tbuckley/cabot-search huggingface dataset:
EFFECT OF THROMBOTIC AND BLEEDING RISK ACCORDING TO PLATELET REACTIVITY ON 2-YEAR MORTALITY: THE ADAPT-DES STUDY
Authors: Jaya Chandrasekhar, Roxana Mehran, George Dangas, Thomas McAndrew, Yiran Zhang, Philippe Genereux, Ajay Kirtane, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Glucocorticoid receptors: finding the middle ground
Authors: Sofie J. Desmet, Karolien De Bosscher
Journal: Journal of Clinical Investigation (2017)

Glucocorticoids (GCs; referred to clinically as corticosteroids) are steroid hormones with potent anti-inflammatory and immune modulatory profiles. Depending on the context, these hormones can also mediate pro-inflammatory activities, thereby serving as primers of the immune system. Their target receptor, the GC receptor (GR), is a multi-tasking transcription factor, changing its role and function depending on cellular and organismal needs. To get a clearer idea of how to improve the safety profile of GCs, recent studies have investigated the complex mechanisms underlying GR functions. One of the key findings includes both pro- and anti-inflammatory roles of GR, and a future challenge will be to understand how such paradoxical findings can be reconciled and how GR ultimately shifts the balance to a net anti-inflammatory profile. As such, there is consensus that GR deserves a second life as a drug target, with either refined classic GCs or a novel generation of nonsteroidal GR-targeting molecules, to meet the increasing clinical needs of today to treat inflammation and cancer.
01.06 B-cell phenotype and igd-cd27- memory b cells are affected by tnf-inhibitors and tocilizumab treatment in rheumatoid arthritis
Authors: Rita A Moura, Cláudia Quaresma, Ana R Vieira, Maria J Gonçalves, Joaquim Polido-Pereira, Vasco C Romão, Nádia Martins, Helena Canhão, João E Fonseca
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. <h3>Materials and methods</h3> Blood samples were collected from untreated early RA (ERA) patients (&lt;1 year of disease duration), established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterised by flow cytometry and B-cell gene expression was analysed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA. <h3>Results</h3> The frequency of total CD19+ B-cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN) IgD-CD27- memory B-cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B-cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab. <h3>Conclusions</h3> In RA, treatment with either TNF-inhibitors or tocilizumab affects B-cell phenotype and the frequency of memory B-cell subpopulations in peripheral blood, particularly DN (IgD-CD27-) B-cells, but not B-cell gene expression or serum levels of CXCL13, sCD23 and BAFF, when comparing baseline with post-treatment follow up. Overall, our results may suggest that TNF-inhibitors and tocilizumab inhibit B-cell trafficking towards inflammatory sites, thus supporting activated B-cell recirculation from tissues through blood and lymphatic systems.
