TPS466 Background: Many cancer patients, especially those with pancreatic cancer, suffer from severe back/epigastric pain. Contemporary approaches (opioids, celiac blocks, systemic chemotherapy) are often inadequate. This clinical trial investigates a new approach in which high-dose radiation (radiosurgery) is focused on the retroperitoneal celiac plexus nerve bundle. Preliminary results from a single institution pilot trial NCT02356406 are promising: pain relief is substantial and side effects minimal. The main aim of the trial is to establish safety/efficacy in the setting of an international multicenter study. Exploratory analyses will examine the relationship between pain reduction and subjects’ quality-of-life, functionality, and caregiver burden. Methods: Eligibility criteria include a diagnosis of metastatic/unresectable malignancy, uncontrolled pain defined as ≥ 5 on 11-point BPI-SF scale despite analgesic use, typical retroperitoneal pain syndrome, prognosis > 8 weeks, ECOG 0-2, anatomical involvement of the celiac plexus (e.g. any pancreatic cancer, or any other cancer involving the celiac trunk). Exclusion criteria include previous upper abdo. radiation. The intervention consists of a single 25 Gy radiation fraction delivered to the celiac plexus, using anterolateral aspect of the aorta from the 12th thoracic to 2nd lumbar vertebral body as a surrogate structure. The primary tumour may be irradiated at physicians’ discretion. Dose-painting technique limits dose to organs at risk. Pain intensity will be measured using Brief Pain Inventory Short Form (BPI-SF), and quality of life with FACT-Hep. The primary endpoint is complete or partial pain response, defined as a decrease between the score immediately before treatment and 3 weeks’ post-treatment. A change of two or more on the BPI 11-point pain scale is defined as clinically significant. Secondary endpoints include other BPI pain endpoints, pain at 6 weeks, analgesic use, toxicity (CTCAE v4.03), quality of life and functional measures. Analgesia is not restricted. Expected accrual is 100 subjects over three years. Supported by Gateway for Cancer Research, additional support from Israel Cancer Association. Clinical trial information: NCT03323489.

IntroductionPancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer.Methods and analysisA single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients" be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association.Ethics and disseminationEthic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications.Trial registration numberNCT03323489.

662 Background: Upper abdominal / lower back pain characterizes celiac plexus involvement from pancreatic and other cancers which may impair HRQOL; its satisfactory treatment is an unmet clinical need. We hypothesized that ablative radiation delivered to the celiac plexus would decrease pain and improve HRQOL. Methods: An international single arm Phase II study included patients with an average pain level ≥ 5/11 on the brief pain inventory (BPI), ECOG 0-2, and anatomical involvement of the celiac axis. The intervention was a single fraction of 25Gy delivered to the celiac plexus. The primary endpoint was ‘complete or partial (≥2 points) pain response’ based upon the BPI ‘average pain’ 11-point scale. Changes in Health-related QOL at 3 & 6 weeks compared to baseline were secondary endpoints as measured by FACT-Hep, > 8 point change being the minimal clinically important difference (MCID). Evaluable patients included eligible irradiated subjects, who had stable pain levels pre-treatment, and were alive 3 weeks’ post-treatment. The sample size was 90 evaluable patients, giving 90% power to show response rate ≥ 40%. Opioid usage was assessed using intravenous morphine equivalent dose. Sensitivity HRQOL analyses imputed worsened outcomes (-9 for total FACT-Hep) for missing data. Results: Between 2018 and 2022, 149 patients were enrolled, 90/125 who received treatment were evaluable. Median age was 65.5 years (range 28-88), 65% were female, 92% had pancreatic cancer, and 86% had metastatic disease. Median Zubrod PS was 1, median number of systemic treatment lines was 1 (range 0-5), and median baseline opioid use 31 mg/d. At 3 weeks, 48 (53.3%, 95% CI 42.5-63.9) had at least a partial pain, the BPI ‘average pain’ score decreased by a mean of 2.5 points at 3 weeks (86/90 reported) and 3.2 points at 6 weeks (67/90 reported), both p < 0.001. Opioid usage decreased by 0.6 mg/d at 3 weeks (NS) and 16.9 mg/d at 6 weeks (p = 0.005). The FACT-Hep total score increased by 7.8 points at 3 weeks (54/90 reported, NS diff. from 8) and 16.6 points at 6 weeks (45/90 reported, sig. > 8, p = 0.01), showing an improvement in patients’ HRQOL. Changes in FACT-Hep were especially noted in the Physical Well Being subscale. The Trial Outcome Index (sum of physical, functional & disease-specific concerns) increased markedly at 3 weeks (6.6 points, p = 0.005) after treatment and even more after 6 weeks (14.5 points, p < 0.). Sensitivity analyses demonstrated improvements in HRQOL at 3 and 6 weeks (1.1, 3.8), but these were less than MCID. Conclusions: Celiac plexus SBRT decreases pain and opioid use amongst patients with pancreatic cancer and other tumors invading the celiac axis. The treatment appears to improve HRQOL. Supported by Gateway for Cancer Research and the Israel Cancer Association. Clinical trial information: NCT03323489 .

