Radiation Therapy For Liver Metastases Research Articles

The Tumor Microenvironment and Clinical Implications of Radiotherapy and Immunotherapy for Liver Metastases from Non-Small Cell Lung Cancer (NSCLC)

Immunotherapy emergence has triggered a profound change in the approach to treating advanced non-small cell lung cancer (NSCLC). However, challenges arise when tumors metastasize to critical sites such as the brain, bones, and liver, impeding the efficacy of immunotherapeutic interventions. Particularly, liver metastases exhibit a considerably unfavorable prognosis in comparison to other metastatic sites, owing in part to the prevailing immunosuppressive microenvironment within the liver that hampers immune-based therapies. Hence, it is imperative to investigate novel strategies that can bolster immune responses and prolong the survival of individuals with liver metastases (LM). Radiotherapy (RT) stands out as a primary modality in cancer treatment. Preclinical studies have revealed its capability to reshape the tumor microenvironment (TME), shifting it from an immunosuppressive setting to one that promotes immune activity. This transformative mechanism holds the promise of amplifying the effectiveness of immune-based treatments. This article will discuss the mechanisms by which radiotherapy improves the immunosuppressive microenvironment in the liver, provide a comprehensive review of the research progress on the combined application of RT and immunotherapy for LM, and offer insights into the establishment of novel therapeutic strategies for patients with LM.

155: Outcomes of Stereotactic Ablative Radiation Therapy for Liver Metastases from Colorectal Carcinoma

155: Outcomes of Stereotactic Ablative Radiation Therapy for Liver Metastases from Colorectal Carcinoma

The role of selective internal radiation therapy for liver metastases from pancreatic adenocarcinoma after progression on prior chemotherapy.

e16272 Background: Selective internal radiation therapy (SIRT) has established benefit for liver metastases in colorectal cancer. Very little data exists on the use of SIRT for liver dominant metastatic pancreatic cancer. A 2015 phase II trial by Gibbs et al suggested that SIRT at diagnosis may be beneficial in liver metastases in pancreatic cancer, particularly in those who have had a previous primary resection. Methods: In this single-institute retrospective audit we identified eleven patients who had liver predominant metastatic adenocarcinoma of the pancreas who received SIRT at any stage of their treatment. Data was analysed from our electronic patient databases. Results: 11 patients with adenocarcinoma of the pancreas, who had SIRT following progression on chemotherapy were identified. 3 had a primary surgical resection. All patients had received a minimum of one line of chemotherapy and had ECOG performance status of 2 or less. The median time from diagnosis to SIRT was 13 months (range 5-24 months). Patients received Yttrium-90 microspheres with a median activity of 2.1GBq with all eleven receiving concurrent infusional 5-FU 225mg/m2/day for 7 days prior and 14 days after. The median survival after SIRT therapy was 6 months (range 2-19 months). The median overall survival from diagnosis was 20 months (range 12-31 months). SIRT appeared safe and well-tolerated with no associated 30 day all-cause mortality. One patient developed radiation induced asymptomatic portal hypertension and liver cirrhosis. Conclusions: This is the first report of the use of SIRT with radiosensitising concurrent infusional 5FU for metastatic pancreatic cancer after failure of prior chemotherapy. We conclude that SIRT with concurrent infusional 5FU offers an additional treatment option for patients with liver dominant metastatic pancreatic cancer, who maintain a good PS who have progressed on prior lines of chemotherapy. This can provide a durable treatment response and requires further exploration.

The Dutch–Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 515 Patients and 668 Metastases

Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases

We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study. Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control. Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%. For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.

Long Term Results of a Phase I Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Radiation Therapy for Liver Metastases

