bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations of circulating KRAS amount as a biomarker to monitor chemotherapy response in pancreatic cancer.
Authors: Del Re Marzia , Vivaldi Caterina , Rofi Eleonora , Vasile Enrico , Miccoli Mario , Fornaro Lorenzo , Restante Giuliana , Crucitta Stefania , Caparello Chiara , D'arienzo Paolo Davide , Falcone Alfredo , Danesi Romano 
Published: September 2018

e15794 Background: Current treatment of pancreatic ductal adenocarcinoma (PDAC) is FOLFIRINOX or gemcitabine + nab-paclitaxel, and CA19-9 is the only approved biomarker to monitor tumor response. However, CA19-9 has several limitations (i.e. sensitivity and specificity), highlighting the need for new biomarkers. Being the majority of PDAC (75-95%) KRAS mutated (mutKRAS), the present study developed an analysis tool based on circulating tumor DNA (ctDNA) to monitor the variation of mutKRAS in PDAC undergoing first-line chemotherapy. Early variation of ctDNA mutKRAS after 15 days of treatment was correlated with response to therapy. Methods: Three ml of plasma were collected from patients with PDAC undergoing first-line FOLFIRINOX or gemcitabine + nab-paclitaxel. Patients underwent standard disease evaluation by imaging according to RECIST 1.1 criteria. Blood samples were drawn prior to cycle 1, after 14 days and at each radiological evaluation. ctDNA was extracted using a QIAmp Circulating nucleic acid Kit (Qiagen, Valencia, CA) and the KRAS codon 12 and p.G13D analysis was performed by digital droplet PCR (ddPCR, BioRad, Hercules, CA). Results: A total of 27 patients with locally advanced (15%) and metastatic (85%) PDAC were included in this study. mutKRAS in ctDNA was detected in 19 patients (70.3%) at baseline. There were no statistically significant differences in median PFS and OS in patients with baseline positive or negative ctDNA mutKRAS (p = 0.15). However, there was a statistically significant difference in PFS and OS between patients with increase vs. stability/reduction of ctDNA at the 14 day-evaluation (median PFS: 2.5 vs 7.5 months, p = 0.03; median OS: 9 vs 11.5 months p = 0.009). The imaging evaluation performed at 2 months after initiation of therapy demonstrated that all patients with an increase in ctDNA at 14 days had radiological progression of disease. Conclusions: The results of this pilot study support the use of ctDNA as a new marker for monitoring treatment outcome and disease progression in PDAC, suggesting that ctDNA mutKRAS is a non-invasive predictive factor of response in PDAC.
The prognostic value of baseline neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for predicting clinical outcome in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan (nal-IRI; MM-398) + 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV.
Authors: Wang-Gillam Andrea , Chen Li-Tzong , Li Chung-Pin , Bodoky Gyorgy , Dean Andrew , Lee Kyung-Hun , Cunningham David , Hubner Richard , Braiteh Fadi S. , Pipas J. Marc , Belanger Bruce , de Jong Floris A. , Mody Purvi D. , Von Hoff Daniel D. , Siveke Jens T. 
Published: September 2018

