Lymphoma Current Approach
Bouthaina Dabaja, M. D UT MD Anderson CCtCancer Center No disclosures Overview
Hodgkin’’ s Lyypmphoma (standard treatment ): – Early disease – Early Unfavorable – Advanced
Aggressive Lymphoma: – DLBCL (early stage I and II): – standard chemotherapy and role of radiation – Other aggressive types: PCNSL,NK cell, PML, Testicular
Low grade lymphoma: – Follicular lymphoma – MALT Lymphoma Hodgkin’’ s Lymphoma
Unique history:
Discovered 1832 Radiation used in 1930 Wide field 1950 (Kaplan, Peters) MOPP 6060’’ss ABVD 70’’s70 s Hig h cure ra te ac hieve d Live long to see what we have done Hodgkinkin’’ss Lymphoma we changed the survival
Hodgkin's Lymphoma by Era Hodgkin's Lymphoma by Era
n = 2167 n = 2167 101.0 101.0 .9 1990 1990 .8 1980 .8
.7 1970 1980
.6 .6 vival vival rr rr .5 1970 .4 1960 .4
Cum Su .3 Cum Su .2 .2 1960 .1 0.0 0.0 0 10 20 30 40 0 10 20 30 40
Disease Specific Survival (y) Overall Survival (y)
British Columbia HL Diagnosis
Most common is Nodular sclerosis, unimodal with younger age, Mixed cellularity older age
Viral association: EBV (40%), HIV ((),less common), Autoimmune disease (MTX)
Family history, increased in first degree relatives Presentation identifying risk group
SStagetage according to Ann Arbor Sites location and number Presence of B symptoms (>38 C), > 10% body weight loss, drenching night sweats Presence of Bulk: – MediastinalMediastinal:: 10 cm or >1/3 of mediastinum at T5T5--66 on UR CXR – > 5cm any mass else where Age > 45 Male gender Laboratory: Sedimentation rate Hemoglobin < 10g/dl High LDH, High b2 microglobulin (advanced stage) High WBC count > 15000, < 8% lymphocytes ( advanced stage) Albumin< 4 (advanced stage) HL Diagnosis
B cell in origin ReedReed-- Sternberg cells (multinucleate)+mononuclear HHododgkin cells CD30 positive CoCo--ExpressExpress CD 15
PAX 5: identity keeper of B lymphocytes, used when CD20 or CD79 are not detected.
Normal Karyotype HL Diagnosis
Classical Hodgkin: Nodular Sclerosis (RS +fibrosis+inflammatory cells eosinophiles and plasma cells) Mixed Cellularity (RS, inflammatory cells) Lymphocyte rich (RS + lymphocytes no eos. or neut.) Lymphocyte depleted (rarely mentioned)
Lymphocyte predominance (germinal B cell) with a nodular growth pattern. Diffuse pattern might not exist: may be T cell rich Large cell or lyypmphoc yte rich classical HL HL Presentation
Asymptomatic suprasupra--diaphragmaticdiaphragmatic Waxing and waning (inflammatory background) Mixed cellularity: abdominal, older age, male, advanced stage, b symptoms, rare mediastinal site, developing countries,
Contiguous involvement Neck and inguinal nodes without mediatinum is rare
Liver and marrow rarely involved
Bone marrow involvement/ the need for BM biopsy: PiiiPositivity corre late w ihblk/bith bulk/b symptoms /stage Baseline is always helpful HL Diagnosis
Staging work up: Core biopsy Not a FNA
Laboratory work CBC, diff, plats, ESR, LDH, liver function, albumin, creat.creat. BUN, pregnancy test, HIV
PET CT with contrast
Bone marrow biopsy Comorbid conditions: autoimmune disease Heart disease Family history of cancer Hepatitis Viral infections Identify the risks
GHSG EORTC Stanford Risk Factors a- Bulky a-Bulky a-Bulky mediastinum mediastinum mediastinum b-Extranodal b- Age >=50 b-Age>= 40 disease ESR>=50 with no
c-ESR>=50 with c-B symptoms c- ESR >=50 no 3-B symptoms Or >=30 with B Or >=30 with B symptoms symptoms
d->=3 nodal sites d- >=4 nodal sites d->=3 nodal sites Sites of Disease
12
4 3
Unfavorable (GHSG) Identify the risks
GHSG EORTC Stanford Risk Factors a- Bulky mediastinum a-Bulky mediastinum a-Bulky mediastinum
