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Radiation therapy with mantle field for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

A standard mantle field includes all lymph node stations over the diaphragm. The mantle field originated as extended field treatment of supradiaphragmal spreading of Hodgkin's lymphoma.  

The standard mantle field is rarely used today, but many long-term survivors of HL have received this treatment. Many examples of involved field radiation therapy to the diaphragm can be considered a section of the mantle field. Further, fields with sizes close to a mantle field are also considered involved field irradiation in some situations today. It is therefore advantageous to know the principles for modeling a mantle field as for the inverted Y field.

  • High mantle field includes treatment of the upper cervical lymph nodes (preaurciular and possibly retroauricular lymph nodes) and Waldeyer's ring including the tonsil field.
  • Low mantle field includes the submental, submandibular, and nuchal lymph nodes as the upper stations. The upper field border was at the level of the point of the chin and the bottom of the posterior skull.
  • Minimantle was the expression for fields where the mediastinum could be excluded. 

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

  • Patients must be evaluated by a dentist and treated if necessary before immobilization and start of treatment. 
  • The patient is immobilized supine on a VacFix® and with a mask. It is important the patient has their chin stretched sufficiently (5° extension of the mandible). The arms should be abduced to 90° when irradiating the axilla. The arms should be rotated upward for a low mantle field and downward when the tonsil field is joined.
  • In women, the breasts should be moved out of the field with lung blocks. 
  • It should be considered to mark papable lymph nodes or biopsy scars with lead thread to locate again on simulation film. 
  • Fields resembling mantle fields may be suitable for CT dose-planned treatment. Immobilization of the arms abduced to 90° is not possible on CT machines. Immobilization of the arms can be done over the head with with a wing board, or the arms slightly abduced along the upper body. The reproduceability of the position may be a problem with slightly abduced arms. A 5-point mask with immobilization of the shoulder area may improve stability. With skin folds, skin reactions may be more problematic with doses up to 40 Gy. A side field cannot be given toward the neck if the arms are immobilized over the head with a wing board.

Implementation

Conventional simulation

Low mantle field

  • A large field (up to 50 x 50 cm) is modeled with a cranial border of 1 cm above the jaw angle, which with an adequate chin stretch, represents a line from the point of the chin, under the ear canal and to the bottom of the posterior skull.  If there is visible tumor in this area, a higher field border should be considered (more of the oral cavity and posterior skull is included).  the alternative is a field border caudal to the palpable tumor that joins the tonsil field (side field to periauricular lymph nodes and Waldeyer's ring) outside the macrotumor. 
  • The caudal field limit is by Th10/11.
  • If there will be a joining of the tonsil field or later paraaortal field/inverted Y field, the field limits must be placed to facilitate movement of joinings, but should be go through macroscopically involved areas.  This must be planned before simulations and a physicist must be consulted. 
  • Field borders on the sides must be outside the thoracic wall and include part of the humerus so that lateral parts of the axillar are well included.
  • Placement of blocks must be defined.
  • It is standard to place a larynx block over the larynx in the front field and a medulla block over the cervical spine in the rear field. A larynx block and medullablock should be exluded for cervical tumors near the midline. 
  • Lung blocks, humerus blocks, and axilla blocks are use in both fields. Lung blocks are drawn around 0.5-1  within the thoracic walls laterally, follow the underside of rib 4 (to cover infraclavicular regions) and should follow the contour of the upper mediastinum and hilum with 1.5–2 cm margin in the lung parenchym. The blocks do not follow the shadows of the heart on the left side, but instead turn in under the hilum, such that the left stomach and lung in the front and back of the heart are shielded. 
  • Humerus blocks are drawn from the center of the humerus head and half of the humerus shaft within the radiation field. This allows for irradiation of the lateral and apical parts of the axilla. 
  • Soft tissue and lung caudal to the axilla are shielded with an axillary block, typically at the level of the breast. 
  • Contouring of blocks may vary depending on the extent of the tumor, for example tumor invasion of the anterior thoracic will necessitate inclusion of larger parts of the thoracic.  
  • For many patients, it is necessary to block out large parts of the lower mediastinum during the entire or parts of treatment to reduce the dose to the heart and heart valve level.

