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Background: Poor patients often reside in neighborhoods of lower socioeconomic status (SES) with high levels of airborne pollutants. They also have higher mortality from non–small cell lung cancer (NSCLC) than those living in wealthier communities. We investigated whether living in polluted neighborhoods is associated with somatic mutations linked with lower survival rates, i.e., TP53 mutations. Methods: In a retrospective cohort of 478 patients with NSCLC treated at a comprehensive cancer center between 2015 and 2018, we used logistic regression to assess associations between individual demographic and clinical characteristics, including somatic TP53 mutation status and environmental risk factors of annual average particulate matter (PM2.5) levels, and neighborhood SES. Results: 277 patients (58%) had somatic TP53 mutations. Of those, 45% lived in neighborhoods with “moderate” Environmental Protection Agency–defined PM2.5 exposure, compared with 39% of patients without TP53 mutations. We found significant associations between living in neighborhoods with “moderate” versus “good” PM2.5 concentrations and minority population percentage [OR, 1.06; 95% confidence interval (CI), 1.04–1.08]. There was a significant association between presence of TP53 mutations and PM2.5 exposure (moderate versus good: OR, 1.66; 95% CI, 1.02–2.72) after adjusting for patient characteristics, other environmental factors, and neighborhood-level SES. Conclusions: When controlling for individual- and neighborhood-level confounders, we find that the odds of having a TP53-mutated NSCLC are increased in areas with higher PM2.5 exposure. Impact: The link between pollution and aggressive biology may contribute to the increased burden of adverse NSCLC outcomes in individuals living in lower SES neighborhoods.

Background: City of Hope (COH) is an NCCN academic cancer center in Duarte CA and delivers care in 36 geographically dispersed community sites in Los Angeles, Riverside, San Bernardino, Orange and Ventura counties. We implemented a multi-departmental tobacco use control program (TUCP) (J Clin Med 2020; 1820). In order to facilitate implementation of the TUCP, we developed a multi-level multi-departmental program of clinician/nurse tobacco cessation champions using implementation science principles. Methods: A TUCP centered in Population Science included representatives of all clinical specialties. Cancer center leadership was engaged for resource allocation, and monthly staff communications (Moonshot Shout-outs). Tobacco-using patients were referred for tobacco cessation. To incentivize and promote cessation referrals and patient participation, TUCP worked with physician leaders and nurse leaders to name a clinician and nurse in each academic center clinic and each community site as champions. Results of this program were evaluated by tobacco use assessments and clinician attitude surveys. Results: Among the 36 COH sites and the Duarte academic center, 6 sites were selected for pilot implementation of the champion program. Champions (physicians, advanced practice providers, and nurses in multiple oncology specialties) were appointed and received structured training. Champions were tasked to promote cessation referrals by clinicians and staff, provide support for any problems, meet with TUCP leaders, report barriers to effective cessation implementation, and provide assistance in prescribing tobacco control medications. Tobacco use screening was nearly universal (96%), and showed 5.87% current use overall. Among patients who were smokers, 7.92% were African American, 17.61% were Hispanic, 5.18% were Asian/Pacific Islanders, and 44.09% were non-Hispanic white. Current tobacco use was more prevalent in the community sites than in the academic center and more prevalent in minority patients in community sites. Clinician attitude surveys at the academic center versus community sites revealed similar importance of tobacco cessation, feeling that continued smoking adversely impacted treatment outcomes, referral of patients for cessation, and need for increased training in tobacco control and cessation. Clinicians at the community site with the highest rate of tobacco use and greatest percent of non-white patients, Antelope Valley, expressed the highest need for training into availability of tobacco control services and program support. Conclusions: Tobacco use is widely perceived by clinicians as an important component of cancer treatment, but requires increased resource allocation and leadership, especially at sites with higher tobacco use and greater percentage of racial/ethnic minorities, and worse social determinants of health. Among resources important for tobacco control, multi-level champions (e.g. physicians, nurses, and advanced practice providers) can help promote and implement a TUCP in both academic centers and community sites. Citation Format: Cary A. Presant, Kimlin Tam Ashing, Sophia Yeung, Jonjon Macalintal, Brian Tiep, Argelia Sandoval, Dan Raz, Ravi Salgia, Loretta Erhunmwunsee, Arya Amini, Amar Merla, Heather Graves, Ranjan Pathak, Shaira Dingal, TingTing Tan, Kelly Tarkeshian, Liana Nikolaenko, Kathleen Burns, Sagus Sampath, Beverly Laksana, Steven Rosen. Use of clinician and nurse tobacco cessation champions to implement a tobacco control program in a geographically disseminated academic center-led clinical network analyzed by patient racial/ethnic group [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-011.

