ROLE OF PET-CT IN MANAGEMENT OF LYMPHOMA

Malkit S Riyat MBChB, FRCPath(UK), FCPath ECSA

Aga Khan University Hospital, Nairobi
Consultant Haematologist
riyat.malkit@aku.edu

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 LYMPHOMAS
NON-HODGKIN LYMPHOMA

• B-CELL NEOPLASMS
• T-CELL NEOPLASMS
• Mature T-cell and NK-cell neoplasms

HODGKIN LYMPHOMA

• NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA (NLPHL)

• CLASSIC HODGKIN LYMPHOMA (cHL)
- Nodular sclerosis Hodgkin lymphoma
- Mixed cellularity Hodgkin lymphoma
- Lymphocyte-rich classic Hodgkin lymphoma
- Lymphocyte depleted Hodgkin lymphoma
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IMAGING USED IN COURSE OF LYMPHOMA MANAGEMENT

• PET - involves IV administration of F18 FDG. Uptake of FDG is

increased in malignancies and a gamma camera used to image
glucose metabolism in vivo
• CT-produces anatomic image
• PET-CT – enables both anatomy and function to be assessed

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 FDG-avidity of lymphoma

Variably FDG-avid
Marginal zone lymphoma (MZL)
Highly FDG-avid
Chronic / small lymphocytic (CLL/SLL)
Hodgkin’s lymphoma
Diffuse large B cell (DLBCL)
Burkitt’s

Usually FDG-avid
Follicular lymphoma (FL) Rare lymphomas
Mantle cell lymphoma (MCL) NK T cell
Peripheral T cell (PTCL)
Cutaneous lymphoma
Angioimmunoblastic T cell
Anaplastic large T cell (ALCL)
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 FDG-avidity of lymphoma
(Activity above surrounding tissues)

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www.intercancer.com Weiler-Sagle et al,. JNM 2010 51: 25 - 30 1. 8
 Role of imaging in lymphoma
Provides important information for
• Staging
• Treatment planning
• Response assessment

- Most prognostic scoring systems use imaging stage

- Fluorodeoxyglucose (FDG) PET/CT is an essential imaging test
particularly for Hodgkin lymphoma and diffuse large B-cell lymphoma

J Clin Oncol 2014;32(27):3048–3058

Eur J Nucl Med Mol Imaging 2014;41(5):1004–1027
Ann of Oncol 2011; 22;739 - 745
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 Role of PET-CT for staging
PET-CT most accurate modality for staging lymphomas

• Staging in clinical practice and clinical trials

• Recommended for routine staging of FDG avid lymphomas - Not routinely recommended
in lymphomas with low FDG avidity
• CT reserved for other lymphomas and where PET not available
• Particularly sensitive for extra nodal disease
• PET-CT can be used for assessment of bone marrow in HL/DLBCL- more sensitive than
bone marrow biopsy
J Clin Oncol 7:1630- 1636
N Engl J Med 329:987-994, 1993
Blood 104:1258-1265, 2004
Ann Hematol 86:897-903, 2007
Ann Oncol 17:117-122, 2006
Ann Oncol 19: 1770-1773, 2008
International Cancer Institute 2020. Radiol Med 113: 578-590, 2008
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 Role of PET-CT for staging (cont)

• Upstaging occurs more often than down staging, with

• Management alterations in some patients
• The intensity of FDG uptake is higher in aggressive than indolent
lymphomas
• FDG PET-CT may be used to target sites for biopsy in patients with
suspected transformation - used to select best site to biopsy
J Clin Oncol 7:1630- 1636
N Engl J Med 329:987-994, 1993
Blood 104:1258-1265, 2004
Ann Hematol 86:897-903, 2007
Ann Oncol 17:117-122, 2006
Ann Oncol 19: 1770-1773, 2008
International Cancer Institute 2020. Radiol Med 113: 578-590, 2008
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J Clin Oncol 29:1844- 1854, 2011
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 PET/CT staging

• PET allows more accurate staging than

CT alone in 10-40%
Tatsumi Radiology 2005 237: 1038
Schoder J Nuc Med 2001 42: 1139

In another study

• PET led to
- Change in stage 44%
- Change in management >60%
Schoder J Nuc Med 2001 42: 1139

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Tatsumi Radiology 2005 237: 1038 1. 13
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 Improved detection with PET

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 PET and Bone Marrow Biopsy

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 Improved detection with PET

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 False negative PET for BM in DLBCL

• PET is more
sensitive than BM
biopsy

• Misses low volume

disease in 10 - 20 %

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 Updated recommendations – staging assessment