FNDC3B is another novel partner fused to RARA in the t(3;17)(q26;q21) variant of acute promyelocytic leukemia
Authors: Chi Keung Cheng, Angela Z. Wang, Terry H. Y. Wong, Thomas S. K. Wan, Joyce S. Cheung, Radha Raghupathy, Natalie P. H. Chan, Margaret H. L. Ng
Journal: Blood (2017)
The use of dose volume constraints to achieve rectal isotoxicity: A phase II prostate cancer radiation therapy dose escalation study
Authors: C. E. Vargas, L. L. Kestin, D. Yan, D. S. Brabbins, D. M. Lockman, J. Liang, G. S. Gustafson, F. A. Vicini, J. W. Wong, A. A. Martinez
Journal: Journal of Clinical Oncology (2004)

4628 Background: The primary limiting factor for prostate cancer irradiation is the risk of rectal toxicity. Rectal toxicity is associated with the dose and volume of the rectum irradiated. This dose escalation study has the unique feature of using dose volume histogram (DVH) constraints to determine the prescribed dose. Methods: From 1999–2002, 331 patients with clinical stage T1-T3N0M0 prostate cancer were prospectively treated with 3D conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed based on multiple CT scans. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined using a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: 1) <30% of the rectal wall volume can receive >75.6 Gy. 2) <5% of the rectal wall can receive >82 Gy. The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. Median follow-up was 1.6 years. Results: 34 patients (10%) experienced grade 2 chronic rectal toxicity (9% rectal bleeding, 6% proctitis, 3% diarrhea, 1% rectal pain) at a median interval of 1.1 years. Nine patients (3%) experienced grade ≥3 chronic rectal toxicity (1 grade 4) at a median interval of 1.2 years (table). The 3-year rates of grade ≥2 and grade ≥3 chronic rectal toxicity were 20% and 4%, respectively. There was no significant difference by dose level in the 2-year rate of grade ≥2 chronic rectal toxicity. These rates were 27%, 15%, 14%, 17% and 24% for the ≤72, 73.8, 75.6, 77.4, and 79.2 Gy dose level groups respectively (p = 0.27). Conclusions: High dose levels (79.2 Gy) can be safely delivered if selected DVH constraints are met. The prescribed dose should be based on DVH information (toxicity risk) and the benefit of a specific dose level. No significant financial relationships to disclose.
A1A-ADRENERGIC RECEPTOR OVEREXPRESSION PROTECTS AGAINST THE DEVELOPMENT OF ARRHYTHMIAS FOLLOWING CORONARY ARTERY OCCLUSION
Authors: John Guers, Seonghun Yoon, Jie Zhang, Xin Zhao, Dorothy E. Vatner, Robert Graham, Stephen F. Vatner
Journal: Journal of the American College of Cardiology (2017)
DIAGNOSTIC VALUE OF QT EVALUATION IN ANTERIOR ST SEGMENT ELEVATION MYOCARDIAL INFARCTION FOR PREDICTION OF MYOCARDIAL SALVAGE INDEX, AS COMPARED TO CMR
Authors: Gianluca Pontone, Andrea Igoren Guaricci, Patrizia Carità, Daniele Andreini, Marco Guglielmo, Saima Mushtaq, Andrea Baggiano, Massimo Verdecchia
Journal: Journal of the American College of Cardiology (2017)
Proton radiotherapy for T4 nasopharyngeal carcinoma
Authors: A. W. Chan, L. J. Liebsch, D. G. Deschler, J. A. Adams, L. V. Vrishali, J. F. McIntyre, P. Pommier, R. L. Fabian, P. M. Busse
Journal: Journal of Clinical Oncology (2004)

5574 Background: To evaluate the outcome and toxicity of treatment of T4 nasopharyngeal carcinoma using proton radiotherapy. Methods: Between 1990 and 2002, 17 patients with newly diagnosed T4 nasopharyngeal carcinoma received combined conformal proton and photon radiotherapy. There were 3 females and 14 males, with a median age of 41 (range 14 - 73). The N staging distribution was as follows: N0, 8; N1, 3; N2, 5; N3, 1. The WHO histology classification was type 1 in 5 cases, type 2–3 in 12 cases. The median gross tumor volume was 83 cc (range 46 - 216 cc). The median total prescribed dose to the gross target volume was 73.6 Cobalt-Gray-Equivalent (CGE) (range 69 - 76.8). The radiation fractionation schedule was 1.6 CGE twice-daily in 10 patients, 1.2 CGE twice-daily in 1, and 1.8 - 2.0 CGE once-daily in 6. Ten patients received chemotherapy: 3 with induction docetaxel, cisplatin, 5FU, leucovorin; 5 with concurrent cisplatin; 1 with concurrent carboplatin; 1 with concurrent taxol. Results: All patients received the planned concurrent radiation and chemotherapy treatments. One patient was hospitalized for acute toxicities. Two patients required unplanned treatment break of 1 - 5 days. With a median follow-up of 43 months, 1 patient developed local failure and 2 with systemic failures. There was no neck recurrence. The local-regional control and disease-free survival rates at 3 years were 92% and 75%, respectively. The overall 3-year overall survival rate was 74%. Late toxicities included 5 patients with radiographic changes of the temporal lobes, 1 osteoradionecrosis of the mandible, and 2 patients with endocrine dysfunction. Conclusions: Proton radiotherapy, with and without chemotherapy, results in excellent local-regional control rate in patients with T4 nasopharyngeal carcinoma. The use of proton with concurrent chemotherapy in the treatment of nasopharyngeal carcinoma will be further investigated in a Phase II trial at our Northeast Proton Therapy Center. No significant financial relationships to disclose.
