bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomic texture analysis correlates with PDAC patient outcomes on SM-88.
Authors: Ocean Allyson J. , Korn Ronald Lee , Kim Semmie , Burkett Andre , Hindosh Ziad , Nolte Zak , Del Priore Giuseppe 
Published: May 2020

e16776 Background: SM-88 (racemetyrosine) is a dysfunctional tyrosine derivative; previous studies demonstrated a well-tolerated profile with encouraging efficacy. Recent advances in image analysis using Quantitative Textural Analysis (QTA) have uncovered non-invasive biomarkers that correlate with molecular drivers of cancer and prognostic signatures of response in PDAC. Earlier radiomic data from subjects treated with SM-88 showed a positive correlation between circulating tumor cells and tumor texture at baseline. This study extends those findings to focus on radiomic changes associated with SM-88 doses in a Phase II dose escalation trial (NCT03512756). Methods: Retrospective evaluation of 18 subjects with >1 prior therapy, ECOG PS <2, with no restriction on size, number, or locations of mets, and had baseline (BL) and follow up (FUP) contrast enhanced CTs. Subjects received > 1 cycle of SM-88 at either 460mg (n = 8) or 920mg (n = 10) QD oral doses. CTs were analyzed by the QTA platform (TexRad, Essex, UK) for tumor texture. The largest met of each subject was selected using portal venous phase images. A region of interest was posited on the axial slice with the longest tumor diameter and features automatically generated using voxel resampling to correct for scanner variability across subjects and time points. Results were displayed as histogram frequency curves (HFCs) of pixel densities (Hounsfield Units). First order HFC analysis (mean, StDev, MPP, skewness, kurtosis) at spatial scale filters (SSF) ranging from no filter, to fine, to coarse texture (SSF:0, SSF:2, SSF:6, respectively) were reported. Results: Subjects whose largest lesions showed greater changes in tumor texture at FUP vs. BL were more likely to develop tumor progression (StDev in PD (n = 10) vs SD (n = 7) (1 N/A): -0.07 vs -0.25, p = 0.05). Greater tumor textural changes were associated with poor survival at 180 days (Skewness: Chi-Sq. = 4.81, p = 0.03; HR = 4.1 for above median □Skewssf3). There was a negative change in FUP kurtosis vs BL in the 6 subjects who developed new lesions vs the 12 who did not (mean □kurtosis = -0.67 vs +2.63, p = 0.05). Greater change in tumor texture on FUP vs BL scans was seen in the 460mg vs 920mg group (MPPLD = -0.29, MPPHD = -0.04; p = 0.05) suggesting more tumor stability (less change in texture and better outcomes) was associated with the 920mg dose. Conclusions: Tumor lesions in subjects on 920mg of SM-88 were less likely to show a change in tumor texture and were associated with better outcomes. Using radiomic QTA, less tumor texture variability from baseline may be associated with better outcomes in PDAC subjects.
Predictors of recurrence and implications for overall survival in borderline resectable pancreatic cancer patients treated with total neoadjuvant therapy: A retrospective cohort study.
Authors: Kaplan Jori Lee , Powers Benjamin , Fan Wenyi , Schell Michael J. , Centeno Barbara , Kim Dae Won , Frakes Jessica , Hoffe Sarah E. , Malafa Mokenge Peter , Hodul Pamela Joy , Fleming Jason B. , Carballido Estrella M. 
