bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing magnetic resonance imaging/ultrasound-fusion biopsy and systemic 12-core transrectal ultrasound biopsy for whole gland pathology.
Authors: Su Daniel , George Arvin , Siddiqui Minhaj , Rais-Bahrami Soroush , Stamatakis Lambros , Hong Cheng William , Rothwax Jason , Okoro Chinonyerem , Raskolnikov Dima , Shakir Nabeel , Walton-Diaz Annerleim , Simon Richard , Turkbey Baris , Wood Bradford J. , Choyke Peter L. , Pinto Peter A. 
Published: February 2017

84 Background: Historically, pathologic findings from standard 12-core prostate biopsies are upgraded in 25 to 33% of patients after radical prostatectomy (RP). MRI/US fusion prostate biopsy has been shown to upgrade prostate cancer compared to standard 12-core biopsy in 32% of patients. MRI/US fusion biopsy may offer a more accurate representation of whole gland pathology. We evaluate the rate of pathologic upgrade in standard 12-core biopsy and MRI/US fusion biopsy when compared with whole gland pathology from RP. Methods: Patients who underwent random prostate biopsy, fusion biopsy and subsequently RP for prostate cancer from 2012 to 2013 were included. Pathology was reviewed by a single pathologist. The cohort was divided into clinically significant high-grade (Gleason score 4+3 or higher) and clinically insignificant low-grade (Gleason score 3+4 or lower) sub cohorts. Pathological upgrade was defined as any increase in Gleason sum or primary Gleason score. McNemar’s test was used to compare the proportion of patients who were upgraded from random biopsy to RP versus the proportion that were upgraded from fusion biopsy to RP. Results: Sixty eight patients underwent 12-core and fusion prostate biopsy then subsequently RP. Mean prostate-specific antigen was 9.2ng/ml. There are total of 43 patients with clinically insignificant low-grade and 25 patients with clinically significant high-grade. Fusion biopsy upgraded 19 patients (28%) compared to 12-core biopsy, eight of these patients had negative 12-core biopsy. Pathology on the RP specimen upgraded 18 of the 12-core results (26%) compare to only eight fusion biopsy results (11%). (p =0.0095) 14 patients (20%) who had clinically insignificant low-grade disease on 12-core biopsy were upgraded to clinically significant high-grade on RP. Only two patients (3%) with clinically insignificant low-grade from fusion biopsy were upgraded on RP. (p< 0.0005) Conclusions: Prostate cancer detected on MRI/US fusion prostate biopsy has significantly lower rates of pathologic upgrade than standard 12-core biopsy when both were compared to prostatectomy specimens. MRI/US fusion biopsy may represent whole gland pathology more accurately compared to 12-core biopsy.
Elective versus therapeutic neck dissection in the clinically node negative early oral cancer: A randomised control trial (RCT).
Authors: D'Cruz Anil , Dandekar Mitali , Vaish Richa , Arya Supreeta , Pantvaidya Gouri , Chaturvedi Pankaj , Chaukar Devendra , Pai P. S. , Deshmukh Anuja , Kane Shubhada , Nair Deepa , Nair Sudhir Vasudevan , Patil Asawari , Hawaldar Rohini W , Dhopeshwarkar Manasi , Agarwal Jaiprakash 
Published: February 2017

