bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcomes of well-differentiated high-grade (G3) neuroendocrine tumors.
Authors: Liu Alex John , Ueberroth Benjamin Edward , Buckner Petty Skye , McGarrah Patrick Walsh , Kendi Ayse T. , Hobday Timothy J. , Halfdanarson Thorvardur Ragnar , Sonbol Mohamad Bassam 
Published: May 2020

e16691 Background: Recent WHO classification of NET has defined high-grade well-differentiated NET (NET G3) as a distinct entity that is clinically different from neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aims to evaluate NET G3 response to different treatment regimens. Methods: This is a retrospective study of NET G3 patients within the Mayo Clinic database (Arizona, Florida, and Minnesota). Patient demographics along with treatment responses and survival were assessed. Primary end points were progression-free survival (PFS) and objective response rate (ORR) by RECIST 1.1 criteria. Results: 71 patients with NET G3 were identified. Systemic treatment data was available in 30 patients who had a median age of 59.5 years at time of diagnosis. The primary tumor was most commonly pancreatic (73.3%). Ki 67 index was ≥55% in 26.7% of cases. 56.7% of cases had > 1 metastatic site. Treatment regimens included: capecitabine+temozolomide (CAPTEM) (n = 20), somatostatin analog (SSA) (n = 14), carboplatin/cisplatin+etoposide (EP) (n = 7), everolimus (n = 2), FOLFOX (n = 7), and lutetium Lu 177 DOTATATE (PRRT) (n = 10). CAPTEM was the most commonly used regimen (10 first-line, and 10 second-line) with ORR of 35%, disease control rate (DCR) of 65%, and median PFS of 9.4 months. The table summarizes the treatment data and responses rates for the various therapies used. Conclusions: Among NET G3 patients treated at Mayo Clinic, CAPTEM was found to be the most commonly used treatment with reasonable efficacy and disease control. Other treatment options include SSA, PRRT, FOLFOX, and EP. Prospective studies evaluating different treatments effects in NET G3 patients are needed to determine an optimal treatment strategy. [Table: see text]
Retrospective analysis of Peptide Receptor Radionuclide Therapy (PRRT) in Japanese patients with unresectable neuroendocrine tumor.
Authors: Kobayashi Noritoshi , Wild Damian , Kaul Felix , Ichikawa Yasushi 
Published: May 2020

e16700 Background: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is an innovative treatment for inoperable or metastasized, well/moderately differentiated, neuroendocrine tumors (NETs). Currently PRRT cannot be performed in Japan, because there is no approval and insurance cover until now. Methods: We rely on University Hospital Basel to perform PRRT for Japanese patients with NET since 2011. In this retrospective analysis we evaluated the efficacy and safety of PRRT for Japanese patients with NET (IRB B180100019). Inclusion criteria were pathologically confirmed NET, inoperable or metastasized disease, and visible tumor uptake in the pre-therapeutic somatostatin receptor scintigraphy. We excluded patients with concurrent antitumor treatment, concomitant severe illness, and pre-existing severe hematologic, renal, and liver damage. 5.55GBq(150mCi) of 177Lu-DOTATOC was used as standard treatment and patients received three infusions every 8 weeks. Until end of 2017, combination treatment with 90Y-DOTATOC and 177Lu-DOTATOC was performed using the same protocol. We checked blood count and renal function parameter every two weeks after PRRT. CT or MRI examination were performed 10-12 weeks after the last PRRT cycle. We evaluated the morphological changes according to RECIST 1.1 criteria. With the execption of Somatostatin analogues further treatments were refrained until tumor progression. Results: Thirty-three patients (male: 16, female: 17) were recruited with a median age of 56 years. (range: 26-71). Primary lesions were pancreas (n = 18), rectum (n = 6), small intestine (n = 3), stomach (n = 1), and other locations (n = 5). The period between diagnosis and PRRT was about 3years. Median Ki67 index was 6.3% (range: 0.7%-30%). Partial response rate was 39.3% and disease control rate is 63.6%. Progression free survival (PFS) was 421 days (95%CI:269-572 days) and overall survival was 580 days (95%CI:259-900days). We compared PFS with the treatment line (front line: first or second-line vs late line: third or fourth-line), there was no significant difference between the two groups (front line: 329.0 days vs late line: 497.0 days Log Rank test P = 0.189). Conclusions: PRRT in Japanese patients with NET was effective and a reliable treatment option.
Phase IIa safety and efficacy of milciclib, a pan-cyclin dependent kinase inhibitor, in unresectable, sorafenib-refractory or -intolerant hepatocellular carcinoma patients.
Authors: Villa Erica , Piscaglia Fabio , Geva Rabit , Dalecos George , Papatheodoridis George , Ciomei Marina , Davite Christina , Crivori Patrizia , Palejwala Vaseem , Jacob Jules , Hamzeh Fayez , Shailubhai Kunwar , Santoro Armando , Sangiovanni Angelo 
Published: May 2020

