ResearchPad - genitourinary https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Diagnosis of a small Leydig cell tumor by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging]]> https://www.researchpad.co/article/N53eea213-969f-430f-b3c3-bb30c30cb6b7 Leydig cell tumors are usually small and resemble normal ovarian stroma, so they are often difficult to localize. Here, we present a rare case in 39-year-old woman which dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging findings showed some differences between a Leydig cell tumor and normal ovarian stroma. Combining these 2 MRI techniques may be useful for diagnosing a Leydig cell tumor.

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<![CDATA[Feasibility of establishing an HIV vaccine preparedness cohort in a population of the Uganda Police Force: Lessons learnt from a prospective study]]> https://www.researchpad.co/article/Ne890bb8a-5661-4c39-82f7-6f40a2e69675

Background

Members of uniformed armed forces are considered to be at high risk for HIV infection and have been proposed as suitable candidates for participation in HIV intervention studies. We report on the feasibility of recruitment and follow up of individuals from the community of the Uganda Police Force (UPF) for an HIV vaccine preparedness study.

Methods

HIV-negative volunteers aged 18–49 years, were identified from UPF facilities situated in Kampala and Wakiso districts through community HIV counselling and testing. Potential volunteers were referred to the study clinic for screening, enrolment and quarterly visits for one year. HIV incidence, retention rates were estimated and expressed as cases per 100 person years of observation (PYO). Rate ratios were used to determine factors associated with retention using Poisson regression models.

Results

We screened 560 to enroll 500 volunteers between November 2015 and May 2016. One HIV seroconversion occurred among 431 PYO, for an incidence rate of 0.23/100 PYO (95% confidence interval [CI]: 0.03–1.64). Overall, retention rate was 87% at one year, and this was independently associated with residence duration (compared to <1 year, 1 to 5 years adjusted rate ratio (aRR) = 1.19, 95%CI: 1.00–1.44); and >5 years aRR = 1.34, 95%CI: 0.95–1.37); absence of genital discharge in the last 3 months (aRR = 1.97, 95% CI: 1.38–2.83, absence of genital ulcers (aRR = 1.90, 95%CI: 1.26–2.87, reporting of new sexual partner in the last month (aRR = 0.57, 95%CI: 0.45–0.71, being away from home for more than two nights (aRR = 1.27, 95%CI: 1.04–1.56, compared to those who had not travelled) and absence of knowledge on HIV prevention (aRR = 2.67, 95%CI: 1.62–4.39).

Conclusions

While our study demonstrates the feasibility of recruiting and retaining individuals from the UPF for HIV research, we did observe lower than anticipated HIV incidence, perhaps because individuals at lower risk of HIV infection may have been the first to come forward to participate or participants followed HIV risk reduction measures. Our findings suggest lessons for recruitment of populations at high risk of HIV infection.

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<![CDATA[Guidelines for Transrectal Ultrasonography-Guided Prostate Biopsy: Korean Society of Urogenital Radiology Consensus Statement for Patient Preparation, Standard Technique, and Biopsy-Related Pain Management]]> https://www.researchpad.co/article/N6424040e-7692-42cb-b414-6c3a7922e02a

