P.R. Patel

Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation.

As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control with optimal radiotherapy may be critical. Although conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT) is an emerging approach with promising results. With no studies to date comparing SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to evaluate these 2 modalities.

Concomitant Chemotherapy and Radiotherapy with SBRT Boost for Unresectable Stage III Non–Small Cell Lung Cancer: A Phase I Study

Objectives: Stereotactic body radiation therapy (SBRT) is now the standard of care in medically inoperable stage I NSCLC, yielding high rates of local control. It is unknown whether SBRT can be safely utilized in the locally advanced NSCLC setting. This multi‐institution phase I study evaluated the safety of 44 Gy of conventionally fractionated thoracic radiation with concurrent chemotherapy plus dose‐escalated SBRT boost to both the primary tumor and involved mediastinal lymph nodes. The primary end point of this study was to establish the maximum tolerated dose (MTD) of the SBRT boost. Methods: Inclusion criteria included unresectable stage IIIA or IIIB disease, primary tumor 8 cm or smaller, and N1 or N2 lymph nodes 5 cm or smaller. Tumors were staged with positron emission tomography/computed tomography (CT), and four‐dimensional CT simulation was used for radiation planning. The treatment schema was 44 Gy of thoracic radiation (2 Gy/d) with weekly carboplatin and paclitaxel chemotherapy. A second CT simulation was obtained after 40 Gy had been delivered, and a SBRT boost was planned to the remaining gross disease at the primary site and involved mediastinal lymph nodes. Consolidation chemotherapy was given at the discretion of the treating medical oncologist. Four SBRT boost dose cohorts were tested: cohort 1 (9 Gy × 2), cohort 2 (10 Gy × 5), cohort 3 (6 Gy × 5), and cohort 4 (7 Gy × 5). Patients were treated in cohorts of three patients, and the Bayesian escalation with overdose control method was used to determine the MTD of the SBRT boost. Dose‐limiting toxicities (DLTs) were defined as any grade 3 or higher toxicities within 30 days of treatment attributed to treatment, not including hematologic toxicity, or any grade 5 toxicity attributed to treatment. Results: The study enrolled 19 patients from November 2012 to December 2016. There were four screen failures, and 15 patients were treated on study. There were no DLTs in dose cohort 1 (n = 3) and 2 (n = 6). DLT developed in one patient in dose cohort 3 (n = 3) and in 2 patients in dose cohort 4 (n = 3). The calculated MTD was 6 Gy × 5. The DLT observed at this dose level was a tracheoesophageal fistula; given this substantial toxicity, there was investigator reluctance to enroll further patients at this dose level. Thus, the calculated MTD was 6 Gy × 5; however, 10 Gy × 2 is thought to be a reasonable dose as well, given that no grade 5 toxicities occurred with that dose. Conclusions: The MTD of a SBRT boost combined with 44 Gy of thoracic chemoradiation was 6 Gy × 5. A SBRT boost dose of 10 Gy × 2 could be considered safer, with no grade 3 or higher toxicities observed at this dose level during the follow‐up period in this study.

Guideline-concordant Care Improves Overall Survival for Locally Advanced Non–Small-cell Lung Carcinoma Patients: A National Cancer Database Analysis

Background Current evidence‐based guideline‐concordant care (GCC) for locally advanced non–small‐cell lung cancer (NSCLC) patients with good performance status is concurrent chemoradiation. In this study we evaluated factors associated with lack of GCC and its effects on overall survival (OS). Patients and Methods Unresectable stage III NSCLC patients, diagnosed from 2005 to 2013 with a Charlson–Deyo score of 0, were identified from the National Cancer Database. Primary outcomes were receipt of GCC, defined as concurrent chemoradiation (thoracic radiotherapy, starting within 2 weeks of chemotherapy, to at least 60 Gy), and OS. Multivariable logistic regression modeling identified variables associated with non‐GCC. Cox proportional hazard modeling was used to examine OS. Results Twenty‐three percent of patients (n = 10,476) received GCC. Uninsured patients were more likely to receive non‐GCC (odds ratio [OR], 1.54; P < .001) compared with privately insured patients. Other groups with greater odds of receiving non‐GCC included: patients treated in the western, southern, or northeastern United States (ORs, 1.39, 1.37, and 1.19, respectively; all Ps < .001) compared with the Midwest; adenocarcinoma histology (OR, 1.48; P < .001) compared with squamous cell carcinoma; and women (OR, 1.08; P = .002). Those who received non‐GCC had higher death rates compared with those who received GCC (hazard ratio [HR], 1.42; P < .001). The uninsured (HR, 1.53; P < .001), patients treated in the western, southern, or northeastern United States (HRs, 1.56, 1.41, and 1.34, respectively; P < .001), adenocarcinomas (HR, 1.39; P < .001), and women (HR, 1.44; P < .001) also all had lower OS for non‐GCC versus GCC. Conclusion Socioeconomic factors, including lack of insurance and geography, are associated with non‐GCC. Patient‐ and disease‐specific factors, including increasing adenocarcinoma histology and sex, are also associated with non‐GCC. Non‐GCC diminishes OS. Micro‐Abstract Several socioeconomic factors, including lack of insurance and geography, and patient‐ and disease‐specific factors, including increasing adenocarcinoma histology and sex, are associated with receipt of non–guideline‐concordant care. Non–guideline‐concordant care is associated with poorer survival outcomes.

