bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupling relationship between current in-situ stress and natural fractures of continental tight sandstone oil reservoirs
Authors: Cui Xinying , Radwan Ahmed E. 
Published: February 2022

We have integrated rock mechanics and acoustic experiments, full-wave array acoustic testing, formation microscanner image logging, and hydraulic-fracturing data to evaluate the coupling relationship between current in-situ stress and natural fractures. We used the data of the Yanchang Formation in the DL block of the western Ordos Basin, China, as an example. Our results find that the Yanchang Formation mainly develops high-angle fractures and vertical fractures. Furthermore, the in-situ stress state of the target sandstone strata satisfies [Formula: see text]. Nearly vertical and high-angle fractures are formed in the environment when [Formula: see text] is the maximum principal stress. Therefore, the current in-situ stress state of the target layer matches the induced fractures (longitudinal tensile-induced fractures) and natural fractures. As the buried depth increases, the difference between the horizontal maximum and minimum stresses ([Formula: see text]) has a tendency to first decrease and then increase, and its conversion depth is approximately 2000 m. Natural fractures are not developed in the distributary bay (the lowest horizontal stress area) and the thick sand area in the middle of the main river channel (the largest horizontal stress area). Natural fractures are mainly developed on the two wings of the main channel, and their horizontal stress is approximately 2–4 MPa lower than the central part of the main channel. We determined a correlation between fractures and sedimentary facies, and we have an important reference value for improving the drilling success rate of tight oil reservoirs. Furthermore, our study provides insights into the prediction of fractures and sweet spots for further exploration and hydraulic fracturing activities in the studied area and elsewhere in continental tight sandstone reservoirs.
Comprehensive genomic profiling of penile squamous cell carcinoma and impact of HPV status on immune-checkpoint inhibition-related biomarkers.
Authors: Nazha Bassel , Wu Sharon , Brown Jacqueline T , Magee Daniel , Carthon Bradley Curtis , Kucuk Omer , Korn W. Michael , Barata Pedro C. , Heath Elisabeth I. , Ryan Charles J. , McKay Rana R. , Master Viraj A. , Bilen Mehmet Asim 
Published: February 2022

4 Background: Penile squamous cell carcinoma (SCC) is a rare and aggressive malignancy with few treatments in the advanced setting and little success of immune-checkpoint inhibitions (ICI). Around half of penile SCC cases are linked to HPV infection. We aimed to report the landscape of somatic alterations and ICI-related biomarkers in penile SCC in the Caris Life Sciences dataset and to establish signatures for HPV-dependent and HPV-independent oncogenesis. Methods: Penile SCC tumors were analyzed using next-generation sequencing of DNA (TruSeq, 45 genes; NextSeq, 592 genes and NovaSeq, whole exome sequencing (WES)) and RNA (NovaSeq). PD-L1 expression was tested by IHC using SP142. Microsatellite instability (MSI) was tested by fragment analysis, IHC and NGS. Tumor mutational burden (TMB) was measured by counting all somatic mutations found per tumor (TMB-high: >10 mutations per MB). HPV16/18 status was determined using WES when available. Significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons (q-value <0.05). Results: Among the entire cohort (N=108), the median age was 66 years and 79.6% of tumors were primary and 20.4% of tumors were metastatic. In the overall cohort, the most frequently detected mutations were TP53 (46%), CKDN2A (26%), PIK3CA (25%), TERT promoter (22%), KMT2C (16%) and NOTCH1 (14%), consistent with previous reports. Overall, 51% of tumors were PD-L1+ (SP142, >1%), 10.7% had high TMB, and 1.1% had dMMR/MSI-H. Of the 108 tumors, 29 had HPV status tested by WES (HPV16/18+, n=13 and HPV16/18-, n=16). KMT2C mutations (33% vs 0%) and FGF3 amplifications (30.8% vs 0%) were specific to HPV16/18+ tumors, while CDKN2A mutations (37.5% vs 0%) were exclusive to HPV16/18- tumors. HPV16/18+ tumors also had a trend towards decreased TP53 (7.7% vs 63%) and TERT promoter (25% vs 77%) alterations (Table). TMB-high were exclusively found in the HPV16/18+ group (30.8% vs 0%), while PD-L1 and dMMR/MSI-H status were comparable between the two groups. Conclusions: To our knowledge, our comprehensive NGS study of penile SCC somatic alterations is the largest to date. HPV16/18+ vs HPV16/18- penile SCC were molecularly distinct tumors, consistent with previous reports. Our finding that TMB-high was exclusive to patients with HPV16/18+ tumors requires confirmation in larger datasets and could be used for better patient stratification in ICI clinical trials.[Table: see text]
Impact of COVID-19 on the incidence of prostate cancer among White and Black Veterans.
Authors: Lee Kyung Min , Guram Kripa , Alba Patrick , Anglin-Foote Tori , Robison Brian , Rose Brent S , Lynch Julie Ann 
Published: February 2022

