bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric prostate MRI and MRI/ultrasound fusion biopsy as tools to follow prostate cancer progression for men on active surveillance.
Authors: Shakir Nabeel , Walton-Diaz Annerleim , Rais-Bahrami Soroush , Turkbey Baris , Rothwax Jason , Hong Cheng William , Stamatakis Lambros , George Arvin , Okoro Chinonyerem , Raskolnikov Dima , Siddiqui Minhaj , Su Daniel , Simon Richard , Wood Bradford J. , Choyke Peter L. , Pinto Peter A. 
Published: February 2017

63 Background: Active surveillance (AS) is an option for patients with low risk prostate cancer (PCa); however, determining disease progression is challenging. At the NCI, multiparametric MRI (MP-MRI) with our biopsy protocol (MR-US fusion-guided plus 12 core extended sextant biopsy) has been used to confirm eligibility for AS. We evaluated the utility of these modalities in monitoring patients on AS. Methods: Patients who underwent MP-MRI of the prostate with biopsy per our protocol between 2007-2012 were reviewed. We selected a subset who met Johns Hopkins criteria for AS (Gleason score≤6, PSA density≤0.15, tumor involvement of ≤2 cores, and ≤50% of any single core) by outside 12−core TRUS biopsy. Patients with Gleason score≤6 confirmed at first NCI biopsy session were followed with annual MP-MRI and biopsy. MRI progression was defined as an increase in MP-MRI suspicion level, lesion diameter, or number of lesions. Pathologic progression was defined as an increase to Gleason score≥7 in either 12-core or MR-fusion biopsy. We determined the association between MRI and pathologic progression. Results: 129 patients met JHU criteria for AS by outside biopsy. Mean age was 61.6 years and mean PSA 5.16ng/mL. 28/129 (21.7%) patients had Gleason score ≥7 at first NCI biopsy session.31 patients had at least two biopsy sessions (mean follow up 18 months, range 12-54 months) of which 9/31 (29%) increased in Gleason score, all to 3+4=7. Fusion biopsy detected more pathologic progression than did standard biopsy (Table). The positive predictive value of MP-MRI for pathologic progression was 50%, while the negative predictive value was 84%. The sensitivity and specificity of MP-MRI for increase in Gleason score was 67% and 73%, respectively. Conclusions: Stable findings on MP-MRI are associated with Gleason score stability in patients with low-risk PCa choosing AS. The majority of patients who had pathologic progression were detected on fusion biopsy, which may suggest that random biopsies are unnecessary in this population. Larger studies are needed to validate these findings. [Table: see text]
Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers to detect clinically significant disease: Results from the initial screening round of the IMPACT study.
Authors: Mikropoulos Christos , Castro Elena , Bancroft Elizabeth , Page Elizabeth , Taylor Natalie , Ahmed Mahbubl , Goh Chee Leng , Eeles Ros A. ,   IMPACT Collaborators
Published: February 2017

8 Background: Men with germline BRCA1/2 mutations have a higher risk of developing prostate cancer (PrCa) than non-carriers. IMPACT is an international consortium of 62 centers in 20 countries evaluating the use of targeted PrCa screening in men with BRCA1/2 mutations. This analysis reports the first year’s screening results for all men at enrolment in the study. Methods: We recruited men aged between age 40 and 69 with germline BRCA1/2 mutations and a control group that tested negative for a BRCA1/2 mutation. All men underwent prostate-specific antigen (PSA) testing at enrollment and those with a PSA of greater than 3ng/ml threshold were offered prostate biopsy. All men are offered a biopsy irrespective of PSA level after five years of screening. Results: We recruited 2,481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls) of whom 199 (8%) presented with a PSA greater than 3ng/ml. We performed a total of 162 biopsies and diagnosed 59 PrCas (18 BRCA1 carriers, ten BRCA1 controls; 24 BRCA2 carriers, seven BRCA2 controls); 66% of the tumors were classified as intermediate or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3·0ng/ml in BRCA2 mutation carriers was 48%, double that reported in population screening studies. A significant difference in detecting intermediate or high-risk disease was observed in BRCA2 carriers using this threshold. Conclusions: The IMPACT screening network will be useful for targeted PrCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this yields a high proportion of aggressive disease. Early data indicate that the majority of BRCA1/2 mutation carriers diagnosed with prostate cancer at biopsy had developed clinically significant disease (requiring radical treatment). Clinical trial information: NCT00261456.
Influence of one-year androgen deprivation therapy on lipid and glucose metabolism in patients with newly diagnosed prostate cancer.
Authors: Mitsuzuka Koji , Kyan Atsushi , Orikasa Kazuhiko , Fukushi Yasuo , Aoki Hiroshi , Narita Shintaro , Koie Takuya , Miyazato Minoru , Kakoi Narihiko , Arai Yoichi ,   Michinoku Japan Urological Cancer Study Group
Published: February 2017

