Purpose: Stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are widely used therapies for the treatment of intrahepatic metastases; however, direct comparisons are lacking. We sought to compare outcomes for these 2 modalities. Methods and Materials: From 2000 to 2015, 161 patients with 282 pathologically diagnosed unresectable liver metastases were treated with RFA (n = 112) or SBRT (n = 170) at a single institution. The primary outcome was freedom from local progression (FFLP). The effect of treatment and covariates on FFLP was modeled using a mixed-effects Cox model with application of inverse probability treatment weighting to adjust for potential imbalances in treatment modality. Results: The median follow-up period was 24.6 months. Patients receiving SBRT had larger tumors than those treated with RFA (median, 2.7 cm vs 1.8 cm; P < .01). On univariate analysis, tumor size was associated with worse FFLP for RFA(hazard ratio [HR]; 1.57; 95% confidence interval [CI], 1.15-2.14; P < .01) but not for SBRT (HR, 1.38; 95% CI, 0.76-2.51; P = .3). The 2-year FFLP rate was 88.2% compared with 73.9%, favoring SBRT (P = .06). For tumors >= 2 cm in diameter, SBRT was associated with improved FFLP (HR, 0.28; 95% CI, 0.09-0.93; P < .01). On multivariate analysis, treatment with SBRT (HR, 0.21; 95% CI, 0.07-0.62; P = .005) and smaller tumor size (HR, 0.65; 95% CI, 0.47-0.91; P = .01) were associated with improved FFLP. The 2-year overall survival rate was 51.1%, with no difference between groups (P = .8). Grade >= 3 treatment-related toxicity was rare, with no difference between SBRT (n = 4) and RFA (n = 3). Conclusions: Treatment with SBRT or RFA is well tolerated and provides excellent and similar local control for intrahepatic metastases <2 cm in size. For tumors >= 2 cm in size, treatment with SBRT is associated with improved FFLP and may be the preferable treatment. (C) 2017 Elsevier Inc. All rights reserved.

The weighted average treatment effect (WATE) is a causal measure for the comparison of interventions in a specific target population, which may be different from the population where data are sampled from. For instance, when the goal is to introduce a new treatment to a target population, the question is what efficacy (or effectiveness) can be gained by switching patients from a standard of care (control) to this new treatment, for which the average treatment effect for the control (ATC) estimand can be applied. In this paper, we propose two estimators based on augmented inverse probability weighting to estimate the WATE for a well defined target population (i.e., there exists a target function that describes the population of interest), using observational data. The first proposed estimator is doubly robust if the target function is known or can be correctly specified. The second proposed estimator is doubly robust if the target function has a linear dependence on the propensity score, which can be used to estimate the average treatment effect for the treated (ATT) and ATC. We demonstrate the properties of the proposed estimators through theoretical proof and simulation studies. We also apply our proposed methods in a comparison of glucagon-like peptide-1 receptor agonists therapy and insulin therapy among patients with type 2 diabetes, using the UK clinical practice research datalink data.

Dynamic treatment regimes (DTRs) are sequences of treatment decision rules, in which treatment may be adapted over time in response to the changing course of an individual. Motivated by the substance use disorder (SUD) study, we propose a tree-based reinforcement learning (T-RL) method to directly estimate optimal DTRs in a multi-stage multi-treatment setting. At each stage, T-RL builds an unsupervised decision tree that directly handles the problem of optimization with multiple treatment comparisons, through a purity measure constructed with augmented inverse probability weighted estimators. For the multiple stages, the algorithm is implemented recursively using backward induction. By combining semiparametric regression with flexible tree-based learning, T-RL is robust, efficient and easy to interpret for the identification of optimal DTRs, as shown in the simulation studies. With the proposed method, we identify dynamic SUD treatment regimes for adolescents.