29 Background: Early-stage prostate cancer (PCa) is typically detected on prostate-specific antigen (PSA) screening and subsequent prostate biopsy, healthcare interventions that are considered routine elective procedures. The COVID-19 pandemic disrupted routine healthcare screenings and interventions. We sought to determine whether delayed screening and diagnostic workup of PCa was associated with increased rates of incident PCa, high-grade Gleason, and metastatic disease at diagnosis. Methods: We used the Corporate Data Warehouse of the Veterans Health Administration to collect PSA, prostate biopsy, PCa diagnosis, Gleason score, and metastasis information of White and Black Veterans aged 40 years or older newly diagnosed with PCa from January 2019 through June 2021. For each month, we calculated rates of PSA, prostate biopsy, and incident PCa per 100,000 men and plotted monthly rates by race. We performed descriptive analyses to compare age at first PSA, age at diagnosis, baseline PSA, Gleason scores, and metastasis pre- and post-January 2020, the month in which the U.S. declared COVID-19 a public health emergency. Results: The decrease in the rate of PSA screening immediately after January 2020 was similar in both White and Black Veterans (7% vs. 6%). However, the magnitude of reduction in the rate of prostate biopsy and the rate diagnosis of incident PCa were five times larger among Black Veterans compared to White Veterans (11% vs. 2% for both biopsy and diagnosis rates). Among the 17,771 White and 9,610 Black Veterans with incident PCa, the rate of Gleason of 4+3 or greater and the rate of metastatic disease at diagnosis increased three months after the pandemic in both race groups with comparable magnitude (2-3% increase in high-grade Gleason, 1% increase in metastatic disease). Conclusions: Utilization patterns indicated that while the decrease in PSA screening after the pandemic was similar in White and Black Veterans, reductions in prostate biopsy and diagnosis of incident PCa were five times greater in Blacks than Whites. Further research including risk-adjusted modeling is needed to determine whether Black Veterans were disproportionately affected by the pandemic-related disruptions in PSA screening and diagnostic workup of prostate cancer.[Table: see text]
Real-world health-related quality of life and caregiver need in patients with metastatic hormone-sensitive and metastatic castration-resistant prostate cancer.
Authors: Boye Mark , Ribbands Amanda , Leith Andrea , Clayton Emily , Butcher Jake , Rybowski Sarah 
Published: February 2022

54 Background: Prostate cancer (PC) is one of the most common cancers in men. When making treatment decisions, patient health-related quality of life (HRQoL) and caregiver need are important considerations, and as such it is imperative to understand the impact that PC has on HRQoL. We aimed to assess the impact of metastatic hormone-sensitive PC (mHSPC) and castration-resistant PC (mCRPC) on HRQoL and associated caregiver need. Methods: Real-world data were drawn from the PC Disease Specific Programme, a point-in-time survey conducted in the United States of America and Europe (France, Germany, Italy, Spain and the United Kingdom) between Jan-Aug 2020. Physicians completed patient record forms for their next 8 consecutively consulting adult metastatic PC patients (4 mHSPC/4 mCRPC). Eligible patients were invited to complete a voluntary patient self-reported form on caregiver need and HRQoL including EuroQol 5-dimension 5-level (EQ-5D-5L), EuroQol Visual Analogue Scale (EQ-VAS), Functional Assessment of Cancer Therapy – General/Prostate (FACT-G/P) and Brief Pain Inventory (BPI) questionnaires. Higher scores indicate better HRQoL and more pain. Data were analysed descriptively. Results: 376 mHSPC and 331 mCRPC patients completed patient self-reported forms. Demographics and clinical characteristics for mHSPC/mCRPC patients were: mean age 71.1/71.5 years, 77%/69% of patients had an ECOG performance status of 0-1, 82%/83% of patients were retired and 42%/44% of patients had a caregiver. At data collection, mean HRQoL scores for mHSPC/mCRPC patients were: 66.4/63.4 (EQ-VAS), 0.76/0.72 (EQ-5D-5L), 66.2/62.9 (FACT-G) and 94.6/90.2 (FACT-P). Patients with mHSPC had FACT-P social, emotional, functional and physical well-being subscale scores of 18.2, 14.7, 13.6 and 19.7, respectively. These scores were 17.7, 14.0, 12.7 and 18.5 in mCRPC patients, respectively. Mean “worst pain” scores were mild (3.6/3.9 on BPI for mHSPC/mCRPC patients). In terms of both non-professional and professional caregivers, mHSPC/mCRPC patients reported a mean of 31.6/28.9 care hours/week. Most caregivers were partners/spouses (in 89% of mHSPC and 82% of mCRPC patients) providing a mean of 29.0 and 27.7 care hours/week, respectively. Conclusions: We showed that HRQoL and well-being are impacted in both mHSPC and mCRPC patients, and that there is a considerable time burden on caregivers. Patients with mCRPC reported the lowest HRQoL scores and highest pain scores, suggesting that patients who are sicker may have greater disease burden. Our findings suggest an unmet need for HRQoL in patients with mHSPC and mCRPC, and also a need for greater caregiver support in these patients.
Treatment outcomes for metastatic castration-resistant prostate cancer (mCRPC) following progression on upfront androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPI) for metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Khalaf Daniel Joseph , Chen Liheng , Sunderland Katherine , Vergidis Joanna , Noonan Krista , Finch Daygen L. , Zulfiqar Muhammad , Chi Kim N. 
Published: February 2022

