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Complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with incorrect level treatments of the spine. The purpose of this work was to mitigate such challenges by fully automating the treatment planning process for diagnostic and simulation computed tomography (CT) scans.Vertebral bodies are labeled on CT scans of any length using 2 intendent deep-learning models-mirroring 2 different experts labeling the spine. Then, a U-Net++ architecture was trained, validated, and tested to contour each vertebra (n = 220 CT scans). Features from the CT and auto-contours were input into a random forest classifier to predict whether vertebrae were correctly labeled. This classifier was trained using auto-contours from cone beam computed tomography, positron emission tomography/CT, simulation CT, and diagnostic CT images (n = 56 CT scans, 751 contours). Auto-plans were generated via scripting. Each model was combined into a framework to make a fully automated clinical tool. A retrospective planning study was conducted in which 3 radiation oncologists scored auto-plan quality on an unseen patient cohort (n = 60) on a 5-point scale. CT scans varied in scan length, presence of surgical implants, imaging protocol, and metastatic burden.The results showed that the uniquely designed convolutional neural networks accurately labeled and segmented vertebral bodies C1-L5 regardless of imaging protocol or metastatic burden. Mean dice-similarity coefficient was 85.0% (cervical), 90.3% (thoracic), and 93.7% (lumbar). The random forest classifier predicted mislabeling across various CT scan types with an area under the curve of 0.82. All contouring and labeling errors within treatment regions (11 of 11), including errors from patient plans with atypical anatomy (eg, T13, L6) were detected. Radiation oncologists scored 98% of simulation CT-based plans and 92% of diagnostic CT-based plans as clinically acceptable or needing minor edits for patients with typical anatomy. On average, end-to-end treatment planning time of the clinical tool was less than 8 minutes.This novel method to automatically verify, contour, and plan palliative spine treatments is efficient and effective across various CT scan types. Furthermore, it is the first to create a clinical tool that can automatically verify vertebral level in CT images.

Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA gene sequencing was used to perform diversity and taxonomic characterization of the SCCA microbiome. Wilcoxon signed-rank tests were used to compare microbial diversity and abundance over time. Wilcoxon rank-sum tests were used to compare microbial profiles of high and low toxicity groups.Twenty-two patients with SCCA were included in this study with a median age of 58.5 years (range, 39-77 years), and 18 (82%) were women. Alpha diversity remained relatively stable throughout chemoradiation therapy except for decreases in the Observed Features (P = .03) index at week 5 relative to baseline. Tumor microbial compositions changed significantly by the end of treatment (P = .03). Differential enrichment of bacteria at specific time points occurred during treatment, including the enrichment of Clostridia at follow-up (vs week 5, q = 0.019) and Corynebacterium at week 5 (vs baseline, q = 0.015; vs follow-up, q = 0.022). Patients experiencing high toxicity at week 5 had higher relative counts of Clostridia, Actinobacteria, and Clostridiales at baseline (P = .03 for all).The tumor microbiome changes during and after chemoradiation therapy, and patient-reported toxicity levels are associated with patients' microbial profiles. Further studies into these microbial characterizations and toxicity associations will elucidate the tumor microbiome's role in predicting treatment-related outcomes for patients with SCCA.

Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumor-specific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16+ patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non–HPV-specific T cells did not. In HPV16+ patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.

Background Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. Method Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient’s clinical characteristics. Results Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. This community was prevalent in patients with larger, advanced stage tumors. Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. This community was prevalent in patients with smaller, early-stage tumors. Conclusions In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors.

In multiple anatomic sites, patients with cancers associated with the Human Papillomavirus (HPV) experience better locoregional control and overall survival after radiotherapy and/or chemoradiotherapy than patients with HPV-negative cancers. These improved outcomes suggest that relatively unique biological features in HPV-positive cancers may increase sensitivity to DNA damaging agents as well as an impaired DNA damage response. This review will address potential biological mechanisms driving this increased sensitivity of HPV-positive cancer to radiation and/or chemotherapy. This review will discuss the clinical and preclinical observations that support the intrinsic radiosensitivity and/or chemosensitivity of HPV-positive cancers. Furthermore, this review will highlight the molecular mechanisms for increased radiation sensitivity using the classical "4 Rs" of radiobiology: repair, reassortment, repopulation, and reoxygenation. First, HPV-positive cancers have increased DNA damage due to increased oxidative stress and impaired DNA damage repair due to the altered activity TP53, p16, TIP60, and other repair proteins. Second, irradiated HPV-positive cancer cells display increased G2/M arrest leading to reassortment of cancer cells in more radiosensitive phases of the cell cycle. In addition, HPV-positive cancers have less radioresistant cancer stem cell subpopulations that may limit their repopulation during radiotherapy. Finally, HPV-positive cancers may also have less hypoxic tumor microenvironments that make these cancers more sensitive to radiation than HPV-negative cells. We will also discuss extrinsic immune and microenvironmental factors enriched in HPV-positive cancers that facilities responses to radiation. Therefore, these potential biological mechanisms may underpin the improved clinical outcomes often observed in these virally induced cancers.

Purpose Women remain underrepresented at all levels within the field of radiation oncology. We sought to study current female residents’ experiences and concerns to inform interventions to promote gender equity. Furthermore, we evaluated interest in a professional society specifically for women radiation oncologists. Methods and Materials An anonymous 76-item survey was designed and distributed to current women residents in radiation oncology in 2017-2018. Analyses describe personal, program, and family characteristics and experiences before and after joining the field. Results Of 170 female residents surveyed, 125 responded (74% response rate). Over one-quarter were in programs with ≤2 female residents (29%) and ≤2 female attendings (29%). One-third (34%) reported having children. Over half (51%) reported that lack of mentorship affected career ambitions. Over half (52%) agreed that gender-specific bias existed in their programs, and over a quarter (27%) reported they had experienced unwanted sexual comments, attention, or advances by a superior or colleague. Only 5% reported no symptoms of burnout. Almost all (95%) agreed that radiation oncology is perceived as family friendly; however, only 52% agreed that it actually is. An overwhelming majority (90%) expressed interest in joining a professional group for women in radiation oncology. Conclusions In the first study to our knowledge to focus specifically on the experiences of women residents in radiation oncology, a number of areas for potential improvement were highlighted, including isolation and underrepresentation, mentorship needs, bias and harassment, and gender-based obstacles such as need for support during pregnancy and motherhood. These findings support the organization of groups such as the Society for Women in Radiation Oncology, which seeks to target these needs to promote gender equity.

