bluuebunny/crossref_metadata_2025 huggingface dataset:
PARADIGM study: A multicenter, randomized, phase III study of mFOLFOX6 plus panitumumab or bevacizumab as first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer.
Authors: Yoshino Takayuki , Uetake Hiroyuki , Tsuchihara Katsuya , Shitara Kohei , Yamazaki Kentaro , Watanabe Jun , Oki Eiji , Sato Takeo , Naitoh Takeshi , Komatsu Yoshito , Kato Takeshi , Mori Ikuo , Yamanaka Kazunori , Hihara Masamitsu , Soeda Junpei , Yamanaka Takeharu , Akagi Kiwamu , Ochiai Atsushi , Muro Kei
Published: January 2021

85

Background: The optimal choice of monoclonal antibodies (mAbs) for first-line treatment in patients (pts) with RAS ( KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC) remains controversial. The meta-analyses of subgroup analyses in phase III studies of pts with KRAS exon 2 wild-type mCRC suggested a longer overall survival (OS) with an anti-EGFR mAb over bevacizumab in pts with RAS wild-type mCRC or with left-sided primary tumors. However, there has been no prospective study comparing the two mAbs in these pt populations. This randomized phase III study was originally designed to demonstrate the superiority of panitumumab versus bevacizumab, both in combination with mFOLFOX6, for RAS wild-type mCRC, but we have revised the protocol to analyze efficacy in pts with a left-sided primary tumor as the primary (final) analysis. Methods: Eligible pts are aged 20-79 years with histologically/cytologically confirmed RAS wild-type chemotherapy-naive mCRC, and ECOG performance status 0-1. Between May 29, 2015 and Jun 8, 2017, 823 pts were randomized 1:1 to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6 by the minimization method and the randomisation was stratified by institution, age (20-64 vs. 65-79 years), and liver metastases (present vs. absent). The primary analysis was revised to adopt a hierarchical testing procedure; we first compare OS between the two arms in left-sided primary tumor population, and only if there is statistically significant difference, then ITT population analysis will be performed. In this revised plan, the expected number of deaths is 420 in the left-sided population to provide 80% power to detect an OS hazard ratio of 0.74 at a one-sided significance level of 0.02101 determined on the alpha spending function approach after one interim analysis. A large-scale exploratory biomarker substudy to identify potential biomarker candidates using tumor tissue and circulating tumor DNA is also underway (Clinical trial no.: NCT02394834). The data cut off for the primary analysis is expected to be during 1Q 2021. Results: Results are expected in 2021. Conclusions: Results are expected in 2021. Clinical trial information: NCT0239475.
Demographics and clinical characteristics of metastatic colorectal cancer patients treated with bevacizumab-awwb in real-world oncology clinics.
Authors: DeClue Richard , Rhodes Whitney , Accortt Neil A , Jin Ran , Sandschafer Darcie , Wertz Debra , Patel Kashyap B.
Published: January 2021

