Until 1960s Radiotherapy was theonly non surgical treatment forlymphoma
Current issues in lymphomaradiotherapy• Who to treat• What volume to irradiate• What dose to use
Overview• Why use radiotherapy to treat lymphomas• Practicalities of radiotherapy delivery- Why fractionate- Treatment planning and delivery• Indications for external beam radiotherapyin:-Hodgkin lymphoma-Non Hodgkin lymphoma
Why use radiotherapy to treatlymphomas?• Lymphoma is very radiosensitive• Relatively small doses of radiotherapy arerequired• Local relapse within an irradiated area israre• Radiotherapy fields are now smaller,reducing late toxicities
Differential effects of irradiation ontumour and normal tissue
Practicalities of radiotherapy• Patient must be able to lie still
Radiotherapy Planning (1)• Identify the treatment volume-Essential to have pre-chemotherapy imaging- Need up to date diagnostic imaging- Radiotherapy planning scan• Treatment volumes- The visible tumor (GTV)- Sites of possible microscopic disease (CTV)- The area to be treated with a margin to allowfor movement and set up accuracy (PTV)
Radiotherapy Planning (2)Considering the best way to deliver theradiotherapy• Ensure that PTV receives the intendedtreatment dose• Minimise the dose to normal surroundingtissues- Conform fields to treatment volume- Field arrangements
Use of PET to identify the GTVTerezakis SA, Yahalom J. 2011
what is the role for RT as part ofcombined-modality treatment inaggressive lymphoma?
IFRT remains the treatment of choice of for localizedstage IA and selective stage IIA patients and deliverslong-term disease-free survival and potential cure forsome patients.
The conventional dose of curative RT used inthe early studies was considerably larger at30–40 Gy. However, a British randomized studydemonstrated equivalence of 24 Gy with 40 Gy.
Localized LDRT appears to induce apoptosis and thisfollicular lymphoma cell death may then elicit a hostimmune response mediated by macrophages anddendritic cells.This exquisite radiation-induced apoptosis andsubsequent immune response may underlie thedurability of responses seen with both LDRT andradioimmunotherapy (RIT).
What is the role for RT in the modernmanagement of HL?
Identify the risksGHSG EORTC StanfordRisk Factors a- Bulky mediastinum a-Bulky mediastinum a-Bulky mediastinumb-Extranodal disease b- Age >=50 b-Age>=40ESR>=50 with noc-ESR>=50 with out B symptoms c-B symptoms c- ESR >=50Or >=30 with B symptoms Or >=30 with B symptomsd->=3 nodal sites d->=4 nodal sites D->=3 nodal sitesGHSG EORTC StanfordFavorable CS I-II CS I-II CS I-IINo risk factors No risk factors No risk factorsUnfavorable CS I- IIA with >=1 CS I- IIA with >=1 CS I- IIA with >=1risk factor risk factor risk factorCS IIB with c or dnot a+b (otherwiseadvanced)
The use of RT also allows a shorter andsafer course of chemotherapy.
The combination of reduced chemotherapyfollowed by mini-RT has produced diseasecontrol and even overall results that aresignificantly superior to those achieved withchemotherapy alone.
The analysis included five randomized controlledtrials involving 1245 patients. Although the completeremission rate was similar in the two groups, bothtumour control and OS were significantly better inpatients receiving combined-modality therapy.
The authors’ conclusions were that adding RT tochemotherapy improves tumour control and OS inpatients with early-stage HL.
The conclusion from these studies was that after fourcycles of ABVD, 30 Gy is recommended for early-stageunfavourable Hodgkin lymphoma,whereas 20 Gy isadequate for early-stage favourable Hodgkin lymphomaafter two cycles ABVD.
The principal distinction between involved-noderadiotherapy and involved-site radiotherapy isthat no additional margin around the nodevolume is added in involved-node radiotherapy.Typical margins are as follows:(a) Head and neck: 0.5-1 cm, depending on local set-up.(b) Mediastinum: 1 cm transversely and 1.5 cm craniocaudally(c) All other sites: 1 cm.
This is based on defining the site of grossdisease before chemotherapy, the GTV andusing a CT-based volume with anexpansion to form a CTV in the cranio-caudal direction. The post-chemotherapyinvolved nodal chain and residual diseaseform the CTV in all other directions.
Involved Field(A&B) v Involved Site(C&D)RadiotherapyGrinsky, et al 2006
Involved field v involved siteradiotherapyGrinsky, et al 2006
Role of RT in Advanced Hodgkin DiseaseOffering RT after effective chemotherapy is not standardpractice and is still undergoing investigation.
Although a meta-analysis and studies by the GELAand EORTC groups showed no benefit ofconsolidation RT after effective chemotherapy withsuggestions of worsened outcome when RT wasadded, more recent data have emerged from 2 largerandomized control trials (RCT) in support ofconsolidation RT.
Indications for radiotherapy inDLBC NHL• In early stage disease with short coursechemotherapy• In advanced disease- Bulky disease at the outset (MINT Study,Pfreundschuh 2008))• Risk of relapse increases with size of mass• Should irradiate masses >10cm at diagnosis- PET positive at the end of treatment (Sehn et al,2010)• Dose 30 Gy in 15 # (Hoskin et al, 2011)
Current evidence-based recommendations for radiation doses inlymphoma are shown below:Hodgkin lymphoma1.Early-stage favourable Hodgkinlymphoma, after two cycles of ABVD,may be treated with 20 Gy.2.Early-stage unfavourable, or forresidual or refractory disease inadvanced Hodgkin lymphoma, shouldreceive 30 Gy.3.If early-stage unfavourable disease istreated using BEACOPP rather thanABVD, the dose may be reduced to20 Gy.
Non-Hodgkin lymphoma1.Indolent lymphomas (follicular,marginal zone, small lymphocytic orchronic lymphocytic lymphoma (CLL)should be given 24 Gy in 12 fractions.2.In the palliative setting, follicularlymphoma patients will respond to 4 Gyin two fractions.3.Natural killer cell lymphoma shouldreceive at least 50 Gy in 25 fractions.4.All other non-Hodgkin lymphomasshould receive 30 Gy in 15 fractions
The planning of radical radiotherapy for lymphomapatients, both Hodgkin and non-Hodgkin lymphoma,should be based upon contrast-enhanced 3 mmcontiguous CT imaging with three-dimensionaldefinition of volumes using the convention of GTV, CTVand PTV.
All patients should be treated with involved-siteradiotherapy unless no pre-chemotherapyimaging is available,when involved-fieldradiotherapy is used.