The Korean Society of Urogenital Radiology (KSUR) aimed to present a consensus statement for patient preparation, standard technique, and pain management in relation to transrectal ultrasound-guided prostate biopsy (TRUS-Bx) to reduce the variability in TRUS-Bx methodologies and suggest a nationwide guideline. The KSUR guideline development subcommittee constructed questionnaires assessing prebiopsy anticoagulation, the cleansing enema, antimicrobial prophylaxis, local anesthesia methods such as periprostatic neurovascular bundle block (PNB) or intrarectal lidocaine gel application (IRLA), opioid usage, and the number of biopsy cores and length and diameter of the biopsy needle. The survey was conducted using an Internet-based platform, and responses were solicited from the 90 members registered on the KSUR mailing list as of 2018. A comprehensive search of relevant literature from Medline database was conducted. The strength of each recommendation was graded on the basis of the level of evidence. Among the 90 registered members, 29 doctors (32.2%) responded to this online survey. Most KSUR members stopped anticoagulants (100%) and antiplatelets (76%) one week before the procedure. All respondents performed a cleansing enema before TRUS-Bx. Approximately 86% of respondents administered prophylactic antibiotics before TRUS-Bx. The most frequently used antibiotics were third-generation cephalosporins. PNB was the most widely used pain control method, followed by a combination of PNB plus IRLA. Opioids were rarely used (6.8%), and they were used only as an adjunctive pain management approach during TRUS-Bx. The KSUR members mainly chose the 12-core biopsy method (89.7%) and 18G 16-mm or 22-mm (96.5%) needles. The KSUR recommends the 12-core biopsy scheme with PNB with or without IRLA as the standard protocol for TRUS-Bx. Anticoagulants and antiplatelet agents should be discontinued at least 5 days prior to the procedure, and antibiotic prophylaxis is highly recommended to prevent infectious complications. Glycerin cleansing enemas and administration of opioid analogues before the procedure could be helpful in some situations. The choice of biopsy needle is dependent on the practitioners' situation and preferences.

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<![CDATA[EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4–Positive Solid Tumors, Including Metastatic Urothelial Carcinoma]]> https://www.researchpad.co/article/N9b61e74f-1cd6-4ed6-bb05-7b2a38867569

PURPOSE

To assess the safety/tolerability and antitumor activity of enfortumab vedotin (EV), a novel investigational antibody-drug conjugate that delivers the microtubule-disrupting agent, monomethyl auristatin E, to cells that express Nectin-4.

METHODS

EV-101 is a phase I dose escalation/expansion study that enrolled patients with Nectin-4–expressing solid tumors (eg, metastatic urothelial carcinoma [mUC]) who progressed on ≥ 1 prior chemotherapy regimen and/or programmed death-1 receptor/programmed death ligand-1 [PD-(L)1] inhibitor, including a cohort of patients with mUC who received prior anti–PD-(L)1 therapy. Patients received escalating doses of EV up to 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle. Primary objectives were evaluation of safety/tolerability and pharmacokinetics; antitumor activity was a secondary objective.

RESULTS

Enrolled patients with mUC (n = 155) were heavily pretreated, with 96% having prior platinum-based chemotherapy and 29% receiving ≥ 3 lines of prior treatment. Maximum tolerated dose of EV was not established; however, the recommended phase II dose was identified as 1.25 mg/kg. Rash, peripheral neuropathy, fatigue, alopecia, and nausea were the most common treatment-related adverse events (TRAEs); the most common TRAEs were grade 1-2 in severity. Among the 112 patients with mUC treated with single-agent EV 1.25 mg/kg, the investigator-assessed confirmed objective response rate (ORR) was 43%, and duration of response was 7.4 months. Median overall survival (OS) was 12.3 months, and the OS rate at 1 year was 51.8%. Similar ORR and estimated median OS were observed in patients ≥ 75 years of age with and without prior anti–PD-(L)1 treatment, liver metastases, or upper-tract disease.

CONCLUSION

Single-agent EV was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging. A pivotal phase II and a confirmatory phase III study are ongoing.

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<![CDATA[Massive inguino-scrotal herniation of urinary bladder in an infant (scrotal cystocele)—case report☆☆]]> https://www.researchpad.co/article/Naf3f02e4-e592-4e74-bb71-b79a002cf5c7

Scrotal cystocele (massive inguino-scrotal herniation of urinary bladder) is an extremely rare event occurring in pediatric population. Authors present a case of a massive herniation of urinary bladder into the scrotum in a 1-year-old male infant who presented with markedly enlarged scrotum. Extremely rare case of massive urinary bladder herniation into scrotum, as we were able to find only one reported case in literature search. Enlarged scrotum in infants can be due to multiple causes in which one of them can be herniation of urinary bladder and it is key to know the contents of hernia sac before any intervention.

