bladder

    Radiation-induced cystitis may occur.

    Gonads

    The dose to the gonads should be as small as possible to preserve fertility. Reliable birth control during treatment is necessary, and is recommended until a year has passed after treatment. 

    Femur head and femur neck

    Osteoporosis of the femur head and femur neck may occur after radiation therapy and increases the chance of fracture.


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