bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of serratiopeptidase after impacted third molar surgery: a randomized controlled clinical trial
Authors: Tamimi Zaid , Al Habashneh Rola , Hamad Islam , al-Ghazawi Mutasim , Roqa’a Ala’ Abu , Kharashgeh Hamza
Published: March 2021

Background

Serratiopeptidase has been clinically used in controlling surgical and non-surgical inflammatory conditions. This study was conducted to assess the therapeutic effect of Serratiopeptidase in patients undergoing surgical removal of impacted mandibular third molar.

Methods

This randomized clinical trial investigated the efficacy of Serratiopeptidase and Paracetamol after surgical removal of impacted third molar for 5 days (n = 67) as compared with an equivalent dose of placebo and Paracetamol (n = 66). Outcome measures were reported pain, trismus and swelling using Laskin method. All outcome measures were recorded on days 0, 1, 2, 4, and 5 post-surgeries.

Results

In this clinical trail 133 patients (mean age 23 years, 54% female) completed the study. Baseline characteristics were comparable across treatment groups. Serratiopeptidase significantly improved trismus compared with control on the 4thday (27.30 ± 7.3 mm and 32.06 ± 7.7 mm, respectively (P < 0.001) Swelling markedly improved, The distance from the lower edge of the earlobe to the midpoint of the symphysis for cases vs control were 111.49 ± 8.1 mm and 115.39 ± 9.9 mm, respectively (P < 0.001). Reported pain, showed no statistical significance difference.

Conclusion

Serratiopeptidase resulted in better inflammation improvement than placebo over 5 days. Further studies are warranted to assess longer-term and clinical outcomes, as well as safety.

Clinical relevance

Serratiopeptidase administered postoperatively helps in improving trismus and swelling after removal of impacted lower third molars.

Trial registrationThe study was registered in ClinicalTrial.gov under the number NCT02493179.Registered 1st of June 2015,https://clinicaltrials.gov/ct2/results?cond=serratiopeptidase.
Co-culture of Vel1-overexpressed Trichoderma asperellum and Bacillus amyloliquefaciens: An eco-friendly strategy to hydrolyze the lignocellulose biomass in soil to enrich the soil fertility, plant growth and disease resistance
Authors: Karuppiah Valliappan , Zhixiang Lu , Liu Hongyi , Vallikkannu Murugappan , Chen Jie
Published: March 2021

Background

Retention of agricultural bio-mass residues without proper treatment could affect the subsequent plant growth. In the present investigation, the co-cultivation of genetically engineeredT. asperellumandB. amyloliquefacienshas been employed for multiple benefits including the enrichment of lignocellulose biodegradation, plant growth, defense potential and disease resistance.

Results

TheVel1gene predominantly regulates the secondary metabolites, sexual and asexual development as well as cellulases and polysaccharide hydrolases productions. Overexpression mutant of theTrichoderma asperellum Vel1locus (TA OE-Vel1) enhanced the activity of FPAase, CMCase, PNPCase, PNPGase, xylanase I, and xylanase II through the regulation of transcription regulating factors and the activation of cellulase and xylanase encoding genes. Further, these genes were induced upon co-cultivation withBacillus amyloliquefaciens(BA).The co-culture of TA OE-Vel1 + BA produced the best composition of enzymes and the highest biomass hydrolysis yield of 89.56 ± 0.61%. The co-culture of TA OE-Vel1 + BA increased the corn stover degradation by the secretion of cellulolytic enzymes and maintained the C/N ratio of the corn stover amended soil. Moreover, the TA OE-Vel1 + BA increased the maize plant growth, expression of defense gene and disease resistance againstFusarium verticillioidesandCohilohorus herostrophus.

Conclusion

The co-cultivation of genetically engineered T.asperellumandB. amyloliquefacienscould be utilized as a profound and meaningful technique for the retention of agro residues and subsequent plant growth.
Microbial biotechnological approaches: renewable bioprocessing for the future energy systems
Authors: Ramamurthy Praveen C. , Singh Simranjeet , Kapoor Dhriti , Parihar Parul , Samuel Jastin , Prasad Ram , Kumar Alok , Singh Joginder
Published: March 2021

The accelerating energy demands of the increasing global population and industrialization has become a matter of great concern all over the globe. In the present scenario, the world is witnessing a considerably huge energy crisis owing to the limited availability of conventional energy resources and rapid depletion of non-renewable fossil fuels. Therefore, there is a dire need to explore the alternative renewable fuels that can fulfil the energy requirements of the growing population and overcome the intimidating environmental issues like greenhouse gas emissions, global warming, air pollution etc. The use of microorganisms such as bacteria has captured significant interest in the recent era for the conversion of the chemical energy reserved in organic compounds into electrical energy. The versatility of the microorganisms to generate renewable energy fuels from multifarious biological and biomass substrates can abate these ominous concerns to a great extent. For instance, most of the microorganisms can easily transform the carbohydrates into alcohol. Establishing the microbial fuel technology as an alternative source for the generation of renewable energy sources can be a state of art technology owing to its reliability, high efficiency, cleanliness and production of minimally toxic or inclusively non-toxic byproducts. This review paper aims to highlight the key points and techniques used for the employment of bacteria to generate, biofuels and bioenergy, and their foremost benefits.
GM-CSF enhanced the effect of CHOP and R-CHOP on inhibiting diffuse large B-cell lymphoma progression via influencing the macrophage polarization
Authors: Zhang Yu , Xiang Jingjing , Sheng Xianfu , Zhu Ni , Deng Shu , Chen Junfa , Yu Lihong , Zhou Yan , Lin Chenjun , Shen Jianping
Published: March 2021

Background

Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown.