Stereotactic ablative radiotherapy (SabR) is an increasingly utilized treatment modality for liver metastases, but limited data are available on outcomes and toxicity from single fraction treatment. We report long term outcomes from a Phase I dose-escalation study to determine the maximum tolerated dose of single-fraction liver SabR pooled with our subsequent single institutional experience with patients treated post-protocol at the highest dose level (40 Gy) from the Phase I study. Patients with liver metastases from solid tumors located outside of the central liver zone, defined as a 2-cm expansion around the course of the portal vein to its bifurcation in the liver, were treated with single-fraction SabR on a Phase I dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients were enrolled to the first dose level (prescription dose of 35 Gy). Dose was then escalated to 40 Gy in a single fraction, and seven more patients were treated. An additional 19 patients with liver metastases from solid tumors were subsequently treated to 40 Gy in a single fraction post-protocol. Treatment plan was defined by multidisciplinary team in all cases. Patients were followed for toxicity and underwent serial imaging to assess for local control. Median imaging follow up for the combined cohort (n = 33, 39 lesions) was 21.3 months; 38.9 months for protocol patients and 12.8 months for subsequent patients. Fourteen patients with 17 liver metastases were treated on protocol, and subsequently 19 additional patients with 22 liver metastases were treated to 40 Gy. All patients had confirmed metastatic disease, and 36.3% had other non-hepatic sites of metastatic disease at time of treatment. Median lesion size was 2.1 cm (range 0.5-5.0 cm). The majority of patients had colorectal (45.5%) or renal (21.1%) malignancies. As previously reported, there were no dose-limiting toxicities observed at either dose level for protocol patients, and only three Grade 2 toxicities (abdominal pain, nausea/vomiting, alkaline phosphatase elevation) were observed in the entire cohort, with no Grade ≥ 3 toxicities attributable to treatment. There were two local failures (5.1% crude rate of failure); one marginal failure in the protocol group in the 40 Gy cohort (73.5 months post-treatment), and one in-field failure in the subsequent group (14.5 months post-treatment); both patients’ lesions were colorectal histology. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.2%; 100% in the protocol group and 91% in the subsequent patients, respectively. Two- and four-year overall survival for all treated patients was 80% and 45.7%, respectively. For selected patients with liver metastases, single-fraction SabR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long term follow-up; results in subsequent patients treated with single-fraction SabR doses of 40 Gy confirm our earlier results.

A single-institutional experience with low dose stereotactic body radiation therapy for liver metastases.

This study reports a single-institutional experience treating liver metastases with stereotactic body radiation therapy (SBRT). 107 patients with 169 lesions were assessed to determine factors predictive for local control, radiographic response, and overall survival (OS). Machine learning techniques, univariate analysis, and the Kaplan-Meier method were utilized. Patients were treated with a relatively low median dose of 30 Gy in 3 fractions. Fractions were generally delivered once weekly. Median biologically effective dose (BED) was 60 Gy, and the median gross tumor volume (GTV) was 12.16 cc. Median follow-up was 7.36 months. 1-year local control was 75% via the Kaplan-Meier method. On follow-up imaging, 43%, 40%, and 17% of lesions were decreased, stable, and increased in size, respectively. 1-year OS was 46% and varied by primary tumor, with median OS of 34.3, 25.1, 12.5, and 4.6 months for ovarian, breast, colorectal, and lung primary tumors, respectively. Breast and ovarian primary patients had better OS (p < 0.0001), and lung primary patients had worse OS (p = 0.032). Higher BED values, the number of hepatic lesions, and larger GTV were not predictive of local control, radiographic response, or OS. 21% of patients suffered from treatment toxicity, but no grade ≥3 toxicity was reported. Relatively low-dose SBRT for liver metastases demonstrated efficacy and minimal toxicity, even for patients with large tumors or multiple lesions. This approach may be useful for patients in whom higher-dose therapy is contraindicated or associated with high risk for toxicity. OS depends largely on the primary tumor.

Dosimetric Validation of Digital Megavolt Imager for Flattening Filter Free Beams in the Pre-Treatment Quality Assurance of Stereotactic Body Radiation Therapy for Liver Metastases.

Aim:The aim is to evaluate the use of digital megavolt imager (DMI) aS1200 in portal dosimetry with flattening filter free (FFF) beams. Materials and Methods:Dosimetric properties of DMI is characterized at 6MV FFF beams for signal saturation, dose linearity, dependency on dose-rate and source-detector distance (SDD), signal lag (ghosting), and back scatter. Portal dosimetry is done for twenty volumetric modulated arc therapy (VMAT) based stereotactic body radiotherapy (SBRT) plans for the treatment of liver metastases and the results are compared with repeated measurements of Octavius 4D. Results:The detector signal to monitor unit (MU) ratio drops drastically below 25MU. The detector linearity with dose is within 1% and no evidence of signal saturation as such. The aS1200 response variation across various dose rates and SDD is <0.4% and <0.2% respectively. The effect of ghosting increased distinctly at higher dose rate but however it is negligible (0.1%). The impact of back scatter is <0.3% because of additional shielding provided at the back of the detector. The portal dosimetry results of SBRT QA plans evaluated at the gamma criteria of 2mm/2% (DTA/DD) both under global and local mode analysis has shown an average gamma passing rate of area gamma (<1) 97.9±0.8% and 96.4±0.9%. The SBRT QA results observed in aS1200 are inline and consistent with Octavius 4D measured results. Conclusion:The characteristics of aS1200 evaluated at FFF beams have shown its potential ability as QA tool and can be used in SBRT QA for liver metastases with greater confidence.

