bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic-directed personalized matched targeted therapy approach may improve clinical outcomes among patients with advanced pancreatic cancer.
Authors: Shaya Justin , Kato Shumei , Patel Hitendra , Fanta Paul T. , Kurzrock Razelle 
Published: May 2020

e16794 Background: Despite advances in pancreatic cancer management, 2-year overall survival (OS) remains to be less than 10% in patients with metastatic disease. Given this, novel therapeutic approaches are urgently needed. We hypothesize that a matched combination targeted therapy approach, which is customized based on patient’s cancer genomics, may have clinical efficacy among advanced pancreatic cancer patients. Methods: This is a single center retrospective analysis of advanced pancreatic adenocarcinoma patients treated at UC San Diego. All patients (N = 26) received matched targeted therapy based on genomic alterations detected by tissue NGS and/or blood cell-free DNA assays. This study followed the guidelines of the IRB-approved UCSD PREDICT study (NCT02478931). Results: In the cohort, median age was 67 and 62% (N = 16) were female. 27% (N = 7) received matched therapy front line and 73.1% (N = 19) received matched therapy in the second line or later. The median number of targeted agents administered was 3 (range 1-4). There was a significant improvement in progression-free survival (PFS) when matched therapy was administered in the first line when compared to second line or greater (7.0 vs 2.8 months, hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.19-0.90, P = 0.031) and there was a difference in OS (1st line vs 2nd line or greater: 9.2 vs 4.4 months, HR: 0.58, 95% CI: 0.24-1.42, P =0.23). When stratified by Matching Score of ≥50% (high) and < 50% (low) (Matching Score is roughly equivalent to the number of alterations targeted by therapy divided by the total number of characterized alterations), patients who were treated with a high Matching Score demonstrated significantly prolonged PFS and OS when compared to those with a low Matching Score (PFS: 3.8 vs 2.0 months, HR: 0.34, 95% CI: 0.13-0.91, P =0.031, OS: 5.6 vs 3.3 months, HR: 0.33, 95% CI: 0.13-0.85, P =0.022). In patients with a Matching Score of ≥50%, the disease control rate (DCR) (defined as complete response, partial response, and stable disease ≥ 6 months) was 36.8% and among patients who received matched therapy first line, DCR was 71.3%. Representative cases who were successfully treated with matched targeted therapy will be presented. Conclusions: Combination matched targeted therapy, particularly in patients with a high degree of matching, showed improved clinical outcomes. While the sample size here is small and these data warrant further prospective investigation, matched combinatorial targeted therapy may offer patients a novel option for therapy.
POLO: Radiologic assessment of the impact of maintenance olaparib in patients (pts) with metastatic pancreatic cancer (mPaC).
Authors: Schwartz Lawrence Howard , Kindler Hedy L. , Hammel Pascal , Reni Michele , Van Cutsem Eric , Macarulla Teresa , Hall Michael J. , Park Joon Oh , Hochhauser Daniel , Arnold Dirk , Oh Do-Youn , Reinacher-Schick Anke , Tortora Giampaolo , Alguel Hana , O'Reilly Eileen Mary , Fromageau Jeremie , Ghiorghiu Dana C. , McGuinness David , Locker Gershon Y. , Golan Talia 
Published: May 2020