e15795 Background: Increased NLR and PLR have been associated with poor survival in several malignancies. Here we report the association of NLR and PLR with overall survival (OS) and progression-free survival (PFS) in the NAPOLI-1 trial (NCT01494506), which evaluated nal-IRI+5-FU/LV for the treatment of mPDAC patients (pts) after disease progression following gemcitabine-based therapy. Methods: Pts missing baseline NLR/PLR data were excluded. Medians reflect Kaplan-Meier estimates; hazard ratios (HRs) reflect Cox regression analysis. P values in this exploratory analysis are descriptive. Results: Of 116 evaluable pts in the nal-IRI+5-FU/LV arm, 82 (71%) had NLR ≤5 and 44 (38%) had PLR ≤150 (data cutoff: Nov 16, 2015). Of 105 evaluable pts in the 5-FU/LV control arm, 73 (70%) had NLR ≤5 and 36 (34%) had PLR ≤150. In pts with baseline NLR ≤5 or PLR ≤150, median OS and PFS were significantly longer in the nal-IRI+5-FU/LV treatment arm vs the 5-FU/LV control arm (Table). In pts with baseline NLR >5 or PLR >150, median OS and PFS were numerically longer in the treatment vs control arm, but differences were less compelling (95% CIs for HRs included 1). Conclusions: Median OS and PFS were improved with nal-IRI+5-FU/LV vs 5-FU/LV in pts with baseline NLR ≤5 or PLR ≤150. This exploratory analysis extends the prognostic significance of NLR and PLR to the post-gemcitabine setting. Clinical trial information: NCT01494506. [Table: see text]
Decision dissonance/alignment scale to promote patient-centered decisions about urinary diversion with cystectomy for bladder cancer.
Authors: Gilbert Scott Michael , Leo Michael C , Wendel Christopher , Krouse Robert S. , Grant Marcia , Danforth Kim N. , Kwan Marilyn L. , Harrison Teresa , Bulkley Joanna E , McMullen Carmit K. 
Published: September 2018

e16010 Background: The choice of urinary diversion (UD) with cystectomy is an opportunity to provide preference-driven care. We adapted a decision dissonance scale to measure concordance of patient goals with choice of ileal conduit (IC) vs. neobladder (NB) UD. Methods: With patient and clinician input, we identified 6 IC- and 4 NB-aligned goals, each rated on an 11-point scale (0 = not at all important to 10 = very important). Kaiser Permanente members rated the importance of these goals in a comprehensive survey mailed 6 months post-op (71% response rate (269/381)). Excluding respondents (n=93) with contraindications to NB and missing data on goals, we examined structural validity with principal axis factor analysis and convergent validity using correlations with other decision-making measures. Results: Items aligned to IC vs. NB factored separately as hypothesized (Table 1). NB patients prioritized (p<.05) NB-aligned goals (M=8.8, SD=1.8) over NB-dissonant goals (M=4.3, SD=2.4). IC patients’ alignment (M=5.4, SD=2.7) and dissonance (M=5.6, SD=2.1) ratings were similar. Dissonance was negatively correlated with informed decision-making (r=-.27) and satisfaction with care (r=-.21), and positively correlated with decision regret (r=.28) (each p<.01), but not correlated with shared decision making or decision style preference. Alignment was not significantly correlated with decision-making measures. Conclusions: Our measure distinguished patient values that could guide shared decision-making about UD choice. Patients who chose a NB had strong preferences for maintaining body integrity and function. [Table: see text]
Combined FDG and NaF PET/CT study in patients (pts) with metastatic genitourinary tumors (mGU) treated with cabozantinib + nivolumab +/- ipilimumab (CaboNivo+/-Ipi).
Authors: Lin Jeffrey , Mortazavi Amir , Stein Mark N. , Pal Sumanta K. , Davarpanah Nicole N. , Nadal Rosa Maria , Francis Deneise C , Berniger Marilise Anne , Monk Paul , Kempf Jeffrey , Becker Murray , Sokol Levi , McKinney Yolanda , Knopp Michael V. , Wright Chadwick , Jung Alex , Choyke Peter L. , Mena Esther , Lindenberg Liza , Apolo Andrea B. 
Published: September 2018