Methods

In the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF.

Results

CHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF.

Conclusions

Our work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL.

Trial registration Not applicable.
Addressing key gaps in implementation of mosquito larviciding to accelerate malaria vector control in southern Tanzania: results of a stakeholder engagement process in local district councils
Authors: Mapua Salum A. , Finda Marceline F. , Nambunga Ismail H. , Msugupakulya Betwel J. , Ukio Kusirye , Chaki Prosper P. , Tripet Frederic , Kelly Ann H. , Christofides Nicola , Lezaun Javier , Okumu Fredros O.
Published: March 2021

Background

Larval source management was historically one of the most effective malaria control methods but is now widely deprioritized in Africa, where insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are preferred. However, in Tanzania, following initial successes in urban Dar-es-Salaam starting early-2000s, the government now encourages larviciding in both rural and urban councils nationwide to complement other efforts; and a biolarvicide production-plant has been established outside the commercial capital. This study investigated key obstacles and opportunities relevant to effective rollout of larviciding for malaria control, with a focus on the meso-endemic region of Morogoro, southern Tanzania.

Methods

Key-informants were interviewed to assess awareness and perceptions regarding larviciding among designated health officials (malaria focal persons, vector surveillance officers and ward health officers) in nine administrative councils (n = 27). Interviewer-administered questionnaires were used to assess awareness and perceptions of community members in selected areas regarding larviciding (n = 490). Thematic content analysis was done and descriptive statistics used to summarize the findings.

Results

A majority of malaria control officials had participated in larviciding at least once over the previous three years. A majority of community members had neutral perceptions towards positive aspects of larviciding, but overall support for larviciding was high, although several challenges were expressed, notably: (i) insufficient knowledge for identifying relevant aquatic habitats of malaria vectors and applying larvicides, (ii) inadequate monitoring of programme effectiveness, (iii) limited financing, and (iv) lack of personal protective equipment. Although the key-informants reported sensitizing local communities, most community members were still unaware of larviciding and its potential.

Conclusions

The larviciding programme was widely supported by both communities and malaria control officials, but there were gaps in technical knowledge, implementation and public engagement. To improve overall impact, it is important to: (i) intensify training efforts, particularly for identifying habitats of important vectors, (ii) adopt standard technical principles for applying larvicides or larval source management, (iii) improve financing for local implementation and (iv) improve public engagement to boost community awareness and participation. These lessons could also be valuable for other malaria endemic areas wishing to deploy larviciding for malaria control or elimination.
The integration of sex and gender considerations in health policymaking: a scoping review
Authors: Williams Allison , Lyeo Joonsoo Sean , Geffros Sophie , Mouriopoulos Alexander
Published: March 2021

While the terms ‘sex’ and ‘gender’ represent distinct concepts, their influence may intersect as important determinants of health. Despite their influence in shaping individual health outcomes, there is often inaccuracy and inconsistency in the degree to which sex and gender considerations are integrated in the health policymaking process. This primary aim of this paper is to fill the gap in the current understanding of how sex and gender considerations are integrated in this process. A scoping review methodology was used with the objective of assessing the extent to which sex and gender were considered inclusively and comprehensively in established examples of health policy planning and development. One hundred seventy-five documents from the academic and grey literature were found to meet the inclusion criteria for this scoping review. The authors charted the data from these publications, assessing the ways in which sex and gender were incorporated in their policy development process. Five key findings were ascertained from this review: (1) the terms sex and gender are often used interchangeably; (2) the terms sex and gender are often used with a limited and binary scope; (3) the most inclusive and comprehensive documents included transgender and gender diverse populations; (4) there are significant variations in the degree of inclusivity and comprehensivity of these documents based on geographic distribution; and (5) documents published within the last 5 years were more inclusive than older documents. This paper concludes with an acknowledgment of the limitations of the study design, a summary of the findings, future research directions, and implications for policymakers.
NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging, drug delivery and combined photothermal chemotherapy for triple negative breast cancer
Authors: Jiang Qunjiao , Liu Li , Li Qiuying , Cao Yi , Chen Dong , Du Qishi , Yang Xiaobo , Huang Dongping , Pei Renjun , Chen Xing , Huang Gang
Published: March 2021

Background

Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy.

Methods

Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2′-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC.

Results

The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency.

Conclusion

A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.