When pancreatic cancer cannot be removed surgically, patients frequently experience morbidity and death from progression of their primary tumor. Radiation therapy (RT) cannot yet substitute for an operation because radiation causes fatal bleeding and ulceration of the nearby stomach and intestines before achieving tumor control. There are no FDA-approved medications that prevent or reduce radiation-induced gastrointestinal injury. Here, we overcome this fundamental problem of anatomy and biology with the use of the oral EGLN inhibitor FG-4592, which selectively protects the intestinal tract from radiation toxicity without protecting tumors. A total of 70 KPC mice with autochthonous pancreatic tumors received oral FG-4592 or vehicle control ± ablative RT to a cumulative 75 Gy administered in 15 daily fractions to a limited tumor field. Although ablative RT reduced complications from local tumor progression, fatal gastrointestinal bleeding was observed in 56% of mice that received high-dose RT with vehicle control. However, radiation-induced bleeding was completely ameliorated in mice that received high-dose RT with FG-4592 (0% bleeding, P < 0.0001 compared with vehicle). Furthermore, FG-4592 reduced epithelial apoptosis by half (P = 0.002) and increased intestinal microvessel density by 80% compared with vehicle controls. EGLN inhibition did not stimulate cancer growth, as treatment with FG-4592 alone, or overexpression of HIF2 within KPC tumors independently improved survival. Thus, we provide a proof of concept for the selective protection of the intestinal tract by the EGLN inhibition to enable ablative doses of cytotoxic therapy in unresectable pancreatic cancer by reducing untoward morbidity and death from radiation-induced gastrointestinal bleeding. Significance: Selective protection of the intestinal tract by EGLN inhibition enables potentially definitive doses of radiation therapy. This might allow radiation to be a surgical surrogate for unresectable pancreatic cancer.

PURPOSE/OBJECTIVE(S) Pelvic insufficiency fractures and decreased bone mineral density (BMD) can occur in women treated with radiotherapy (RT) for gynecologic cancers. The purpose of this study was to compare the magnitude of BMD changes inside and outside of the radiation field in patients treated with radiation +/- chemotherapy for cervical cancer. MATERIALS/METHODS In an IRB-approved prospective study, women (N = 78) with cervical cancer were assessed with serial tomographic scans and dual-energy x-ray absorptiometry (DXA) scans to evaluate the incidence of pelvic fractures (previously reported) and post-treatment BMD changes. Patients were treated with definitive RT or chemoradiation (CRT) at a single institution between 09/2008 and 07/2015. DXA scans were obtained at baseline (before CRT), 3 months, 1 year, and 2 years after completion of therapy. Serial BMD values at L1, L2, L3 and L4 were extracted from DXA reports. Patients with a pre-treatment history of pelvic fractures, bone metastases, or pelvic RT were excluded. The current analysis focused on a subset of 78 patients whose RT fields had upper borders below L1 and above L4, permitting a comparison of BMD changes in the field (L4) with those in a vertebral body outside the field (L1). Linear mixed models (LMM) were performed to examine the impact of radiotherapy on BMD change over time, and were adjusted for covariates (age, menopausal status, BMI, number of chemotherapy cycles). RESULTS The median age of 78 patients was 45.5 years (range 23-88); all received RT and 76/78 (97.5%) received concurrent CRT. Treatment was associated with a significant decline in BMD in all 4 lumbar vertebral bodies over time, P < 0.05 with nadir at 3 months (L4) and 1 year (L1). By pairwise comparisons at 3 months and 2 years after treatment, BMD in L4 (inside RT field, P = 0.037) significantly improved while BMD in L1 (outside RT field) did not significantly change. After controlling for covariates noted above, there was no significant difference in BMD between 3 months and 2 years. Levels of C-terminal telopeptide of type I collagen (P = 0.018), bone alkaline phosphatase (P < 0.001), and number of chemotherapy cycles (P = 0.031) were significant predictors of L1 BMD loss. A trend of higher BMD at all time points was found for patients who were premenopausal versus postmenopausal at study entry. At 1- and 2-years of follow-up, trends towards BMD at levels higher than baseline were seen for patients who received hormone replacement therapy (HRT) after RT. CONCLUSION Significant BMD loss following radiation treatment in all lumbar vertebrae (both in and out of field) was observed. On multivariate analysis, in-field vertebral bodies experienced no additional significant BMD decline earlier than those out-of-field, suggesting multifactorial contributors to bone density loss. HRT may improve BMD recovery and emphasizes the need for HRT after radiotherapy in appropriate premenopausal women. AUTHOR DISCLOSURE J. Wu: None. D.S. Lakomy: None. B. Fellman: None. M.P. Salcedo: IGCS-International Gynecologic Cancer Society, Brazilian Federation of Gynecology and Obstetricians (FEBRASGO)/BRAZIL (Federacao Brasileira de Ginecologia e Obstetricia, FEBRASGO). A. Sood: Consultant; Kiyatec, Astra Zeneca. Stock; BioPath. sponsored research; M-Trap. A. Jhingran: American Board of Radiology. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant. R.B. Iyer: None. C. Jimenez: None. L. Colbert: None. K. Schmeler: None. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca.

Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumor-specific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy (CRT) or affects survival. We used functional T-cell assays to identify candidate HPV-specific T-cells and T- cell motifs common across 86 patients with HPV-related cancers. These HPV-specific clones and E7-related motifs expanded over the course of treatment, whereas non-HPV-specific T-cells did not. In HPV16+ patients, improved recurrence-free survival was associated with this HPV-responsive T-cell expansion during CRT.

The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.

