Utility of Interim and Post-Therapy PET/CT in T-Cell and NK-Cell Lymphoma: A Single Institutional Analysis over 9 Years

Introduction: Positron emission tomography combined with computed tomography (PET-CT) is functional imaging test and has been widely used in malignant lymphoma (ML) for initial staging and monitoring response to treatment. Interim PET-CT (iPET) and post-therapy PET-CT (ePET) is also used to assess the early response and guide subsequent treatment, although its role is still controversial other than in Hodgkin's disease and diffuse large B cell lymphoma. Peripheral T cell lymphoma (PTCL) and natural killer (NK) cell lymphomas are relatively rare and heterogeneous types of ML. The prognosis of T and NK (T/NK) cell lymphoma is poor and no standard treatment is available. Therefore, there is a need to find better prognostic factors or tools for these patients. PET-CT is both sensitive and specific for initial staging of T/NK cell lymphoma, although there have been few studies using i- and ePET in these lymphomas. We investigated the prognostic value of i- and ePET in T/NK cell lymphoma in a retrospective single-center study.

Methods: Between June 2006 and June 2015, 79 patients with T/NK cell lymphomas had iPET after 2 to 4 courses of treatment and at the end of treatment at Kameda Medical Center, Japan. iPET was performed just before the next cycle of treatment. Treatment responses were scored according to the Deauville score using a 5-point scale (DS). We defined DS scores 1 – 3 as complete metabolic response (CMR). Standardized uptake value (SUV) measurement was normalized relative to the injected dose and lean body mass. The SUV was measured for all lesions and the highest value for each scan was recorded as maximum SUV (SUVmax). These lesions were identified as indicator lesions. For mid- and end-treatment scans, we recorded the change in SUVmax (DSUV), comparing the index lesion and the highest SUVmax in the scan regardless of the index lesion. Differences in overall survival (OS) and progression-free survival (PFS) were calculated by two-sided log-rank test. PET-CT status was assessed for its ability to predict PFS and OS.

Results: The study population consisted of 48 men and 31 women with a median age of 70 years. The most frequent lymphoma diagnoses were peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) (n = 29), angioimmunoblastic T cell lymphoma (AITL) (n = 21), anaplastic large cell lymphoma (ALCL) (n = 6), adult T cell leukemia/lymphoma (ATLL) (n = 12), enteropathy-associated T cell lymphoma (EATL) (n = 2), and NK/T cell lymphoma (NKTCL) (n = 9). Most patients except for ATLL and NK cell lymphoma were instituted with the CHOP-like regimen. Baseline PET scan was positive in all cases and median SUVmax was 13.7 (range, 2.6 – 37.4).  iPET results were negative in 17 cases (26%), and ePET results were negative in 22 of 46 (48%) cases. With a median follow up of 30 months, 5-year PFS rate was 66% for obtaining CMR vs. 9.2% for not obtaining CMR (P < 0.001). The percentages of patients that obtained CMR were 48% (14/29), 62% (13/21), 67% (4/6), 33% (3/9), 50% (1/2), and 56% (5/9) for those with PTCL-NOS, AITL, ALCL, ATLL, EATL, and NKTCL, respectively. The patients who obtained CMR showed significantly longer PFS and OS compared to those who did not. We also analyzed DSUVmax. Using the ROC curve, DSUVmax values between baseline and iPET of > 62% and > 85% were predictive of better PFS and OS (sensitivity 96%, specificity 67%, area under the curve (AUC) 0.89, 95% confidence interval (CI) = 0.82 – 0.97 and sensitivity 49%, specificity 97%, AUC 0.80, 95% CI = 0.70 – 0.90, respectively). We examined the positive and negative predictive values (PPV and NPV) and accuracy in predicting PFS and OS in 66 patients who underwent iPET. Of 35 iPET-positive patients, 31 (89%) showed progression, and 26 (74%) died during the follow-up. On multivariate Cox regression analysis, obtaining CMR at iPET emerged as an independent prognostic factor for PFS and OS (P<0.001 and P<0.001, respectively).

Conclusions: Our data suggest that patients with positive results on i- or ePET should be considered candidates for intensive therapeutic strategies to improve their clinical outcome. Large prospective studies of patients with tumors of a homogeneous histological subtype within the T/NK cell lymphoma, treated with a uniform protocol, and evaluated on the basis of standardized criteria are warranted.