60 Background: Combined ADT and ARPI is associated with improved overall survival (OS) compared with ADT alone in patients with mCSPC. The activity of subsequent therapies for mCRPC is not well characterized. Methods: We conducted a retrospective analysis of patients enrolled on a biobank at 6 cancer centres in British Columbia, Canada. Patients who received abiraterone or apalutamide for mCSPC were included. Data including baseline clinical prognostic factors and clinical outcomes (per Prostate Cancer Working Group III) were collected from patient records. Survival was analyzed by Kaplan-Meier method and Log Rank test and prognostic variables were determined using Cox regression. Results: 168 patients were identified of which 126 (75%) received abiraterone, 38 (23%) received apalutamide, and 4 (2%) received one ARPI and switched to the other for toxicity. Median age was 69 years and Gleason score ≥ 8 in 61%. Site of metastasis (mets) at mCSPC was lymph node (n=91), bone (n=141), and liver (n=6). As of August 28 2021, a total of 46 patients progressed to mCRPC, of which 38 received subsequent systemic therapy. First-line mCRPC treatments were docetaxel (n=12), Radium-223 (10), enzalutamide (6), platinum chemotherapy (3), and others (7) including immune checkpoint inhibitors (1) and Lutetium177-PSMA-617 (1) and other investigational agents (5). Outcomes are shown in the table. On univariate Cox analysis, clinical factors at time of mCRPC associated with worse OS were: LDH above upper limit of normal (HR 5.0, 95% CI 1.7-14.5), hemoglobin below lower limit of normal (5.2, 1.1-23.8), presence of ≥ 20 bone mets (3.7, 1.4-9.8), and increasing PSA (1.002, 1.001-1.003). Conclusions: PSA decline rates and survival are modest for patients who have progressed following upfront abiraterone or apalutamide plus ADT for mCSPC. Further follow-up is required to accurately determine outcomes with current mCRPC standard therapies following up-front ADT+ ARPI. Recently approved treatment options such as Lutetium177-PSMA-617 and PARP inhibitors for DNA damage repair deficient tumors may help to improve outcomes for these patients.[Table: see text]
Baseline parameters of patients with prostate cancer (PCa) initiating a triptorelin treatment for at least 12 months in real life, TALISMAN study interim analysis.
Authors: Thiery-Vuillemin Antoine , Rigaud Jerome , Crehange Gilles , Pello Leprince Ringuet Nathalie , Grandoulier Anne-Sophie , Lebret Thierry 
Published: February 2022

