The use of PETCT in Hodgkin’s lymphoma

Background Lymphoma is a haematological malignancy that affects both old and young. It is the most common indication for PETCT in the young adult. Lymphoma is the fifth commonest malignancy in the UK after breast, lung, colorectal and prostate cancer, accounting for 11,861 cancer cases in 2008 (4%). The current conventional treatments provide good cure rates, with overall 10-year survival rates of 51%. The use of PETCT helps with staging, monitoring and tailoring of therapies, in part to avoid the long-term morbidity and mortality associated with treatment of the young. Lymphoma is subdivided into Hodgkin’s (20% of all lymphomas) and non-Hodgkin’s (80% of all lymphomas). Hodgkin’s disease is characterised by the presence of Reed Sternberg cells and is a relatively aggressive malignancy that affects a younger population than the NHL group. It has a bimodal distribution presenting commonly between the ages of 15 and 35, with a second peak in the over 50s. The non-Hodgkin’s group is a heterogeneous set of conditions that are grouped together. The average age of diagnosis is 65. There are many sub-types of non-Hodgkin’s lymphoma, but they can all be put into one of two broad categories, high grade and low grade. This can be problematic in predicting response to treatment and interpreting imaging findings on PETCT, as the subtypes have a wide spectrum of natural histories reacting differently to treatments. This makes the use of PETCT in NHL more controversial and difficult to have confidence in its findings. In general, lymphoma does not obey the same rules as other malignancies discussed elsewhere. It often has a large inflammatory soft tissue component that is not part of the active disease. The active disease can be confined to a small number of cells that phosphorylate and accumulate FDG. This produces imaging problems as active disease and quiescent disease look morphologically similar and monitoring response to treatment is not as clear cut as in malignancies that produce high SUV values. Thus, interpreting these PETCT scans becomes difficult and poorly reproducible limiting, among other things, further standardised research. With this in mind, a European congress met to decide on a method that was reproducible and reliable in assessing response and progression of the disease. The semi-quantitative method they decided upon was the Deauville criteria (table 1). These have shown good inter-observer concordance in HL. As standardised uptake values (SUVs) are calculated for each individual based on injected activity, weight, height, etc, they are prone to variation. To combat this, reference points are used; these are the background uptake in the mediastinum and liver. This reduces some of the variation between patients and is more reproducible. These criteria will not exclude microscopic disease, so there will be a small number of false negatives, but the aim is to prevent a larger number of false positives. As you will read, this high negative predictive value (NPV) and poor positive predictive value (PPV) is the main limiting factor in the use of FDG PETCT. The consequences of treatment can produce significant morbidity and mortality. The patient group is generally younger so the identification of early disease is important as it is eminently treatable with conventional therapies. Overtreating will lead to a cure but produce delayed morbidity and mortality from cardiac damage and radiation-induced cancers. So, it is important to differentiate early on those with more benign disease who could be cured with less aggressive therapy and those whose only chance is the aggressive therapies. Having a test with high false positives (or a poor PPV) exposes a group of cured patients to unnecessary and potentially damaging treatments. A systematic review looking at post-treatment assessment gave PETCT a pooled negative predictive value of 96% (84-100%) and a positive predictive value of 77% (60-100%). FDG PETCT has proved to be a highly sensitive and specific tool and is a mainstay of current imaging. Several studies have shown that progression-free survival (PFS) when using CT alone can vary little from those with positive or negative post-therapy CT scans. FDG PETCT has a high sensitivity for nodal staging, performing particularly well in accurately identifying mediastinal nodes, peripheral nodes and extra nodal disease often overlooked in conventional imaging. Pre-treatment staging Pre-treatment staging with PET/CT has shown an upstaging of 10-25% when compared to conventional imaging. This can be due to the superior identification of involved nodes and the detection of extra nodal disease such as splenic metastases or marrow involvement. These pre-treatment scans also provide a baseline from which to assess response of the treatments. This allows the de-escalation of more toxic therapies. Monitoring The timing of the scan during therapy is still debatable. There are many papers and trials in progress looking for the optimum time to rescan. The ideal timing would be after an interval that would identify a definite response, allowing one to alter treatments with confidence, but not so delayed that 1. No uptake