Published: May 2020

e16781 Background: Borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) is a subset of pancreatic cancer with unique prognostic implications. A multimodality, neoadjuvant therapy (NAT) approach has known benefits such as downstaging tumors, reducing the risk of a positive margin, and treating micrometastatic disease. Patient selection and therapy sequencing are controversial owing to the high risk of recurrence. Therefore, we aimed to identify factors predicting recurrence and overall survival (OS) in BR PDAC patients undergoing NAT. Methods: We identified BR PDAC patients treated with NAT followed by surgery at Moffitt Cancer Center between 2008-2015. We evaluated clinical, demographic, and perioperative factors to identify predictors of recurrence and OS. Statistical analyses were performed with univariate and multivariable Cox regression models. Results: 117 patients with BR PDAC who received NAT were evaluated; 53 (45%) were female and 64 (55%) were male. Of those, 91 (78%) received gemcitabine/xeloda/taxotere and the remainder received other gemcitabine or 5FU regimens. 107 (91%) patients received neoadjuvant radiation, mainly 5-day dose painted SBRT. Post- NAT CA 19-9 normalized in 39 (33%) and 11 (9%) additional patients normalized after surgery. Pathologic treatment effect was appreciated in 85 (73%) patients and pathologic complete response (pCR) was seen in 18 (15%). 95 (81%) patients initiated adjuvant therapy. In multivariable analysis, the strongest predictor of recurrence was higher log(10) post-operative CA 19-9 (HR 2.29; 95% CI, 1.40-3.75). Time from initiation of NAT to surgery ≥ 5 months also predicted recurrence (HR 2.08; 95% CI, 1.16-3.72). In OS analysis, 71 patients had recurrence after multimodality treatment; 61 (86%) died and 10 (14%) were alive. In multivariable analysis, the strongest predictors of prolonged OS from recurrence were female gender (HR 0.47; 95% CI, 0.26-0.84) and presence of a treatment effect (HR 0.37; 95% CI, 0.15-0.93). Conclusions: We observed treatment effects and pCR comparable to other institutions, supporting a multimodality approach to BR PDAC. Higher post-operative CA 19-9 and time to surgery ≥ 5 months from initiation of NAT were associated with an increased risk of recurrence. These data suggest that timely receipt of surgery after completion of NAT may impact recurrence and OS in BR PDAC.
BMK_PANC: Search for new predictive/prognosis biomarkers (BKs) in potentially resectable pancreatic adenocarcinoma (PDAC).
Authors: Viudez Antonio , González-Borja Iranzu , Goñi Saioa , Ghanem Ismael , Amat Irene , Arrazubi Virginia , Pérez-Sanz Jairo , Hernandez Irene , Feliu Batlle Jaime , Vera Ruth , Fernández-Irigoyen Joaquin 
Published: May 2020

e16782 Background: New BKs are urgently needed in order to improve PDAC patient’s outcome. In this sense, the main aim of this multicenter and prospective project is to find predictive and/or prognostic BKs based on many cytokines that are produced in cancer microenvironment and can nowadays be accurately analyzed. Methods: Patients diagnosed of potentially resectable PDAC with poor prognostic factors and treated with neoadjuvant treatment are being included. Serial analyses (basal, with TC, with surgery and time of relapse/or after 1y of follow-up) of serum levels of 80 cytokines are being done. Results: With a median follow-up of 11,25 months (m) (4,67-38,28) 22 patients (pt) with median of age of 62,5 y-0, most of them men (63.6%) have been included, with radical surgery performed in 14 of them (2 pts with bypass). Seven operated pt received adjuvant treatment and 12 operated pt developed progression of disease. 18 pt have received nab-paclitaxel and gemcitabine as perioperative treatment and 4 received Folfirinox. Perineural and vascular invasion were confirmed after surgery in 45,5% and 27,3% of cases, respectively. Positive nodes were found in 40,9% of them, being the median of positive and resected nodes of 1 (0-14) and 26 respectively. Surgical margins were negative (R0) in 64,3% of cases (35,7% R1). Pathological response was described as partial in 13,6%, with no changes in 31,8% and progression in 13,6%. Globally, PFS and OS were 13,50 m (CI95%: 6,44-20,55) and 17,31 m (CI 95% 8,86-25,76). Significant differences (p = 0,002) were observed in cases in which radical surgery had been performed with PFS of 13,5 m (9,34-17,66) and 3.97 m (0-8,23) for unresectable patients. Regarding the cytokine array, we observed different PFS outcome based on basal MCP3 levels (low: 16,32 m CI 95%: 5,02-27,63; high: 7,52 m CI95%: 6,23-8.81, p = 0,023), basal Oncostatin (high: 7,12 m CI95%: 3,09-11,15, low: not reached; p = 0,007) or basal Eotaxin (low: 7,12 m CI 95%: 5,75-8,50; high: not reached, p = 0,029). A cytokine score was created based on these results, maintained significant differences for PFS (16,32 m CI95%: 5,07-27,57 vs 6,53 m CI95%: 2,75-10,32, p = 0.003). Our cytokine score showed a significant role as independent prognosis factor in multivariate analysis (HR: 0,196 CI95%: 0,042-0,918; p = 0.039). Conclusions: In potentially resectable/borderline PDAC our basal cytokine score seems to be able to discriminate as independent prognosis factor between those patients that will get significant benefit from neoadjuvant treatment from those that will not
Pembrolizumab in combination with the oncolytic virus pelareorep in patients progressing on systemic chemotherapy for advanced pancreatic adenocarcinoma: A phase II study.