e16711 Background: Current hepatocellular carcinoma (HCC) therapeutics, tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CI), provide limited improvement in overall survival, suggesting the need to identify drugs with broad-spectrum mechanisms of action, used alone or in combination with a TKI or CI. Milciclib, a pan cyclin dependent kinase inhibitor, exhibited anti-cancer activity in refractory solid malignancy patients. The primary objective of this trial was to evaluate safety and tolerability of milciclib in sorafenib-refractory or intolerant advanced HCC patients. Methods: Single arm and multi-center study in advanced HCC patients was conducted in Italy, Greece and Israel. Milciclib was administered orally for up to 6 cycles. Each cycle consisted of 100mg milciclib daily for 4d on/3d off/week for 4 weeks. Safety assessment was the primary endpoint and secondary endpoints included progression free survival (PFS), time to progression (TTP) and clinical benefit rate (CBR). Results: A total of 31 patients were enrolled and 28 were evaluable for efficacy, of which 14 (50%) completed 6-months of treatment. Milciclib was well-tolerated with manageable toxicities. Eighteen of 31 treated patients had drug-related adverse events (AEs) with most frequent (≥5%) occurrence of drug-related diarrhea, nausea, asthenia, fatigue, retinal hemorrhage, rash and myalgia. No drug-related deaths were recorded. Nine of 14 patients (64%) continued treatment under Compassionate Use after study completion. Seven patients received milciclib until 9, 9, 10, 11, 13, 13 and 16 months. The remaining 2 patients are in the 16th month of treatment. Clinical response to treatment, assessed by mRECIST (independent radiological review), is shown in the Table. Both median TTP and PFS were 5.9 months. Conclusions: Milciclib, acting via a new mechanism, was safe, well-tolerated and met primary and secondary endpoints with 61% CBR. These promising clinical data warrant further evaluation of milciclib. Clinical trial information: NCT03109886 . [Table: see text]
The oncogenic role of ARG2 in hepatocellular carcinoma.
Authors: Lin Pin-Jen , Chiu Fang-Yen , Wang Shu-Chi , Li Chia-Yang 
Published: May 2020

e16713 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adult and is a leading cause of cancer-related death worldwide. In most mammals, two isoforms of arginase have been identified (ARG1 and ARG2). Clinical Data revealed that ARG2 is highly expressed in various types of cancers including HCC. However, the role of ARG2 in regulating the progression of HCC has not yet been examined. The present study aimed to examine the role of ARG2 on the progression of HCC. Methods: Cell growth and proliferation were examined by MTT assay and colony formation assay, respectively. Cell migration was determined using wound-healing assay. The expression of ARG2 and its correlated survival rate in HCC was analyzed by DriverDBv3 database. Results: Our experimental results showed that knockdown of ARG2 suppresses cell growth, colony formation and migration ability in HepG2 cells. In HCC patients, ARG2 is highly expressed in primary solid tumor and recurrence solid tumor samples comparing to solid tissue normal samples. In addition, high level of ARG2 is associated with poor overall survival in HCC patients. Conclusions: These results suggest that ARG2 plays an oncogenic role in modulating HCC progression.
HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: A phase I clinical trial.
Authors: Yang Tong 
Published: May 2020

