Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING: Vifor Pharma.

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.

PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.