LBA3 Background: Management of the neck in early oral cancers has been a matter of debate with clinical equipoise between elective (END) or therapeutic neck dissection (TND). Methods: This is a prospective phase III RCT (NCT00193765) to test the superiority of END at the time of primary surgery over TND (neck dissection at the time of nodal relapse) in patients with lateralized T1 or T2 squamous carcinoma of oral cavity, amenable to peroral excision. Patients were stratified based on size, site, sex and preoperative neck ultrasound. The primary end point was overall survival (OS) and secondary end point was disease-free survival (DFS). The trial was planned to demonstrate a 10% superiority (1-sided α = 0.05 and β = 0.2) in OS for END vs. TND, assuming 60% 5-year OS in TND arm, with a planned sample size of 710. Results: This trial was terminated after 596 patients were randomized between January 2004 and June 2014. An interim intent-to-treat analysis of initial 500 patients (255 in TND, 245 END) with a minimum follow-up of 9 months was performed as mandated by Data and Safety Monitoring Committee based on the number of observed deaths in each arm. Both arms were balanced for site and stage. There were 427 tongue, 68 buccal mucosa and 5 floor of mouth tumors; 221 were TI and 279 T2. At a median follow-up of 39 months there were 146 recurrences in TND and 81 in END arms respectively. The 3-year OS was significantly higher in END compared to TND arm (80.0% vs. 67.5%, HR = 0.63, 95%CI 0.44-0.89, p = 0.01) as was 3-year DFS (69.5% vs. 45.9%, HR = 0.44, 95%CI 0.34-0.58, p < 0.001). After adjusting for stratification factors in Cox regression, END continued to be significantly superior to TND for both OS and DFS. Conclusions: There were 8 excess deaths for every 15 excess recurrences in the TND arm. Elective neck dissection in patients with early oral SCC results in 37% reduction in mortality and should be considered the standard of care. Clinical trial information: NCT00193765.
PALOMA3: A double-blind, phase III trial of fulvestrant with or without palbociclib in pre- and post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy.
Authors: Turner Nicholas C. , Ro Jungsil , Andre Fabrice , Loi Sherene , Verma Sunil , Iwata Hiroji , Harbeck Nadia , Loibl Sibylle , Bartlett Cynthia Huang , Zhang Ke , Giorgetti Carla , Randolph Sophia , Koehler Maria , Cristofanilli Massimo 
Published: February 2017

LBA502 Background: The growth of hormone receptor (HR) positive breast cancer (BC) is dependent on the cyclin dependent kinases CDK4/6, that promote G1-S phase cell cycle progression. Resistance to endocrine treatment remains a major clinical problem for patients with hormone receptor positive breast cancer. The PALOMA3 study assessed the efficacy of palbociclib and fulvestrant in endocrine-resistant advanced breast cancer. Methods: In this double-blind phase 3 study women with HR positive/HER2 negative advanced metastatic BC whose cancer had relapsed or progressed on prior endocrine therapy, were randomized 2:1 to palbociclib (Palbo, 125 mg/d orally for 3 wk followed by 1 wk off) and fulvestrant (F, 500 mg per standard of care) or placebo (PLB) and F. Pre- and peri-menopausal women also received goserelin. One previous line of chemotherapy for metastatic disease was permitted. The primary endpoint was investigator assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), response assessment, patient-reported outcomes, and safety and tolerability. A pre-planned interim analysis was performed after 195 PFS events by an independent data monitoring committee. Results: 521 pts were randomized, 347 to receive Palbo+F and 174 to PLB+F. Baseline characteristics were well balanced. The median age was 57 and 56 years, 79% were post-menopausal, 60% had visceral disease, and 79% were sensitive to prior endocrine therapy. Prior therapy included chemotherapy for advanced disease in 33% of pts. At the time of the interim analysis the study met the primary endpoint, median PFS was 9.2 months for Palbo+F and 3.8 months for PLB+F (HR 0.422, 95% CI 0.318 to 0.560, P<0.000001). Consistent benefit from Palbo was seen in pre- and post-menopausal women. The most common adverse effects Palbo+F versus PLB+F were neutropenia (78.8% vs. 3.5%), leucopenia (45.5% vs. 4.1%), and fatigue (38.0% vs. 26.7%). Febrile neutropenia was reported in 0.6% pts on Palbo+F and 0.6% pts on PLB+F. The discontinuation rate due to adverse events was 2.0% on Palbo and 1.7% on PLB. Conclusions: Palbociclib combined with fulvestrant improved progression free survival in hormone receptor positive advanced breast cancer that had progressed on prior endocrine therapy, and can be considered as a treatment option for these patients. Clinical trial information: NCT01942135.
Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort.
Authors: Seiwert Tanguy Y. , Haddad Robert I. , Gupta Shilpa , Mehra Ranee , Tahara Makoto , Berger Raanan , Lee Se-Hoon , Burtness Barbara , Le Dung T. , Heath Karl , Blum Amy , Dolled-Filhart Marisa , Emancipator Kenneth , Pathiraja Kumudu , Cheng Jonathan D. , Chow Laura Q. 
Published: February 2017