e16715 Background: Previous studies showed that high intensity focused ultrasound (HIFU) treatment could treat liver tumor and pancreatic cancer, with fewer serious adverse reactions.To evaluate the safety and efficacy of HIFU for patients with colorectal liver metastases(CRLM) that were contraindicated for resection and radiofrequency ablation. Methods: Patients between 20 to 80 years of age with 1-3 liver metastases from colorectal cancer were included. The primary colorectal lesions were thoroughly resected and any case with extra-hepatic metastasis was excluded. Ultrasound guided HIFU system was employed and target region ablation was achieved with repeated sonications from the deep to shallow regions of the tumor section by section. Results: Thirteen patients were enrolled. Pain was the most common adverse events(AEs) (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase(ALT) (n = 5), and skin edema (n = 4). No grade≥3 AEs occurred.The majority of patients (76.9%) had a complete response and the remaining three patients achieved partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but most were isolated only in the liver (8/9). The median follow-up was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and median OS was 25 months. Conclusions: This study indicates that HIFU treatment is safe, has an excellent tumor response and long-termprognosis even when the foci in risky locations, and is probably a considerable option for patients who were unsuitable for other local treatments.
A new prognostic model for high-grade appendiceal mucinous neoplasms with peritoneal carcinomatosis.
Authors: Mouabbi Jason A , Malapati Sindhu Janarthanam , Abdalla Ahmed , Biedny Adam , Hayward David , Szpunar Susan , Hadid Tarik H. , Berri Richard N , Kafri Zyad 
Published: May 2020

e16718 Background: Peritoneal carcinomatosis of appendiceal origin (PCAO) is a rare malignancy accounting for less than 1% of all cancers. High-grade appendiceal mucinous neoplasms (HAMN) have a poor prognosis and are often treated with cytoreductive surgery (CRS), with hyperthermic intraperitoneal chemotherapy (HIPEC) followed by adjuvant systemic chemotherapy (ASC). Peritoneal cancer index (PCI) and completeness of cytoreduction score (CCR) are useful prognostic tools in patients with PCAO undergoing CRS/HIPEC. However, neither PCI nor CCR take response to ASC into account. Therefore, we propose an enhanced prognostic scoring system (tumor response index, TRI) that incorporates response to ASC as assessed at the completion of treatment. Methods: We retrospectively reviewed the charts of patients with PCAO who received care at the Van Elslander Cancer Center between January 2011 until December 2018. All patients with HAMN who underwent CRS/HIPEC followed by ASC were included. TRI was assessed by comparing the patients' performance status, tumor markers and imaging at the completion of ASC to those prior to the initiation of ASC. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used to estimate correlations between TRI and clinical outcomes (PFS and OS). TRI was also compared to PCI and CCR using the Akaike’s Information Criteria (AIC). Results: A total of 84 charts were reviewed. Patients were divided into groups based on their TRI score. The median age was 57 years with 55% females and 85% Caucasians. Approximately 20% of patients had signet-ring features. The most common ASC regimen used was a combination of 5-fluorouracil, oxaliplatin (FOLFOX) and bevacizumab (65%). The table depicts the median PFS and OS of each TRI group. Lower TRI was associated with significantly better PFS and OS. For all outcomes, AIC was substantially reduced by adding TRI to PCI and CCR, suggesting that TRI is a better predictor of PFS and OS. Conclusions: This study proposes TRI as an effective prognostic tool in patients with PCAO and HAMN after CRS/HIPEC/ASC. [Table: see text]
Real-world hypothesis-generating cohort of pancreatic cancer patients with brain metastases.
Authors: Cridebring Derek , Hadley David , Scott Timothy S , Vilner Alex B , Heckman Tammy M , Gosselin Kevin , Jameson Gayle S. , Haag Susan , Borazanci Erkut Hasan 
Published: May 2020