Graphic abstract
Meaningful measurements of maneuvers: People with incomplete spinal cord injury ‘step up’ to the challenges of altered stability requirements
Authors: Ochs Wendy L. , Woodward Jane , Cornwell Tara , Gordon Keith E.
Published: March 2021

Background

Many people with incomplete spinal cord injury (iSCI) have the ability to maneuver while walking. However, neuromuscular impairments create challenges to maintain stability. How people with iSCI maintain stability during walking maneuvers is poorly understood. Thus, this study compares maneuver performance in varying external conditions between persons with and without iSCI to better understand maneuver stabilization strategies in people with iSCI.

Methods

Participants with and without iSCI walked on a wide treadmill and were prompted to perform lateral maneuvers between bouts of straight walking. Lateral force fields applied to the participants’ center of mass amplified or attenuated the participants’ movements, thereby increasing the capability of the study to capture behavior at varied levels of challenge to stability.

Results

By examining metrics of stability, step width, and center of mass dynamics, distinct strategies emerged following iSCI. The minimum margin of stability (MOSmin) on each step during maneuvers indicated persons with iSCI generally adapted to amplified and attenuated force fields with increased stability compared to persons without iSCI, particularly using increased step width and reduced center of mass excursion on maneuver initiation. In the amplified field, however, persons with iSCI had a reduced MOSmin when terminating a maneuver, likely due to the challenge of the force field opposing the necessary lateral braking. Persons without iSCI were more likely to rely on or oppose the force field when appropriate for movement execution. Compared to persons with iSCI, they reduced their MOSmin to initiate maneuvers in the attenuated and amplified fields and increased their MOSmin to arrest maneuvers in the amplified field.

Conclusions

The different force fields were successful in identifying relatively subtle strategy differences between persons with and without iSCI. Specifically, persons with iSCI adopted increased step width and reduction in center of mass excursion to increase maneuver stability in the amplified field. The amplified field may provoke practice of stable and efficient initiation and arrest of walking maneuvers. Overall, this work allows better framing of the stability mechanisms used following iSCI to perform walking maneuvers.
An analysis of energy detector based on improved approximations of the chi-square distributions
Authors: Elias Felipe G. M. , Fernández Evelio M. G.
Published: March 2021

Closed-form expressions for the detection probability, the false alarm probability and the energy detector constant threshold are derived using approximations of the central chi-square and non-central chi-square distributions. The approximations used show closer proximity to the original functions when compared to the expressions used in the literature. The novel expressions allow gains up to 6% and 16% in terms of measured false alarm and miss-detection probability, respectively, if compared to the Central Limit Theorem approach. The throughput of cognitive network is also enhanced when these novel expressions are implemented, providing gains up to 9%. New equations are also presented that minimize the total error rate to obtain the detection threshold and the optimal number of samples. The analytical results match the results of the simulation for a wide range of SNR values.
Prevalence of IgM and IgG antibodies to SARS-CoV-2 in health care workers at a tertiary care New York hospital during the Spring COVID-19 surge
Authors: Talbot Lillian R. , Romeiser Jamie L. , Spitzer Eric D. , Gan Tong J. , Singh Sunitha M. , Fries Bettina C. , Bennett-Guerrero Elliott
Published: March 2021

Background

Health care workers (HCW) such as anesthesiologists, surgeons, and intensivists face high rates of exposure to SARS-CoV-2 through direct contact with COVID-19 patients. While there are initial reports of the prevalence of COVID-19 antibodies among the general population, there are few reports comparing the seroprevalence of IgM/IgG COVID-19 antibodies in HCW of different exposure levels as well as different HCW professions.

Methods

A convenience sample of health care workers provided blood for COVID-19 antibody testing and a review of medical history and work exposure for correlative analyses.

Results

Overall, 474 HCW were enrolled in April 2020 including 102 front-line physicians (e.g., anesthesiologists, surgeons, intensivists, emergency medicine), 91 other physicians, 135 nurses, 134 other clinical staff, and 12 non-clinical HCW. The prevalence of IgM or IgG antibodies to SARS-CoV-2 was 16.9% (95% CI 13.6–20.6) (80/474). The proportion of positive antibodies in the PCR + group was significantly higher than health care workers without symptoms (84.6% [95% CI 54.6–98.1] vs. 12.3% [95% CI 8.5–17.2], p < 0.001). No significant differences in proportions of COVID-19 antibodies were observed among the different exposure groups (e.g., high vs minimal/no exposure) and among the different HCW professionals.

Conclusions

Despite exposure to COVID-19 patients, the prevalence of antibodies in our HCW was similar to what has been reported for the general population of New York State (14%) and for another New York HCW cohort (13.7%). Health care workers with higher exposure rates were not more likely to have been infected with COVID-19. Therefore, these data suggest that infection of HCW may result from exposure in the community rather than at work.