87 Background: The adverse events of androgen deprivation therapy (ADT) are widely recognized, but ADT-induced alterations in lipid and glucose metabolism may be race-dependent. We prospectively recruited Japanese patients with newly diagnosed prostate cancer who underwent at least one year of ADT and examined changes in lipid and glucose metabolism in these patients. Methods: Patients with newly diagnosed prostate cancer were recruited between January 2011 and August 2012. Body weight, abdominal circumference, and blood testing results were recorded every three months, and visceral and subcutaneous fat were measured by computed tomography before and after one year of ADT. Results: One hundred three patients completed a one year course of ADT. Median age was 74 (range, 50 to 85). Thirty nine patients underwent ADT with luteinizing hormone-releasing hormone (LHRH) agonist monotherapy, while 64 patients underwent ADT with LH-RH agonist plus bicalutamide. Median prostate-specific antigen (PSA) before ADT was 16.7 ng/ml (range, 3.6-3316 ng/ml). Clinical stage was B (46.6%), C (28.2%), and D (25.2%). Mean increase in body weight, abdominal circumference and body mass index after one year of ADT was 3.8%, 4.1%, and 3.8%, respectively. Mean decrease of hemoglobin was 5.5%. Mean increase of total, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides was 9.0%, 10.8%, 5.0%, and 21.0%, respectively. Mean increase in fasting blood sugar and HbA1c was 4.6% and 1.7%, respectively. Changes in each variable from baseline to 0, 3, 6, 9, and 12 months was as follows: body weight, 0, 0.9, 2.7, 3.3, and 3.8%; hemoglobin, 0, 4.5, 3.7, 5.5, and 5.5%; total cholesterol, 0, 12.9, 11.4, 9.7, and 9.0%; triglycerides, 18, 26, 25, 21%; and HbA1c, 0, 2.1, 1.2, 1.2, and 1.7%. Increase of visceral and subcutaneous fat measured by computed tomography before and after one year of ADT was 32.4% and 35.4%, respectively. Conclusions: One year of ADT caused significant changes, especially in lipid metabolism, in Japanese patients with prostate cancer. Visceral and subcutaneous fat increased more than 30%. These changes were noticeable in the first half of the one year course of ADT. Appropriate monitoring and management of these patients is needed, because these changes might cause critical cardiovascular events. Clinical trial information: UMIN000004709.
A phase II study of 99mTc-trofolastat (MIP-1404) SPECT/CT to identify and localize prostate cancer in high-risk patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (EPLND) compared to histopathology: An interim analysis.
Authors: Slawin Kevin Mark , Ellis William J. , Tenke Peter , Joniau Steven , Alekseev Boris Y. , Buzogány Istvan , Mishugin Sergey , Klein Eric A. , Karnes R. Jeffrey , Scherr Douglas , Yuh Bertram E. , Jarrard David Frasier , Trabulsi Edouard John , Stolz Josef , Babich John , Youssoufian Hagop , Stambler Nancy , Armor Thomas , Israel Robert Joseph 
Published: February 2017