PET/CT is the gold standard for staging of all FDG-avid nodal lymphomas
• Everything except
-CLL/SLL
-Lymphoplasmacytic/Waldenstrom’s macroglobulinemia
-Mycosis fungoides
-Marginal zone lymphoma*

*Unless there is suspected aggressive transformation

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 Role of iPET
Interim imaging frequently performed in clinical practice and trials

Purpose of iPET
• to ensure the effectiveness of treatment
• exclude possibility of progression
• iPET is a strong prognostic indicator in HL and aggressive NHL

PET-CT
- shows metabolic response earlier than anatomic response and
- has the potential to replace CT
- outperforms the International Prognostic Score and International Prognostic Index

These findings highlight the potential of using iPET to tailor

Cancer 107:2678-2687, 2006
treatment according to individual response Clin Oncol 27:1906-1914, 2009
J Clin Oncol 25:3746-3752, 2007
J Nucl Med 54:683-690, 2013
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www.intercancer.com J Clin Oncol 30:184-190, 2012
PET‐adapted
Therapy for
Hodgkin
Lymphoma

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PET‐adapted Therapy
for Hodgkin
Lymphoma
(early‐stage disease)

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PET‐adapted Therapy
for Hodgkin
Lymphoma
(early‐stage disease)

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PET‐adapted Therapy
for Hodgkin Lymphoma
(advanced‐stage
disease)

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PET‐adapted Therapy
for Hodgkin
Lymphoma
(advanced‐stage
disease)

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PET‐adapted Therapy
for Hodgkin
Lymphoma
(advanced‐stage
disease)

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 DLBCL -EFS according to PET status
after two cycles

1.00
PET negative (n=49) 2 years EFS = 80%

0.75
Probability

0.50

PET positive (n=32) 2 years EFS = 46%

0.25

0
p=0.0003
0 1 2 3 4 5
Years
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 DLBCL
(A) PFS and (B) OS according to interim PET/CT

ONCOLOGY LETTERS 14: 6715-6723, 2017

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 Risk Stratification of Diffuse Large B-cell Lymphoma with
Interim PET/CT by combining Deauville Scores and
International Prognostic Index

Cancer Management and Research 2019:11 9449–9457

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 Role of PET at the End of Treatment

• End-of-treatment remission assessment is more accurate with

PET-CT than CT alone in patients with HL, DLBCL and high–
tumor burden FL
• PET-CT is the standard of care for remission assessment in FDG-
avid lymphoma
• Post-treatment PET seems to be a better predictor than iPET
J Nucl Med 54:683-690, 2013
Lancet 379: 1791-1799, 2012
Eur J Cancer 47:1312-1318, 2011
Cancer 117: 1010-1018, 2011
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 Timing of PET CT scans for prediction of
Treatment Response in HL

• iPET-CT (scans performed during treatment)

- as long as possible after the last chemotherapy administration

• End of treatment scan

- 6-8 weeks post chemotherapy (a minimum of 3 weeks)
- > 3months after radiotherapy

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 Timing of iPET in DLBCL and FL

• Cycle 4 may be more predictive than cycle 2 but for clinical

outcomes still less important
• Post-treatment PET seems to be a better predictor than iPET

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 iPET Guided Therapy

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 Utility of routine post-therapy imaging in DLBCL
552 patients after treatment (surveillance)
Every 6 months X 3 years, then annual
Relapse in 112 (20 %) – 104 evaluable

• 67 patients identified before

scheduled visit

• 24 of other 37 patients had

suspicious clinical features
• (labs, symptoms or
examination)

• Only 13 patients
asymptomatic and identified
by imaging (CT or PET)

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 Surveillance imaging does not affect clinical outcome

• 1200 patients with

DLBCL after initial
therapy
• Danish patients had
routine imaging,
Swedish did not

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 Deauville Criteria
STAGING
RESPONSE

NO UPTAKE FDG < MBP FDG >MBP ≤LIVER FDG>LIVER FDG>>LIVER

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 ESCALATION
OR
DEESCALATION

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 PET-CT and ASCT
Another potential role of PET/CT is predicting
outcome (PFS and OS) in patients who are
candidates for ASCT

A positive scan before ASCT is highly predictive

of relapse

The 2-year PFS is up to 82% better in patients

with a negative pre-ASCT scan

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www.intercancer.com Bone Marrow Transplant. 2008;41(11):919-25
 SUMMARY

• Use PET for staging of most lymphomas

• PET can replace bone marrow biopsy
• Use PET for response assessment
• Use 5 point Douville criteria to assess response
• Not recommended for surveillance after completion of
treatment

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