Authors: Mahalingam Devalingam , Kalyan Aparna , Kircher Sheetal Mehta , Maurer Victoria , Kocherginsky Masha , Xu Jiahui , Viveiros Pedro Antonio Hermida de , Vagia Elena , Wilkinson Grey A , Coffey Matthew C. , Mulcahy Mary Frances , Benson Al Bowen , Zhang Bin 
Published: May 2020

e16789 Background: Pelareorep is an intravenously delivered oncolytic reovirus that can induce a T-cell-inflamed phenotype in pancreatic ductal adenocarcinoma (PDAC). Analysis of tumor tissue from patients treated with pelareorep have shown reovirus replication, T-cell infiltration, and upregulation of PD-L1. We hypothesized that pelareorep in combination pembrolizumab in patients with PDAC would lead to improved response, effective T-cell recognition of tumor antigens and expand peripheral T-cell repertoire. Methods: This investigator-initiated phase II study enrolled PDAC patients who progressed after first-line treatment. Patients received pelareorep at a dose of 4.5x1010TCID50IV on Days 1, 2, 3 & 8of Cycle (C) 1, and Days 1 & 8 with C2 onwards. Pembrolizumab was administered on Day 1 of each 21-day cycle at 200 mg IV. Primary objective was overall response rate (ORR) by RECIST v 1.1 criteria. Secondary objectives included evaluation for reovirus replication and immune analysis in peripheral blood and tumor biopsies. The study was designed using Simon’s two-stage design with 90% power and one-sided alpha = 0.025 to compare 10% vs. 35% ORR. A total of ≥2/11 responses were needed to proceed to stage 2. Results: Thirteen patients were enrolled. Disease control was achieved in 30% of the 12 efficacy-evaluable patients. One patient achieved partial response. Three additional patients achieved stable disease. Treatment was well tolerated, with mostly grade 1 or 2 treatment-related adverse events, including flu-like symptoms. Viral replication was observed in on-treatment tumor biopsies. T-cell receptor sequencing from peripheral blood revealed a high degree of peripheral repertoire turnover and creation of new T-cell clones during treatment. Immune correlation with efficacy analysis is ongoing. Conclusions: Pelareorep with pembrolizumab showed manageable safety profiles and modest efficacy in an unselected PDAC population. The study will not proceed to stage II, however further evaluation of anti-tumor activity of pelareorep and anti-PD-1 therapy is now planned in biomarker defined patients. Clinical trial information: NCT03723915 .
DNA damage repair (DDR) gene mutations (mut) are predictors of response to platinum-based chemotherapy in advanced pancreatic cancer (PC) patients (pts).
