Predictive value of baseline metabolic tumor volume for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis

Zhu, Ke; Su, Danqian; Wang, Jianbo; Cheng, Zhouen; Chin, Yiqiao; Chen, Luyin; Chan, Chingtin; Zhang, Rongcai; Gao, Tianyu; Ben, Xiaosong; Jing, Chunxia

doi:10.3389/fonc.2022.951557

Cited by 3 publications

(11 citation statements)

References 45 publications

(134 reference statements)

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“…Secondly, in a recently published meta-analysis on the predictive value of FDG-PET/CT in NSCLC, Zhu et al included patients in various recent publications with a mean follow-up of 11.9 months, while our mean observation time was longer: 18.9 months, presumably improving the assessment of the prediction power of the generated multivariate prediction model in the long-term. Additionally, our number of patients treated with ICIs was comparable to the average cohort size of those in recent relevant publications on similar topics [ 4 ]. Finally, all the effects of the included outcome predictors emerging from our prediction model were all statistically highly significant in the patients treated with ICIs.…”

Section: Discussionsupporting

confidence: 66%

“…Thirteen original manuscripts have been published between 2020 and 2022 on the predictive value of FDG-PET/CT in NSCLC patients, along with a meta-analysis [ 4 , 12 , 15 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Our study is different in many aspects from these previously published data.…”

Section: Discussionmentioning

confidence: 99%

“…Lung cancer is the leading cause of cancer-related death worldwide, responsible for more deaths than prostate, breast and colon cancer taken together. The annual mortality rate of lung cancer is still rising worldwide, with 1.80 million deaths in 2020 [ 1 , 2 , 3 , 4 ]. Nonsmall cell lung cancer (NSCLC) accounts for 80–85% of the cases, with small cell lung cancer SCLC contributing the remaining 15–20% [ 2 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, this groundbreaking treatment approach also has some limitations. In fact, only 20% of advanced NSCLC patients receiving ICIs achieve an objective response; on the other hand, 7–27% experience severe immune-related adverse events (IRAEs) [ 4 , 8 , 9 , 12 , 13 ]. Given their limited response rate and high immunotoxicity, the accurate selection of NSCLC patients eligible for ICIs appears crucial.…”

Section: Introductionmentioning

confidence: 99%

“…Given their limited response rate and high immunotoxicity, the accurate selection of NSCLC patients eligible for ICIs appears crucial. Therefore, several biomarkers for responses to ICIs have been extensively discussed in the recent literature, such as PD-L1 status and tumor mutational burden (TMB) [ 4 , 7 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Predictive Value of Baseline FDG-PET/CT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors

Kudura

Ritz

Kutzker

et al. 2022

Cancers

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Objectives: We aimed to investigate the predictive value of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for durable responses to immune checkpoint inhibitors (ICIs) by linking the morphological and metabolic features of primary tumors (PTs) in nonsmall cell lung cancer (NSCLC) patients. Methods: For the purpose of this single-center study, the imaging data of the patients with a first diagnosis of NSCLC and an available baseline FDG-PET/CT between 2020 and 2021 were retrospectively assessed. The baseline characteristics were collected based on clinical reports and interdisciplinary tumor board documentation. The metabolic (such as standardized uptake value SUV maximum and mean (SUVmax, SUV mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG)) and morphological (such as volume, morphology, margin, and presence of lymphangiosis through imaging) features of all the PTs were retrospectively assessed using FDG-PET/CT. Overall survival (OS), progression-free survival (PFS), clinical benefit (CB) and mortality rate were used as endpoints to define the long-term response to therapy. A backward, stepwise logistic regression analysis was performed in order to define the best model for predicting lasting responses to treatment. Statistical significance was assumed at p < 0.05. Results: A total of 125 patients (median age ± standard deviation (SD) 72.0 ± 9.5 years) were enrolled: 64 men (51.2%) and 61 women (48.8%). Adenocarcinoma was by far the most common histological subtype of NSCLC (47.2%). At the initial diagnosis, the vast majority of all the included patients showed either locally advanced disease (34.4%) or metastatic disease (36.8%). Fifty patients were treated with ICIs either as a first-line (20%) or second-line (20%) therapy, while 75 patients did not receive ICIs. The median values ± SD of PT SUVmax, mean, MTV, and TLG were respectively 10.1 ± 6.0, 6.1 ± 3.5, 13.5 ± 30.7, and 71.4 ± 247.7. The median volume of PT ± SD was 13.7 ± 30.7 cm3. The PTs were most frequently solid (86.4%) with irregular margins (76.8%). Furthermore, in one out of five cases, the morphological evidence of lymphangiosis was seen through imaging (n = 25). The median follow-up ± SD was 18.93 ± 6.98 months. The median values ± SD of OS and PFS were, respectively, 14.80 ± 8.68 months and 14.03 ± 9.02 months. Age, PT volume, SUVmax, TLG, the presence of lymphangiosis features through imaging, and clinical stage IV were very strong long-term outcome predictors of patients treated with ICIs, while no significant outcome predictors could be found for the cohort with no ICI treatment. The optimal cut-off values were determined for PT volume (26.94 cm3) and SUVmax (15.05). Finally, 58% of NSCLC patients treated with ICIs had a CB vs. 78.7% of patients in the cohort with no ICI treatment. However, almost all patients treated with ICIs and with disease progression over time died (mortality in the case of disease progression 95% vs. 62.5% in the cohort without ICIs). Conclusion: Baseline FDG-PET/CT could be used to predict a durable response to ICIs in NSCLC patients. Age, clinical stage IV, lymphangiosis features through imaging, PT volume (thus PT MTV due to a previously demonstrated linear correlation), PT SUVmax, and TLG were very strong long-term outcome predictors. Our results highlight the importance of linking clinical data, as much as morphological features, to the metabolic parameters of primary tumors in a multivariate outcome-predicting model using baseline FDG-PET/CT.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictive Value of Baseline FDG-PET/CT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors

Kudura

Ritz

Kutzker

et al. 2022

Cancers

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Correlation between Radiological Characteristics, PET-CT and Histological Subtypes of Primary Lung Adenocarcinoma–A 102 Case Series Analysis

Colic,

Stevic,

Savic

et al. 2023

Preprint

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Summarizing radiological characteristics between primary lung adenocarcinoma subtypes and correlate them with FDG uptake on PET-CT are important for further treatment. A PET-CT examination was performed on some of the patients and the values of SUV-max were also correlated with the histological and morphological characteristics of masses in the lungs. Results of this analysis showed that the mean size of AIS-MIA cancer was significantly lower than for all other cancer types, while mean size of the acinar cancer was smaller than in solid type of cancer. Metastases were significantly more frequent in solid adenocarcinoma than in acinar, lepidic and AIS-MIA cancer subtypes. The maximum standardized FDG uptake was significantly lower in AIS-MIA than in all other cancer types, and in acinar compared to solid cancer. Papillary adenocarcinoma had higher odds to develop contralateral lymph node involvement compared to other types. Solid adenocarcinoma was associated with higher odds of having metastases and with higher SUVmax. AIS-MIA was associated with lower odds of one unit increase in tumour size, ipsilateral lymph node involvement. Radiology has a significant role in the diagnosis and monitoring of the disease, and in determining its prognosis, and influence on the decision on the method of treatment.

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Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition

Kudura

Ritz

Templeton

et al. 2023

JCM

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Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. Conclusions: Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.

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Predictive value of baseline metabolic tumor volume for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis

Cited by 3 publications

References 45 publications

Predictive Value of Baseline FDG-PET/CT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors

Predictive Value of Baseline FDG-PET/CT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors

Correlation between Radiological Characteristics, PET-CT and Histological Subtypes of Primary Lung Adenocarcinoma–A 102 Case Series Analysis

Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition

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