Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy.

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.

Positron-emission tomography/computed tomography (PET/CT) in the initial staging of primary rectal cancer.

OBJECTIVE: The aim of this study was to assess the role of (18)flourodeoxyglucose positron-emission tomography/computed tomography (PET/CT) in the initial staging of primary rectal adenocarcinoma. METHOD: A total of 20 patients with adenocarcinoma of the rectum were assessed with both PET/CT and conventional staging (CT chest/abdomen/pelvis, MRI rectum). Discordance with conventional imaging and incidental findings on PET were recorded and the patients presented to a colorectal cancer multidisciplinary team to assess management changes. Patients were followed up so that discordant or incidental findings could be verified by intra-operative examination, imaging or histology where possible. RESULTS: Positron-emission tomography/computed tomography correctly identified the primary tumour in all 20 patients. Comparing PET/CT with conventional staging modalities, there were 11 discordant or incidental findings in nine patients (45%). This resulted in a potential change in stage in 30% (four patients downstaged and two upstaged). PET/CT suggested additional neoplastic pathology in three patients and excluded the same in two patients. The incidental neoplastic findings were of minor clinical significance and one was eventually deemed false positive. While PET/CT resulted in potential management changes in five patients (25%), no changes in surgical management occurred. When tumours were grouped according to conventional stage, PET/CT resulted in fewer changes in stage in stage I (0%), compared with stages II to IV (43%) (P = 0.08). CONCLUSION: Positron-emission tomography/computed tomography provides additional information to conventional staging in primary rectal cancer. This information produced minor management changes in this study and did not effect surgical management. PET/CT may be most appropriately used selectively in more advanced stages and where indeterminate findings exist with conventional staging.

Segmental colonic transit after oral 67Ga-citrate in healthy subjects and those with chronic idiopathic constipation.

UNLABELLED: Measurement of segmental colonic transit is important in the assessment of patients with severe constipation. 111In-diethylenetriamine pentaacetic acid (DTPA) has been established as the tracer of choice for these studies, but it is expensive and not readily available. 67Ga-citrate is an inexpensive tracer and when given orally is not absorbed from the bowel. It was compared with 111In-DTPA in colonic transit studies in nonconstipated control subjects and then in patients with idiopathic constipation. METHODS: Studies were performed after oral administration of 3 MBq (81 microCi) 67Ga-citrate or 4 MBq (108 microCi) 111In-DTPA in solution. Serial abdominal images were performed up to 96 h postinjection, and computer data were generated from geometric mean images of segmental retention of tracer, mean activity profiles and a colonic tracer half-clearance time. RESULTS: There were no differences in segmental retention of either tracer or in mean activity profiles between control subjects and constipated patients. Results in constipated subjects were significantly different from those in controls. The mean half-clearance times of tracer for control subjects were 28.8 h for 67Ga-citrate and 29.9 h for 111In-DTPA in control subjects and 75.0 h for 67Ga-citrate and 70.8 h for 111In-DTPA in constipated patients. CONCLUSION: Oral 67Ga-citrate can be used as a safe alternative to 111In-DTPA for accurate measurement of segmental colonic transit.

99mTechnetium labelled leucocyte scanning in acute lower abdominal pain: can it reduce the negative appendectomy rate?

While the incidence of 'negative' appendectomy has long been justified as a necessary evil in the management of acute appendicitis, attempts to improve diagnostic accuracy have met with mixed results. In a prospective study of 34 selected patients who presented with acute lower abdominal pain the potential role of 99mTechnetium labelled leucocyte scanning in the diagnosis of acute appendicitis has been evaluated. Patient management was not based on the result of the nuclear scan. The clinical outcome was correlated with the scan diagnosis. There was one false positive and one false negative scan result with respect to the clinical diagnosis of appendicitis yielding a sensitivity of 90% and a specificity of 96%. 99mTechnetium labelled leucocyte scanning may have an important role in the assessment of selected patients presenting with acute lower abdominal pain.

Drug-induced depression and attempted suicide.

Sixty-eight patients who had attempted suicide were matched with non-suicidal patients with similar diagnoses to assess the extent to which excessive drug ingestion by the suicidal group might have contributed to their behaviour. It was found that the suicidal patients were consuming more drugs, particularly those of a potentially depressing kind. The implications of this finding are discussed.