Introduction: Oropharyngeal squamous cell (OPSCC) is a subset of head and neck cancers and is known to be associated with human papillomavirus (HPV). We designed a retrospective analysis to determine differences in survival and functional outcomes of OPSCC patients treated at City of Hope (COH) Cancer Center’s main campus versus selected satellite sites with COH-associated faculty and facilities. Methods and Materials: A retrospective analysis was done on patients diagnosed with OPSCC and treated with concurrent chemoradiation therapy from May 2009 to February 2017 at COH main campus or satellite sites. Eligible patients (N=94) had available demographic data, treatment data, survival and functional outcomes, and recent follow-up at a COH site. Results: 50 patients underwent treatment at the COH main campus and 44 at its satellite sites. Majority of patients were Caucasian (38 patients at main campus, 32 patients at satellite sites), male (40 at main campus, 39 at satellite sites), diagnosed with stage IV locally advanced OPSCC by AJCC 7th edition (43 vs. 32 patients), and p16 positive (42 vs. 30 patients). There was an equal smoking history distribution within our cohort (50% never smokers, 50% former/current smokers at both sites). A small subset of patients at both sites underwent surgical resection prior to concurrent chemoradiation (N=23, 25%). Chemotherapy agents chosen for treatment included cisplatin, carboplatin, cetuximab, and platinum/paclitaxel. Cisplatin was highly favored at the main campus (N=39, 78%); cisplatin (N=21, 48%) and cetuximab (N=21, 48%) use was equally distributed at the satellite sites. Of the 60 cisplatin-treated patients, 58 (98%) received the recommended total minimum dose of 200 mg/m2. Majority of patients completed their prescribed cumulative radiation therapy dose (50-70 Gray) (49 [98%] at main campus, 43 [98%] at satellite sites) and had a complete response to treatment (35 [70%] at main campus, 37 [84%] at satellite sites). There were few hospitalizations during the course of treatment (6 at the main campus, 4 at the satellite sites). 12 patients (24%) at the main campus and 19 patients (43%) at the satellite sites underwent feeding tube placement. A trend toward significant difference in feeding tube dependency at 6 months was observed between the main campus (N=2) and satellite sites (N=11) (17% vs. 58%, p=0.08). No significant difference in the 2-year recurrence rate was observed between the main campus (N=5) and the satellite sites (N=7) (10% vs. 16%, p>0.05). Conclusion: Our retrospective analysis highlights comparable recurrence rates between a major tertiary cancer center and selected satellite sites with dedicated radiation and medical oncology faculty and facilities. Discrepancies in the feeding tube dependency rates could be potentially overcome by integration of supportive services between satellites and main campus. This study also highlights the importance of telehealth services in major institutions. Citation Format: Rebecca R. Pharaon, Ellie Maghami, Arya Amini, Atish Mohanty, Nayana Vora, Sue Chang, Thomas Gernon, Robert Kang, Lalit Vora, Samuel Chung, Sagus Sampath, Erminia Massarelli. Analysis and comparison of survival and functional outcomes in oropharyngeal squamous cell carcinoma patients within City of Hope Cancer Center sites [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B26.

Background and Objectives: While radiation therapy (RT) and certain types of chemotherapy are potentially immunogenic, they rarely generate antitumor immune responses. Our previous studies in mice showed that effects of RT on solid tumors are limited by the activation of tumor-promoting and immunosuppressive protein STAT3 in tumor-associated myeloid cells. Current study focused on determining whether STAT3 plays similar role in promoting immune evasion and therapeutic resistance in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemo-radiation therapy. Patients, Materials, and Methods: 15 patients with stage III-IV HNSCC who received CRT with curative intent consented to collect blood and tissue biopsy (IRB#14255). Before and during week 2 of RT, tissue biopsies were collected of a cancer-involved lymph node that received full dose radiation. Blood specimens were collected from patients before and during RT on weeks 1, 2, 4, 6, and 7, as well as 6-12 weeks after treatment completion. After isolation, PBMCs and plasma samples were cryopreserved and stored in liquid nitrogen for no longer than 12 months. For flow-cytometric analysis, PBMC were thawed in 37°C water bath, washed and pre-incubated in RPMI1640 media supplemented with 20% of autologous plasma for 2 h. Cells were then stained with fluorescently-labeled antibodies specific for CD14, CD15, CD33, and HLA-DR (eBioscience). For intracellular staining of phosphorylated-STAT3 (pSTAT3), cells were fixed, permeablized and then stained with fluorescently-labeled antibodies specific to tyrosine 705-phosphorylated STAT3 (pSTAT3; BD Biosciences) or an isotype control. mRNA was isolated from PBMC from baseline and Week 2 draw during RT from 6 patients. Expression of 730 genes selected for immune profiling was evaluated by nCounter Immune Cell Profiling Assay (Nanostring) and data was analyzed using nSolver software (Nanostring). Results: CRT resulted in the accumulation of potently immunosuppressive polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs; HLA-DRloCD14-CD15+) in circulation of HNSCC patients. The PMN-MDSCs had high levels of activated STAT3, which correlated with the expression of immune checkpoint inhibitor, programmed death-ligand 1 (PD-L1). The analysis of gene expression in patients' PBMC indicated increased expressions of multiple protein mediators that promote immune suppression and MDSC functions such as IL-1β (20.7 fold, p=1.59E-5), IDO (3.6 fold, p=0.1) and VEGF (13.2 fold, p=7.97E-6) during RT. Pathway analysis using KEGG data base predicted that RT enhanced NF-κB signaling in PBMC. In contrast, number of circulating CD3+ T cell was significantly reduced and expression of genes involved in T-cell cytotoxicity including Granzymes A/K/M and Perforin-1 were decreased by greater than twice (p Conclusion: The data suggest that RT induces accumulation of PMN-MDSC in circulation and activation of STAT3 which positively regulates suppressive function of MDSC. Correspondingly, the percentage of T cells in circulation and the expression level of genes regulating cytotoxic functions were significantly reduced during RT. Taken together, the results suggest that RT could induce tolerogenic effects in HNSCC patients. Our further studies will test the feasibility of using the TLR9-targeted STAT3 inhibitors, alone or combination with checkpoint inhibitors, to overcome immune suppression and improve RT efficacy in syngeneic mouse models of HNSCC. Citation Format: Haejung Won, Sagus Sampath, Erminia Massarelli, Ellie Maghami, Marcin Kortylewski. Chemo-radiotherapy induces tolerogenic STAT3 signaling in circulating myeloid-derived suppressor cells in patients with head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 35.