As brachytherapy utilization rates decline, we sought to evaluate the state of brachytherapy training during radiation oncology residency.US radiation oncology residents in the Association of Residents in Radiation Oncology database were sent an online questionnaire regarding brachytherapy training. Survey questions addressed a wide array of topics, and responses were often given on a 1 to 5 Likert-type scale that reflected strength of opinion. Postgraduate year (PGY) 4/5 respondents' answers were analyzed. Descriptive statistics were generated, and rank correlation analyses (Kendall's τ coefficient and Wilcoxon signed-rank test) were used for comparisons.The survey was completed by 145 of 567 residents (62% being PGY4/5). Of PGY4/5 respondents, 96% (86 of 90) believed learning brachytherapy during residency was important, and 72% (65 of 90) felt their program valued brachytherapy training. Resident brachytherapy comfort varied by site, decreasing as follows: gynecologic, prostate, breast, skin. The current intracavitary 15-case minimum was believed adequate by most, but only a minority believed the 5-case interstitial minimum was adequate. Most respondents (59%) believed that caseload was the greatest barrier to achieving independence in brachytherapy. Significant support exists for American Brachytherapy Society training courses and on-the-job education to enhance training, but enthusiasm about pursuing brachytherapy fellowship training was low. Most respondents expressed confidence in developing a brachytherapy practice (54%); however, this was significantly lower than the rate of those confident in developing a stereotactic body radiation therapy/stereotactic radiosurgery program (97%) (P .001). Furthermore, there was an association between aggregate number of brachytherapy cases performed and resident confidence in starting a brachytherapy practice (τ = 0.37; P .001).Brachytherapy is an important component of residency training that is valued by residents and programs. Because caseload was the greatest perceived barrier in brachytherapy training, with confidence correlated with case volume, attempts should be made to expand opportunities for training experiences that are feasible to complete during residency.

Purpose Radiation therapy has direct cytotoxic effects on tumor-infiltrating lymphocytes, but it also has immune stimulatory effects that increase immune cell infiltration. The dynamics of these competing effects on immune cells at the site of the tumor are poorly characterized during chemoradiation treatment (CRT) because of the difficulty of obtaining consecutive tumor biopsies. We used a minimally invasive cervical cytobrushing method to analyze the kinetics of intratumoral immune cell changes in patients with cervical cancer during CRT. Methods and Materials Cervical brushings were obtained from 20 patients with cervical cancer at baseline and during fractionated radiation therapy and cisplatin (weeks 1, 3, and 5). Matching peripheral blood mononuclear cells were obtained from 9 patients at the same time points. Cells were analyzed using multispectral flow cytometry to identify T cell and myeloid cell subsets and their activation status. Changes in immune cell subsets throughout treatment were calculated using matched-pair analysis with Wilcoxon rank sum test. Results We observed a significant decline in CD3+ total T cells, as well as CD8+ and CD4+ T-cell subsets in the first week of treatment from baseline, followed by variable expansion at weeks 3 and 5. This coincided with higher levels of proliferating CD8+ T cells expressing Ki67 at week 3 of treatment. The percentages of activated CD8+ T cells expressing CD69 continuously increased over the course of treatment, whereas the percentage of activated CD11c+CD11b– dendritic cells was highest during the first week. Many of these changes were not observed in the blood. Conclusions Our results identified immune dynamic changes during CRT, indicating that CRT may be immune activating at the site of the tumor. This study also suggests the importance of sequential analyses of the local tumor microenvironment in addition to peripheral blood.

Purpose/Objective(s) Radiation therapy (RT) has been shown to prolong survival for patients with select oligometastatic cancers. Limited long-term follow-up data exist to determine if the prolonged survival correlates with cure versus a delayed relapse. To investigate this, we evaluated the clinical and disease characteristics of long-term survivors treated with definitive RT for oligometastatic gynecological cancer at our institution. Materials/Methods We performed a landmark analysis in patients with oligometastatic gynecological cancer (OMGC) who survived for at least 5 years following treatment of their metastasis. OMGC was defined as metastasis (maximum of 5 total and 3 per site) present at a distant site at time of diagnosis or at a regional or distant site at time of recurrence. All patients received definitive RT between 2000 and 2015. Demographic and clinical variables were extracted from the medical record. Disease-free survival (DFS) after treatment of the first ROMGC was modeled using Kaplan Meier curves. Results 48 patients with OMGC were analyzed; 20 (41.7%) had ovarian cancer, 16 (33.3%) had uterine cancer, 11 (22.9%) had cervical cancer, 1 (2.1%) had vaginal cancer. Median age was 52 years. A majority (45.8%) were stage III at primary diagnosis. The most common histology was adenocarcinoma (35.4%). The most common site of OMGC was in the pelvic lymph nodes (LN) (40.7%), with the following other sites: para-aortic LN (38.9%), supraclavicular LN (7.4%), lung (5.6%), mediastinal LN (3.7%), and axillary LN (3.7%). The median size was 2 cm. The median [interquartile range (IQR)] total RT dose and fractionation was 62.1 [52.5-64.5] Gy and 2.1 [2-2.2] Gy/fraction. The majority (70.8%) were treated with intensity-modulated RT. 25 (52.1%) patients received concurrent chemoRT (CRT) for their OMGC. After a median follow-up of 9.9 years after OMGC treatment, median [range] DFS for all patients was 73 [4-212] months (mo). 5-year DFS for cervical, uterine, and ovarian cancers was 82% (95% confidence interval [CI], 45-95%), 69% (CI, 41-86%), and 35% (CI, 16-55%), respectively. Patients who received CRT had better median DFS than those treated with RT alone (103 vs. 65 mo, P = 0.18). Patients with nodal OMGC had similar median DFS as those with non-nodal OMGC (73 vs. 66 mo, P = 0.86). During the first OMGC course, patients treated for 1 site had worse median DFS than those treated for 2+ sites (65 vs. 103 mo, P = 0.61). Of all 48 patients, 8 (16.7%) died of gynecologic cancer, 11 (22.9%) died of other causes, 3 (6.3%) had progression of disease. The remaining 26 (54.2%) patients were disease free at long-term follow up. Conclusion Cure is possible for patients treated definitively for OMGC. Patients with cervical cancer, a greater number of treated OMGC sites, and treated with CRT had the longest DFS among this selected cohort. A randomized trial in oligometastatic gynecologic cancer is needed to determine if RT increases overall survival. Author Disclosure K.L. Corrigan: None. A.K. Yoder: None. L.L. Lin: Employee; VA Hospital. Research Grant; Astra Zeneca. Travel Expenses; Astra Zeneca. A. Jhingran; American Board of Radiology. M.M. Joyner: Consultation with executive management and participation in board meetings; Frontline Bioenergy. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L. Colbert: None. K.H. Lu: None. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant.