e16017 Background: The primary objective of the study is to assess the feasibility of obtaining combined FDG and NaF PET/CT in detecting soft-tissue and bone metastatic disease in mGU pts treated with CaboNivo+/-Ipi. Methods: Pts in this single-arm, multicenter, phase I trial had FDG PET/CT followed by NaF PET/CT within 1 hour, at baseline and 8 weeks. The number and location of metastatic lesions on FDG PET/CT and on NaF PET/CT were captured. Lesions were considered positive when there was focal abnormal radiotracer uptake with CT correlation. We analyzed soft tissue and bone lesions distribution and the concordance of baseline metastatic bone disease. Results: From 7/14/15 to 9/9/16, 27 pts (urothelial carcinoma N = 11, bladder squamous cell carcinoma N = 2, sarcomatoid renal cancer N = 1, sertoli cell N = 1, germ cell tumor N = 4, trophoblastic testicular cancer N = 1, urachal N = 4, castrate-resistant prostate cancer N = 2, prostate neuroendocrine N = 1) had scans. Median age was 55 (range 35-75 yr), 24 (89%) were male. Pts completed the dual PET/CTs on the same day (imaging time 3-4 hours) without complications. On FDG, the distribution of 340 lesions were lymph node 41%, bone 35%, lung 18%, liver 11%, soft tissue 4%, kidney 0.6%, adrenal 0.3%, spleen 0.3%, pancreas 0.3%. On NaF, the distribution of 130 lesions was spine 33%, rib 16%, pelvis 13%, femur 10%, scapula 9%, sacrum 8%, skull 5%, humerus 4%, sternum 3%, manubrium 2%, clavicle 2%. Of the 130 lesions on FDG/NaF PET/CT, 38% were not seen on initial FDG. The combination of the two tracers did not affect the quality of the PET/CTs given distinct radiotracer uptake in the anatomical locations with no distortions. Residual FDG activity on combined FDG-NaF images required background intensity to be adjusted to delineate focal radiotracer uptake. There was no difficulty in identifying metastatic lesions, and no instances of prior FDG uptake affecting the determination of metastatic disease. Conclusions: Combination FDG-NaF PET/CT is a feasible imaging modality that offers convenience to pts without compromising detection of metastatic disease in mGU pts. FDG alone detected fewer bone lesions than combined FDG-NaF PET/CT. Clinical trial information: NCT02496208.
Molecular features underlying response to neoadjuvant gemcitabine, cisplatin, and sorafenib (S-GC) in muscle-invasive urothelial bladder carcinoma (MIBC): Insights for trials of new agents combined with chemotherapy in the field.
Authors: Necchi Andrea , Raggi Daniele , Busico Adele , De Cecco Loris , Giannatempo Patrizia , Nicolai Nicola , Piva Luigi , Biasoni Davide , Catanzaro Mario , Torelli Tullio , Stagni Silvia , Calareso Giuseppina , Togliardi Elena , Colecchia Maurizio , Mariani Luigi , Salvioni Roberto , Paoli Alessandro , Daidone Maria Grazia , Sensi Marialuisa , Perrone Federica 
Published: September 2018

e16018 Background: S-GC neoadjuvant chemotherapy (NACT) was active in a phase 2 trial in MIBC, showing a response rate (downstaging to pT < 2) of 54.3% in 46 pts within a single-arm, phase 2 trial ( Necchi et al, GU ASCO 2017). The addition of S to GC may help investigators unravelling key molecular features underlying response in MIBC. Methods: Analyses were made on pre- and post-treatment TURB and cystectomy (Cy) specimens (10µm sections) and matched germline DNA of 29/46 pts. Analyses included measurements of ERCC1 (by immunohistochemistry, IHC) on TURB specimens, baseline circulating VEGF levels (ELISA), copy number variations (CNV, Affymetrix), and next generation sequencing (NGS, custom gene panels through the Ion AmpliSeq Library Kit2.0™ and the Ion Torrent Personal Genome Machine™ platform). Results: We analyzed TURB samples from 15 responders (R) and 4 non-R (NR). An additional 10 Cy samples were used for NR. Baseline VEGF levels were not associated with PFS or OS on univariable analyses (p = 0.943 and p = 0.669, respectively). Differences in R vs. NR pts were found according to CNVs and NGS. CN gains on regions of chromosome (chr) 18 and 20 and loss in chr 5 were found in 56-60% of R and in none of the NR. Gains on regions of chr 3 and losses in chr 1 and 20 were more frequent in the NR ( > 50%) vs. R ( < 20%). The median number of somatic mutations (mut) per sample was 3 (range, 0-19). Missense mut in DNA-repair genes ( POLK; FANCM; PRKDC; BLM; MSH2; MSH6; RAD50) were found in 63.6% R vs 16.7% NR, in RAS-RAF pathway genes ( CDKN2A; RAC1; KRAS; NF1) in 45.4% vs 7.1%, in chromatin-remodelling genes ( ARID1A; ARID2; KDM5C; SMARCA4; ATRX; KMT2C; DAXX; SETD2) in 54.5% vs 16.7%, and in HER-family genes in R only (36.4%). ERCC1 IHC expression was found in 55.6% R vs 93.3% NR (p = 0.047). Conclusions: We identified distinct molecular features of R vs NR to S-GC in MIBC. These features may be linked to a potentially-additive effect of S and CT. The identification of the targets of CNVs will further elucidate the underlying biology. These results may help developing personalized medicine in MIBC with new more potent targeted agents with CT. Clinical trial information: NCT01222676.
Real world outcomes in advanced urothelial cancer and the role of neutrophil to lymphocyte ratio.
Authors: Yip Steven , Kaiser Jeenan , Li Haocheng , North Scott A. , Heng Daniel Yick Chin , Alimohamed Nimira S. 
Published: September 2018