e16720 Background: Pancreatic cancer (PC) is the third most lethal form of cancer in the United States, and is most often diagnosed having already metastasized, making its 5-year survival rate one of the lowest. Metastatic PC (mPC) is most common at sites such as liver, lymph nodes, and lung while, in contrast, brain metastases from PC are rare. Brain metastases present a major challenge for future oncological research, as they are difficult to treat. If PC patients most likely to develop brain metastases can be identified earlier, there is an opportunity for rapid therapeutic intervention. There is limited research and understanding of the relationship between pancreatic cancer and brain metastases. Methods: We performed a retrospective, non-interventional study using deidentified data. Inteliquet’s data was aggregated from its consortium of 175 US healthcare locations, which includes a variety of source systems at each site. These sources include electronic medical record systems, laboratory information management systems, and other sources. A subset of the adult mPC data originally treated at HonorHealth was identified as an exploratory cohort. Results: 833 patient records were identified with drug treated mPC, 33 (4%) of which had metastasized to the brain. The PC dataset had a median diagnosis age of 65 and was 46% female. The site of the primary tumor within the pancreas was acquired from ICD10 code: 35% were in the head, 14% in the tail, 15% in the body, 5% in overlapping sites, 6% in other parts and 26% where location was unspecified. Metastatic locations came from secondary malignancy ICD10 codes: 63% had liver and 25% had lung metastases, which aligns with prior studies. For patients with brain metastases, the gender distribution was 42% female, while the distribution of primary PC site was: 33% head, 9% tail, 6% body, 6% in overlapping locations, 12% in other parts and 33% with unspecified location. The median age of diagnosis in the brain metastasis group was 67 years. Conclusions: This is the largest study of PC patients with brain metastases that we could find. 33 patients out of 833 had brain metastases compared to a recent review which had 25 cases. Our data suggests that specification of the primary pancreatic site is more difficult, aside from the head of the pancreas. Analyses are underway to explore correlations between other clinical factors and brain metastases, and to calculate the time in between the initial pancreatic cancer diagnosis and detection of the brain metastasis. This hypothesis-generating cohort will be tested in patient data from the rest of the consortium.
A multicenter chart review study of patients with metastatic pancreatic ductal adenocarcinoma receiving liposomal irinotecan after gemcitabine-based therapy.
Authors: Yu Kenneth H. , Hendifar Andrew Eugene , Alese Olatunji B. , Draper Amber , Abdelrahim Maen , Burns Ethan , Khan Gazala Naaz , Cockrum Paul , Bhak Rachel , DerSarkissian Maral , Nguyen Catherine , Duh Mei Sheng , Bahary Nathan 
Published: May 2020

e16733 Background: Real-world data allows healthcare decision-makers to assess and manage therapeutic and economic options for patients, including those who would and would not have met eligibility criteria for randomized control trials (RCT) and are instead managed under usual care. This retrospective multi-academic center chart review study describes real-world characteristics and outcomes of US patients receiving liposomal irinotecan for the management of metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: Patients with mPDAC treated with liposomal irinotecan were eligible. Initiation of liposomal irinotecan defined index date; covariates assessed included clinical characteristics and treatment patterns; real-world overall survival (rwOS) was assessed via Kaplan-Meier methodology. The target enrollment is 300 patients. The study centers included were Memorial Sloan Kettering Cancer Center, Cedars-Sinai Medical Center, Emory Winship Cancer Institute, Houston Methodist Cancer Center, Henry Ford Cancer Institute, and University of Pittsburgh Medical Center. Results: Data on 26 patients were available for initial analyses. Mean age was 68 years; 58% were female and 65% Caucasian. 54% of patients had stage IV disease at first diagnosis, and 17%, 65%, and 17% had index ECOG score of 0, 1, and 2, respectively. Common genetic mutations include KRAS (40%) and TP53 (40%). Prior to liposomal irinotecan, treatments received for metastatic disease include gemcitabine+nab-paclitaxel (77%) and fluorouracil (5-FU)/leucovorin (LV)+irinotecan+oxaliplatin (19%). Patients had received 0 (12%), 1 (23%), and ≥2 (65%) lines of therapy in the metastatic setting prior to liposomal irinotecan. Mean duration of liposomal irinotecan use was 3.0 months; liposomal irinotecan was mostly received with 5-FU (23%) or 5-FU/LV (69%). Median rwOS was 4.9 months (95% CI: 3.0, 6.3). Conclusions: Real-world data of the first 26 patients in this study show patients treated with liposomal irinotecan are older, sicker, and have had more lines of therapy than previously reported in RCT data.
Error-free, automated data integration of exosome cargo protein data with extensive clinical data in an ongoing, multi-omic translational research study.
Authors: Oromendia Ana , Ismailgeci Dorina , Ciofii Michele , Donnelly Taylor , Bojmar Linda , Jyazbek John , Chatterjee Arnaub , Lyden David , Yu Kenneth H. , Kelsen David Paul 
Published: May 2020