Authors: Verdaguer Helena , Guardiola-Fernandez Magda , Mancuso Francesco M , Acosta Daniel , Buxó Elvira , Hernando Jorge , Diez Marc , Laquente Berta , Baraibar Iosune , Ros Javier , Garcia Alejandro , Matito Judit , Martin Agatha , Sierra Alexandre , Villacampa Guillermo , Molero Cristina , Miquel Josep M , Vivancos Ana , Dienstmann Rodrigo , Macarulla Teresa 
Published: May 2020

e16805 Background: Somatic DDR mut have been reported in close to 10% of PC samples. In this study we investigate their predictive value for response to platinum-based chemotherapy. Methods: Case-control study with pts deriving response to oxaliplatin-based treatment (partial or complete response at any line) [n = 30] versus no response (progression in first restaging at 1st line) [n = 18]. An in-house NGS panel test of 420 genes was performed on tumor samples. DDR mut were classified in 2 subgroups: (a) functional BRCA1, BRCA2 or PALB2; and (b) any functional DDR gene mut, including those in (a). Results: 48 pts were included, median ages was 54.5 years (30-74), 29 male, 26 were diagnosed with stage IV, 36 pts (75%) received FOLFIRINOX and 37 received platinum-based chemotherapy as 1st. line treatment. Prevalence of DDR mut are described in the table. Among responders, 3 tumors had BRCA2 mt, 3 BRCA1, 2 ATM, and 1 each with BRCA2 + MSH2, PALB2, PMS2, MUYTH, RECQL4 + MDC1. Among non-responders 1 tumor each had ATM, FANCD2 and BLM. Median progression-free survival (PFS) with oxaliplatin-based chemotherapy in pts with BRCA1, BRCA2 or PALB2 mut tumors was 21.7 months (95% CI 12.3-NA); among those with any DDR mt was 12.3 months (95% CI 9.13-NA); while in pts whose tumors had no DDR mut was 6.4 months (95% CI 3.07-13)(Log-rank P-value = 0.02 comparison subgroup [a] vs. others; P-value = 0.1 subgroup [b] vs. others). Conclusions: The subgroup of pts with PC whit tumors harboring DDR gene mut, particularly functional BRCA1, BRCA2 or PALB2, have higher response rate and longer PFS with oxaplatin-based chemotherapy. [Table: see text]
Efficacy of carboplatin-based chemotherapy regimens in patients with bladder cancer in the neoadjuvant setting.
Authors: Aslam Hafiz , Bukhari Sumera , Nadeem Muhammad , Awwal Talha 
Published: May 2020

e17001 Background: There is paucity of evidence regarding efficacy of neoadjuvant chemotherapy regimens in bladder cancer patients. Radical cystectomy has been standard of care for patients with T2-T4, N0, M0 bladder cancer. However, recent trials have shown better survival rates in patients who underwent neo-adjuvant chemotherapy. Our meta-analysis is based on the data from non-randomized clinical trials on the efficacy of carboplatin based regimens. Methods: We conducted a systematic search of Medline (Pubmed) and Cochrane (from inception through May, 2018). Only published single arm clinical trials, abstracts of single arm clinical trials and data from one randomized trial on efficacy of neoadjuvant Carboplatin based therapies in patients with bladder cancer were included in our meta-analysis. Total of > 70 studies were identified. Studies which were duplicate, included adjuvant therapy, systematic reviews or meta-analysis, trials not based on neoadjuvant therapy were excluded. A random effect model was used to calculate pooled proportions. Studies based on ITT protocol were analyzed separately as well as studies based on per protocol analysis. Comprehensive Meta-Analysis software version 3.0 was used. Results: The pooled proportion of pCR (pathologic complete response) calculated from trials based on ITT analysis was 0.23 (95% CI 0.19 to 0.28, P= 0.000). Tests for statistical heterogeneity was non-significant heterogeneity p-value = 0.79 (I2 = 0 %). The pooled proportion of pCR calculated from trials based on per-protocol analysis was 0.29 (95% CI 0.19 to 0.42, P= 0.002). Tests for statistical heterogeneity show nonsignificant heterogeneity p-value = 0.95 (I2 = 0 %). The pooled proportion of ORR (objective response rate) calculated from trials based on per-protocol analysis was 0.69 (95% CI 0.57 to 0.78, P= 0.001). Tests for statistical heterogeneity showed heterogeneity p-value = 0.203 (I2 = 37.3). The pooled proportion of cCR (clinical Complete response) calculated from trials based on per-protocol analysis was 0.25 (95% CI 0.18 to 0.34, P= 0.000). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.80 (I2 = 0%). The pooled proportion of cPR (clinical Partial Response) calculated from trials based on per-protocol analysis was 0.47 (95% CI 0.39 to 0.56, P= 0.59). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.93 (I2 = 0%). Conclusions: Carboplatin based chemotherapy has shown significant efficacy in terms of over-all response rate, pathologic complete response and clinical complete response.