Stereotactic body radiation therapy for liver metastases: Clinical outcomes and literature review.

The role of stereotactic body radiation therapy (SBRT) in the management of liver metastasis is increasing, using ablative doses with the goal of local control and ultimately improving survival. The aim of this study is to evaluate our initial results regarding local control, overall survival and toxicity in patients with liver metastases treated with this technique, due to the lack of evidence reported in Latin America. We performed a retrospective chart review from November 2012 to June 2018 of 24 patients with 32 liver metastases. Kaplan-Meier curves were constructed for local control and overall survival. Clinical and prognostic factors were further analyzed by independent analysis. Median follow-up period was 22 months (range, 1-65 months). Median age was 62 years (range, 40-84 years). Colorectal carcinoma was the most common primary cancer. Overall 1-year and 2-years local control rates were 82% (95% Confidence Interval [CI], 70-98%) and 76.2% (95% CI, 45-90%), respectively. Median overall survival rate was 35 months (95%, CI 20.5-48 months). Overall 1-year and 2-year survival rates were 85.83% (95% CI, 64-99%) and 68% (95% CI, 45-84%), respectively. No acute or late grade 3 or 4 toxicity was observed during the follow-up period. SBRT achieves excellent local control and overall survival rates with low toxicity in patients with liver metastases. Based on our literature review, our results are consistent with larger reports. Further randomized trials are required to compare with other local therapies.

Clinical and genomic factors associated with outcome following ablative radiotherapy for oligometastatic and oligoprogressive liver tumors.

515 Background: There is increasing use of ablative radiotherapy (RT) for oligometastatic and/or oligoprogressive cancer, but the population who may benefit from this more aggressive treatment remains poorly defined. We aimed to identify factors associated with improved outcomes following ablative RT for oligometastatic/oligoprogressive liver tumors. Methods: We retrospectively analyzed 106 patients who had tumor genomic profiling and received a 5, 6, or 15-fraction course of ablative RT for liver metastases from 2008-2019. The interval off systemic therapy post-RT was calculated for patients who did not continue treatment through RT. Overall survival (OS) was estimated using the Kaplan-Meier method. The association between clinical and genomic variables and OS were assessed using uni- and multivariable Cox regression. Results: Median follow-up was 12.6 months. Median age was 61.3 years and 57% were male. The most common primary site was colorectum (42%), followed by pancreas (25%) and non-small cell lung cancer (10%). 42% had colorectal adenocarcinoma, 46% had other adenocarcinoma, and 12% had other histology. A BRAF/RAS family mutation (KRAS, NRAS, and/or BRAF) was present in 41%, 69% had &gt; 1 metastasis, and 38% had extra-hepatic disease. Median biological effective dose (α/β = 10) (BED) was 92 Gy. The RT field encompassed all liver metastases in 91%, and 11% received radiosensitizing chemotherapy. Median time off systemic agents was 5 months. Patients with 1 vs &gt; 1 metastasis had a longer interval off systemic therapy (9 vs 4 months, p = 0.026). Median OS was 12.6 months. The table shows the multivariable Cox model for OS. Conclusions: Presence of a BRAF/RAS family mutation, extra-hepatic metastases, exclusion of liver metastases from RT fields, lower BED, and concurrent radiosensitizing chemotherapy were associated with worse OS. This may inform patient selection and RT delivery for aggressive local therapy for liver metastases. [Table: see text]

132 Prognostic Index for Localized Liver Radiation - Metastatic (PILLiR-M): Development and Analysis of a Clinical Prognostic Tool to Improve Patient Selection for Liver Directed Radiotherapy for Liver Metastases

132 Prognostic Index for Localized Liver Radiation - Metastatic (PILLiR-M): Development and Analysis of a Clinical Prognostic Tool to Improve Patient Selection for Liver Directed Radiotherapy for Liver Metastases

The Dutch-Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 416 Patients with 560 Metastases

Purpose Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. Methods and Materials A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). Results Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. Conclusions This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases

PurposeThis study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases. Methods and materialsNonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT. ResultsA total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed. ConclusionsTreatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting.