e16293 Background: Upper abdominal / lower back pain characterizes celiac plexus involvement from pancreatic and other cancers which may impair HRQOL; its satisfactory treatment is an unmet clinical need. We hypothesized that ablative radiation delivered to the celiac plexus would decrease pain and improve HRQOL. Methods: An international single arm Phase II study included patients with an average pain level ≥ 5/11 on the brief pain inventory (BPI), ECOG 0-2, and anatomical involvement of the celiac axis. The intervention was a single fraction of 25Gy delivered to the celiac plexus. The primary endpoint was ‘complete or partial (≥2 points) pain response’ based upon the BPI ‘average pain’ 11-point scale. Changes in Health-related QOL at 3 & 6 weeks compared to baseline were secondary endpoints as measured by FACT-Hep, > 8 point change being the minimal clinically important difference (MCID). Evaluable patients included eligible irradiated subjects, who had stable pain levels pre-treatment, and were alive 3 weeks’ post-treatment. The sample size was 90 evaluable patients, giving 90% power to show response rate ≥ 40%. Opioid usage was assessed using intravenous morphine equivalent dose. Sensitivity HRQOL analyses imputed worsened outcomes (-9 for total FACT-Hep) for missing data. Results: Between 2018 and 2022, 149 patients were enrolled, 90/125 who received treatment were evaluable. Median age was 65.5 years (range 28-88), 65% were female, 92% had pancreatic cancer, and 86% had metastatic disease. Median Zubrod PS was 1, median number of systemic treatment lines was 1 (range 0-5), and median baseline opioid use 31 mg/d. At 3 weeks, 48 (53.3%, 95% CI 42.5-63.9) had at least a partial pain, the BPI ‘average pain’ score decreased by a mean of 2.5 points at 3 weeks (86/90 reported) and 3.2 points at 6 weeks (67/90 reported), both p<0.001. Opioid usage decreased by 0.6 mg/d at 3 weeks (NS) and 16.9 mg/d at 6 weeks (p=0.005). The FACT-Hep total score increased by 7.8 points at 3 weeks (54/90 reported, NS diff. from 8) and 16.6 points at 6 weeks (45/90 reported, sig. > 8, p = 0.01), showing an improvement in patients’ HRQOL. Changes in FACT-Hep were especially noted in the Physical Well Being subscale. The Trial Outcome Index (sum of physical, functional & disease-specific concerns) increased markedly at 3 weeks (6.6 points, p=0.005) after treatment and even more after 6 weeks (14.5 points, p<0.). Sensitivity analyses demonstrated improvements in HRQOL at 3 and 6 weeks (1.1, 3.8), but these were less than MCID. Conclusions: Celiac plexus SBRT decreases pain and opioid use amongst patients with pancreatic cancer and other tumors invading the celiac axis. The treatment appears to improve HRQOL. Clinical trial information: NCT03323489 .