tbuckley/cabot-search huggingface dataset:
Assessing different sequencing regimens of atezolizumab (atezo) and sipuleucel-T (sipT) in patients who have asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer.
Authors: Tanya B. Dorff, Jared David Acoba, Sumanta K. Pal, Mark C. Scholz, David Jon Tamura, Jeffrey Huang, Charles Joel Rosser
Journal: Journal of Clinical Oncology (2020)

141 Background: Combining an immune checkpoint inhibitor with a vaccine may leverage complementary mechanisms of action for treatment of mCRPC. We present a randomized study evaluating atezo (anti PD-L1) + sipT in patients (pts) with mCRPC. Methods: Pts who met standard criteria for sipT were randomized to receive (Arm1): atezo 1200 mg IV every 3 weeks for 2 doses then SipT every 2 weeks for a total of 3 infusions (induction) followed by maintenance atezo every 3 weeks until toxicity or loss of clinical benefit or (Arm2) sipT every 2 weeks for a total of 3 infusions followed by atezo 1200 mg IV every 3 weeks for 2 doses (induction) followed by maintenance atezo every 3 weeks until same. The primary endpoint was safety (CTCAE v4.0); secondary endpoints were PFS by PCWG2, objective response (modified RECIST1.1) and systemic immune responses after induction. Results: 37 pts, median age 75 [range 53–86] enrolled; median prior treatments was 4 [range 1-8] and 76% had ECOG PS = 0. Three patients did not complete induction (1 withdrew consent, 1 due to toxicity, and 1 progressed). There were no delays in induction dosing for Arm1 but 9 delays (1 week) for Arm2 (collection failure=6, holiday=2 and other=1). There were no grade 5 toxicities attributed to study drugs. 1 grade 4 toxicity was noted in each arm (Arm 1 bronchitis, Arm 2 hypotension). Eight grade 3 toxicities were noted in arm 1 (hyponatremia, pulmonary embolus x3, bone pain, hypophosphatemia, shock, fall with tooth fracture), while 4 grade 3 toxicities were noted in arm 2 (anemia, hypertension x 2, pneumonia). None of the grade 3 or 4 AEs were immune related. AEs led to discontinuation in 5 patients in Arm1 and 1 patient in Arm2. In Arm1 11 patients were RECIST evaluable at 6 months, with 1 PR (5.8%), 4 SD (23.5%) and 6 PD. In Arm2 13 patients were evaluable, with 1 PR (5.8%), 6 SD (32%) and 6 PD. 10/24 evaluable patients (41.7%) had stable disease at 6 months. Conclusions: The combination of atezo with sipT was safe, AEs consistent with the agents as monotherapy, with no immune related AEs. 2 pts had RECIST PR and 10 had stable disease at 6 months, more than expected with monotherapy. Clinical trial information: 03024216.
KEYNOTE-365 cohort A updated results: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Evan Y. Yu, Josep M. Piulats, Gwenaelle Gravis, Brigitte Laguerre, Jose Angel Arranz Arija, Stephane Oudard, Peter C.C. Fong, Michael Paul Kolinsky, Marinela Augustin, Susan Feyerabend, Audrey E. Kam, Howard Gurney, Ali Tafreshi, Margitta Retz, William R. Berry, Nataliya Mar, Helen Wu, Charles Schloss, Christian Heinrich Poehlein, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