A phase I trial of Proton stereotactic body radiation therapy for liver metastases.

A phase I trial to determine the maximum tolerated dose (MTD) of Proton stereotactic body radiation therapy (SBRT) for liver metastases in anticipation of a subsequent phase II study. An institutional IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5 cm, and no metastases location within 2 cm of the GI tract. Dose escalation was conducted with three dose cohorts. The low, intermediate, and high dose cohorts were planned to receive 36, 48, and 60 respectively to the internal target volume (ITV) in 3 fractions. At least 700 mL of normal liver had to receive <15. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort. Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume (GTV) 11.1 mL (range, 2.14-89.3 mL); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the low dose cohort had local recurrence and repeat SBRT was done to previously treated lesions without any toxicities. Biologically ablative Proton SBRT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II Proton SBRT study of 60 over 3 fractions for liver metastases.

A phase I study on stereotactic body radiotherapy of liver metastases based on functional treatment planning using positron emission tomography with 2-[18F]fluoro-2-deoxy-d-galactose

Background and purpose: The galactose analog 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) is used for quantification of regional hepatic metabolic capacity by functional positron emission tomography computerized tomography (PET/CT). In the present study, FDGal PET/CT was used for functional treatment planning (FTP) of stereotactic body radiotherapy (SBRT) of liver metastases with the aim of minimizing radiation dose to the best functioning liver tissue.Material and methods: Fourteen patients referred for SBRT had FDGal PET/CT performed before and one month after the treatment. The planning CT and the FDGal PET/CT images were deformable co-registered.Results: A reduction in the mean dose of approximately 2 Gy to the best functioning sub-volumes was obtained. One patient developed grade 2 acute morbidity and no patients experienced grade 3 or higher acute morbidities. The regional hepatic metabolic function post-treatment was linearly correlated to the regional radiation dose and for each 10-Gy increase in dose (γ10Gy), the metabolic function was reduced by 12%. A 50% reduction was seen at 22.9 Gy in 3 fractions (CI 95%: 16.7–30.4 Gy).Conclusion: The clinical study demonstrates the feasibility for FTP in patients with liver metastases and it was possible to minimize the radiation dose to the best functioning liver tissue.

Local Control Outcomes Using Stereotactic Body Radiation Therapy for Liver Metastases From Colorectal Cancer

To evaluate the effective dose and patterns of recurrence after stereotactic body radiation therapy (SBRT) for hepatic metastases that arise from colorectal cancer. A cohort of 70 patients with 103 colorectal liver metastases were treated with SBRT at a single institution. The prescribed doses were 45 to 60Gy in 3 to 4 fractions, but these were modified according to the tolerance of the adjacent normal tissue. To allow for dose comparisons, a biological equivalent dose was calculated. The median follow-up period was 34.2months (range, 5.3-121.8months). The 2-year overall survival and progression-free survival rates were 75% and 35%, respectively. In subgroups, the 2-year local control rates for biological equivalent dose ≤80Gy (group 1), 100 to 112Gy (group 2), and ≥132Gy (group 3) were 52%, 83%, and 89%, respectively. Cox proportional hazards model revealed a significant difference between groups (hazard ratio 0.44, P=.03 for group 2; hazard ratio 0.17, P=.17 for group 3; P=.01 for total). The major pattern of failure was a new liver metastasis out of the SBRT field. There was no grade ≥3 toxicity. Stereotactic body radiation therapy of liver metastases derived from colorectal cancer offers a locally effective treatment without significant complications. Longer local control can be expected if higher doses are used. Further studies will be needed to compare the efficacies of SBRT with those of surgical resection or radiofrequency ablation.

