No abstract

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs.

Purpose Our aim was to compare a widely distributed commercial tool with an older free software (i) one another, (ii) with a clinical motor score, (iii) versus reading by experts. Procedures We analyzed consecutive scans from one-hundred and fifty-one outpatients submitted to brain DAT SPECT for a suspected parkinsonism. Images were post-processed using a commercial (Datquant®) and a free (BasGanV2) software. Reading by expert was the gold standard. A subset of patients with pathological or borderline scan was evaluated with the clinical Unified Parkinson’s Disease Rating Scale, motor part (MDS-UPDRS-III). Results SBR, putamen-to-caudate (P/C) ratio, and both P and C asymmetries were highly correlated between the two software with Pearson’s ‘r’ correlation coefficients ranging from .706 to .887. Correlation coefficients with the MDS-UPDRS III score were higher with caudate than with putamen SBR values with both software, and in general higher with BasGanV2 than with Datquant®. Datquant® correspondence with expert reading was 84.1% (94.0% by additionally considering the P/C ratio as a further index). BasGanV2 correspondence with expert reading was 80.8% (86.1% by additionally considering the P/C ratio). Conclusions Both Datquant® and BasGanV2 work reasonably well and similarly one another in semi-quantification of DAT SPECT. Both tools have their own strength and pitfalls that must be known in detail by users in order to obtain the best help in visual reading and reporting of DAT SPECT.

9062 Background: Upfront Immune Checkpoint Blockers (ICB) alone or in combination with chemotherapy (CT) have become the backbone treatment of non-oncogene addicted aNSCLC. PD-L1 remains the only predictive biomarker, but additional biomarkers are mandatory to better discriminate the population more suitable for the combination approach (CT-ICB). We hypothesized that TLG, a parameter that measure tumor burden and metabolic activity, may help to select the optimal first-line regimen. Methods: We performed a multicentric (n = 5) retrospective study including pts treated either with ICB alone, CT-ICB or CT alone. Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional Hazard models adjusting for relevant covariates (neutrophil/lymphocyte ratio, ECOG PS, liver, bone metastases). TLG was calculated on PET scans as the product of metabolic tumor volume (with a threshold of 42% of SUV max) and SUV mean. Results: 250 pts with aNSCLC initiated first-line treatment (94 ICB, 102 CT-ICB and an hystorical control group of 54 CT) within 42 days from PET. Median follow up was 22 months for ICB, 16 for CT-ICB and 47 for CT. 170 pts were male (68%), 210 had non-squamous histology (84%), 110 (44%)and 38 (15%) had bone and liver metastasis, respectively. On the 194 pts with PD-L1 status available: 20%, 29% and 50% had PD-L1 < 1%, 1-49% and > 50%, respectively. No correlation was seen between PD-L1 and TLG. Presence of liver metastases (13% vs 2%) and ECOG PS > 1 (16% vs 3%) were associated with elevated TLG. PFS correlated with TLG, with longer median PFS in the lower quartile (TLG < 380) either with ICB (12.4 vs 4.7 months, HR 1.9, 95% CI1.1 – 3.35, p 0.025) and CT-ICB (17.9 vs 7.3, HR 1.9, 95% CI1.1 – 3.7, p 0.032) but not with CT (4.2 vs 3.5, p 0.986), whereas OS was correlated with TLG < 380 in all 3 groups. The risk of progression under ICB was lower in tumors with TLG < 380 (15% vs.29%, p = 0.02), but no difference was seen in other 2 groups. In PD-L1 ≥50% pts with elevated TLG, treatment with CT-ICB (n = 20) increased the PFS respect with ICB (n = 55) (10.7 vs 3.9, HR 0.54, 95% CI 0.29 – 0.99, p = 0.048).The analysis was underpowered to find a difference in OS (HR 0.49, 95% CI 0.21 - 1.12, p = 0.092). Conclusions: TLG retains a prognostic validity in aNSCLC identifying pts with an increased rate of early progression on ICB, who may benefit from CT-ICB. Further analyses are required to compare CT-ICB and ICB in PD-L1 ≥50% according to TLG. Enrollement from other centers is ongoing, an update will be presented.

Purpose. Our aim was the head-to-head comparison between two automatic tools for semi-quantification of striatal dopamine transporter (DAT) specific-to-non displaceable (SBR) ratio brain SPECT values in a naturalistic cohort of patients. Procedures. We analyzed consecutive scans from one-hundred and fifty-one outpatients submitted to brain DAT SPECT for a suspected parkinsonism. Images were post-processed using a commercial (Datquant®) and a free (BasGanV2) software. Reading by expert was the gold-standard. A subset of patients with pathological or borderline scan was evaluated with the clinical Unified Parkinson’s disease rating scale, motor part (MDS-UPDRS-III). Results. SBR, putamen-to-caudate (P/C) ratio, and both P and C asymmetries were highly correlated between the two software with Pearson’s ‘r’ correlation coefficients ranging from .706 to .887. Correlation coefficients with the MDS-UPDRS III score were higher with caudate than with putamen SBR values with both software, and in general higher with BasGanV2 than with Datquant® . Datquant® correspondence with expert reading was 84.1% (94.0% by additionally considering the P/C ratio as a further index). BasGanV2 correspondence with expert reading was 80.8% (86.1% by additionally considering the P/C ratio). Conclusions. Both Datquant® and BasGanV2 work reasonably well and similarly one another in semi-quantification of DAT SPECT. Both tools have their own strength and pitfalls that must be known in detail by users in order to obtain the best help in visual reading and reporting of DAT SPECT.