Academic discussion on Non-Hodgkin Lymphoma for students of Radiation Oncology (MD, DNB) by Dr. Abhishek Basu(MD, DNB)

1. Management of Non Hodgkin
Lymphoma
Dr. Abhishek Basu
Clinical Tutor, MCH
dr.abhishekbasu1123@gmail.com

3. NHL
Categories
Low-grade NHL
Follicular ( G1,G2,G3A), SLL, MALT, MF
Intermediate-grade NHL
Follicular G3B, DLBCL, Mantle, T/NK cell, peripheral T cell, anaplastic large
cell ( ALCL)
High-grade NHL
Burkitt’s lymphoma, Lymphoblastic lymphoma.

4. Special case Work up
CSF – HIV, Testicular, epidural, paranasal sinus involvement, double
expressor lymphoma, bone marrow involved in large cell lymphoma.
MRI – If getting lumbar puncture for CSF study.
ECHO – if getting anthracyclin.
EUS, rapid urease test for Gastric MALT.
Blood – LDH, beta2 microglobulin

5. Genetics of Indolent (low grade) Lymphoma

6. Genetics of High Grade Lymphoma

7. Low Grade Indolent NHL
GELF Criteria
Criteria for treating FL
≥ 3Nodal sites (each > 3cm)
Mass > 7 cm, B symptom
Splenomegaly,
Effusion/ Ascites,
Cytopenia,
Leukemia.

8. Treatment of Follicular Lymphoma
Stage I, II ( G1-2) - ISRT alone , 24 Gy/12# , CTV = GTV + 5 cm Prox &
distal , 1.5 cm radially.
If CR/PR then observe , If SD/PD- Treat like stage III,IV.
Stage I,II G3 – Treat like DLBCL
Stage III,IV – Observe ( H&P 6m for 5yrs, CT annually 2yrs then if indicated.)
Indication for treatment in stage III,IV
End organ dysfunction, disease progression, symptomatic, bulky, for RCT
Options of treatment - R CHOP/RCVP/BR
Palliative RT – 2Gy × 2# , 90% response rate, 60% achieve CR , also called ‘ Boom
Boom’ regime.
Relapse case: I131 - tositumomab ( beta/gamma) [ Radioimmunotherapy]
Y-90- ibritumomab ( pure beta) Both causes cytopenia in 6-8 weeks.

9. MZL: Marginal Zone Lymphoma
 3 Subtypes- Splenic, Nodal, Extranodal ( includes MALT)
 MC Stage is IE,IIE
 Here lies the Role of Surgery in Lymphoma: Breast, bowel, thyroid, lung
– after surgery if R0 then observe else RT 24 Gy/12# ( MALT cases).
Lung MALT – Advanced stage – Chemo +_ ISRT
 Other MALTs
Orbital – c/b Chlamydia psittaci. 24Gy in 12-16# to entire orbit. [ Orbital
DLBCL dose is ]
SKIN – c/b Borrelia burgdorferi Surgery or electron beam therapy (24-30Gy)
Salivary/ Lacrimal – 24-30 Gy ISRT.

10. Gastric MALT
 Commonly caused by H. pylori, Tx starts with RUT, Quadruple therapy(
Bismuth, lansoprazole, tetracycline, metronidazole).
 High grade MALT likely to be transformed to DLBCL , DLBCL of
stomach is treated by R-CHOP 3-6 Cycle ( Based on IPI)+ ISRT.
 RT indication- H.pylori neg, t(11,18), deeply invasive lesion, rapid
symptomatic progression.
 RT Dose – MALT (30 Gy), DLBCL ( 36-40Gy)
 CT sim- fasting for 3hrs then small vol oral contrast, 3mm slice.
 CTV= Whole stomach+ perigastric node, ITV= 1-2 cm, breath hold
technique is ideal, PTV = ITV+1 cm.

11. Splenic MZL
 Most definitely diagnosed at splenectomy, IHC- CD20,21,3,5,10 & cyclinD1
 Karyotype or FISH – t(11,18), t(14,18) D/D Hairy cell leukemia.
 Bone marrow biopsy is need if IHC is inconclusive.
 Treatment: Asymptomatic without progressive cytopenia - Observe.
Splenomegaly – Rituximab (RCHOP,BR) 6# or splenectomy (less preferred)
 Vaccines to be given at least 2 weeks prior splenectomy- Pneumococcal,
meningococcal, Hep B .
 Recurrence after treatment – Splenectomy if not done already, Pall ISRT,
Lenalidomide + R, ibrutinib, PI3K inhibitors, confirm histologic
transformation to DLBCL ( Anti CD19 CAR T cell therapy-
Tisagenlecleucel)

12. NODAL Marginal Zonal Lymphoma
Stage I, II – Contiguous spread ISRT alone preferred ± RCHOP
Non contiguous spread- R CHOP + ISRT
Stage III, IV – Indication for treatment: Bulky, cytopenia, rapid progression,
threatened end organ dysfunction.
Treatment – RCHOP, RCVP, BR etc. or Pall RT 2×2Gy.
SLL/CLL – del13, t(14,19),trisomy 12 , CD5,19,20 +
In 5% cases, SLL/CLL is transformed to DLBCL – Richter syndrome.
SLL Tx- R + Bendamustine/ (fludarabine +cyclophosphamide)/ ibrutinib
ISRT for early stages.