b-EtExtranod dldial disease b- A50Age >=50 b-A40Age>=40 ESR>=50 with no c-ESR>=50 with no 3-B symptoms c-B symptoms c- ESR >=50 Or >=30 with B symptoms Or >=30 with B symptoms
d->=3 nodal sites d->=4 nodal sites D->=3 nodal sites
GHSG EORTC Stanford FblFavorable CS I-II CS I-II CS I-II No risk factors No risk factors No risk factors
Unfavorable CS I- IIA with >=1 CS I- IIA with >=1 CS I- IIA with >=1 risk factor risk factor risk factor CS IIB with c or d not a+b (otherwise advanced) Why are we here today
GHSG EORTC Stanford
Favorable: CS I-II CS I-II CS I-II 2ABVD+20 Gy No risk factors No risk factors No risk factors IFRT
GHSG 10 Unfavorable CS I- IIA with >=1 CS I- IIA with >=1 CS I- IIA with >=1 risk factor risk factor risk factor 1-4 ABVD CS IIB with c or d 2- not a+b for HD 11 2BEACOPPes.+2 ABVD
+ 30 GyGHSG IFR T11,14 Shifting from Extensive Radiation to combined moda lity
Radi ati on al on e an d l ack of Im agin g Staging Laparotomy
EORTC 6: clinical stage is sufficient for: stage II--II,II, No B, No bulky, ESR<30
Combined chemo-radiation started with MOPP
Trials with MOPP are not relevant to todaytoday’’ss practice Introduction of ABVD step 1
ABVD Introduced in 1975: Milan Randomized trial – advanced stage – ABVD was found superior
6 cycles of ABVD 300mg/m2 Adriamycin – Tolerance is 450450--500500 mg/m2 IVP ABVD established
CALGB in US compared ABVD to MOPP to MOPP ABVD in advanced stage no radiation Canellos 2002 NEJM Type of chemotherapy
Stanford V introduced 1995 reported on for both early and advanced stage 8 or12 weeks of chemotherapy RRadiationadiation from 20 to 36 Gy
Excellent outcome LLowow toxicity Step 2: delete extensive radiation as sole modality
GHSG HD7 addition of 2 ABVD to EFRT dramatically improved the FFF from 75% to 91% at 5 years (Engert 2007)
Fred Hutchinson 348 CS I II A no Bulky or B symptoms randomized to STLI or CMT 3 DV and STLI closed early for the marked superiority of chemotherapy (Press 2001 ) Comparing extensive to IF +chemotherapy
Trials comparing extended field to IF+ chemotherapy Bonnadonna et al showing no OS or FFP in early favorable
EORTC/GELA H8F 3 MOPP/ABVD +IFRT vs STLNI superiority was shown but neither are accepted now (Ferme 2007 )
H8U 2 of the three arms compared 4 MOPP/ABV followed by EFRT or IFRT 7 y EFS 86% and 84%
HD 8 GHSG 1204 with CS I II HL randomized to COPP + ABVD followed by extended RT or IFRT MEDIAN FU 54 M 5Y FFF 86% VS 84% (O.56) OS 91 AND 92% (Engert 2003) IFRT meaning in these trials was unclear At the door of what we do today
9 No use for extended field 9 No use for MOPP 9 Now we need to tailor combined modality based on risk factors 9 Should avoid falling into the trap of the side effects that results for the early approaches What are the side effects Second malignancies
Solid tumors Continuous with time, no plateau, associated with : EF radiation Hig h doses Mantle field Younger age 25 years of follow up the risk 28% 34% < 20 of aggpe developed breast cancer ,g, 22% age 2020--2929, 18 fold the risk of general population for all cancers, 8 Fold breast, 38 thyroid, 11 cervix, 11 for GI
Hematological malignancy: is highest at 5-5-1010 years Over 1000 patients treated with ABVD in contrast to MOPP no increased incidence of SM ((valagussavalagussa 1982, 488) Travis 2003 breast canccancerer is dependent on dose 42 Gy to as low as 4 GyGy,, confirmed by Van LeeuwenLeeuwen,, pediatrics: ((InskipInskip 2009) a linear radiation dose response was obdithtitRRf64t20bserved with estimate RR of 6.4 at 20 Gyyanand118d 11.8 a t40t 40 Gyy..