100 Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study evaluating pembro + other agents in mCRPC. Updated results from cohort A (pembro + olaparib) are reported. Methods: Docetaxel-pretreated, molecularly unselected pts with mCRPC with progression within 6 mo of screening per PSA or radiologic bone/soft tissue progression enrolled. Pts may have received 1 other chemotherapy and ≤2 2nd-generation hormone therapy (HT). Pts received pembro 200 mg IV Q3W + olaparib 400 mg PO BID. Primary end points: safety, PSA response rate (confirmed PSA decline ≥50%), and ORR per blinded independent central review. Results: Of 84 treated pts, 42 discontinued, primarily due to progression (n=29). Median age was 71 y (range, 47-83); 26% were PD-L1+, 26% had visceral disease, and 57% had RECIST-measurable disease. Median follow-up was 3 mo for all pts (n=81) and 14 mo for pts with ≥27 wks’ follow-up (n=41). See Table for efficacy outcomes. Treatment-related AEs occurred in 70 (83%) pts. Most frequent (≥30%) were nausea (33%) and anemia (31%). Grade 3-5 treatment-related AEs occurred in 29 (35%) pts. Three pts died of AEs (2 treatment related [l myocardial infarction, 1 unknown cause]). Conclusions: With additional follow-up, pembro + olaparib continued to show activity in docetaxel-pretreated, molecularly unselected pts who previously received HT for mCRPC. Safety of the combination was consistent with individual profiles of each agent. Clinical trial information: NCT02861573. [Table: see text]
Cabozantinib real-world effectiveness in the first through fourth-line settings for the treatment of metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Chun Loo Gan, Shaan Dudani, Connor Wells, Frede Donskov, Sumanta K. Pal, Nazli Dizman, Nityam Rathi, Benoit Beuselinck, Flora Yan, Aly-Khan A. Lalani, Aaron Richard Hansen, Bernadett Szabados, Guillermo de Velasco, Ben Tran, Jae-Lyun Lee, Ulka N. Vaishampayan, Georg A. Bjarnason, Mathushan Subasri, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2020)

639 Background: Cabozantinib (Cabo) is approved for mRCC patients based on the METEOR and CABOSUN trials. The real-world effectiveness of Cabo in mRCC patients in the first- (1L), second- (2L), third- (3L) and fourth-line (4L) settings requires characterization. Methods: This retrospective analysis included mRCC patients who were treated with Cabo and stratified using IMDC risk groups. Overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were calculated. Results: A total of 413 patients (82.6% with clear cell and 17.4% non-clear cell) were identified. The median age was 57 years. Overall, 63% of patients had a Karnofsky performance status score of &gt;80 and 82.6% had prior nephrectomy. 23.1%, 75.4% and 88.3% of patients received immunotherapy as a prior line of treatment, before receiving Cabo in the 2L, 3L and 4L settings, respectively. For patients treated with 1L PD(L)1 combination or monotherapy (n=31), 2nd line Cabo had ORR of 20.8%, median TTF of 5.4 months and median OS of 17.4 months. When segregated into IMDC favorable, intermediate, and poor risk groups, the median OS was 34.8 months (95% CI 5.52-NR), 18.0 months (12.3-35.6) and 9.8 months (7.4-20.8), p=0.0088, respectively for 2L Cabo; and 31.5 months (23.6-39.3), 20.5 months (10.1-21.8), and 6.9 months (4.1-10.9), p=&lt;0.0001), respectively for 3L Cabo. Conclusions: The ORR and TTF of Cabo were maintained from the 1L to the 4L therapy settings. In the 2L and 3L settings, the IMDC criteria appropriately stratified patients into favorable, intermediate and poor risk groups for OS. Cabo has activity after first line immunotherapy.[Table: see text]
Effect of comorbidities/comedications on treatment outcomes with sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC): Subgroup analyses from the STAR-TOR registry.
Authors: Stephan Bernhardt, Marcus Hubbe, Michael Rink, Lothar Bergmann, Martin Boegemann, Michael Moran, Katrin Schlack, Arne Strauss, Marianne Schmid
Journal: Journal of Clinical Oncology (2020)