For patients with a limited number of unresectable intrahepatic metastases, stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are appealing focal liver therapies; however, direct comparisons of these modalities are lacking. We hypothesized that both modalities would provide excellent freedom from local progression (FFLP) for small metastases, with an advantage favoring SBRT when treating larger lesions. From 2000 to 2015, 161 patients with 282 pathologically diagnosed unresectable liver metastases were treated with RFA or SBRT at a single institution. Retrospective analysis of these patients was approved through the local institutional review board. The primary outcome, FFLP, was defined as the time from the start of SBRT/RFA until local progression of the treated lesion. Overall survival (OS) was measured at the patient level as the time from treatment start to death from any cause. The effect of treatment and covariates on FFLP was modeled using a mixed-effects Cox model with patient-level random effects to adjust for correlation between multiple lesions in the same patient. We applied inverse probability of treatment weighting to the Kaplan-Meier method and Cox models for FFLP to adjust for potential imbalances in treatment assignment. Sixty-nine patients were treated with RFA to 112 metastases and 92 patients were treated with SBRT to 170 metastases. Median follow-up for all patients was 24.6 months. Patients receiving SBRT had larger tumors than those treated with RFA (2.7 cm vs. 1.8 cm, P < 0.01). The most common histology in both groups was colon/rectal adenocarcinoma (66% overall). On univariate analysis tumor size was associated with worse FFLP for RFA (HR = 1.57, 95% CI = 1.15-2.14, P < 0.01), but not SBRT (HR = 1.38, 95% CI = 0.76-2.51, P = 0.3). The 2-year FFLP for patients treated with SBRT was 88.2% compared to 73.9% for patients receiving RFA, which approached statistical significance (P = 0.06). For tumors larger than 2 cm in diameter, RFA was associated with worse FFLP (HR = 3.54, 95% CI = 1.08-11.6, P < 0.01). 2-year OS was 51.1% and there was no difference between SBRT and RFA (P = 0.81). On multivariate analysis, treatment with SBRT (HR = 0.22, 95% CI = 0.08-0.60, P = 0.003) and decreasing tumor size (HR = 0.64, 95% CI = 0.48-0.85, P < 0.01) were associated with improved FFLP. Grade 3+ treatment related toxicity was rare and there was no difference in toxicity between SBRT (n = 4) and RFA (n = 6). Treatment with SBRT or RFA is well tolerated and provides excellent and similar local control for intrahepatic metastases less than 2 cm in size. For tumors greater than 2 cm in size, treatment with SBRT is associated with improved FFLP, and may be the preferable treatment option.

Purpose: To conduct a large single-institution comparison of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes in similar groups of patients with hepatocellular carcinoma (HCC). Methods and Materials: From 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed. Results: The TACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease, and baseline liver function. Patients treated with SBRT were older (65 vs 61 years, P=.01), had smaller tumors (2.3 vs 2.9 cm, P<.001), and less frequently underwent liver transplantation (8% vs 18%, P=.01). The 1-and 2-year LC favored SBRT: 97% and 91%, respectively, for SBRT and 47% and 23% for TACE (hazard ratio 66.5, P<.001). For patients treated with TACE, higher alpha-fetoprotein (hazard ratio 1.11 per doubling, P=.008) and segmental portal vein thrombosis (hazard ratio 9.9, P<.001) were associated with worse LC. Predictors associated with LC after SBRT were not identified. Grade 3thorn toxicity occurred after 13% and 8% of TACE and SBRT treatments, respectively (P=.05). There was no difference in OS between patients treated with TACE or SBRT. Conclusions: Stereotactic body radiation therapy is a safe alternative to TACE for 1 to 2 tumors and provides better LC, with no observed difference in OS. Prospective comparative trials of TACE and SBRT are warranted. (C) 2017 Elsevier Inc. All rights reserved.

