Detection of Recurrent Prostate Cancer With 18F-Fluciclovine PET/MRI.

OBJECTIVE: Simultaneous PET/MRI combines soft-tissue contrast of MRI with high molecular sensitivity of PET in one session. The aim of this prospective study was to evaluate detection rates of recurrent prostate cancer by 18F-fluciclovine PET/MRI. METHODS: Patients with biochemical recurrence (BCR) or persistently detectable prostate specific antigen (PSA), were examined with simultaneous 18F-fluciclovine PET/MRI. Multiparametric MRI (mpMRI) and PET/MRI were scored on a 3-point scale (1-negative, 2-equivocal, 3-recurrence/metastasis) and detection rates (number of patients with suspicious findings divided by total number of patients) were reported. Detection rates were further stratified based on PSA level, PSA doubling time (PSAdt), primary treatment and inclusion criteria (PSA persistence, European Association of Urology (EAU) Low-Risk BCR and EAU High-Risk BCR). A detailed investigation of lesions with discrepancy between mpMRI and PET/MRI scores was performed to evaluate the incremental value of PET/MRI to mpMRI. The impact of the added PET acquisition on further follow-up and treatment was evaluated retrospectively. RESULTS: Among patients eligible for analysis (n=84), 54 lesions were detected in 38 patients by either mpMRI or PET/MRI. Detection rates were 41.7% for mpMRI and 39.3% for PET/MRI (score 2 and 3 considered positive). There were no significant differences in detection rates for mpMRI versus PET/MRI. Disease detection rates were higher in patients with PSA≥1ng/mL than in patients with lower PSA levels but did not differ between patients with PSAdt above versus below 6 months. Detection rates in patients with primary radiation therapy were higher than in patients with primary surgery. Patients categorized as EAU Low-Risk BCR had a detection rate of 0% both for mpMRI and PET/MRI. For 15 lesions (27.8% of all lesions) there was a discrepancy between mpMRI score and PET/MRI score. Of these, 10 lesions scored as 2-equivocal by mpMRI were changed to a more definite score (n=4 score 1 and n=6 score 3) based on the added PET acquisition. Furthermore, for 4 of 10 patients with discrepancy between mpMRI and PET/MRI scores, the added PET acquisition had affected the treatment choice. CONCLUSION: Combined 18F-fluciclovine PET/MRI can detect lesions suspicious for recurrent prostate cancer in patients with a range of PSA levels. Combined PET/MRI may be useful to select patients for appropriate treatment, but is of limited use at low PSA values or in patients classified as EAU Low-Risk BCR, and the clinical value of 18F-fluciclovine PET/MRI in this study was too low to justify routine clinical use.

Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX).

PURPOSE: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. METHODS: High-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. RESULTS: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. CONCLUSIONS: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.

Denosumab in patients with giant-cell tumor of bone in Norway: results from a nationwide cohort.

BACKGROUND: Denosumab is a relatively new treatment option for patients with giant-cell tumor of bone (GCTB). The purpose of this study was to report the results for patients treated in Norway. MATERIALS AND METHODS: Patients treated with denosumab for GCTB were identified from the clinical databases at the Norwegian sarcoma reference centers. Data were retrieved from the clinical databases and supplemented by retrospective review of patient records. Denosumab was given as a subcutaneous injection every 4 weeks with loading doses on day 8 and 15 in cycle 1. RESULTS: Eighteen patients treated with denosumab for GCTB were identified. Denosumab was given for recurrent disease in seven cases and as first-line treatment in 11 patients, of which 6 received therapy as part of a neoadjuvant/adjuvant strategy and 5 for surgically unsalvageable primary tumor. Ten of 12 patients with unresectable disease are still on denosumab without progression with median treatment duration of 41 months (range 18-60). Two patients discontinued treatment due to osteonecrosis of the jaw and reduced compliance, respectively. In the adjuvant group, four patients experienced disease recurrence after stopping denosumab. In three of six patients, the extent of surgery was reduced due to neoadjuvant therapy. Seventeen of 18 patients underwent response evaluation with 18F-FDG PET/CT at median 4.7 weeks from starting denosumab. Median baseline SUVmax was 11.0 and median SUVmax at evaluation was 4.9 (p < 0.001). CONCLUSIONS: In a nationwide GCTB patient cohort, denosumab was an effective agent and durable responses were observed. Our results do not support the use of adjuvant therapy in routine clinical practice. 18F-FDG PET/CT could be a valuable tool for early response evaluation.