Trial registration

This investigator-initiated study was observational; therefore, no registration was required. Not applicable.
Risk factors for postpartum intrauterine device expulsion among women delivering at a tertiary Hospital in Uganda: a prospective cohort study
Authors: Muhumuza Joy , Migisha Richard , Ngonzi Joseph , Kayondo Musa , Mugyenyi Godfrey
Published: March 2021

Background

Postpartum intrauterine device (PPIUD) use refers to intrauterine device (IUD) insertion after delivery but within 48 h of birth. In Uganda, the general use of modern methods of contraception is low with < 1% of the women adopting the IUD as a method of contraception. An important limiting factor to increased uptake of immediate postpartum IUD insertion may be its expulsion rates which vary widely. There is minimal documentation PPIUD expulsion rates and factors associated with PPIUD expulsion during puerperium in Uganda.

Objective

We aimed to determine the proportion of TCu380A (copper) intrauterine devices expelled by 6 weeks postpartum, and identify risk factors for expulsion among women delivering at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda.

Methods

We conducted a prospective cohort study from September 1, 2014 to January 31, 2015 at MRRH. We administered a structured questionnaire to all participants, to capture data on their baseline demographic, clinical and obstetric characteristics. We followed up women who accepted the PPIUD insertions at 6 weeks post insertion for any IUD expulsion. We fit multivariable log binomial regression models to identify risk factors for IUD expulsion.

Results

We enrolled 167 women who had PPIUDs inserted. Of the144 women who returned at 6 weeks for follow up, 13 (9%; 95%CI:4.9–15%) of them had the IUDs expelled. In the multivariable model, the significant risk factors for PPIUD expulsion were: IUD insertion more than 10 min post-delivery (aRR 8.1, 95%CI 1.26–51.98, p = 0.027) and bloody lochia flow of ≥15 days (aRR 8.5, 95%CI 1.47–48.47, p = 0.017).

Conclusion

The cumulative expulsion rate of postpartum IUDs among women delivering at MRRH was low and comparable to expulsion rates in interval insertions. Longer duration from delivery to IUD insertions and longer duration of bloody lochia flow were key risk factors for postpartum IUD expulsion. More emphasis should be put on prenatal counseling for postpartum family planning to allow for postplacental IUD insertions, which are associated with lower expulsion rates.
Shape memory polymer ovarian vein embolisation in a patient with nickel allergy
Authors: Castellano Davide , Boghi Andrea , Di Maggio Luca , Rapellino Alessandro , Savio Daniele
Published: March 2021

Background

Ovarian vein embolization in pelvic varicocele is usually obtained using nitinol coils. These devices can not be used in patients with proven nickel allergy.

Case presentation

Shape memory polymer is a new embolic material available to interventionalists. A patient presented with pelvic congestion syndrome requiring embolisation of the left ovarian vein. The target vessel consisted of two twisted branches, each 5–6 mm in diameter. The patient also had a known allergy to nickel. Considering the anatomy and allergy status, embolisation with polyurethane shape memory polymer vascular plugs was considered a good case strategy. The embolisation procedure was technically successful with the deployment of two shape memory polymer plugs into each of the two left ovarian vein branches. Follow-up magnetic resonance imaging at 4 months showed sustained occlusion of the treated vessels and the patient showed no signs of allergy to the implanted material.

Conclusions

In conclusion, our case presented an opportunity to utilise a new embolic material and achieve a good outcome in a patient with an allergy that may have resulted in complications when using metallic implants.
Final analysis results from TITAN: A phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT).
Authors: Chi Kim N. , Chowdhury Simon , Bjartell Anders , Chung Byung Ha , Pereira de Santana Gomes Andrea Juliana , Given Robert , Juárez Soto Álvaro , Merseburger Axel Stuart , Ozguroglu Mustafa , Uemura Hirotsugu , Ye Dingwei , Triantos Spyros , Mundle Suneel , McCarthy Sharon Anne , Larsen Julie S. , Sun Weili , Bevans Katherine , Zhang Ke , Bandyopadhyay Nibedita , Agarwal Neeraj ,   For the TITAN Investigators
Published: March 2021