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<![CDATA[Outcomes in Black and White Patients With Metastatic Renal Cell Carcinoma Treated With First-Line Tyrosine Kinase Inhibitors: Insights From Two Large Cohorts]]> https://www.researchpad.co/article/Nf9a7e651-8fd6-4924-8ed9-032ae6869640

PURPOSE

To investigate whether black race is an independent predictor of overall survival (OS) in metastatic renal cell carcinoma (mRCC).

METHODS

We performed a retrospective 2-cohort (International Metastatic Renal Cell Carcinoma Database Consortium [IMDC] and trial-database) study of patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). Unmatched (UM) and matched (M) analyses accounting for imbalances in region, year of treatment, age, and sex between races were performed. Cox models adjusting for histology, number of metastatic sites, nephrectomy, and IMDC risk compared time to treatment failure (TTF; IMDC cohort), progression-free survival (PFS; trial-database cohort), and OS.

RESULTS

The IMDC cohort included 73 black versus 3,381 (UM) and 1,236 (M) white patients. The trial-database cohort included 21 black versus 1,040 (UM) and 431 (M) white patients. Median OS for black versus white patients was 18.5 versus 25.8 months in the IMDC group and 21.0 versus 25.6 months in the trial-database group. Differences in OS were not significant in multivariable analysis in the IMDC group (hazard ratio [HR]M, 1.0; 95% CI, 0.7 to 1.5; HRUM, 1.1; 95% CI, 0.8 to 1.4) and trial-database (HRM, 1.5; 95% CI, 0.8 to 2.7; HRUM, 1.4; 95% CI, 0.8 to 2.6) cohorts. TTF for black patients was shorter in the UM IMDC cohort (HRUM, 1.4; 95% CI, 1.1 to 1.8; P = .003), but not in the M analysis. PFS was shorter for black patients in both analyses in the trial-database cohort (HRM, 2.3; 95% CI, 1.4 to 3.9; P = .002; HRUM, 2.3; 95% CI, 1.4 to 3.9; P = .002).

CONCLUSION

Black patients had more IMDC risk factors and worse outcomes with TKIs versus white patients. Race was not an independent predictor of OS. Strategies to understand biologic determinants of outcomes for minority patients are needed to optimize care.

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<![CDATA[Survival Outcomes After Adding Stereotactic Body Radiotherapy to Metastatic Renal Cell Carcinoma Patients Treated With Tyrosine Kinase Inhibitors]]> https://www.researchpad.co/article/N0a8b720f-9eac-4e4d-8394-1b150e4e3825

Supplemental Digital Content is available in the text.

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<![CDATA[Primary malignant mediastinal germ cell tumors: A single institutional experience]]> https://www.researchpad.co/article/Na1050a52-1a6a-4c57-a122-bdcf7390d073

Background:

Primary mediastinal malignant germ cell tumour (PMMGCT) is rare with unsatisfactory prognosis and pose difficulty in management due to lack of guidelines.

Methods:

All cases of PMMGCT diagnosed and treated between years 2014 to 2018 were retrospectively evaluated for clinico-pathological features, multimodality treatment and follow up.

Results:

Among a total of five PMMGCT cases, three were seminomatous and two were non seminomatous tumour [Yolk- sac tumour (n-1) and Mixed tumour (n-1)]. Four of these cases were non - metastatic with locally advancement and another one presented with metastasis to supraclavicular lymph node. All patients received platinum based induction chemotherapy. Post-induction chemotherapy, two cases of non seminomatous tumours underwent surgery. Among the three seminoma cases, one patient showed complete metabolic response; one with metastasis succumbed to the disease and the in-operable case of seminoma received local radiotherapy.

