Miller, Robert C.

e14555 Background: This study was done to assess the toxicity and efficacy of IMRT for anal cancer in a multi-institutional setting. Methods: Records of 152 total patients (pts) were reviewed retrospectively. Data on disease control and toxicity were collected as well as pt and treatment characteristics. Acute (<6 months) and late (>6 months) severe toxicity (grade >3) were recorded at each institution. Four were excluded for either presence of metastatic disease (2) or stage TX (2). There was data for late toxicity on 120 pts. Results: T stage was T1 in 28, T2 in 79, T3 in 29 and T4 in 12 pts. N stage was N0 in 77, N1 in 40, N2 in 19 and N3 in 12 pts. The median age was 56 yrs and median follow-up was 26.8 months. Cumulative IMRT dose was 51.25 Gy (median) (range: 4.32-61.2 Gy) in a median of 28 fractions (2-34). Chemotherapy was given in all but 2 pts and the most common regimen was 5- fluorouracil plus mitomycin-C. The median total elapsed treatment time was 40 days. Local control at 3 yrs was 87% and was significantly worse for patients with T3-4 disease (79% vs 90% at 3 years; p=0.04). There was no correlation between dose and local control. Regional control, distant control and overall survival were 97%, 91%, and 87% at 3 yrs, respectively. Nodal status was associated with regional and distal control as well as overall survival (p<0.01 for each). The most common acute severe toxicity was hematologic (41%). Severe acute GI, skin or other toxicity was 11%, 20% and 1% respectively. There were two grade 5 toxicities (hematologic and GI). Severe late toxicity was limited to skin (1%) and GI (3%). Conclusions: IMRT resulted in excellent local control in this multi-institutional cohort of pts. Although T stage did predict for worse local control, most pts with T3-4 disease were controlled with IMRT. Nodal status predicts for regional and distal control as well as overall survival. Severe toxicity was acceptable with this technique.

e14507 Background: Serious gastrointestinal injury (SGI) is a rare but documented side effect that can occur independently with agents that affect the vascular endothelial growth factor (VEGF) receptor or with stereotactic body radiotherapy (SBRT). The risk of SGI in patients treated with the combination of SBRT sequentially followed by a VEGF inhibitor (VEGF-i) is not yet quantified. We explored the incidence of SGI in patients treated with SBRT with or without VEGF-i therapy at a single institution. Methods: From May 2008 to August 2011, 76 patients with 84 primary or metastatic intraabdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Twenty of these patients (26%) received a VEGF-i within two years of completing SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The most common site treated with SBRT was the liver (n=43, 57%), and the most common histology was colorectal adenocarcinoma (n=18, 24%). Other common histologies included melanoma of the skin (n=14, 18%) and non-small cell lung cancer (n=10, 13%). The incidence of SGI (CTCAE v4.0 grade 3 to 5 ulceration or perforation) after SBRT was obtained, and the relationship between SGI and VEGF-i was examined. Other factors that could potentially contribute to SGI, such as radiotherapy dose to bowel, were also analyzed. Results: Seven patients (9%) experienced SGI at a median 4.6 months (range, 3-17 months) after SBRT. All seven had received a VEGF-i prior to SGI and within 13 months of completing SBRT, and five received the VEGF-i within three months of SBRT. The six-month estimate of SGI in patients receiving a VEGF-i within three months of SBRT was 38%. No SGI was noted in the 63 patients not receiving VEGF-i therapy after SBRT. The Log-Rank test showed a significant correlation between SGI and VEGF-i therapy within three months of SBRT (p=0.0006) but not between SGI and maximum radiotherapy bowel dose (p=0.20). Conclusions: The combination of SBRT and VEGF-i therapy results in a much higher risk of SGI than would be expected with either treatment given independently. Local therapies other than SBRT should be considered if a patient is likely to be treated with a VEGF-i in the future.