631 Background: Sunitinib remains an important treatment option for mRCC, but the effect of comorbidities/comedications on sunitinib treatment outcomes have not been fully explored. Methods: Data were collated from STAR-TOR, an ongoing real-world registry. Cutoff date for analysis was 19 June 2019. This subgroup analysis assessed the presence or absence of hypertension (HTN), and the use or non-use of statins and proton pump inhibitors (PPIs), determined at the time of entry to the registry. Treatment endpoints were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). OS and PFS were analyzed by Kaplan-Meier methods. Differences within subgroups were tested using Log-rank test for OS and PFS, and Fisher’s exact test for ORR. Results: 557 sunitinib-treated pts were analyzed; 366 had HTN and 191 did not, 130 used statins and 427 did not, and 165 used PPIs and 392 did not. Median (m) OS (95% confidence intervals) was similar in pts with and without HTN (25.4 [21.1, 31.5] vs 21.5 [15.2, 28.0] months; p = 0.215). mPFS (8.0 [6.5, 9.9] vs 6.3 [5.4, 8.2] months; p = 0.140) and ORR (31.2% vs 30.9%; p = 1.000) were also similar in pts with and without HTN. mOS was similar in pts who used statins vs those who did not (27.8 [20.2, 35.4] vs 24.0 [19.4, 27.3] months; p = 0.884), while mPFS was significantly longer in pts who used statins (9.4 [6.5, 13.6] vs 6.9 [5.7, 8.2] months; p = 0.044). ORR was 37.8% vs 29.0% in pts who did and did not use statins (p = 0.072). mOS was significantly shorter in pts who used PPIs vs those who did not (20.2 [14.9, 28.3] vs 25.7 [22.7, 33.0] months; p = 0.021). mPFS (5.8 [4.6, 8.2] vs 8.0 [6.5, 9.8] months; p = 0.091) and ORR (26.6% vs 33.0%; p = 0.177) were similar in pts who did and did not use PPIs. Conclusions: In sunitinib-treated pts with mRCC in a real-world registry, mPFS was significantly longer and there was a trend toward better ORR in pts who used statins, whereas mOS was significantly shorter and there was a trend toward shorter mPFS in pts who used PPIs. Common comedications may affect sunitinib treatment outcomes in pts with mRCC.
Benefit of prophylactic anticoagulation before and during first-line chemotherapy on patients with metastatic germ cell tumors.
Authors: Christian Daniel Fankhauser, Ben Tran, Jose Manuel Ruiz Morales, Enrique Gonzalez-Billalabeitia, Christoph Alexander Seidel, Carsten Bokemeyer, Thomas Hermanns, Alexey Rumyantsev, Margarida Brito Goncalves, Aude Flechon, Edmond Michael Kwan, Daniel Castellano, Xavier Garcia del Muro, Anis Hamid, Margaret Ottaviano, Alison Helen Reid, Philippe L. Bedard, Christopher Sweeney, Jean M. Connors
Journal: Journal of Clinical Oncology (2020)

402 Background: Recent trials randomising patients (pts) receiving systemic cancer therapy showed that prophylactic anticoagulation (PAK) halves the risk of venous thromboembolic events (VTE) and doubles the risk of bleeding (Khorana et al. &amp; Carrier et al., both NEJM 2019). In pts with metastatic germ cell tumors (mGCT) VTE is a frequent complication but it remains unclear whether PAK should be recommended because the number of mGCT pts in those trials was small. We aimed to determine the risk of VTE before, during and after chemotherapy and in mGCT pts without and with risk factors for VTE (retroperitoneal lymph nodes, Khorana score, venous access device) and to calculate the number needed to treat (NNT) and number needed to harm (NNH) of PAK. Methods: This retrospective analysis included mGCT pts treated with first-line platinum-based chemotherapy. We excluded patients who received PAK, with a known history of coagulopathy or VTE and extracted data about VTE and bleeding events. Cumulative VTE incidence was calculate for patients without and with increasing number of known risk factors for VTEs. NNT and NNH were calculated by assuming similar hazard ratios (HR) to reduce VTEs and increase bleeding as previously published (HR 0.66 and 1.96, Khorana et al., NEJM 2019). Results: Out of 1039 pts, 132 (13%) presented with VTE, 6 (1%) with bleeding. One patients died of VTE and 1 because of bleeding. Patients without any VTE risk factors experience VTE in 20/347 (5%) which translated into a NNT of 55 compared to the NNH of 84 respectively. Before start of chemotherapy 52 (5%) pts (NNT=60) presented with VTE of which 22 were reported symptomatic 21 asymptomatic/incidentally detected VTE on staging scans (9 unknowns). During chemotherapy 79 (8%) pts (NNT=40) were diagnosed with VTE whereas 19 (2%) pts (NNT=162) were diagnosed with VTE after chemotherapy. Conclusions: Our analysis revealed that even mGCT patients without risk factors for VTE show a relevant cumulative VTE incidence of 7%. Especially before and during but not after chemotherapy the benefits of PAK to prevent VTE outweighs the small increased risk of bleeding.
Quality of life of prostate cancer (PCa) patients with testosterone deficiency symptoms (TDS) before initiation of gonadotropin-releasing hormone (GnRH) agonist therapy: Subgroup analysis of EQUINOXE study.
Authors: Stephane Droupy, Marie-Helene Colson, Nathalie Pello Leprince Ringuet, Valérie Perrot, Aurelien Descazeaud
Journal: Journal of Clinical Oncology (2020)