Conclusion:

PMMGCT needs a multi-disciplinary approach for appropriate diagnosis and management. Clinicopathological features like tumour site, extension, histopathological type, tumour stage and serum tumour marker are necessary for prognostication and decision making of further treatment plan.

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<![CDATA[A tertiary care audit of using abiraterone acetate in patients of metastatic castrate-resistant prostate cancer]]> https://www.researchpad.co/article/N1014d340-07b5-4d87-930e-dba559528304

Introduction:

This is a retrospective analysis to assess the safety and efficacy of abiraterone acetate (AA) in metastatic castrate-resistant prostate cancer (mCRPC) patients treated at tertiary care institute.

Materials and Methods:

The clinical records of mCRPC patients treated with AA at our tertiary care institute between July 2013 and December 2015 were reviewed. The treatment efficacy, toxicities, and its determinants were analyzed.

Results:

A total of 59 mCRPC patients treated with AA were reviewed, of whom 37 were chemo-naive and 22 had received prior chemotherapy (postchemo). The median follow-up duration was 10.0/15.0 months for chemo-naïve/postchemotherapy patients. 43.2%/36.36% of chemo-naive/postchemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 15/7.8 months and 10/5.3 months for chemo-naive/postchemo patients, respectively. Median time to best prostate-specific antigen response was 3.4 months. Abiraterone was relatively well tolerated with no grade 4 toxicity or treatment-related death. We found the presence of previous taxene use and baseline symptoms to be significantly determinant of OS with abiraterone.

Conclusion:

The present study reported the efficacy of abiraterone in both chemo-naïve and postchemo patients of mCRPC outside clinical trial setting. We found lower OS and PFS with abiraterone as compared to that reported in the clinical trial setting in both chemo-naïve and postchemo patients, and particularly in those patients with the visceral disease, and further clinical trial for abiraterone in this subgroup of patients is warranted.

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<![CDATA[Atypical dermoid cyst of the ovary during pregnancy: A multi-modality diagnostic approach]]> https://www.researchpad.co/article/Nf5eef978-96b4-48e2-b8e9-189c50f5cc5b

We report a case of a sixth-month-pregnant 37-year-old woman with abdominal pain with the presence of a dermoid cyst of the left ovary. The diagnostic work-up required a multi-modality imaging approach. In particular, US and MR examinations were initially performed but resulted with an inconclusive outcome of a final diagnosis. Hence, a CT scan was successively used to formulate lesion characterization. Thus, integrated imaging approach would be recommended.

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<![CDATA[Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series]]> https://www.researchpad.co/article/Ne7ebe4b8-b927-4fd1-a438-3fd04efc5df6

Purpose

To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC).

Materials and methods

We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test.

Results

We identified 873 patients who underwent surgery for RCC between the years 2000–2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265–1.614) and Nuclear grade (HR 2.376, 95% CI 1.734–3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343–5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001).

Conclusions

We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease.

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<![CDATA[Imaging findings of a torsed pedunculated uterine leiomyoma: A case report]]> https://www.researchpad.co/article/Nd52bc40e-af1e-4464-ab2b-7baab602cb0c

Torsion of a pedunculated uterine leiomyoma is an incredibly rare occurrence, considered a surgical emergency due to the risk of ischemic gangrene and resulting reactive peritonitis. Imaging modalities have traditionally played a limited role in evaluation of leiomyoma torsion due to modest sensitivity and specificity. We present the case of a 58-year old female with a known pedunculated fibroid who presented with acute abdominal pain. Computed tomography and ultrasound findings suggested a preoperative diagnosis of leiomyoma torsion, confirmed intraoperatively. While direct visualization at surgery remain the primary means of diagnosis of pedunculated fibroid torsion, familiarity of potential imaging findings in conjunction with the clinical presentation may enable the interpreting radiologist to consider this entity in the differential prospectively.