e16743 Background: Major advances in understanding the biology of cancer have come from genomic analysis of tumor and normal tissue. Integrating extensive patient-related data with deep analysis of omic data is crucial to informing omic data interpretation. Currently, such integrations are a highly manual, asynchronous, and costly process as well as error-prone and time-consuming. To develop new blood assays that may detect very early stage PDAC, a multi-omic investigation with deep clinical annotation is needed. Using pilot data from an on-going study, we test a new platform allowing automated error-free integration of an extensive clinical database with extensive omic data. Methods: Demographic, clinical, family pedigree and pathology data were collected on the Rave EDC platform. Exosomes were purified from 46 plasma samples from 14 controls and 24 PDAC patients and cargo proteins were quantified via SILAC. The Rave Omics platform was used to ingest and integrate clinical and omic data, run quality checks and generate integrated clinical-omic datasets. Data fidelity was validated by systematically computing differences between corresponding values in the source flies with those present in the extracted data object (integrated data). The root mean squared error (RMSE) was calculated for numeric values in each sample. Additional validation was conducted by manual inspection to ascertain data integrity. Results: We demonstrated automatic integration, without human intervention, of a subset of the clinical data and all available SILAC data into an analysis-ready data object. Data transfer was completely faithful, with 100% concordance between the source and the integrated data without loss of features. All proteins (n = 1515) and clinical variables (n = 64) were imported. Their nomenclature and corresponding sample values (n = 69690) and clinical values (n = 2432) matched exactly between datasets. In all samples, the RMSE was exactly zero, indicating no deviation between data sources. Conclusions: We demonstrated that automatic, efficient, and reliable integration of clinical-omic data is achievable during an in-flight PDAC trial. Automatic exploratory analytics supporting biomarker discovery are currently being used to uncover associations between omic and clinical features. The Rave Omics platform is disease-agnostic and we plan to expand to trials of varying size, indication, and completion status where systematic, automated integration of clinical and (multi)omic data is needed.
Nanomaterials augmented LDI-TOF-MS for pancreatic ductal adenocarcinoma diagnosis and classification.
Authors: Xu Yaolin , WANG Dansong , Kuang Tiantao , Wu Wenchuan , Xu Xuefeng , Jin Dayong , Zhang Hua , Zhong Sheng , Wang Yunbing , Lou Wenhui 
Published: May 2020

e16761 Background: Pancreatic ductal adenocarcinoma (PAAD) is one type of cancer with poor prognosis. Although CA 19-9 was the most common serological marker for cancer screening and surveillance after treatment, there are still unignorable limitations, including low sensitivity, possible false-negatives/positives owing to confounding conditions. Reliable non-invasive diagnostics is in urgent need. As PAAD is increasingly considered as a metabolic disorder, serum metabolite profiling is becoming critical to reveal important cancer-related bioinformation. This work proposes a novel LDI-TOF-MS technique for PAAD screening and diagnosis. Methods: An LDI-TOF-MS platform was established for cancer screening. All mass spectrum was collected within a mass range of 100 to 1,100 Da, while the spectra were manually examined using the FlexAnalysis 3.4 software (Bruker Daltonics, Bremen, Germany). In a typical process, 0.5 uL of serum samples were spotted on a polished steel target plate MTP 384 and air-dried followed by another 1 uL of GNS or SiNW nanomaterials. The spectra were then acquired in the reflection positive mode with smartbeam-II laser at 355 nm with laser frequency of 1,000 Hz. A random walk of 25 shots at raster spot and 20 different spots were measured for each individual sample, therefore, 500 satisfactory shots were obtained. Results: By taking advantage of 3D nanostructures and machine learning, we applied proposed approach to 94 patients with PAAD, as well as 203 healthy controls (Table). The results demonstrated an average sensitivity of 99% and a specificity over 98% in detecting cancers. 11 of 94 PAAD patients (11.70%) were CA 19-9 negative (CA19-9 < 37U/ml, stage I n = 2, stage II n = 7, stage III n = 1 and stage IV n = 1). LDI-TOF-MS recognized almost all CA 19-9-negative PAAD. The sensitivity and specificity were obviously superior to CA 19-9 in PAAD: only 1 of 94 PAAD (1.06%) were misclassified as healthy controls. In contrast, CA19-9 positive and CA 19-9 negative PAADs were not readily distinguished by this method. Therefore, this method was independent of tumor markers. Conclusions: Result suggested strong potential of proposed technique as a low-cost, superior precision, and high-throughput procedure for PAAD diagnosis and beyond. [Table: see text]