Heart disease 55--7%7% risk at 10years 1010--20%20% at 1010--2020 years 8 fold increase in valvular disease All associated with radiation What are the side effects? Heart disease and breast cancer
Involved field Not Extended/Extended/ Mantle --LowerLower dose 2020--3030 Gy Not 45-45- 50Gy --1.81.8 GyGy--2gy/day2gy/day and NOT 3 GyGy/port/port No Cobalt Current studies on the risk
9 Hodgson et al validated radiobiological model 9 taking into consideration cell initiation, inactivation and ppygpyroliferation after varying doses of radiation therapy 9 to quantify the excess risk
9 compared mantle 35 Gy given historically to IFRT 20 Gy the estimated relative risk was in agreement with the literature with the modern treatment using IFRT to 35 Gy 9 there was an estimated reduction by 63% and 21% for breast and lung cancer, 9potential reductions of 77% and 57% for IFRT at 20 Gy
9 Hancock et al showed: 9 a dose above 30 Gy is significantly associated with cardiac risk disease
9 De bruin showed lower risk of breast cancer with smaller fie ld o f ra dia tion Here is what we achieved
Radiation alone – EORTC,GHSG HD7 showed CTRT is equivalent to EF RT
MOPP or MOPP/ABV – trial Established ABVD (equivalent OS)
Extended Field with CT (HD8) – ABVD +EF vs. ABVD +IF
Drop the dose of RT – Loeffler compared 40 vs. 30 Gy
Drop staging laparotomy GHSG 10 early favorable HL
9 Earlyyg favorable: low risk stage 9 2x2 randnomisation 9 Median FU of 5 years 9 FFF 93 % 30GY vs 92% 20Gy GHSG 10 early favorable HL Early Unfavorable GHSG 11 GHSG 11 early unfavorable HL
All arms were equivalent, only ABVD +20 Gy was inferior GHSG 14 early unfavorable HL
1528 patients assigned to : 4 ABVD +30Gy RT Or 2 BEACOPPes +2 ABVD+30 Gy RT
5% gain in FFT and 6.2% gain in PFS Combination of Chemotherapy Future GHSG 13 Stages I, II without RF (HD13)
ABCD ABVD ABV AVD AV ABVD ABV AVD AV
30 Gy IF - RT 30 Gy IF - RT 30 Gy IF - RT 30 Gy IF - RT Treatment Treatmentof Advanced of Hodgkin ’’ s
Longo et al in 80’’ s MOPP can give a DFS of 66% at 10 years
Santoro et al.: suppyeriority of ABVD+RT (fig)
2 US trials tested ABVD vs. MOPP alt. ABVD vs. MOPP/ABV equally effective Stanford V in advanced stage
MSKCC experience Stanford experience Italian study challenging Stanford V in favor of ABVD compared to MOCOPPEBVCAD BEACOPP
GHSG HD 9 compared
BEACOP escalated. Vs BEACOPPbaseline Vs. COPP/ABVD HD 12 BEACOPP Final TreatmentAnalysis of HD of 12 Meta-analysis on the role of radiation in advanced HL Since the meta analysis Role of radiation in advanced
GELA H89
EORTC showed no benefit
HD 12 showed a benefit if residual on CT (10% in observation arm got RT Use of RT in advanced Indian Experience
No consensus yet for advanced stage
