18 FDGPET positivity post radiotherapy is a biomarker

18 FDG-PET positivity post radiotherapy is a biomarker for relapse in patients with plasmacytoma DR. FAYE SHARPLEY UKMF&AMGEN TRAVEL BURSARY WINNER 2017

First, a bit of background…. .

Why Myeloma…. . ?

And so to Oxford… Dr. Ramasamy had a cohort of 24 patients with solitary plasmacytoma

Rather than chemotherapy, radiotherapy or surgical resection forms the mainstay of treatment, with curative intent. A precise diagnosis is therefore essential to differentiate these focal lesions from systemic Myeloma…. .

Stratification – Higher Risk of progression to myeloma • BM involvement, by morphology and aberrant phenotype by Flow cytometry ( 72% vs 12. 5% at 3. 7 years fu)1 • Abnormal s. FLC ratio ( 44% vs 26% at 5 years)2 • Size (>5 cm) of plasmacytoma 3, 6 • Persistence of paraprotein following radiotherapy 4 • PET positive lesions 2, 5 • Age > 60 years 6 1. Hill QA, et al. . Blood 2014; 124: 1296– 99 24. 2. Warsame R, et al. Am J Hematol 2012; 87: 647– 51. 3. Tsang et al. Int J Radiat Oncol Biol Phys 2001; 50: 113 -20. 4. Wilder RB et al Cancer 2002; 94: 1532 -7. 5. Fouquet G et al Clin Cancer Res 2014 Jun 15; 20(12): 3254 -60 6. Knobel D BMC Cancer 2006; 6: 118

Morie A. Gertz, Philip R. Greipp

Historically, we have relied upon the skeletal survey to image patients at diagnosis Concern that this may miss other plasmacytomas/ multiple myeloma was how this project started out Now widely acknowledged that MRI or PET-CT required rather than skeletal survey

Unanswered questions… 1) Which imaging modality should be used for Plasmacytoma patients? 2) What proportion of patients are upgraded to multiple Plasmacytoma when PET-CT is used, and did this lead to a change in their treatment pathway? 3) Can FDG PET scans assess risk of progression to myeloma?

24 patients, all with a histological diagnosis of plasmacytoma referred over a three year period. We recorded patient baseline characteristics, size and location of their plasamcytoma, imaging findings, light chain and BM results.

Comparison of imaging findings All patients were imaged by either conventional skeletal survey, PET-CT, or by both imaging techniques. A single radiologist retrospectively reviewed all images and reported the number and size of plasmacytomas seen on both imaging modalities.

9/24 patients (38%) were imaged with both skeletal survey and 18 F PET-CT, 18 F PET-CT detected additional lesions in 55. 6% (5/9 patients). In all 5 of these patients the management plan was changed, allowing systemic chemotherapy to be started

How do our survival stats compare? The median follow-up was 37. 3 months. There were two deaths in this time, median OS was not reached at 3 years. Median PFS was 36. 7 months.

How did PET-CT help? 50% (12/24) patients with plasmacytoma progressed to multiple plasmacytoma/ Multiple Myeloma. In 66. 7% of these cases, (8/12 patients) repeat imaging with PET-CT was positive. Biochemical evidence of relapse was present in only 50% of cases.

We decided to combine with Brazilian cohort This retrospective analysis looked at 66 SP patients (23 UK, 43 Brazil) over a 15 year period. Baseline patient and disease characteristics were recorded including: serum free light chains (SFLC), bone marrow (BM) examination, imaging by skeletal survey, CT/MRI and functional imaging by 18 F-FDG PET-CT (FDG PET-CT) or 99 m. Tc-Sestamibi scintigraphy +/- SPECT-CT (MIBI). The proportion of patients progressing to MP/MM was calculated and the effect of surgery and radiotherapy (RT) on disease recurrence/progression was analysed. Progression free survival (PFS) and overall survival (OS) from diagnosis and time of repeat functional imaging were measured using Kaplan-Meier analyses 17

Risk of progression Fig. 1: Cumulative Incidence of MM by SP type: SBP and EMD Fig. 3: How radiotherapy dose (radical >40 Gy, or palliative <40 Gy) affects PFS Fig. 2: The effect of Plasmacytoma Type on PFS: SBP vs EMD

PFS and OS: Median follow-up 53. 6 months, median OS 10. 4 years, median OS not reached at 3 years in UK, Brazilian 11 yrs. Median PFS 5 years (42 M UK, 67 M Brazil) with 48% (32/66) progressing to MM/MP in this time. 20

Surveillance Functional Imaging • • 21 All patients in the UK cohort had PET-CT (n=23) and, the Brazilian cohort was imaged by MIBI (n=12). FU imaging was performed in 62. 1% cases at a median of 174 days ~ 6 months post diagnosis. 16 patients (39%) were scanned on the suspicion of relapse, 9/16 (56. 2%) showed progressive disease. 20 patients (48. 7%) were scanned as routine surveillance, one patient (5%) showed disease progression. PET SUVmax value was not found to be useful in predicting outcome. The positive predictive value of first FU imaging to determine clinical outcome was high regardless of whether the scan was for routine surveillance or suspected progression. Negative predictive value was low (60%, 95%CI: 40. 6%-77. 3%) and particularly poor (14. 3%, 95%CI: 0. 4 -58%) in cases of suspected relapse, suggesting a more diffuse infiltration in marrow

Conclusions and future direction. . SBP has a higher risk for progression to MM as previously reported Use of radiotherapy dose < 40 Gy is associated with higher risk of progression ( although not UK clinical practice) FDG-PET is superior to conventional imaging in the diagnosis of suspected solitary plasmacytoma Surveillance Functional imaging is a biomarker for disease progression Further work is required to validate functional follow up imaging and SUV indices and whether this can be reliably used to quantify risk of progression.