232 Background: Both PCa and TDS risk increase with age. Patients may therefore suffer from both conditions, and their quality of life (QoL) be reduced. Unexpectedly, multivariate analysis of the EQUINOXE study (NCT02630641) identified baseline TDS as a significant factor improving QoL after 6 months of GnRH agonist therapy. We therefore aim to analyze baseline parameters of this subgroup. Methods: EQUINOXE was a French prospective, multicenter, non-interventional study. Urologists recruited partner-patient couples with PCa for whom androgen deprivation therapy (ADT) was indicated. Data were collected at inclusion and after 6 months of treatment, on QoL (WHOQOL-BREF), perception of disease (B-IPQ), symptoms of the disease (QLQ-PR25) and perception of cohesion within the patient-partner relationship (dyadic adjustment, DAS-16). TDSat baseline, determined by QLQ-PR25 “treatment related symptoms” score ≥25/100, was the main parameter identified by multivariate analysis in improvement of QoL (OR [95% CI]: 3.0 [1.46, 6.17]. Post hoc subgroup analysis was made to compare baseline parameters of patients with and without TDS. Results: 487 patients were included in this analysis, 26% of whom had TDS at baseline. Symptoms were (quite a bit or very much): feeling of less masculinity (55.2%), hot flushes (41%), weight gain (40.1%) and enlarged nipples (23.1%). Patients with TDS were slightly older than those without TDS (75.3±8.3vs 73.8±8y.o), had significantly worse performance Status (0-1-2+ in 37.0-45.7-17.3% vs 52.8-36.4-10.8%, p=0.0153) and suffered more frequently from recurrent PCa (35.7% vs 24.7%, p=0.0175). Symptoms other than urinary and sexual (but including asthenia) were more frequent (p=0.0126). All dimensions of WHOQOL-BREF were rated significantly worse. Total score of illness (B-IPQ) was worse: 42.2±8.2 vs39.1±9.4, p=0.0040. Cohesion in the couple (DAS score) was worse: 98.6±22.3 vs107.3±20.9, p=0.0006. Conclusions: Patients with TDS experienced at baseline a worse cohesion of the couple and a lower QoL than patients without TDS but benefited relatively more from ADT in term of QoL. Clinical trial information: NCT02630641.
Predicting biochemical recurrence after prostatectomy: Can machine learning beat CAPRA score? Results of a multicentric retrospective analysis on 4,700 patients.
Authors: Paul Sargos, Nicolas Leduc, Nicolas Giraud, Giorgio Gandaglia, Mathieu Roumiguie, Guillaume Ploussard, Tamim Niazi, Ahmad Chaddad, Jean-Baptiste Beauval
Journal: Journal of Clinical Oncology (2020)