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<![CDATA[MR imaging of paratesticular bilateral leiomyoma: A case report]]> https://www.researchpad.co/article/5c9d2c01d5eed0c4840b2638

Paratesticular leiomyoma is a rare benign neoplasm that may arise from smooth muscle cells contained in either the epididymis, the spermatic cord, or the tunica albuginea. Usually patients present a palpable, asymptomatic mass, with a higher prevalence among the fourth and fifth decade of life. In this case report we describe a 57-year-old man with bilateral scrotal palpable masses evaluated with ultrasound and magnetic resonance imaging that were suggestive for leiomyoma. The lesions were surgically removed and pathology revealed no signs of malignancy confirming the diagnostic hypothesis of leiomyoma. Ultrasound is considered the imaging modality of choice for the initial evaluation of testicular masses since it allows an accurate localization (ie testicular vs paratesticular) and can identify signs of malignancy. Magnetic resonance imaging is less frequently performed but can considerably improve lesion characterization.

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<![CDATA[Urea-mediated dissociation alleviate the false-positive Treponema pallidum-specific antibodies detected by ELISA]]> https://www.researchpad.co/article/5c8823e2d5eed0c484639234

The serological detection of antibodies to Treponema pallidum is essential to the diagnosis of syphilis. However, for the presence of cross-reaction, the specific antibody tests [e.g., enzyme-linked immunosorbent assay (ELISA)] always have false-positive results. In this study, we derived and validated the dissociation of urea in an attempt to alleviate the situation of false-positive antibodies to T. pallidum detected by ELISA. Six serum samples that were false-positive antibodies to T. pallidum detected by ELISA, and 16 control serum samples (8 sera positive for both specific IgG and IgM, and 8 IgG-positive and IgM-negative sera) were collected to select the appropriate dissociated concentration and time of urea. Our goal was to establish improved an ELISA method based on the original detection system of ELISA. The sensitivity of the improved ELISA was evaluated by 275 serum samples with class IgM-positive antibodies to T. pallidum. At 6 mol/L with 10 minutes dissociation of urea, 6 samples with false-positive antibodies to T. pallidum were converted to negative, and compared with true-positive antibodies to T. pallidum. The sensitivity of the improved ELISA was 100% by detecting the class IgM-positive antibodies to T. pallidum in sera of patients with syphilis. Considering the importance at the diagnosis of syphilis, antibodies to T. pallidum in serum samples should be retested by the improved ELISA method to avoid false-positive results.

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<![CDATA[Profile of the tprK gene in primary syphilis patients based on next-generation sequencing]]> https://www.researchpad.co/article/5c784fecd5eed0c484007915

Background

The highly variable tprK gene of Treponema pallidum has been acknowledged to be one of the mechanisms that causes persistent infection. Previous studies have mainly focused on the heterogeneity in tprK in propagated strains using a clone-based Sanger approach. Few studies have investigated tprK directly from clinical samples using deep sequencing.

Methods/Principal findings

We conducted a comprehensive analysis of 14 primary syphilis clinical isolates of T. pallidum via next-generation sequencing to gain better insight into the profile of tprK in primary syphilis patients. Our results showed that there was a mixture of distinct sequences within each V region of tprK. Except for the predominant sequence for each V region as previously reported using the clone-based Sanger approach, there were many minor variants of all strains that were mainly observed at a frequency of 1–5%. Interestingly, the identified distinct sequences within the regions were variable in length and differed by only 3 bp or multiples of 3 bp. In addition, amino acid sequence consistency within each V region was found among the 14 strains. Among the regions, the sequence IASDGGAIKH in V1 and the sequence DVGHKKENAANVNGTVGA in V4 showed a high stability of inter-strain redundancy.

Conclusions

The seven V regions of the tprK gene in primary syphilis infection demonstrated high diversity; they generally contained a high proportion sequence and numerous low-frequency minor variants, most of which are far below the detection limit of Sanger sequencing. The rampant variation in each V region was regulated by a strict gene conversion mechanism that maintained the length difference to 3 bp or multiples of 3 bp. The highly stable sequence of inter-strain redundancy may indicate that the sequences play a critical role in T. pallidum virulence. These highly stable peptides are also likely to be potential targets for vaccine development.