LBA6008 Background: Pembrolizumab (MK-3475) is a humanized monoclonal antibody that blocks interaction of PD-1 with its ligands, PD-L1 and PD-L2, thereby promoting activity of tumor-specific effector T cells. KEYNOTE 012 (NCT01848834) had previously demonstrated clinical activity of pembrolizumab 10 mg/kg every 2 weeks in patients (pts) with recurrent/metastatic SCCHN enriched for PD-L1–positive tumors with a response rate of 20%. We now report on the larger SCCHN expansion cohort of KEYNOTE 012, irrespective of biomarker status using a 3-weekly fixed dose. Methods: Pts with advanced SCCHN irrespective of PD-L1 expression or HPV status received a fixed dose of 200 mg pembrolizumab, intravenously, every 3 weeks. Pts were evaluated every 8 weeks with radiographic imaging. The primary end point was overall response rate (ORR) per investigator assessment (RECIST 1.1). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were assessed according to CTCAE v4. PD-L1 was assessed retrospectively by immunohistochemistry. Results: 132 pts with recurrent/metastatic SCCHN were enrolled. Mean (SD) age was 58.9 (9.7) years; 83.3% were male; 56.8% had ≥ 2 lines of therapy for recurrent disease. 73/132 pts (55.3%) remain on treatment. Out of 132 treated pts, 99 pts were available for this preliminary efficacy analysis with a post-baseline scan or discontinued therapy prior to the scan due to clinical progression or AE. ORR (confirmed and unconfirmed) per RECIST 1.1 was 18.2% (95% CI, 11.1-27.2) with 18 partial responses and 31.3% with stable disease. Biomarker analysis is ongoing and results will be presented. Drug-related AEs of any grade occurred in 47% of all enrolled pts, and drug-related grade ≥ 3 AEs occurred in 7.6%. The most common drug-related AEs ( ≥ 5%) of any grade were fatigue (12.1%), decreased appetite (6.8%), pyrexia (6.1%), and rash (5.3%). Conclusions: Pembrolizumab given at a fixed dose of 200 mg every 3 weeks was well tolerated and demonstrated a clinically meaningful ORR of 18.2% in pts with recurrent/metastatic SCCHN. Clinical trial information: NCT01848834.
Results of the PERSIST-1 phase III study of pacritinib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF).
Authors: Mesa Ruben A. , Egyed Miklos , Szoke Anita , Suvorov Aleksandr , Perkins Andrew , Mayer Jiri , Ganly Peter , Jourdan Eric , Schouten Harry C. , Tosi Patrizia , Farber Charles Michael , Zachee Pierre , Scheid Christof , Dean James P. , Cernohous Paul , Nangalia Jyoti , Kiladjian Jean-Jacques , Vannucchi Alessandro M. , Mead Adam , Harrison Claire N. 
Published: February 2017

LBA7006 Background: PAC is a potent JAK2 inhibitor without significant JAK1 inhibition with minimal myelosuppression in early-phase studies in MF. Methods: The efficacy and safety of daily oral PAC was compared to BAT (2:1 randomization stratified for risk and platelet count). The 10 endpoint was the proportion of ITT patients (pts) achieving ≥ 35% spleen volume reduction (SVR) at week (wk) 24 by centrally reviewed MRI or CT. Secondary endpoints included the proportion achieving ≥ 50% reduction in total symptom score (TSS) at wk 24 using the MPN Symptom Assessment Form. Results: Patients:327 were enrolled (PAC:220, BAT:107), 62% with 10 MF. Median time from diagnosis was 1.12 years (PAC 0.99, BAT 1.60): 32% and 15% had a platelet counts < 100,000/µL or <50,000/ µL; 75% were JAK2V617F positive. Efficacy: The median duration of treatment was 16.2 months PAC and 5.9 months BAT. Sixty-two percent of BAT patients received active disease directed therapy. The SVR rates at week 24 were 19.1% for PAC vs. 4.7% for BAT (p=0.0003) in ITT and 25% vs. 5.9% (p=0.0001) in the evaluable population. 79% of BAT patients crossed over to PAC; 21% had achieved a >35% reduction in spleen volume at data cutoff. TSS composite V1 + V2 response rates were 24.5%for PAC vs. 6.5% for BAT (p<0.0001) by ITT, and were 40.9% vs. 9.9% in evaluable pts (p<0.0001). Efficacy with baseline cytopenias: In pts with <100,000 and <50,000 platelets/μ/L, the SVR rates were 16.7% for PAC vs. 0% for BAT (p=0.009), and 22.9% vs. 0% (p=0.045) by ITT and 23.5% vs. 0% (p=0.007) and 33.3% vs. 0% (p=0.037) in evaluable pts. In RBC transfusion dependent pts, 25.7% of PAC pts became RBC independent vs. 0% of BAT pts (p=0.043). Safety: The most common adverse events (AE) for PAC were diarrhea, nausea, and vomiting; (grade 3 were <5%, <1%, <1% respectively). Hematologic AEs were similar between PAC and BAT. Conclusions: This study demonstrated PAC was well tolerated and induced significant and sustained SVR and symptom control even in patients with severe thrombocytopenia. PAC therapy resulted in RBC transfusion independence in a significant proportion of pts. Clinical trial information: NCT01773187.
Biological indicators of response and resistance to PARP inhibition in BRCA wild-type breast cancer.
Authors: Hassan Saima Noor , Esch Amanda , Heiser Laura , Gray Joe W. 
Published: February 2017

