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Radiation therapy with inverted-Y field for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

A standard inverted-Y field covers all paraaortal, iliacal, and inguinal lymph nodes as well as upper femoral nodes. The inverted-Y field originated from the extended field for treating Hodgkin's lymphoma with infradiaphragmal spreading. 

The standard inverted-Y field is seldom used today. Many examples of involved field radiotherapy under the diaphragm are considered parts of an inverted Y field. Fields the size of an inverted-Y field are also considered involved field irradiation in some instances. Like the mantle field, it is therefore advantageous to know the principles of modeling an inverted-Y field.

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

Palliative radiotherapy

  • As palliative radiation therapy, the method is based on guidelines for curative treatment with individual modifications.

     


Definitions

The following definition is partly based on StrålevernRapport 2003:13, which is referring to ICRU50 and 62 as well as NACP.

 

Definitions of target volumes in accordance with the ICRU (International Commission on Radiation Units and Measurements)

GTV (Gross tumor volume)

Gross palpable or visible/identifiable area of malignant growth.

CTV (Clinical target volume)

Macroscopic tumor volume including any remaining tumor tissue.

ITV (Internal Target Volume)

Volume containing CTV and internal margin to allow for internal movements and changes to CTV.

PTV (Planning Target Volume) Geometric volume containing ITV with set-up margin taking into accound patient movements, variations in patient positioning, and field settings.
OAR (Organ-at-Risk) Normal tissue senstive to radiation that may significantly affect planning and/or dose.

PRV (Planning organ-at-risk volume)

Geometric volume containing risk volume with set-up margin.
TV (Treated Volume) Volume within an isodose surface considered sufficient based on the treatment intention.
IV (Irradiated Volume) Volume-to-receive dose that is of significance with regard to normal tissue tolerance.
CI (Conformity Index) Relationship between the planning target volume and treated volume (PTV/TV).

 

Field Limits

The field limit is defined as the required course for the 50% isodose curve outside the target volume to give a therapeutic isodose (90% isodose) to the target volume which is intended 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

For radiation therapy of malignant lymphomas, a table is formulated which summarizes standards used for GTV, margins for CTV and ITV, as well as shaping of field limits.

 

Target volume for radiation therapy
GTV Current tumor for indolent NHL stage I/II1, original tumor(before chemotherapy minus balloon effect) for aggressive NHL stage I/II1 and HL stage I/IIA

Residual tumor for aggressive NHL stage II2/IV and HL stage IIB/IV

CTV GTV + 2 cm craniocaudal for limited disease/short chemotherapy

GTV + 1 cm craniocaudal for residual tumor from extensive disease after full chemotherapy

GTV + 1cm in transverse plane

CTV should always contain the entire lymph node region in the levels to be radiated (limited for lungs and bone, if there is no suspicion of infiltration).

CTV may for indolent NHL stage I/II1 contain the nearest unaffected lymph node region or parts of it.

ITV CTV if internal movement can be ignored (CNS, ENT)

CTV + 1 cm craniocaudal and + 0.5 cm transverse in the mediastinum

CTV + 2–3 cm in mesentery

CTV + 0-0.5 cm transverse retroperitoneally

PTV

Not routinely defined

Field limits ITV + Setup margin and penumbra (1.2 cm)

The field limits should be such that later junctions are simple (on one side of the spine, in vertebral discs etc.)

Involved node

The radiation field which surrounds the macroscopically involved lymph node only with margin. Thus far, this definition is rarely used in Norway, but increasingly in international studies.

 

Involved field

Radiation field which includes the involved macroscopic lymph node region or organ with margin. After limited chemotherapy for localized lymphomas, the originally affected macroscopic area is used as a basis for field shaping (with the exception of the balloon effect). For residual changes after full chemotherapy in advanced stages, the residual tumor is usually used as a basis (multiple exceptions). What are adequate margins from the macroscopic tumor to the field limit depend on multiple factors. For early stages of NHL and HL without previous chemotherapy or after chemotherapy (3-6 CHOP-based treatments, 2-4 ABVD or equivalent), the margins from the initial extention to the field limit should be 3-4 cm in the vertical direction, from the initial extent and 2 cm in the transversal plane (with the exception of the balloon effect). For residual changes after full chemotherapy for advanced NHL and HL and relatively little internal mobility, then 2 cm from the residual tumor to the field limit is used. Wider margins must be considered in areas of large internal mobility (abdomen, structures near the diaphragm). Regularly, for nodal involvement, the target volume includes the entire lymph node region in the transversal plane for those levels included in the field.