61 Background: Little is known on modalities of use of androgen deprivation therapy (ADT) in real life. They may depend on tumor aggressiveness, patient frailty and physician habits. Our purpose was to describe reasons of choice of planned total duration of triptorelin treatment, mainly according to circumstances of prescription. Methods: Initiated in November 2020, a prospective, multicenter, non-interventional study is conducted in France (TALISMAN). Urologists, radiation oncologists and medical oncologists recruited patients with histologically confirmed PCa, eligible for triptorelin therapy within its label, with a planned total duration of at least 12 months. Decision of triptorelin treatment was made before inclusion, in routine practice. 786 patients were planned to be enrolled, with a 12-month follow-up. Primary objective is to describe the proportion of patients treated continuously with triptorelin during the 12 months following treatment initiation. Interim analysis was planned when 50% of patients are enrolled, its objective was description of subgroups according to circumstance of prescription, planned total duration of triptorelin treatment, formulation/route of triptorelin prescribed, specialty of investigators. No statistical test was performed. Results: 509 patients were included in the interim analysis. Patients were mostly enrolled by urologists (56.8%) and radiation oncologists (40.1%). Mean age ±SD was 73.9±8.0 years; 70.9% had at least one comorbidity; 72.1% had a Gleason score ≥ 4+3; 65.2% had at least one concomitant PCa treatment. Main baseline parameters are presented in Table. Subgroups description showed that patients with high risk localized and patients with locally advanced PCa were most often offered a [24-36] month planned treatment duration (respectively 53.6% and 40.6%), in accordance with the guidelines. Reasons of choice of the planned total duration mainly refer to Gleason score (27.6%) and PSA level (19.4%). Reasons of choice of formulation/route of triptorelin prescribed mainly refer to physician preferred formulation/route (47.7%) and planned total duration of ADT (29.9%). Conclusions: The ongoing TALISMAN study is collecting data on patients, PCa aggressiveness, supportive care, which may impact total duration of triptorelin treatment. Statistical analyses at completion of study will give additional results. Clinical trial information: NCT04593420. [Table: see text]
Treatment trends among men with metastatic castration sensitive prostate cancer (mCSPC): Results from the US component of an international study.
Authors: Barata Pedro C. , Leith Andrea , Ribbands Amanda , Montgomery Rachel , Last Matthew , Arondekar Bhakti , Niyazov Alexander , Ivanova Jasmina 
Published: February 2022

66 Background: Novel hormonal therapies (NHTs) and taxane-based chemotherapy (CT) were initially approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) and are now approved for use in mCSPC. Little is known about the recent uptake of these treatments in mCSPC. This study evaluated mCSPC treatment trends from 2016 to 2020 in the US. Methods: Participating physicians collected information from medical charts for the next consecutive 8 men with advanced prostate cancer (4 men with mCSPC, and 4 men with mCRPC) during January-August 2020. A subset of men with current mCRPC had historical mCSPC treatment information available. Treatments were categorized into 4 mutually exclusive categories: (1) androgen deprivation therapy (ADT) ± first-generation anti-androgen (1st gen AA); treatment intensification with (2) NHT, (3) taxane CT ± NHT, and (4) other treatments (e.g., radium-223, sipuleucel-T, non-taxane CT). To account for the availability of new mCSPC treatments, treatment patterns across all lines of mCSPC therapy were described for men initiating treatment in 2016-2018 and 2019-2020. Results: 239 men with mCSPC were included (146 with mCSPC at data collection; 93 with mCRPC at data collection and who had historical information on mCSPC treatments). Mean age was 69 years; 69% had bone metastases and 30% had visceral metastases. Most patients were managed by oncologists (75%), while 48% were treated at academic/cancer centers. From 2016-2018 to 2019-2020, mCSPC treatment intensification with NHT increased while treatment intensification with taxane CT or other therapies declined. (Table) Conclusions: In this real-world study of adult men with mCSPC, increased use of NHT was observed over time indicating that more men will have been exposed to NHT when they progress to mCRPC. This suggests an unmet need for novel therapies in mCRPC. Funding: Pfizer. [Table: see text]
Association between patient-reported outcomes (PROs) and changes in prostate-specific antigen (PSA) in patients (pts) with advanced prostate cancer treated with apalutamide (APA) in the SPARTAN and TITAN studies.
Authors: Small Eric Jay , Chi Kim N. , Chowdhury Simon , Bevans Katherine B. , Bhaumik Amitabha , Saad Fred , Chung Byung , Karsh Lawrence Ivan , Oudard Stephane , De Porre Peter , Brookman-May Sabine D. , McCarthy Sharon Anne , Mundle Suneel , Uemura Hirotsugu , Smith Matthew Raymond , Agarwal Neeraj ,   On behalf of the SPARTAN and TITAN investigators
Published: February 2022