Given the distinct survival differences among molecular subgroups of anaplastic glioma, we investigated whether disease-associated function and symptom measures varied by subgroup and were associated with survival. Fifteen patients with grade III glioma treated on a phase I protocol of gemcitabine plus local-field radiation (RT, 60 Gy/30 fractions) without progression at 6 months post RT and available IDH1 and/or 1p/19q status were included in this retrospective study. MMSE, KPS, and EORTC QLC-30/BN20 disease-associated domains of cognitive and physical function, visual and motor dysfunction were compared between IDH1 (IDHm, n=10 vs IDHwt, n=3) and 1p/19q (codeleted, n=4 vs intact, n=8) subgroups using Fisher’s exact test, and associated with progression-free (PFS) and overall survival (OS) using Cox univariate analysis. Median age was 46 years (23-70), median pre-RT MMSE was 30 (24-30) and KPS 90 (70-100), with no significant baseline differences in these factors between subgroups. PFS and OS were higher in favorable (OS IDHm 72.1 months, codeleted inestimable) vs unfavorable subgroups (OS IDHwt 25.5 months, intact 72.1 months). Sixty percent (6/10) of IDHm patients retained stable self-reported cognitive function, and 3 (30%) had improved function whereas 2 (100%) of 2 IDHwt patients with available data improved at 6 months. Fifty percent (4/8) of 1p/19q intact patients had improved report of physical function vs 1 (25%) codeleted patient at 6 months. Although 1p/19q intact patients had worse visual and motor dysfunction at baseline, no significant difference between subgroups was seen at 6 months. Baseline and change in factors were not significantly associated with PFS or OS. In these pilot data, unfavorable molecular subgroups had worse survival and baseline neurologic dysfunction, but experienced significant recovery of physical and cognitive function after treatment. Whether tumor or patient-related factors account for this selective recovery will be explored in future studies.

Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG).Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m(2) during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity.Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [ CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m(2)/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen.Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG. Published by Elsevier Inc.

Dynamic treatment regimes (DTRs) are sequential decision rules that focus simultaneously on treatment individualization and adaptation over time. To directly identify the optimal DTR in a multi-stage multi-treatment setting, we propose a dynamic statistical learning method, adaptive contrast weighted learning. We develop semiparametric regression-based contrasts with the adaptation of treatment effect ordering for each patient at each stage, and the adaptive contrasts simplify the problem of optimization with multiple treatment comparisons to a weighted classification problem that can be solved by existing machine learning techniques. The algorithm is implemented recursively using backward induction. By combining doubly robust semiparametric regression estimators with machine learning algorithms, the proposed method is robust and efficient for the identification of the optimal DTR, as shown in the simulation studies. We illustrate our method using observational data on esophageal cancer.

The purpose of this study was to assess how xerostomia affects dysphagia.

the results of 224 patients with inoperable nonmetastatic hepatocellular (HCC) with (RFA) or stereotactic body (SBRT). and an inverse probability of weighting in the Kaplan-Meier Cox models for the treatment-related bias.