e16800 Background: The Phase III POLO study (NCT02184195) demonstrated a benefit of maintenance olaparib over placebo in the radiologically assessed primary endpoint of progression-free survival (PFS) in pts with mPaC (median 7.4 vs 3.8 months [mo]; 12-mo rate 34% vs 15%). The impact of radiologic assessment of pancreatic lesions, which is considered challenging, was explored. Methods: Tumors were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review (BICR) in pts with mPaC treated with maintenance olaparib or placebo. PFS was analyzed in subsets of pts based on various event criteria. Results: All 154 randomized pts had mPaC prior to chemotherapy, of whom 122 had disease in the pancreas at POLO baseline (BL); 34% (53/154) had pancreas-only target lesions (TL), 26% (40/154) also had ≥1 TL outside of the pancreas, and in 19% (29/154) pancreatic disease was recorded as non-TL. Sensitivity analyses were consistent with the primary PFS analysis (Table), including when all pancreas lesion assessments were discounted (median PFS 7.4 vs 4.7 mo; 12-mo rate 38% vs 22%). Of 53 pts with pancreas-only TLs at BL, 34 had disease progression (PD); in 20 pts this was not solely based on TL measurements (16 had new lesions; 4 had multiple-cause PD). Confirmed objective responses occurred during study maintenance treatment in 20% of olaparib pts (18/92) and 10% of placebo pts (6/62). In pts with pancreas-only TLs at BL there were 7 responses in the olaparib arm (1 complete response [CR], 6 partial responses [PR]) and 2 (2 PR) in the placebo arm. In pts who had ≥1 TL outside of the pancreas at BL there were 11 (1 CR, 10 PR) and 4 (4 PR) responses, respectively. Responses were generally durable irrespective of TL location. Conclusions: The significant PFS benefit with maintenance olaparib over placebo shown in the primary analysis was consistent across all sensitivity analyses and was not impacted by radiologic assessment of pancreatic TLs. Taken together, these findings suggest that contrary to historically held belief, primary pancreas TLs may be appropriate for inclusion as sites of RECIST-evaluable disease and for assessment of treatment outcome. Clinical trial information: NCT02184195 . [Table: see text]
Prognostic biomarker potential of quantifying endotrophin in serum from pancreas cancer patients.
Authors: Willumsen Nicholas , Chen Inna , Nissen Neel Ingemann , Johansen Astrid Zedlitz , Johansen Julia S. , Karsdal Morten A. 
Published: May 2020

e16804 Background: Pancreas cancer (PC) is the most stroma rich tumor type defined by increased collagen deposition and remodeling (desmoplasia/tumor fibrosis), which result in poor prognosis and lack of treatment response. The cleavage product of the type VI collagen alpha 3 (COL6a3) chain, also knowns as endothrophin, has been shown to signaling properties and affect several pro-tumorigenic events by augmenting desmoplasia, angiogenesis, inflammation and tumor growth. Here we evaluate the clinical utility of a biomarker (PRO-C6) quantifying endothrophin in serum from patients with PC. Methods: Serum PRO-C6 was measured by ELISA (Nordic Bioscience) in 814 PC patients (n = 15, 201, 164 and 434 for stage 1-4, respectively) and 87 patients with benign conditions from the clinical study BIOPAC (NCT03311776, Denmark). PC was histologically confirmed, and patients received standard of treatment (surgical resection or palliative chemotherapy). PRO-C6 was compared between PC and benign conditions and correlated to stage. Association between OS and PRO-C6 in PC patients was analyzed by Kaplan-Meyer curves and Cox regression analysis alone, and after adjusting for age, gender, BMI, diabetes, smoking, performance status, cachexia, CA19-9, stage and metastatic sites. Results: PRO-C6 was elevated in PC compared to benign disease (p = 0.009) and increased with tumor stage (p = 0.0006). When dividing PRO-C6 into quartiles (Q1-Q4) a stepwise decrease was detected in median OS time (Q1:380 days, Q2:264 days, Q3:236 days, Q4:176 days, p < 0.0001). Patients in Q4 had 85% increased risk of dying compared to Q1 (HR:1.85, p < 0.0001). High PRO-C6 (Q4) remained associated with poor OS after adjusting for co-variates (HR: 1.66, p = 0.0018). Conclusions: Pretreatment serum PRO-C6 (a measure of the COL6a3 chain/endothrophin) is associated with PC and has independent prognostic value. This suggests that endothrophin, and the desmoplastic reaction, plays a key role in PC and indicate that PRO-C6 may provide means for a theragnostic approach for stratifying and treating PC patients in the future. Clinical trial information: NCT03311776 .
Adjuvant chemotherapy impact on the overall survival of completely resected small bowel adenocarcinoma: An updated meta-analysis.
Authors: Haddad Philip A. , Hammoud Dalia A. , Gallagher Kevin M. 
Published: May 2020

