Prognostic models integrating quantitative parameters from baseline and interim positron emission computed tomography in patients with diffuse large B‐cell lymphoma: post‐hoc analysis from the SAKK38/07 clinical trial

Zucca, Emanuele; Cascione, Luciano; Ruberto, Teresa; Facchinelli, Davide; Schär, Sämi; Hayoz, Stefanie; Dirnhofer, Stefan; Giovanella, Luca; Bargetzi, Mario; Mamot, Christoph; Ceriani, Luca

doi:10.1002/hon.2805

Cited by 15 publications

(12 citation statements)

References 58 publications

(140 reference statements)

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“…Patients in the high-risk subgroup had more frequently elevated LDH and high IPI scores than the other groups. This is not surprising as LDH is a surrogate marker of disease burden: we might speculate that increased LDH levels reflect the elevated MTV, which this analysis confirmed to be an optimal individual parameter to identify patients at high risk of progression or death [ 17 , 22 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 76%

“…The metabolic response in 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) scan at the end of treatment is currently the best predictor of patient survival [ 18 ]. Increasing evidence suggests that baseline PET/CT parameters, including metabolic tumor volume (MTV), total lesion glycolysis (TLG) [ 19 , 20 , 21 , 22 , 23 ], and metabolic heterogeneity (MH) and radiomic features indicating lymphoma dissemination, represent independent and powerful prognostic factors in DLBCL [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…We already developed prognostic models based on functional parameters from PET/CT scans [ 24 , 25 ] of DLBCL patients homogeneously treated with the R-CHOP14 regimen in the SAKK38/07 clinical trial [ 34 ]. In the same cohort, phenotypic and genotypic studies identified several potential biomarkers [ 35 , 36 ], with CREBBP and EP300 mutations being strongly associated with worse outcomes at multivariable analysis [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Integration of Baseline Metabolic Parameters and Mutational Profiles Predicts Long-Term Response to First-Line Therapy in DLBCL Patients: A Post Hoc Analysis of the SAKK38/07 Study

Genta

Ghilardi

Cascione

et al. 2022

Cancers

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Accurate estimation of the progression risk after first-line therapy represents an unmet clinical need in diffuse large B-cell lymphoma (DLBCL). Baseline (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) parameters, together with genetic analysis of lymphoma cells, could refine the prediction of treatment failure. We evaluated the combined impact of mutation profiling and baseline PET/CT functional parameters on the outcome of DLBCL patients treated with the R-CHOP14 regimen in the SAKK38/07 clinical trial (NCT00544219). The concomitant presence of mutated SOCS1 with wild-type CREBBP and EP300 defined a group of patients with a favorable prognosis and 2-year progression-free survival (PFS) of 100%. Using an unsupervised recursive partitioning approach, we generated a classification-tree algorithm that predicts treatment outcomes. Patients with elevated metabolic tumor volume (MTV) and high metabolic heterogeneity (MH) (15%) had the highest risk of relapse. Patients with low MTV and favorable mutational profile (9%) had the lowest risk, while the remaining patients constituted the intermediate-risk group (76%). The resulting model stratified patients among three groups with 2-year PFS of 100%, 82%, and 42%, respectively (p < 0.001).

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integration of Baseline Metabolic Parameters and Mutational Profiles Predicts Long-Term Response to First-Line Therapy in DLBCL Patients: A Post Hoc Analysis of the SAKK38/07 Study

Genta

Ghilardi

Cascione

et al. 2022

Cancers

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“…Response to interim F 18 flurodeoxyglucose positron emission tomography/computed tomography (PETCT) during frontline chemoimmunotherapy has been explored as a prognostic marker in newly diagnosed DLBCL in multiple studies with small sample size, heterogeneous timing of interim PETCT, heterogeneous populations, variable study treatments and conflicting results [ 5 – 12 ]. Three major prospective studies have evaluated impact of PETCT after cycles 2 of frontline chemoimmunotherapy (PET2) on outcomes of newly diagnosed DLBCL with conflicting results [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

PET2 response associated with survival in newly diagnosed diffuse large B-cell lymphoma: results of two independent prospective cohorts

et al. 2022

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Studies evaluating Positron Emission Tomography scan after 2 cycles of chemotherapy (PET2) in newly diagnosed diffuse large B cell lymphoma (DLBCL) are heterogeneous in patient characteristics, treatments and have conflicting results. Here we report association of PET2 with outcomes in two large independent prospective cohorts of newly diagnosed DLBCL pts treated with two RCHOP-based regimens. The discovery cohort consisted of pts enrolled in single arm phase 2 MC078E study of lenalidomide with RCHOP (R2CHOP). The validation cohort consisted of RCHOP-treated pts from the Molecular Epidemiology Resource (MER) cohort. Pts who received 3-6 cycles of therapy and had PET2 were included in the study. Patients who progressed on PET2 were excluded. Revised response criteria 2007 were used to define PET2 response PET2 positive (PET2 + ) pts had inferior EFS [24-month EFS 45.5% vs 87.9%, HR 4.0, CI95 (2.1–7.9), p < 0.0001) with a trend towards lower OS [24-months OS 77% vs 94.8%, HR 2.0, CI95 (0.9–4.8), P = 0.1] than PET2 negative (PET2−) pts in MC078E cohort. PET2 + pts had an inferior EFS (24 month EFS 48.7% vs 81.6%, HR 2.9, CI95 2.0–4.2, p < 0.0001) and OS (24-month OS 68.6% vs 88.1%, HR 2.3, CI95: 1.5–3.5, p < 0.0001) in the MER cohort. These results were consistent regardless of age, sex and in the subgroup of advanced stage and high-risk international prognostic index (IPI). For MER, PET2 + pts also had higher odds of positive end of treatment PET (OR: 17.3 (CI95 7.9–37.7), p < 0.001). PET2 is an early predictor DLBCL pts at high risk of progression and death in two independent prospective cohorts. PET2-guided risk-adapted strategies may improve outcomes, and should be explored in clinical trials.

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“…DLBCL patients are traditionally evaluated after 2–4 regimens, and residual disease after treatment also indicates prognosis. Several studies found that interim evaluation results from PET-CT or CT scans are predictors of survival ( 13 – 15 ), but given the considerable portion of false-positive PET-CT scans, interim evaluation is not strictly associated with survival.…”

Section: Introductionmentioning

confidence: 99%

Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study

Xue

Liu

et al. 2021

Front. Oncol.

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The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.

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Prognostic models integrating quantitative parameters from baseline and interim positron emission computed tomography in patients with diffuse large B‐cell lymphoma: post‐hoc analysis from the SAKK38/07 clinical trial

Cited by 15 publications

References 58 publications

Integration of Baseline Metabolic Parameters and Mutational Profiles Predicts Long-Term Response to First-Line Therapy in DLBCL Patients: A Post Hoc Analysis of the SAKK38/07 Study

Integration of Baseline Metabolic Parameters and Mutational Profiles Predicts Long-Term Response to First-Line Therapy in DLBCL Patients: A Post Hoc Analysis of the SAKK38/07 Study

PET2 response associated with survival in newly diagnosed diffuse large B-cell lymphoma: results of two independent prospective cohorts

Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study

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