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Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) have potentially complementary advantages and limitations for treating inoperable renal cell carcinoma (RCC). Combining SBRT and MWA may optimize tumor control and toxicity for patients with larger (>5 cm) RCCs or those with vascular involvement. We retrospectively reviewed patients at our institution with RCC treated between 2014 – 2018 to identify patients treated with a combination of SBRT and MW ablation. Seven patients with RCC were treated with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, two with grade 1 hematuria and one with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR preceding and following SBRT and MW ablation was 69 mL/min/1.73m2 and 68 mL/min/1.73m2 (p=0.19) respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

Purpose: Chemoradiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers. Experimental Design: An SUVmax most prognostic for freedom from progression (FFP) was identified and compared with known prognostic clinical variables in a cohort of 318 patients treated with definitive radiation with prospectively collected clinical data. Gene set enrichment analysis (GSEA) and CIBERSORT of whole-transcriptome data from 68 patients were used to identify biological pathways and immune cell subpopulations associated with high SUVmax. IHC using a tissue microarray (TMA, N = 82) was used to validate the CIBERSORT findings. The impact of macrophages on cervical cancer glucose metabolism was investigated in coculture experiments. Results: SUVmax Conclusions: SUVmax is a prognostic marker in cervical cancer that is associated with activation of inflammatory pathways and tumor infiltration of myeloid-derived immune cells, particularly macrophages. Macrophages contribute to changes in cervical cancer glucose metabolism. See related commentary by Williamson et al., p. 4136

BACKGROUND This study evaluates the prognostic significance of 18 F-fluorodeoxyglucose-positron emission tomography ([F-18]FDG-PET)-derived metabolic tumor volume (MTV) in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) in the context of AJCC 8th edition staging. METHODS We performed a retrospective study of HPV-associated OPSCCs treated with postoperative or definitive radiation. The prognostic significance of pretreatment MTV for freedom from recurrence (FFR), freedom from distant metastasis (FFDM), and overall survival (OS) was determined using Kaplan-Meier analysis. Multivariate analysis (MVA) was performed using Cox regression. RESULTS In this 153-patient cohort, stratifying by the optimum MTV (24 cm3 ) was prognostic for FFR (P = .0002), FFDM (P = .001), and OS (P < .0001). Metabolic tumor volume (MTV) was prognostic of FFR in AJCC 8th edition stage I/II (P = .03), and stage III patients (P = .04). On multivariate analysis only MTV was a significant factor for OS. CONCLUSION Metabolic tumor volume (MTV) is a significant prognostic factor in HPV-associated OPSCCs, independent of AJCC 8th edition stage.

Background This study investigated the spatial relationship of 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography ([18F]FDG-PET) standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) derived from magnetic resonance (MR) diffusion imaging on a voxel level using simultaneously acquired PET/MR data. We performed an institutional retrospective analysis of patients with newly diagnosed cervical cancer who received a pre-treatment simultaneously acquired [18F]FDG-PET/MR. Voxel SUV and ADC values, and global tumor metrics including maximum SUV (SUVmax), mean ADC (ADCmean), and mean tumor-to-muscle ADC ratio (ADCT/M) were compared. The impacts of histology, grade, and tumor volume on the voxel SUV to ADC relationship were also evaluated. The potential prognostic value of the voxel SUV/ADC relationship was evaluated in an exploratory analysis using Kaplan-Meier/log-rank and univariate Cox analysis. Results Seventeen patients with PET/MR scans were identified. There was a significant inverse correlation between SUVmax and ADCmean, and SUVmax and ADCT/M. In the voxelwise analysis, squamous cell carcinomas (SCCAs) and poorly differentiated tumors showed a consistent significant inverse correlation between voxel SUV and ADC values; adenocarcinomas (AdenoCAs) and well/moderately differentiated tumors did not. The strength of the voxel SUV/ADC correlation varied with metabolic tumor volume (MTV). On log-rank analysis, the correlation between voxel SUV/ADC values was prognostic of disease-free survival (DFS). Conclusions In this hypothesis-generating study, a consistent inverse correlation between voxel SUV and ADC values was seen in SCCAs and poorly differentiated tumors. On univariate statistical analysis, correlation between voxel SUV and ADC values was prognostic for DFS.