Abstract CT109: HITM-SIR: Phase Ib trial of CAR-T hepatic artery infusions and selective internal radiation therapy for liver metastases

Abstract OBJECTIVES: There are no effective treatment options for patients with unresectable CEA+ liver metastases (LM) from gastrointestinal adenocarcinoma refractory to conventional systemic therapy. In the previous Hepatic Immunotherapy for Metastases (HITM) phase I study we demonstrated the safety and biologic activity of anti-CEA CAR-T cell hepatic artery infusions (HAI). HITM-SIR was a single arm phase Ib trial testing anti-CEA CAR-T HAI followed by selective internal radiation therapy (SIRT) in patients with refractory CEA+ LM. METHODOLOGY: We enrolled 8 patients with unresectable, chemotherapy refractory CEA+ LM and 6/8 completed the study. Two patients were withdrawn for disease progression prior to CAR-T infusion and biliary obstruction due to centrally located disease. Limited extrahepatic disease (EHD) was permitted. Subjects received 3 HAI of anti-CEA CAR-T cells (1e10 cells per dose) along with low dose continuous IL-2 infusions (50,000 IU/kg/day). SIRT was administered in standard fashion 2 weeks following the 3rd CAR-T HAI. Primary objective was to establish safety of the CAR-T/SIRT combination. Secondary objectives included response assessed by modified RECIST (mRECIST), immune-related response criteria (irRC), and tumor marker kinetics. RESULTS: The mean age for enrolled subjects was 54.6 years (39-61) with 3 women and 5 men. Histologies (completed patients): 2 colon, 2 rectal, and 2 pancreas. This heavily pre-treated, advanced disease group of patients received an average of 2.3 lines of prior chemotherapy, 3/6 had &amp;gt;10 LM, and the average largest LM size was 7.3 cm. The average transduction efficiency as measured by CAR expression was 60.4%, with 90.9% viability, and an average production time for &amp;gt;3e10 cells of 13.8 days. There were no grade (G) 4/5 events related to the CAR-T, SIRT, or combination. Toxicities included G 1/2 liver function test elevations (n=5/6), fever (n=5/6), hypereosinophilia (n=2/6), and edema (n=2/6). G3 toxicities included colitis (n=2/6), fever (n=2/6), and edema (n=2/6). One patient experienced a hypertensive crisis during a single CAR-T infusion but tolerated 2 infusions without incident. All colitis episodes resolved with IL-2 dose reductions. Post-SIRT serum CEA decreases were noted in 2/6 patients (-40% and -71%) with CA19-9 decreases in 2/5 detectable patients (-31% and -32%). When considering all on-study time points, 5/6 patients had CEA responses (mean decrease 59.7%) and 4/5 patients expressing CA 19-9 decreases (mean 59.6%). At completion of the study, 3/6 patients had stable disease (SD) in the liver by mRECIST and irRC, and 3/6 SD overall by irRC. Target liver lesion decreases in size among patients with SD ranged from 6-28%. Regression of extrahepatic tumors or abscopal effects were noted in 2/6 at lung and bone sites. One patient remains without evidence of viable liver disease at 10.8 months follow-up. The median overall survival time for all patients is 6.9 months (range 3.8-10.8+). CONCLUSIONS: Following this phase Ib trial, the recommended phase 2 dose for anti-CEA CAR-T HITM infusions is 1010 cells with or without SIRT. The favorable safety profile and evidence of biologic activity indicate that CAR-T HITM infusions should be further studied in a phase 2 trial. Clinical trial information: NCT02416466. Citation Format: Steven C. Katz, Ethan Prince, Marissa Cunetta, Prajna Guha, Ashley Moody, Vincent Armenio, Li J. Wang, N. Joseph Espat, Richard P. Junghans. HITM-SIR: Phase Ib trial of CAR-T hepatic artery infusions and selective internal radiation therapy for liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT109. doi:10.1158/1538-7445.AM2017-CT109

PV-0320: Stereotactic body radiotherapy for liver metastases based on functional treatment planning

PV-0320: Stereotactic body radiotherapy for liver metastases based on functional treatment planning

834 - Monitoring circulating tumour DNA in patients receiving selective internal radiation therapy for liver metastases and intrahepatic cholangiocarcinoma

834 - Monitoring circulating tumour DNA in patients receiving selective internal radiation therapy for liver metastases and intrahepatic cholangiocarcinoma

Changes and Dosimetric Correlates of Health-Related Quality of Life After Stereotactic Ablative Radiation Therapy for Liver Metastases

Changes and Dosimetric Correlates of Health-Related Quality of Life After Stereotactic Ablative Radiation Therapy for Liver Metastases