VALVULOARTERIAL IMPEDANCE AND LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN PROVIDE INCREMENTAL PROGNOSTIC VALUE IN PATIENTS WITH SIGNIFICANT AORTIC STENOSIS AND PRESERVED LEFT VENTRICULAR EJECTION FRACTION
Authors: Chetan Huded, Andrew Goodman, Kenya Kusunose, Lars Svensson, A. Gillinov, Brian Griffin, Milind Desai
Journal: Journal of the American College of Cardiology (2017)
Androgen deprivation therapy (ADT) use in Medicare beneficiaries with nonmetastatic (M0) prostate cancer (PC) in the United States.
Authors: Thomas J. Arneson, Karynsa Cetin, Scott Stryker, Alexander Liede, Tom Murray, Shuling Li, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2012)

e15169 Background: ADT is well-established for metastatic PC but is also used in men with less advanced PC. Patterns of ADT use in the M0 PC setting have not been well-described. Methods: Medicare claims in 2005 for men aged ≥66 years (yrs) were assessed for use of gonadotropin-releasing hormone agonists or bilateral orchiectomy. The cohort was limited to men who, during the 15 months (mos) prior to their first 2005 ADT claim, had continuous Parts A + B coverage, a diagnosis code for PC, no claims for metastases (except lymph nodes), and no claims for ADT. Follow-up (f/u) was from ADT initiation to 3 yrs, death, or change in Medicare coverage. Regimen duration was defined by combining claim service count and dosage with FDA label dosing. Because ADT has biologic activity beyond the recommended regimen duration, active dose time was calculated by adding 3 and 6 mos to claims for regimens &lt;6 mos and ≥6 mos, respectively. Interruption was defined as ≥180 days from end of active dose time to next ADT claim. Results: We identified 3246 M0 PC patients aged ≥66 yrs who initiated ADT in 2005 but describe results in the 2161 who had 3 full yrs of f/u (data for the entire cohort were similar). Nearly 70% received only 1 type of ADT agent during f/u (25% had 2 types, 5% had 3 or 4 types), and 73% started on a 3-or 4-month regimen. The distribution of patients by first ADT type (and by type received at any point) was: leuprolide injection: 54% (67%); goserelin implant: 36% (43%); triptorelin injection: 6% (19%); leuprolide implant: 2% (4%); orchiectomy: &lt;1% (1%); and histrelin implant: 0% (3%). Use of &gt;1 type of ADT agent was more common in men who began with goserelin (45%) or triptorelin (53%) versus leuprolide (≤24%). At three years after ADT initiation, 36% received ADT for the entire 36-month period, 15% for 24-35 mos, 17% for 12-23 mos, and 32% for &lt;12 mos. Interruption in active therapy occurred in only 13%. Conclusions: Most elderly men with M0 PC initiating ADT in 2005 started on a 3- or 4-month leuprolide or goserelin regimen. Though these agents remained the most commonly used throughout f/u, switching was common (30% used &gt;1 type during f/u). ADT was continued for at least 2 yrs in nearly half and extended to 3 yrs in over one-third of the cohort.