Metabolic reprogramming is a hallmark of cancer. Altered metabolism provides a survival advantage for cancer cells during tumorigenesis by supplying resources needed for uncontrolled growth and increased rates of cell division. As tumors grow beyond the limits of diffusion, altered metabolism provides a selective advantage in the context of nutrient deprivation. Many cancer therapies, including radiation, are known to impact tumor metabolism while the metabolic state of a cancer may contribute to radioresistance. Preclinical and clinical evidence exists to support combinations of radiation therapy with drugs that affect, for example, oxidative, glucose, glutamine, one-carbon, nucleotide, or iron metabolism in cancers. Work is ongoing to determine optimal strategies for combining these drugs with conventionally fractionated and hypofractionated radiation schemes. New strategies, including dietary manipulation during the course of radiation therapy, are currently being explored. Targeting tumor metabolism is a rapidly evolving and promising field of oncology and will be reviewed here in more detail.

34 Background: Management of BCR PCa requires accurate assessment of location and extent of recurrent disease. FACBC has been shown to be a sensitive modality for detection and localization of recurrent disease but treatment guidelines are based on the findings of conventional (conv) imaging, including computed tomography, magnetic resonance imaging, or bone scintigraphy, and little is known about how prior treatment impacts FACBC findings and concordance with conv scans. Methods: This single-center retrospective study included 137 patients (pts) who had FACBC for BCR at the University of Wisconsin-Madison from 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts were classified by type of primary treatment for localized PCa, either radical prostatectomy (RP) or radiation therapy (RT). Findings of conv scans performed within 4 weeks prior or any time after FACBC were collected. Results: 105 pts had RP and 32 pts had RT as their primary PCa treatment. Gleason score and PSA at diagnosis were similar between groups. Median PSA at time of FACBC was higher in the RT compared to RP group (3.3 vs 0.7 ng/dL) and median time from initial diagnosis to FACBC was longer (70 vs 55 months). Frequency of (+) FACBC findings was higher in the RT group (66% vs 47%); only 3% of pts in the RT group had a (-) FACBC compared to 29% in the RP group. The rate of (+) lesions in the prostate/prostate bed was higher in the RT group (41% vs 22%), while the rate of (+) lesions in pelvic nodes and distant sites was similar between groups. Of 69 pts who also had conv imaging, 61% had concordant conv imaging findings. In the RT group, conv and FACBC findings were similar in 47% of pts and not similar in 28%. In the RP group, conv and FACBC findings were similar in 26% of pts and not similar in 17%. Management after FACBC is listed in table. Median time from FACBC to first (+) conv scans was 6 (range: 0-18) and 5 (range: 0-17) months for RT and RP groups, respectively. Conclusions: In this large retrospective cohort, pts treated with initial RT had a longer median time from diagnosis to FACBC and higher median PSA at the time of FACBC compared to the RP group. RT patients had a higher rate of (+) FACBC findings but were more likely to continue on observation. The median time from FACBC to first (+) conv scan was 5-6 months, supporting the role of FACBC in earlier detection of recurrent disease in both groups of patients. Further analysis of concordance between FACBC and conv imaging is in process. [Table: see text]

BACKGROUND Atypical teratoid rhabdoid tumors (ATRTs) are rare brain tumors that occur primarily in children under the age of 3 years. This report evaluates the treatment approach and survival outcomes in a large cohort of patients treated in the United States. METHODS Using the National Cancer Database, the analysis included all ATRT patients aged 0 to 18 years who were diagnosed between 2004 and 2012 and had complete treatment data. RESULTS Three hundred sixty-one ATRT patients were evaluated. The 5-year overall survival (OS) rate was 29.9%, and it was significantly lower for children who were less than 3 years old (5-year OS, 27.7%) versus those who were 3 years old or older (5-year OS, 37.5%; P