Laskar JCO 2003 Use of RT in advanced Pediatric data (Nachman)
-All s tages i nc lu de d -COPP/ABV
Group 1= early no RF Group 2= early +AF Group 3= stage IV
Nachman 2002 JCO Standard of Care
Stage I,IIA No risk factors ABVD 2 cycles +IFRT/ INRT 20 Gy Stage I,IIA + risk factors ABVD 4 cycles + IFRT/ INRT 30 Gy 2 BEACOPPes.+2 ABVD +IFRT 30 Gy Advanced stage 6ABVD or BEACOPP ? IFRT for bulky sites/ residual mass on CT Hot topics
Chemotherapy alone/ using PET to stratify
Use of RT in advanced stage
Use of RT in relapsed //BMTBMT
Use of technology to decrease side effects Canadian Trial: Chemotherapy alone 405 p ts s tage I-IIA non b ulk y Canadian Trial: Chemotherapy alllone
OS
-14 additional second cancers were reported, 10 in radiation arm -Use of extended field is not justified Canadian Trial: Chemotherapy alone
Problems: – Use of Extended Field Chemotherapy to EF+Chemotherapy – Use of more chemotherapy 6 cycles of chemotherapy HD6/NCIC 2012 treatment Stanford: LongLong--termterm follow-follow-upup is available from retrospective data on chemo+modern XRT
Advani et al., IJROBP 2011 H10 EORTC /GELA ROLE OF PET IN EARLY FAVORABLE H10 EORTC /GELA ROLE OF PET IN EARLY FAVORABLE RolePET of PETin HD /HD 15 15 Use of PET
HDHD--16:16: Early stages: 2 ABVD PET: neg: 1 ABVD NO RT PET pos: 2 BEA escÆPET+:RT
HDHD--17:17: Intermed.stages: 2BEA esc PET neg: 2 ABVD no RT PET pos: 2 BEA esc +/+/--RTRT
HDHD--18:18: Adv. Stages: neg Æ 44--66 ABVDÆPET negÆ nil 2BEA2 BEA escÆ PET posÆ 22--44 BEA esc PETÆneg: nil
PETÆpos: RT Use of RT Progression, relapse, BMT
1-Radiation has to be used in any radiotherapy naïve patients IFRT Can not be the sole modality
2-For primary progressive transplant has TbthTo be the next tt step
Radiation can be considered before salvage chemo or transplant
3-In the setting of transplant radiation has to be given either before or after What is Involved field? It is the involved field Yahalom & Mauch, 2002 That is what it means What is Involved field? IiIt is t he invo lve dfildd field What is Involved nodal? It is the involved site?
• PET CT can change the contouring ( 36% )
• yet no evidence on outcome
• To be on the safe side we shldhould use both
CT postive PET negative wait for chemo Steps to INRT
Spleen Liver
Kidney Heart Word of caution?
1-PET negative CT positive if regress after chemo should be included 2-CT can not be reliable with no contrast 3-PET positive should be included
If prechemo imaging is missing we resort To involved site. You have to see to treat
INRT radiation: – Do you know the location of disease, do you have all prechemo imaging Did you scan patient in treatment position
– Do you know the internal motion – Do you know lymphoma CTV – Use breath hold, IMRT, Proton, CT on rail.