SAFETY OF PERFLUTREN-BASED ECHOCARDIOGRAPHIC CONTRAST AGENT ADMINISTRATION IN THE SETTING OF A PATENT FORAMEN OVALE (PFO): A MULTICENTER STUDY CONDUCTED IN TERTIARY CARE CENTERS BASED IN THE NEW YORK/CHICAGO METROPOLITAN AREAS
Authors: Valentin Suma, Karthik Seetharam, Hadi Halazun, Sergie Ziad, Jeffrey J. Silbiger, Benoit Bewley, Farhan Bajwa, Suraj Sookhu, Jyothy Puthumana, Arif Jivan, Ajay Yadlapati, Issam A. Mikati, Edgar Argulian, Jasjit Bhinder, Lakshmi Muthukumar, Rena Toole, Aasha Gopal, Farooq A. Chaudhry
Journal: Journal of the American College of Cardiology (2017)
DIFFERENCE IN HEMODYNAMIC MICRO-ENVIRONMENT IN VESSELS SCAFFOLDED WITH ABSORB BVS AND MIRAGE BRMS: INSIGHTS FROM A PRE-CLINICAL ENDOTHELIAL SHEAR STRESS STUDY
Authors: Erhan Tenekecioglu, Ryo Torii, Christos Bourantas, Yohei Sotomi, Rafael Cavalcante, Yaping Zeng, Pannipa Suwannasom, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2017)
Prostate-specific antigen decline (PSA) as a surrogate for overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) who failed first-line chemotherapy.
Authors: Susan Halabi, Andrew J. Armstrong, A. Oliver Sartor, Johann Sebastian De Bono, Ellen B Kaplan, Eric Jay Small
Journal: Journal of Clinical Oncology (2012)

4515 Background: PSA kinetics, and more specifically a 30% decline in PSA following initiation of first-line chemotherapy with docetaxel, has been reported to be a surrogate endpoint for OS in mCRPC pts. The objective of this analysis was to evaluate PSA kinetics as surrogate endpoints for overall survival (OS) in patients who were receiving second line chemotherapy following progression after docetaxel front line therapy. Methods: Data from a phase III trial of 755 mCRPC pts randomized to treatment with cabazitaxel in combination with prednisone (C+P) every 3 weeks or mitoxantrone in combination with prednisone (M+P) were used. All pts were previously treated with a docetaxel-containing regimen. PSA decline (≥30% and ≥50% ) and PSA velocity within the first three months of treatment were evaluated as potential surrogate endpoints for OS. The proportional hazards (PH) model was used to test for Prentice’s criteria and the proportion of treatment explained (PTE) was computed as a second test of surrogacy. PTE was defined as one minus the ratio of the treatment coefficient in the adjusted PH model (includes PSA decline or velocity) to the treatment coefficient in the unadjusted PH model. Results: Of 755 men, 654 had sufficient PSA data to be included in the analysis. Treatment arm (C+P vs. M+P) was prognostic of OS with a hazard ratio (HR) of 0.65 (95% CI=0.54-0.79, p&lt;0.001). A 30% PSA decline within three months of treatment was associated with a HR of 0.46 (95% CI 0.37-0.57, p-value&lt;0.001) for OS. After adjusting for treatment effect, the HR for 30% PSA decline was 0.50 (95% CI= 0.40-0.62, p&lt;0.001) but treatment arm remained statistically significant thus failing Prentice’s third criterion. The PTE for ≥30% decline in PSA within three months was 0.39 (95% CI= 0.36-0.42) indicating a lack of surrogacy for OS. Similar results were observed for pts who experienced ≥50% decline in PSA and PSA velocity. Conclusions: Neither PSA decline (≥30% and ≥50%) nor PSA velocity within the first three months of therapy are surrogate endpoints for OS in pts receiving second line chemotherapy.