Antibiotics affect microbial diversity in the gut, leading to dysbiosis and impaired immunity. However, the impact of antibiotics on microbial communities at other sites, such as vagina is less understood. It is also not clear whether changes induced by antibiotics in both microbiomes affect the development of cervical cancer. In this study, we utilized the murine model to evaluate these questions. We show that oral application of broad-spectrum antibiotics in mice changed not only diversity, but composition and sharing of gut and vaginal microbiomes in mice and influenced cervical cancer development in an orthotopic tumor model. Antibiotics decreased richness and diversity indexes in the gut but increased them in the vagina. Some beneficial taxa, such as Bacteroides, Ruminococcaceae, and Lachnospiraceae increased their abundance in the vagina while other pathogenic species, such as Proteobacteria, were decreased. As a result of the changes, mice with greater richness and diversity of the vaginal microbiome after antibiotics exposure were less likely developed tumors. No association between richness and diversity of the gut microbiome and tumor development was identified.

Purpose Patients receiving pelvic radiation for cervical cancer experience high rates of acute gastrointestinal (GI) toxicity. The association of changes in the gut microbiome with bowel toxicity from radiation is not well characterized. Methods and Materials Thirty-five patients undergoing definitive chemoradiation therapy (CRT) underwent longitudinal sampling (baseline and weeks 1, 3, and 5) of the gut microbiome and prospective assessment of patient-reported GI toxicity. DNA was isolated from stool obtained at rectal examination and analyzed with 16S rRNA sequencing. GI toxicity was assessed with the Expanded Prostate Cancer Index Composite instrument to evaluate frequency, urgency, and discomfort associated with bowel function. Shannon diversity index was used to characterize alpha (within sample) diversity. Weighted UniFrac principle coordinates analysis was used to compare beta (between sample) diversity between samples using permutational multivariate analysis of variance. Linear discriminant analysis effect size highlighted microbial features that best distinguish categorized patient samples. Results Gut microbiome diversity continuously decreased over the course of CRT, with the largest decrease at week 5. Expanded Prostate Cancer Index Composite bowel function scores also declined over the course of treatment, reflecting increased symptom burden. At all individual time points, higher diversity of the gut microbiome was linearly correlated with better patient-reported GI function, but baseline diversity was not predictive of eventual outcome. Patients with high toxicity demonstrated different compositional changes during CRT in addition to compositional differences in Clostridia species. Conclusions Over time, increased radiation toxicity is associated with decreased gut microbiome diversity. Baseline diversity is not predictive of end-of-treatment bowel toxicity, but composition may identify patients at risk for developing high toxicity.

e15504 Background: Among patients with anal cancer undergoing chemoradiotherapy, the association between the microbiome and toxicity is not well documented. We sought to quantify the gastrointestinal-related patient-reported outcomes (PROs) and local microbiome profiles of patients with anal cancer receiving chemoradiotherapy in order to check for potential profiles that can help in predicting toxicity during treatment. Methods: We prospectively followed patients with non-metastatic squamous cell carcinoma of the anal canal who received definitive chemoradiotherapy. Anorectal swab samples were collected before treatment initiation and at 4 subsequent timepoints. Consequently, PROs were collected using the bowel subdomain of the Expanded Prostate Cancer Index Composite (EPIC). Samples were sequenced using 16S rRNA of the V4 region. Sequence reads were grouped by amplicon sequence variants (ASV’s) representative of unique bacterial species. We then used Linear discriminant analysis Effect Size (LEfSe) with an effect size of 4 to identify taxa at baseline that were differentially enriched in patients with high vs. low toxicity by end of treatment. We compared the EPIC scores with the relative abundance of species identified in the LEfSe using a paired Wilcoxon test. Results: The study included 22 patients (18 women and 4 men), whose median age was 59 years. Most patients were Stage III (59%) with negative HIV status (94%). The majority of patients (91%) received standard of care chemoradiotherapy. Overall toxicity was the highest at week 5 of treatment. At all individual time points, alpha diversity of the microbiome did not correlate with patient-reported GI function, additionally overall baseline diversity was not predictive of eventual GI outcomes. The LEfSe identified that patients with low patient reported toxicity at week 5 had higher of abundance of Selenomonas at baseline, while patients with higher toxicity had high abundance of baseline Actinobacteria, Peptoniphilus, Clostridiales , and Clostridia. When comparing the relative abundance of bacterial species among patients with high and low toxicities, patients with higher relative abundance of Clostridia and Actinobacteria had significantly higher toxicity (p = 0.03). Conclusions: Certain microbiome profiles at baseline are associated with anal cancer patients’ gastrointestinal-related PROs during chemoradiation. Our data provide novel avenues to study the potential uses of the local microbiome as a biomarker in predicting treatment toxicities in anal cancer.

24 Background: A rapid access bone metastases clinic (RABC) was instituted at MD Anderson Cancer Center (MDACC) to allow outpatient consult, simulation and radiation treatment (RT) initiation in < 6 hours for patients with painful bone metastases. Patients underwent multidisciplinary evaluation with orthopedics and radiation oncology. One aspect of financial toxicity is distress due to out-of-pocket (OOP) cost associated with a treatment. We hypothesized the RABC would decrease financial toxicity for MDACC patients over traditional RT. Methods: RABC patients surveyed between April 2018 and January 2020 were included. Patients were asked to estimate OOP cost for RT (including travel and treatment cost) and perceived cost burden of treatment. Travel distance was hometown distance to MDACC. Subset analyses were performed for patients receiving single fraction (1fx) and 2-5 fractions (2-5fx). Estimated OOP cost (1fx: RABCN= 34, nonRABCN= 20; 2-5fx: RABCN= 4, nonRABCN= 22), perceived cost burden (1fx: RABCN= 32, nonRABCN= 27; 2-5fx: RABCN= 7, nonRABCN= 38) and travel distance (1fx: RABCN= 34, nonRABCN= 28; 2-5fx: RABCN= 7, nonRABCN= 38) were compared using a Mann-Whitney U Test. Travel distance was also compared to OOP cost. Patients treated with 6+ fractions were excluded. Results: Median estimated OOP cost was significantly lower for 1fx RABC patients vs. 1fx non-RABC patients ($450 [IQR $187.5-$1,050] vs. $2,000 [$625-$4,000]; p = 0.008), but there was no significant difference for 2-5fx ($1,900 vs. $1,375; p = 0.593). Overall patient satisfaction with cost burden was high regardless of treatment setting (1fx: 10 [8-10]; 2-5fx: 10 [8-10]). Median travel distance was not significantly different between clinics (1fx: 245 [39.8-351.5] vs. 262.5 [83-879.3], p = 0.3651; 2-5fx: 274 [36-1293] vs. 176 [25-626], p = 0.2721). Travel distance was directly correlated with out of pocket cost for single fraction (1fx: R2= 0.125, p = 0.0109; 2-5fx: R2= 0.037, p = 0.3433). Conclusions: The establishment of a RABC at MDACC significantly decreased financial toxicity for 1fx patients receiving palliative RT, but not in the 2-5fx cohort. Increased financial toxicity was associated with longer travel distance for 1fx palliative radiation. Implementation of a similar model in local community centers may decrease financial toxicity for patients receiving palliative radiation.