Comprehensive genomic landscape in Chinese patients with urothelial carcinoma.
Authors: Chen Haige , Zhang Ruiyun , Chen Shiqing , Bai Yuezong 
Published: May 2020

e17009 Background: Recent therapeutic advances, such as immunotherapy and FGFR-targeted therapy, have greatly improved the prognosis of patients with urothelial carcinoma (UC). Revealing comprehensive genomic features could evolve our understanding of UC, however the genomic landscape in Chinese UC has not been fully elucidated. In the present study, we investigated the molecular features of Chinese UC patients. Methods: Genomic profiling was performed through next generation sequencing (NGS) from Chinese patients with UC between January, 2017 and November, 2019 in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab. DNA was extracted from formalin fixed paraffin-embedded (FFPE) tumor specimens or fresh tumor tissue. IHC staining for PD-L1 expression was performed using PD-L1 IHC 22C3 pharmDx assay or Ventana PD-L1 SP263 assay. Data analyses were performed using SPSS and R 3.6.1. Results: A total of 298 Chinese UC patients who have undergone NGS were included in this study, including 210 (70.5%) male and 88 (29.5%) female patients. The median age was 66 (range, 19-91) years old. The most common somatic alterations were detected in TP53 (57.0%), KMT2D (42.6%), TERT (28.2%), KDM6A (26.5%) and PIK3CA (18.8%). Of the 243 patients who were evaluated for PD-L1 expression, 78 (32.1%) had a PD-L1 Tumor Proportion Score (TPS) of 1% or greater, and 18 (7.4%) had a PD-L1 TPS of 50% or greater. The median TMB value was 9.7 muts/Mb (range: 0-175.0). 138 (46.3%) patients harbored alterations in DNA damage repair (DDR) genes, including pathogenic or likely pathogenic mutations (MUT) and variants of unknown significance (VOUS). The most common somatic alterations in DDR genes were detected in ATM (9.4%), BRCA2 (9.4%), BRIP1 (5.0%), ATR (4.7%) and BRCA1 (4.7%). Significant differences of TMB were observed among DDR-MUT group, DDR-VOUS group and DDR-WT group (mTMB = 16.1, 14.0 and 7.3 muts/Mb, respectively, P < 0.001). Seven (2.4%) patients were identified as MSI-H, including five patients in DDR-MUT group (12.8%) and two patients in DDR-VOUS group (2.0%). Conclusions: This is the first large-scale comprehensive genomic analysis for Chinese patients with UC. These results provide a better understanding of molecular features in Chinese UC patients which may lead to an improvement in the personalized treatment for these patients.
Functional outcomes of older adults treated with radical cystectomy for muscle-invasive bladder cancer.
