Predictive Value Of Interim PET Research Articles

The Role of Interim PET/CT on Survival in Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma is the most frequent aggressive non-Hodgkin lymphoma. Predicting response and estimating prognosis earlier makes management of this heterogeneous lymphoma more satisfying. Interim PET response is established in Hodgkin Lymphoma to tailor the therapy but results for non-Hodgkin Lymphoma is unconvincing. In the current study evaluation of interim PET and survival outcomes of 103 DLBCL patients is performed. About 103 Patients with DLBCL followed up in a single center between 2009 and 2019 were enrolled the study. All patients received R-CHOP chemoimmunotherapy at first line. Interim PET was performed after at least one or more cycles. All PET scans were performed with 18F-FDG isotope as PET/CT. PET scoring results were evaluated according to the 5-Point Deauville Scoring system defined in the National Comprehensive Cancer Network clinical guidelines for iPET and eotPET. 5-P DS of scores of 1 to 3 were defined as negative scans, and scores of 4 to 5 were considered to be positive scans. Forty-six (44.7%) Female and 57 (55.3%) male aged between 25 and 83 (median 57) years newly diagnosed DLBCL patients were enrolled in the study. Median PFS was 21 (interquartile range 8.5-53.7) months and median OS was 33.5 (interquartile range 12.5-62.9) months for the total cohort. Positive predictive value of interim PET according to Deauville scoring system was 65.4% and negative predictive value was 77.9%. Our study showed that according to Deauville 5 point scale (D 5PS) scoring system, interim PET-positive patients have shorter both PFS and OS than iPET-negative patients.

Correlation of 18-fluorodeoxyglucose PET/computed tomography parameters and clinical features to predict outcome for diffuse large B-cell lymphoma.

To determine if the correlation between different metabolic parameters along with clinical features can create an improved model of prognostication for diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively evaluated 89 patients with DLBCL. All patients had a baseline and an interim 18F-FDG PET/CT. Seventy-nine also had an end-of-treatment PET/CT (EOT-PET). For each scan, we collected standardized uptake value (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmaxsum, SUVmeansum, MTVsum, and TLGsum. These metabolic parameters were combined with clinical features in order to identify a new prognostic model. The predictive value of interim PET and EOT-PET using Deauville score was also determined. Baseline SUVmaxsum and SUVmeansum were significantly correlated to overall survival (OS) (P value = 0.012 and 0.011, respectively). The percentage change of MTV and TLG sum from baseline to EOT was predictive of progression-free survival (PFS) (P value = 0.003 and 0.022, respectively). The combination of either Deauville score at the EOT and SUVmaxsum at baseline significantly predicted OS (P value <0.001); Eastern Cooperative Oncology Group performance status, presence of extranodal disease and percentage change of MTVsum from baseline to EOT were significant predictors of PFS (P value = 0.001). SUVmaxsum and SUVmeansum at baseline and percentage change in MTV and TLG sum from baseline to EOT are predictors of outcome in DLBCL patients. These metabolic parameters combined to Deauville score and some clinical features could be used together to stratify patients.

Enhanced Outcome Prediction in Early Stage Classical Hodgkin Lymphoma Using Pre-Treatment Biomarkers and Interim PET (BioPET); A Sub-Analysis of the UK NCRI RAPID Trial

Enhanced Outcome Prediction in Early Stage Classical Hodgkin Lymphoma Using Pre-Treatment Biomarkers and Interim PET (BioPET); A Sub-Analysis of the UK NCRI RAPID Trial

SUV Max Reduction Criteria of Interim Positron Emission Tomography Improves Prognostic Value in Diffuse Large B-Cell Lymphoma: A Single-Center Retrospective Review

