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Radiation therapy for the paraaortic region for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

Paraaortic, paracaval, and interaorticaval lymph nodes from the diaphragm to the aortic bifurcature are covered by one paraaortic field. Radition therapy to the paraaortal region is given in many circumstances.

Curative radiotherapy

  • 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 involved area with margin (involved field).

Palliative radiotherapy

  • 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 paraaortal field is considered part of an inverted Y field. 

  • Sperm banking for men and possibly freezing of ovarian tissue should be assessed before treatment starts. 
  • Evaluate the need for ovariopexy in girls/women of fertile age before simulation. 
  • The patient lies supine with their arms by their side. The doctor will ensure the patient is immobilized on the simulator. In male patients, there should be sufficient spread between the legs for placement of gonadal shielding.    
  • If there is uncertainty of the patient's kidney function, GFR with renography should be done 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

  • For modeling of the paraortal field by direct simulation, the upper field border is usually located at Th10/11 and the lower border is at the bottom edge of L4 or L5. Craniocaudally, the field limit should then have a minimum of 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 residual tumor after full chemotherapy of advanced disease.  
  • Standard field width is such that the transverse processes are within the field with about a 1 cm margin giving field width of 8-10 cm. Lateral field limits must be individualized depending on the extent of the tumor, localization of the kidneys, kidney function, and total dose. Tumor spreading in the transversal plane with a 2 cm margin defines the field breadth. For early stages of lymphoma after short systemic treatment where reduction of the tumor may lead to a better margin to the kidney and intestines after chemotherapy (balloon effect), the residual tumor can usually be used as basis for the field width.  
  • As for other regions, the paraaortal region is irradiated in the entire width of the levels where indicated. 
  • If a mediastinal field has previously been given and a joining is necessary, the field and joining must be calculated by a physicist. Consider using a medulla block, such as a block in the posterior field over the nearest 2-3 cm of medulla to the joining.
  • Areas of recurrence between the paraortal field and earlier mediastinal field should be avoided since they may be difficult to retreat.

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.
  • Margin to ITV in the transversal plane is 0–0.5 cm.
  • An alternative is to first define the desired field borders in the coronal slice on the CT planning program according to the guidelines that apply for direct simulation. An ITV can then be generated by subtracting the margin from the set-up variation and penumbra (1–1.2 cm). This ITV can be modified if necessary for the situation.
  • Standard field set-up is with an anteroposterior beam, but in many situations tumor spreading to the kidney region, side differences in kidney function etc. necessitates other field field set-up with better shielding of healthy kidney tissue, for example a diagonal field or side field.
  • If a mediastinal field has previously been given and a joining is necessary, the field and joining must be calculated by a physicist. Consider using a medulla block, such as a block in the posterior field over the nearest 2-3 cm of medulla to the joining. 
  • Areas of recurrence between the paraortal field and earlier mediastinal field should be avoided since they may be difficult to retreat.

CT dose plan, paraaortal field

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 4 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
  • 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

Organs at risk

Stomach and intestines

Nausea can be expected in most patients undergoing this treatment. Nausea prophylaxis should be started before the first fraction. Dyspepsia, diarrhea, and pain may be a sign of mucositis in the stomach and intestines. Ulcerations and perforation can also occur.

Bone marrow 

Depending on bone marrow function, a fall in counts may occur and should be measured in patients during and shortly after treatment. Regular follow-up may be necessary during this time. 

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.

Kidney 

Depending on the dose received by the kidneys, a reduction in kidney function and renal hypertonia may occur in the long run.


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