The risk of carotid stenosis in head and neck cancer patients after radiation therapy

OBJECTIVES Head and neck radiotherapy (RT) is a risk factor for cerebrovascular disease. We performed a retrospective cohort study to evaluate carotid artery stenosis (CAS) incidence in head and neck cancer (HNC) patients undergoing RT, characterizing associated risk factors. MATERIALS AND METHODS Records were retrospectively reviewed for HNC patients undergoing carotid ultrasound screening after definitive or adjuvant RT between January 2000 and May 2016. CAS was defined as ≥50% stenosis on imaging, stroke, or transient ischemic attack. Actuarial CAS rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses predicted CAS risk based on carotid dosimetric and clinical parameters. RESULTS 366 patients met inclusion criteria. Median time from RT completion to last follow-up was 4.1 yr. Actuarial risk for CAS was 29% (95% CI 22-36%) at 8 years. Univariate analysis showed that smoking (HR 1.7; 95% CI 1.1-2.7), hyperlipidemia (HR 1.6; 95% CI 1.03-2.6), diabetes (HR 2.8; 95% CI 1.6-4.8), coronary artery disease (HR 2.4; 95% CI 1.4-4.2), and peripheral artery disease (HR 3.6; 95% CI 1.1-11.6) were significantly associated with increased CAS. In multivariate analysis, diabetes was predictive of time to CAS (HR 1.9; 95% CI 1.1-3.4). Carotid dose parameters were not significantly associated with CAS. CONCLUSIONS CAS incidence is high after head and neck radiotherapy, gradually rising over time. No clear dose-response effect between carotid dose and CAS was identified for HNC patients. Carotid artery screening and preventative strategies should be employed in this high-risk patient population.

Impact of intensity modulated radiation therapy on survival in anal cancer

Background This study was designed to investigate the impact of intensity modulated radiation therapy (IMRT) on overall survival (OS) in patients treated with chemoradiation (CRT) for anal cancer (AC). Methods We performed a case-control, propensity score (PS) matched analysis of the National Cancer Data Base (NCDB) of patients diagnosed with non-metastatic AC from 2004 to 2013. Only patients receiving concurrent CRT were included. Patients were stratified into two groups based on the RT technique: IMRT vs. non-IMRT. Multivariate analysis (MVA) and Kaplan-Meier (KM) plots for OS were obtained for the matched and unmatched groups. Results A total of 8,108 patients diagnosed between 2004 and 2013 were eligible for the study, of which 3,307 (40.8%) and 4,801 (59.2%) were in the IMRT and non-IMRT groups, respectively. Median follow-up for all patients was 54.4 months. After PS matching, MVA for OS showed that IMRT was associated with improved OS compared to non-IMRT (HR 0.83, 95% CI: 0.74-0.94; P=0.002). Adjusted KM analysis showed that the 5-year OS for patients treated with IMRT was 74.6% vs. 70.5% (P=0.0022). Conclusions To our knowledge, this is the largest study to date that evaluates the impact of IMRT on OS for patients with AC. Our investigation shows that IMRT based concurrent CRT for non-metastatic AC is associated with improved survival when compared to similar patients treated with non-IMRT based therapy. In the absence of randomized evidence, our analysis might provide additional support for increasing the use of IMRT for patients with AC receiving concurrent CRT.

Hypofractionated external beam radiation therapy in combination with HDR boost for localized prostate cancer: patient reported quality of life outcomes

Purpose There is limited data to support the use of hypofractionated external beam radiation (HypoF) in combination with high-dose-rate brachytherapy (HDR). We report our quality of life (QOL) outcomes when treating intermediate and high-risk prostate cancer patients with external beam radiation (EBRT) plus HDR. Material and methods The charts of 54 patients with localized adenocarcinoma of the prostate treated with standard fractionation (SF) or HypoF EBRT plus HDR boost at a single institution between 2012 and 2015 were reviewed. All patients completed the American Urological Association Symptom Score (AUASS) and Expanded Prostate Index for Prostate Cancer – Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and completed at least one follow-up survey. Linear mixed models were performed to test for significant changes and differences in each outcome over time. Results There was no significant difference in AUA score (p = 0.98), incontinence (urge) and urinary irritation/obstruction scores (p = 0.81 and p = 0.62, respectively), and bowel QOL (p = 0.97) between the two dosing groups over time or at any discrete time point. For both groups, AUA scores peaked at 0-2 months before improving. Likewise, sexual function, vitality score, and QOL scores were also not significantly different between the dose groups over time (p = 0.59, p = 0.37, and p = 0.71, respectively). All QOL categories, except sexual function, trended toward baseline with increasing time from intervention. Conclusions Our study suggests HypoF EBRT can be delivered in combination with HDR for patients with ntermediate-risk and high-risk adenocarcinoma of the prostate without increasing toxicity compared to SF with an HDR boost.

