Paediatric Anatomical Models in Radiotherapy Applications.

Anatomical models have key applications in radiotherapy, notably to help understand the relationship between radiation dose and risk of developing side effects. This review analyses whether age-specific computational phantoms, developed from healthy subjects and paediatric cancer patient data, are adequate to model a paediatric population. The phantoms used in the study were International Commission on Radiological Protection (ICRP), 4D extended cardiac torso (XCAT) and Radiotherapy Paediatric Atlas (RT-PAL), which were also compared to literature data. Organ volume data for 19 organs was collected for all phantoms and literature. ICRP was treated as the reference for comparison, and percentage difference (P.D) for the other phantoms were calculated relative to ICRP. Overall comparisons were made for each age category (1, 5, 10, 15) and each organ. Statistical analysis was performed using Microsoft Excel (version 16.59). The smallest P.D to ICRP was for Literature (-17.4%), closely followed by XCAT (26.6%). The largest was for RT-PAL (88.1%). The rectum had the largest average P.D (1,049.2%) and the large bowel had the smallest (2.0%). The P.D was 122.6% at age 1 but this decreased to 43.5% by age 15. Linear regression analysis showed a correlation between organ volume and age to be the strongest for ICRP (R2 = 0.943) and weakest for XCAT (R2 = 0.676). The phantoms are similar enough to ICRP for potential use in modelling paediatric populations. ICRP and XCAT could be used to model a healthy population, whereas RT-PAL could be used for a population undergoing/after radiotherapy.

Comparative genomic characterization of melanoma of known and unknown primary

BackgroundThis study aims to genomically characterize melanoma of unknown primary (MUP) in comparison to melanomas of cutaneous primary (MCP).MethodsEligible cases were collected from the MSK-IMPACT™ Clinical Sequencing Cohort published in the cBioPortal database. Genomic analysis was performed using a hybridization-capture-based next-generation sequencing assay designed to detect mutations, small insertions and deletions, copy number alterations, and genomic rearrangements.ResultsAmong 462 patients of whom 18.4% had MUP, brain metastasis was more common among patients with MUP (23% vs 7.1%). The differences in genomic profiling between MCP and MUP did not reach statistical significance. The 187 MCP and 44 MUP patients treated with immune checkpoint inhibitors had a median overall survival of 49 and 44 months, respectively (p = 0.705).ConclusionsThe differences in somatic mutation patterns and survival outcomes were not statistically significant. These findings may allude to similar carcinogenic processes but should be considered exploratory and interpreted with caution. (AU)

Comparative genomic characterization of melanoma of known and unknown primary.

BACKGROUND: This study aims to genomically characterize melanoma of unknown primary (MUP) in comparison to melanomas of cutaneous primary (MCP). METHODS: Eligible cases were collected from the MSK-IMPACT™ Clinical Sequencing Cohort published in the cBioPortal database. Genomic analysis was performed using a hybridization-capture-based next-generation sequencing assay designed to detect mutations, small insertions and deletions, copy number alterations, and genomic rearrangements. RESULTS: Among 462 patients of whom 18.4% had MUP, brain metastasis was more common among patients with MUP (23% vs 7.1%). The differences in genomic profiling between MCP and MUP did not reach statistical significance. The 187 MCP and 44 MUP patients treated with immune checkpoint inhibitors had a median overall survival of 49 and 44 months, respectively (p = 0.705). CONCLUSIONS: The differences in somatic mutation patterns and survival outcomes were not statistically significant. These findings may allude to similar carcinogenic processes but should be considered exploratory and interpreted with caution.

Overview on the role of preoperative therapy in the management of kidney cancer.

The advent of molecular therapy through targeted kinase inhibitors (TKI) has revolutionized the management of renal cell carcinoma. Although surgical resection remains the cornerstone of any therapeutic plan, an increased risk of morbidity and mortality can be of concern in large and complex bulky tumors. Preoperative therapy with TKIs is hypothesized to facilitate resectability, reduce surgical morbidity and allow nephron-sparing surgery. Many concerns on the safety, efficacy and tolerability of these agents before surgery have halted the progress in this setting. In this paper, we will review the indications and safety of preoperative TKIs in RCC as well as the future approaches.

Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder.

Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances. Several trials with novel regimens, including immune checkpoint inhibitors and targeted therapy, to salvage relapsed urothelial carcinoma of the bladder have recently been published. However, the choice of an optimal treatment regimen remains challenging in the absence of randomized trials comparing regimen sequences. Daily clinical cases provoke the question of whether there is a preferred second-line regimen. This paper provides an overview of recent trials and proposes a management algorithm based on subgroup analyses and prognostic features.

Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

INTRODUCTION AND OBJECTIVES: MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. MATERIAL AND METHODS: We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). RESULTS: The study included 74 men with a median age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). CONCLUSIONS: In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. LEVEL OF EVIDENCE: 4.

Chemotherapy-induced differentiation to cure botryoid rhabdomyosarcoma: a case report and review of the literature.

Rhabdomyosarcoma (RMS) occurs rarely in adults and constitutes 2-6% of all uterine neoplasms. The authors report the case of a 26-year-old woman diagnosed with botryoid RMS that presented discordant progression results on follow up imaging and cytodifferentiation on pathologic control. This case showed that radiological evaluation could be misleading as the tumor demonstrated chemotherapy-induced differentiation without volume reduction. This case illustrates the limitations of using the imaging anatomical dimensions of sarcomas for treatment planning and highlights the potential role of functional imaging to assess the response to treatment.

Value of electrocardiograms ordered by junior medical officers in the emergency department.

The diagnostic rationale for patients with chest pain requires an electrocardiogram (ECG) often limited by low pretest values and widely variable post-test values. We assess the value of ECG ordered and interpreted by internal medicine junior medical officers in our emergency department (ED). Participants enrolled in this study included patients who presented to the ED for chest pain between June and October 2014. Seventeen leads ECG were performed systematically when an ECG was judged required by the medical officer in charge and interpreted by a blinded medical officer and ED attending. Ultrasensitive troponin T (usTrop T) and creatinine were also withdrawn. Junior medical officers ordered ECG more commonly for atypical chest pain (57 vs 43%, P = 0.049). Univariate and multivariate analysis did not demonstrate a statistically discordant diagnosis between the medical officer and the attending throughout the study period and between the different rotations. We demonstrated 97% sensitivity, 95% specificity, 92% positive predictive value, 98% negative predictive value and 96% accuracy. Our junior medical officers demonstrated an overall high proficiency in the clinical and bedside setting. This finding reinforces our ECG education in the undergraduate curriculum, highlights the importance of the intensive recapitulation sessions undergone at the beginning of the training programme and our daily internal medicine staff discussions rarely performed in other EDs as reported with our experience.

Experience of morning reports in the emergency department.

Morning report in the emergency medicine departments is an emerging teaching modality in the medicine curriculum. Our institution, Hotel-Dieu de France hospital, a multidisciplinary tertiary care university hospital affiliated to the Saint Joseph University of Medical Sciences, is the only hospital in Middle East to hold morning reports in the emergency department (ED). We evaluate the usefulness of the morning report as a pedagogic tool as it assesses the content, quality of the discussions, professionalism, leadership, participation and duration of the morning report. The particularity of this paper is that it takes into consideration the interns' input often under-recognised in the studies. An anonymous questionnaire was diffused to the residents and interns that rotated in the ED during the previous year. It consisted of seven multiple-choice questions to evaluate the quality of the presentations, targeted discussions, ethics and professionalism, evidence-based medicine, clinical reasoning, relation of cases to discussions and implication of the ED physician. Overall, of the 63 patients who answered the survey, 65.1% were satisfied by the content. The majority considered the quality of the discussions acceptable and the leadership and participation satisfactory, professionalism was judged poor. Both residents and interns were satisfied of the teaching point of the morning reports. The only fail back observed was professionalism and pathophysiological discussions that require to be added to the sessions, whereas clinical management, teaching points, leadership and time management were completely satisfactory.