1. PET / CT in lymphoma Dr Bhuey Sharma Consultant Radiologist
The Royal Marsden Hospital
Lymphoma Masterclass 2016

2. More questions than answers

3. PET negative DOES NOT = no lymphoma
PET positive DOES NOT = active lymphoma
PET negative DOES NOT = no lymphoma

4. Timeline oncological imaging
Sharma B, Martin A, Stanway S, Johnston SR, Constantinidou A. Imaging in Oncology- over a century of advances. Nat Rev Clin Oncol. 2012; 9(12):

5. Timeline oncological imaging
Sharma B, Martin A, Stanway S, Johnston SR, Constantinidou A. Imaging in Oncology- over a century of advances. Nat Rev Clin Oncol. 2012; 9(12):

6. Timeline: the development of lymphoma staging and response assessment guidelines
1965 Rye Classification
1971 Ann Arbor
Hodgkin’s disease. Contiguous spread; extended field radiotherapy; chemotherapy advanced disease. Localised extranodal disease related to adjacent lymph node disease does not adversely affect survival, E; laparotomy and splenectomy. Two systems of classification, clinical staging (CS) and pathological staging (PS).
1989 Cotswolds Meeting
Hodgkin’s disease. 1. Computed tomography for nodes 2. spleen and liver involvement includes focal defects on 2 imaging techniques 3. bulky disease concept (>10cm) X 4. CR(u) ‘uncertain/unconfirmed’ new category, to accommodate difficulty persistent radiological abnormalities of uncertain significance.
1999 International Working Group Criteria
Non-Hodgkin’s lymphomas. Standardised response guidelines. Anatomic definition response, normal lymph node size after treatment 1.5 cm largest transverse diameter CT. CRu (unconfirmed) >75% reduction tumour size with residual mass. Gallium scans encourage valuable adjunct, but such scans require appropriate expertise.
2007 International Harmonization Project
PET for response assessment in Hodgkin’s disease and non-Hodgkin’s lymphoma. PET after therapy completion at least 3 weeks, preferably 6-8 weeks post chemo/chemoimmunotherapy, 8-12 weeks post radiation. Visual assessment adequate. Residual mass > 2 cm, reference mediastinal blood pool activity; smaller or normal sized node (< 1 x 1 cm) surrounding background. Liver, spleen, lung, bone marrow criteria. Use of PET response assessment during therapy part of clinical trial or prospective registry.
2014 The Lugano Classification
Hodgkin’s disease and non-Hodgkin’s lymphoma. PET staging (BMB HD & NHL). 5-point scale for PET response. Modification of Ann Arbor descriptive terminology and CT response. Routine surveillance imaging discouraged.

7. Having (high-grade) lymphoma was bad for you Even if you were treated
Once upon a time….
Having (high-grade) lymphoma was bad for you
Even if you were treated
Standard Staging Investigations: CXR + lymphography + Splenectomy
Standard treatment: Mantle field radiotherapy
Standard outcome: not very good 7

8. Evolution of clinical PET imaging
Sharma B, Martin A, Stanway S, Johnston SR, Constantinidou A. Imaging in Oncology- over a century of advances. Nat Rev Clin Oncol. 2012; 9(12):

9. Staging Accuracy PET > CT per lesion
PET and CT discordant up to ^ 30% patients
Stage migration up to ^ 30% patients
Treatment change up to circa 15% patients
No evidence improvement patient outcome

11. Presented in June 2004 with back and groin pain
Presented in June 2004 with back and groin pain. MRI from December 2004 and February 2005 demonstrated disease in the vertebral body between T2 and T4. A PET scan confirmed uptake in these areas as well as the 4th rib. Core biopsy from T3 confirmed follicular lymphoma final staging 1AE. He received a total of 30Gy in 20# from T1 to T5 completed in July An MRI scan performed at Barnet Hospital in November 2005 was reported to have shown a new lesion at L4 of 1.5cm in size. A subsequent PET scan showed no activity in the lumbar spine but low grade uptake in the right 4th rib at the lower end of the sternum and in the lower thoracic vertebra which was felt to constitute evidence of disease relapse. He was seen in September 2007 with a 2 month history of increasing cervical and lumbar pain which was poorly controlled. 
Radiology Review:
An MRI scan shows suspicious lesions at T4 toT6 but these are likely to represent radiotherapy change. PET scan performed 1st November - FDG uptake in the left transverse process of T4 and the left pedicle of T7. There is also abnormal uptake in the right 4th rib.  11

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15. FEBRUARY 2008 15

16. Deauville criteria No uptake Uptake < mediastinum
Uptake > mediastinum but < liver
Uptake moderately higher than liver
Uptake markedly higher than liver and / or new lesions
New areas of uptake unlikely to be related to lymphoma
Interim and end of treatment
Good inter observer agreement reported in HL, DLBCL, FL
Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on interim PET scan in lymphoma. Leuk Lymphoma. 2009; 50(8):

17. PET ‘post therapy assessment’
Terasawa T, Nihashi T, Hotta T, et al. 18F-FDG PET for posttherapy assessment of Hodgkin’s disease and aggressive non-Hodgkin’s lymphoma: a systematic review. J Nucl Med. 2008;49(1):13-21
Advanced stage Hodgkin’s disease, HD15 trial
The negative predictive value for PET at 12 months was 94.1% (95% CI ); and 225 (11%) of 2126 patients received additional radiotherapy.
Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379(9828):
EORTC H10 trial
Raemaekers JM, André MP, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014; 32(12):
RAPID trial
Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med. 2015; 372(17):
Estimated dependence of lifetime radiation induced risk of cancer on age at exposure
Brenner DJ, Hall EJ. Computed Tomography – an increasing source of radiation exposure. N Engl J Med. 2007; 357(22):

24. Diagnostic improvements
Clear national/international guidelines
Haemato-oncology specialist radiologists
Network (regional) MDTs
National (mandatory) training program
E-learning (haematology/NIHR) national program
Template approach
Education/training (e-journal approach)

25. Staging – The future 25

26. NATURE REVIEWS | CLINICAL ONCOLOGY
Imaging in oncology—over a century of advances
Bhuey Sharma, Axel Martin, Susannah Stanway, Stephen R. D. Johnston and Anastasia Constantinidou
Abstract | Over the past 120 years, the discipline of oncology has evolved so that a multitude of anatomical and increasingly complex functional imaging techniques are now applicable in both clinical and research platforms. This Timeline article revisits the achievements of the pioneer techniques in cancer imaging, discusses how these techniques have changed over time, provides some examples of clinical importance, and ventures to explain how imaging will remodel the future of modern oncology.
Sharma, B. et al. Nat. Rev. Clin. Oncol. advance online publication 13 November 2012; doi: /nrclinonc

27. Conclusions Lymphoma tremendous development over 50 years
Complex imaging landscape across clinical and research platforms
Persistent challenge assessment ‘as close as possible to the truth’
Understanding imaging science to provide ‘appropriate’ and ‘optimal’ patient care
Appropriate and efficient use of health care tests, resources
Future multiparametric anatomolecular / functional imaging; more-accurate diagnosis, detection of minimal disease, prognostication, early response evaluation and treatment guidance
More questions than answers