A double-blind, randomized, crossover comparison between single-dose and double-dose immediate-release oral morphine at bedtime in cancer patients.

The European Association for Palliative Care guidelines for treatment of cancer pain recommend a double dose (DD) of immediate-release morphine at bedtime instead of single doses (SD) repeated every four hours throughout the night. A previous open controlled study reported more side effects after DD than after SD. The present study was a randomized, double-blind, crossover study comparison of DD and SD of immediate-release morphine during the night, followed by an open pharmacokinetic study. The primary outcome was average pain intensity during the night, as measured on an 11-point numerical rating scale. Secondary outcomes were morning pain, number of rescue medications, adverse effects (nausea, xerostomia, tiredness, sleep quality, and number of awaking episodes) and patient preference. Morphine and metabolites were quantified by a validated liquid chromatography-tandem mass spectrometry method. Nineteen patients completed the clinical study; 13 participated in the pharmacokinetic follow up. Average pain during the night for DD vs. SD was close to statistical significance (mean 0.8 and 1.4, respectively, P=0.058; mean [95% confidence interval] for the difference was 0.50 [0.02, 1.0]). A similar trend was observed for strongest night pain (P=0.069) and sleep quality (P=0.077). Only two patients required rescue morphine. Four patients had no treatment preference; nine and six favored DD and SD, respectively. DD patients displayed higher area under the curve for morphine and morphine-6-glucuronide during the first part of the night. Although DD tended to perform slightly better than SD, a difference in average pain during the night of 0.50 has little clinical significance, and the two procedures are, therefore, clinically equivalent. It is speculated whether the initial higher exposure to morphine-6-glucuronide may have clinical significance.

[Application of pupillometry and pupillary reactions in medical research]. / Bruk av pupillometri og pupillreaksjonar i medisinsk forsking.

BACKGROUND: The iris is a dynamic organ in which the autonomic nervous system regulates the activity. Iris activity reflects physiological reactions to different sensory stimuli, resulting in a variation in pupil size. There are many different diagnostic tools which assess iris activity. The present paper reviews the methods of pupillary assessment as a research tool and in clinical use. MATERIAL AND METHODS: The basis for this paper was obtained by searches on Medline and ISI Web of Knowledge. Reference lists were further checked for other relevant studies. RESULTS AND INTERPRETATION: Pupillometry is a research tool that is adopted in an increasing number of medical fields. In the past this method was used mostly within ophthalmology and neurology; today it has spread to a wide range of medical fields, for instance pharmacology and physiology. There are continuous improvements in the flexibility and recording capacity of pupillometers and they are used in an increasing number of medical fields, though they are still most useful within research.

The validity of EORTC QLQ-C30 fatigue scale in advanced cancer patients and cancer survivors.

Fatigue is a major complaint among advanced cancer patients. Several instruments are available for measuring fatigue. The EORTC QLQ-C30 is one of the most frequently used health-related quality of life (HRQOL) instruments, and it includes a three-item fatigue subscale. Limited knowledge exists about the validity, performance and sensitivity of EORTC QLQ-C30 fatigue scale as compared with a fatigue-specific instrument. The aim of the present study was to validate the EORTC QLQ-C30 fatigue scale (FA) against the Fatigue Questionnaire (FQ). The FQ is frequently used and was developed to measure fatigue in both cancer and noncancer populations. The FQ measures physical (PF, seven items) and mental fatigue (MF, four items). The study population included two different cohorts: A) patients with advanced metastatic cancer included in a prospective randomized study of palliative radiotherapy (n = 238); B) patients with leukaemia and malignant lymphoma curatively treated with stem-cell transplantation and high-dose chemotherapy (n = 128). The analysis demonstrated that the FA correlated higher with the PF scale (r = 0.67-0.75) as compared with the MF scale (r = 0.49-0.61). The item scale correlations between FA items and the PF scale were consistently higher than between FA items and the MF scale. A factor analysis including all the items within the FA and the FQ identified two factors. All FA items loaded on a PF factor (0.70-0.85). A floor/ ceiling effect, indicating a high number of respondents with lowest, respectively, highest scores was observed more frequently in the FA as compared with the FQ. The PF discriminated better between diagnostic groups with different levels of fatigue than the FA did. In conclusion, the EORTC QLQ-C30 fatigue scale is measuring physical fatigue. A floor/ ceiling effect seems to appear for the EORTC QLQ-C30 fatigue scale. The validity of the EORTC QLQ-C30 fatigue scale is to be questioned for use in palliative care patients. In studies with fatigue as a defined end point, a domain-specific instrument should, therefore, be added.