Breath hold / CT on rail for mediastinal cases Breath hold /CT on rail for abdominal lymphoma Lymphocyte predominant Pathology: Negative CD 15,30 CD 20 + ,CD 45+, L&H cells, EMA-
Early stage common 80%
Neck presentation
Rare extdltranodal presenttitation European Task Force Lymphoma
Diehl JCO1999 Europpypean Task Force Lymphoma European Task Force Lymphoma Europpypean Task Force Lymphoma LymphocyteLymphocyte--PredominantPredominant Hodgkin Lymphoma A Retrospective Multicenter Study of the Australasian Radiation Oncology Lymphoma Group
Long-Term Outcome after Radiotherapy Alone for Cancer 2005
Lymphocyte predominant Dose 30 Gy is sufficient
6 Gy boost can be added for bulky disease
Involved field
Long follow needdded Aggressive Lymphoma Aggressive Lymphoma we are usiWHOing WHO
Working formulation: – LowLow--intermediateintermediate--highhigh Based on morphology – Ignored immunophenotyping – MissingMissing:: Mantle,Mantle, MALT, Anaplastic, viral, T-T-subtypessubtypes
WHO based on: – Clinical, – Immunophenotyygping – Cytogenetics Working formulation Working formulation
Mantle cell Chronic lymphocytic leukemia CD 10-, CD 5- CD23 – CD5+ CD10-CD23+ T 11, 14 Trisomy 3 Aggressive behavior Low grade GI involvement Large B cell Lymphoma Subtypes, it is not one entity!
Proposed revision of the WHO 2008 Etiology still unknown for most
HIV with l ow CD4 coun t HyperHyper--endemicendemic malaria and childhood EBV = Burkitt EBV infection= Angioimmnoblastic,T/NK cell, lymphomatous hyperplasia Gluten enteropathy = enteropathic associated T cell lymphoma Immunosuppression: primary or secondary ChronChron’’s,s, use of methotrexate, useuse of interferon, kidney transplant Chronic inflammation (accumulation of abnormal growth promoting cytokines cells IL6 Genes signature: Activated B-B-cellcell vs. Germinal center B cell like Upfront risk stratification Diagnosis/Pathology: Core biopsy Immunohistochemistry (Hans algorithm) BCL6, CD10, MUM1/IRF4 Gene expression profile GC B cell ABC PML Morphologic Immunoblastic CtbltiCentroblastic Typical panel: CD20+, CD45+, CD3-CD3-,, CD138-CD138-,, BCL2, BCL6, C-myc Identify the double hit Upfront risk stratification
Presentation: 6th decade, 1/3 bulky disease, 40 % extranodalextranodal,, 20% marrow involvement Staggging work u p: blood work , b2 microglobulin,,y, liver kidney function, PET CT/diagnostic CT with contrast Determine special locations: paranasal sinus, testicular_____brain invasion LP is needed
Adverse Risk group Number of 5 year 5 year OS factor factors DFS(%) (%) Age > 60 Low 0-1 70 73 PS ≥ 2 Low/Intermedi 25051 ate LDH > normal High/Intermed 34943 iate Extranodal 4-5 40 26 sites ≥ 2 Stage III-IV Prognostic factors model APLES
The International Non -Hodgkin's Lymphoma Prognostic Factors Project NEJM, 1993 For practical Purposes be fore dec iding on therapy Limited : Stage I and II No B symptoms < 10 cm mass Advanced: Stage III and IV B syypmptoms > 10 cm IPI score,,g gene sig nature , Ki 67%, double hit. Limited stage DLBCL
Reason for using CHOP Limited stage DLBCL
Cyclophosphamide 750mg/m2
Doxorubicine 50 mg/m2
Vincristine 1.4 mg/m2 not exceeding 2mg
Prednisone 40 mg/m2 CHOP vs. RCHOP ACVBP
Adriamycin 75mg/m2
Cyclophosphamide 1200/m2
Vindesine 2m/m2
Bleomycine 10mg day 1,5
Prednisone 60mg/m2 d1-5
Methotrexate 3g/m2 + Leucovorin Etoposide 300mg/m2 Ifosphamide 1500/m2 Cytarabine 100mg/m2
GELA DADA--EPOCHEPOCH--RR
Wilson NCI Treatment DLBCL
Limited stage: – Chemotherapy +Radiation
