Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.     

Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta-analysis

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.     

Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome

Objective

To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality.

Current fluconazole treatment regimens result in under-dosing of critically ill adults during early therapy

European Journal of Clinical Microbiology & Infectious Diseases - To evaluate current fluconazole treatment regimens in critically ill adults over the typical treatment course. Data from...     

3D Quantitative Synthetic MRI in the Evaluation of Multiple Sclerosis Lesions

BACKGROUND AND PURPOSE:Synthetic MR imaging creates multiple contrast-weighted images based on a single time-efficient quantitative scan, which has been mostly performed for 2D acquisition. We assessed the utility of 3D synthetic MR imaging in patients with MS by comparing its diagnostic image quality and lesion volumetry with conventional MR imaging.MATERIALS AND METHODS:Twenty-four patients with MS prospectively underwent 3D quantitative synthetic MR imaging and conventional T1-weighted, T2-weighted, FLAIR, and double inversion recovery imaging, with acquisition times of 9 minutes 3 seconds and 18 minutes 27 seconds for the synthetic MR imaging and conventional MR imaging sequences, respectively. Synthetic phase-sensitive inversion recovery images and those corresponding to conventional MR imaging contrasts were created for synthetic MR imaging. Two neuroradiologists independently assessed the image quality on a 5-point Likert scale. The numbers of cortical lesions and lesion volumes were quantified using both synthetic and conventional image sets.RESULTS:The overall diagnostic image quality of synthetic T1WI and double inversion recovery images was noninferior to that of conventional images (P = .23 and .20, respectively), whereas that of synthetic T2WI and FLAIR was inferior to that of conventional images (both Ps < .001). There were no significant differences in the number of cortical lesions (P = .17 and .53 for each rater) or segmented lesion volumes (P = .61) between the synthetic and conventional image sets.CONCLUSIONS:Three-dimensional synthetic MR imaging could serve as an alternative to conventional MR imaging in evaluating MS with a reduced scan time.

MS is a chronic, immune-mediated, demyelinating disorder of the CNS that usually affects young adults and leads to chronic disability.^1,2 The diagnostic criteria for MS are based on the lesion number, size, and location.³ Although diffuse periventricular lesions are most commonly observed, previous studies have shown that the cortical and juxtacortical lesion load is associated with cognitive impairment.^4,5 Additionally, the detection of cortical and juxtacortical lesions may contribute to early diagnosis because these lesions are characteristic of MS. MR imaging plays an integral role in the diagnosis and management of patients with MS through the in vivo detection and characterization of lesions. Although MR imaging is highly sensitive in detecting periventricular lesions and is considered as a standard biomarker in the monitoring of treatment response,⁶ conventional MR imaging techniques have a relatively low sensitivity for detecting (juxta)cortical lesions. Phase-sensitive inversion recovery (PSIR) and double inversion recovery (DIR) are recently developed imaging techniques useful for detecting MS lesions, especially (juxta)cortical ones.^7,8 The PSIR preserves the positive and negative polarities of tissues as they recover from the inversion pulse, thus providing a T1-weighted contrast with higher SNR and GM-WM contrast. DIR is an imaging technique that suppresses both WM and CSF signals, thus significantly increasing lesion conspicuity in both GM and WM compared with FLAIR or T2-weighted images. PSIR and DIR have been shown to improve sensitivity compared with FLAIR or T2-weighted images in the detection of cortical lesions. However, the additional scanning time associated with PSIR and DIR has hindered the use of these techniques in clinical practice. Thus, a rapid imaging technique that can acquire these contrast-weighted images with high spatial resolution is desired.Quantitative synthetic MR imaging is a time-efficient MR imaging technique that enables simultaneous quantification of T1 and T2 relaxation times and proton attenuation and allows the creation of any contrast-weighted image, including DIR and PSIR, without additional scanning time.^9–13 Previous studies have shown that synthetic MR imaging is useful for detecting and characterizing MS lesions.^10,11,14 However, these studies were based on a multisection 2D acquisition, providing a relatively low resolution in the section direction. 3D quantitative synthetic MR imaging, enabling the simultaneous quantification of T1, T2, and proton attenuation of the whole brain in 3D,^15–17 with smaller section thickness, should allow for more detailed delineation of MS lesions. With the combination of high spatial resolution 3D acquisition and DIR as well as PSIR contrasts, 3D quantitative synthetic MR imaging could serve as a clinically useful technique for monitoring MS lesions.Here, we assessed the utility of the recently developed 3D quantitative synthetic MR imaging for evaluating MS lesions by comparing the synthetic and conventional MR image sets. We hypothesized that 3D synthetic MR imaging would have a comparable diagnostic quality with that of a conventional image set (including 3D FLAIR and DIR) while shortening the total acquisition time.     

The Financial Impact on Reimbursement of Moderately Hypofractionated Postoperative Radiation Therapy for Breast Cancer: An International Consortium Report

AimsModerately hypofractionated breast irradiation has been evaluated in several prospective studies, resulting in wide acceptance of shorter treatment protocols for postoperative breast irradiation. Reimbursement for radiation therapy varies between private and public systems and between countries, impacting variably financial considerations in the use of hypofractionation. The aim of this study was to evaluate the financial impact of moderately hypofractionated breast irradiation by reimbursement system in different countries.Materials and methodsThe study was designed by an international group of radiation oncologists. A web-questionnaire was distributed to representatives from each country. The participants were asked to involve the financial consultant at their institution.ResultsData from 13 countries from all populated continents were collected (Europe: Denmark, France, Italy, the Netherlands, Spain, UK; North America: Canada, USA; South America: Brazil; Africa: South Africa; Oceania: Australia; Asia: Israel, Taiwan). Clinicians and/or departments in most of the countries surveyed (77%) receive remuneration based on the number of fractions delivered to the patient. The financial loss per patient estimated resulting from applying moderately hypofractionated breast irradiation instead of conventional fractionation ranged from 5–10% to 30–40%, depending on the healthcare provider.ConclusionAlthough a generalised adoption of moderately hypofractionated breast irradiation would allow for a considerable reduction in social and economic burden, the financial loss for the healthcare providers induced by fee-for-service remuneration may be a factor in the slow uptake of these regimens. Therefore, fee-for-service reimbursement may not be preferable for radiation oncology. We propose that an alternative system of remuneration, such as bundled payments based on stage and diagnosis, may provide more value for all stakeholders.