What is the effect of MRI with targeted biopsies on the rate of patients discontinuing active surveillance? A reflection of the use of MRI in the PRIAS study

Background The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification. Methods Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation. Results In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable. Conclusions Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted.Peer reviewe

False positives in PIRADS (V2) 3, 4, and 5 lesions:relationship with reader experience and zonal location

PURPOSE: To investigate the effect of reader experience and zonal location on the occurrence of false positives (FPs) in PIRADS (V2) 3, 4, and 5 lesions on multiparametric (MP)-MRI of the prostate. MATERIALS AND METHODS: This retrospective study included 139 patients who had consecutively undergone an MP-MRI of the prostate in combination with a transrectal ultrasound MRI fusion-guided biopsy between 2014 and 2017. MRI exams were prospectively read by a group of inexperienced radiologists (cohort 1; 54 patients) and an experienced radiologist (cohort 2; 85 patients). Multivariable logistic regression analysis was performed to determine the association of experience of the radiologist and zonal location with a FP reading. FP rates were compared between readings by inexperienced and experienced radiologists according to zonal location, using Chi-square (χ2) tests. RESULTS: A total of 168 lesions in 139 patients were detected. Median patient age was 68 years (Interquartile range (IQR) 62.5-73), and median PSA was 10.9 ng/mL (IQR 7.6-15.9) for the entire patient cohort. According to multivariable logistic regression, inexperience of the radiologist was significantly (P = 0.044, odds ratio 1.927, 95% confidence interval [CI] 1.017-3.651) and independently associated with a FP reading, while zonal location was not (P = 0.202, odds ratio 1.444, 95% CI 0.820-2.539). In the transition zone (TZ), the FP rate of the inexperienced radiologists 59% (17/29) was significantly higher (χ2P = 0.033) than that of the experienced radiologist 33% (13/40). CONCLUSION: Inexperience of the radiologist is significantly and independently associated with a FP reading, while zonal location is not. Inexperienced radiologists have a significantly higher FP rate in the TZ

Genetic properties of feed efficiency parameters in meat-type chickens

<p>Abstract</p> <p>Background</p> <p>Feed cost constitutes about 70% of the cost of raising broilers, but the efficiency of feed utilization has not kept up the growth potential of today's broilers. Improvement in feed efficiency would reduce the amount of feed required for growth, the production cost and the amount of nitrogenous waste. We studied residual feed intake (RFI) and feed conversion ratio (FCR) over two age periods to delineate their genetic inter-relationships.</p> <p>Methods</p> <p>We used an animal model combined with Gibb sampling to estimate genetic parameters in a pedigreed random mating broiler control population.</p> <p>Results</p> <p>Heritability of RFI and FCR was 0.42-0.45. Thus selection on RFI was expected to improve feed efficiency and subsequently reduce feed intake (FI). Whereas the genetic correlation between RFI and body weight gain (BWG) at days 28-35 was moderately positive, it was negligible at days 35-42. Therefore, the timing of selection for RFI will influence the expected response. Selection for improved RFI at days 28-35 will reduce FI, but also increase growth rate. However, selection for improved RFI at days 35-42 will reduce FI without any significant change in growth rate. The nature of the pleiotropic relationship between RFI and FCR may be dependent on age, and consequently the molecular factors that govern RFI and FCR may also depend on stage of development, or on the nature of resource allocation of FI above maintenance directed towards protein accretion and fat deposition. The insignificant genetic correlation between RFI and BWG at days 35-42 demonstrates the independence of RFI on the level of production, thereby making it possible to study the molecular, physiological and nutrient digestibility mechanisms underlying RFI without the confounding effects of growth. The heritability estimate of FCR was 0.49 and 0.41 for days 28-35 and days 35-42, respectively.</p> <p>Conclusion</p> <p>Selection for FCR will improve efficiency of feed utilization but because of the genetic dependence of FCR and its components, selection based on FCR will reduce FI and increase growth rate. However, the correlated responses in both FI and BWG cannot be predicted accurately because of the inherent problem of FCR being a ratio trait.</p

Whole-genome profiling of primary cutaneous anaplastic large cell lymphoma

Primary cutaneous anaplastic large cell lymphoma (pcALCL), a hematological neoplasm caused by skin-homing CD30+ malignant T cells, is part of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders. To date, only a small number of molecular alterations have been described in pcALCL and, so far, no clear unifying theme that could explain the pathogenetic origin of the disease has emerged among patients. In order to clarify the pathogenetic basis of pcALCL, we performed high-resolution genetic profiling (genome/transcriptome) of this lymphoma (n=12) by using whole-genome sequencing, whole-exome sequencing and RNA sequencing. Our study, which uncovered novel genomic rearrangements, copy number alterations and small-scale mutations underlying this malignancy, revealed that the cell cycle, T-cell physiology regulation, transcription and signaling via the PI-3-K, MAPK and G-protein pathways are cellular processes commonly impacted by molecular alterations in patients with pcALCL. Recurrent events affecting cancer-associated genes included deletion of PRDM1 and TNFRSF14, gain of EZH2 and TNFRSF8, small-scale mutations in LRP1B, PDPK1 and PIK3R1 and rearrangements involving GPS2, LINC-PINT and TNK1. Consistent with the genomic data, transcriptome analysis uncovered upregulation of signal transduction routes associated with the PI-3-K, MAPK and G-protein pathways (e.g., ERK, phospholipase C, AKT). Our molecular findings suggest that inhibition of proliferation-promoting pathways altered in pcALCL (particularly PI-3-K/AKT signaling) should be explored as potential alternative therapy for patients with this lymphoma, especially, for cases that do not respond to first-line skin-directed therapies or with extracutaneous disease