e16806 Background: While the small intestine represents around 75% of the length and more than 90% of the gastrointestinal tract mucosal surface, it contributes around 2% of gastrointestinal tumors. Adenocarcinoma which constitutes 40% of all small bowel tumors is the most common histology. Complete surgical resection of early-stage small bowel adenocarcinoma (SBAC) is the only proven potentially curative therapy. Due to the rarity of this disease and the absence of randomized trials, the benefit of postoperative adjuvant chemotherapy (ACT) in patients with completely resected localized SBAC has been controversial. A meta-analysis conducted in 2018 found no survival benefit for adjuvant therapies in SBAC. However, this meta-analysis combined studies that used adjuvant chemotherapy and chemoradiotherapy and included studies contaminated by other less chemosensitive histologies and more advanced and sometimes metastatic disease. The purpose of this meta-analysis is to evaluate the impact of ACT on the overall survival (OS) of patients with completely resected SBAC incorporating more recent studies. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of resected small bowel adenocarcinoma, English language, publications from 2000 to the present, and comparative studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves of patients that underwent ACT versus those that did not. Adjuvant chemoradiotherapy studies and those that reported aggregate OS for a cohort with mixed histologies were excluded. A meta-analysis was conducted using an inverse variance method with a random-effects model. Results: Nine retrospective series which included 2082 patients were selected and analyzed. The majority of SBAC patients that received ACT belonged to stages II & III. ACT was found to be significantly associated with better OS in patients with completely resected SBAC (HR 0.66, 95%CI: 0.56-0.78, p < 0.001). Conclusions: This is the first meta-analysis to show that adjuvant chemotherapy is associated with a survival benefit in patients with completely resected small bowel adenocarcinoma. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of ACT in this patient population.
Comparison of oncologic outcomes for robotic-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) among locally advanced and node-positive patients: An analysis of the National Cancer Database (NCDB).
Authors: Reddy Akshay G , Sparks Andrew D , Darwish Christina , Whalen Michael Joseph 
Published: May 2020

e17002 Background: Despite recent concerns of atypical recurrence following RARC, utilization of the modality is increasing. The presumed mechanisms are especially relevant in more aggressive disease, where the metastatic potential of tumor cells may be greater. This study aims to compare the oncologic efficacy of RARC to ORC among patients with stage pT3-4 or node-positive bladder cancer. Methods: A retrospective cohort analysis of pT3-4N0-3 and pT(any)-4N1-3 patients who underwent RARC or ORC from 2010-2016 was performed using the NCDB. Appropriate univariate and multivariable analysis were performed between treatment cohorts. Results: RARC was significantly associated with superior unadjusted survival compared to ORC (median survival relative to ORC; 23.6 mo. vs. 21.6 mo.; P= 0.001). Additionally, RARC was associated with lower proportions of unadjusted 30- and 90-day mortality, positive margin status, and shorter surgical inpatient stay (all respective P< 0.05). However, after adjusting for confounding covariates, multivariable analysis revealed no difference in mortality hazard or odds of secondary outcomes with the exception of inpatient stay (Table). RARC was also significantly associated with higher lymph node yield (increased incidence of > 14 lymph nodes examined relative to ORC; 55% vs. 40%; P< 0.01). Conclusions: RARC is no less safe than ORC for patients with locally advanced or node-positive bladder cancer on the basis of overall, 30- and 90-day survival outcomes. Unadjusted mortality and surgical outcomes in this population demonstrate advantages to the robotic modality. Perioperative benefits may favor RARC, but further randomized control studies are necessary to better elucidate differences between surgical approaches. [Table: see text]
Emerging clinical phenotype of bone metastatic urothelial cancer (mUC): Association of early osseous metastases (EOM) and outcomes.
Authors: Nelson Ariel Ann , Cronk Robert , Szabo Aniko , Lemke Emily , Giever Thomas A. , Burfeind John D. , Kilari Deepak , Riese Matthew John , Bylow Kathryn A. , Diamantopoulos Leonidas Nikolaos , Khaki Ali Raza , Nezami Behtash , MacLennan Gregory , Draves Mary Ann , Goolamier Gordon , Rosey Samantha , Calaway Adam , Grivas Petros , Ponsky Lee Evan , Hoimes Christopher J. 
Published: May 2020