e16020 Background: Advanced urothelial carcinoma (UC) patients have a poor prognosis. In the first and second line UC treatment setting, we investigated real world outcomes and evaluated the prognostic role of the neutrophil to lymphocyte ratio (NLR). Methods: A retrospective analysis was performed on advanced UC patients treated with systemic therapy. Overall response rates (ORR), time to treatment failure (TTF) and overall survival (OS) were calculated. Cox regression analysis was performed to examine the association between baseline NLR (low NLR<3 vs high NLR≥3) and TTF and OS. Results: We evaluated 233 advanced UC patients. In the first line setting, the ORR was 25%. Median TTF and OS were 6.9 mo and 9 mo, respectively. Low baseline NLR was significantly associated with improved 8.3 mo median TTF, versus 5.8 mo for high NLR patients (p=0.05). Low NLR was significantly correlated with a longer median OS of 13.1 mo, in comparison to 8.2 mo in patients with high NLR (p=0.007). In the second line, an ORR of 22%, a median TTF of 4.1 mo and a median OS of 8 mo were observed. Low NLR in the second line was significantly associated with improved median TTF at 7.9 mo, versus 3.6 mo for patients with high NLR (p=0.03). Second line low NLR was also significantly associated with a longer median OS of 12.2 mo, in comparison to 6.8 mo in patients with high NLR (p=0.003). Conclusions: In this real world analysis of advanced UC patients, first line outcomes were lower than expected, while response rates in the second line compared favorably to the literature, suggesting a highly selected patient population actually receives second line treatment. A low baseline NLR in the first and second line is associated with improved TTF and OS and warrants further prospective evaluation. [Table: see text]
Association of muscle mass with pathologic response and toxicity in localized bladder cancer patients treated by neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).
Authors: Fenioux Charlotte , Huillard Olivier , Xylinas Evanguelos , Tlemsani Camille , Boudou-Rouquette Pascaline , Carton Edith , Peyromaure Michael , Alexandre Jerome , Goldwasser Francois 
Published: September 2018