Role of Radiation in early stage – The benefit is still challenged Role of Radiotherapy
4 trials determine the standard: – ECOG, SWOG, 2 GELA – 2 differen t tak e h ome message be tween medical oncologist and the radiation oncologist ECOG 1484
Despite more bulky disease in RT arm -PR had excellent DFS 63% at 6y -6% gain in OS not statistically significant -5,10,15 estimates: RT group 82%, 78%,78% No RT group 71, 67%,64% 73% 56%
75% 56%
Horning JCO 2004 SWOG 8736 8 CHOP vs. 3 CHOP+RT
77% 82%
72% 64%
Stage I bulky, stage II, 1 extranodal Dose 4040--55Gy55Gy More cardiac death in 8 CHOP
Miller 1998 SWOG 8736 8 CHOP vs. 3 CHOP+RT
Updated results: OS curves cross at 9 years DFS cross at 7 years 15 Late relapses (5-10) in abbreviated chemo arm 8 in the chemotherapy arm OS IPI score 0 =94% OS IPI =1 =71%
More chemotherapy is needed for higher risk patients
Miller 1998 GELA 8989--01:01: < 60 years ACVBP vs. 3CHOP/ RT
90% 81% 90%
••MedianMedian time to relapse was 21 m vs. 15 m But the Relapse at initial site: 41 % (ACVBP) vs. 23% (CHOP+RT)!! Out of field 38%(ACVBP) vs. 72% (CHOP+RT)
••1616 second malignancies (7 ACVBP, 9 CHOP+RT (3/9 in field) GELA > 60 4CHOP vs. 4 CHOP+RT
64%
Relapse: 61% chemo 47 % initial site chemo RT 21% initial site
Inferior outcome for both arms Inspite of the low risk group 72%
68% Conclusions from the 4 trials
Althoug h SWOG an d GELA 93-1 are used to refute the role of radiation – The real message is radiation can not replace inadequate chemotherapy IhIn the prepre--Ritux ima b era Higher dose, large field of radiation Non consistency in patients characteristics or outcome Bullky is a continuous Variable, > 10 cm suggested
Pfreundschuh 2008 Phan 2010 Phan 2010 Radiation in advanced DLBCL Conclusion for limited stage DLBCL
Consolidation radiation should be recommended for limited stage, Abbreviated chemo should be cautiously given to: Worrisome features Head neck sites Nex t t o CNS Bulky sites High Ki67%
IFRT/INRT 30 GyGy--6 Gy boost (for residual mass on CT) PET negative CT residual mass MDACC Role of PET scan
There was a complete agreement on the interim PET reading in 68-71% 3 nuclear medicine physician blinded to the actual results
Trials as of now are conflicting for the benefit (GELA vs. Italian) As of now it should not be used to determine the length of therapy Or the need for RT Interim PET can not be fully trusted MDACC data role of midterm PET
Positive Midterm PET is predictive DFS,OS for al 296 1.00 1.00 55 55 0.7 0.7 0.50 0.50 Overall survival Overall survival Overall .25 0.25 00 0.00 0.00 0 2 4 6 8 10 0 2 4 6 8 10 Interval FU Years Interval FU Years
Mid cycle PT = Negative Mid cycle PT = Positive Mid cycle PT = Negative Mid cycle PT = Positive
Positive Midterm PET is no predictive DFS,OS all patients receiving consolidation RT 1.00 1.00 5 5 l 77 77 aa 0. 0. 0.50 0.50 Overall survival Overall Progression free surviv free Progression 0.25 0.25 0.00 0.00 0 2 4 6 8 10 0 2 4 6 8 10 Interval FU Years Interval FU Yearsanalysis time
Mid cycle PT = Negative Mid cycle PT = Positive Mid cycle PT = Negative Mid cycle PT = Positive Intensive chemotherapy
RCHOP 14 ACVBP DADA--EPOCHEPOCH R High dose therapy/Transplant, No evidence How to manage stage II DLBCL
PETPET--larlargggpgge infiltrative mass in the gastrohepatic ligament infiltrating the adjacent lesser curvature of the stomach. Discrete adenopathy is identified along the common hepatic artery and portocaval nodes Stage IIE
