PET/CT in Lymphoma Dr. Felix Sundram Nuclear Medicine Physician - PowerPoint PPT Presentation

PET/CT in Lymphoma Dr. Felix Sundram Nuclear Medicine Physician Wijaya International Medical Centre Sime Darby Medical Centre Honorary Lecturer, University Sains Malaysia

Staging of Lymphoma  Ann-Arbor Classification  WHO Classification  Clinical staging  Decides treatment plan  Factors taken into account include  Ann-Arbor Staging  B-symptoms  Age  Extranodal disease  Bulky disease  Categorized as limited, intermediate & advanced

Gallium-67 citrate  CT/MRI unable to differentiate residual disease from fibrosis  Gallium -67 has low specificity, and low sensitivity for infradiaphragmatic disease  Limitations in low-grade NHL  ? Does patient have a gallium - avid lymphoma  Logistics of supply from overseas

Non- Hodgkin’s lymphoma of thyroid in a patient with Chronic Thyroiditis and with a solitary nodule in the left lobe. Normal uptake in the nodule Uptake only in the nodule 201 Tl Scan 67 Ga Scan

Role of PET/CT in Lymphoma  Anatomic imaging such as CT assesses size of tumor mass  PET/CT uses metabolic imaging to give a more reliable indication of tumour burden  Considerable evidence to support the use of FDG PET/CT in Lymphomas (PFS, OS)

Therapy Response Assessment  Biochemical response  Histopathological response  Morphological response (CT,MRI,US) RECIST: Response Evaluation Criteria in Solid Tumours PERCIST: PET Response Criteria in Solid Tumours

PET Response Assessment in Lymphomas  Residual masses at end of therapy are frequent (70% HD; 50% NHL) but only a minority of patients relapse (<20% HD; 25% NHL )  Patients in apparent complete remission also relapse  Early treatment of residual disease may improve survival.

Revised Response Criteria for Malignant Lymphoma  J Clin Oncol 2007; 25: 579-586

 Cheson et al. JCO 2007 Any IWC but PET – ve and BMB – ve  CR except IWC p.d. lesion <1.5cm  PR IWC PR/CR, PET +ve in >1 previously involved sites  SD IWC SD but PET +ve in previously involved sites  PD IWC PD but PET +ve in previously involved sites IWC PD for new lesion <1.5cm

RECIST 1.1 (January 2009 Update)  Measurable lesion  > 15mm short axis diameter on CT for lymph- nodes.  Target lesion  Overall 5 target lesions (not > 2 organs) are to be considered.  Additional PET (FDG) scan interpretation

PERCIST  PET assessment of response to therapy using FDG has a substantial biological relevance and biological predictive value of PET seems higher than anatomic modalities.

PET/CT in Lymphoma  Staging PET (prognosis/decide treatment)  Interim PET (prognosis/change treatment)  End of treatment PET (prognosis/further more aggressive treatment)  Recurrence PET (distinguish the changes from new disease)

Staging  FDG( F-18 Fluorodeoxyglucose) PET is accurate in HL and high-grade/aggressive NHL  Frequently identifies sites/nodes missed by CT  Upstaging and downstaging  Advanced indolent Lymphoma: rarely positive uptake

NHL Bone Marrow Involvement  FDG PET does not reliably demonstrate bone-marrow involvement – especially in low grade lymphoma such as MCL  False positive uptake in HL  Bone-marrow trephine If clinically indicated

NHL – Cutaneous T-cell Lymphoma  Not all lymphoma types are PET positive  Use to assess response but pre-treatment PET required

Prognosis at Diagnosis  Stage  Prognostic scores ( Int’l prognostic index , WHO etc.in HL/NHL)  Tumour response to treatment (PET/CT)

Response Assessment in Interim PET  In aggressive NHL post 2-3 cycles  PET +ve :10-50% PFS at 1 year  PET – ve : 75-100% PFS at 1 year  In HL post 2-3 cycles  PET +ve : 39% PFS at 5 years  PET – ve :: 92% PFS at 5 years Hutchings Ann Oncol 2005

 Early PET response – adapted therapy  Can therapy be changed based on the interim PET/CT scan  Trials currently in progress  PET positive disease – increase therapy?  PET negative disease – decrease therapy?

End of Treatment Response  Tumour size reduction – main criterion previously  End of treatment PET highly predictive of PFS & OS in aggressive NHL  Less clear for indolent NHL

Activity in Residual Mass  HL: high NPV, Less high PPV as false positives may occur due to inflammation.  NHL: high PPV, less high NPV as negative result post-treatment cannot exclude minimal residual disease and late relapses with a negative PET are possible.

End of Treatment Response and Follow-up  Negative PET post treatment cannot exclude microscopic disease  Studies show that routine follow-up of patients with PET/CT offers no advantage over CT

Recurrence  Main advantage of PET/CT over CT is the ability to distinguish residual fibrosis or inactive tumour mass from active disease  Guide excision biopsy if multiple residual lymph-nodes

Antologous Stem Cell Transplantation (ASCT)  FDG PET/CT can predict outcome following ASCT  PET performed after salvage chemotherapy and before high-dose chemotherapy and SCT in 60 patients  25/30 patients with a negative PET study prior to SCT remained in remission post SCT (median follow-up – 1510 days)  26/30 patients with abnormal PET study developed disease progression Spaepen K et. al. Blood 2003; 102: 53-59

Other PET Tracers 18 F-FLT (Fluorothymidine) – high sensitivity  in NHL and potential role in response assessment? 11 C-thymidine – staging and response  assessment? Most work and staging research is still with FDG

Conclusion  PET/CT has a proven role in staging, and assessment of response of most lymphoma types  PET/CT has prognostic significance (staging, interim and end of treatment)