L.E. Henke

BRAF V600E mutational status in pediatric thyroid cancer

Clinical outcome of papillary thyroid carcinoma (PTC) in children differs significantly from that of adults. There is no clear explanation of this difference although previous studies have demonstrated a lower prevalence of the BRAFV600E mutation in PTC of children. However, data are limited due to the rarity of this diagnosis. BRAFV600E mutation prevalence and its relationship with outcome in pediatric PTC remain unclear.

BRAF mutation is not predictive of long‐term outcome in papillary thyroid carcinoma

The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence‐free survival (RFS) and disease‐specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long‐term outcomes in the largest, single‐institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1–2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1–2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1–2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan–Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high‐risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy.

Treatment Patterns and Survival Outcomes for Patients with Small Cell Carcinoma of the Bladder

BACKGROUND Small cell carcinoma of the bladder (SCCaB) is a rare tumor without a standard treatment algorithm. Treatment patterns and survival outcomes from the National Cancer Database (NCDB) may provide insight into optimal treatment strategies. OBJECTIVE To investigate the relationship between overall survival (OS) and treatment strategy. DESIGN, SETTING, AND PARTICIPANTS This was an observational study of treatment-naïve patients who received treatment from 2004 to 2013. Patients with cT1-4aN0M0 SCCaB were identified from the NCDB, a hospital-based tumor registry that captures >70% of incident cancer cases in the USA. INTERVENTION Treatment strategies included local therapy alone, chemotherapy (CT), radiation therapy (RT), chemoradiation therapy (CRT), radical cystectomy (RC), and RC plus chemotherapy (RC+C). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS OS was analyzed as a function of treatment modality adjusting for patient, demographic, and tumor-related factors. The Kaplan-Meier survival method, and the log-rank test and Cox regression were used for univariable and multivariable analyses. RESULTS AND LIMITATIONS We identified 856 patients with median follow-up of 18.3 mo. The median OS for the entire cohort was 20.7 mo (95% confidence interval [CI] 18.3-23.2) and estimated 3-yr and 5-yr OS were 37.5% and 28.2%, respectively. The most common treatment modality was CT (225 patients; 26.3%) followed by CRT (203 patients; 23.7%) and RC+C (201 patients; 23.5%). The median OS was 18.4 mo (95% CI 15.2-21.5) for CT, 34.1 mo (95% CI 22.5-45.8) for CRT, and 32.4 mo (95% CI 20.8-44.1) for RC+C. OS did not significantly differ between CRT and RC+C (p=0.42). On multivariable analysis, the best OS was associated with CRT (hazard ratio [HR] 0.41, 95% CI 0.32-0.53; p<0.0001) and RC+C (HR 0.45, 95% CI 0.34-0.59; p<0.0001). CONCLUSIONS RC+C and CRT are associated with better OS compared to monotherapy among patients with SCCaB. PATIENT SUMMARY Small cell carcinoma of the bladder is a rare and highly aggressive cancer. According to National Cancer Database data, radical cystectomy plus chemotherapy and chemoradiation therapy are associated with better overall survival compared to monotherapy.

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience

AIMS Magnetic resonance image-guided radiotherapy (MRIgRT) has been clinically implemented since 2014. This technology offers improved soft-tissue visualisation, daily imaging, and intra-fraction real-time imaging without added radiation exposure, and the opportunity for adaptive radiotherapy (ART) to adjust for anatomical changes. Here we share the longest single-institution experience with MRIgRT, focusing on trends and changes in use over the past 4.5 years. MATERIALS AND METHODS We analysed clinical information, including patient demographics, treatment dates, disease sites, dose/fractionation, and clinical trial enrolment for all patients treated at our institution using MRIgRT on a commercially available, integrated 0.35 T MRI, tri-cobalt-60 device from 2014 to 2018. For each patient, factors including disease site, clinical rationale for MRIgRT use, use of ART, and proportion of fractions adapted were summated and compared between individual years of use (2014-2018) to identify shifts in institutional practice patterns. RESULTS Six hundred and forty-two patients were treated with 666 unique treatment courses using MRIgRT at our institution between 2014 and 2018. Breast cancer was the most common disease, with use of cine MRI gating being a particularly important indication, followed by abdominal sites, where the need for cine gating and use of ART drove MRIgRT use. One hundred and ninety patients were treated using ART in 1550 fractions, 67.6% (1050) of which were adapted. ART was primarily used in cancers of the abdomen. Over time, breast and gastrointestinal cancers became increasingly dominant for MRIgRT use, hypofractionated treatment courses became more popular, and gastrointestinal cancers became the principal focus of ART. DISCUSSION MRIgRT is widely applicable within the field of radiation oncology and new clinical uses continue to emerge. At our institution to date, applications such as ART for gastrointestinal cancers and accelerated partial breast irradiation (APBI) for breast cancer have become dominant indications, although this is likely to continue to evolve.

Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: A hospital-based analysis of patterns of care, RT fractionation scheme, and overall survival

Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC‐RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC‐RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan‐Meier method, log‐rank test, Cox proportional hazards models, and propensity score‐matched analyses. A total of 2255 (85.4%) patients were included in the LC‐RT group and 386 (14.6%) patients in the SC‐RT group. SC‐RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32‐2.20), treatment at an academic center (OR: 1.76, 1.20‐2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05‐1.83), treatment to the rib (OR: 2.99, 1.36‐6.60), and in 2014 (OR: 1.73, 1.19‐2.51). RT to the spine was more commonly long course (P < .0001). In the propensity‐matched cohort, LC‐RT was associated with improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC‐RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC‐RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center.

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiotherapy

Purpose Daily magnetic resonance (MR)–guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment. Methods and materials Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test. Results The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively. Conclusions This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

EP-1225: MRI-defined GTV change during SBRT for unresectable or oligometastatic disease of the central thorax

Purpose or Objective: Background: There is great potential to utilise a large range of retrospective clinical data as an evidence base in decision support systems (DSS) for cancer prognosis and subsequent personalised treatment decisions. Recently, there were several DSSs built for this purpose using machine learning tools, mainly regression models, Bayesian Networks (BN) and Support Vector Machines (SVM). These machine learning tools provide only a prediction of a class (decision), based on input attributes that were used to build the model, without providing additional information to clinicians about how and why this prediction was made. Objective: To investigate the performance of an alternative machine learning tool in building a lung cancer radiotherapy DSS that provides clinicians with an estimated prediction together with the influencing attributes and their values (evidence) in supporting the decision reached. This will provide contextual justification to clinicians regarding the decisions, which will further help them in deciding whether to adopt the machine prediction or not.

TU-AB-BRA-11: Indications for Online Adaptive Radiotherapy Based On Dosimetric Consequences of Interfractional Pancreas-To-Duodenum Motion in MRI-Guided Pancreatic Radiotherapy

PURPOSE Dose limiting structures, such as the duodenum, render the treatment of pancreatic cancer challenging. In this multi-institutional study, we assess dosimetric differences caused by interfraction pancreas-to-duodenum motion using MR-IGRT to determine the potential impact of adaptive replanning. METHODS Ten patients from two institutions undergoing MRI-guided radiotherapy with conventional fractionation (n=5) or SBRT (n=5) for pancreatic cancer were included. Initial plans were limited by duodenal dose constraints of 50 Gy (0.5 cc)/31 Gy (0.1 cc) for conventional/SBRT with prescriptions of 30 Gy/5 fractions (SBRT) and 40-50 Gy/25 fractions (conventional). Daily volumetric MR images were acquired under treatment conditions on a clinical MR-IGRT system. The correlation was assessed between interfractional GTV-to-duodenum positional variation and daily recalculations of duodenal dose metrics. Positional variation was quantified as the interfraction difference in Hausdorff distance from simulation baseline (ΔHD) between the GTV and proximal duodenal surface, or volume overlap between GTV and duodenum for cases with HD0 =0 (GTV abutting duodenum). Adaptation was considered indicated when daily positional variations enabled dose escalation to the target while maintaining duodenal constraints. RESULTS For fractions with ΔHD>0 (n=14, SBRT only), the mean interfraction duodenum dose decrease from simulation to treatment was 44±53 cGy (maximum 136 cGy). A correlation was found between ΔHD and dosimetric difference (R2 =0.82). No correlation was found between volume of overlap and dosimetric difference (R2 =0.31). For 89% of fractions, the duodenum remained overlapped with the target and the duodenal dose difference was negligible. The maximum observed indication for adaptation was for interfraction ΔHD=11.6 mm with potential for adaptive dose escalation of 136 cGy. CONCLUSION This assessment showed that Hausdorff distance was a reasonable metric to use to determine the indication for adaptation. Adaptation was potentially indicated in 11% of the treatments (fractions where GTV-to-duodenum distance increased from simulation), with a feasible average dose escalation of 7.0%. MB, LH, JO, RK, PP: research and/or travel funding from ViewRay Inc. PP: research grant from Varian Medical Systems and Philips Healthcare.