90

Background: Bevacizumab-awwb is a biosimilar to bevacizumab approved by the FDA based on evidence obtained in a phase 3 study in non-squamous non-small cell lung cancer. The present real-world evidence study evaluated experience with bevacizumab-awwb (launched 07/19/2019) in patients with metastatic colorectal cancer (mCRC) in a real-world oncology setting to gain insight into biosimilar use for a bevacizumab-awwb approved indication lacking clinical trial data. Methods: This retrospective analysis identified patients, age ≥ 18 years (y), within existing medical records diagnosed with mCRC who initiated bevacizumab-awwb as first- or later-line treatment. Patients were identified from the ConcertAI Definitive Oncology Dataset, a consolidated EMR database of CancerLinQ and Vector Oncology, representing geographically diverse practice locations, including rural and urban centers, within the United States. Results: A total of 304 patients were eligible for this analysis. First use of bevacizumab-awwb in mCRC occurred within 20 days of product launch. Most patients (n = 262, 86%) were treated in a community setting and more than half of all eligible patients received prior bevacizumab (n = 162, 53%). Among 42 patients treated in academic settings 29 (69%) had not received bevacizumab prior to receiving bevacizumab-awwb. In the 162 patients with prior bevacizumab use, 134 (83%) had no recorded disease progression between the last bevacizumab infusion and start of bevacizumab-awwb. Among these 134 patients, 111 (83%) received bevacizumab-awwb within 28 days of last bevacizumab dose. Demographic and clinical characteristics of patients stratified by prior bevacizumab use were comparable (Table). In both subgroups most patients had an adenocarcinoma histological diagnosis with primary tumors in the rectum or sigmoid colon. Overall, most frequent comorbidities of mCRC patients were diabetes (24%), chronic obstructive pulmonary disease (10%), and renal disease (8%). Conclusions: Patients with mCRC who received bevacizumab-awwb in this real-world oncology setting in the first year post product launch were similar regardless of prior bevacizumab use. Among patients with prior bevacizumab use, 83% continued with bevacizumab-awwb in the same line. In the subset of patients without progression post bevacizumab, most received bevacizumab-awwb within 28 days of last bevacizumab dose demonstrating use of bevacizumab-awwb in new and continuing patients. [Table: see text]
A multicenter phase Ib/II study of DNA-PK inhibitor peposertib (M3814) in combination with capecitabine and radiotherapy in patients with locally advanced rectal cancer.
Authors: Romesser Paul Bernard , Holliday Emma B. , Philip Tony , Garcia-Carbonero Rocio , Capdevila Jaume , Tuli Richard , Sarholz Barbara , Kuipers Mirjam , Rodriguez Almudena , Diaz-Padilla Ivan , Miller Eric David
Published: January 2021

TPS144

Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.
Olaparib ± bevacizumab versus bevacizumab + fluorouracil in patients with unresectable or metastatic colorectal cancer not progressing on first-line FOLFOX + bevacizumab: Phase III LYNK-003 study.
Authors: Mayo Carlos Alberto , Gurary Ellen B. , Marinello Patricia
Published: January 2021

TPS156

Background: Patients with metastatic colorectal cancer (CRC) often receive intensive platinum-based regimens, such as FOLFOX (fluorouracil [5-FU], leucovorin, oxaliplatin), as first-line (1L) therapy. For patients who do not progress during 1L platinum-based induction therapy, maintenance with a less intensive regimen can enhance clinical benefit and reduce toxicity. The CAIRO3 study showed a progression-free survival (PFS) benefit and a trend toward overall survival (OS) benefit in patients who received maintenance treatment with a fluoropyrimidine and bevacizumab versus observation following induction treatment of six cycles of platinum-based therapy. Olaparib is an oral PARP inhibitor that has efficacy in platinum-sensitive cancers. The randomized, open-label, phase 3 LYNK-003 trial will investigate the efficacy and safety of olaparib, alone or with bevacizumab, compared with bevacizumab plus 5-FU in advanced CRC that has not progressed during 1L induction treatment with FOLFOX plus bevacizumab. Methods: Patients aged ≥18 years with histologically confirmed metastatic or unresectable CRC that has not progressed after 1L induction of ≥6 cycles of FOLFOX plus bevacizumab and who can no longer tolerate oxaliplatin are eligible. Patients must have an ECOG performance status of 0-1, adequate organ function, and provide tumor tissue for biomarker analysis. Patients will be randomly assigned 1:1:1 to olaparib 300 mg twice-daily (BID), olaparib 300 mg BID plus bevacizumab 5 mg/kg every 2 weeks (Q2W), or bevacizumab 5 mg/kg Q2W plus 5-FU 2400 mg/m2 over 46-48 hours Q2W. Randomization will be stratified by response to prior FOLFOX plus bevacizumab (stable disease vs partial response/complete response), mutation status ( BRAFmut and/or Rasmut vs BRAFwt plus Raswt), and number of prior FOLFOX plus bevacizumab cycles (6-8 vs > 8 cycles). Response will be assessed by computed tomography or contrast-enhanced magnetic resonance imaging per RECIST 1.1 by blinded independent central review (BICR) every 8 weeks for the first 12 months and every 12 weeks thereafter. Treatment will continue until documented disease progression, unacceptable toxicity, investigator’s decision to discontinue, or patient withdrawal. The primary endpoint is PFS per RECIST 1.1 by BICR. Secondary endpoints are OS, objective response rate, duration of response, and safety. Approximately 525 patients will be enrolled. Currently, patients are being enrolled at 18 locations in 4 countries. Clinical trial information: NCT04456699.
A phase Ib multicenter study of trifluridine/tipiracil (FTD/TPI) in combination with irinotecan (IRI) in patients with advanced recurrent or unresectable gastric and gastroesophageal adenocarcinoma (aGEC) after at least one line of treatment with a fluoropyrimidine and platinum containing regimen.
Authors: Dayyani Farshid , Tam Kit , Kim Edward , Keshtmand Parvin , Ejadi Samuel , Lee Fa Chyi , Cho May Thet
Published: January 2021

