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Radiation therapy for lung for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

With advanced lymphoma, the lungs are often involved and usually with multiple lesions. This applies to both Hodgkin's lymphoma and all forms of Non-Hodgkin lymphoma. In most cases, these patients will be candidates for primary chemotherapy as for advanced disease. With residual lesions, radiation therapy is considered in some cases. Since the tolerance for ionizing radiation for the entire lung is slightly below 18–20 Gy (TD5/5 for lung failure), irradiation of the entire organ is often difficult if it is desired to give doses the same as for malignant lymphoma. Therefore, consolidative radiaion therapy is given only under special circumstances to the entire lung or both with lower fractions and total doses than otherwise for lymphomas. Primary extranodal involvement of the lungs with only one localized focal lymphoma manifestation (considered stage PeI) is very rare, and even then it must be considered whether such cases should be treated as advanced disease and whether surgery should be chosen as local treatment in a curative plan.  

Curative radiation therapy

  • Residual lesions after chemotherapy each lymphoma where the clinical profile indicates that the chemotherapy effect should be consolidated in the lungs. This may apply to, for example, patients with recurrence of aggressive lymphomas or Hodgkin's lymphoma who are treated to cure the disease, and where lung manifestations (possibly together with mediastinal recurrence manifestations) dominate the clinical profile.
  • Patients under 18 years with Hodgkin's lymphoma with lung involvement will have radiation therapy for the lungs in primary treatment based on guidelines from protocol GPOH-HD-95 (selected patients only).   
  • Primært ekstranodal affeksjon i lungen med lokalisert fokal lymfomutbredelse (tenkt stadiumPeI) er svært sjelden. Dersom slikt forekommer, må en likevel vurdere om slike tilfeller bør behandles som utbredt sykdom med egnet kjemoterapi og om kirurgi skal velges som lokalbehandling i et kurativt opplegg.

Palliative radiation therapy

  • Palliative radiation therapy of entire or both lungs is almost never indicated. 

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

  • Consider whether lung function must be evaluated before radiation therapy begins. Regardless, this may be advantageous for further follow-up.
  • For conventional simulation, the patient lies in a position similar to the mantle field, with their arms abduced to 90°. Or, their arms and legs are along their sides but sufficiently away from their upper body. 
  • For CT-based planning, the patient lies with their arms and legs along their sides but as far away from their upper body as possible. Immobilization in a wing board is a possible alternative. 

Implementation

Conventional simulation  

  • A large field is modeled such that the field borders cover all parts of the lung(s) for both normal expiration and inspiration. There should be an adequate margin to lung tissue to cover set-up variation and penumbra, or a minimum of 1.5–2 cm.
  • The posterior sinus is identified by side images from the simulator. The upper spleen and liver are always included in the radiation field. 
  • For unilateral lung irradiation without the mediastinum, the field border should be on the same side of the medulla in the soft tissue of the mediastinum. In children, irradiation of the thoracal column should be symmetric to avoid growth imbalances.   

CT-based simulation

Lung irradiation can also be done by CT planning.

  • Both lungs and the entire medistinum are drawnn on the inside of the thoracic wall as a CTV. 
  • To take into account respiration movements, there must be a 1 cm margin to ITV in the transversal plane and 1-2 cm margin craniocaudally (ITV1).
  • Any structures in the mediastinum to be treated simultaneously with another fraction are defined as a separate ITV (ITV2).
  • Any fractionated doses larger than the what the lungs receive must be given as a concomitant boost. Dosing to ITV1 is then, for example 1.2 Gy x 10 and to ITV2 1.75 Gy x 17, where 0.55 Gy is given to ITV2 as concomitant boost at the first 10 fractions, and ITV2 alone is given 1.75 Gy at the last 7 fractions.
  • The field set-up should be checked by illumination on the simulator to make sure the lungs are included both during inspiration and expiration as for conventional simulation. 

 CT dose plan, lung  

Fractionation

The total dose to whole or parts of the lung should not exceed 15 – 18 Gy. The regular dose/fraction in later years given by Oslo University Hospital has been, depending on previous chemotherapy/high dose treatment, 12 or 15 Gy in 1.2–1.5 Gy fractions.

Usually, bilateral lung irradiation is given together with irradiation of the mediastinum. The mediastinum should be given 1.75– 2 Gy per fraction and a higher total dose of 30–40 Gy. This is achieved by using a lung filter which allows a full fractionated dose of 1.75–2 Gy to the mediastinum, but reduces the dose to the lungs to 1.2 –1.5 Gy at each fraction, or, by giving mediastinal irradiation as a concomitant boost after the fraction to the lungs is given. The mediastinum must often be given multiple fractions after lung irradiation is concluded. When calculating the lung doses, the lung correction factor must be used. 


Follow-up

Risk organ

Lung

It is possible to develop acute and subacute pneumonitis during and in the months following treatment, as well as chronic lung function disturbances. A chest X-ray should be taken after treatment is finished and for pulmonary symptoms during and in the months following treatment. A thoracic CT is more sensitive in showing radiation-reactive changes. Radiation-induced pneumonitis is treated with steroids in cooperation with a lung specialist.

Lung fibrosis and lung failure can occur in the long-term.


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