94 Background: Technetium (Tc99m) trofolastat (USANC) is a novel urea-based small molecule SPECT radiotracer with utility in imaging overexpression of PSMA in prostate cancer (PCa). Unlike earlier agents targeting PSMA, this ligand is rapidly internalized and retained in tumors. We conducted an open-label, multicenter phase 2 study in the US and Europe (NCT01667536). An interim analysis was performed at approximately 50% accrual. Methods: Patients (pts) with confirmed adenocarcinoma of the prostate scheduled for RP with EPLND at high risk for disease outside of the prostate gland were eligible. High risk pts were ≥cT3 or Kattan nomogram score ≥130. Within 30 days of screening, pts required a bone scan and pelvic MRI. After enrollment, pts received trofolastat followed by whole-body planar and SPECT/CT imaging 3 to 6 hrs later. Pts then underwent RP with EPLND within 21 days. SPECT/CT images were evaluated centrally by 3 readers blinded to clinical information and compared to on-site pathology assessments using a common scoring template. The primary endpoint was the ability of trofolastat to detect PCa within the gland. Secondary endpoints included detection of extent and location within the gland, pelvic lymph nodes and comparative performance against MRI. Results: 84 pts were enrolled to date from 16 centers. Interim data is available for 54 pts. A majority (≥2/3) of SPECT/CT readers correctly identified the presence or absence of primary PCa in 51/54 (94%, 85-98 95% CI) patients including 2 true-negative cases treated with neoadjuvant enzalutamide. Sensitivity and specificity were 94% (84-98 95% CI) and 100% (34-100 95% CI) respectively. Conclusions: Based on the interim data available, trofolastat has accurately detected primary prostate carcinoma within the gland with high sensitivity and specificity in high-risk pts prior to surgery. Updated results, analyses of secondary endpoints, pelvic lymph nodes, and comparative performance vs. MRI from this ongoing study will be presented. Clinical trial information: NCT01667536. [Table: see text]
Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040.
Authors: El-Khoueiry Anthony B. , Melero Ignacio , Crocenzi Todd S. , Welling Theodore Hobart , Yau Thomas Cheung , Yeo Winnie , Chopra Akhil , Grosso Joseph , Lang Lixin , Anderson Jeffrey , Dela Cruz Christine Marie , Sangro Bruno 
Published: February 2017

LBA101 Background: Overexpression of PD-L1 in HCC has a poor prognosis. Safety and preliminary antitumor efficacy of nivolumab, a fully human IgG4 monoclonal antibody PD-1 inhibitor, was evaluated in a multiple ascending-dose, phase I/II study in patients (pts) with HCC. Methods: Pts with histologically confirmed advanced HCC with Child-Pugh (CP) score ≤ B7 and progressive disease (PD) on, intolerant of, or refusing sorafenib were enrolled. Dose escalation occurred in parallel cohorts based on etiology: no active hepatitis virus infection or virus-infected HCC pts. Pts received nivolumab 0.1 – 10 mg/kg intravenously for up to two years. The primary endpoint was safety. Secondary endpoints included antitumor activity using mRECIST criteria, pharmacokinetics, and immunogenicity. Results: The study has enrolled 41 pts with a CP score of 5 (n = 35) or 6 (n = 6), ECOG score of 0 (n = 26) or 1 (n = 15), 73% with extrahepatic metastasis and/or portal vein invasion, and 77% with prior sorafenib use. Eighteen pts remain on study, and 23 discontinued treatment due to PD (n = 17), complete response (CR; n = 2), drug-related adverse events (AEs; n = 2) and non-drug–related AEs (n = 2). Drug-related AEs of any grade occurred in 29 pts (71%; 17% grade 3/4), with ≥ 10% of pts experiencing aspartate aminotransferase (AST) increase and rash (each 17%), alanine aminotransferase(ALT) and lipase increase (each 15%), and amylase increase (12%). Grade 3 and 4 AEs ≥ 5% were AST increase (12%), ALT increase (10%) and lipase increase (5%). A dose-limiting toxicity occurred in an uninfected pt at 10 mg/kg; no maximum tolerated dose was defined in any cohort. Response was evaluable in 39 pts: 2 CR (5%) and 7 partial responses (PR; 18%). Response duration was 14–17+ months for CR, < 1–8+ months for PR, and 1.5–17+ months for stable disease (SD). Overall survival (OS) rate at 6 months is 72%. Conclusions: Nivolumab has a manageable AE profile and produced durable responses across all dose levels and HCC cohorts, with a favorable 6-month OS rate. Updated safety, antitumor activity, and biomarker data will be presented. Clinical trial information: NCT01658878. [Table: see text]
GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma.
Authors: Sehn Laurie Helen , Chua Neil Sun , Mayer Jiri , Dueck Gregory Scott , Trněný Marek , Bouabdallah Kamal , Fowler Nathan Hale , Delwail Vincent , Press Oliver W. , Salles Gilles A. , Gribben John G. , Lennard Anne , Lugtenburg Pieternella J. , Franklin Natalie , Wassner Fritsch Elisabeth , Fingerle-Rowson Guenter , Cheson Bruce D. 
Published: February 2017