TPS251

Background: In 2L+ aGEC, taxanes +/- ramucirumab or IRI are recommended treatment options. IRI has been tested in multiple single arm and randomized trials in second line (2L)+ aGEC, with reported objective response rates (ORR) in the 15-29% range and median progression-free survival (PFS) of <3 months (mo). Outcomes for aGEC remain poor with a median overall survival (OS) of 9.6 mo and PFS at 6 mo (PFS6) of only 36%. The TAGS trial in third line (3L)+ aGEC showed a significant improvement in OS from 3.6 mo to 5.7 mo with FTD/TPI over placebo. A 2L treatment with taxanes after 1L platinum containing regimens is currently associated with worsening peripheral neuropathy, which often leads to dose reductions, treatment delays, and a reduced quality of life for patients. The feasibility of FTD/TPI combined with IRI (+/- bevacizumab) in a modified 14-day schedule has been published for advanced colon cancer (PMID: 31924737) with no new safety signals while also encouraging activity in a cohort of heavily pretreated patients. Methods: Hypothesis:The combination of FTD/TPI with IRI in 2L+ aGEC is feasible, clinically active, and provides a treatment option which is not associated with development of peripheral neuropathy. Trial Design: 2-center, prospective, open label, non-randomized phase 1b trial. Eligibility: Diagnosis of aGEC, 1+ line of treatment including a fluoropyrimidine/platinum, ECOG 0-2, adequate organ function. Treatment:FTD/TPI 25mg/m2 on days 1-5 and IRI 180mg/m2 on day 1 every 14 days. G-CSF in allowed as needed. Primary objective: Feasibility of the regimen and estimate of efficacy. Primary endpoint: PFS6. Secondary objectives: OS, ORR, adverse events. Total number of pts to be enrolled N=20. Current enrollment (September 2020) N=14. Clinical trial information: NCT04074343.
A phase IIb, open-label, single-arm study of zanidatamab (ZW25) monotherapy in subjects with advanced or metastatic HER2-amplified biliary tract cancers.
Authors: Pant Shubham , Ducreux Michel , Harding James J. , Javle Milind M. , Oh Do-Youn , Wasan Harpreet Singh , Fortenberry Allison , Josephson Neil C. , Mwatha Anthony , Wang Kui , Fan Jia
Published: January 2021

TPS352

Background: Advanced biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CC), have a poor prognosis. Zanidatamab (ZW25) is a novel bispecific antibody that targets HER2 domains ECD2 and ECD4, resulting in increased antibody binding density and improved receptor internalization and downregulation relative to trastuzumab. In an ongoing phase I trial (ZWI-ZW25-101; NCT02892123), single-agent zanidatamab was well tolerated and showed promising anti-tumor activity across HER2-expressing solid tumors, including BTCs. These results formed the basis for a phase IIb study of zanidatamab in patients with BTC. Methods: Study ZWI-ZW25-203 (NCT04466891) is a global, multicenter, open-label, single-arm, phase IIb trial designed to evaluate the anti-tumor activity of zanidatamab monotherapy in patients with HER2-amplified, inoperable and advanced or metastatic BTCs, including GBC and CC. Patients must have received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease and have experienced disease progression after (or developed intolerance to) their most recent prior therapy. New or archival tumor tissue is required from all patients for HER2 amplification and protein expression testing at a central lab using in situ hybridization (ISH) and immunohistochemistry (IHC) assays. Approximately 100 patients with HER2 amplification by ISH will be enrolled. Zanidatamab 20 mg/kg will be administered intravenously every 2 weeks until one of the treatment discontinuation criteria is met. The primary endpoint of the study is the confirmed objective response rate (ORR) by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints include duration of response (DOR), proportion of patients with DOR ≥ 16 weeks, disease control rate, progression-free survival, overall survival, safety, quality of life, and disease-related pain. The safety and tolerability of zanidatamab will be assessed by recording the frequency and severity of adverse events, serious adverse events, and laboratory abnormalities, as well as the frequency of zanidatamab dose modifications. The study is currently open for enrollment. Clinical trial information: NCT04466891.
Perioperative chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone in gallbladder carcinoma or in front of radical resection in BTC: The phase III GAIN trial.
Authors: Goetze Thorsten Oliver , Lorenzen Sylvie , Bankstahl Ulli Simone , Lang Sven A. , Wittel Uwe A , Heeg Steffen , Bechstein Wolf Otto , Schnitzbauer Andreas , Pession Ursula , Reim Daniel , Keck Tobias , Königsrainer Alfred , Piso Pompiliu , Vogel Arndt , Wirth Thomas , Rahbari Nuh N. , Reissfelder Christoph , Belle Sebastian , Pauligk Claudia , Al-Batran Salah-Eddin
Published: January 2021