TPS4670 Background: Local progression causes up to 30% of deaths from pancreatic cancer (PC) and is also a significant source of morbidity. Stereotactic body radiotherapy (SBRT) offers the potential for improved therapeutic index over standard fractionation, but current regimens of 5 fractions of 5-7 Gy/fraction are constrained by nearby organ tolerance and offer only palliation without improving survival. Safe dose escalation may be necessary to improve SBRT efficacy. Avasopasem, a superoxide dismutase mimetic, selectively converts superoxide (O2•-) to hydrogen peroxide (H2O2) and oxygen. O2•-initiates normal tissue damage due to RT. Avasopasem is in a Phase 3 trial (NCT03689712) to reduce RT-induced oral mucositis in head and neck cancer, based on positive results in a randomized Phase 2 trial for that indication (Anderson, JCO 2019). Avasopasem improved the survival of mice receiving 8.5 Gy x 5 to the upper abdomen. Cancer cells are less tolerant to elevated H2O2, and more tolerant to elevated O2•-, than normal cells, and avasopasem demonstrated mechanism-dependent synergy with high dose-fraction RT in a human tumor xenograft with inducible expression of catalase (Sishc, AACR 2018). Thus, adding avasopasem to SBRT may increase both the efficacy and the safety of the latter. Methods: 48 patients with locally advanced PC, who have completed medically-indicated induction chemotherapy, are randomized 1:1 to placebo or avasopasem, 90 mg IV, prior to each of 5 consecutive daily (M-F) SBRT fractions. A phase I/II Late Onset Efficacy/ Toxicity tradeoff (LO-ET) based adaptive design adaptive model drives assignment of SBRT dose escalation in each arm based on a dual endpoint (Gr 3-4 GI toxicity or death; local stable disease or better) by 90 days post SBRT. The planned dose levels are 10, 11 and 12Gy x 5 fractions (BED10 = 100,112.5 and 132Gy, respectively) as an integrated boost to the gross tumor volume (GTV). Primary endpoint: Maximum tolerated dose of SBRT with avasopasem or placebo. Secondary endpoints progression-free survival, response rate, and acute (90 day) and late (12 month) radiation toxicity with avasopasem vs placebo. Exploratory correlative studies include ctDNA, tumor exome/transcriptome sequencing, and immune profiling. Clinical trial information: NCT03340974 .

6036 Background: Diversity of the gut microbiome is associated with response rates for patients receiving immunotherapy. Studies investigating the gut microbiome and outcomes in cancer patients often do not adjust for confounding patient and tumor characteristics. We sought to identify independent gut microbial risk factors in cervical cancer (CC) patients receiving chemoradiation (CRT) and to evaluate their impact on survival. Methods: We analyzed baseline 16S rDNA fecal microbiomes of CC patients receiving standard CRT. Patient and tumor characteristics were analyzed by univariate and multivariate Cox regression models for Recurrence-free survival (RFS) and Overall survival (OS) based on univariate p-value>0.2. Characteristics included age, body mass index (BMI), race, stage, grade, histology, nodal status, and max tumor size. Alpha (within sample) diversity was evaluated using Shannon diversity index (SDI). Kaplan-Meier curves were generated for patients with normal BMI and overweight/obese BMI based on Cox analysis. Results: 55 CC patients were included. Univariate analysis identified older age (Hazard Ratio (HR) of 0.93 (95% CI = 0.87-0.98, p = 0.0096)), SDI (HR of 0.51 (95% CI = 0.23-1.1, p = 0.087)) and BMI (HR of 0.92 (95% CI = 0.84-1, p = 0.096)) as risk factors for RFS. Multivariate survival analyses identified BMI and SDI as independent prognostic factors for RFS with a HR of 0.87 (95% CI = 0.77-0.98, p = 0.02) and 0.36 (95% CI = 0.15-0.84, p = 0.018) respectively. For OS, multivariate survival analyses again identified BMI and SDI as independent prognostic factors with a HR of 0.78 (95% CI = 0.623-0.97, p = 0.025) and 0.19 (95% CI = 0.043-0.83, p = 0.028) respectively. Conclusions: Gut diversity is a significant factor for predicting OS in CC patients undergoing CRT when BMI is accounted for, and may help explain the “obesity paradox” in cancer response. Studies exploring the relationship between gut diversity, CRT, and treatment efficacy are needed to further understand the role of the gut microbiome in treatment outcomes. [Table: see text]

4055 Background: Among patients with anal cancer, chemoradiotherapy tends to offer an excellent prognosis but is often associated with undesirable toxicities that diminish quality of life. We sought to quantify the gastrointestinal-related patient-reported outcomes (PROs) of anal cancer patients receiving chemoradiotherapy in order to improve patient-physician communication and shared decision making. Methods: We prospectively followed patients with non-metastatic squamous cell carcinoma of the anal canal who received definitive chemoradiotherapy. Patients reported outcomes were collected using the bowel subdomain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before treatment and at 4 subsequent timepoints. We used descriptive statistics to summarize the patients’ characteristics and EPIC scores, then used the paired Wilcoxon test to compare EPIC scores at different timepoints. Results: The study included 21 patients (16 women and 5 men), whose median age was 57 years. Most patients (52%) had T2, and either N0 (38%) or N1 (43%) disease. Most patients (91%) received standard of care chemoradiotherapy. Compared with the patients’ median overall summary score at baseline (66), their median score at 1 week (82) was significantly higher (p = 0.009), whereas their median score at 5 weeks (54) was significantly lower (p = 0.025). However, the patients’ median overall summary score at baseline and at 3 months did not differ significantly (p = 0.919). Three months after radiotherapy, most patients (73%) reported rarely or never having bloody stools, and most (82%) reported rarely or never being bothered by bloody stools. Overall, EPIC scores show initial improvement of all domains, followed by some worsening of symptoms before returning to baseline levels. Conclusions: Anal cancer patients’ gastrointestinal-related PROs tend to fluctuate during radiotherapy but return to baseline by 3 months, at which time most patients report few or no residual side effects. Our data provide a clear timeline of gastrointestinal acute toxicity using sequential PRO measurements that will improve patient-physician communication regarding expectations for cancer treatment and help in shared decision making.