e17007 Background: Outcomes of patients (pts) with mUC with EOM have not thoroughly been described in the age of immuno-oncology. We hypothesized that EOM is associated with worse outcomes when compared to pts with non-osseous metastases (NOM). Methods: We used a multi-institutional database of pts with mUC who received systemic treatment (trt) between March 2005 and August 2019, to assess survival and palliative outcomes of pts with EOM vs NOM at the time of metastatic diagnosis (met dx). Wilcoxon rank-sum and chi-square tests were performed. Survival was estimated by Kaplan-Meier method, Cox regression analysis was performed. Results: We identified 270 pts, 72% men, mean age 67 ± 11 years, 28% never smokers. At met dx, 27% (n = 72) had ≥ 1 EOM; these pts were more likely to have de novo metastases vs. those with recurrent metastases (42% vs 19%, p < 0.001). Pts with EOM were more likely to have a change or stop in 1st line trt due to clinical progression (30.6% vs 15.7%, p = 0.006), and received fewer total lines of systemic trt, median of 1.0 (1.0-5.0) vs. 2.0 (1.0-8.0), p = 0.05. Pts with EOM had shorter median overall survival (OS) vs. those with NOM, (6.1 vs 13.7 months, p < .0001), HR = 2.79 (95% CI:1.95-3.97, p < .0001). Median OS was shorter for pts with EOM who received 1st line immune checkpoint inhibitor (n = 14) vs platinum-based chemotherapy (n = 43), (1.6 vs 9.1 months, p = 0.003). Pts with EOM received higher opioid analgesic doses at the first and last oncology outpatient visits compared to pts with NOM with mean morphine milligram equivalent (MME) dose of 60 ± 91 vs 28 ± 65 at first visit, p = 0.004, and 171 ± 214 vs. 94 ± 229 at last visit, p < 0.001. Conclusions: The presence of EOM in mUC is associated with worse outcomes vs. pts with NOM. Pts with EOM may benefit from 1st line platinum-based chemotherapy vs. checkpoint immunotherapy. Furthermore, pts with EOM experience more pain than pts with NOM and may benefit from early engagement with palliative care. Pts with EOM represent a population with a highly unmet need for systemic, targeted and/or radiation interventions. Molecular subtypes may further define these pts and analysis is planned. We encourage ongoing clinical trials to report outcomes in pts with EOM. A consensus on reporting of non-measurable disease is also needed. [Table: see text]
Systemic immune-inflammation index to predict survival in patients with metastatic urothelial carcinoma treated with second-line vinflunine.
Authors: Palacka Patrik , Katolicka Jana , Albertova Tana , Rejlekova Katarina , Obertova Jana , Hrncar Matej , Chovanec Michal , Slopovsky Jan , Mego Michal 
Published: May 2020

e17019 Background: Based on our previous study, the systemic immune-inflammation index (SII) is a prognostic factor in patients with metastatic urothelial cancer (MUC) treated with platinum-based first-line chemotherapy. The objective of this retrospective analysis was to explore prognostic value of the SII at baseline of second-line chemotherapy with vinflunine in MUC population. Methods: We evaluated 70 consecutive MUC (53 bladder, 21 upper tract) patients (54 men) treated with second-line chemotherapy with vinflunine at four oncological departments since 2010. ECOG performance status (PS) ≤ 1 had 44 patients (pts.), haemoglobin < 10 g/dL was present in 25 pts. and liver involvement in 18 pts. SII was based on platelets (P), neutrophils (N) and lymphocytes (L) counts defined as PxN/L. This study population was dichotomized by median into low SII and high SII groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with logrank test. Results: At median follow-up of 9.0 months (1-29 months), 68 pts. experienced disease progression and 62 died. Pts. with low SII at baseline had significantly better PFS and OS opposite to those with high SII (HR = 0.61, 95% CI 0.37-1.00, p = 0.0318 for PFS, HR = 0.60, 95% CI 0.36-1.00, p = 0.0312 for OS, respectively). In addition to the prognostic factors by Bellmunt (ECOG PS ≥ 1, liver involvement, haemoglobin < 10 g/dL), we identified peritoneal metastases as a factor associated with significantly worse survival (HR = 0.28, 95% CI 0.11-0.72, p < 0.00001 for PFS, HR = 0.30, 95% CI 0.12-0.75, p < 0.00001 for OS, respectively). Conclusions: The SII at baseline of treatment with second-line vinflunine represents a prognostic factor for pts. with MUC. Based on SII, pts. could be stratified into clinical trials in future. MUC pts. with high SII might be candidates for a different treatment approach. Key Words: Metastatic Urothelial Carcinoma. Systemic Immune-Inflammation Index. Vinflunine. Progression-Free Survival. Overall Survival.
Single-institution experience of small cell bladder cancer at a community center.
Authors: Makary Mina , Garg Tullika , Bakht Delnaz , Solangi Zeeshan , Hassanzadeh Karen , Liu Haiyan , Panikkar Rajiv Prasanna , Vadakara Joseph , Zhang Li 
Published: May 2020