THIRTY-DAY READMISSION RATE AND COST AFTER PERCUTANEOUS CORONARY INTERVENTION IN THE UNITED STATES: A NATIONAL READMISSION DATABASE ANALYSIS
Authors: Avnish Tripathi, J. Abbott, Gregg Fonarow, Abdur Khan, Sadip Pant, Sohail Ikram, Rita Coram, Harsh Golwala, Brahmajee Nallamothu, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2017)
Impact of prior autologous stem cell transplant (ASCT) in patients receiving bortezomib or dexamethasone for relapsed/refractory multiple myeloma in the APEX trial
Authors: D. T. Vogl, E. A. Stadtmauer, P. G. Richardson, P. Sonneveld, M. W. Schuster, D. Irwin, T. Facon, J. M. Harousseau, A. Boral, K. C. Anderson
Journal: Journal of Clinical Oncology (2006)

7546 Background: The phase 3 international APEX trial demonstrated significantly superior overall survival (OS), time to progression (TTP), and overall response rate (ORR: CR+PR, EBMT criteria) with bortezomib (VELCADE [Vc]) therapy for relapsed myeloma compared with dexamethasone (Dex). ASCT is a common component of initial therapy and may affect the outcome of salvage therapies. Methods: This analysis aimed to evaluate the impact of prior ASCT on the APEX results. TTP, OS, and ORR were analyzed by prior ASCT treatment. Results: Of 669 randomized patients, 451 (67%) had received prior ASCT (median follow-up in survivors was 21.9 months); in this group, Vc led to higher ORR compared with Dex (41% vs 18%, p &lt; 0.001), higher CR rate (8% vs 0.5%, p &lt; 0.001), and longer TTP and OS (see table), the latter despite crossover to Vc of &gt;62% of patients originally assigned to Dex. A subset of 156 (23%) patients had ASCT as their only prior line of therapy (median follow-up in survivors was 20.0 months), with similar superiority of Vc compared with Dex in ORR (48% vs 29%, p = 0.004), CR rate (6% vs 2%, p &gt; 0.05), and TTP. Among 218 (33%) patients with no prior ASCT (median follow-up in survivors was 21.7 months), Vc was also superior to Dex in ORR (32% vs 18%, p = 0.025), CR rate (4% vs 1%, p &gt; 0.05), and TTP. Conclusions: Vc is consistently superior to Dex in ORR, CR rate, and TTP, regardless of prior ASCT status, and OS is superior in patients who had received prior ASCT. Vc is an effective therapy for myeloma relapsing after ASCT. NE = not estimable. [Table: see text] [Table: see text]
Size distribution and metastasis in discarded intrapulmonary lymph nodes (LN) after lung cancer resection.
Authors: Laura Elizabeth Miller, Robert A. Ramirez, Christopher Gene Wang, Courtney A Adair, Allen Berry, Thomas O'Brien, Raymond U Osarogiagbon
Journal: Journal of Clinical Oncology (2012)

7072^ Background: Lymph node (LN) status is the most important prognostic determinant after resection of lung cancer. 18% of a SEER cohort and 12% of a Memphis cohort had no LNs examined (pNx). Patients with pNx have inferior survival to T-category matched pN0 patients with at least 1 LN examined. The optimal number of LN needed to safely declare a patient pN0 may be &gt;10. Less than 20% of resections in SEER achieve this. We hypothesized that a significant number of intrapulmonary LNs are left unexamined and some may harbor metastatic disease. We report the size characteristics of materials examined in a re-dissection protocol to test this hypothesis. Methods: Prospective study of lung resection specimens re-dissected after signout of the final pathology report. Remnant lung material was dissected with thin cuts and all LN-like material was retrieved for microscopic examination, irrespective of size or location. The size of non-LN tissue, LN without metastasis and LN with metastases were compared using the Wilcoxon-Mann-Whitney test. Results: 112 specimens were examined and 1,094 LN-like materials were retrieved. 749 (69%) proved to be LN tissue. 