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A replication-selective herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) has shown efficacy both in vitro and in vivo against human non-small cell lung cancer (NSCLC) cell lines but complete eradication of tumor has not been accomplished with a single viral treatment in our murine xenograft models. Therefore, strategies to enhance the efficacy of this treatment were investigated. We determined the oncolytic activity of HSV-1716 in NCI-H460 cells in combination with each of four chemotherapeutic agents: mitomycin C (MMC), cis-platinum II (cis-DDP), methotrexate (MTX), or doxorubicin (ADR). Isobologram analysis was performed to evaluate the interaction between the viral and chemotherapeutic agents. The oncolytic effect of HSV-1716 in combination with MMC was synergistic in two of five NSCLC cell lines. In the other three cell lines, the combined effect appeared additive. No antagonism was observed. The in vivo effect of this combination was then examined in a murine xenograft model. NCI-H460 flank tumors were directly injected with HSV-1716 (4 x 106 PFU) followed by intravenous MMC administration (0.17 mg/kg) 24 hr later. After 3 weeks, the mean tumor weight in the combined treatment group was significantly less than either individual treatment in an additive manner. The synergistic dose of MMC neither augmented nor inhibited viral replication in vitro and HSV-1716 infection did not upregulate DT-diaphorase, which is the primary enzyme responsible for MMC activation. In summary, the combination of HSV-1716 with common chemotherapeutic agents may augment the effect of HSV-based therapy in the treatment of NSCLC.

Objective: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. Summary of Background Data: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. Methods: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. Results: The 320 enrolled patients were randomly assigned to the RAL group (n ¼ 157) and the VAL group (n ¼ 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P ¼ 0.76) and the rate of postoperative complications (P ¼ 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P ¼ 0.

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Objective: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). Summary Background Data: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. Methods: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. Results: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS (P < 0.0001) and OL (P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P<0.02). Compared to VATS, RL had lower conversion rate (P<0.0001), shorter hospital stay (P<0.0001) and a lower postoperative transfusion rate (P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. Conclusions: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.

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