A baseline PET-CT scan (PET) is a more sensitive staging modality than standard contrast enhanced CT scanning in lymphoma patients, obviating the need for bone marrow biopsy in patients with Hodgkin’s lymphoma (HL) and most with diffuse large B-cell lymphoma (DLBCL). It can also be used at the end of induction after first line therapy to predict outcome to therapy.

Speaking at the H3 conference held in Sydney at the weekend Professor Judith Trotman, Director of the Clinical Research Unit in Haematology at Concord Hospital, said: “It’s clear cut that bone marrow biopsy is no longer required for staging patients with Hodgkin’s lymphoma although I’m not entirely confident that has penetrated clinical practice 100 percent.”

“PET may also obviate the need for biopsy in DLBCL unless you feel that discordant histology might be considered important for management,” she added.

“The most important role for a baseline PET scan is actually for its comparison with subsequent responses, along with the more accurate staging given that significant upstaging that occurs for low grade lymphomas, with greater detection of extra-nodal disease” Professor Trotman told the conference.

In the absence of any data demonstrating a clear association of SUVmax with either progression free survival or risk of histologic transformation Professor Trotman advises against repeating biopsies of more FDG avid lesions in patients with follicular lymphoma.

“There has been no correlation between high SUVmax and inferior outcome in a number of prospective trials now,” she said.

She told the audience that given the poor correlation between SUVmax and histologic grade, caution is advised on using pre-treatment SUV as an indicator of possible histologic transformation.

Full contrast enhanced CT should be reserved for the measurement of nodal size for trials, radiation planning and distinguishing bowel from nodes or assessing compression thrombosis of central/mediastinal vessels if required at staging, she said.

Indeed, a prospective study by Emmanuel Itti¹ and colleagues involving 237 PET-CT scans followed by a contrast enhanced CT (CECT) performed 1 hour later showed that full dose CT had no clinical impact in 92% of patients and had a positive impact in 3% because it diagnosed DVT in 5 patients and upstaged 2 patients.

“But we all know in practice that many patients have a separate contrast enhanced CT scan before PET-CT and I suggest than one way of reducing this is to allow GPs to refer patients for PET scan once the diagnosis of lymphoma has been confirmed…then we might see a slight reduction in the use of CT scans as well,” Professor Trotman said.

Professor Trotman was instrumental in Australia becoming one of the first countries in the world to publicly fund PET scanning in patients with indolent lymphoma.

This means MBS reimbursement is now available for staging of untreated non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL), assessment of response to first-line therapy in NHL and HL (during or within 3 months after treatment), restaging of suspected occurrence and assessment of response to 2L chemo when stem cell transplant is being considered.

When to scan

According to the Lugano classification² and the Malignant Lymphomas Imaging Working Group³ patients should have a PET-CT scan as long as possible after their last chemotherapy treatment before their interim scan.

“If you’re going to do a PET scan on someone with HL on Adriamycin, bleomycin, vinblastine and darcabazine (ABVD). Ideally, you’ll try and get the scan on day 26 so that you can see them on day 27/28 in order to make a decision about their therapeutic management going forward,” Professor Trotman told delegates.

Likewise, at the end of treatment you should ideally wait 6-8 weeks post chemotherapy to get your end of treatment PET scan and more than three months after radiotherapy, she noted.

The five-point scale, the Deauville criteria⁴, continue to be the basis on which interim and end of treatment scans are assessed: a score of 1 or 2 is a complete metabolic response (CMR). A score of 3 is also a CMR with standard treatment but in response adapted trials exploring de-escalation a score of 3 may be deemed inadequate, Professor Trotman noted.

A score of 4 or 5 with lower uptake from baseline is considered a partial metabolic response (PMR), which at an interim scan can indicate responding disease but at the end of treatment can suggest residual disease.

The same score with no change in uptake from baseline means no metabolic response (NMR), and a 4- or 5 score with an increase in uptake from baseline and new lesions is progressive metabolic disease. An interim and end of treatment NMR and PMD indicates treatment failure.

Take home messages from Professor Trotman’s talk:

• PET-CT should be used to stage FDG-avid lymphomas
• Patients with Hodgkin’s lymphoma and many with diffuse large B-cell lymphoma (DBCL) can be spared bone marrow biopsy
• PET-CT is recommended for mid-treatment assessment in place of CT if imaging is clinically indicated with assessment, and ideally reviewed in the multidisciplinary setting. In addition to the 5PS, consider ∆ SUV in DLBCL patients presenting with high SUV max
• The Deauville five-point scale is an internationally recommended scale for clinical routine and clinical trials using FDG-PET/CT in the initial staging and assessment of treatment response where:

1. no uptake
2. uptake ≤ mediastinum
3. uptake > mediastinum but ≤ liver
4. moderately increased uptake compared to liver
5. markedly increased uptake compared to liver/and/or new lesions

References

1. Itti, E. et al. Leukemia & Lymphoma 2014; doi: https://doi.org/10.3109/10428194.2014.900761
2. Cheson BD et al. J Clin Oncology 2014; 32 (27) 3059-68.
3. Barrington SF et al. J Clin Oncology 2014; 32:(27):3048-58;
4. Deauville 5-point score (5-PS)