e17021 Background: Small cell bladder cancer (SCBC) is a rare malignancy with poor prognosis. Previous retrospective studies mainly focused on answering whether radical cystectomy is superior to radiation. Little is known about the disease characteristics and clinical course. Methods: Patients were identified via Geisinger cancer registry from 1991 to 2019, and retrospective chart review was performed through the electronic health records, EPIC. We described patient characteristics and outcomes. OS was measured from time of initial diagnosis to death or last follow up. Kaplan-Meier analyses were done on OS. Results: 50 patients were identified; 7 patients were excluded due lack of information. M: F≈1, 60% patients had pure small cell carcinoma (SCC) histology (≥ 95%), 37% with SCC and urothelial carcinoma mixed histology, MIB-1 index was 80-100%. Median OS for localized disease (IQR) was 22 months (9,73), and 11 months (7,16) for metastatic disease. For localized disease, OS were similar between patients with or without pure small cell history (P = 0.47). 8 patients were alive at 5 years; 3 patients received neoadjuvant chemotherapy followed by radical cystectomy, 2 patients underwent radical cystectomy alone, 2 patients had concurrent chemotherapy with radiation; 1 patient had complete pathological response to Cisplatin and etoposide chemotherapy, did not receive additional therapy and recurred 6 years later. Recurrence ranged from 6 to 79 months. 10 patients had disease progression despite of palliative chemotherapy. Conclusions: Small cell bladder cancer is a heterogenous disease, early stage disease can be curable but late recurrence does occur, continued surveillance is warranted even after 5 years. New treatment modality is in need to improve outcome for patients with metastatic disease.
Correlation of tumor mutational burden (TMB) with molecular profiling and clinical characteristics in patients with bladder cancer.
Authors: Natesan Divya , Martell Henry , Devine Patrick , Stohr Bradley A. , Grenert James P. , Van Ziffle Jessica , Joseph Nancy M. , Bastian Boris C. , Umetsu Sarah E , Onodera Courtney , Chan Emily , Desai Arpita , Wong Anthony C. , Porten Sima P. , Chou Jonathan , Friedlander Terence W. , Small Eric Jay , Fong Lawrence , Sweet-Cordero Eric Alejandro , Koshkin Vadim S 
Published: May 2020

e17025 Background: Bladder cancers (BC) are frequently highly mutated. Next generation sequencing (NGS) can both shed light on mutational burden and the specific alterations that provide insights into the underlying biology of individual tumors. Methods: We retrospectively reviewed BC cases assessed with UCSF500, an institutional NGS assay that uses hybrid capture enrichment of target DNA to interrogate approximately 500 frequently mutated cancer genes. Hypermutated tumors were defined as having TMB > 10 mutations/Mb. Fisher’s exact test was used to compare patients (pts) with hypermutated (HM) and non-hypermutated (NHM) tumors. Results: From 2015 to 2019, 74 pts with BC underwent UCSF500 testing; 48 pts were evaluable for TMB, of which 19 pts (40%) had HM tumors. 17/19 pts were evaluable for mutational signatures; all 17 had APOBEC signatures. Signatures were not assessed in NHM tumors due to low TMB. Clinicopathologic characteristics and most common alterations in the two groups are listed in the table. More HM pts had responses to immunotherapy (IO) treatment (86% vs 40%, p = 0.13). Conclusions: In this single-institution BC cohort, HM tumors were common and APOBEC mutational signature was the common underlying biology in HM tumors. There were relevant differences in common alterations between HM and NHM tumors, including more FGFR3 mutations in NHM tumors. HM status and APOBEC signature were suggested as relevant predictive biomarkers of response to IO, which should be investigated further in larger BC cohorts. [Table: see text]