Authors: Osterman Chelsea K. , Deal Allison Mary , Nyrop Kirsten A. , Milowsky Matthew I. , Muss Hyman B. , Smith Angela 
Published: May 2020

e17010 Background: Older patients with muscle-invasive bladder cancer (MIBC) may not be offered standard of care treatment with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) based on their chronological age and concern for functional decline following therapy. Age-based differences in post-RC functional status or time to recovery are unknown. Methods: A total of 80 patients were included in this study. Patients ≥ 70 years were categorized as “older” and < 70 years as “younger.” To measure functional status, patients completed an initial geriatric assessment (GA) post-NAC and pre-RC, which was repeated at 1, 3, and 12 months post-RC. Results: Median age was 62 years for younger patients (41-69 years; n = 42) and 75 years for older patients (70-83 years; n = 38). Clinical stage at presentation was not different between groups, but older patients were significantly less likely to receive NAC (63% vs 83%, p = 0.047). There was no significant difference between groups in any physical function measure at baseline. At 1 month post-RC, older patients had significantly lower clinician (c) and patient (p) rated Karnofsky Performance Status (KPS) than younger patients (cKPS: 70 vs 80, p = 0.02; pKPS 60 vs 80, p = 0.03), with a significantly greater decrease from baseline (20 points vs 0 points) in both KPS scores compared to younger patients (cKPS p = 0.001; pKPS p = 0.005). Both groups had a significant decline in ability to complete instrumental activities of daily living (IADLs), but older patients also had significantly increased social activity limitations. At 3 months post-RC, older patients took significantly longer to complete the timed up and go test than younger patients (10.2 secs vs 9 secs, p = 0.02), but had no other differences in physical function measures. Older patients had no significant difference in any measure at 3 months post-RC compared to baseline, while younger patients had a significant improvement in social activity over this time frame. Conclusions: Older patients with MIBC experience a greater short-term decline in functional status post-RC compared to younger patients. However, they return to their baseline status within the same time frame as younger patients.
Systemic immune-inflammation index to predict survival in muscle-infiltrating urothelial carcinoma.
Authors: Obertova Jana , Palacka Patrik , Gallik Dalibor , Slopovsky Jan , Chovanec Michal , Kollárik Boris , Rejlekova Katarina , De Angelis Valentina , Sycova-Mila Zuzana , Hapakova Nikola , Mego Michal 
Published: May 2020

e17022 Background: Systemic immune-inflammation index (SII) is a prognostic factor in patients with metastatic urothelial cancer (MUC). The objective of this prospective study was to evaluate the prognostic value of the SII at baseline before neoadjuvant cisplatin-based chemotherapy start in patients with muscle-infiltrating urothelial cancer (MIUC). Methods: Seventy-two patients (49 men) with MIUC (71 bladder, 1 upper tract) were treated with cisplatin-based neoadjuvant chemotherapy (NACT). Thitrty-nine patients (pts.) underwent radical cystectomy (RC), 18 pts. external radiotherapy (EXRT) with concomitant cisplatin chemotherapy, and 15 pts. had no local treatment (NLT) afterwards. SII was defined as PxN/L, based on platelets (P), neutrophils (N) and lymphocytes (L) counts. This study population was dichotomized by median SII into low and high groups. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared with logrank test. Results: At median follow-up of 13 months (range 2-40), 26 pts. relapsed and 24 of them died. Pts. with low SII at baseline had better DFS and OS compared to those with high SII (NR vs. 19 months, HR = 0.37, 95% CI 0.17-0.88, P = 0.0185 for DFS, 31 months vs. 20 months, HR = 0.43, 95% CI 0.19-0.98, P = 0.052 for OS, respectively). Subgroup analysis showed significant benefit for EXRT regarding of SII, however no differences were observed in both, RC and NL. Conclusions: The level of SII at baseline before neoadjuvant cisplatin-based chemotherapy initiation predicted survival in MIUC pts. Based on the level of SII, stratification of pts. into clinical trials could be possible. Pts. with high level of SII might be the candidates for the different therapeutic approaches. Key Words: Muscle-Infiltrating Urothelial Carcinoma. Systemic Immune-Inflammation Index. Neoadjuvant Chemotherapy. Disease-Free Survival. Overall Survival.