TPS353

Background: Radical surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) and Gallbladder Carcinoma (GBC). Nevertheless, 5-year OS is only 20–40% after curatively intended resection. GBC is the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. The majority of gallbladder carcinoma cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication, so called incidental gallbladder carcinomas. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. Encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase management of GBC and intrahepatic as well extrahepatic cholangiocarcinoma, especially because data regarding pure adjuvant chemotherapy in BTC`s are currently conflicting. Methods: GAIN is a multicenter, randomized, controlled, open-label phase III trial, including pts with GBCs in front of radical liver resection and pts with resectable/borderline resectable intra- and extrahepatic cholangiocarcinomas (ICC/ECC). Pts. are randomized to either neoadjuvant systemic chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) followed by radical surgery or to direct surgery without neoadjuvant treatment. Primary endpoint is OS; secondary endpoints are PFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. A total of N = 333 patients with GBC or BTC will be included. Recruitment has just started; first patient in was on December 6th, 2019. Clinical trial information: NCT03673072.
A phase II study of infigratinib in previously treated advanced/metastatic cholangiocarcinoma with FGFR gene fusions/alterations.
Authors: Javle Milind M. , Kelley Robin Kate , Springfeld Christoph , Abou-Alfa Ghassan K. , Macarulla Teresa , Tanasanvimon Suebpong , Goyal Lipika , Borbath Ivan , Bitzer Michael , Yong Wei-Peng , Philip Philip Agop , Alvarez-Gallego Rafael , Pande Amit , Shepherd Stacie Peacock , Fontaine Jacki , Roychowdhury Sameek
Published: January 2021

TPS356

Background: The FGFR family plays an important role in cholangiocarcinoma, with FGFR2 gene fusions detected in about 15% of patients with cholangiocarcinoma. Infigratinib is an FGFR1–3-selective oral tyrosine kinase inhibitor under evaluation in multiple indications including front-line and pre-treated cholangiocarcinoma. CBGJ398X2204 is an ongoing phase II study evaluating the efficacy of single-agent infigratinib in patients with advanced or metastatic cholangiocarcinoma with FGFR genetic alterations who have received prior gemcitabine. Methods: Study CBGJ398X2204 consists of 3 cohorts and patients in all cohorts receive oral infigratinib once daily for 21 days of a 28-day treatment cycle. Treatment will continue until progressive disease, intolerance, withdrawal of consent, or death. Cohort 1 includes patients with FGFR2 gene fusions or translocations. Cohort 2 includes patients with FGFR genetic alterations other than FGFR2 gene fusions (patients in both Cohorts 1 and 2 must not have received any prior FGFR inhibitors). Cohort 3 includes patients with FGFR2 gene fusions who have received prior treatment with a selective FGFR inhibitor other than infigratinib. The primary endpoint is objective response rate (ORR, RECIST v1.1 per central review). Secondary endpoints include overall survival and overall response rate (per investigator). Safety, pharmacokinetics, and exploratory genetic alterations/biomarkers will also be measured. The study was initiated in 2014 and has a planned enrollment of up to 160 patients across all 3 cohorts (120 in Cohort 1, 20 in Cohort 2, and 20 in Cohort 3). Cohort 1 has completed enrollment and findings from this Cohort are the focus of a separate abstract submitted to the meeting. Results are not currently available from Cohorts 2 and 3 (trial in progress). Clinical trial information: NCT02150967.
Systemic therapy with a loco-regional treatment in patients with locally advanced pancreatic cancer: The SMART study.
Authors: Ahmed Shahid , Ahmed Osama , Anderson Deborah , Beck Gavin , Chalchal Haji I. , Dwernychuk Lynn , Gitlin Josh , Hammond Austin , Iqbal Mussawar , Lim June , Pati Sukanya , Sari Nazmi , Shaw John , Souied Osama , Wall Christopher , Zaidi Adnan , Moser Michael
Published: January 2021