e16022 Background: Sarcopenia, the condition of low muscle mass, is a prognostic factor across many cancer types including bladder cancer. Moreover, sarcopenia was shown to predict severe toxicity induced by many anticancer agents. Conversely, NAC may increase the prevalence of sarcopenia before surgery. This retrospective study aimed to investigate the association of sarcopenia with pathologic response and toxicity in localized bladder cancer patients treated by NAC and RC. Methods: Among the 52 patients who underwent RC after NAC between Jan 2010 and Dec 2016, the preoperative sarcopenia status could be determined for 39 patients. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured on CT scan images, and sarcopenia was defined as skeletal muscle index of < 43 cm2/m2 for men with body mass index (BMI) < 25 kg/m2, SMI < 53 cm2/m2 for men with BMI > 25 kg/m2, and SMI < 41 cm2/m2 for women. The criteria for efficacy was pathologic response defined by pathological down-staging to ≤ pT1N0. Patients were compared using χ2 or Fischer’s exact test when appropriate. Results: 48% of patients were sarcopenic before RC. A significant higher rate of pathological response was found in non-sarcopenic patients compared to sarcopenic patients (13/20 vs 5/19, P = 0.01). More severe chemotherapy related toxicity was found in sarcopenic patients compared to non-sarcopenic patients for neutropenia (P = 0.06), thrombopenia (P = 0.15), and neuropathy (P = 0.23). Among the 21 patients for whom sarcopenia status before chemotherapy was available, 3 patients became sarcopenic and 4 patients initially sarcopenic gained muscle mass on post-chemotherapy CT scan. Conclusions: Sarcopenia is frequent in localized bladder cancer patients. Muscle mass correlates with pathological response to NAC.
Clinical characterization of febrile neutropenia episodes in patients with testicular germ cell tumors.
Authors: Bezan Angelika , Posch Florian , Bauernhofer Thomas , Pichler Martin , Szkandera Joanna , Hutterer Georg C. , Pummer Karl , Partl Richard , Zurl Brigitte , Kapp Karin , Stoger Herbert , Gerger Armin , Stotz Michael 
Published: September 2018

e16038 Background: Febrile neutropenia (FN) is a serious complication of chemotherapy (CTX). Here, we aim to characterize the clinical course of FN in patients (pts) with testicular germ cell tumors (TGCT). Methods: 413 TGCT patients who underwent at least one cycle of CTX in adjuvant or curative intent were studied within this single-center observational cohort study. Baseline characteristics of the subpopulation with FN are reported in Table 1. Results: During a total number of 1,196 CTX cycles in 413 patients, we observed 70 episodes of febrile neutropenia (16.9%). 55 (79%) of these episodes occurred during the 1stcycle of CTX. The median time between CTX start and FN onset was 14 days [IQR: 12-15, range: 7-18]. One (1%) FN episode was fatal, and 56 patients (80%) had to be hospitalized. Median time in hospital was 7 days [IQR: 6-8, range: 3-12], and the median number of days with an absolute neutrophil count below 0.5G/L was 2 [IQR: 2-3, range: 1-7]. Twelve (20%) FN episodes occurred in the 60 pts who received primary G-CSF support. There was very little treatment delay due to FN (median: 0 days [IQR: 0-0, range: 0-7]. 3 patients (4%) developed a second FN episodes. Conclusions: This study supports prior reports that FN is a relatively frequent complication of CTX in TGCT. However, the case-fatality-rate of FN in TGCT appears to be very low. [Table: see text]
Brachyury, a driver of epithelial mesenchymal transition, as an independent prognostic factor in high-grade testicular germ cell tumors.
Authors: Carcano Flavio Mavignier , Pinto Filipe , da Silva Eduardo CA , Vidal Daniel Onofre , Scapulatempo Neto Cristovam , Lopes Luiz Fernando , Reis Rui Manuel 
Published: September 2018

e16039 Background: The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis and poor prognosis. However, its clinical association with testicular germ cell tumor (TGCT) is unknown. Methods: We analyzed the expression of Brachyury both at protein and transcript levels in a series of 96 TGCT samples and by in silico analysis, respectively. Additionally, we investigated the clinical significance of Brachyury in TGCT. Results: Brachyury protein showed to be over-represented in 89.6% (86/96) of TGCT cases with nuclear staining in 24% (23/96) of them. Microarray expression analysis in two independent cohorts of TGCTs showed similar results with increased levels of Brachyury in TGCTs and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk TGCTs. Multivariate analysis showed that Brachyury nuclear subcellular localization was an independent predictor of poor prognosis (HR: 3.56, p = 0.06). Conclusions: These results indicate that Brachyury plays an oncogenic role in TGCTs and its subcellular localization in the nucleus is a potential novel biomarker of poor prognosis and an oncotarget for intermediate/high-risk TGCTs treatment.
Management of pure metastatic teratoma in chemotherapy naïve testis cancer patients.
Authors: Ahmed Shahid Sattar , Jacob Joseph , Cary Clint , Foster Richard , Einhorn Lawrence H. 
Published: September 2018

