Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial.

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).

Magnetic resonance colonography with a limited bowel preparation and automated carbon dioxide insufflation in comparison to conventional colonoscopy: patient burden and preferences.

OBJECTIVES: To evaluate patient burden and preferences for MR colonography with a limited bowel preparation and automated carbon dioxide insufflation in comparison to conventional colonoscopy. METHODS: Symptomatic patients were consecutively recruited to undergo MR colonography with automated carbon dioxide insufflation and a limited bowel preparation followed within four weeks by colonoscopy with a standard bowel cleansing preparation. Four questionnaires regarding burden (on a five-point scale) and preferences (on a seven-point scale) were addressed after MR colonography and colonoscopy and five weeks after colonoscopy. RESULTS: Ninety-nine patients (47 men, 52 women; mean age 62.3, SD 8.7) were included. None of the patients experienced severe or extreme burden from the MR colonography bowel preparation compared to 31.5% of the patients for the colonoscopy bowel preparation. Colonoscopy was rated more burdensome (25.6% severe or extreme burden) compared to MR colonography (5.2% severe or extreme burden) (P<0.0001). When discarding the bowel preparations, the examinations were rated equally burdensome (P=0.35). The majority of patients (61.4%) preferred MR colonography compared to colonoscopy (29.5%) immediately after the examinations and five weeks later (57.0% versus 39.5%). CONCLUSION: MR colonography with a limited bowel preparation and automated carbon dioxide insufflation demonstrated less burden compared to colonoscopy. The majority of patients preferred MR colonography over colonoscopy.

Magnetic resonance colonography with automated carbon dioxide insufflation: Diagnostic accuracy and distension.

OBJECTIVES: To evaluate the diagnostic performance of MR colonography using automated carbon dioxide (CO2) insufflation for colonic distension, with colonoscopy serving as the reference standard. METHODS: Ninety-eight symptomatic patients underwent MR colonography with faecal tagging and automated CO2 insufflation. Three readers (one expert (reader 1), and two less experienced (readers 2 and 3)) evaluated the images for the presence of colorectal lesions. Bowel distension was evaluated on a 4-point scale. Results were verified with colonoscopy and histopathological analysis. RESULTS: Per-patient sensitivity for lesions ≥10mm was 91.7% (11 of 12) (reader 1), 75.0% (9 of 12) (reader 2), and 75% (9 of 12) (reader 3). Specificity was 96.5% (82 of 85) (reader 1), 97.7% (83 of 85) (reader 2), 95.3% (81 of 85) (reader 3). Per-patient sensitivity for lesions ≥6mm was 85.7% (18 of 21) (reader 1), 57.1% (12 of 21) (reader 2), and 57.1% (12 of 21) (reader 3). Specificity was 86.8% (66 of 76), 98.7% (75 of 76), 90.8% (69 of 76), respectively. Per-patient sensitivity for advanced neoplasia of ≥10mm and ≥6mm was 88.9% (8 of 9) for all readers. Specificity for ≥10mm and ≥6mm was 98.9% (87 of 88) (reader 1), 97.7% (86 of 88) (reader 2), 96.6% (85 of 88) (reader 3). 94.4% of the colon segments were adequate to optimal distended with dual positioning. CONCLUSION: MR colonography can accurately detect lesions ≥10mm, and advanced neoplasia ≥6mm. Sufficient distension was achieved using automated CO2 insufflation for colonic distension in MR colonography.

The feasibility of colorectal cancer detection using dual-energy computed tomography with iodine mapping.

AIM: To assess the feasibility of colorectal cancer detection using dual-energy computed tomography with iodine mapping and without bowel preparation or bowel distension. MATERIALS AND METHODS: Consecutive patients scheduled for preoperative staging computed tomography (CT) because of diagnosed or high suspicion for colorectal cancer were prospectively included in the study. A single contrast-enhanced abdominal CT acquisition using dual-source mode (100 kV/140 kV) was performed without bowel preparation. Weighted average 120 kV images and iodine maps were created with post-processing. Two observers performed a blinded read for colorectal lesions after being trained on three colorectal cancer patients. One observer performed an unblinded read for lesion detectability and placed a region of interest (ROI) within each lesion. RESULTS: In total 21 patients were included and 18 had a colorectal cancer at the time of the CT acquisition. Median cancer size was 43 mm [interquartile range (IQR) 27-60 mm] and all 18 colorectal cancers were visible on the 120 kV images and iodine map during the unblinded read. During the blinded read, observers found 90% (27/30) of the cancers with 120 kV images only and 96.7% (29/30) after viewing the iodine map in addition (p = 0.5). Median enhancement of colorectal cancers was 29.9 HU (IQR 23.1-34.6). The largest benign lesions (70 and 25 mm) were visible on the 120 kV images and iodine map, whereas four smaller benign lesions (7-15 mm) were not. CONCLUSION: Colorectal cancers are visible on the contrast-enhanced dual-energy CT without bowel preparation or insufflation. Because of the patient-friendly nature of this approach, further studies should explore its use for colorectal cancer detection in frail and elderly patients.

Patient compliance in the treatment of Burkitt's lymphoma in rural Zambia: a retrospective study on 80 Burkitt's lymphoma patients in Katete, Zambia.

BACKGROUND: In African settings the treatment results of Burkitt's lymphoma (BL) seem to be less favourable compared with Western settings. The aim of this retrospective study was to analyse some factors that affect the treatment of BL. PATIENTS AND METHODS: Over a 16 year period, data were extracted of 80 patients. RESULTS: Complete remission 5%, very good partial response 35%, partial response 16%, no response 10%, data missing 34%. Of all patients, 56% did have a positive response to treatment. However, 51% of this subgroup of patients did not finish treatment. There was no difference in completion of treatment between patients living in Katete district finishing treatment vs. living outside Katete district (respectively 25% vs. 32%, P = 0.7148). CONCLUSION: There is potential for higher cure rates for BL in tropical settings if full effort is put into compliance since a majority of patients, even while having a good prognosis, abandon treatment. Large distance to hospital makes no difference in completing the chemotherapy course.

Patient compliance in the treatment of burkitt's lymphoma in rural Zambia: a retrospective study on 80 burkitt's lymphoma patients in Katete, Zambia

Background : In African settings the treatment results of Burkitt's lymphoma (BL) seem to be less favourable compared with Western settings. The aim of this retrospective study was to analyse some factors that affect the treatment of BL. Patients and Methods : Over a 16 year period; data were extracted of 80 patients. Results : Complete remission 5; very good partial response 35; partial response 16; no response 10; data missing 34. Of all patients; 56did have a positive response to treatment. However; 51of this subgroup of patients did not finish treatment. There was no difference in completion of treatment between patients living in Katete district finishing treatment vs. living outside Katete district (respectively 25vs. 32; P = 0.7148). Conclusion: There is potential for higher cure rates for BL in tropical settings if full effort is put into compliance since a majority of patients; even while having a good prognosis; abandon treatment. Large distance to hospital makes no difference in completing the chemotherapy course