scholarly journals Differential role of residual metabolic tumor volume in inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition

2021 ◽  
Author(s):  
Marcus Unterrainer ◽  
Julian Taugner ◽  
Lukas Käsmann ◽  
Amanda Tufman ◽  
Niels Reinmuth ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Pet Ct ◽  
Stage Iii Nsclc ◽  
Fdg Pet Ct ◽  
Nsclc Patients

Abstract Background The PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI). Methods Fifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS). Results Overall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses. Conclusion In stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.

Differential role of residual metabolic tumor volume in patients with inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20558-e20558
Author(s):  
Marcus Unterrainer ◽  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Wolfgang G. Kunz ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Fdg Pet ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Stage Iii ◽  
Free Survival ◽  
Pet Ct ◽  
Stage Iii Nsclc ◽  
Fdg Pet Ct ◽  
Nsclc Patients

e20558 Background: PET-derived metabolic-tumor-volume (MTV) has shown to be an independent prognosticator in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). We analysed the prognostic value of residual MTV after completion of thoracic irradiation (TRT) in inoperable stage III NSCLC patients treated with CRT with and without immune check-point inhibition (ICI). Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median age: 65 years) underwent 18F-FDG PET/CT at the same institution before and after completion of CRT. MTV was delineated on 18F-FDG PET/CT using a standard threshold (hepatic SUVmean + 2 x standard-deviation). Patients were divided in volumetric subgroups using median split dichotomization (residual MTV ≤4.0 ml & > 4.0 ml). Residual MTV, clinical features and ICI maintenance (RCT-IO; 21/56 (37.5%) patients) were correlated with clinical outcome (progression-free survival (PFS), local PFS (LPFS), metastasis-free survival (MFS), and overall survival (OS). Results: Median follow-up was 52.0 months. 52 (93%) patients were treated with CRT, 12 (21%) patients with CRT followed by durvalumab, and 9 (16%) patients treated with CRT plus nivolumab (concurrent and sequential). In the entire cohort, smaller residual MTV was associated with longer PFS (median 29.3 vs. 10.5 months, p = 0.015); PFS in patients treated with CRT and ICI was also significantly longer compared to the CRT-only subgroup (median 29.3 vs. 11.2 months, p = 0.010). However, residual MTV was predictive for longer PFS in CRT-only (median 33.5 vs. 8.6 months, p = 0.001), but not in the CRT-ICI patients (p = 0.909). Analogously, patients with smaller MTV had a longer LPFS (median 49.9 vs. 16.3 months, p = 0.002); CRT-ICI patients showed a significantly longer LPFS compared to CRT-only patients (median not reached vs. 16.9 months, p = 0.016). Residual MTV remained a significant prognosticator for LPFS in the CRT-only (median 49.9 vs. 10.1 months, p = 0.01), but not in CRT-ICI patients (p = 0.291). Again, smaller residual MTV remained a significant prognosticator for OS in the CRT-only subgroup (median 63.0 vs. 16.3 months, p = 0.004), but not in CRT-ICI patients (p = 0.720). Even in patients with larger residual MTV, the application of ICI significantly improved OS compared to CRT-only subgroup (median not reached vs. 22.9 months, p = 0.004). Conclusions: Smaller residual MTV is associated with superior clinical outcome in inoperable stage III NSCLC, especially in patients undergoing CRT-only. In contrast, in patients undergoing concurrent or sequential consolidation clinical outcome was independent of residual MTV. Hence, even patients with extensive residual MTV might significantly profit from ICI consolidation.

scholarly journals Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

2021 ◽  
Author(s):  
Julian Taugner ◽  
Lukas Käsmann ◽  
Monika Karin ◽  
Chukwuka Eze ◽  
Benedikt Flörsch ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Immune Checkpoint ◽  
Target Volume ◽  
Continuous Variable ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Platinum Based Chemotherapy ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

SummaryBackground. The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Method and patients. Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local–regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). Results. All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7–34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p < 0.001) and 3.6 months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65 years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263–22.942, p = 0.023)). Conclusion. In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Julian Taugner ◽  
Monika Karin ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Julian Guggenberger ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Progression Free Survival ◽  
Target Volume ◽  
Continuous Variable ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p < 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.

Total lesion glycolysis (TLG) at baseline FDG-PET/CT compared with maximum standard uptake value (SUVmax) to predict survival in non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7579-7579
Author(s):  
Ling Li ◽  
Feng-Ming (Spring) Kong ◽  
Nan Bi ◽  
Jingbo Wang ◽  
Pawinee Mahasittiwat ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Fdg Pet ◽  
Tumor Volume ◽  
Background Level ◽  
Metabolic Tumor Volume ◽  
Significant Prognostic Factor ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Nsclc Patients

7579 Background: SUVmaxat baseline FDG-PET has been reported as a significant prognostic factor while recent studies suggest that metabolic tumor volume (MTV) may be more important factor in patients with NSCLC. We hypothesized that TLG is a better prognostic factor than either SUVmax or MTV alone for overall survival (OS) and progression free survival (PFS) in NSCLC because it integrates both volumetric and biologic activity. Methods: The study population included a prospectively recruited cohort of stage I-III NSCLC patients treated with chemoradiation. FDG PET/CT scans were performed within 2 weeks from treatment start. The SUV in the tumor was normalized to that of the background level in the middle of ascending aorta to minimize the confounding effect from inter-scan variation in SUV measurement. MTV was delineated by auto-threshold at 1.5 times background level in the aorta followed by knowledge based manual editing. Mean and maximum SUV normalized to the background level were computed. TLG was calculated as the product of lesion SUVmean and MTV. Results: A total of 96 patients with minimum follow-up of 1 year were eligible. The median follow-up among survivors was 30 months. Univariate analysis demonstrated that MTV and TLG were significant factors for both OS and PFS (all P<0.05). There was a significant correlation between SUVmean and PFS (P=0.013), but there was no significant association between SUVmean and OS. SUVmax was not a significant factor for either OS or PFS (all P>0.05). Under multivariate Cox regression analysis, MTV (HR= 2.62, P= 0.003) and NSUVmean (HR=0.351, P=0.003) were significantly associated with PFS; but only TLG was significantly associated with OS (HR=2.14, P=0.006)adjusted by of TNM stage and other clinical factors. Conclusions: These results support our hypothesis that metabolic tumor volume and biologic average glucose metabolic activity of this volume are more important prognostic factors for overall prognosis than SUVmax in NSCLC patients treated with chemoradiation. Should this be validated by independent studies, future clinical trial should take this into consideration for individualized care.

scholarly journals Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using 18F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma

2019 ◽  
Vol 60 (7) ◽  
pp. 604 ◽  
Author(s):  
You Jin Chun ◽  
Hei-Cheul Jeung ◽  
Hyung Soon Park ◽  
Ji Soo Park ◽  
Sun Young Rha ◽  
...  
Keyword(s):  
Gallbladder Carcinoma ◽  
Fdg Pet ◽  
Tumor Volume ◽  
Locally Advanced ◽  
Metabolic Tumor Volume ◽  
Total Lesion Glycolysis ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct
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