R-CHOP X cycles ?XRT
Treatment
Pre-Chemo Primary mediastinal lymhoma
Young females Stage I and II Prognosis is controversial Radiation is standard in most centers – 39.6 Gy to initial involved sites Chemotherapy:RCHOP or RMACOB – Reported 3 years DFS 70-70-80%80%
Duplicating the outcome and feasibility of administering the regimen Chemotherapy toxicity was not mentioned (4% death from previous publication) – Who survived therapy? SdliihSecond malignancy with Etoposide ihflliis worth following Dose painting
Dose 30 -39.6 Gy Primary mediastinal
I do not want to give RT to every body although i n my h and i s very saf e
I am suggesting to use radiation in cases that is needed – Do not give more chemotherapy to avoid radiation – Causing risk of death – Depletion of marrow – Risk of second leukemia from Etoposide containing – CHF form Anthracycline containing regimens – Bulk of disease has to be taking into consideration Any doxorubicin use associated with 29 % CHF – BtBut pati titents were eld ldlerly > >65 65 – And another SEER data Diffuse Large B cell Lymphoma
Paranasal sinus
PML PBL PCNSL DLBCL: Testicle
Staging: LP is needed Stage I but give 6 RCHOP no exception Radiation to the testis 30 Gy CNS pppyrophylaxis IT MTX or HD MTX
NK cell nasal lymphoma
Rare but aggressive CD 56 + Early stage Radiosensitive: Dose response 50.4 GyGy--5454 Gy Radiation outcome: Best local control 4040-- 67% Chemoth erapy has a mo des t ro le Primary CNS Lymphoma
Treatment: HD MTX based Whole brain radiation + eyes up to anterior chamber – Age 60 is cutoff for neurotoxicity – Dose used to be 45 Gy? – Strugg le w ith neuro tox ic ity repor te d up to 30 % w ith WBRT (>60 years of age)
30 patients treated with MTX based +R followed by WBRT 23.4 if CR 2 year PFS 57% , OS 67% Reduced dose of RT was not associated with neurocognitive decline Excellent disease control
Conclusions
1-Radiation improve DFS in early stage especially in bulky disease (ECOG, SWOG) 22--AbreviatedAbreviated chemotherapy sh oul d be used wi th cauti on Radiation is indicated in sites: – Testis 30 Gy, p aranasal sinuses 40Gy, PCNSL 23.4 Gy,PML 3030--39.6 Gy (bulky disease) Low ggyprade Lymphomas Low grade Lymphomas Follicular Lymphoma
B cell in origin in > 90% 20-30% at least will transform The majority will present with advanced stage – Median survival 66--1010 years – 50% BM involvement at presentation Only 20% are localized (curablity?) T(14;18) is pathognomonic Nodal and extranodal presentation FLIPI score Follicular Lymphoma
Stage I, II vs. III, IV
Grade 1,2 vs. 3a,3a,3b3b – Presence of Large cells Standard of care we do not have one No standard of care Single agent chemotherapy Alkylating agents Rituximab With chemo, maintenance, with bendamustine Interferon Valcade (proteosome inhibitor) Fludarabine Cyclop hosp ha mi de Aggressive chemotherapy Transplant Observation Involved field radiation for stage II--IIII G 1-1-22 Observation Stanford approach 43 patients stage I,II grade 1,2 MDACC/combined modality
10 year OS 80% What is the standard of care stage I,II grade 1,2
Varies among physicians IF radiation is given: – Definitive: organ +draining lymphatics Dose 3030--3636 Gy – Adjuvant: involved field Dose 30 Gy – 24 Gy can be used Grade 3 a,b: managed like aggressive lymphoma :back to same argument
Stage III ,IV
No role for radiation 2x 2 Gy can be suggested in some shtfdihort of doing no thing MALT Lymphoma MALT Lymphoma Prognostic Factors MALT Lymphoma