LBA8502 Background: Treatments are limited and outcomes poor in rituximab-refractory (Rit-Ref) iNHL. Bendamustine (B) has a 9 mo median PFS and 10 mo response duration in ph II trials. Obinutuzumab (GA101/Gazyva [G]) is a glycoengineered type II aCD20 mAb with activity and acceptable safety in Rit-Ref NHL. Methods: GADOLIN (NCT01059630) is a ph III open label study in pts with CD20+ Rit-Ref iNHL. In the B arm, pts received B 120 mg/m2 (d1+2, c1–6) alone; GB arm pts received B 90 mg/m2 (d1+2, c1–6) with G 1000 mg (d1, 8, 15 c1, d1 c2–6) for up to six 28d cycles. Non-PD GB pts then received G monotherapy every 2 mo for up to 2 yrs. Primary endpoint was PFS assessed by an independent radiology facility (IRF), with 80% power to detect 43% improvement in median PFS. Results: In the protocol specified interim analysis, 396 pts were randomized to receive B (n = 202 [198 treated]) or GB (n = 194). The IDMC recommended to unblind the study as the primary endpoint had been reached (4 Feb 2015). Baseline characteristics were balanced between arms. Median age was 63 yrs and pts had a median of 2 prior therapies. Median observation time was 20 mo (B) and 22 mo (GB). IRF-assessed median PFS was 14.9 mo (B) and not reached (NR) for GB (HR 0.55, 95% CI 0.4–0.74; p = 0.00011). Median investigator-assessed PFS was 14 mo for B and 29 mo for GB (HR 0.52, 95% CI 0.39–0.70; p < 0.0001). There were no significant differences in IRF-assessed ORR (63.0% B vs 69.1% GB) or CR (12.2% B vs 11.2% GB) at end of induction, in IRF-assessed best overall response up to 12 mo from start of treatment (76.6% B vs 78.6% GB), or in preliminary OS (median OS NR in either arm). In the treatment period, there were fewer Grade ≥ 3 adverse events with B than GB (62.1% B vs 68% GB), notably neutropenia (26.3% B vs 33.0% GB) and infusion-related reactions (3.5% B vs 8.8% GB), but more Grade ≥ 3 thrombocytopenia (16.2% B vs 10.8% GB), anemia (10.1% B vs 7.7% GB) and pneumonia (5.6% B vs 2.6% GB). Conclusions: G combined with B (90 mg/m2) followed by G maintenance significantly improved PFS vs B alone (120 mg/m2) in Rit-Ref iNHL. The clinically meaningful PFS improvement with GB is the first randomized evidence of benefit for a novel aCD20 mAb in Rit-Ref iNHL. Clinical trial information: NCT01059630.
Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius).
Authors: Lonial Sagar , Weiss Brendan M. , Usmani Saad Zafar , Singhal Seema , Chari Ajai , Bahlis Nizar J. , Belch Andrew , Krishnan Amrita Y. , Vescio Robert A. , Mateos María-Victoria , Mazumder Amitabha , Orlowski Robert Z. , Sutherland Heather J , Blade Joan , Scott Emma Catherine , Feng Huaibao , Khan Imran , Uhlar Clarissa M. , Ahmadi Tahamtan , Voorhees Peter Michael 
Published: February 2017

LBA8512 Background: DARA, a human anti-CD38 IgG1κ mAb, has single agent activity and is well-tolerated in rel/ref MM (Lokhorst HM et al. ASCO 2014). This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥ 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or double refractory to a PI and IMiD. Preliminary results are reported. Methods: MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw x 8 wk, q2w x 16 wk, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC). Results: Data for the 16 mg/kg DARA group are presented (n = 106). Baseline characteristics: median time since diagnosis, 4.8 y; median prior treatment lines, 5; 75% ISS ≥ 2. Refractory to: last line of therapy, 96%; last PI and IMiD, 95%; pomalidomide, 63%: carfilzomib, 48%; alkylating agents, 78%. Adverse events (AE; ≥ 20%) were fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during first infusion (grade 3 4.7%; no grade 4). No patients discontinued study due to IRRs; 5 (4.7%) discontinued treatment due to AEs. None of these AEs were assessed by the investigator to be DARA-related. ORR (IRC assessed) was 29.2%, with 3 sCR, 10 VGPR, and 18 PR with a 7.4 month median duration of response. ORR was consistent across clinically relevant subgroups. Median time to progression was 3.7 months. Median overall survival has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy. Conclusions: In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile. Clinical trial information: NCT01985126.
Mammographic imaging after partial breast reconstruction: Impact of a bioabsorbable breast implant.
Authors: Harms Steven , Lebovic Gail , Kaufman Cary Steven , Cross Michael 
Published: February 2017