4087 Background: TACE is a standard treatment for patients (pts) with HCC. SBRT is a newer, noninvasive therapy. There have been no comparative studies to date. Thus, we examined TACE and SBRT outcomes. Methods: After IRB approval, institutional HCC and radiotherapy databases were queried for pts receiving TACE or SBRT for 1-2 tumors and combined with a diagnosis and billing code query for HCC, TACE, and SBRT. Pts with main branch portal venous (PV) involvement, extrahepatic spread, and Child Pugh C cirrhosis were excluded, since they are not candidates for TACE. Inverse probability weighting, via a propensity score, was used to adjust for imbalances between treatment groups. Local control (LC), overall survival (OS), and toxicity were compared. LC for was defined as no tumor growth within or immediately adjacent to the TACE cavity or original tumor. Results: From 2006-2014, 84 pts with 114 tumors were treated with TACE and 125 pts with 173 tumors with SBRT. Median follow-up was 28 months (1.8-103) and 16 months (0.2-98) for pts treated with TACE or SBRT, respectively (p<0.001). Pts treated with TACE were younger (61 vs 65 yrs, p=0.01) and had slightly larger tumors (2.9 vs 2.3 cm, p<0.001). In propensity adjusted analysis, 1- and 2-yr LC favored SBRT: 97% and 91% for SBRT and 41% and 18%, for TACE (HR 18.8, 95% CI 6.7-52.7, p<0.001). Increasing tumor size (HR 1.2 per cm, 95% CI 1.05 - 1.23, p<0.001) and partial PV tumor thrombus (HR 7, 95% CI 2.73 - 15.2, p<0.001) predicted for worse LC in pts treated with TACE, but not with SBRT. Grade 3+ toxicity occurred after 14% and 7% of TACE and SBRT treatments, respectively (p=0.05). From HCC diagnosis, SBRT was initiated a mean of 9 months later than TACE (p<0.001), and more patients underwent liver transplantation after TACE (18% vs. 8%, p=0.01). After adjustment for baseline liver function and transplantation, overall survival was not significantly different (HR = 0.73, 95% CI 0.48 – 1.12, p =0.15). Conclusions: SBRT is a safe alternative to TACE for 1-2 tumors, and provides better LC, with no difference in OS. Prospective comparative trials of TACE, SBRT, and other ablative therapies are warranted.

Purpose/objectives Radiation injury to parahippocampal cingulum white matter is associated with cognitive decline. Diffusion tensor imaging (DTI) detects micropathologic changes in white matter. Increased radial diffusion (RD) and decreased axial diffusion (AD) correspond to demyelination and axonal degeneration/gliosis respectively. We aimed to develop a predictive model for radiation-induced cognitive changes based upon DTI changes. Materials/methods Twenty-seven adults with benign or low-grade tumors received partial brain radiation therapy (RT) to a median dose of 54 Gy. Patients underwent DTI before RT, during RT, and at the end of RT. Cognitive testing was performed before RT, and 6 and 18 months after RT. Parahippocampal cingulum white matter was contoured to obtain mean values of AD and RD. Results By univariate analysis, decreasing AD and increasing RD during RT predicted declines in verbal memory and verbal fluency. By multivariate analysis, baseline neurocognitive score was the only clinical variable predicting verbal memory change; no clinical variables predicted verbal fluency change. In a multivariate model, increased RD at the end of RT significantly predicted decline in verbal fluency 18 months after RT. Conclusions Imaging biomarkers of white matter injury contributed to predictive models of cognitive function change after RT.

Aggressive management of oligometastases from sarcoma can result in long-term survival and a chemotherapy-free holiday. Surgical resection is considered to be the treatment of choice, with stereotactic body radiotherapy (SBRT) generally offered to patients who are not candidates for surgical resection due to co-morbidities or concern about residual lung function. We examined outcomes of resection and SBRT for patients with sarcoma oligometastases at our institution and identified predictive factors for local control, with the hypothesis that overall local control would be similar. After IRB-approval, we queried our institutional thoracic surgery and radiation oncology databases, supplemented with an institutional query using diagnosis and billing codes for sarcoma, lung metastases, lung resections, and SBRT. We applied inverse probability of treatment weighting to adjust for imbalances in treatment assignment. Freedom from local progression (FFLP) for surgical resection was defined as absence of recurrence at the resection line, while FFLP for SBRT was defined as the absence of progression within or at the PTV margin. Between 1997 and 2014, 78 patients (pts) with 127 lung lesions were treated with surgical resection and 26 pts with 47 pulmonary metastases were ablated with SBRT. Median tumor size was 1.5 cm (0.1-12.8) and 1.4 cm (0.4-4.8), respectively, for surgically and SBRT-managed pulmonary metastases. Median follow-up was 20.9 months (1 to 224) and 15.3 months (2 to 57) for patients treated with surgical resection and SBRT, respectively (P = 0.01). On average, pts in the SBRT group were older (age 60 v 52, P = 0.03), had received more prior systemic therapies (1.98 vs. 1.29, P = 0.01) and had a higher presence of active extrathoracic disease at treatment start (59.6% vs. 29.9%, P < 0.001). Local control was not different between groups when adjusted for size, other sites of active disease, age, and performance status (HR = 1.47, 95% CI 0.20 – 10.9, P = 0.71). 1- and 2-yr FFLP rates for all resected lung lesions vs SBRT were 96.8% and 96.8% vs 97.4% and 97.4%. 1 and 2- year overall survival (OS) were 92.6% and 62.2% for surgery pts and 88.1% and 57.9% for SBRT pts, with no difference between groups (HR = 0.71, 95% CI = 0.39 – 1.29, P = 0.27). 1 and 2- year progression free survival (PFS) were 33.4% and 15.7% for surgery pts and 42.3% and 21.6% for SBRT pts, with no significant difference between groups (HR = 1.21, 95% CI = 0.87 – 1.68, P = 0.25). Grade 3+ adverse events were observed in five pts treated with surgery vs. none in pts with SBRT. In this series SBRT provides similar LC, PFS, and OS compared with surgical resection of lung metastases from sarcoma, and thus may serve as a safe alternative to surgical resection. A randomized, prospective study is required to determine if there is comparable long-term survival with SBRT vs. surgery for treatment of sarcoma lung metastases.