Traditionally, the entire involved lymph node region has been included completely in the craniocaudal direction (direction for lymph drainage). This provides a recognizable geometric field (parts of mantle field or inverted Y-field) which has advantages for standardizing, reproducibility, later junctioning etc. The lymph node regions, as they are defined in the Ann-Arbor classification, represent no functional biological unit and are not intended as a basis for radiation therapy. In this way, it is natural to see the regions as coherent in the vertical direction of the lymph drainage and to use margins to the involved lymph nodes to avoid radiation of entire regions (for example neck/supraclavicular region, mediastinum, and retroperitoneum). Parts of the neighboring regions may be included to compensate for the minimum margins given above. Field shaping should still follow the geometric forms as much as possible, making later field junctioning easier and to avoid border recurrences in areas which are difficult to re-irradiate.

For extranodal lymphomas/organ manifestations, the entire organ is sometimes included (thyroid gland, stomach, brain, spinal cord). Internal mobility must also be taken into consideration here, for example stomach movement, movement of lungs etc. For several organ localizations, it is not possible to give full doses to the entire organ due to the tolerance for ionizing radiation (lungs, liver, kidney), and the fields/doses must be adapted accordingly.

Extended field

This concept is utilized for fields which include macroscopically involved regions/organs and lymph node regions where it is assumed there is microscopic disease. This may be the nearest macroscopic normal region or multiple, more distant areas. The concept was developed for Hodgkin's lymphoma at a time when radiation therapy was the only modality used 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). For today's purposes, the concept is not of much benefit. For localized stages of low-grade NHL, where radiation therapy is given alone with the intention of curing the disease, we have chosen to include the nearest unaffected region in the radiation field, that is, a "minimally extended field." However, this is not practiced at all radiation therapy centers.


Preparation

  • 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 along their side. The doctor ensures the patient is immobilized on the simulator. For men, there must be a sufficient spread between the legs for gonadal shielding.
  • 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 large rectangular field is modeled with the upper field border at Th10/11. The lower field border runs below the groin with adequate margin to palpable findings. If the femoral lymph node regions will also be included, the caudal field border can be on the thigh. The field ends laterally at the greatest width of the groin, which is standardly the lateral border of the acetabulum.   
  • Blocks are placed over the primary field in the shape of an inverted-Y. A block is placed parallel with the lower thoracal and lumbar spine down to L4 to shield the kidneys and intestines. The standard field width which covers the transverse processes bilaterally with a 0.5-1 cm margin gives a typical width of 8-10 cm. From the lower edge of L4, a block is drawn diagonally to the acetabulums lateral border. From the acetabulum, the field border continues vertically down. 
  • A block is placed in the midline of the pelvis to shield the bladder, rectum, and genitals. A standard block template was previously used for this, which was a lead block placed in a filter holder in the lower part of the field to shield the testicles in men, and a rectangular displaceable part that could be extended cranially to block the bladder for men and women. Today, a multileaf collimator with additional block material (together 10 half value layers) is a more appropriate alternative (see below).
  • At Oslo University Hospital, a filter was previously used in large parts of the frontal field with diagonal lines in the lower edge. The lower edge of this filter (flat filter) would lie caudal to the inguinal ligament and the diagonal sides of the lower edge had a standard angle of 20º, which produced a line from the symphysus up to the lateral edge of the acetabulum on both sides. Below the filter border, the target volume was covered only by the frontal field (for example with 2 Gy per fraction). Above the filter border, the frontal field gave half a dose (1 Gy). This was done to avoid irradiation of the hip area (which only receives a dose from the lower part of the frontal field) and thereby reducing the dose to the head of the femur. A flat filter is no longer used today. For irradiation of the inguinal and iliacal region on one side, a simplified procedure has been developed for direct simulation, where the flat filter is replaced by the half-beam block technique. 
  • If the patient was previously irradiated with a mantle field, the lower border of the mantle field should have been reconstructed in the actual position. The joining was calculated and it was routine to place a 20 mm medulla block in the posterior field. 
  • The Y field usually covers both groin areas, but more recently, it is more common that only parts of this large area are covered, for example the paraaortal regions down to the bifurcature of the large vessels, paraaortal region with one side of the pelvis and goin (L field or dog leg field) or only lymph nodes in the groin on one side possibly with the distal iliac region. Sometimes the spleen is included with the target volume. These fields are considered modifications of the same inverted Y field. 

Gonadal shielding for inverted-Y field

  • 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.

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. When treating the original tumor volume, one should consider drawing in the actual tumor volume in the transversal plane where the original tumor volume has pushed healthy organs to the side and then moved back to their original place after chemotherapy (balloon effect). 
  • 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 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, inverted-Y field 

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.

Bladder

Radiation-induced cystitis may 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.

Fertility

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.

Kidney 

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

Head and neck of the femur

Osteoporosis of the head and neck of the femur may occur after irradiation, which increases the risk of fracture. 

Secondary cancer

Like the mantle field, there is an increased risk for other cancer forms, especially for organs within the radiation field receiving a full therapeutic dose. 


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