TPS445

Background: Pancreatic cancer is a major cause of cancer-related death. About 40% of patients with pancreatic cancer present with locally advanced disease and are not candidates for curative surgery. Most patients are treated with chemotherapy with a limited life expectancy. The role of local treatment such as radiation is not well defined. Other conventional ablative therapies, such as thermal or cryoablation have limited role due to the risk of collateral damage to the adjacent structures. Irreversible electroporation (IRE) is a novel non-thermal ablation technology that does not cause injury to nearby blood vessels, ducts, and bowel and has the potential to provide longer disease control and thereby better overall survival. We hypothesized that addition of IRE to combination chemotherapy in patients with locally advanced pancreatic cancer will improve their outcomes, and patients with undetectable 12-week post IRE circulating tumor cell DNA will have better prognoses. Methods: It is a prospective, multicenter, single-arm phase II study. The primary objective is to determine 12-month PFS rate of patients with locally advanced pancreatic cancer who are treated with combination chemotherapy and IRE. Secondary objectives include identification of prognostic and predictive biomarkers, 24-months survival rate, quality of life of subjects, as well as cost-effectiveness and complication rates of IRE. Based on the assumption that treatment with IRE and chemotherapy would result in doubling of PFS versus chemotherapy alone a sample of n = 27 of patients with locally advanced pancreatic adenocarcinoma is estimated. Eligible patients will be recruited at the two major cancer centers in Saskatchewan. All IRE-eligible patients will receive 12 weeks of induction combination chemotherapy and will undergo IRE if there is no disease progression. An additional 12 weeks of chemotherapy will be recommended. Patients who are not eligible for IRE will receive chemotherapy at the discretion of treating oncologist until disease progression or until they become eligible for IRE. Circulating tumor DNA and a panel of genes will be examined using next-generation sequencing for their correlation with prognosis. Quality of life will be assessed, and cost-effectiveness analysis of IRE will be performed.The results of this study will be used to develop a future multicenter, national phase III trial. Clinical trial information: NCT04276857.
A phase III trial of tumor-treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally-advanced pancreatic adenocarcinoma (LAPC): PANOVA-3.
Authors: Picozzi Vincent J. , Macarulla Teresa , Philip Philip Agop , Becerra Carlos Roberto , Dragovich Tomislav
Published: January 2021

TPS448

Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma. TTFields at specific frequency (150-200 kHz) are delivered via transducer arrays placed on the skin in proximity to the tumor site. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The phase 2 PANOVA study, the first trial testing TTFields in pancreatic cancer patients, demonstrated the safety and preliminary efficacy of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and LAPC. The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy and safety of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Methods: Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2 once weekly). TTFields (150 kHz) will be delivered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint and progression-free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Clinical trial information: NCT03377491.
Resection of Retro-Hepatic Vena Cava (RHVC) En-bloc with Caudate Lobe without Vascular Exclusion for a Low Grade Leiomyosarcoma of Inferior Vena Cava
Authors: Altomare Michele , Sposito Carlo , Regalia Enrico , Coppa Jorgelina , Flores Maria , Manzo Elena , Droz Dit Busset Michele , Mazzaferro Vincenzo
Published: January 2021

Background

Leiomyosarcomas (LMS) of the inferior vena cava (IVC) originate in the retrohepatic (RHVC) portion in 15% of cases.1 Due to complex anatomy and need to preserve venous outflow from the infra-diaphragmatic viscera, the operation may require total vascular exclusion, veno-venous bypass and hypothermic liver resections.2,3 In this video, virtual planning of the operation allowed a parenchyma-sparing radical resection in a patient with limited liver reserve.