Introduction: 16S RNA sequencing and whole-genome sequencing (WGS) techniques have been previously shown to have a significant degree of correlation, particularly for higher-order-level taxa. However, the large majority of those studies utilize data derived from samples collected in similar but not identical contexts. This project provides a unique opportunity in that both 16S RNA and WGS sequencing datasets were derived from a single fecal sample originating from each patient while undergoing chemoradiation therapy. Using this high-quality information, we investigated the correlation of these two datasets in terms of microbial composition and taxa abundances. Methods: Forty-one rectal swab samples were collected at the time of pelvic examination before the initiation of chemoradiation treatment and sequenced via Illumina platforms. Alpha and beta diversity was evaluated using PCoA ordination derived from several distance metrics (Bray-Curtis, Jaccard, Weighted and Unweighted UniFrac, and Euclidean). Diversity measures from different data analysis tools were also compared to highlight differences in data processing. Taxa with the highest relative abundances within each set of sequencing data were used to evaluate consensus between the datasets. Results: Alpha diversity assessed by different measures from WGS analysis correlated (Spearman rho value) with the same measures derived from 16S rRNA sequencing. These measures include OTU abundances (rho = 0.763, p = 6.61e−09), Shannon diversity (rho = 0.809, p = 4.40e−09), and InvSimpson (rho = 0.797, p = 2.11e−08). Beta diversity analysis highlighted a greater level of similarity within WGS samples than 16sRNA samples and a high degree of dissimilarity between the two datasets. Among the top fourteen most abundant taxa identified in 16S rRNA sequencing, the four best correlated with WGS results were Faecalibacterium, rho = 0.475, p = 1.68e−03; Mollicutes, rho = 0.302, p = 5.48e−02; Clostridiales, rho = 0.021, p = 8.98e−01; and Bacteria, rho = 0.016, p = 9.23e−01. The remaining ten taxa were negatively correlated. Conclusions: The use of whole-genome sequencing approaches in microbiome analysis is expanding in order to provide greater depth of information about microbial function. However, comparisons of results from 16S rRNA sequencing and WGS will need to be evaluated with caution due to differences in the interpretation of relative abundances of specific taxa. Future efforts may help to better harmonize these analyses to facilitate comparisons across platforms. Citation Format: Greyson Biegert, Xiaogang Wu, Tatiana V. Karpinets, Melissa Mezzari, Jianhua Zhang, Lauren Colbert, Ann Klopp. Comparisons of microbial composition identified via 16s rRNA sequencing and whole-genome sequence-based analysis using gut samples for patients with cervical cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B11.

A study was conducted to determine if a structured didactic curriculum for the medical student radiation oncology clerkship improved objective knowledge compared with clerkships not utilizing a structured curriculum. Results demonstrated improved objective knowledge postcurriculum. In addition, students receiving the curriculum scored higher at early and late time points compared with students not receiving the curriculum. These results support including a structured didactic curriculum as a standard component of a radiation oncology clerkship. PURPOSE: A structured didactic radiation oncology clerkship curriculum for medical students is in use at multiple academic medical centers. Objective evidence supporting this educational approach over the traditional clerkship model is lacking. This study evaluated the curriculum efficacy using an objective knowledge assessment. METHODS AND MATERIALS: Medical students received the Radiation Oncology Education Collaborative Study Group (ROECSG) curriculum consisting of 3 lectures (Overview of Radiation Oncology, Radiation Biology/Physics, and Practical Aspects of Simulation/Radiation Emergencies) and a radiation oncology treatment-planning workshop. A standardized 20-item multiple choice question (MCQ) knowledge assessment was completed pre- and post-curriculum and approximately 6 months after receiving the curriculum. RESULTS: One hundred forty-six students at 22 academic medical centers completed the ROECSG curriculum from July to November 2016. One hundred nine students completed pre- and post-clerkship MCQ knowledge assessments (response rate 74.7%). Twenty-four students reported a prior rotation at a ROECSG institution and were excluded from analysis. Mean assessment scores increased from pre- to post-curriculum (63.9% vs 80.2%, P < .01). Mean MCQ knowledge subdomain assessment scores all improved post-curriculum (t test, P values < .01). Post-scores for students rotating de novo at ROECSG institutions (n = 30) were higher compared with pre-scores for students with ≥1 prior rotations at non-ROECSG institutions (n = 55) (77.3% vs 68.8%, P = .01), with an effect size of 0.8. Students who completed rotations at ROECSG institutions continued to demonstrate a trend toward improved performance on the objective knowledge assessment at approximately 6 months after curriculum exposure (70.5% vs 65.6%, P = .11). CONCLUSIONS: Objective evaluation of a structured didactic curriculum for the radiation oncology clerkship at early and late time points demonstrated significant improvement in radiation oncology knowledge. Students who completed clerkships at ROECSG institutions performed objectively better than students who completed clerkships at non-ROECSG institutions. These results support including a structured didactic curriculum as a standard component of the radiation oncology clerkship.

Purpose To evaluate nuclear hypoxia-inducible factor 1α (HIF-1α) expression as a prognostic factor for distant recurrence (DR) and local recurrence (LR) after pancreatic adenocarcinoma resection. Methods and Materials Tissue specimens were collected from 98 patients with pancreatic adenocarcinoma who underwent resection without neoadjuvant therapy between January 2000 and December 2011. Local recurrence was defined as radiographic or pathologic evidence of progressive disease in the pancreas, pancreatic bed, or associated nodal regions. Distant recurrence was defined as radiographically or pathologically confirmed recurrent disease in other sites. Immunohistochemical staining was performed and scored by an independent pathologist blinded to patient outcomes. High HIF-1α overall expression score was defined as high percentage and intensity staining and thus score >1.33. Univariate analysis was performed for HIF-1α score with LR alone and with DR. Multivariate logistic regression was used to determine predictors of LR and DR. Results Median follow-up time for all patients was 16.3 months. Eight patients (8%) demonstrated isolated LR, 26 patients (26.5%) had isolated DR, and 13 patients had both LR and DR. Fifty-three patients (54%) had high HIF-1α expression, and 45 patients (46%) had low HIF-1α expression. High HIF-1α expression was significantly associated with DR ( P =.03), and low HIF-1α expression was significantly associated with isolated LR ( P =.03). On multivariate logistic regression analysis, high HIF-1α was the only significant predictor of DR (odds ratio 2.46 [95% confidence interval 1.06-5.72]; P =.03). In patients with a known recurrence, an HIF-1α score ≥2.5 demonstrated a specificity of 100% for DR. Conclusions High HIF-1α expression is a significant predictor of distant failure versus isolated local failure in patients undergoing resection of pancreatic adenocarcinoma. Expression of HIF-1α may have utility in determining candidates for adjuvant local radiation therapy and systemic chemotherapy.