73 Background: In phase 3 placebo (PBO)-controlled studies, addition of APA to androgen deprivation therapy (ADT) improved overall survival, resulted in rapid and deep PSA declines, and reduced risk of disease progression while preserving health-related quality of life (HRQoL) in nonmetastatic castration-resistant prostate cancer (nmCRPC; SPARTAN) and metastatic castration-sensitive prostate cancer (mCSPC; TITAN). This post hoc analysis evaluated the association of a deep PSA decline with PROs in these studies. Methods: Pts on ADT were randomized to APA (240 mg QD) or PBO: SPARTAN 2:1 (N = 1,207; APA n = 806), TITAN 1:1 (N = 1,052; APA n = 525). Each cycle was 28 d. PROs were assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory-Short Form (BPI-SF; TITAN only), and Brief Fatigue Inventory (BFI; TITAN only) at baseline, specific cycles during study treatment, and post progression up to 1 yr. A landmark analysis at Month 3 evaluated association between deep PSA decline (≤ 0.2 ng/mL) and time to subsequent deterioration in PROs (defined as decrease ≥ 10 points FACT-P total, ≥ 3 points Physical Wellbeing, ≥ 30% baseline for BPI-SF worst pain, or ≥ 2 points for BFI worst fatigue). At time of the landmark analysis, only pts continuing treatment were included; all deep PSA responses after, and all PRO deterioration events before, were ignored. Time-to-event end points were analyzed by Kaplan-Meier method and Cox proportional hazards model. Results: Median treatment durations were 32.9 mo (SPARTAN) and 39.3 mo (TITAN). Per assessment, > 90% (SPARTAN, cycles 1-81) and > 50% (TITAN, cycles 1-33) of eligible pts completed FACT-P; BPI-SF and BFI, both > 62% (TITAN, cycles 1-33). Pts in either study who achieved PSA ≤ 0.2 ng/mL at Month 3 had a lower risk of deterioration in FACT-P total or Physical Wellbeing (Table). Pts in TITAN with PSA ≤ 0.2 ng/mL at Month 3 had a lower risk of BPI-SF worst pain intensity or BFI worst fatigue intensity progression (Table). Conclusions: Deep and rapid PSA responses with APA were associated with prolonged time to deterioration in HRQoL, FACT-P Physical Wellbeing, BPI-SF worst pain intensity, and BFI worst fatigue intensity in pts with advanced PC. Clinical trial information: NCT02489318 (TITAN); NCT01946204 (SPARTAN). [Table: see text]
Daily symptom monitoring commonly leads to treatment modification in older adults receiving treatment for metastatic prostate cancer (mPC).
Authors: Breunis Henriette , Sudharshan Abirami , Emmenegger Urban , Hansen Aaron Richard , Soto Perez De Celis Enrique , Finelli Antonio , Tomlinson George , Warde Padraig , Krzyzanowska Monika K. , Matthew Andrew , Clarke Hance , Santa Mina Daniel , Puts Martine , Alibhai Shabbir M.H. 
Published: February 2022

82 Background: Treatment options for older adults with mPC expanded significantly in recent years but commonly include chemotherapy with Docetaxel (Chemo), androgen receptor-axis-targeted therapies (ARAT), and Radium-223 (Ra-223). Symptom burden associated with Chemo, ARAT, and Ra-223 is frequently observed and often leads to treatment modification, especially in older men. The objective of this study is to explore how often, and which moderate to severe symptoms during treatment for mPC and triggered follow-up, lead to treatment delay and/or dose reduction. Methods: Men aged 65+ with mPC starting standard dose (n=24) or reduced dose (n=1) Chemo, standard dose (n=41) or reduced dose (n=1) ARATs, or Ra223 (n=12) from two tertiary cancer centres in Toronto, Canada, were enrolled in a prospective cohort study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment Scale (ESAS) for 3-4 weeks either through a web-based interface or phone calls. ESAS scores of >4 were followed by ‘triggered’ detailed questionnaires. The oncology care team was informed of reportable events based on scores of triggered questionnaires and patients were advised to call their care team. Clinical and treatment data were abstracted from electronic patient records and descriptive analysis was used. Results: 52/79 participants (66%) reported 345 moderate to severe symptoms that merited triggered questionnaires (table) with an adherence of 83%. Tiredness (n=74), appetite (n=49), insomnia (n=49), and pain (n=48) were the most frequently reported symptoms. 28 patients reported high scores on triggered questionnaires that led to informing the oncology care team and 79% of these patients were contacted by the care team, or an appointment with the Most Responsible Physician was scheduled. Moderate to severe symptom reporting resulted in treatment modification for 9 patients, Chemo (n=5), ARAT (n=3), and Ra-223 (n=1). Conclusions: Daily monitoring identified clinically relevant symptoms and actionable concerns. Informing care teams of reportable adverse events resulted in contacting patients and ultimately in treatment modification in a considerable number of patients. [Table: see text]