Brian Czito

<h4>Purpose/objective(s)</h4>Radiation is increasingly used to treat oligometastatic patients (OM). Following metastasis directed radiation therapy, progression in nearby nodal basins or bones is common. We previously reported clinical outcomes of OM treated with an elective simultaneous integrated boost (SIB) technique delivering higher doses to known metastases and reduced doses to adjacent bones/nodal basins. Here we compare outcomes of OM receiving radiation to metastases alone (MA) versus those treated via an SIB. We hypothesized that use of SIB would maintain treated metastasis control (TMC) while reducing MR.<h4>Materials/methods</h4>OM patients with ≤5 active metastases treated with either SIB or MA at our IRB approved sites from 2013-2018 were analyzed for toxicities, pain control, and recurrence patterns. TMC was defined as absence of progression in high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside elective PTV, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as any recurrence outside of the treatment PTVs not meeting other criteria. Outcome rates were estimated using the Kaplan-Meier method. Patients treated with the two techniques were compared using the log rank test.<h4>Results</h4>101 patients were treated to 90 SIB (58% nodal and 42% osseous) and 46 MA (22% nodal and 78% osseous) sites. The most common primary tumors were prostate (37%), lung (15%), and breast (7%). Median follow up among surviving patients was 24.6 months (range 1.4-71.0). Of the MA treated patients, doses ranged from 18 Gy in 1 fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No patients in either cohort experienced acute grade ≥3 toxicity. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis n = 1, vertebral body compression n = 2) and no MA patients. There was similar crude pain relief between cohorts: 82% with MA (9/11 patients reporting improved pain) and 86% with SIB (19/22). Crude MR were more frequent in the MA group 13% (n = 6) compared to SIB group 2% (n = 2). MR-free survival at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (P = 0.07). Crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences found in DR-free survival (P = 0.24) or Disease-free survival (P = 0.4) and Overall survival (P = 0.26) between MA and SIB cohorts.<h4>Conclusion</h4>Both SIB and MA irradiation of OM achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for OM treated with SIB. Although more late grade 3 toxicities were seen in the SIB cohort, these were mechanistically related to the high dose PTV and not the elective volume, with differences in treated metastasis location/characteristics. Further investigation of this technique with prospective trials is warranted.

<h4>Purpose/objective(s)</h4>Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity.<h4>Materials/methods</h4>We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity.<h4>Results</h4>149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BED_{α/β = 10}) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement).<h4>Conclusion</h4>SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.