Locally advanced pancreatic cancer (LAPC) almost always fatal since it is unresectable and chemotherapy is only modestly effective. The efficacy of radiation therapy (RT) for LAPC is limited by the potentially fatal toxicity to nearby intestines. There are no FDA-approved medications that can prevent this radiotoxicity, but we find that FG-4592, a small molecule inhibitor of EGLN proteins, significantly reduces radiation damage to the intestines without radioprotecting tumors. KPC (KrasLSL/+; Trp53FL/+; Ptf1aCre/+) animals received dose-escalated radiation treatments with and without FG-4592 for radioprotection. High-dose RT reduced death from local progression, improved survival, and shifted the patterns of failure to a late metastatic death compared to controls. The addition of FG-4592 to RT further improved survival compared to vehicle controls by eliminating radiation-induced gastrointestinal toxicity. Thus, selective protection of the intestinal tract by EGLN inhibition may enable higher, and potentially definitive doses of cytotoxic therapy to be delivered to LAPC.One Sentence SummaryThe EGLN inhibitor FG-4592 allows higher, and potentially definitive, doses of radiation to be delivered to pancreatic cancer by reducing normal tissue toxicity without protecting tumors.

TPS4164 Background: Local progression causes up to 30% of deaths from pancreatic cancer (PC) and is also a significant source of morbidity. Stereotactic body radiotherapy (SBRT) offers the potential for improved therapeutic index over standard fractionation, but current regimens of 5-7 Gy/fraction x 5 are constrained by nearby organ tolerance and offer only palliation without improving survival. Safe dose escalation is necessary to improve SBRT efficacy. GC4419, a superoxide dismutase mimetic, selectively converts superoxide (O2•-) to hydrogen peroxide (H2O2) and oxygen. O2•-initiates normal tissue damage due to RT. GC4419 is in a Phase 3 trial (NCT03689712) to reduce RT-induced oral mucositis in head and neck cancer, based on positive results in a randomized Phase 2 trial for that indication (Anderson, ASCO 2018). GC4419 improved the survival of mice receiving 8.5 Gy x 5 to the upper abdomen. Cancer cells are less tolerant to elevated H2O2, and more tolerant to elevated O2•-, than normal cells, and GC4419 demonstrated mechanism-dependent synergy with high dose-fraction RT in a human tumor xenograft with inducible expression of catalase (Sishc, AACR 2018). Thus, adding GC4419 to SBRT may increase both the efficacy and the safety of the latter. Methods: 48 patients with localized, unresectable PC without frank duodenal invasion, who have received 3+ cycles of induction chemotherapy, are to be randomized 1:1 to placebo or GC4419, 90 mg IV, prior to each of 5 consecutive daily (M-F) SBRT fractions. A phase I/II Late Onset Efficacy/ Toxicity tradeoff (LO-ET) based adaptive design adaptive model drives SBRT dose escalation in each arm based on a dual endpoint (Gr 3-4 GI toxicity or death ;stable disease or better) by 90 days post SBRT. The planned dose levels are 10, 11 and 12Gy x 5 fractions (BED10=100,112.5 and 132Gy, respectively) as an integrated boost to the gross tumor volume (GTV). Primary endpoint: Maximum tolerated dose of SBRT with GC4419 or placebo. Exploratory endpoints include change in tumor radiographic resectability, correlative studies (ctDNA, exosomal DNA, tumor exome/transcriptome sequencing, immune profiling). Supported by Galera Therapeutics, Inc. Clinical trial information: NCT03340974.

BACKGROUND Pancreatic adenocarcinoma (PAC) has low overall survival (OS) rates and high recurrence rates following surgical resection. The role for preoperative radiation therapy (prRT) for PAC versus postoperative RT (poRT) remains uncertain. The authors used the National Cancer Data Base (NCDB) to report prRT outcomes for the largest multi-institutional patient cohort to date. METHODS NCDB data were obtained for all patients who underwent resection and external beam radiation (RT) for PAC from 1998 to 2002. Patients with metastatic (M1) disease, intraoperative RT, RT both before and after surgery, missing OS, or missing RT variables were excluded. Univariate (UV) and multivariate (MV) analysis were run using treatment characteristics, tumor characteristics, and patient demographics. The difference in patients' known characteristics was described by a chi-square test or analysis of variance. RESULTS A total of 5414 patients were identified. Of these, 277 received prRT and 5137 received poRT. Overall, 92.9% received chemotherapy and 7.1% received RT alone; 56% (2990 of 5307) of patients had stage III disease, according to American Joint Commission on Cancer (AJCC) staging manual, 5th edition. Median tumor size was 3 cm (range: 0-9.9 cm); 82% (199 of 244) of patients with prRT had negative surgical margins; 72% (3383 of 4699) of patients with poRT had negative margins. Forty-one percent (71 of 173) of patients with prRT were lymph node (LN)-positive; 65% (3159 of 4833) of patients with poRT were LN-positive. Median OS for patients with prRT was 18 months (95% CI = 18-19 months) and for patients with poRT, 19 months (95% CI = 17-22 months). CONCLUSIONS Receipt of prRT was associated with lower stage, higher rates of negative margins, and lower rates of lymph node positivity at resection. However, there was no significant difference in median OS versus that of the poRT group. Cancer 2014;120:499–506. © 2014 American Cancer Society.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

Background Mixed lineage kinase domain-like protein (MLKL) is a necrosome component mediating programmed necrosis that may be an important determinant of cancer cell death. The goal of the current study was to evaluate the prognostic value of MLKL expression in patients with pancreatic adenocarcinoma (PAC).

