Jeffrey R. Olsen

Stereotactic body radiotherapy for primary hepatic malignancies – Report of a phase I/II institutional study

BACKGROUND AND PURPOSE To report outcomes and toxicities of a single-institution phase I/II study of stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular cancer (HCC) and intrahepatic cholangiocarcinoma (IHC). MATERIALS AND METHODS Patients with Child-Pugh score less than 8 were eligible. A total of 32 lesions in 26 patients were treated with SBRT. Kaplan-Meier survival analysis was performed. Toxicities were graded by CTCAEv4 criteria and response was scored by EASL guidelines. RESULTS Median prescribed dose was 55Gy (range 40-55Gy) delivered in 5 fractions. Mean tumor diameter was 5.0cm and mean GTV was 107cc. Median follow-up was 8.8months with a median survival of 11.1months, and one-year overall survival was 45%. Overall response rate was 42% and one-year local control was 91%. Nine patients experienced a decline in Child-Pugh class following treatment, and two grade 5 hepatic failure toxicities occurred during study follow-up. CONCLUSIONS Primary hepatic malignancies not amenable to surgical resection portend a poor prognosis, despite available treatment options. Though radiation-induced liver disease (RILD) is rare following SBRT, this study demonstrates a risk of hepatic failure despite adherence to protocol constraints.

Efficacy and toxicity of rectal cancer reirradiation using IMRT for patients who have received prior pelvic radiation therapy

Purpose Locally recurrent rectal cancer may cause significant morbidity. Prior reports of rectal cancer reirradiation following local recurrence suggest treatment efficacy, with variable rates of late toxicity. Modern techniques including intensity modulated radiation therapy (IMRT) may improve the therapeutic index. We report outcomes for pelvic reirradiation as treatment for rectal cancer using IMRT. Methods and materials The records of 31 patients undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed. All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5-Gy fractions delivered twice daily, n=15) or once-daily fractionation technique (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median cumulative dose was 77 Gy (range, 59-113), and the median interval from prior pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery was generally reserved for patients with an isolated local recurrence. Concurrent chemotherapy was administered for 25/31 patients, most frequently capecitabine (n=11) or continuous infusion 5-fluorouracil (n=10). Results Median follow-up was 11.3 months. The prescribed treatment was completed in 29/31 patients (93.5%). Among 18 patients with symptoms attributable to recurrent disease, successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at 1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was 21.9 months, and 1-year survival was 66.7% for patients who had surgical resection versus 58.7% for those who did not (P = .0802). Conclusions Rectal cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic radiation therapy. Given significant risk of local progression, further dose escalation may be warranted for patients with life expectancy exceeding 1 year.

Predictors of Survival after Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases

PURPOSE To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses. RESULTS The median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4-12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR) <5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (>20 ng/mL), high AST (>40 IU/L), NLR ≥5, and extrahepatic metastases (P values of <.001, <.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively). CONCLUSIONS The prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.

Quantitative FDG-PET/CT predicts local recurrence and survival for squamous cell carcinoma of the anus

Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography–(PET)/computed tomography (CT) imaging is used for staging and treatment planning of patients with anal cancer. Quantitative pre- and posttreatment metrics that are predictive of recurrence are unknown. We evaluated the association between pre- and posttreatment FDG-PET/CT parameters and outcomes for patients with squamous cell carcinoma of the anus (SCCA). Methods and materials The records of 110 patients treated between 2003 and 2013 with definitive radiation therapy for SCCA were reviewed under an institutional review board–approved protocol. The median radiation therapy dose was 50.4 Gy (range, 35-60 Gy). Concurrent chemotherapy was administered for 109 of 110 patients and generally consisted of 5-fluorouracil and mitomycin C (n = 94). All patients underwent pretreatment FDG-PET/CT and 101 of 110 underwent posttreatment FDG-PET/CT 3 months after completion of radiation therapy. The maximum standard uptake value (SUVmax) was analyzed, in addition to multiple patient and treatment factors, by univariate and multivariate Cox regression for correlation with local recurrence (LR) and overall survival (OS). Results The median follow-up was 28.6 months. LR occurred in 1 of 15 (6.7%), 5 of 47 (10.6%), and 6 of 48 (12.5%) patients with stage I, II, and III disease, respectively. On univariate analysis, a significant association was observed between reduced LR and posttreatment SUVmax <6.1 (P = .0095) and between increased OS and posttreatment SUVmax <6.1 (P = .0086). On multivariate analysis, a significant association was observed between reduced LR and posttreatment SUVmax <6.1 (P = .0013) and the use of intensity modulated radiation therapy (P < .001). A significant multivariate association was observed between increased OS and posttreatment SUVmax <6.1 (P = .0373) and the use of 5-fluorouracil/mitomycin C chemotherapy (P = .001). Conclusion Posttreatment SUVmax <6.1 is associated with reduced LR and increased OS after chemoradiation therapy for SCCA independent of T and N stage on multivariate analysis. Greater follow-up is required to confirm this association with late patterns of failure.

