CT or CT/PET Surveillance in Asymptomatic Adult and Pediatric Patients Following Curative Intent Therapy for Hodgkin Lymphoma and Aggressive Non-Hodgkin Lymphoma: A Systematic Review

Background:

Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) both have relatively high curative-potential with contemporary treatment strategies. Despite this, a substantial number of patients will relapse, and a principal objective of follow-up is to identify recurrent disease. The optimal method for detection of relapsed disease has been debated extensively in the literature. Previous guidelines recommended routine surveillance imaging (SI) as a means to detect relapsed disease; however, recent recommendations have de-emphasized routine SI. Nonetheless, controversy remains and approaches vary dramatically across different regions. Aim:We completed a comprehensive systematic review to evaluate whether routine surveillance with computed tomography (CT) and/or positron emission tomography (PET) for patients in complete remission following curative intent therapy for HL and/or aggressive NHL identifies more relapses than clinical vigilance strategies, and if it improves progression free (PFS) and/or overall survival (OS).

Methods:

We searched Medline, [1946 to Oct 18, 2015] andEMBASE [1980 to Oct 18, 2015] for English-language studies assessing one or more surveillance strategies in adult and/or pediatric patients in remission from HL and/or aggressive NHL. Reviews, conference abstracts, case reports, letters, comments, books, and editorials were excluded.

Results:

Our search identified 8719 potentially relevant titles for review. Two authors reviewed all titles and abstracts. A total of 120 papers were selected for full text review; of these, thirty-two papers (30 adult, 2 pediatric) were included and four were unavailable for full text review. Twenty-seven retrospective studies, four prospective cohort studies, and one randomized control trial were included. A majority of adult studies (29/30) reported on surveillance strategies in NHL/HL survivors (16/16 NHL, 11/12 HL, 2/2 evaluating both NHL and HL) as well as all pediatric studies (1/1 NHL, 1/1 HL). Almost all studies (15/16 adult NHL, 11/12 adult HL, 2/2 pediatric) reported patient-level data on the number of asymptomatic relapses identified through SI versus clinical signs or symptoms. There were a total of 797 documented relapses in the adult NHL studies and 523 relapses in the adult HL studies. Of the relapsed adult NHL patients, 78.2% (623/797) were diagnosed clinically and 19.6% (156/797) were diagnosed by SI. Among the adult HL patients, 63.1% (330/523) of relapses were diagnosed clinically and 36.5% (191/523) were diagnosed by SI. Of the two pediatric studies included, one NHL study showed that all 3 relapses were detected clinically, and one HL study showed 76.0% (19/25) of relapses were detected clinically or due to lab abnormalities, and 24.0% (6/25) were detected by SI.

Fifteen adult studies reported comparative data on PFS and/or OS rates with SI versus clinical surveillance strategies (9 NHL studies, 4 HL studies, 2 NHL/HL studies). The majority of studies (12/15) documented no difference in PFS and/or OS with imaging versus clinical surveillance strategies (8/9 NHL, 3/4 HL, 1/2 NHL/HL). In the remaining three studies, the first demonstrated a significant reduction in risk of death (HR 0.47 for HL, 0.57 for DLBCL) with SI on univariate analysis, but this was not seen on multivariate analysis for DLBCL (data not analyzed for HL). A second study in NHL patients demonstrated a non-significant trend towards improved PFS (p = 0.12) and OS (p = 0.13) with SI, while the third suggested that asymptomatic individuals with HL do not benefit from SI, with the exception of those with a morphological residual mass (p < 0.00016, HR = 3.84) or advanced stage (p = 0.03644, HR 1.99).

Conclusions:

The preliminary analysis of this systematic review indicates that even when routine imaging surveillance is employed, a majority of NHL and HL relapses come to attention due to the development of clinical signs and/or symptoms. A small number of comparative studies have reported on PFS and/or OS, with the vast majority demonstrating no improvement in PFS or OS with routine imaging surveillance. Our study supports clinical vigilance as the predominant strategy for follow-up in asymptomatic patients following curative intent therapy for HL and aggressive NHL.