Celiac plexus radiosurgery for pain management in advanced cancer: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain. METHODS: This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external-beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete. FINDINGS: Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 65·5 years (IQR 58·3-71·8), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1]). INTERPRETATION: Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted. FUNDING: Gateway for Cancer Research and the Israel Cancer Association.

The Impact of Disease Progression on Health-Related Quality of Life Outcomes in Patients With Oligometastatic Disease at 12 Months Post Stereotactic Body Radiation Therapy.

PURPOSE: There is a paucity of published health-related quality of life (HRQOL) outcomes in patients with oligometastatic disease (OMD) who receive stereotactic body radiation therapy (SBRT) and no available data assessing the effect of disease progression post-SBRT on HRQOL in this patient population. METHODS AND MATERIALS: Patients with OMD who received SBRT in a phase II single-arm research ethics board approved study were included. HRQOL was a secondary outcome. This study hypothesized that there is a different pattern of change from baseline HRQOL in patients with OMD treated with SBRT that have disease progression by 12 months (progressors) compared with those that do not progress by 12 months (nonprogressors), as measured by the European Organisation of Research and Treatment in Cancer Quality of Life Questionnaire Core 30. RESULTS: A total of 107 patients were included in this analysis, 41 without progression and 66 with progression by 12 months; median time to progression was 7.7 (0.3-57) months. A statistically significant decline in the mean global health/quality of life (GHQOL) score (73 [SD, 21.8] to 67.2 [SD, 27.1]; P = .04) from baseline in the entire population at the 12-month follow-up was found. Mean GHQOL change score in nonprogressors was -0.8 and in progressors was -8.8 (P = .07). However, only progressors demonstrated a difference between baseline and 12-month mean GHQOL scores (71.2 vs 62.4; P = .01), which was both statistically and clinically significant (-8.8) in the range of small minimal clinically important difference. There was a higher proportion of patients who experienced a minimal clinically important difference deterioration in progressors compared with nonprogressors (37.4% vs 24.4%; P = .14). CONCLUSIONS: Patients who progressed by 12 months did not have a statistical or clinically significant difference in mean GHQOL change score compared with nonprogressors. However, there were signals to suggest that patients who progressed by 12 months post-SBRT experienced a different pattern of change compared with nonprogressors, which was worse compared with baseline.

Health related quality of life outcomes following stereotactic body radiotherapy in patients with oligo-metastatic disease: A systematic review and individual patient data meta-analysis.

INTRODUCTION: Published health-related quality of life (HRQOL) outcomes are lacking in patients treated for oligo-metastatic disease (OMD). The aim of this systematic review and individual patient data meta-analysis is to determine the effect of stereotactic body radiotherapy (SBRT) on HRQOL outcomes of patients with OMD. METHODS: Studies screened included adults with extra-cranial OMD, defined as ≤ 5 metastases, SBRT intended as definitive treatment, and HRQOL as primary or secondary outcome. Primary outcome was change in HRQOL at 12-months from baseline in patients with OMD who received SBRT (versus not), reported as standardized mean difference (SMD). RESULTS: A total of 7556 publications were identified, four studies met inclusion criteria (2 single arm interventional studies and 2 randomised controlled trials [RCTs]), and individual patient data was available from 3 studies (175 patients). In the two RCTs, there was no SS difference in the SMD between patients who received SBRT and those that did not (0.09 [95 % CI -0.32, 0.5], P = 0.66). On meta-analysis of patients (N = 107) who received SBRT the SMDwas -0.23 (95 % CI [-0.42, -0.04], versus -0.25 (95 % CI [-0.57, 0.07]) in those who did not (N = 37) receive SBRT, demonstrating a small deterioration from baseline. CONCLUSION: In patients with OMD, there is no difference in HRQOL at 12-months from baseline between patients who received SBRT and those that did not. However, a small HRQOL deterioration was found in both groups of patients. More in-depth analysis of relevant HRQOL domains, in the setting of OMD, is required to better understand the potential impact of SBRT.

Temporal patterns of late bowel and bladder radiotherapy toxicity in a randomised controlled trial assessing duration of neo-adjuvant hormones in prostate cancer.

BACKGROUND: To assess the temporal patterns of late gastrointestinal (GI) and genitourinary (GU) radiotherapy toxicity and resolution rates in a randomised controlled trial (All-Ireland Cooperative Oncology Research Group 97-01) assessing duration of neo-adjuvant (NA) hormone therapy for localised prostate cancer. MATERIAL AND METHODS: Node negative patients with > 1 of: PSA > 20 ng/mL, Gleason score ≥ 7, and stage T3 or more, were included. Follow-up, including toxicity assessment, was three-monthly in the early stages and yearly thereafter. RESULTS: Median follow-up from the end of RT was 6.8 years. In the interval between 90 days following the end of RT and the last toxicity assessment, GI and GU toxicity (any grade) was found in 50% and 51% of 240 and 241 patients, respectively. For those who did develop toxicity, the median time from end of RT until the first development of any grade GI or GU toxicity was 1.2 years and 1.6 years, respectively, whilst median time to final resolution was 1.6 years and 2.2 years, respectively. Grade 2 (G2) or greater GI and GU toxicity occurred in 29 (12.1%) and 40 (16.6%) patients, respectively. The proportion with unresolved G2 + GI and GU toxicity was 89% and 79%, respectively, in year 1, 69% and 65% in year 2, 59% and 52% in year 3 and 27% and 32% in year 5. CONCLUSION: Long-term toxicities continue to occur many years after NA hormone therapy and RT. The rate of occurrence does not appear to reduce within the time frame during which our patients were followed. The percentage of patients suffering from G2 + toxicity at any time is however low. Resolution of these toxicities continues for the duration of the follow-up.