e17019 Background: To report the role of combined chemotherapy in SGT. Methods: 251 patients with SGC treated in 2001-2011 were included in a collaborative IRB-approved retrospective RCN study. Chemotherapy is empirically administered based on extrapolation from conventional head and neck squamous cell carcinoma (Ca) (SCC) and data on systemic treatment in localized SGC are lacking. Results: Median age was 60 yo with 2/5 females/males. Tumor sites were the parotid 74.9%, submandibular 16%, sublingual 2.8% or minor gland 4%. Histologic findings were adenoid cystic (ACC) 17.3%, mucoepidermoid (MEC) 19.8%, adenoCa 15.6%, salivary duct (SDC) 10.3%, acinic cell (Aci) 6.2%, ex-pleomorphic 7.8%, undifferentiated 4.9%, myoepithelial 3.3%, epithelial myoepithelial 1.6%, basal cell 1.2%, lymphoepithelial 1.2%, others 4.0%. Surgery was performed in 95.1% (complete resection 38.1%). T stages 1, 2, 3 and 4 were 17.2%, 41.2%, 18.1% and 23.5% respectively. N stages were N0 61%, N1 13%, N2 24%, N3 2%. Perineural, vascular or lymphatic emboli were present in 47%, 24%, 27% respectively. Irradiation was performed postoperatively 96% or exclusively 4% (unilateral 84%, performed w/ photons only 78%, IMRT 41%). Chemotherapy was administered in 18%, dependent on grade, N stage, and emboli (p ≤ .05). None of 17 ex-pleomorphic, 25% of undifferentiated, 36% of SDC, and 66.7% of lymphoepithelial Ca received chemotherapy (p NS). With a median follow-up of 42 months for living patients, crude local, regional, metastatic relapse rates were 112% (in field 85%), 10%, 25%, respectively. Crude death rate was 28% including 77% from SGC. 5-year survival (5y OS) was 63%. The only prognostic factor was nodal involvement (p .002). However, 5y OS differed by histology: ACC 79%, MEC 84%, Aci 67%, SCC 43%, adenoCa NOS 40%, SDC 37%. Chemotherapy did not improve survival whatever histology. Conclusions: Further prospective studies are warranted to define the role of chemotherapy by histology in the setting of localized SGT. Also molecular profile-driven systemic treatments should be investigated.

e16572 Background: The Bowel Function Questionnaire (BFQ) has been used in clinical trials to document patient-reported symptoms following pelvic radiation therapy (RT). This study evaluated the importance patients placed on the symptoms included in the BFQ as measured by a Content Validity Questionnaire (CVQ). Methods: Patients treated with pelvic RT assessed symptoms and importance at baseline, after completion of RT (4 weeks), and 12 and 24 months. BFQ measured quality of life (QOL) and symptoms of: nocturnal bowel movements, incontinence, greater than one bowel movement in 30 minutes, need for protective clothing, inability to differentiate stool and gas, liquid bowel movements, urgency, cramping, and bleeding. Bowel movement frequency was also assessed. Symptoms were rated via the CVQ as “not very important,” “moderately unimportant,” “neutral,” “moderately important,” or “very important." Summary statistics were compiled. Fisher Exact, Chi-Square and Wilcoxon methodology compared BFQ and CVQ results. Results: 125 patients participated. All symptoms were rated as moderately important or very important by most patients.Measures of bowel function of greatest importance (moderately or very important) at baseline were ability to control bowel movements (94%), not having to wear protective clothing (90%), and not having rectal bleeding (93%). In general, patients gave similar ratings of symptom importance at all time points in the study and ratings were independent of whether the symptom was experienced. With the exception of the need for protective clothing, the presence of a symptom at 4 weeks was associated with significantly worse QOL (p-values < 0.001 to 0.005). Conclusions: The BFQ has excellent content validity. Patients rated most symptoms measured by the BFQ as moderately important or very important, indicating the BFQ is an appropriate tool for symptom assessment during and after pelvic RT. With the exception of the need for protective clothing, the presence of every symptom measured by the BFQ was associated with worse QOL. These criteria make them appropriate targets for future research to mitigate radiation-related bowel dysfunction.