Purpose We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before routine integration into the treatment planning process.

BACKGROUND Adjuvant radiotherapy (A-RT) for patients with resected pancreatic adenocarcinoma (PAC) is controversial. In the current study, the authors aim to determine whether there is an association between overall survival (OS) and A-RT dose. METHODS National Cancer Data Base (NCDB) data were obtained for all patients who received A-RT for resected PAC from 1998 through 2002. Univariate and multivariate survival analyses were performed along with Kaplan-Meier estimates for A-RT levels

79 Background: MD Anderson Cancer Center is a large cancer center with 44,000 new patients per year. Radiation therapy (RT) is an effective treatment for bone metastases that can reduce pain medication use and improve quality of life. Our goal was to assess the effect of implementing a rapid access multidisciplinary clinic for bone metastases (RABC). Methods: RABC was instituted to schedule patients for radiation oncology and orthopedic surgery consult within 48 hours of referral. Same day simulation and treatment times were held for these patients for one 8Gy fraction. Thirty sequential patients treated with one fraction to bony sites in the outpatient setting prior to implementation of the clinic were chosen as a comparison group. Time from consult order to consult visit (OTV) and from consult visit to treatment completion (CTT) were recorded, in addition to frequency of multidisciplinary care (MDC; orthopedic surgery and radiation oncology). Overall Time (OT) was calculated from referral to treatment completion. T-test and chi-square test were used for analyses. Results: Between April 2018 and July 2018, 72 patients were referred to RABC. 23 patients were seen in consultation and received RT. Sites treated were pelvis (N = 10), spine (N = 6), lower extremity (N = 4) and upper extremity (N = 3). Patients had one site (N = 20), two sites (N = 2) or three sites treated (N = 1). Histologies included breast (N = 5), thoracic (N = 7), gastrointestinal (N = 6), genitourinary (N = 2) and head/neck (N = 2). OTV was shorter for RABC patients (mean 3.3 [+/-5.7] vs. 9.5 days [12.4]; p = 0.02). CTT was also significantly shorter for RABC patients (mean 5.4 hours [+/-1.8] vs. 6.5 days [+/-6.5]; p < .0001). OT was also shorter (3.5 days [+/-5.6] vs. 16.4 days [+/-14.8]; p < .0001). RABC clinic patients were more likely to receive MDC (100% vs 28%; p < .0001). Conclusions: The rapid access bone metastases clinic significantly decreased overall time from consult to completion of treatment and also decreased time to access radiotherapy. Patients were also more likely to receive multidisciplinary evaluation. The RABC approach is a promising model to improve palliation for patients with painful bony metastases.

155 Background: Although electronic medical records (EMR) offer numerous potential benefits, there are significant challenges to balance high quality patient care and clinical efficiency with the rising demands of required documentation. Our objective was to propose and implement a strategy to standardize and optimize EMR documentation. Methods: An EMR taskforce was created within our institution’s radiation oncology (RO) department consisting of representatives of the clinical staff and EMR coders. To optimize clinical documentation, disease-site specific consult templates were created using EMR standard data elements and personalized drop down menus (Smartlists). Meetings were held with the billing department for template review and with the analytics team to begin automated data extraction into research databases. Quality metrics such as the average number of clinic visits billed at levels 4 or 5 (B45) and the average number of hours per visit (AHV) were compared in different clinics within a 6-month pre- and post- template implementation time period. Results: Within 3 months of establishing the taskforce, 32 RO disease-specific templates were created and distributed for usage in clinic. Optimized template features include consistent cancer staging, standardized oncologic history entry, usage of macros for patients’ symptoms for multiple provider verification, imbedded disease-specific protocol list to improve patient screening and enrollment, and multiple Smartlists for common treatment recommendations. In the GI Clinic, B45 increased from 49.3 to 61.4 per month and similar trends were seen in the Thoracic Clinic (B45, 51.4 to 85.2 per month). The AHV decreased in both the GI (21 to 10 hours) and Thoracic (22 to 13 hours) clinics, showing a significant added value to use of standard documentation. Conclusions: EMR systems can be challenging to navigate; however, they also present a unique opportunity to optimize clinical and research efficiency if used properly. The implementation of standard documentation in our department led to significant improvement in clinical efficiency. Further efforts are being made to adopt these changes on an institutional-wide level.

Rationale: Pancreatic cancer is almost always fatal since chemotherapy is only modestly effective and surgery is often not possible. Radiation therapy (RT) can be a definitive treatment in localized pancreatic cancer, but gastrointestinal toxicity to the nearby duodenum limits its efficacy. There are no known medications that can prevent or treat this gastrointestinal radiotoxicity, but we find that FG-4592, a small molecule inhibitor of EGLN proteins, reduces radiation damage to the intestines by selectively enhancing HIF expression within normal intestines but not within tumors. Methods: We developed a murine model of spontaneous pancreatic cancer (KrasLSL/+; Trp53FL/+; Ptf1aCre/+) that behaves similarly to locally advanced disease. KPC mice were screened for tumors by weekly ultrasounds and upon diagnosis were sequentially assigned to receive one of four possible treatments: Vehicle only (VEH), FG-4592 (FG), RT concurrent with vehicle (RT+VEH), or RT concurrent with FG-4592 (RT+FG). Mice were enrolled on a rolling basis and the total time from diagnosis to treatment end was approximately three weeks. Radiation treatments were planned to administer a total of 75Gy in 15 daily fractions. Results: A total of 70 KPC mice were evaluated. The administration of high-dose radiation therapy of >65Gy (high-dose) with or without radioprotection improved survival compared to all animals that received ≤65Gy (low-dose) of treatment or no RT (37 days [95% CI 33-41] vs. 15 days [10-21] vs. 15 days [10-20], respectively; p=0.005). KPC animals that received dose-escalated radiation lived significantly longer compared to unirradiated controls that received vehicle or FG-4592 alone. The median overall survival was compared amongst the treatment groups and was highest (p Citation Format: Cullen M. Taniguchi, Tara N. Fujimoto, Lauren E. Colbert, Jessica M. Moilkentine, Amit Deorukhkar, Laura J. Baseler, Ramesh Tailor, Gabriel O. Sawakuchi. EGLN inhibition reduces gastrointestinal radiation toxicity and improves survival in a murine model of locally advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 979.