125 Background: Although PARP inhibitors are currently being tested in clinical trials in breast cancer patients, it is not well understood which subgroup of patients will best respond to such therapy or how to combine anti-PARP therapy to improve therapeutic response. Methods: We assessed the response of a panel of 8 HER2-negative breast cancer cell lines against three PARP inhibitors: veliparib, olaparib, and BMN 673. Efficacy of carboplatin as a single agent and in combination with PARP inhibitors was determined. Therapeutic response and cellular phenotype were elucidated using live-cell imaging, high-content imaging and immunofluorescence. We computed IC50 as the measure of sensitivity to each PARP inhibitor across the panel of cell lines. Cellular phenotype was ascertained by quantifying endpoints for apoptosis and DNA damage. Results: BMN 673 demonstrated the highest potency, with IC50 values in the nanomolar range, while the IC50 values of olaparib and veliparib were in the micromolar range. Drug sensitivity was independent of BRCA mutational status. Biomarkers of apoptosis and DNA damage varied with the PARP inhibitor and across different cell lines. The resistant cell lines could be classified into two groups that varied in DNA damage response and cell death due to DNA damage. A combined DNA damage – cell death (DDD) Response Score was developed and correlated strongly with IC50 values in BRCA wild-type breast cancer cell lines. The DDD Response Score identified cell lines that were highly sensitive to single-agent PARP inhibitors or carboplatin. A Response Score that identified intermediate sensitivity may predict which cell lines may benefit from the combination of anti-PARP therapy and carboplatin. Conclusions: Overall, a spectrum of response to three different PARP inhibitors was identified in a panel of eight breast cancer lines. Cellular phenotype can help classify resistant cancer cell lines. We have developed an experimental approach that may help to inform which breast cancer subtypes may benefit from PARP inhibitors and carboplatin, both as single agents, and in combination.
Delta 32 mutation in CCR5 gene and its association with breast cancer.
Authors: Azhar Abid , Fatima Faria , Hameed Abdul , Saleem Saima 
Published: February 2017

17 Background: Chemokine C-C motif receptor type 5 (CCR5) is a chemokine receptor protein, which is present on the cell surface. Its potential role in cancer progression and metastasis has been implicated. Deletion mutation of 32 base pairs (bp) in the open reading frame of the CCR5 gene (CCR5Δ32) may lead to the malformation of the protein. This study aimed to examine the role of CCR5Δ32 mutation and its association with breast cancer. Methods: Blood samples of 500 breast cancer patients were included in the study. The samples were compared with age and sex matched healthy controls. Mutation of CCR5Δ32 was analyzed by sequence specific primers by polymerase chain reaction (PCR). They were examined on agarose gel electrophoresis. Statistical analyses were performed using software SPSS 17.0 (Chicago, IL., USA). The genotypic frequencies of patients and controls were tested by applying the chi‐square test. Results: Two types of CCR5 allelic mutations were found in the breast cancer samples. The mutation was of a 32 (bp) DNA fragment. Homozygous insertion (I/I) and heterozygous deletion (I/D) was found in the open reading frame of the regulatory region of the gene. The chi square analyses showed significant positive association between I/I and I/D allele in breast can patients with CCR5 delta 32 mutation (χ2 15.07, p < 0.01). Conclusions: This deletion in the promoter region of the CCR5 gene produces a non-functional receptor which may increase inflammation, leading to the enhanced progression of tumor.
Aromatase inhibitors and the risk of contralateral breast cancer in BRCA mutation carriers.
Authors: Nemati Shafaee Maryam , Gutierrez-Barrera Angelica M. , Lin Heather Y. , Arun Banu 
Published: February 2017