Methods

A 12-cm LMS of RHVC invading the entire segment 1 (i.e., Spiegel’s lobe, paracaval portion, and caudate process) was diagnosed in a man with metabolic steato-hepatitis (BMI: 34). He had no response to previous chemotherapy. Major hepatectomy was excluded considering the high risk of postoperative liver failure. 3D-reconstruction of regional anatomy allowed planning of a parenchymal-sparing, en bloc resection of tumor, RHVC, and caudate lobe while avoiding hilar and suprahepatic venous clamping.

Results

The operation strategy relied on the en bloc separation of caudate lobe, RHVC, and tumor from the hepatic veins confluence and the posterior segments after complete mobilization of the liver. Vessel loop-assisted hanging maneuver, encircling tumor, and RHVC with superimposed 3D-reconstructions guided the parenchymal transection, while preserving the middle hepatic vein outflow. RHVC was replaced with prosthetic material.

Conclusions

Complex resection of primary tumor of the IVC en bloc with caudate lobe and RHVC can be attempted in chronic liver diseases at-risk of postoperative failure. Preservations of transhepatic flow and liver function depends on tumor size and preservation of noninvaded hepatic-veins confluence. Preoperative virtual 3D reconstruction is crucial in surgical planning.
Narratives on Migration
Authors: Ioannou Nasia
Published: January 2021

no abstract
Testing at the Source: Analytics-Enabled Risk-Based Sampling of Food Supply Chains in China
Authors: Jin Cangyu , Levi Retsef , Liang Qiao , Renegar Nicholas , Springs Stacy , Zhou Jiehong , Zhou Weihua
Published: January 2021

This paper illustrates how supply chain (SC) analytics could provide strategic and operational insights to evaluate the risk-based allocation of regulatory resources in food SCs, for management of food safety and adulteration risks. This paper leverages data on 89,970 tests of aquatic products extracted from a self-constructed data set of 2.6 million food safety tests conducted by the China Food and Drug Administration (CFDA) organizations. The integrated and structured data set is used to conduct innovative analysis that identifies the sources of adulteration risks in China’s food SCs and contrasts them with the current test resource allocations of the CFDA. The analysis highlights multiple strategic insights. Particularly, it suggests potential gaps in the current CFDA testing allocation by SC location, which is heavily focused on retail and supermarkets. Instead, the analysis indicates that high-risk parts of the SC, such as wholesale and wet markets, are undersampled. Additionally, the paper highlights the impact that SC analytics could have on policy-level operational decision making to regulate food SCs and manage food safety. The hope is that the paper will stimulate the interest of academics with expertise in these areas to conduct more work in this important application domain.

This paper was accepted by Charles Corbett, operations management.
A Ideia da Consideração Positiva Incondicional como Epoché: Limites e Suspensão do Quê?
Authors: Branco Paulo Coelho Castelo
Published: January 2021

Este artigo objetiva refletir os limites da ideia de consideração positiva incondicional como uma epoché, de modo questionar o que é suspenso. Para isso, apresenta as noções husserliana de epoché e rogeriana de consideração positiva incondicional. Depois, situa as origens das apropriações da epoché pela clínica fenomenológica e pela abordagem rogeriana. Posteriormente, desenvolve reflexões que demarcam alguns limites entre essas atitudes. Conclui que a consideração positiva incondicional poderia ser a suspensão dos juízos que procedem dos afetos de simpatia, apatia e antipatia. Em uma meta-teoria, isso serve para descrever o procedimento de escuta não-diretiva sem julgamentos, a qual parte da assimilação de uma visão de mundo oriunda da Fenomenologia, mas não se trata de uma Fenomenologia pura, filosofia fenomenológica ou Psicologia Fenomenológica. A consideração positiva incondicional é uma atitude de escuta que se desenvolveu fora do método fenomenológico e não precisa ser legitimada pela epoché, não propõe nenhuma redução, não suspende a crença na tendência à autorrealização e sua suspensão não é fenomenológica.
A Autoconsciência na Teoria de Aron Gurwitsch: Posição e Crítica
Authors: Marangoni Pedro Henrique Santos Decanini , Verissimo Danilo Saretta
Published: January 2021

