Tissue Is the Issue: Accuracy of PET Imaging to Detect Bone Marrow Clearance in Patients with Peripheral T-Cell Lymphoma

INTRODUCTION: 

Adult mature T- and NK-cell neoplasms are a heterogeneous group of aggressive lymphomas comprising approximately 10% to 20% of all non-Hodgkin lymphomas (NHL) with an estimated 5-year overall survival of 40%.  Staging and treatment strategies are guided by malignant involvement on PET/CT scan and bone marrow (BM) biopsy.  The Lugano Criteria, established in 2014, suggested that focal FDG uptake within the bone marrow was highly sensitive for both Hodgkin (HL) and diffuse large B-cell lymphoma (DLBCL) potentially obviating the need for a bone marrow biopsy if no lesions were seen.  Limited data exist regarding the sensitivity of PET for BM involvement in T-cell lymphoma.  This study compares PET/CT scans and repeat BM biopsy in patients who have undergone treatment for peripheral T-cell lymphomas (PTCL) by evaluating BM avidity on PET scans.

METHODS:

This is a single institution study using the Mayo Clinic Lymphoma Database between January 1, 2001 and January 1, 2015.  We retrospectively identified all patients with a diagnosis of PTCL, biopsy proven BM involvement at diagnosis, and a concomitant PET for staging.  Patients were then reviewed to assess completion of induction therapy and availability of both PET/CT and bone marrow results post-therapy. Evaluation for concordance and discordant BM involvement were then determined using BM biopsy as the gold standard. 

RESULTS:

Sixteen patients had both PET/CT and BM biopsy after completing induction therapy.  Median age at diagnosis was 63 years (range 34-72) and 69% were male.  PTCL subtype was peripheral T-cell lymphoma, not otherwise specified in seven patients; ALK negative anaplastic large cell lymphoma in one patient; and angioimmunoblastic in 8 patients.  Pre-treatment PET/CT scans demonstrated eight patients (50%) with false negative scans.  Post-treatment biopsy results demonstrated that ten (62.5%) had biopsy proven residual bone marrow involvement after induction.  Eight patients (50%) were found to have BM biopsy proven disease with a negative PET scan.  Two patients (12.5%) had both positive BM biopsy and PET scans; 5 patients (31.3%) had negative BM biopsies and PET scans.  One patient (6.25%) had a negative BM biopsy, but had a PET scan that revealed positive disease.  This patient was considered to have had a false positive PET scan and indeed has remained in remission since April 2009 without any further relapse or treatment.  Sensitivity of PET for BM involvement was very poor at 20% (2/10) with a specificity of 50% (2/4) (Table 1 and 2).

CONCLUSIONS: 

This study in PTCL indicates that PET scans at the completion of therapy have a 50% false negative rate.  These patients should not be assumed to have negative bone marrow involvement based solely on PET/CT scans.  A bone marrow biopsy at the end of therapy is necessary in PTCL patients to confirm complete response.

Table 1

Bone Marrow Involvement	Pre-Therapy PET Scan Imaging
		PET Negative	PET Positive	Total Patients
	Bone Marrow Negative	NA	NA	NA
	Bone Marrow Positive	8	8	16
	Total Patients	8 (50%)	8 (50%)	16

Abbreviations: NA, not applicable. The study defined that all patients had to have a positive bone marrow at baseline to be eligible for the study.

Table 2

Bone Marrow Involvement
		PET Negative	PET Positive	Total Patients
	Bone Marrow Negative	4	2	6 (37.5%)
	Bone Marrow Positive	8	2	10 (62.5%)
	Total Patients	12 (75%)	4 (25%)	16

Table 1 and 2:  Involvement of bone marrow with peripheral T-cell lymphoma based on evaluation by PET scans versus bone marrow biopsy.