11

Background: TITAN evaluated APA or PBO added to ADT in pts with mCSPC. Pts with high- and low-volume disease, prior docetaxel, prior treatment for localized disease, and prior ADT (≤ 6 mos) were eligible. At the first interim analysis, with 22.7 mos median follow-up, APA significantly improved dual primary end points of overall survival (OS) (hazard ratio [HR] 0.67) and radiographic progression-free survival (rPFS) (HR 0.48) compared with PBO (Chi et al. NEJM. 2019). At that time, OS analysis was first planned interim while rPFS was final. TITAN was unblinded, allowing pts without progression who were still receiving PBO to cross over to APA. Herein, we report the final analysis of efficacy and safety results from TITAN. Methods: 1052 mCSPC pts were randomized 1:1 to receive APA (240 mg QD) or PBO plus ADT. Time-to-event end points were analyzed by Kaplan-Meier method and Cox proportional hazards model. A preplanned sensitivity analysis for OS, accounting for crossover using inverse probability censoring weighted (IPCW) log-rank test, was conducted. No formal statistical retesting was performed; nominal p values were reported without multiplicity adjustment. Change from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score was assessed using a mixed-effect repeated-measures model. Results: With 44 mos median follow-up, 405 OS events had occurred. After unblinding, 208 PBO pts (39.5%) crossed over to APA. Median treatment duration was 39.3 mos for the APA group, 20.2 mos for the entire PBO group, and 15.4 mos for the PBO→APA crossover group. OS was superior in the APA group compared with the PBO group despite crossover (Table). 48-mo survival rates were 65% (APA) vs 52% (PBO). Other end points also favored APA vs PBO (Table). Health-related quality of life (HRQoL), per total FACT-P, was maintained in the APA group through the study and was not different from the PBO group. Safety was consistent with previous reports. Conclusions: With close to 4 yrs of follow-up, the final analysis of TITAN demonstrated that in a broad population of pts with mCSPC, APA plus ADT provides an improvement in OS with a 35% reduction in risk of death, which increased to 48% reduction after adjusting for pts who crossed over from PBO to APA. In addition, there was consistent benefit with APA in other end points, including delaying castration resistance, and HRQoL continued to be maintained with an acceptable safety profile. Clinical trial information: NCT02489318. [Table: see text]
Prevalence of oligoprogression in metastatic hormone-resistant prostate cancer patients on androgen targeted therapies: Could targeted radiotherapy improve patient outcomes?
Authors: Patel Priyanka , Tunariu Nina , Tree Alison
Published: March 2021

110

Background: Androgen receptor-targeted therapies (ART) such as Abiraterone and Enzalutamide have shifted the management paradigm of metastatic castrate-resistant prostate cancer (mCRPC). These treatments are well-tolerated with less toxicities compared to chemotherapy, therefore methods to delay chemotherapy are beneficial to patients. Patients eventually become resistant to ARTs, and some patients will progress in a limited number of sites. This study investigated the prevalence of oligoprogressive disease (OPD) amenable to Stereotactic-body radiotherapy (SBRT). OPD is defined as ≤3 metastatic lesions which are progressing or new whilst all other sites of disease are well-controlled by ART. Methods: Retrospective analysis of electronic patient records and imaging studies of 95 patients treated with ART for mCRPC between April 2015 – 2017 from a single centre was undertaken. Data was analysed at the time of first tumour progression on ART. Results: The median (IQR) age of patients was 78.8 (74.4-83.6) years. OPD was found in 27 (28%) patients, 18 (19%) had lesions suitable for SBRT (Table). Seventeen (63%) patients were treated with abiraterone, 10 (27%) patients with enzalutamide. Median (IQR) time from starting ART to OPD was 16.4 (8.6-19.9) months. Five (19%) patients had 3 sites of OPD, 8 (29%) patients had 2 sites of OPD and 14 (52%) patients had 1 site of OPD. Nineteen patients continued ART beyond OPD for ≥3months. OPD was diagnosed using CT scan (56%), whole body diffusion-weighted MRI (22%), choline PET/CT (19%) and bone scan (3%). Six (22%) patients were treated with radiotherapy for OPD, 3 as participants of the TRAP trial (NCT03644303). Median time to subsequent progression after OPD for the 3 patients treated off trial with radiotherapy was 20.5 months. The OPD lesions treated with radiotherapy included the prostate (2 patients, 30 Gy in 5 and 24 Gy in 4 fractions) and para-aortic lymph node (1 patient, 30 Gy in 5 fractions). Median time to subsequent progression after OPD for those who did not receive radiotherapy was 6.4 months. There was no significant difference between median overall survival between patients with OPD and those who progressed with > 3 lesions (7 vs 9.2 years, P= 0.54). Ten (66%) patients who progressed after initial OPD on continuation of ART progressed with further OPD (≤3 lesions including original OPD lesion). Conclusions: OPD is prevalent in patients on ART for mCRPC. The most frequent site of OPD was in bone and majority of patients had only 1 site of OPD at presentation. These results identify a cohort of patients who may benefit from SBRT to maximise ART treatment. Fourteen (14%) patients met entry criteria for TRAP trial which is currently testing the role of SBRT to sites of OPD in mCRPC. [Table: see text]
SPOP mutation as a predictive marker for treatment of metastatic castration-resistant prostate cancer.
Authors: Stangl Andrew , Willner Christopher , Maahs Lucas , Burmeister Charlotte , Hwang Clara , Pilling Amanda
Published: March 2021