71 (10%) LNs retrieved had metastasis. Non-LN tissue was significantly smaller than LN tissue (p&lt;0.0001). LNs with metastasis were significantly larger than those without metastasis (p &lt;0.0001). 60% of materials &gt;2cm were LNs with metastasis. 7% of materials &lt;1cm were LN with metastasis. 52% of LNs with metastasis, and 55% of LNs without metastasis measured from 0.5 to 1.5cm (Table). Majority of LNs &gt;2cm had metastatic disease, but 40% did not; a notable proportion of LNs with metastasis were small. Nearly equal percentages of LNs with and without metastasis were found in the range of 0.5-1.5cm. Conclusions: Statistical differences in size between lymph nodes with and without metastasis is clinically meaningless due to broad overlap. LN size alone is not an adequate predictor of LN metastasis. [Table: see text]
Targeting NF-KB Activation in Novel Intracranial Models of CNS Lymphoma
Authors: Huimin Geng, Huaxin Gao, Cigall Kadoch, Ming Lu, Lingjing Chen, Rana Anjum, Lisa Drew, Sebastien Degorce, Keith Dillman, Michele Mayo, Shawn Anderson, Colin Collins, Clifford A. Lowell, James L. Rubenstein
Journal: Blood (2016)
ASSOCIATION BETWEEN DURATION OF DUAL ANTIPLATELET THERAPY AND ANGIOGRAPHIC MULTI-VESSEL DISEASE ON OUTCOMES IN PATIENTS TREATED WITH NEWER-GENERATION DRUG-ELUTING STENTS
Authors: Seung-Yul Lee, Myeong-Ki Hong, Eui Im, Dong-Ho Shin, Chul Min Ahn, Jung-Sun Kim, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, Hyo-Soo Kim, Marco Valgimigli, Antonio Colombo, Martine Gilard, Tullio Palmerini, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Is tumor burden a better predictor of drug activity than progression-free survival?
Authors: J. Fridlyand, L. Kaiser, G. Fyfe
Journal: Journal of Clinical Oncology (2009)

e17521 Background: Improving the ability of Phase (Ph) II trials to better predict Ph 3 outcome is critical. Percentage change in tumor burden (%SLD) is a potentially earlier marker of drug activity than an early evaluation of progression-free survival (PFS) and includes aspects of tumor response not captured by PFS. We describe a statistical evaluation of the ability of %SLD vs PFS to identify an active agent in randomized Ph 2 trials. Methods: Ph 2 trials were simulated with data from bevacizumab (B) and trastuzumab (T) mBC and mCRC Ph3 trials of &gt; 1800 patients total. 2/3 B trials and 1 T trial showed improved PFS (+) &amp; OS (+ or trend), and 1 mBC B study was negative. We repeatedly sampled patients, with their treatment assignments, tumor assessments and PFS values from these studies to emulate randomized Ph 2 trials with different sample sizes, enrollment patterns and follow-up. We determined the probability of correctly identifying an approvable regimen, based on 5% 1-tailed tests of PFS (log-rank) and %SLD (last &amp; nadir, Wilcoxon). All endpoints have equal follow up given a landmark. Results: We performed analyses on 6–8 week assessments and on up to 20–24 week assessments in patients enrolled over 6 months. The estimated probability of a correct Ph 3 decision is reported below for a 100-patient Ph 2 trial. We found:1) For B, PFS consistently outperforms %SLD; 2) for T, %SLD is modestly better than an early PFS, especially with shorter patient follow up. The results were similar across other assessments and varying enrollment times. Conclusions: More trial data are needed to determine if the usefulness of %SLD for decision making is dependent on the drug's MOA/indication. For B, its utility is inferior to PFS at all time points, with the last %SLD generally outperforming the nadir %SLD. In the T study the %SLD analyses displayed a slight advantage. PFS and %SLD should be incorporated into Ph 2 design, analysis, and decision making. [Table: see text] [Table: see text]