e16043 Background: Management of metastatic testicular cancer often requires post-chemotherapy resection of teratoma. This is well known and described in literature. However, the ability of teratoma to metastasize independently is not as well appreciated, making chemotherapy futile in patients with pure metastatic teratoma. Methods: 15 patients with metastatic teratoma were identified of which 13 had only teratoma in the orchiectomy and 2 had predominantly teratoma. All 15 had normal serum hCG and AFP. Cases were derived from a retrospective review of patients seen from 1989-2016. Results: Mean age of patients was 27 years. 12 patients presented initially with Stage II disease and 2 presented with stage III disease. Median RP mass size was 6 cm with a range of 1.5-24 cm. 2 of 15 patients were treated initially with a single course of chemotherapy with BEP and showed no response. The remaining 13 patients only received resection(s). All 15 patients underwent RPLND with 2 patients requiring additional mediastinal and retrocrural resection and 1 requiring lobectomy. All surgical specimens showed pure teratoma on pathology with no other active germ cells. Patients were followed for a median duration of 5 years and all 15 remain with no evidence of disease at most recent follow up. However, 1 patient needed subsequent surgery for a late relapse of teratoma and 1 patient had a second extra-gonadal primary. Conclusions: Teratoma can metastasize in the absence of other germ cells. Surgical treatment alone for patients with pure metastatic teratoma of any stage can result in cure for the majority of patients and this approach can help avoid unnecessary chemotherapy.
Single institution experience on papillary renal cell carcinoma PD-1/PD-L1 expression, pathological analysis, and outcomes after nephrectomy.
Authors: Carthon Bradley Curtis , Tabba Manal , Harris Wayne , Kucuk Omer , Master Viraj A. , Ogan Kenneth , Osunkoya Adeboye O. , Ellis Carla 
Published: September 2018

e16048 Background: The PD-1/PD-L1 pathway plays an important role in tumor growth and tolerance among renal cancer cells. Renal cell carcinoma (RCC) consists of several different histological subtypes, including clear cell and non-clear cell varieties. Papillary RCC is the most common non-clear cell type and accounts for almost 13% of RCC cases. Our center has a large volume of papillary RCC patients treated by nephrectomy or with systemic therapy. This retrospective study examines pathological criteria, outcomes, and PD-1/PD-L1 expression in a defined cohort. Methods: Institutional review board (IRB) approval was obtained to access and retrospectively review clinical and pathological data of patients that presented with papillary RCC and had a partial or radial nephrectomy during a 1 year duration at our institution. We collected data on survival, systemic treatments, and pathological staging. Tumor samples from the patients were also stained and analyzed for PD-1 and PD-L1 expression. Results: 31 patients were identified with papillary histology after nephrectomy. 45% (14/31) of the patients underwent a radial nephrectomy while 55% (17/31) underwent a partial nephrectomy. Of these 31 patients, 23 had tumor slides available for staining and review. 65% (15/23) of the tumor samples were type 1 papillary RCC, and 35% (8/23) were type 2. PD-L1 was expressed in 13% (3/23) of the cases and PD-1 was expressed in 52% (12/23) of the cases. 71% of the patients were pT1 and 84% of the patients were alive at 5 years. Only 1/31 patients required use of systemic therapy. 74% (17/23) of patients were African American. Conclusions: Patients undergoing nephrectomy for papillary RCC at our institution commonly had small primary tumors with excellent survival. 46% of the tumors expressed PD-1, whereas only 12% expressed PD-L1. Trials that study the inhibition of the PD-1/ PD-L1 pathway may be helpful in strategies for treating both localized and metastatic papillary RCC. Further genomic and pathological examination of additional samples is currently underway.