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<![CDATA[Renal imaging in 199 Dutch patients with Birt-Hogg-Dubé syndrome: Screening compliance and outcome]]> https://www.researchpad.co/article/5c8accc2d5eed0c48498ff04

Birt-Hogg-Dubé syndrome is associated with an increased risk for renal cell carcinoma. Surveillance is recommended, but the optimal imaging method and screening interval remain to be defined. The main aim of our study was to evaluate the outcomes of RCC surveillance to get insight in the safety of annual US in these patients. Surveillance data and medical records of 199 patients with Birt-Hogg-Dubé syndrome were collected retrospectively using medical files and a questionnaire. These patients were diagnosed in two Dutch hospitals and data were collected until June 2014. A first screening for renal cell carcinoma was performed in 172/199 patients (86%). Follow-up data were available from 121 patients. The mean follow-up period per patient was 4.2 years. Of the patients known to be under surveillance, 83% was screened at least annually and 94% at least every two years. Thirty-eight renal cell carcinomas had occurred in 23 patients. The mean age at diagnosis of the first tumour was 51. Eighteen tumours were visualized by ultrasound. Nine small tumours (7–27 mm) were visible on MRI or CT and not detected using ultrasound. Our data indicate that compliance to renal screening is relatively high. Furthermore, ultrasound might be a sensitive, cheap and widely available alternative for MRI or part of the MRIs for detecting clinically relevant renal tumours in BHD patients,but the limitations should be considered carefully. Data from larger cohorts are necessary to confirm these observations.

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<![CDATA[Indirect treatment comparisons including network meta-analysis: Lenvatinib plus everolimus for the second-line treatment of advanced/metastatic renal cell carcinoma]]> https://www.researchpad.co/article/5c8823dbd5eed0c484639163

Background

In the absence of clinical trials providing direct efficacy results, this study compares different methods of indirect treatment comparison (ITC), and their respective impacts on efficacy estimates for lenvatinib (LEN) plus everolimus (EVE) combination therapy compared to other second-line treatments for advanced/metastatic renal cell carcinoma (a/mRCC).

Methods

Using EVE alone as the common comparator, the Bucher method for ITC compared LEN + EVE with cabozantinib (CAB), nivolumab (NIV), placebo (PBO) and axitinib (AXI). Hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) estimated the impact of applying three versions of the LEN+EVE trial data in separate ITCs. Last, to overcome exchangeability bias and potential violations to the proportional hazards assumption, a network meta-analysis using fractional polynomials was performed.

Results

Bucher ITCs demonstrated LEN + EVE superiority over EVE for PFS, indirect superiority to NIV, AXI, and PBO, and no difference to CAB. For OS, LEN + EVE was superior to EVE and indirectly superior to PBO, applying original HOPE 205 data. Using European Medicines Agency data, LEN + EVE was directly superior to EVE for OS. Fractional polynomial HRs for PFS and OS substantially overlapped with Bucher estimates, demonstrating LEN+EVE superiority over EVE, alone, NIV, and CAB. However, there were no statistically significant results as the credible intervals for HR crossed 1.0.

Conclusions

Comparing three Bucher ITCs, LEN + EVE demonstrated superior PFS when indirectly compared to NIV, AXI, and PBO, and mixed results for OS. While fractional polynomial modelling for PFS and OS failed to find statistically significant differences in LEN + EVE efficacy, the overall HR trends were comparable.