Objective(s): Dysgeusia is a significant factor reducing quality of life and worsening dysphagia in patients receiving chemoradiation therapy for head and neck cancer. The factors affecting dysgeusia severity are uncertain. We investigated the effects on patient-reported dysgeusia of doses to the oral cavity, salivary output (required to dissolve food particles), and patient-reported xerostomia.Methods and Materials: Seventy-three patients with stage III to IV oropharyngeal cancer (OPC) (N = 73) receiving definitive intensity modulated radiation therapy concurrently with chemotherapy participated in a prospective, longitudinal study of quality of life (QOL), including assessment of patient-reported gustatory function by taste-related questions from the Head and Neck QOL instrument (HNQOL) and the University of Washington Head and Neck-related QOL instrument (UWQOL), before therapy and periodically after treatment. At these intervals, patients also completed a validated xerostomia-specific questionnaire (XQ) and underwent unstimulated and stimulated major salivary gland flow rate measurements.Results: At 1, 3, 6, and 12 months after treatment, dysgeusia improved over time: severe dysgeusia was reported by 50%, 40%, 22%, and 23% of patients, respectively. Significant associations were found between patient-reported severe dysgeusia and radiation dose to the oral cavity (P =. 005) and tongue (P =. 019); normal tissue complication probability for severe dysgeusia at 3 months showed mean oral cavity D-50 doses 53 Gy and 57 Gy in the HNQOL and WUQOL questionnaires, respectively, with curve slope (m) of 0.41. Measured salivary output was not statistically significantly correlated with severe taste dysfunction, whereas patient-reported XQ summary scores and xerostomia while eating scores were correlated with severe dysgeusia in the UW-QOL tool (P =. 04).Conclusions: Taste impairment is significantly correlated with mean radiation dose to the oral cavity. Patient-reported xerostomia, but not salivary output, was correlated with severe dysgeusia in 1 of the 2 QOL questionnaires. Reduction in oral cavity doses is likely to improve dysgeusia. (C) 2016 Elsevier Inc. All rights reserved.