111 Background: Marking the site of the excised tumor bed during partial mastectomy is critical for radiation targeting and surveillance for breast cancer recurrence. However, delineating the lumpectomy cavity margins is challenging, and dense fibrosis and scarring often present obstacles when reviewing post-operative mammograms for signs of early recurrence. To determine whether implantation of a "mini" breast implant used for partial breast reconstruction adversely affected post-operative breast imaging, we reviewed clinical imaging of 100 patients that had been implanted with a new bioabsorbable breast implant over a three year period. Methods: Following informed consent, 110 patients were implanted at the time of partial mastectomy with a bioabsorbable implant with a primary purpose of marking the surgical site of tumor excision for radiotherapy. In each case, the surgeon sutured the implant into the cavity at the location believed to be at greatest risk for recurrence. Implants were used for partial breast reconstruction, a guide for radiation treatment planning and routine mammographic follow-up. Mammograms were reviewed for implant visibility, presence of artifacts and other diagnostic criteria. Results: In all cases the implant was rated as easily visible on mammography and CT without appreciable artifact or interference with diagnostic capabilities. In addition, there was notably less dense fibrotic tissue visualized on mammographic imaging at the tumor excision site containing the implant. In some cases, the marker clips coalesced in the center of the surgical cavity. The marker was also seen on US and MRI during routine follow-up. Conclusions: Mammographic imaging in patients implanted with this new device was not adversely affected by its presence. The implant visually assisted with verification of the excised tumor bed without introducing any artifact or diagnostic interference and there was notable in-growth of normal breast tissue clearly seen on mammography. In this group of patients there were no abnormal calcifications in or around the implant and there were no recurrent cancers detected within this 36 month period.
Predictive and prognostic value of tumor-infiltrating lymphocytes in breast cancer treated with neoadjuvant chemotherapy.
Authors: Matsumoto Akiko , Jinno Hiromitsu , Hiraiwa Kunihiko , Nakamura Tetsuya , Saito Junichi 
Published: February 2017

128 Background: The prognostic importance of tumor-infiltrating lymphocytes (TILs) in triple-negative (TN) and HER2-positive breast cancer has been suggested in recent trials. The aim of this study is to evaluate a relationship between TILs and response to neoadjuvant chemotherapy (NAC) as well as long-term outcome in breast cancer including luminal, TN and HER2 subtypes. Methods: Twenty-seven patients receiving NAC from January 2010 to March 2015 at Inagi Municipal Hospital were analyzed. Intratumoral lymphocytes (ItuLy) and stromal lymphocytes (StrLy) were evaluated in hematoxylin and eosin-stained sections from pretherapeutic core needle biopsies. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors with > 50% of ItuLy or StrLy. Results: A total of 27 patients were divided into 13 luminal (48.1%), 3 TN (11.1%) and 11 HER2 (40.7%) subtypes. The median age was 58 years and the median tumor size was 3.0 cm. A significant correlation between ItuLy (the median percentage: 5%) and StrLy (25%) was observed (Pearson correlation coefficient = 0.628, P< 0.01). LPBC comprised 29.6% (8/27) of total population, with higher frequencies of 33.3% and 54.5% in the TN and HER2-positive subtypes, when compared with 7.7% in luminal subtype (P= 0.044). LPBC group had a significantly higher pathological complete response (pCR) rate of 62.5% (5/8), compared with 5.3% (1/19) for non-LPBC group (P= 0.004). LPBC showed the modest correlation with pCR in luminal (100% (1/1) vs. 0% (0/12), P= 0.077) and HER2-positive subtypes (66.6% (4/6) vs. 25% (1/5), P= 0.175). In TN subtype, neither LPBC nor non-LPBC showed pCR. After a median follow-up of 24.3 months, patients with any TILs were significantly associated with better disease-free survival (DFS) than those without TILs (24.3 vs. 23.6 months, P= 0.016). The most significant impact of TILs on DFS was observed in HER2-positive subtype (23.2 vs. 15.2 months, P= 0.046), whereas TILs did not associate with DFS in luminal and TN subtypes. Conclusions: The presence of TILs was a significant predictor for response to NAC and would provide useful information of prognosis in breast cancer.