Outcomes and Practice Patterns for Aggressive Local Therapy in Newly Diagnosed Stage IV Soft Tissue Sarcoma: An NCDB Analysis

Time Session Type Abstract # Author Title Innovation Hub, Exhibit Hall 3 1:15PM 2:45PM Poster Viewing Q&A 1 2204 Benjamin Fischer-Valuck, MD Effectiveness of Adjuvant Radiation Therapy After Radical Cystectomy for Locally Advanced Bladder Cancer Innovation Hub, Exhibit Hall 3 1:15PM 2:45PM Poster Viewing Q&A 1 2035 Neil Pfister, MD, PhD HIV-Positive Anal Cancer Patients Treated with Definitive Chemoradiation: Factors Impacting Clinical Outcomes Innovation Hub, Exhibit Hall 3 1:15PM 2:45PM Poster Viewing Q&A 1 2152 Daniel Tanenbaum, MD Size of hepatic metastases on PET/CT versus pathologic specimen: implications for radiation treatment planning Stars at Night Ballroom 3:45PM 3:55PM Clinical Trials Session 01 3 Deborah Bruner, PhD, RN, FAAN Patient Reported Outcomes of NRG Oncology/RTOG 0232: A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone in Intermediate Risk Prostate Cancer

Targeted sequencing and intracranial outcomes of patients with lung adenocarcinoma brain metastases treated with radiotherapy: Sequencing Outcomes in Lung Brain Metastases

Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next‐generation sequencing results and investigate molecularly based outcomes for patients with AC‐BMs treated with radiotherapy.

Fine-tuning the normal tissue objective in eclipse for lung stereotactic body radiation therapy

The purpose of this study was to characterize the effects of the normal tissue objective (NTO) on lung stereotactic body radiation therapy (SBRT) dose distributions. The NTO is a spatially varying constraint used in Eclipse to limit dose to normal tissues by steepening the dose gradient. However, the multitude of potential NTO setting combinations challenges optimal NTO tuning. In the present study, a broad range of NTO settings are investigated for lung SBRT treatment planning with volumetric modulated arc therapy(VMAT). Ten prior lung SBRT cases were replanned using NTO priorities of 1, 50, 100, 200, 500, and 999 in combination with fall-off values of 0.01, 0.05, 0.10, 0.15, 0.20, 0.30, 0.50, 1.00, and 5.00 mm-1 and the automatic NTO. NTO distances to planning target volume (PTV), start dose, and end dose were 1 mm, 100%, and 10%, respectively, for all 600 plans. Prescription dose covered 95% of the PTV. The following metrics were recorded: conformity index (CI), ratio of the 50% prescription isodose volume to PTV (R50%), maximum dose 2 cm away from PTV (D2cm), lung volume of ≥20 Gy (V20Gy), maximum PTV dose (PTVmax), and monitor units (MUs). Differences between prior plans and NTO plans were evaluated using the Wilcoxon signed-rank test. Different combinations of NTO settings resulted in wide-ranging plan quality metrics: CI (1.00 to 1.54), R50% (3.95 to 7.57), D2cm (33.4% to 67.9%), V20Gy (1.66% to 2.75%), MU (1.81 cGy-1 to 4.69 cGy-1), and PTVmax (118% to 175%). Although no settings were optimal for all metrics, a fall-off of 0.15 mm-1 and a priority of 500 best satisfied institutional criteria. Compared with prior plans, NTO plans resulted in significantly lower R50% (4.00 vs 4.35, p = 0.002), lower V20Gy (1.22% vs 1.32%, p = 0.006), and higher PTVmax (138% vs 122%, p = 0.002). All of the prior and well-tuned NTO plans met Radiation Therapy Oncology Group (RTOG) 0813 guidelines. Lung SBRT dose distributions were characterized across a range of NTO settings. NTO plans with well-tuned settings compared favorably with prior plans.

Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: analysis of the national cancer data base

Background To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation (CRT) in the National Cancer Data Base (NCDB). Methods The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis (UVA) was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n=498, 46.8%) and HPV- (n=565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR: 0.60, 95% CI: 0.38-0.96; P=0.034). However, for women, HPV infection did not significantly influence survival (HR: 1.47, 95% CI: 0.96-2.25; P=0.074). Conclusions To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.