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Radiation therapy for the stomach for malignant lymphoma


Medical editor Alexander Fosså MD
Oncologist
Oslo University Hospital

General

Indications

In addition to Waldeyer's ring, the stomach is a common extranodal localization for malignant lymphomas. Among indolent lymphomas, marginal zone lymphomas dominate, other entities are more rare. For patients with marginal zone lymphomas with infection of H. pylori, triple treatment is considered standard treatment in Norway as long as guidelines are followed for diagnostics, treatment, and follow-up. Aggressive stomach lymphomas constitute most mantel cell lymphomas, diffuse giant cell lymphomas and Burkitt's lymphoma. Serious bleeding and/or massive invasion to serosa with danger of perforation are considered for a stomach resection or gastrectomy as a primary measure after consultation between oncologist and surgeon. 

Curative radiation therapy

  • Patients with marginal zone lymphoma stage PeI
    • Without H. pylori infection
    • Patients who cannot or do not wish to follow the recommended follow-up schedule for eradicative treatment. 
    • Unfavorable cytogenetic aberrations or a thickened stomach wall are also possible grounds for primary radiation therapy. 
  • Patients with marginal zone lymphoma also in regional lymph nodes (stage Pe II1)
  • Patients without effect of or with local recurrence after eradicative treatment.
  • Other forms of indolent stomach lymphomas in stages Pe l and Pe ll1
  • If primary surgery is completed for indolent stomach lymphoma and the surgery is radical, no additional treatment is given for stage PeI. If there is residual lymphoma in the stomach or involvement of regional lymph nodes (stadium Pe II1), supplementary radiotherapy is given to residual areas and regional lymph nodes. 
  • Aggressive lymphomas in the stomach are treated from protocols for their respective histology. Diffuse giant cell B cell lymphoma stages Pe I-Pe II are treated as desribed for DLBCL stage I/II. Three to six CHOP-based cycles followed by radiation therapy with 2 Gy x 20 (40 Gy) are given. Stages Pe II2- IV are treated as advanced disease of DLBCL and supplementary radiotherapy is considered for any residual lesions. Mantel cell lymphomas are treated analagous to DLBCL with suitable chemotherapy followed by radiotherapy, or are considered for inclusion of ongoing protocols. Burkitt's lymphoma is treated from the GMALL-NHL-2002 protocol where radiotherapy to the stomach may be appropriate after chemotherapy.

Palliative radiation therapy 

  • For palliative radiotion therapy, the method normally follows the same guidelines as the curative plan with individual modifications.

Definitions

Target Volume

 

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

  • GFR with renography should be completed before treatment planning to evaluate kidney funciton. 
  • Large parts of the sleen are often within the radiation field. Immunization against Streptococcal pneumona is considered.
  • It may be necessary to give a small amount of oral contrast fluid (water alone may function well) for CT uptake for better visualization of the stomach. 
  • Other standards may exist for stomach content and CT uptake to achieve a reproduceable size of the stomach. At Oslo University Hospital, we recommend the patient is fasts for early morning CT. The patient is given a small glass of water as oral contast agent before CT. The patient must fast for each treatment, and we try to schedule treatment in the morning before breakfast.

Implementation

CT-based simulation

Radiation therapy of the stomach and regional lymph nodes should be done with the help of CT. 

  • The patient lies supine.
  • Standards should exist for the patient for CT uptake with a reproducible stomach size for simulation and treatment (see above).
  • Any visible tumors/lymph node manifestations represent GTV. Any endoscopic findings may also be of help to define visible tumor. 
  • CTV is generated with a 1 cm margin to GTV.  Regardless, the entire stomach or any residual areas after surgery are included in CTV. For stage PeI, uninvolved draining lymph nodes assumed to lie along the curvature minor and major, hilum of the spleen, by the celiac trunk and subpyloric lymph nodes areas are included, or contoured on a separate CTV. For stage PeII1, where the nearest draining lymph nodes are involved, it should be considered whether the secondary lymph nodes stations are included in CTV. 
  • The stomach is a mobile organ and should have good margins to ITV (1–2 cm), especially in craniocaudal extensivenss.
  • A multiple field technique will usually be the result, usually as anteroposterior and lateral opposing fields. In this way, the dose to the left kidney can be reduced compared to purely anteroposterior technique. 

CT dose plan, stomach

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.

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.

Gonadal organs

The dose to the gonads should be as small as possible to preserve fertility. Reliable birth control during treatment is necessary, and is recommended until a year has passed 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.


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