This paper introduces a dynamic paging scheme based on the semi-realtime movement information of an individual user, which allows a more accurate predication of the user location at the time of paging. In general, a realtime location tracking scheme may require complex control schemes and incur unacceptably high computation and messaging cost. Our proposed approach, namely velocity paging scheme, relaxes the realtime constraints to semirealtime to provide a good combination of cost reduction and esse of implementation.The proposed velocity paging scheme utilizes semi-realtime velocity information, namely velocity classes, of individual mobile terminal and dynamically generates a paging zone (a list of cells to be paged) for it. Therefore, the total paging cost can be reduced due to the paging area reduction. Much consideration also has been given to reduce the complexity for the proposed scheme. As a result, it only requires minimal extra overhead and is feasible to implement in current cellular/PCS networks. The velocity paging can be combined with movement-based registration or other registration schemes. Analytical results of velocity paging and movement-based registration combination are provided to demonstrate the cost effectiveness of the scheme under various parameters in comparison with location area scheme.

Introduction. Immune-related adverse event (IRAE) onset may represent a clinical biomarker for anti-programmed cell death protein 1 (PD-1) antibody response based on emerging evidence from patients with various advanced malignancies. This phenomenon has not been previously reported in a multidisease cohort of patients with gastrointestinal (GI) cancer with Food and Drug Administration (FDA)-approved indications to receive immune checkpoint inhibitor therapy. Materials and Methods. The study was a multicenter retrospective cohort analysis of 76 patients with GI cancer who had received anti-PD-1 antibodies for FDA-approved indications. The primary and secondary outcomes of the study were progression-free survival (PFS) and overall survival (OS) in patients based upon IRAE presence, respectively. PFS and OS were estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusted for IRAE onset, patient age, and enrolling institution was used to analyze outcomes.

ImportanceAppropriate clinical decision-making relies on accurate data interpretation, which in turn relies on the use of suitable statistical models. Long tails and early crossover—2 features commonly observed in immune checkpoint inhibitor (ICI) survival curves—raise questions as to the suitability of Cox proportional hazards regression for ICI survival analysis. Cox proportional hazards–Taylor expansion adjustment for long-term survival data (Cox-TEL) adjustment may provide possible solutions in this setting.ObjectiveTo estimate overall survival and progression-free survival benefits of ICI therapy vs chemotherapy using Cox-TEL adjustment.Data SourcesA PubMed search was performed for all cataloged publications through May 22, 2022.Study SelectionThe search was restricted to randomized clinical trials with search terms for ICIs and lung cancer, melanoma, or urothelial carcinoma. The publications identified were further reviewed for inclusion.Data Extraction and SynthesisCox proportional hazards ratios (HRs) were transformed to Cox-TEL HRs for patients with short-term treatment response (ie, short-term survivor) (ST-HR) and difference in proportions for patients with long-term survival (LT-DP) by Cox-TEL. Meta-analyses were performed using a frequentist random-effects model.Main Outcomes and MeasuresOutcomes of interest were pooled overall survival (primary outcome) and progression-free survival (secondary outcome) HRs, ST-HRs, and LT-DPs. Subgroup analyses stratified by cancer type also were performed.ResultsA total of 1036 publications was identified. After 3 levels of review against inclusion criteria, 13 clinical trials (7 in non–small cell lung cancer, 3 in melanoma, and 3 in urothelial carcinoma) were selected for the meta-analysis. In the primary analysis, pooled findings were 0.75 (95% CI, 0.70-0.81) for HR, 0.86 (95% CI, 0.81-0.92) for ST-HR, and 0.08 (95% CI, 0.06-0.10) for LT-DP. In the secondary analysis, the pooled values for progression-free survival were 0.77 (95% CI, 0.64-0.91) for HR, 1.02 (95% CI, 0.84-1.24) for ST-HR, and 0.10 (95% CI, 0.06-0.14) for LT-DP.Conclusions and RelevanceThis systematic review and meta-analysis of ICI clinical trial results noted consistently larger ST-HRs vs Cox HRs for ICI therapy, with an LT-DP of approximately 10%. These results suggest that Cox HRs may not provide a full picture of survival outcomes when the risk reduction from treatment is not constant, which may aid in the decision-making process of oncologists and patients.

4116 Background: Despite the therapeutic promise of ICIs for patients (pts) with some advanced malignancies, they are FDA-approved for only a few GI cancer pts. In NSCLC, melanoma and urothelial carcinoma, there is emerging data that pts who experience IRAEs while on ICIs have improved outcomes compared with pts who do not. This association in GI cancer pts has not been reported. Methods: We retrospectively analyzed outcomes for metastatic GI cancer pts receiving ICIs for FDA-approved indications (later-line MSI-H tumors, 2nd line hepatocellular carcinoma (HCC), 3rd line PD-L1+ gastric (GA)/gastroesophageal junction (GEJ) adenocarcinoma), at Vanderbilt Ingram Cancer Center, Winship Cancer Institute and Stanford Cancer Institute. Our primary aim was to compare progression-free survival (PFS) and overall survival (OS) between pts who did and did not experience IRAEs. Secondary aims were comparison of these outcomes within pts who experienced IRAEs, by initial IRAE severity (Grade (G)3/G4 vs G1/G2) (CTCAE v5.0), time-to-onset (TTO) (≤ 6 weeks (w) vs > 6 w) and management (steroids vs drug cessation vs observation). PFS and OS were determined by Kaplan-Meier (KM) analysis; KM comparisons were done by the logrank test. Results: Between 1/2015-12/2018 61 GI cancer pts with HCC (28), colorectal cancer (27) and GA/GEJ cancer (6) were treated with ICIs; median age was 63 years. The majority (59) received single-agent nivolumab or pembrolizumab while minority (2) received nivolumab and ipilimumab; median time on ICIs was 5.9 months (mos). Twenty-four pts experienced initial IRAEs (6 G3/G4, 18 G1/G2); median TTO was 3.8 mos. Pts who experienced any IRAE had improvements in PFS and OS compared to those who did not (PFS: 32.4 mos (95% confidence interval (CI), 32.4-not reached (NR)) vs 4.8 mos (95% CI, 2.9-8.7), p = 0.0001; OS: 32.4 mos (95% CI, 32.4-NR) vs 8.5 mos (95% CI, 6-NR), p = 0.0036). Among pts who experienced IRAEs, PFS and OS differences between above-specified subgroups did not meet statistical significance. Conclusions: GI cancer pts who experienced IRAEs while on ICIs had marked improvements in PFS and OS compared to those who did not, suggesting the predictive potential for IRAEs as a clinical biomarker in this population.