343 Background: Recent advances in machine learning algorithms and deep learning solutions paved the way for improved accuracy in survival analysis. We aim to investigate the accuracy of conventional machine learning and deep learning methods in the prediction of 3-year biochemical recurrence (BCR) as compared to CAPRA score prediction. Methods: A total of 5043 men who underwent RP between 2000 and 2015 for clinically localized PCa iwere analyzed retrospectively. Three-year BCR was predicted using the following models: CAPRA score, Cox regression analysis, logistic regression, k-nearest neighbor, random forest and densely connected feed-forward neural network classifier. The discrimination of the models was quantified using the C-index or the area under the receiver operating characteristics curve. Results: Patients with CAPRA score 2 and 3 accounted for 64% of the population. C-index measuring performance for the prediction of the three-year BCR for CAPRA score was 0.63. C-index values for k-neighbor classifier, logistic regression, Cox regression analysis, random forest classifier and densely optimized neural network were respectively 0.55, 0.63, 0.64, 0.64 and 0.70 (pairwise, adjusted p-value &lt; 0.01). After inclusion of available post-surgical variables, C-index value reached respectively 0.58, 0.77, 0.74, 0.75 and 0.84 (pairwise, adjusted p-value &lt; 0.05). Conclusions: Our results show that CAPRA score performed poorly in intermediate-risk patients undergoing RP. Densely connected neural networks with simple architecture further increased predictive power with low computational cost. In order to predict 3-years BCR, adding post-surgical features to the model greatly enhanced its performance.
Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study
Authors: Gabriela P Peralta, Alessandro Marcon, Anne-Elie Carsin, Michael J Abramson, Simone Accordini, André FS Amaral, Josep M Antó, Gayan Bowatte, Peter Burney, Angelo Corsico, Pascal Demoly, Shyamali Dharmage, Bertil Forsberg, Elaine Fuertes, Vanessa Garcia-Larsen, Thorarinn Gíslason, José-Antonio Gullón, Joachim Heinrich, Mathias Holm, Deborah L Jarvis, Christer Janson, Rain Jogi, Ane Johannessen, Bénédicte Leynaert, Jesús Martínez-Moratalla Rovira, Dennis Nowak, Nicole Probst-Hensch, Chantal Raherison, José-Luis Sánchez-Ramos, Torben Sigsgaard, Valérie Siroux, Giulia Squillacioti, Isabel Urrutia, Joost Weyler, Jan-Paul Zock, Judith Garcia-Aymerich
Journal: Thorax (2020)

Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS).
2019 Community-acquired Pneumonia Treatment Guidelines: There Is a Need for a Change toward More Parsimonious Antibiotic Use
Authors: Benedikt Huttner, Bernadette Cappello, Graham Cooke, Sumanth Gandra, Stephan Harbarth, Monica Imi, Mark Loeb, Marc Mendelson, Lorenzo Moja, Céline Pulcini, Mike Sharland, Evelina Tacconnelli, Mei Zeng, Nicola Magrini
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Step-up to high dose fluticasone furoate in combination with long-acting bronchodilator in inadequately controlled asthma: the CAPTAIN study
Authors: Nicola Hanania, Edward Kerwin, Ian Pavord, Huib Kerstjens, Steven Pascoe, Guy Peachey, Andrew Fowler, Zelie Bailes, Dawn Edwards, Neal Sule, Neil Barnes, Frances Gardiner, Laurie Lee
Journal: Journal of Allergy and Clinical Immunology (2020)
A multicenter phase IIb trial to evaluate the efficacy and tolerability of ModraDoc006/r in subjects with metastatic castration-resistant prostate cancer (mCRPC), suitable for treatment with a taxane (NCT04028388).
Authors: Ulka N. Vaishampayan, Edwin J. De Wit, Neal D. Shore, Robert Dreicer, Daniel J. George, Ralph V. Boccia, Brendan D. Curti, Lajos Geczi, Tibor Csõszi, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2020)