Background: A consensus is yet to be reached on therole of interim fluorine-18 fluorodeoxyglucose (18F-FDG) position emission tomography-computed tomography (PET-CT) for prognosis in diffuse large B-cell lymphoma (DLBCL), but it has been recently reported that maximum standardized uptake value (SUV max) reduction between baseline and midtherapy may be a better predictor of overall survival (OS) and event free survival (EFS).Patients and Method: 456 patients were newly diagnosed with DLBCL in our institute between February 2007 and January 2013. Primary central nervous system lymphoma or primary effusion lymphoma patients were excluded from this study. All patients who were not perfomed PET were also excluded. In order to determine the predictive value of interim PET-CT and SUV max reduction criteria on OS and EFS for patients with DLBCL, we retrospectively analyzed the PET-CT and SUV max data of 104 first-line DLBCL patients treated with 6 to 8 courses of R-CHOP or R-THPCOP therapy.PET-CT was performed at diagnosis (baseline), and after 2 to 4 courses (interim PET). Interim PET was scheduled two weeks after the second to fourth cycle of immunochemotherapy. A visual analysis of interim PET was done with the use of the Deauville criteria, and an analysis of the SUV max reduction criteria was calculated by [(SUV max reduction from baseline to interim PET)/SUV max at baseline]. For each PET image, the tumor with the most intense 18F-FDG uptake was identified among all foci with the use of a graded color scale. The hottest volumetric region was determined, and the SUV max was calculated. To assess the SUV max, the hottest tumor in any region or organ on interim PET was used for comparison, even if its location differed from the initial hottest tumor in baseline PET.Survival curves were estimated with Kaplan–Meier analysis and compared using the log-rank test.Results: One hundred and four patients were enrolled in this study, and their characteristics are detailed in Table 1. With a median follow-up of 38.5 months, the two-year overall survival and EFS were 83.3% and 73.6%. The results forinterim PET were 66.3% (69/104) negative and 33.7% (35/104) positive, respectively.Interim PET negative versus positive two-year OS was 85.0% (95%CI 0.739-0.917) versus 79.9% (95%CI 0.624-0.899) (P value 0.58), and the two-year EFS was 77.7% (95%CI 0.658-0.860) versus 65.7% (0.476-0.789) (P value 0.24), respectively (Figure 1).The SUV max cutoff values 66% estimated by receiver-operating-characteristic (ROC) analysis to distinguish treatment response were similar to other independent cohort studies at 2 to 4 cycles of induction treatment, and this threshold was chosen to analyze our series.For SUV max data, the two-year OS was 84.4% (95%CI 0.750-0.904) for a SUV max reduction ≥66.0% compared with 75.0% (95%CI 0.408-0.912) for a reduction of <66.0% (P value 0.02). The two-year EFS for the former was 75.7% (95%CI 0.654-0.833) compared with 58.3% (95%CI 0.270-0.801) for the latter (P value 0.03) (Figure 2). Baseline characteristics according to SUV max reduction criteria [SUV max≥66%(n=92),and SUV max<66%(n=12)] are summarized in Table 1.Conclusions: Analysis of the data in our study was unable to demonstrate the predictive value of interim PET for OS and EFS, but SUV max reduction criteria may improve the prognostic value of interim PET. However, the 66% cutoff value must be validated in a larger-scale prospective trial, and further investigation and the standardization of SUV max reduction criteria are needed. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

128IN - Pet-Based Decisions in Non Hodgkin'S Lymphoma

ABSTRACT Patients with NHL vary in response to current therapies. Early identification of the non-responders is of utmost importance in order to maximise their chances of a successful second-line therapy. In the search for a predictor of outcome to distinguish responders from non-responders, FDG-PET interim response assessment has been identified as a very promising tool. It provides an excellent basis for ‘personalized medicine’, whereby patients whose tumour is not responding may be shifted early during treatment from the ineffective to an another therapy. Even though the value of FDG-PET for post-treatment response assessment in DLBCL is well established nowadays, its value as a tool for interim response assessment is highly debated. In clinical practice PET scans are typically interpreted by visual methods. The well-established International Harmonization Project) criteria dichotomize PET results into positive and negative relative to the intensity of tracer uptake. These criteria have been designed to assess end-of-therapy response and should not be used to evaluate interim-PET scans. A new visual approach to PET scoring in lymphoma include a 5-point scale, the so-called Deauville criteria. At any observation time during induction chemotherapy, FDG uptake reflects a metabolic state which is a balance between tumour cell kill of chemosensitive components and re-growth of resistant components. When interim-PET is performed after one or two cycles, it evaluates the response of the cells with the highest mitotic index, thereby providing an early evaluation of chemosensitivity. In studies that have been conducted on the predictive value of interim PET, timing of interim PET varies considerably, both between and within studies, ranging from PET having been performed after 1 to 4 treatment cycles. To maximise therapy effectiveness and to minimise delays, toxicity and costs, early response assessment seems an attractive way to go. Interim-PET seems a promising tool but important issues as impact of timing, criteria, therapies on test performance need to be clarified. Randomized clinical trials with interim PET-CT based treatment modifications must ultimately demonstrate whether this strategy will improve patient outcome. Disclosure: The author has declared no conflicts of interest.

Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials?

AbstractDespite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria. A final remark on the appropriate use of interim PET is also provided.

Baseline Metabolic Tumor Volume Is Predictive of Patient Outcome in Diffuse Large B Cell Lymphoma