Magnetic Resonance Imaging for Target Delineation and Daily Treatment Modification

Magnetic resonance (MR) imaging has become a prevalent modality in radiation oncology owing to its excellent soft-tissue contrast and ability to provide functional information. Recent technological developments have combined MR imaging with treatment delivery systems, to provide in-room MR guidance for patient setup and treatment delivery. Availability of in-room MR imaging enables direct visualization of soft-tissue targets and nearby organs at risk, thus providing a platform for fast and accurate target and organs at risk delineation for plan adaptation and target tracking during treatment. This article describes the 2 clinically implemented MR image-guided radiotherapy systems and their role in target localization and in-room treatment adaptation. Clinical data from early adopters of these systems is reviewed.

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.

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.

SP-0620: In-room MR image-guided plan of the day

S295 ______________________________________________________________________________________________________ surrogates or the actual tumor position. Corrections are usually limited to translations, and rotational errors, shape change and intra-fractional changes are not corrected for. For targets with a large day-to-day shape variation, or in case of multiple targets with differential motion, generous safety margins have to be used that partly undo the healthy tissue sparing properties of modern radiation techniques such as IMRT and VMAT. Adaptive radiotherapy (ART), e.g. with a Plan-of-the-Day (PotD) strategy has been proposed to overcome this problem. Guidelines for proper selection of patients that need a replanning (e.g. lung, rectum), or implementation of a more labour-intensive PotDworkflow for groups of patients (e.g. cervix, bladder) have been major research topics in recent years. In this presentation, an overview will be given of current clinical implementations of PotD strategies in literature. The library-based PotD procedure as implemented at Erasmus MC for cervical cancer patients will be discussed in more detail. For these patients, a plan library contains 2 or 3 VMAT plans adequate for target shapes and positions corresponding to smaller and larger bladder volumes. Every treatment day, the best fitting plan is selected based on an in-room acquired cone beam CT scan, showing internal anatomy and markers implanted around the primary tumor. The recent PotD implementation in our record & verify system has pathed the way for a more wide-spread application of safe and efficient delivery of library-based PotD strategies, and for more advanced library-based approaches including dynamic planlibrary updates.

PO-0891: Clinical implementation and experience with real-time anatomy tracking and gating during MR-IGRT

ESTRO 35 2016 ______________________________________________________________________________________________________ produced for each patient. All plans had a mean CTV dose of 18.75 Gy per fraction (=100% dose) and 95% minimum CTV dose coverage. The PTV was covered by 50%, 67%_S, 67% (our standard), 80%, and 95% of the prescribed dose, respectively. The 67%_S plan was an alternative to the standard 67% plan made with maximum conformity, i.e. as steep as possible dose gradient from 95% to 67% outside the CTV. The 50%, 67%_S, 80%, and 95% plans were renormalized to be isotoxic with the standard 67% plan, i.e. to give the same risk of radiation induced liver disease (RILD) according to the NTCPmodel of Dawson et al. (Acta Oncol., 2006). For each patient and plan, the dosimetric effects of the observed intrafraction motion were investigated by calculating the delivered dose by an in-house developed method for motion-including dose reconstruction.

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.