160

Background: Predictive markers linking molecular background to treatment response and clinical outcomes are currently lacking in prostate cancer. Missense mutations in SPOP (speckle-type POZ protein) define a distinct molecular subtype, occurring in about 12% of both clinically localized and metastatic disease. SPOP mutations occur early in prostate tumorigenesis and facilitate dysregulation of the androgen-receptor (AR) signaling network, suggesting mutant SPOP can impact response to AR-directed therapies. We hypothesized that SPOP mutation will be associated with superior response to next-generation AR inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Methods: This is a retrospective study to evaluate patients who progressed to mCRPC and were treated with AR-targeted therapy (i.e. enzalutamide, abiraterone acetate). Eligibility criteria inlcuded androgen deprivation therapy, metastatic disease documented by bone lesion or soft tissue identified on imaging, castrate testosterone level ( < 50g/dL), and evaluable tissue for DNA analysis. SPOP status was determined by next-generation sequencing. Time to PSA progression (PSA TTP) was defined per PCWG2 as PSA increase of 25% from nadir and a minimum of 2 ng/ml calculated from date of primary treatment initiation to the date of PSA progression. Overall survival (OS) was calculated from start of treatment to date of death. Statisitcal comparision of the SPOP mutant or wild-type was determined using Kaplan-Meier and independent t-test analysis. Results: The analysis included 69 men with mCRPC with previous or ongoing ADT and receipt of AR-directed therapy (aberaterone acetate, enzalutamide). SPOP status was determined for all patients: 7 patients SPOP mutant, 62 patients SPOP wild-type. Mutant SPOP was associated with significantly longer PSA TTP (22.5 vs. 9.7 months, p = 0.031) and improved OS (21 vs. 29 months, p = 0.12) with enzalutamide or abiraterone as compared to SPOP wild-type patients. Conclusions: Our data demonstrate that SPOP mutations predict for better outcomes with next-generation AR inhibitors in men with mCRPC. SPOP mutations are a prominent molecular sub-type with potential to impact clinical management in men with metastatic, therapy resistant prostate cancer.
Clinically advanced penile (pSCC) and male urethral (uSCC) squamous cell carcinoma: A comparative genomic profiling (CGP) study.
Authors: Spiess Philippe E. , Mata Douglas A , Bratslavsky Gennady , Jacob Joseph M , Necchi Andrea , Gjoerup Ole , Danziger Natalie , Lin Douglas I. , Decker Brennan James , Sokol Ethan , Huang Richard , Ross Jeffrey S.
Published: March 2021

2

Background: Although SCC of the penile skin (pSCC) and the male urethral surface epithelium (uSCC) arise in nearby locations and can feature similar histology, their clinical manifestations, disease course, and surgical and medical treatment options are distinct. We performed CGP on pSCC and uSCC to examine genomic profiles differences. Methods: Tissues obtained from men with clinically advanced pSCC (n = 230) and uSCC (n = 17) underwent hybrid capture-based CGP to evaluate all classes of genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: The median ages were similar in both groups. pSCC exhibited a slightly higher frequency of HPV-16/18 infection (29% vs. 12%, P = .16), although the TP53 mutation frequencies were nearly identical (55% vs. 59%, NS). CDKN2A inactivation (P = .08), CCND1 amplification trending higher and TERT promoter mutations (P = .01) were more frequent in pSCC, potentially indicating prior HPV infection. GAs in NOTCH1 were exclusively identified in pSCC. Potentially actionable GAs identified in both groups included PIK3CA activating mutations (TKIs) as well as pathogenic alterations in FBXW7 and PTEN (MTOR inhibitors). Rare BRCA1 and BRCA2 inactivation (PARP inhibitors) was seen in pSCC only. High-positive PD-L1 staining was elevated in pSCC (34 vs. 14%, P = .06). Although average TMB was similar in both groups, pSCC exhibited an elevated frequency of cases with CD274 ( PD-L1) amplification as well as TMB >10 mut/Mb which are on label for immune checkpoint inhibitor (ICPI) treatment. Conclusions: CGP of pSCC and uSCC identifies opportunities for both targeted and ICPI therapies. Compared to uSCC, pSCC had genomic features more similar to head and neck SCC including slightly increased cell-cycle perturbation, HPV infection, and NOTCH pathway signaling alterations. Further use of CGP in the treatment planning for pSCC and uSCC may be warranted. [Table: see text]
The impact of telemedicine on patient-reported outcomes in urologic oncology.
Authors: Gadzinski Adam John , Abarro Isabelle O. , Stewart Blair , Gore John L.
Published: March 2021

200

Background: Nearly 20% of Americans live in rural communities. These individuals face barriers to accessing cancer care, including prevalent poverty and substantial travel burden to seeing cancer providers. We aimed to assess the impact of a rurally focused telemedicine program on patient outcomes in our urologic oncology outpatient clinic. Methods: We prospectively identified patients from rural Washington State, or who lived outside Washington, with a known or suspected urological malignancy being evaluated at the University of Washington Urology Clinic via an in person clinic or a telemedicine appointment. Patients were invited to complete a post-visit survey that assessed satisfaction, travel time, costs, and work absenteeism. We compared patient-reported outcomes between those seen as in-person versus telemedicine visits. Results: We invited 1453 eligible patients from August 2019–July 2020 to participate; 615 patients (42%) completed the survey. 198 patients had in person visits and 417 had telemedicine visits. Median age was 68, 89% were male, and 73% were white. 525 patients (85%) were from Washington; the remainder resided out-of-state. Patients were being evaluated for prostate cancer (62%), kidney cancer (14%), urothelial cancer (22%), and testis cancer (2%). Patient-reported outcomes are displayed in Table. Twenty-two patients coming for in-person visits (11%) paid ≥ $1000 in total travel costs. No differences were noted in patient satisfaction between in-person and telemedicine visit types. Conclusions: Patients traveling to our clinic from out-of-state and rural Washington incur significant travel time, costs, and time away from work to receive outpatient urologic cancer care. Telemedicine provides a medium for cancer care delivery that eliminates the significant travel burden associated with in-person clinic appointments. [Table: see text]
Effect of healthcare system on prostate cancer-specific mortality in African American and non-Hispanic white men.
Authors: Klebaner Daniella , Courtney Patrick Travis , Rose Brent S.
Published: March 2021