PURPOSE: Quality payment programs aim to adjust payments on the basis of quality and cost; however, few quality metrics exist in radiation oncology. This study evaluates and predicts the top spenders (TS) after radiation therapy (RT). MATERIALS AND METHODS: Patient characteristics, cancer details, treatments, toxicity, and survival data were collected for patients treated with RT at Mayo Clinic from 2007 to 2016. Standardized costs were obtained and adjusted for inflation. TSs were identified as those with greater than 93rd percentile costs (≥ $120,812). Prediction models were developed to predict TSs using training and validation sets using information available at consultation, after RT, and at last follow-up. RESULTS: A total of 15,131 patients were included and 1,065 TSs identified. Mean cost overall was $55,290 (median, $39,996) for all patients. Prediction models 1, 2, and 3 had concordance statistics of 0.83 to 0.83, 0.85 to 0.85, and 0.87 to 0.88, respectively in training and validation, indicating excellent prediction of TSs. Factors that were most predictive of TSs included stage N/A and stage 4 ( v stage 0; odds ratio [OR], 18.23 and 8.44, respectively; P < .001); hematologic, upper GI, skin and lung cancers ( v breast; OR, 11.45, 7.69, 3.81, and 2.43, respectively; P < .01); immunotherapy, surgery, and chemotherapy use (OR, 4.36, 2.51, and 1.61, respectively; P < .01); hospitalizations within 90 days of RT (OR, 2.26; P < .01); or death during the episode (OR, 1.56; P < .01). CONCLUSION: This is the first study of its kind to predict with high accuracy the highest spenders in radiation oncology. These patients may benefit from pre-emptive management to mitigate costs, or may require exclusion or adjustment from quality payment programs.

PURPOSE The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m 2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

6633 Background: Quality based payment programs in medicine are currently being introduced nationally, aimed to improve care and reduce cost. This study aimed to evaluate the top spenders (TS) after cancer diagnosis and predict TS at two separate time points using predictive analytics. Methods: Patient characteristics, cancer details, treatments, adverse events, and outcomes were collected for patients treated for cancer at Mayo Clinic from 2007 - 2017. Standardized costs over a 2 year period after first treatment were obtained from the Mayo Clinic Cost Data Warehouse with Medicare reimbursements assigned to all services and adjusted to the 2017 GDP Implicit Price Deflator for inflation. TS were identified as those with greater than 93rd percentile costs (≥$113,158) due to a sharp rise in cost at that level. Descriptive statistics and univariate analysis were used for comparison. A prediction model with a training (80%) and validation set (20%) using multivariate selection was used to predict TS and was repeated using information available at 1) the time of consultation and 2) at last follow-up. Results: A total of 80,385 patients were included and 5,626 TS were identified. Mean cost (25th, 75th percentile) overall was $44,953 ($16,776, $51,889). Prediction models at time 1 and 2 had ROC AUC statistics of 0.82 and 0.89 in training and 0.82 and 0.88 in the validation indicating good prediction of high costs. Factors most predictive of TS included need for blood transfusions within 90 days of treatment (OR 5.3), bone marrow transplant (OR 4.0), mild liver disease (OR 3.5), hemiplegia (OR 3.4), weight loss > 10% within 90 days of treatment (OR 3.3), upper GI cancer (OR 3.0), ‘other’ cancer type (OR 2.8), immunotherapy use (OR 2.7), and hospitalizations within 90 days (OR 2.4), all p < 0.001, among others. The largest costs were due to hospital services in the TS and non-TS groups, mean costs $114,258 and $13,185 respectively. Conclusions: This is the first study to predict with high accuracy the top spenders in Oncology. Patient comorbidities and toxicities were among the strongest predictors of high costs, along with certain treatments (bone marrow transplant and immunotherapy). Our findings suggest that quality payment programs should adjust for comorbidities, and that reducing toxicity may be an effective method at reducing costs.