Radiation therapy for mesenterial lymph nodes for malignant lymphomaMedical editor Alexander Fosså MD
Oslo University Hospital
Mesenterial lymph nodes are a separate lymph node region in the Ann Arbor system. The region is large, and characteristically lesions in this area have much internal movement.
Curative radiation therapy
- Limited stages of Hodgkin's lymphoma (stage IA/IIA) with mesenterial involvement is rare, and central infradiaphragmal disease itself is a risk factor. According to guidelines, these patients are given 4 ABVD cycles followed by consolidative radiation therapy to the involved field, but this is based on the premise that involved areas can be included in a reasonable field with adequate margin. If this is not the case, for example due to large tumor masses, the position of the kidneys etc., chemotherapy for advanced disease should be given, and radiation therapy considered for residual lesions.
- 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. This is based on the premise that involved areas can be included in a reasonable field with adeqate margin. If this is not the case, for example due to large tumor masses, the position of the kidneys etc., chemotherapy for advanced disease should be given, and radiation therapy considered for residual lesions.
- 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 is given after chemotherapy (CHOP-based or equivalent) to the original tumor-involved area with margin (involved field). This is based on the premise that involved areas can be included in a reasonable field with adeqate margin. If this is not the case, for example due to large tumor masses, the position of the kidneys etc., chemotherapy for advanced disease should be given, and radiation therapy considered for residual lesions.
- 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 (stage I-II1), radiation therapy alone is given to the involved area with margin (involved field). This is based on the premise that involved areas can be included in a reasonable field with adeqate margin. If this is not the case, for example due to large tumor masses, the position of the kidneys etc., chemotherapy for advanced disease should be given, and radiation therapy considered for residual lesions.
Palliative radiation therapy
- As palliative radiation therapy, the method is based on guidelines for curative treatment with individual modifications.
|Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)
GTV (= Gross 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)
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)
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.
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
||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
||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.
||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
Not routinely defined
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)
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.
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.
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.
The patient lies supine with their arms by their side.
Sperm banking for men and possibly freezing of ovarian tissue or operative elevating or fixing of the ovaries (ovariopexy) in girls/women is considered.
Gonadal shielding may be necessary. In male patients, there must be sufficient spread between the legs to place a shield (gonadal block or lead belt).
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.
Direct simulation of fields to mesentary and other abdominal lymphoma manifestations should only by done for palliative treatment with a relatively short goal for symptoms relief. Much movement oflesions in the mesentary must be expected as well as a low accuracy by X-ray on the simulator.
For direct simulation, the field borders are placed with adequate margins to the tumor to include microscopic growth in the tumor border zone (1 cm), penumbra and set-up variation (minimum 1–1.2 cm) and assumed internal movement. In addition, there is uncertainty because during palpation or X-ray, tumor borders can almost never be defined with certainty. One must depend on information from radiological diagnostics which is transferred to the simulator image (for example the relation of the tumor to bone structures).
The fields are often large.
Treatment should be done based on CT-guided dose planning.
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 with a 1 cm margin in all directions, but is limited to the contact surfaces where infiltration is not expected such as bone structures.
- A 2-3 cm margin is made for internal movement for ITV. ITV should, again, be limited. For example, if the movement in toward the retroperitoneal structures such as the kidney and spine is significantly less that in the peritoneal cavity.
- Standard field set-up is with anteroposterior beams, but in many cases, the extent of the tumor in the kidney region, side differences in kidney function etc. necessitate other field set-up with better shielding of healthy renal tissue, for example a diagonal field or side field.
CT dose plan, mesenterial lymph nodes
CT dose plan, paraaortal region
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.
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.
- For large abdominal fields where doses to the kidneys are limited, fractionation into 1.2 Gy x 15-16 or 1.5 Gy x 12-13 may be considered.
Organs at risk
Organs at risk depend on the localization of the tumor in the abdomen and the size of the radiation fields.
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.
Cases of radiation-induced cystitis can occur. Depending on the dose to the kidneys, kidney function may be reduced and renal hypertonia may occur in the long run.
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.
Great emphasis should be placed on reducing the dose to the gonads to preserve fertility. Reliable birth control during treatment is necessary and is recommended for one year after treatment.
Irradiation under the diaphragm is associated with increased risk for later cancer in organs within or near the fields of radiation.