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  • br Safety br In total patients experienced severe

    2020-08-12


    Safety
    In total, 11 patients (3%) experienced severe day-of-treatment complications (Table 4). Severe adverse events within the first week after SIRT were rare; three patients experienced grade 3 fatigue in the 7 days after SIRT and one patient experienced grade 3 abdominal pain in the first week after SIRT. One hundred and forty-three patients experienced an adverse event. In total, 253 adverse events were recorded, of which 19 (8%) were grade 3 or above (Table 4). The most common events were mild fatigue and abdominal pain (grade 1e2). Relatedness of complications
    Table 2 Treatment planning and procedure details
    Parameter Data for 399 patients
    otherwise stated)
    Location of liver tumour(s)
    Number of liver tumours
    Bilirubin (mmol/l) prior to SIRT Median 9.0
    Arteries embolised before SIRT
    therapy
    SIRT procedure target/type
    in single session)
    two sessions)
    Number of administrations
    SIRT microsphere brand
    Percentage tumour to liver volume Median 15.0
    Prescribed activity (GBq) for SIR- Median 1.64
    Prescribed activity (GBq) for Median 3.91
    Length of stay in hospital following
    SIRT procedure
    Concomitant chemotherapy
    administered with SIRT
    Table 2 (continued )
    Parameter Data for 399 patients
    otherwise stated)
    Concomitant chemotherapy
    received
    Post-SIRT chemotherapy received
    during follow-up
    SIRT, selective internal Nigericin therapy; IQR, interquartile range.
    and adverse events to the SIRT procedure were not routinely recorded. Events categorised as ‘other’ with a free-text description accounted for 53 (21%) of the total. Seven events of grade 3 or above were recorded in the ‘other’ category, which were as follows: acute kidney injury (grade 3; occurred 28 days after SIRT), bowel obstruction (grade 3; 21 days after SIRT); liver abscess (grade 3; 138 days after SIRT), skin rash (grade 3; 90 days after SIRT), delirium/de-mentia (grade 4; 79 days after SIRT), pulmonary emboli (grade 4; 47 days after SIRT); sepsis (grade 4; 18 days after SIRT). In total, 353 events were recorded as abnormal lab-oratory values (Table 4). The most common biochemical event categories were raised aspartate aminotransferase (22%), raised alanine aminotransferase (21%) and hypo-albuminaemia (19%). Eighteen of the 353 events (5%) were grade 3. No severe cases of radiation-induced liver disease (RILD), gastrointestinal ulceration, radiation pneumonitis, radiation cholecystitis or radiation pancreatitis were recorded.
    Fig 1. KaplaneMeier curve of overall survival following selective in-ternal radiation therapy in patients with metastatic colorectal cancer liver metastases. Ninety-five per cent confidence intervals are shaded; the numbers at risk at 3-month intervals are displayed.
    Table 3
    KaplaneMeier analysis and univariate Cox proportional hazards model of survival by baseline characteristics. Statistically significant P-values are shown in bold
    Subgroup n (patients) n (events) Median overall Overall survival Hazard ratio P-value
    survival (months) 95% confidence (95% confidence
    interval interval)
    Number of lines of previous chemotherapy (including biologics); Log-rank test P ¼ 0.098
    Prior biological therapy (includes bevacizumab, cetuximab, aflibercept); Log-rank test P ¼ 0.783
    Presence of extrahepatic metastases; Log-rank test P [ 0.021
    Age (continuous)
    Percentage tumour to liver volume (continuous)
    Percentage tumour to liver volume; Log-rank test P < 0.001
    ECOG, Eastern Cooperative Oncology Group.
    * Reference category for univariate Cox regression analysis.
    Discussion
    SIRT is reimbursed for the treatment of liver metastases from CRC in most developed countries at a national or regional level (Supplementary Table S2), but its effect on overall survival and cost-effectiveness in patients with CRC liver metastases has not been shown in prospective, rand-omised phase III studies. As prospective, randomised controlled clinical trials can take a decade or longer to address specific research questions [9], some health sys-tems have opted to study the treatment in a registry-based commissioning model to address specific deficiencies in the published literature and to accelerate advancement to full commissioning. This study was specifically commissioned to provide ‘real-world’ evidence on the survival of patients 
    treated with SIRT in a salvage setting to inform future commissioning policy decisions.
    Patients with unresectable CRC liver metastases whose disease has progressed following chemotherapy have very few treatment options. New locoregional liver-directed therapies, such as SIRT or transarterial chemo-embolisation with drug-eluting beads, are emerging but have not yet become the standard of care. Patients in the control arm of clinical trials treated with best supportive care (BSC) in a salvage setting have a median overall survival ranging from 2.4 months [10] to 6.6 months [11]. In this same population, NICE has recommended trifluridine-tipiracil on the basis of two randomised controlled trials (RCTs) that showed an improvement in overall survival by 2.0e2.4 months above BSC [11,12]. We carried out a systematic evidence review of