PURPOSEData guiding selection of nonsurgical treatment of hepatocellular carcinoma (HCC) are lacking. We therefore compared outcomes between stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) for HCC.PATIENTS AND METHODSFrom 2004 to 2012, 224 patients with inoperable, nonmetastatic HCC underwent RFA (n = 161) to 249 tumors or image-guided SBRT (n = 63) to 83 tumors. We applied inverse probability of treatment weighting to adjust for imbalances in treatment assignment. Freedom from local progression (FFLP) and toxicity were retrospectively analyzed.RESULTSRFA and SBRT groups were similar with respect to number of lesions treated per patient, type of underlying liver disease, and tumor size (median, 1.8 v 2.2 cm in maximum diameter; P = .14). However, the SBRT group had lower pretreatment Child-Pugh scores (P = .003), higher pretreatment alpha-fetoprotein levels (P = .04), and a greater number of prior liver-directed treatments (P < .001). One- and 2-year FFLP for tumors treated with RFA were 83.6% and 80.2% v 97.4% and 83.8% for SBRT. Increasing tumor size predicted for FFLP in patients treated with RFA (hazard ratio [HR], 1.54 per cm; P = .006), but not with SBRT (HR, 1.21 per cm; P = .617). For tumors ≥ 2 cm, there was decreased FFLP for RFA compared with SBRT (HR, 3.35; P = .025). Acute grade 3+ complications occurred after 11% and 5% of RFA and SBRT treatments, respectively (P = .31). Overall survival 1 and 2 years after treatment was 70% and 53% after RFA and 74% and 46% after SBRT.CONCLUSIONBoth RFA and SBRT are effective local treatment options for inoperable HCC. Although these data are retrospective, SBRT appears to be a reasonable first-line treatment of inoperable, larger HCC.

PurposeRetropharyngeal adenopathy (RPA) is poor prognostic factor in head and neck (HN) cancer. However, the prognostic significance of RPA in Human Papillomavirus-related (HPV+) oropharyngeal cancer (OPC) is unknown.Patients and methods185 patients with HPV+OPC were assessed. Pre-therapy images reviewed by a HN radiologist to determine presence of RPA. Doses to the RPAs were determined from treatment plans. Outcomes analyzed using Kaplan–Meier method, log-rank tests, and correlations determined using Spearman’s rank analyses.Results29 (16%) of the HPV+patients had RPA. At median follow-up 49months, 5-year overall survival (OS), failure-free survival (FFS) and distant failure-free survival (DFFS) were 57% vs. 81% (P=0.02), 63% vs 80% (P=0.015) and 70% vs 91% (P=0.002) for patients with/without RPA, respectively. No differences observed in local/ regional control rates, exceeding 90% in both groups, and No RPA recurrences were observed. In multivariable analysis, stages T4 or N3, and RPA, were independently, statistically significantly associated with both OS and distant failure, while N2c, age, disease site, and smoking status, were not.ConclusionRPA in HPV+OPC is an independent prognostic factor for distant failure, translating into worse OS. Patients with RPA may not be suitable candidates for trials of systemic treatment de-escalation.

Concurrent chemoradiotherapy (concurrent CRT) to treat head and neck cancer is associated with significant reductions of weight, mobility, and quality of life (QOL). An intervention focusing on functional exercise may attenuate these losses.