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<![CDATA[PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery]]> https://www.researchpad.co/article/5c7d95e9d5eed0c484734f7e

Subnuclear promyelocytic leukemia (PML) nuclear bodies (NBs) are targeted by many DNA viruses after nuclear delivery. PML protein is essential for formation of PML NBs. Sp100 and Small Ubiquitin-Like Modifier (SUMO) are also permanently residing within PML NBs. Often, large DNA viruses disassemble and reorganize PML NBs to counteract their intrinsic antiviral activity and support establishment of infection. However, human papillomavirus (HPV) requires PML protein to retain incoming viral DNA in the nucleus for subsequent efficient transcription. In contrast, Sp100 was identified as a restriction factor for HPV. These findings suggested that PML NBs are important regulators of early stages of the HPV life cycle. Nuclear delivery of incoming HPV DNA requires mitosis. Viral particles are retained within membrane-bound transport vesicles throughout mitosis. The viral genome is released from transport vesicles by an unknown mechanism several hours after nuclear envelope reformation. The minor capsid protein L2 mediates intracellular transport by becoming transmembranous in the endocytic compartment. Herein, we tested our hypothesis that PML protein is recruited to incoming viral genome prior to egress from transport vesicles. High-resolution microscopy revealed that PML protein, SUMO-1, and Sp100 are recruited to incoming viral genomes, rather than viral genomes being targeted to preformed PML NBs. Differential immunofluorescent staining suggested that PML protein and SUMO-1 associated with transport vesicles containing viral particles prior to egress, implying that recruitment is likely mediated by L2 protein. In contrast, Sp100 recruitment to HPV-harboring PML NBs occurred after release of viral genomes from transport vesicles. The delayed recruitment of Sp100 is specific for HPV-associated PML NBs. These data suggest that the virus continuously resides within a protective environment until the transport vesicle breaks down in late G1 phase and imply that HPV might modulate PML NB assembly to achieve establishment of infection and the shift to viral maintenance.

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<![CDATA[Real-time adaptive planning method for radiotherapy treatment delivery for prostate cancer patients, based on a library of plans accounting for possible anatomy configuration changes]]> https://www.researchpad.co/article/5c818e8ad5eed0c484cc24c8

Background and purpose

In prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one.

Material and methods

Our adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A “library” of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed.

Results

For the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved.

Conclusions

In our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level.

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<![CDATA[Liver metastasis and Heng risk are prognostic factors in patients with non-nephrectomized synchronous metastatic renal cell carcinoma treated with systemic therapy]]> https://www.researchpad.co/article/5c76fe33d5eed0c484e5b6ea

Objective

This study aimed to determine the prognostic factors of progression-free survival (PFS) and overall survival (OS) in non-nephrectomized patients with synchronous metastatic renal cell carcinoma (mRCC) receiving first-line vascular endothelial growth factor (VEGF)-targeted therapy or immunotherapy.

Methods

Of 70 patients, 57 (81.4%) were treated with targeted therapy, including 5 (7.1%) with previous immunotherapy and 13 (18.6%) with immunotherapy only. The medical records of patients were retrospectively reviewed and analyzed to determine factors of PFS and OS using the Cox proportional hazards model with a statistical significance p-value <0.05.

Results

The median treatment and follow-up periods were 3.9 and 30.9 months, respectively. Disease progression was reported in 90.0% of patients, with an objective response rate and clinical benefit rate of 26.1% and 76.8%, respectively. The lung (77.1%) was the most common site of metastasis. Multivariable analysis showed that poor Heng risk (hazard ratio [HR]: 2.37) and liver metastasis (HR: 2.34) were significant prognostic factors for PFS, and female sex (HR: 2.13), poor Heng risk (HR: 3.14), and liver metastasis (HR: 2.78) were significant prognostic factors for OS (p < 0.05). A subset analysis of risk factors among patients without previous history of immunotherapy also showed poor Heng risk (HR 2.92 and HR 4.24 for PFS) and liver metastasis (HR 2.87 and HR 4.81 for OS) as significant factors for both PFS and OS (p<0.05).

Conclusion

Poor Heng risk, sex, and liver metastasis were associated with survival outcomes after first-line systemic therapy in patients with non-nephrectomized synchronous mRCC.

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