Poor prognostic factors: T (11;14) Bulky disease Age > 60 Large cell component High LDH , b2 microg lblilubulin Poor KPS Gastric MALT
Gastric is the most common . If Associate with H pylori, treatment with ATB w ill ac hieve CR in 2/3 cases Sites of Involvement
Be aware of skin malt Set Up Disposition:
30 Gy in 20 Fractions of 1. 5 Gy each Treatment Radiation 30 Gy/20 Fx
Stomach
Conclusions
Follicular Lymphoma: – Radiotherapy alone 30 Gy (boost 36yGy) – Chemoth erapy+ radi a tion (30 Gy ) – Protocol: Radioimmunotherapy MALT: Stomach +perigastric area 30 Gy/20 Fx Plasmacytoma
History and physical CBC, differential and platelets BUN, creatinine,creatinine, electrolytes, albumin, LDH, calcium BetaBeta--22--microglobulinmicroglobulin Quantitative immunoglobulins Serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (SIFE) 24 hour urine protein electrophoresis (UPEP), free light chains (FLC) Skeletal survey MRI T, L S spine Unilateral bone marrow aspirate and biopsy and flow cytometry Consider PET scan For extramedullary plasmacytomaplasmacytoma:: CT and MRI of affected area Plasmacytoma
If anemia, hypercalcemia, renal failure due to multiple myeloma and/or
If bone survey with greater than 1 bone lesion, and/or
If bone marrow with clonal plasma cells and/or
MM--proteinprotein greater than 2 grams/dL and/or
24 hour urine protein greater than or equal to 500 mg/day and/or
MRI spine with additional lesions and/or Decreased uninvolved immunoglobulins Plasmacytoma Plasmacytoma Value of Protein for outcome
Reed 2011, Wilder Cancer 2002 Factors predictive: – Tumors > 5 cm more failure – PPlaranasal siiinuses – Lower RT dose < 35 was not associated with higher local failure
– The d ose t o use 45 Gy Can be lower to areas at margins Radiation Field
MRI+ PET +CT – MRI pick the marrow signal – CT lytic lesion – PET actual activity 1- 2i2 cm margin Dose 3535--4545 Gy according to size and critical organs Vertebral body: No one up one down Long bone: Do not treat the whole bone
Multiple Myeloma Palliative role Pain control Prevent fracture Relieve nerve pressure Field: very small (No above and below) Save the marrow Be able to retreat Very sensitive Dose 2020--2424 Gy Even 15 Gy can do it Systemic therapy to be considered; Immunotherapy and steroids Leukemia: Craniospinal/WBRT/TBI
CaseMycosis 1 Fungoides # 733129 z Path: Mycosis Fungoides z Prominent epidermotropism z Pautrier microabscess z CD 25+ CD3+, CD4+ z T cell receptor rearrangment z Numerous CD30+ large cells z possible large ce ll trans forma tion Stanford Dual Beam Technique
z Long SSD with scatter/degrader, dual fields, 6 treatment positions MDACC TSEI Technique
60o
PEV TSEI Treatment Position (AP/PA) Fingers and thumb ttth&tddogether & extended Palms of the hands facing directly towards or directly away from the beam Feet shoulder width apart Patient’’ s chin raised to expose the skin under the chin and the neck Arms parallel to plate Navoga
Ann Oncol 2005
Modern Treatment Comparing Chemo/IFRT vs. RT
-No second malignancies at 11.6 years of Follow up
Koontz JCO 2006 Cumulative incidence of CVD 12% at 5 y , 22% at 10y. 40% ha d RT to neck and 30% RT to mediastinum
LymphocyteLymphocyte--PredominantPredominant Hodgkin Lymphoma A Retrospective Multicenter Study of the Australasian Radiation Oncology Lymphoma Group LymphocyteLymphocyte--PredominantPredominant Hodgkin Lymphoma A Retrospective Multicenter Study of the Australasian Radiation Oncology Lymphoma Group Navoga
Ann Oncol 2005