23

Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological differences; however, recent data suggest poorer outcomes may be related to barriers to medical care from the healthcare system in which patients receive care. We sought to evaluate potential drivers of disparities by comparing outcomes between African American and White men in the Surveillance, Epidemiology and End Results (SEER) national cancer registry and a relatively equal-access healthcare system, the Veterans Health Administration (VHA). Methods: We identified African American and White patients diagnosed with prostate cancer between 2004-2015 in the SEER and VHA databases. We analyzed metastatic disease at diagnosis with multivariable logistic regression, and PCSM with cumulative incidence analysis and sequential competing-risks regression adjusting for disease and sociodemographic factors. Results: The SEER cohort included 306,609 men (57,994 [18.9%] African American and 248,615 [81.1%] White) with a median follow-up of 5.3 years (interquartile range [IQR] 2.6-8.1 years), and the VHA cohort included 90,749 men (27,412 [30.2%] African American and 63,337 [69.8%] White) with a median follow-up of 4.7 years (IQR 2.4-7.6 years). In SEER, African American men were significantly more likely to present with metastatic disease (African American 4.3% versus White 3.0%, p< 0.001; multivariable odds ratio [OR] 1.25, 95% confidence interval [CI] 1.19-1.32, p< 0.001), whereas in the VHA, African American men were not significantly more likely to present with metastatic disease (African-American 3.2% versus White 3.3%, p= 0.26; multivariable OR 1.07, 95% CI 0.98-1.17, p= 0.12). In SEER, the 8-year cumulative incidence of PCSM was significantly higher for African American compared with White men (6.9% versus 5.1%, p< 0.001), whereas in the VHA, African American compared with White men did not have a significantly higher 8-year cumulative incidence of PCSM (5.5% versus 5.4%, p= 0.93). African American race was significantly associated with an increased risk of PCSM in SEER (univariable subdistribution hazard ratio [SHR] 1.39, 95% CI 1.33-1.45, p< 0.001), but was not significantly associated with PCSM on uni- and multivariable regression in the VHA. When adjusted for disease characteristics at diagnosis in SEER, disease extent, PSA, and Gleason score contributed to 85% of the risk of PCSM for African American men (adjusted SHR 1.06, 95% CI 1.02-1.12, p= 0.008). Conclusions: Racial disparities in PCSM were present in a national cohort, SEER, but not as pronounced in a relatively equal-access healthcare system, the VHA, potentially due to differences in metastatic disease at diagnosis among African American and White men between cohorts. These findings may be attributable to reduced barriers to care in the VHA.
Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate- and high-risk prostate cancer overall, and in those who also received salvage radiotherapy.
Authors: Trock Bruce J. , Rajamani Saradha , Vidal Igor , Glavaris Stephanie , Jones Tracy , Han Misop , Partin Alan W. , Cohen Todd , Stone Steven , De Marzo Angelo M
Published: March 2021

247

Background: The cell cycle progression (CCP) score and PTEN have never been evaluated together as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of men with National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa), nor in such patients who also received salvage radiation (SRT) alone or with androgen deprivation (SRT+ADT). This study evaluated CCP score and PTEN in both settings. Methods: Participants were treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to clinical outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. For overall evaluation of CCP and PTEN in intermediate- and high-risk men a case-cohort sample was selected. Intermediate- and high-risk men with biochemical recurrence who received SRT or SRT+ADT were also sampled to provide a population at particularly high risk. Metastasis-free survival (MFS) was analyzed with the proportional hazards model, weighted for case-cohort design for the overall analysis, and adjusted for CAPRA-S. The clinical cell-cycle risk (CCR) score, a fixed algorithm combining CCP and CAPRA-S was also analyzed in both contexts. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: The case-cohort consisted of 209 men, including 47% with Gleason score >4+3, 48% extra-prostatic extension, and 18% with seminal vesicle or lymph node involvement; 42 (20%) developed metastasis. In univariate analyses CCP, CAPRA-S, and PTEN were all highly significant. In multivariable analysis, only CCP and CAPRA-S retained significance (Table section A). CCR was also strongly prognostic, HR=7.9 (95% CI 4.4, 14.5) per unit change, p<0.00001. SRT (56%) or SRT+ADT (44%) were received by 172 men, of whom 78% had Gleason >4+3, 48% extra-prostatic extension, and 34% seminal vesicle or lymph node involvement; 19 (11%) developed metastases. Again, CCP and CAPRA-S, but not PTEN, were statistically significant (Table section B). CCR was also statistically significant, HR=1.7 (95% CI 1.2, 2.4), p=0.002. Conclusions: This is the first comparison, in a recent cohort of intermediate- and high-risk men, of CCP score and PTEN as risk factors for metastasis, and first evaluation in such men receiving SRT. In both multivariable settings, CCP score, but not PTEN, was significantly associated with MFS, adjusted for CAPRA-S. CCR, a fixed algorithm that combines CCP and CAPRA-S was also significant in both settings. [Table: see text]
Barriers and facilitators of germline genetic evaluation for prostate cancer.
Authors: Loeb Stacy , Li Randall , Sanchez Nolasco Tatiana , Byrne Nataliya , Cheng Heather H. , Leader Amy , Giri Veda N.
Published: March 2021