AbstractAbstract 1598Tumor bulk assessed by maximum tumor diameter was previously found to influence the outcome of young patients with low risk (aaIPI 0–1) DLBCL (Pfreundschuh et al Lancet Oncol, 2011; 12: 1013), but the prognostic impact of bulk and more generally tumor volume in high-risk DLBCL remains to be explored. Conversely, maximum SUV reduction calculated between baseline PET and PET performed after 4 cycles of immunochemotherapy (ΔSUVmax0–4) was recently shown to predict outcome in this population (Casasnovas et al Blood 2011; 118: 37).In this study, we assessed the metabolic tumor volume (MTV) and the tumor bulk at baseline in 121 patients <60 years with an aaIPI2–3 DLBCL enrolled in the LNH07-3B trial (NCT00498043). We then compared the prognosis value of both parameters to that of ΔSUVmax0–4.MTV was measured by FDG PET/CT with a semi automatic method using various volume shapes and systematic 41% SUVmax thresholding. Tumor mass with a maximum diameter > 10 cm assessed on CT scan was considered as bulky.Median follow-up was 28 months. Median baseline MTV was 303 cc (17–1488). Baseline MTV (≥625 cc vs <625cc, on the basis of a ROC analysis) significantly predicts 2-year progression free survival (2y-PFS) (57 % vs 83%; p=0.0032) and 2-year overall survival (2y-OS) (60% vs 90%; p=0.002). By contrast bulk >10 cm was not predictive of outcome.As previously published ΔSUVmax0–4 (> 70% vs ≤70%) found to predict 2y-PFS (88% vs 40%; p<10-4) and 2y-OS (94% vs 59%; p<10-4). Combining baseline MTV to early response assessed by ΔSUVmax0–4 allows to split the group of good responders patients defined on the basis of ΔSUVmax0–4 >70% after 4 cycles of immunochemotherapy (n=101, 88%) into 2 separated prognosis subsets (2y-PFS: 90% vs. 77%, p<10-4; 2y-OS: 96% vs. 77%, p<10-4). So far MTV could not significantly identify subgroups within the 15 patients with ΔSUVmax≤70% even if patients with higher MTV base line had lower PFS and OS.In our series baseline MTV was predictive of PFS and OS in high risk DLBCL patients while bulk was not. MTV identified different risk categories of DLBCL patients within DLBCL patients with a good interim response (ΔSUVmax0–4 >70%) and may improve the negative predictive value of interim PET. Disclosures:No relevant conflicts of interest to declare.

Interim 18-FDG-Positron Emission Tomography/Computed Tomography (PET) Failed to Predict Different Outcome in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Rituximab-CHOP.

Abstract 99Introduction. The PET scan has a definite role to assess the response at the end of treatment of DLBCL. The evaluation of response by PET after few courses of chemotherapy might be useful to predict chemosensitivity and possibly the outcome in this subset of patients. So far, the predictive value of interim PET in DLBCL pts is still contradictory. The visual analysis of PET results by dichotomous evaluation as positive or negative is often difficult to apply and standardized criteria of interpretation of interim PET have not been established yet. Moreover, published data are often based on retrospective studies, including miscellanea of subtypes and therapies. Our study was aimed to determine the predictive value of interim and final PET on PSF in DLBCL patients. Patients and Methods. From April 2004 to December 2008, 82 newly diagnosed DLBCL patients treated in 5 Hematology Department were included. Clinical features were as follows: median age 56 years (range 19-81); 42 males and 40 females, 29 patients stage I-II and 53 stage III-IV; according to IPI score 47 at low/low-intermediate risk and 35 at intermediate/intermediate-high. All patients were treated according to planned therapy, not modified by PET-2 results, with 6-8 R-CHOP. All patients had PET scan performed at the diagnosis, during treatment (PET-2) and at the end of therapy (PET-3). All PET results were defined as positive or negative by visual dichotomous consensus response criteria. Results. All patients were evaluable for response. PET-2 was performed after 2 R-CHOP in 46 pts, after 3 in 13 and after 4 in 23. At the end of therapy 73 pts (89%) achieved a CR and 9 (11%) were non responders. Fifty-five patients (67%) were negative and 27 (33%) positive at the PET-2 and 69 pts (84%) were negative and 13 (16%) positive at the PET-3. The concordance between clinical CR and PET-3 negativity was 99%: one CR pt was false PET-3 positive due to parothid carcinoma . Correlation between PET results and outcome was evaluated. There was correlation between PET-2 results and CR rate: CR 96% in PET-2 negative pts vs 74% in PET-2 positive (p .004). With a median FU of 18 months, PFS was 78%. PET-2 did not correlate with PFS (p .198): 46/55 (84%) PET-2 negative patients were in CCR and 20/27 (74%) PET-2 positive patients did not progres (Figure 1A). Conversely PET-3 strongly predicted PFS (p .015): 58/69 (84%) were in CCR and 8/13 (61%) did not progressed. (Figure 1B). A further analysis for progression event was performed to adjust the effect of PET-2 analysis for other known risk factors (age up to/over 60, stage, Performance status, LDH, number of extranodal sites, IPI, bulky, Bone Marrow involvement): only LDH (p .005)and IPI 0-2 vs 3-5 (p .001 ) were confirmed as independent predictors of progression event. Conclusions. Our results indicate that in this omogeneous group of DLBCL patients treated with R-CHOP interim PET failed to predict outcome. However, a longer follow up is necessary to validate our data. Conversely PET results at the end of treatment strongly correlate with PFS. Prospective larger studies will be needed to establish the real role of interim PET to predict the outcome in this subset of patients. [Display omitted] Disclosures:Ladetto:CELGENE: Honoraria; JANSSEN-CILAG: Research Funding. Vitolo:Roche: lecture fees.