Radiation therapy for the scrotum and testicles for malignant lymphomaMedical editor Alexander Fosså MD
Oslo University Hospital
Lymphoma occuring in the testicles is often aggressive and dominated by diffuse giant cell B cell lymphoma, Burkitt's lymphoma, or lymphoblastic lymphoma/ALL. Diffuse giant cell B cell lymphomas occur most commonly in elderly patients. Lymphoma is often localized to both testicles, even if only one testicle appears to be involved clinically and/or radiologically.
If tumor in the testicle is the patient's primary symtom, an orchiectomy is usually performed for diagnostic purposes. If the testicles are involved as part of generalized lymphoma or leukemia, this is usually not the case.
Treatment of lymphoma in the testicles follows the given guidelines for the respective histological entity.
Curative radiation treatment
- With giant cell B cell lymphoma, recurrence is not uncommon in the remaining testicle - even after orchiectomy and adequate chemotherapy. Irradiation of the scrotum/remaining testicle may also be important for prophylaxis of later CNS progression.
- With lymphoblastic lymphoma /ALL and Burkitt's lymphoma with testicular involvement, it has been discussed whether radiation therapy to the scrotum is a valuable supplement to systemic chemotherapy with the assumption that the blood-testes barrier can reduce the effect of chemotherapy in the testicles. In the absence of sufficient data in this area however, this is evaluated on an individual basis.
Palliative radiation treatment
- For palliative radiation therapy, the method usually follows the same guidelines as for curative therapy 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 his legs spread. Leg supports may be considered.
The room should be warm and the patient relaxed. The patient should be touched with warm hands.
The penis is immobilized out of the radiation beam, for example on the lower abdomen.
If the anatomy of the patient allows, treatment is given with the scrotum laying on a "bench".
The scrotum and testicles are wrapped in bolus material since the scrotal skin is thin and otherwise would not achieve full coverage of the testicles.
The entire scrotum should be included in the target volume and the cranial border for the field should extend to the root of the penis to ensure that the testicles are within the field also during retraction of the funicle.
Photons or electrons can be given based on depth from the front, but the entire depth of the scrotum must be given a full dose. With use of electrons, 90% of the isodose behind the target volume should lie in the bolus material under the scrotum.
Alternatives to this set-up may be necessary if the scrotal skin is not mobile elastic enough. Electrons can then be considered, for example, at a sufficient depth diagonal from the front toward the scrotum/perineum using a bolus.
For DLBC, 2 Gy x 20 is routinely used.
For consolidative treatment of testicular involvement with Burkitt's lymphoma, ALL or lymphoblastic disease after or during intense chemotherapy protocols, it is more difficult to indicate a sure fractionation and total dose. It is recommended to give a minimum of 24–26 Gy in the literature and higher some places. Oslo University Hospital has most commonly used 2 Gy x 15.
Organs at risk
Acute dermatitis in the scrotal skin may occur since there are many skin folds and the skin is exposed to moisture during fractions.
In the urethra and rectum, mucositis may occur with dysuria and rectal symptoms.
Irradiation of the testicles in the mentioned doses will cause permanent sterility. Reliable birth control is still recommended during treatment and the first year after. Testosterone production may decline many years after treatment and should be evaluated regularly.