SummaryBackgroundData suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.MethodsFOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).FindingsBetween Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least ...

The surprise question is a simple, feasible, and effective tool to identify patients with cancer who have a greatly increased risk of 1-year mortality.

9588 Background: In patients with advanced cancer, failure to accurately estimate and communicate prognoses can lead to overly aggressive care at the end of life with less attention to important palliative care issues such as pain and symptom management and patients’ values and goals for care. The “surprise” question—would I be surprised if this patient died in the next year?—has been recognized as an innovation to improve end-of-life care in the primary care population by identifying patients with a poor prognosis who are appropriate for palliative care. It has not been previously tested in cancer patients. The purposes of this study were to determine the feasibility and outcomes of the use of the “surprise” question in a cancer center population. Methods: Between July and November 2007, oncologists prospectively classified consecutive breast, lung, and colon cancer patients being seen at the Mary Babb Randolph Cancer Center of West Virginia University into “Yes” and “No” groups based on the surprise question. Patients were followed and their status at the end of one year-alive or dead-was determined along with patient demographics, type of cancer, and stage at presentation. A multivariate Cox proportional hazards regression analysis was used to identify variables associated with patient death. Results: Oncologists classified 826 of 853 prospective patients (97%), with 131 (16%) classified into the “No” group and 695 (84%) into the “Yes” group. At the end of the year, 71 patients had died; 41% of the “No” patients compared to 3% of the “Yes” patients (P <.001). The surprise question ‘No‘ response was more predictive of patient death than stage of cancer, cancer type, or age (hazard ratio 7.53, P value <.001). The “Yes” patients lived longer than the “No” patients (359.8±32.8 days versus 270±131.5 days, P <.001). The sensitivity of the surprise question “No” response was 75% and the specificity was 90%. Conclusions: We conclude that the surprise question is a simple, feasible, and effective tool to identify cancer patients with the worst prognoses who should receive the highest priority for palliative care interventions, particularly advance care planning. No significant financial relationships to disclose.

Objectives 1. Discuss the use of the surprise question. 2. Describe outcomes with the use of the surprise question in cancer patient care.

Laboratory studies provide additional evidence that serotonin and SP are involved primarily, though not exclusively, in acute and delayed vomiting, respectively.