What is the effect of MRI with targeted biopsies on the rate of patients discontinuing active surveillance?: A reflection of the use of MRI in the PRIAS study

BACKGROUND: The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification. METHODS: Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation. RESULTS: In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable. CONCLUSIONS: Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted

Prostate cancer upgrading with serial prostate magnetic resonance imaging and repeat biopsy in men on active surveillance: are confirmatory biopsies still necessary?

Objectives: To investigate whether serial prostate magnetic resonance imaging (MRI) may guide the utility of repeat targeted (TBx) and systematic biopsy (SBx) when monitoring men with low-risk prostate cancer (PCa) at 1-year of active surveillance (AS). Patients and Methods: We retrospectively included 111 consecutive men with low-risk (International Society of Urological Pathology [ISUP] Grade 1) PCa, who received protocolled repeat MRI with or without TBx and repeat SBx at 1-year of AS. TBx was performed in Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 lesions (MRI-positive men). Upgrading defined as ISUP Grade ≥2 PCa (I), Grade ≥2 with cribriform growth/intraductal carcinoma PCa (II), and Grade ≥3 PCa (III) was investigated. Upgrading detected by TBx only (not by SBx) and SBx only (not by TBx) was investigated in MRI-positive and -negative men, and related to radiological progression on MRI (Prostate Cancer Radiological Estimation of Change in Sequential Evaluation [PRECISE] score). Results: Overall upgrading (I) was 32% (35/111). Upgrading in MRI-positive and -negative men was 48% (30/63) and 10% (5/48) (P < 0.001), respectively. In MRI-positive men, there was upgrading in 23% (seven of 30) by TBx only and in 33% (10/30) by SBx only. Radiological progression (PRECISE score 4–5) in MRI-positive men was seen in 27% (17/63). Upgrading (I) occurred in 41% (seven of 17) of these MRI-positive men, while this was 50% (23/46) in MRI-positive men without radiological progression (PRECISE score 1–3) (P = 0.534). Overall upgrading (II) was 15% (17/111). Upgrading in MRI-positive and -negative men was 22% (14/63) and 6% (three of 48) (P = 0.021), respectively. In MRI-positive men, there was upgrading in three of 14 by TBx only and in seven of 14 by SBx only. Overall upgrading (III) occurred in 5% (five of 111). Upgrading in MRI-positive and -negative men was 6% (four of 63) and 2% (one of 48) (P = 0.283), respectively. In MRI-positive men, there was upgrading in one of four by TBx only and in two of four by SBx only. Conclusion: Upgrading is significantly lower in MRI-negative compared to MRI-positive men with low-risk PCa at 1-year of AS. In serial MRI-negative men, the added value of repeat SBx at 1-year surveillance is limited and should be balanced individually against the harms. In serial MRI-positive men, the added value of repeat SBx is substantial. Based on this cohort, SBx is recommended to be performed in combination with TBx in all MRI-positive men at 1-year of AS, also when there is no radiological progression

False positives in PIRADS (V2) 3, 4, and 5 lesions : relationship with reader experience and zonal location

PURPOSE: To investigate the effect of reader experience and zonal location on the occurrence of false positives (FPs) in PIRADS (V2) 3, 4, and 5 lesions on multiparametric (MP)-MRI of the prostate. MATERIALS AND METHODS: This retrospective study included 139 patients who had consecutively undergone an MP-MRI of the prostate in combination with a transrectal ultrasound MRI fusion-guided biopsy between 2014 and 2017. MRI exams were prospectively read by a group of inexperienced radiologists (cohort 1; 54 patients) and an experienced radiologist (cohort 2; 85 patients). Multivariable logistic regression analysis was performed to determine the association of experience of the radiologist and zonal location with a FP reading. FP rates were compared between readings by inexperienced and experienced radiologists according to zonal location, using Chi-square (χ2) tests. RESULTS: A total of 168 lesions in 139 patients were detected. Median patient age was 68 years (Interquartile range (IQR) 62.5-73), and median PSA was 10.9 ng/mL (IQR 7.6-15.9) for the entire patient cohort. According to multivariable logistic regression, inexperience of the radiologist was significantly (P = 0.044, odds ratio 1.927, 95% confidence interval [CI] 1.017-3.651) and independently associated with a FP reading, while zonal location was not (P = 0.202, odds ratio 1.444, 95% CI 0.820-2.539). In the transition zone (TZ), the FP rate of the inexperienced radiologists 59% (17/29) was significantly higher (χ2P = 0.033) than that of the experienced radiologist 33% (13/40). CONCLUSION: Inexperience of the radiologist is significantly and independently associated with a FP reading, while zonal location is not. Inexperienced radiologists have a significantly higher FP rate in the TZ