Dysregulated glucose and redox metabolism are near universal features of cancers. They therefore represent potential selectively toxic metabolic targets. This review outlines the preclinical and clinical data for targeting glucose and hydroperoxide metabolism in cancer, with a focus on drug strategies that have the most available evidence. In particular, inhibition of glycolysis using 2-deoxyglucose, and inhibition of redox metabolism using the glutathione pathway inhibitor buthionine sulfoximine and the thioredoxin pathway inhibitor auranofin, have shown promise in preclinical studies to increase sensitivity to chemotherapy and radiation by increasing intracellular oxidative stress. Combined inhibition of glycolysis, glutathione, and thioredoxin pathways sensitizes highly glycolytic, radioresistant cancer models in vitro and in vivo. Although the preclinical data support this approach, clinical data are limited to exploratory trials using a single drug in combination with either chemotherapy or radiation. Open research questions include optimizing drug strategies for targeting glycolysis and redox metabolism, determining the appropriate timing for administering this therapy with concurrent chemotherapy and radiation, and identifying biomarkers to determine the cancers that would benefit most from this approach. Given the quality of preclinical evidence, dual targeting of glycolysis and redox metabolism in combination with chemotherapy and radiation should be further evaluated in clinical trials.

Objectives The goals of this work were (1) to determine the effect of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, and EEG on the decision to perform temporal lobe epilepsy (TLE) surgery, and (2) to determine if FDG-PET, MRI, or EEG predicts surgical outcome. Methods All PET scans ordered (2000–2010) for epilepsy or seizures were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, κ statistics, univariate analysis, and logistic regression. Results Of the 186 patients who underwent FDG-PET, 124 had TLE, 50 were surgical candidates, and 34 had surgery with post-operative follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy ( P P Conclusion MRI showed a trend toward having the most influence on surgical candidacy, but only FDG-PET predicted surgical outcome.

BACKGROUND: We present in vitro and in vivo imaging and therapeutic studies using a novel alkylphosphocholine (APC)-based molecular scaffold (CLR1404) that combines selective targeting of cancer (including cancer stem cells) with broad-spectrum activity against many different cancer types. CLR1404 APC analogs were created to exploit the finding that phospholipid ethers selectively accumulate in many cancers versus normal cells. METHODS: Depending on the iodine isotope used, radioiodinated CLR1404 is either a PET imaging (124I) or molecular radiotherapeutic agent (131I), with fluorescence analogs created by replacing iodide with various fluorophores. Standard tissue culture, xenograft and molecular biology protocols were used for these studies. RESULTS: CLR1404 displayed preferential uptake and retention in cancer and cancer stem cells compared to normal cells in vitro and in vivo. After 24 hours, selective uptake of fluorescent or radioiodinated CLR1404 analogs by multiple human cancer cell lines in vitro compared to patient-matched normal human fibroblasts was observed (2.3-2.8x). CLR1404 showed highly specific labeling of both human patient-matched glioblastoma stem cells and serum-cultured glioblastoma cells (3x over minimal labeling of control normal human astrocytes and neural stem cells). Lipid raft disruption reduced in vitro CLR1404 analog uptake.In vivo, CLR1404 analogs displayed prolonged tumor-selective retention in 55 different rodent and human cancer models (including triple-negative breast, lung, pancreatic, colorectal, prostate, renal, melanoma, GBM). Tumor accumulation was seen by 24 hours with continued normal tissue clearance between 48-120 hours. In vivo cancer stem cell labeling was also demonstrated. CLR1404 analogs do not visualize inflammatory or premalignant lesions (unlike currently used 18F-fluorodeoxy glucose (FDG)-PET tumor imaging).131I-CLR1404 also displayed therapeutic efficacy (tumor growth suppression, survival extension) especially in renal, colorectal, ovarian, prostate and triple-negative breast cancer, GBM models. CONCLUSIONS: The novel APC CLR1404 analogs potentially offer a powerful multi- modality strategy to detect, treat and follow primary and metastatic cancers in humans. Initial clinical trials strongly suggest CLR1404 has similar broad tumor targeting and retention properties in animals and humans. The pathological correlation between CLR1404 imaging and GBM is being tested in an ongoing multi-institutional Phase II clinical trial. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.