28

Background: Genetic counseling and germline testing have an increasingly important role for patients with prostate cancer, with the recent approval of precision therapeutic options and implications for cancer screening in families. Although current guidelines recommend germline genetic evaluation for all men with metastatic prostate cancer and some with localized disease, recent data suggests it is underutilized. Our objective was to perform a qualitative study of barriers and facilitators of genetic counseling and germline genetic testing among physicians who manage prostate cancer. Methods: We conducted semi-structured interviews with medical oncologists, radiation oncologists, and urologists from different U.S. practice settings until thematic saturation was achieved at n = 14. The interview guide was based on the Tailored Implementation in Chronic Diseases Framework to identify key determinants of practice. Interview transcripts were independently coded by ≥2 investigators using a constant comparative method. Disagreements were resolved by team discussion. NVivo12 was used for data organization and analysis. Results: The decision to perform or refer for germline genetic evaluation is affected by factors at multiple levels (Table). Although patient factors play a role in some cases (e.g., refusal of testing for specific reasons), the dominant themes in the decision to conduct germline genetic evaluation were primarily at the physician and organizational level. Physician knowledge of prostate cancer genetics, coordination of care between providers, perceptions of the guidelines for genetic testing, and concerns about cost were most frequently discussed as the main factors affecting utilization of germline genetic evaluation. Conclusions: There are currently numerous barriers to the performance of germline genetic evaluation for prostate cancer. Efforts to expand physician education and to facilitate coordination of care surrounding genetic evaluation are important to promote guideline-concordant care. [Table: see text]
Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with metastatic renal cell carcinoma (mRCC).
Authors: Marteau Florence , Harrow Brooke , McCarthy Christine , Wallace Joel , Monnette Alisha , Wang Yunfei , Doshi Gurjyot K.
Published: March 2021

293

Background: Checkpoint inhibitors (CPIs) are a treatment option for patients with metastatic renal cell carcinoma (mRCC), but there is limited clinical data on the efficacy of targeted therapies following CPI treatment. Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets multiple receptor kinases implicated in tumorigenesis. In the US, cabozantinib is approved for use in patients with advanced RCC including after CPI treatment. Methods: This retrospective observational cohort study (NCT04353765) evaluated outcomes associated with cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment. Eligible patients initiated TKI therapy between May 1, 2016 and Sep 31, 2019 and had received a CPI as their last systemic treatment prior to TKI therapy. Patients were identified from the US Oncology Network iKnowMed electronic health record database through structured queries and a targeted chart review. The following real-world outcomes were assessed: 6-month response rate (RR6months; primary); overall response rate (ORR); overall survival (OS); time to treatment discontinuation (TTD); rates of dose reductions, and discontinuation due to adverse events (AEs). The p value for RR6months was used to test for non-inferiority. Results: Eligible patients ( n = 247) had a mean (SD) age of 65.9 (10.5) years and 74.1% were male; 75.7% ( n = 187) received cabozantinib and 24.3% ( n = 60) received other TKIs. All patients had intermediate or poor MSKCC score; more poor-risk patients received cabozantinib than other TKIs (28.9% vs 20%). Outcomes data are shown in the Table. Compared with other TKIs, cabozantinib was associated with a significantly higher RR6months and ORR, and TTD was twice as long with cabozantinib. Discontinuation due to AEs was more frequent with other TKIs than with cabozantinib, although this was not statistically significant; 21.7% of discontinuations occurred during the first 3 months of treatment. AEs leading to discontinuation were consistent with the known safety profile of the products. Conclusions: In this mRCC population receiving routine care in the US, cabozantinib was used more frequently than other TKIs after CPI treatment. Cabozantinib was an effective and well tolerated option post-CPI, with a high response rate in the real-world setting.abozantinib was associated with a significantly higher response rate and a lower discontinuation rate due to AEs; TTD was double that of other TKIs. [Table: see text]