3 Background: Contralateral breast cancer (CBC) risk in BRCA1 & 2 mutations is up to 64%. Patients (pts) with estrogen receptor positive (ER+) breast cancer (BC) are offered tamoxifen (TAM) or Aromase inhibitors (AI) adjuvantly. Reports suggest that TAM may reduce the risk of CBC in BRCA mutation; however there is no such data on the effect of AIs. Here, we evaluate the effect of TAM and AI as potential CBC risk reducers in a cohort of women with known BRCA status. Methods: 1043 BC pts receiving genetic counseling and BRCA testing were included. 13 had metastasis, 168 had a variant BRCA, and 50 had synchronous BC, and were excluded. Of the 812 remaining pts, 153 had a deleterious BRCA 1 or 2 mutations. Pts were followed from the diagnosis of BC until CBC, death, or last follow-up. The study had IRB approval. Univariate analyses were performed to test the significance of each variable in relation to BRCA status using chi-square tests for categorical variables and t tests for continuous variables. Results: The median age at diagnosis of BC was 42.3 years (range: 21-84). Median follow up was 8.6 years. 86% (700) had ER+ tumors, 80% were diagnosed with T1-2, and 81% had N0-N1. 76% (622) received TAM, and 37% (304) received AI. A total of 68 (8.7%) CBCs occurred of which 14% (21/153) occurred in BRCA carriers vs 7% (47/659) in BRCA non-carriers. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC. Specifically, compared with BRCA negative, pts with BRCA1+ or BRCA2+ had larger hazard of developing CBC, Hazard Ratio (HR) (95% confidence interval (CI)) = 2.49 (1.21, 5.10), p = 0.013 for BRCA1+ vs Negative. HR (95%CI) = 1.97 (1.05, 3.73), p = 0.036 for BRCA2+ vs Negative. Compared to pts who did not receive AI, those who received AI had smaller hazard of developing CBC, HR (95%CI) = 0.42 (0.22, 0.81), p = 0.01. The interaction between AI and BRCA status was not significant (p = 0.4), hence all pts benefited from AI use in terms of CBC risk reduction. TAM use did not show significant effect on the risk of CBC in univariate and multivariate analyses (p > 0.13). Conclusions: This is the first report showing that AIs can reduce risk of CBC in women with BC who have a BRCA mutation. This finding should be validated in larger independent cohorts.
Predictors of chemotherapy-induced peripheral neuropathy among breast cancer patients treated with taxanes.
Authors: Candelario Nellowe , Wongrakpanich Supakanya , Morginstin Mark S. 
Published: February 2017

90 Background: Breast cancer is one of the most common types of cancer. Taxanes are used to treat both early and metastatic breast cancer. Chemotherapy-induced peripheral neuropathy (CIPN) is its most common dose-limiting side effect that is debilitating and that could alter the treatment outcomes. This study aims to assess the predictors in the development and severity of CIPN. Methods: A retrospective review of 229 breast cancer patients was done to identify if age, BMI, race, smoking history, alcohol use, diabetes, chronic kidney disease (CKD), estrogen (ER), progesterone receptor (PR) and HER2 status, type and dose of taxane were predictors in the development and severity of CIPN. Patients who had incomplete data and baseline neuropathy were excluded from the study. Severity of peripheral neuropathy was graded from 1 to 4. Pearson Chi-square and T-test were done to determine the presence of statistical difference in the development and severity of CIPN among the above predictors. Odds ratio was computed using logistic regression analysis. Results: Among the 229 patients in this study, 158 (69%) developed neuropathy, 90 (57%) of whom had grade 1 neuropathy. Majority of the subjects in this study were African American (75.1%). Age, BMI, race, smoking, alcohol use, CKD and diabetes did not show any statistical significance as predictors of development and severity of CIPN (p > 0.05). Patients with ER+/PR- and ER+/PR+ had lower odds of developing neuropathy with OR 0.36 (p = 0.006) and 0.44 (p = 0.026) respectively. HER2 positivity was associated with higher chances of neuropathy (OR 2.11, p = 0.028). Paclitaxel was associated with higher chances of neuropathy compared to docetaxel (OR 2.89, p = 0.02). Dose of paclitaxel did not show any difference in the occurrence of CIPN. Those treated with paclitaxel had more severe neuropathy (p = 0.04). Conclusions: Positive ER and PR receptors have lower chances of developing CIPN. HER2 positivity is a predictor in the development of neuropathy. Paclitaxel is more neurotoxic than docetaxel. Age, race, BMI, smoking, alcohol use, diabetes and CKD were not predictors in the development and severity of CIPN.