TPS268 Background: Docetaxel IV and prednisone is a standard of care in mCRPC with demonstrated overall survival benefit. ModraDoc006 is a novel oral tablet formulation of docetaxel and to enhance bioavailability, it is co-administered with ritonavir (/r), an inhibitor of cytochrome p450 3A4 and P-glycoprotein. The oral combination, denoted as ModraDoc006/r, could be preferable due to patient convenience and elimination of infusion reactions and prophylactic steroids administration. Due to its weekly administration and exposure levels, increased efficacy may be demonstrated. Methods: The study is an open label 1:1 randomized phase 2b trial of ModraDoc006/r bi-daily QW versus docetaxel IV 75 mg/m 2 Q3W. Thirty (30) mg ModraDoc006 combined with 200 mg /r in morning and 20 mg ModraDoc006 with 100 mg /r in evening is administered on days 1, 8 and 15 of a 21 day cycle. Safety and preliminary efficacy of ModraDoc006/r have been established in a phase Ib trial in mCRPC pts. All patients will receive 5 mg oral prednisone twice daily. Treatment is continued until progression, unacceptable toxicity or patient wish. mCRPC pts with measurable disease per RECIST 1.1, suitable for docetaxel therapy, are eligible. No prior treatment with taxanes is allowed. Primary objective is objective response rate (ORR) as assessed by investigators. Secondary objectives include PSA response, PSA-PFS, time to skeletal related events and progression, duration of response, disease control rate and safety assessments. Patient reported outcomes and health-related quality of life will be captured with treatment satisfaction and FACT-P questionnaires. It is expected that ModraDoc006/r will be at least as effective as docetaxel IV. A sample size of 50 evaluable pts per arm will evaluate an estimated ORR of 25% in each arm, with a 5% two-sided alpha and power of 83.7%. Conclusions: ModraDoc006/r represents an advance in prostate cancer therapeutics with convenience of oral administration, reduced myelosuppressive toxicity and potential improved efficacy over IV docetaxel. Clinical trial information: NCT04028388.
US government sues Yale’s teaching hospital for age discrimination in testing older doctors
Authors: Owen Dyer
Journal: BMJ (2020)

The US Equal Employment Opportunity Commission (EEOC) is suing Yale New Haven Hospital over its policy of requiring doctors aged over 70 to undergo a neuropsychological screening evaluation and basic ophthalmologic examination.

Because such tests are demanded only of older doctors, the EEOC argues in its lawsuit,1 Yale’s “late career practitioner policy” breaches the Age Discrimination in Employment Act.

The commission also contends that the policy contravenes the Americans with Disabilities Act, which prohibits subjecting employees to medical examinations that are not job …
Adjuvant therapy in high-risk renal cell cancer: A systematic review and cumulative meta-analysis.
Authors: Rabbia Siddiqi, Irbaz Bin Riaz, Mahnoor Islam, Qurat Ul Ain Riaz Sipra, Alexander J. Ryu, Ammad Raina, M. Hassan Murad, Manish Kohli
Journal: Journal of Clinical Oncology (2020)

708 Background: Patients with high risk non-metastatic renal cell cancer (RCC) are at significant risk of recurrence following nephrectomy. Previously, we reported no benefit of adjuvant tyrosine kinase inhibitor (TKI) treatment in high-risk patients. Since our most recent publication, efficacy results from the multicenter double-blind SORCE trial have become available. We updated our meta-analysis to include these additional data and performed a cumulative meta-analysis. Methods: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched to identify relevant RCTs. A generic variance-weighted random effects model was used to derive estimates for efficacy. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I 2 test. The primary outcome was disease-free survival (DFS), defined as the interval between randomization and the first recurrence, the occurrence of metastasis or a secondary cancer, or death due to any cause. Statistical analysis was performed using Comprehensive Meta-Analysis version 3 (Biostat). Results: Five phase 3 trials were identified, enrolling 6531 patients. Two trials compared sunitinib with placebo (S-TRAC and ECOG-ACRIN), two compared sorafenib with placebo (ECOG-ACRIN and SORCE) and one trial each compared pazopanib (PROTECT) and axitinib (ATLAS) vs placebo. Cumulative evidence suggests that adjuvant therapy with TKIs showed no significant improvement in (DFS) hazard ratio [HR] of 0.93 (95% CI, 0.85-1.02), compared to placebo. There was no significant heterogeneity among included trials ( I 2 = 52%, P= .41). Overall, the trials were at low risk of bias. Conclusions: Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve DFS as compared to placebo. Improved patient selection using better prognostic biomarkers or scoring systems may identify subsets of patients who can benefit from adjuvant treatments. Toxicity estimates will be updated as data from SORCE trial publication becomes available.