Showing papers by "Jack A. Roth published in 2023"

Financial Toxicity in Patients with Resected Lung Cancer.

Abstract: OBJECTIVES We aimed to describe financial toxicity (FT) in patients with resected lung cancer and identify risk factors in this population. SUMMARY BACKGROUND FT describes the financial burden associated with cancer care and its impact on the quality of survivorship. Few prior studies have examined FT in lung cancer patients. METHODS Patients who underwent lung cancer resection at our institution between January 1st 2016 and December 31st 2021 were surveyed to gather demographic information and evaluate FT using a validated questionnaire. A multivariable model was built to identify risk factors for FT. RESULTS 1477 patients were contacted, of whom 463 responded (31.3%). Most patients were stage I (n=349, 75.4%) and lobectomy was performed often (n=290, 62.8%). There were 196 patients (42.3%) who experienced FT. Upon multivariable analyses, divorced marital status (Odds Ratio [OR]= 3.658, 95% confidence interval [CI]: 1.180-11.337), household income <$40,000 (OR=2.544, 95% CI: 1.003-6.455), credit score below 739 (OR=2.744, 95% CI 1.326-5.679), clinical stage > I (OR=2.053, 95% CI: 1.088-3.877), and change in work hours or work cessation (all P<0.05) were associated with FT. Coping mechanisms, such as decreased spending on food or clothing and increased use of savings or borrowing money, were more likely to be reported by patients experiencing FT than those who did not (P<0.001). CONCLUSIONS Patients undergoing lung cancer resection often experienced significant financial stress with several identifiable risk factors. FT should be considered early in the care of these patients to alleviate detrimental coping mechanisms and enhance their quality of survivorship.

Abstract 5120: NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic human NSCLC in a humanized mouse model

Abstract: NPRL2/TUSC4 is a potent tumor suppressor gene whose expression is reduced in many cancers including NSCLC. Restoration of NPRL2 expression in cancer cells induces DNA damages which leads to cell cycle arrest and apoptosis. We investigated the antitumor immune responses to NPRL2 gene therapy on anti-PD1 resistant KRAS/STK11 mutant NSCLC in a humanized mouse model. H1299 cells transfected with NPRL2 showed significant inhibition of colony formation after NPRL2 transfection. Humanized mice were generated by transplanting fresh human cord blood derived CD34 stem cells into sub-lethally irradiated NSG mice. The level of engraftment of human CD45, CD3 T, CD19 B, NK cells was verified before tumor implantation. Mice harboring > 25% human CD45 cells were considered humanized. KRAS/STK11 mutant anti-PD1 resistant A549 NSCLC cells were injected intravenously into humanized NSG mice and developed lung metastasis. Metastases were treated with intravenous injection of NPRL2 gene loaded cationic lipid nanoparticles with or without pembrolizumab (anti-PD1). A dramatic antitumor effect was mediated by NPRL2 treatment, whereas pembrolizumab was ineffective. A significant antitumor effect was also found in non-humanized NSG mice, although the effect was greater in humanized mice suggesting that the possible role of antitumor immunity. The antitumor effect of NPRL2 was associated with increased infiltration of human CD45, CD3 T, cytotoxic T, NK cells, and a decreased number of human regulatory T cells (Treg) in tumors. PD1 expressing exhausted CD8 T cells were downregulated in both the NPRL2 and pembrolizumab groups. The number of activated T cells (CD69+CD8+T), effector (EM) and central memory (CM) CD8 T cells were significantly increased by NPRL2 treatment. NPRL2 induced antigen presenting HLA-DR+ dendritic cells. When NPRL2 was combined with pembrolizumab, no synergistic antitumor effect was found in the KRAS/STK11 mutant anti-PD1 insensitive tumors. However, a robust and synergistic antitumor effect was observed in the KRAS wild type, anti-PD1 sensitive H1299 tumors grown in humanized mice treated with NPRL2 + pembrolizumab. Cytotoxic T cells, NK cells, and HLA-DR+ DC were associated with the antitumor effect. DOTAP-NPRL2 was tested in a syngeneic mouse model with LLC2 tumors that are KRAS mutant and anti-PD1 resistant. Consistent with the A549 humanized mouse model, NPRL2 showed a significantly strong antitumor effect whereas anti-PD1 was not effective in this model. The antitumor effect of NPRL2 was again correlated with the upregulation of HLA-DR+ DC, CD11c DC, TILs, NK and downregulation of Treg and myeloid cells in the tumor microenvironment. Taken together, these data suggest that NPRL2 gene therapy induces antitumor activity on KRAS/STK11 mutant anti-PD1 resistant tumors through DC mediated antigen presentation and cytotoxic immune cell activation. Citation Format: Ismail M. Meraz, Mourad Majidi, Renduo Song, Feng Meng, Gao Lihui, Qi Wang, Jing Wang, Elizabeth Shpall, Jack A. Roth. NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic human NSCLC in a humanized mouse model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5120.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

Abstract: PURPOSE The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). CONCLUSION Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.