13. Cutaneous T cell Lymphoma / CTCL

18. TSEBT
Pt dosimetry TLD s are over umbilicus, sternum, axilla, thigh, extremities,
neck & forehead.

19. Technique
 Extended SSD 3.5-4m , pt rotated through series of 6 different positions.
 Large acrylic sheet placed 20cm from pt surface to scatter electron beam.
 6 MeV electrons used with beam spoiler to make it 4 Mev. Dose prescribed
at skin surface so that 80% IDL covers 4 mm depth.
 Shielding : eyes& nailbeds are shielded to avoid edema, toes & fingernails
are shielded after 9 Gy.
 1Gy / day @ 4 days per week.
 3 patient positions per day, 4 day per week , for 9 weeks.. To total dose
36Gy.
 Boost: Soles, perineum, scalp are often boosted with 20Gy.
 *Stage 3 CTCL – TSEBT 12-24 Gy total skin dose + boost 20-30Gy
 Note- In CTCL limited patch (T1-3)- Topical corticosteroids + 20-30Gy
local RT is needed, Pall RT dose is 8-12 Gy. [ N.G.Zaorsky et al]

20. These positions maximize skin unfolding, hence improving dose homogeneity.
Note* - ALCL ( anaplastic large cell lymphoma) is also a cutaneous lymphoma,
CD30+, needs 30-40 Gy ISRT.

22. IPI scores

23. DLBCL
DLBCL is MC subtype of NHL. AIDS defining illness ( What are others?)
Double hit : bcl2 / bcl6 + c-myc translocation poor prognosis
Triple Hit : bcl2+ bcl6+ c-myc translocation. DA R-EPOCH > RCHOP.
Rituximab is anti CD20. four main RCT showed that in chemo alone arms,
there was 45% relapse, RT improved local control by 70%.
Can we omit RT ? – MDACC retrospective (Phan2010), Unfolder trial,
RICOVER –no RTh(held,2014), SWOG 0014 – RT + RCHOP improves
PFS,OS for early & late stage whenever indicated.
PMBCL – arises in B cell clones in thymus not in nodal B cells. May be
CD30/45+, lies between HL & NHL. 6c DA –R- EPOCH or 6c R-CHOP +
30Gy ISRT.

24. Pre Rituximab era…

25. Treatment of DLBCL
Stage I,II IPI 0-1: RCHOP 3 cycle + ISRT 36 Gy, boost to FDG
avid residual to 40-45 Gy.
IPI 2-4: 6 c RCHOP + ISRT 36 Gy, boost to FDG avid residual to 40-45 Gy.
Stage I,II Bulky 6 c RCHOP + 36-45 Gy ISRT
Stage III, IV R CHOP 4 cycle then PET CT
CR PR
2 more cycle of RCHOP 2 c RCHOP then restage with PET
+ ISRT 36 Gy to initial bulk. Neg positive
ISRT 36 Gy to initial bulk 2nd line/ ASCT

26. Evidences & Regimes

27. Extranodal DLBCL
Testis- 6RCHOP+ 30Gy scrotal
RT. 9-12Mev electron.
Breast- 6 RCHOP+36 Gy
Bone- 3 -6 RCHOP + 36 Gy for
CR, 40-45 Gy for PR. Spare
joint space if not involved,
shrinking field RT. CTV = GTV
+1 cm. MRI is needed for
contouring.
Gastric DLBCL- 3 RCHOP+30-
36Gy.

28. Details of ISRT is discussed in HL slides, remaining part…

30. All are stage IE extra nodal NHL.

32. Work UP

33. Historic treatment of PCNSL
Current guideline: HD (3gm/m2) 4hr IV MTx induction , if
CR then low dose WBRT 23.4Gy @1.8Gy/#, if PR then
WBRT to 24-36Gy f/b involved field boost to 45 Gy. If Cant
tolerate MTx, then use cytarabine,thiotepa,or ifos.

34. Treatment Paradigm in 2020

35. Chemo Toxicity
 Adriamycin : Cardiomyopathy ( limit is 450mg with RT, 550 w/o RT)
 Bleomycin: Pulm fibrosis (limit is 300mg/ 300U), rash, febrile reaction.
 Vinblastin : Neuropathy & hair loss.
 Dacarbazine : leukopenia, thrombocytopenia, vomiting, photo toxicity.
 Procabazine: hair loss, constipation, mouth sores, flu like symptoms rarely.
 Rituximab : Fever, Rash, tumor lysis syndrome, Hep B reactivation,
neutropenia, progressive multifocal leukoencephalopathy.

36. RT Dose Summary in NHL

39. Follow up (NCCN 2020)
H&P and routine CBC every 3-6 month for 5 yr. [ 3monthly for 3yrs,then 6 m
2yrs] after that as clinically indicated.
C/A/P CECT every 6 month for 2 years then as clinically indicated.

41. Management in brief…
Poor Prognostic # - Plasma cell labelling index> 1%,
Albumin <3.5g/dl,
High Beta2 microglobulin.
Treatment:
Chemotherapy – Bortezomib + Lenalidomide+ dexa
Refractory cases – Autologous stem cell transplant.
Supportive – Bisphosphonates.
RT – Pall RT 30 Gy/ 10 #.

42. Thank You