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Radiation therapy of Hodgkin's lymphoma

Radiation therapy is undergoing final approval and will soon be available.

Radiation therapy for Hodgkin's lymphoma is based on experience performed with large fields toward multiple lymph node stations (extended field) such as the mantle and inverted Y fields. Previously, about 40 Gy was given to each field.  Today, these fields are rarely used, but many patients who have received these treatments are still alive. Radiation therapy of lymphatic regions in the head/neck, supraclavicular, infraclavicular, mediastinal, and axilla regions, as well as combinations of these, are based on experience with the mantle field. Also, irradiation of paraaortal, iliacal, and inguinal/femoral lymph nodes can be considered parts of the inverted Y field. Large fields represent modifications of the mantle field and inverted Y and are used occasionally. 

Long term follow-up of patients cured by these large fields of radiation has shown that this treatment is associated with significant morbidity and mortality. Research results from the last 1 0–15 years have shown that large fields are not longer necessary, and that the radiation dosage can be reduced if treatment is combined with chemotherapy. This development in treatment of Hodgkin's lymphoma has determined many of today's treatment principles and the role of radiation therapy. 


Localized disease stage I-IIA

Since 1999, Norway has followed the Nordic protocol for confined disease. Guidelines for radiation therapy for this protocol require using the 'involved field' where a margin of 2 cm is added to the original tumor volume cranio-caudally and this is defined as CTV. Internal target volume (ITV) then involves a margin of about 2–3 cm in the cranio-caudal direction depending on localization and assumed internal movements equivalent to 3-4 cm to the field limit. As a general rule, the CTV includes the entire involved lymph node region in the transversal plane of the levels irradiated, such as all lymph node regions on one side of the neck or mediastinum and lung hilus in full breadth. Lateral margins for ITV in the mediastinum/hilum area should be up to 0.5 cm into healthy lung tissue equivalent to 1.5-2 cm from the mediastinum/hilum to the field limit. If the breadth of the mediastinum/hilum increases before start of therapy, CTV is defined as mediastinal contour/hilum contour only after chemotherapy and not as the original tumor (balloon effect). If the field limits are tuned directly on the simulator, the margins used are equivalent to ITV+1–1.5 cm for set-up margin and penumbra. 

Dosage is the standard 2 Gy x 10 for patients without risk factors and 1.75 Gy x 17 for patients with risk factors (after 4 ABVD cycles). CT-based dosage-planned radiation therapy is used for curative treatment. The greatest advantage of this is the possibility to quality-assure therapy and document strain on healthy organs.    

Stage IIB and III-IV A/B

Randomized studies and metaanalyses have been carried out to investigate the benefit of radiation therapy in patients who have completed full chemotherapy equivalent to 6–8 ABVD cycles. As a general rule, there is no indication for radiation therapy if the patient is in complete radiological remission after chemotherapy or if residual tumor is unchanged over time. Radiation therapy of areas with initial bulky tumor, especially patients with large mediastinal tumors should not be given radiation therapy if there is complete response to chemotherapy. 

For residual tumor after radiation therapy it is more difficult to establish general guidelines. Biopsy of residual changes should be used liberally if possible. With a positive biopsy, irradiation of the area with 29,75–35 Gy is considered. The alternative is to start second line high-dose chemotherapy with subsequent autologous stem cell support. Newer studies indicate that PET may be helpful to differentiate residual fibrosis from active tumor tissue.  

CT-based dosage-planned radiation therapy is used mainly for curative treatment. CTV after full chemotherapy is defined as the residual changes including a margin of 1 cm. ITV is defined with margins including assumed internal movement of CTV. The field limit then involve a margin of 2-3 cm to visible residual tumor. It is reasonable to modify field limits where there are unacceptably large volumes or risk organs involved.  

Children and adolescents (up to and including 18)

Children and adolescents are treated from the special protocol (GPOH-HD 95), or studies in which radiation therapy is given to most patients after chemotherapy despite complete response. The new protocol EuroNet-PHL1 for classical Hodgkin's lymphoma was activated in 2007 and will be open until 2013. In this study, PET-CT will be used to reduce the number of patients treated with radiation therapy without reducing the cure rate of the entire patient group.  

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