CT dose plan, neck region and supraclavicular fossa

CT dose plan, axilla region 

Tonsil field for high mantle field 

  • The tonsil fields, which include large parts of Waldeyer's ring and also known at the periauricular field, are modelled on a simulator as opposing fields toward periauricular lymph nodes and large parts of Waldeyer's ring. When treating the high mantle field, the mantle field is given concomitantly with side fields in this region. The mantle field is standardly set such that the crosspoints of the anterior and posterior fields lie in the frontal plan through the ear canal. When irradiation toward the tonsil field, the side fields lie partly or completely in front of this frontal plane. 
  • Modeling of borders for the tonsil field standardly runs in the middle of the sphenoidal sinus for the upper border (sella turcica with pituitary and eyes), anterior border behind the teeth in the upper and lower jaw and lower border joined with the upper border of the mantle field. The posterior border is normally in front of the outer ear canal, but may lie behind the ear canal in some cases.
  • With joinings toward the tonsil field, a joining is placed based on a standard developed with a physicist. The lower border of the tonsil field with joining should not go into the macro tumor, and with high cervical lymphadenopathy this must be moved caudally compared to the standard high mantle field. The side fields must then include the submandibular and occipital nodes.
  • With joinings farther down the neck toward an extended side field, the joining must also be planned during simulation. 
  • It is today seldom to join the entire mantle field with the tonsil field, or large side fields to Waldeyer's ring and upper cervical lymph nodes. The total field size usually allows for use of the isocentric technique with half-beam block, which avoids problems with field junctions.The side fields with Waldeyer's ring as well as periauricular, submandibular, and occipital lymph nodes are irradiated cranial to the central beam from side to side. The neck and other caudal regions are irradiated with anteroposterior beams caudal to the central beam.

CT-based simulation

The mantle field cannot be directly transferred to CT based simulation because CT machines do not support 90° abduction of the shoulder joint. Involved field irradiation the size of a modified mantle field may then be the case, and it may be possible to use CT for 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 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.
  • Contouring of Waldeyer's ring, neck lymph nodes, axilla, infraclavicular regions and mediastinum is described in their respective chapters.
  • The margin to ITV in the transversal plane in the mediastinum is up to 1 cm in the craniocaudal direction and up to 0.5 cm in the transversal plane. On the neck and in the axilla, there is no margin for internal movement.
  • 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. 

Fractionation

Standard fractionation and total dose for curative treatment is given below. These are also normative for palliative treatment, but should be modified on an individual basis. 

  • For Hodgkin's lymphoma stage I-IIA without risk factors: 2 Gy x 10
  • Otherwise for Hodgkin's lymphoma: 1,75 Gy x 17.
  • Curative treatment of indolent NHL: 2 Gy x 15
  • Aggressive NHL: 2 Gy x 20.  

Follow-up

Risk organs

Mucosa 

Acute mucosa toxicity such as mucositis in the mouth, pharynx, and esophagus during treatment and closely following occurs in most patients and some have significant problems. 

Skin and hair

Reversible alopecia to irradiated areas of the posterior skull and the jaw including beard growth should be expected. Skin and axilla soreness of skin folds may 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.

Lense, eyes, chiasma, pituitary

Fields to the periauricular lymph nodes and Waldeyer's ring may give a small dose to these organs, which is usually under the dose tolerance. It is important to avoid unintended hotspots to these organs.  

Teeth should be evaulated and treated before treatment to prevent later osteoradionecrosis. Caution should be used for dental treatment after irradiation of the jaw region.  

Salivary glands 

Dry mouth can be expected with fields including both parotid glands. If this can be avoided, problems are often moderate in the long run.

Thyroid gland

At least half of lymphoma patients with irradiation to the neck develop hypothyroidism within years. Lifetime follow-up of thyroid status is indicated. Thyroid cancer can occur years after radiation therapy.

Cerebrovascular disease

After radiation therapy to neck vessels, there is a known increased risk for cerebrovascular complications.  

Lungs

Subacute radiation pneumonitis during the first months after treatment may occur. Irradiated areas of the lungs will often develop fibrosis over time.

Heart

Patients have increased cardiovascular mobidity after irradiation which includes the heart valve area and/or parts of the myocardium. Valve problems, coronary heart disease, heart failure, and constrictive pericarditis are the most common side effects. These side effects are especially common in patients previously irradiated with a mantle field for Hodgkin's lymphoma. Guidelines in Norway recommend yearly follow-up with a general practicioner starting 10 years after treatment focusing on reduction of other risk factors (smoking, obesity, hypercholesterolemia, high blood pressure, physical inactivity) and early evaluation of symptoms or changes that my imply heart disease. Patients should be strongly discouraged from smoking.

Secondary cancer

For patients treated with mantle field irradiation for Hodgkin's lymphoma, there is a significant risk for secondary cancer, especially in organs receiving full therapeutic doses. Breast cancer, lung cancer, thyroid cancer, sarcomas, and skin cancer/melanoma are the most common forms. Secondary cancer is a significant cause of death of patients cured for Hodkin's lymphoma by radiation therapy. For younger women treated with mantle field irradiation in ages under 35, it is recommended to have yearly mammography screening starting 8 years after radiation therapy was given. For other cancer forms, there are no defined follow-up routines. Patients should be strongly discouraged from smoking.


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