Objectives-Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT.Materials and Methods-We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 -06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT.Results-The response rate was 86% (n=63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p=. 045 and p=.016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23 -3.67), p =.

Specific viral targeting into intrahepatic tumors remains critical for adenovirus gene therapy in liver cancer. We previously showed that ionizing radiation increases adenovirus uptake and transgene expression in cells and colon cancer xenografts. Here, we tested whether radiation induces viral uptake through virus-cell membrane interaction. We found that radiation (8 Gy) induced adenoviral gene transfer in rat hepatocytes (WB) and human colon carcinoma cells (LoVo). This induction (24.4-and 6.5-fold, respectively) and viral uptake were significantly diminished by preincubation with antibody for Dynamin 2 but not for Coxsackie adenovirus receptor or for integrin A v . Radiation-induced Dynamin 2 expression was detected by immunohistochemical staining and by increased mRNA levels for Dynamin 2 in WB (1.5-fold) and LoVo (2.2-fold) cells. Specific small interference RNA (siRNA) transfection significantly inhibited Dynamin 2 expression in various tumor cell lines (LoVo, D54, and MCF-7) and abolished the radiation induction of Dynamin 2. Likewise, radiation-induced viral gene transfer in these cells (6.5-, 5.5-, and 9.0-fold, respectively) was significantly reduced in siRNAtransfected cells (2.7-, 3.7-, and 5.0-fold, respectively). Moreover, viral uptake in LoVo tumor xenografts was significantly increased in s.c. tumors (10.9-fold) when adenovirus was given i.v. at 24 hours after tumor irradiation, coincident with an elevated Dynamin 2 expression in irradiated tumors. These data suggest that ionizing radiation induces adenovirus gene transfer in cells and tumor xenografts by regulating viral uptake, potentially through interaction with cellular Dynamin 2 and thus should provide insight into improving adenovirus targeting in tumors. (Cancer Res 2005; 65(13): 5493-7)

Purpose: Liver damage by radiation limits its efficacy in cancer treatment. As radiation can generate apoptotic signals, we wished to examine the potential to protect the liver by inhibiting apoptosis through two key mediators, FAS and tumor necrosis factor receptor 1 (TNFR1). Experimental Design: Radiation-induced liver damage was assessed by serum aspartate aminotransferase and alanine aminotransferase, hepatocyte micronucleus formation, and apoptosis assays (terminal nucleotidyl transferase^mediated nick end labeling and caspase-3 cleavage) in mice. Protection was evaluated by pretreating mice with antisense oligonucleotides (ASO) for FAS or TNFR1 prior to radiation. TNF-a production in liver and in Kupffer cells were determined by ELISA. Results: Radiation increased liver FAS and TNFR1 transcription in a dose-and time-dependent manner (maximized at 25 Gy and 8 hours postirradiation). Pretreatment with ASOs for FAS and TNFR1 resulted in the inhibition of liver FAS and TNFR1 by 78% and 59%, respectively. Inductions of serum aspartate aminotransferase and alanine aminotransferase were observed at 2 hours after radiation and could be reduced by pretreating mice with ASO for TNFR1 but not FAS or control oligonucleotide. Radiation-induced liver apoptosis (terminal nucleotidyl transferase^mediated nick end labeling staining and caspase-3 activation on Western blot) and hepatocyte micronucleus formation were reduced by pretreatment with ASO for TNFR1. In addition, radiation stimulated TNF-a production both in irradiated liver and in cultured Kupffer cells by >50% and 100%, respectively. Conclusion:This study suggests that ionizing radiation activates apoptotic signaling through TNFR1 in the liver, and thus provides a rationale for anti-TNFR1 apoptotic treatment to prevent radiation-induced liver injury.

Purpose: FDG-PET adds to clinical factors, such tumor stage and p16 status, in predicting local (LF), regional (RF), and distant failure (DF) in poor prognosis locally advanced head and neck cancer (HNC) treated with chemoradiation. We hypothesized that MRI-based quantitative imaging (QI) metrics could add to clinical predictors of treatment failure more significantly than FDG-PET metrics.Materials and methods: Fifty four patients with poor prognosis HNCs who were enrolled in an IRB approved prospective adaptive chemoradiotherapy trial were analyzed. MRI-derived gross tumor volume (GTV), blood volume (BV), and apparent diffusion coefficient (ADC) pre-treatment and mid-treatment (fraction 10), as well as pre-treatment FDG PET metrics, were analyzed in primary and individual nodal tumors. Cox proportional hazards models for prediction of LRF and DF free survival were used to test the additional value of QI metrics over dominant clinical predictors.Results: The mean ADC pre-RT and its change rate mid-treatment were significantly higher and lower in p16– than p16+ primary tumors, respectively. A Cox model identified that high mean ADC pre-RT had a high hazard for LF and RF in p16– but not p16+ tumors (p = 0.015). Most interesting, persisting subvolumes of low BV (TVbv) in primary and nodal tumors mid-treatment had high-risk for DF (p < 0.05). Also, total nodal GTV mid-treatment, mean/max SUV of FDG in all nodal tumors, and total nodal TLG were predictive for DF (p < 0.05). When including clinical stage (T4/N3) and total nodal GTV in the model, all nodal PET parameters had a p-value of >0.3, and only TVbv of primary tumors had a p-value of 0.06.Conclusion: MRI-defined biomarkers, especially persisting subvolumes of low BV, add predictive value to clinical variables and compare favorably with FDG-PET imaging markers. MRI could be well-integrated into the radiation therapy workflow for treatment planning, response assessment, and adaptive therapy.