Retropharyngeal adenopathy (RPA), a well-established poor prognostic factor in head and neck squamous cell carcinoma (HNSCC), predicts worse local and distant control. Human papillomavirus–positive (HPV+) oropharyngeal cancer (OPC) patients are a distinct population of HNSCC patients with superior tumor control and survival compared to smoking- and drinking-related HSNCC. However, the prognostic significance of RPA in HPV+ OPC is unknown. Therefore, we reviewed our institutional experience of HPV+ OPC patients treated with chemoradiation to determine the impact of RPA on tumor control and survival. We retrospectively reviewed of 231 consecutive OPC cancer patients treated from 2003 to 2010 with chemo–intensity modulated radiation therapy (weekly carboplatin [AUC1] and docetaxel [30mg/m2]). HPV tumor status was determined for 198 patients, 184 of whom were HPV+ by PCR (184 patients), 93% of whom were p16+ by immunohistochemistry (1 additional patient was p16+, HPV-). Pretherapy images were reviewed for the purpose of this study by a single head and neck radiologist blinded to treatment outcome to determine RPA. Doses to the RP nodal regions were determined from treatment plans. Outcomes were analyzed using Kaplan-Meier method, log-rank tests determined statistically significant differences, and correlations were determined using Spearman rank analyses (ρ). Twenty-nine (16%) of the 185 HPV+ patients had RPA. Among these, 3 had N1/N2a disease (RPA only), and 26 had additional nodal involvements in levels II–IV (12 had N2b, 9 had N2c, and 5 had N3 nodal stages). There was no statistically significant correlation between RPA and involvement of other lymph nodes (ρ = 0.07, P = .36) or N stage (ρ = 0.12, P = .11). All patients received 70 Gy to the involved RPA. At median 49 months follow-up, there were no failures in the RPA anatomical compartments. Patients with RPA had overall worse outcomes compared to those without RPA. Five-year overall survival (OS), cancer-specific survival (CSS), and failure-free survival (FFS) were 57% versus 81% (P = .02), 63% versus 85% (P = .02), and 63% versus 80% (P = .015) for patients with and without RPA, respectively. Patterns of failure analysis revealed that presence of RPA was associated with worse distant failure-free survival (DFFS) (70% vs 91%, P = .002), without any impact on either local (P = .87) or regional (P = .88) control rates, which exceeded 95% and 90%, respectively, in both groups. In multivariable analysis T4, N3, and presence of RPA were independently associated with worse OS, CSS, FFS, and DFFS while age, disease site, N2c classification, and smoking status were not. RPA in HPV+ OPC was found to be an independent prognostic factor for distant failure, independent of established risk factors such as T4 and N3 stages, which translated into worse OS. Patients with RPA may not be suitable candidates for trials of systemic treatment de-escalation.

380 Background: When tumors are near organs at risk such as bowel or heart, this results in partial underdosing relative to prescribed dose. We hypothesized that equivalent uniform dose (EUD) may better capture the biologic effect than other dose metrics. Methods: In this IRB-approved retrospective study, 257 primary and metastatic liver tumors from 168 patients treated with SBRT at the University of Michigan Health System between 2005 and 2014 were identified. Univariate analysis and multivariate Cox regression models were used to correlate patient, tumor, and treatment characteristics with rates of LC. Results: 1 and 2 year LC were 93% and 75% for all. Of the 156 primary liver tumors, 1 and 2 year LC were 94% and 76%, compared to 83% and 61%, for patients with colorectal metastases (CRM). 22 tumors locally progressed in 17 patients of which 9 were CRM, 5 hepatocellular carcinomas (HCC), and 3 other. Tumors that locally progressed received a median prescribed dose of 50 Gy (24 - 60), GTV EUD (a=-10) 49 Gy (23 - 72), and PTV EUD 46 Gy (17 - 69). Median gross tumor volume (GTV) was 21 cc (1-103). Tumors that did not locally progress received a median prescribed dose of 50 Gy (19 - 60), GTV EUD (a=-10) 52 Gy (17 - 86), and PTV EUD 47 Gy (7 - 76). Median GTV was 10 cc (0.2 - 2092). On univariate analysis, CRM (p = 0.005) was correlated with higher progression, while high GTV and PTV EUD (a=-10) (p = 0.01, 0.05) were correlated with lower progression. HCC (p = 0.06) was borderline for low progression. Age, gender, primary or metastatic, prescribed dose, biologically equivalent dose (BED), minimum GTV or PTV dose and GTV did not predict for progression. In a multivariable model including age, gender, histology, prescribed dose, BED, GTV EUD and GTV size, only GTV EUD predicted for LC, HR = 0.947, 95% CI = 0.901 - 0.996, p = 0.036. Every 1 Gy increase in EUD decreased the risk of local failure by 5%. Conclusions: EUD was predictive of local progression even when accounting for histology, size, and dose as measured by prescribed dose and BED. GTV EUD (a=-10) over 47.64 Gy yielded a >95% local control. EUD may be the preferred dose metric in future tumor control studies.