O objetivo do presente trabalho é apresentar e discutir o modo como o filósofo lituano Aron Gurwitsch concebe o papel da autoconsciência (self-awareness) e da autoconsciência corporal (bodily self-awareness) no interior de sua teoria do campo de consciência. Em um primeiro momento, apresentamos as dimensões do campo de consciência realçando os princípios organizacionais que estão em jogo na integração entre as diferentes estruturas da experiência consciente. Esta contextualização permite compreender a posição ocupada pela autoconsciência naquilo que o filósofo denomina de "margem" da consciência, domínio da experiência caracterizado pela "irrelevância" ou indiferença em relação à apresentação temática – do objeto da atenção. Em um segundo momento, concentrar-nos-emos em descrever a autoconsciência da dimensão encarnada da existência, com o propósito de avaliar os critérios que permitem a Gurwitsch qualificar a autoconsciência corporal sob a rubrica do conceito de "irrelevância". Ao final, esboçamos certos questionamentos à posição de Gurwitsch desenhados a partir de críticas contemporâneas da fenomenologia e das ciências cognitivas à abordagem do autor.
A Decisão de Tentar o Suicídio sob a Lente Fenomenológico-existencial Sartriana
Authors: Ming-Wau Carlos , Boris Georges Daniel Janja Bloc , Melo Anna Karynne , Silva Raimunda Magalhães da
Published: January 2021

A tentativa de suicídio é uma escolha entre viver ou morrer decidida a partir da vivência da liberdade. Neste artigo, objetivamos compreender a experiência vivida da decisão de tentar o suicídio. Trata-se de uma pesquisa qualitativa com abordagem fenomenológica, cujo suporte teórico-metodológico foi endossado pela fenomenologia existencial de Sartre. Utilizamos entrevistas fenomenológicas para coletar os depoimentos de cinco pessoas adultas que tentaram suicídio, abordadas por meio desta questão: como foi a sua experiência de tentar o suicídio? A análise dos dados revelou os sentidos que os participantes atribuíam à sua decisão de tentar o suicídio. A partir dos depoimentos, elencamos duas unidades de sentido: Morte, vida e liberdade nas tentativas de suicídio e "Acho que a morte é melhor do que viver neste mundo". Analisamos e discutimos como os participantes vivenciaram a decisão de morrer ou viver nas situações de adversidade que surgiam nos contextos reais de suas histórias de vida. Concluímos que a tentativa de suicídio é uma forma de escapar de situações de infortúnios, conflitos, desamparo, desespero, angústia e sofrimento, quando os participantes foram convocados a escolher, como uma expressão da liberdade ontológica, entre suportar os malogros existenciais e decidir dar cabo de suas vidas.
Stainless steel ligatures in orthodontic treatment
Authors: Elhussein Mustafa , Sandler Jonathan
Published: January 2021

Using stainless steel auxiliary ligatures in conjunction with fixed orthodontic appliances is of paramount importance in many stages of orthodontic treatment. There is a lack of articles in the literature that provides a comprehensive review of the uses of different methods of ligation in orthodontic treatment. The aim of this article is to provide an illustrated review of their use with fixed appliances; moreover, it will provide practical tips for their appropriate use.

CPD/Clinical Relevance: This article aims to provide a review, with detailed illustration, of the use of stainless steel ligatures in orthodontic treatment.
Gentamicin pre-soaking of hamstring autografts decreases infection rates in anterior cruciate ligament reconstruction
Authors: Moriarty Peter , Kayani Babar , Wallace Charles , Chang Justin , Plastow Ricci , Haddad Fares S.
Published: January 2021

Aims

Graft infection following anterior cruciate ligament reconstruction (ACLR) may lead to septic arthritis requiring multiple irrigation and debridement procedures, staged revision operations, and prolonged courses of antibiotics. To our knowledge, there are no previous studies reporting on how gentamicin pre-soaking of hamstring grafts influences infection rates following ACLR. We set out to examine this in our study accordingly.

Methods

This retrospective study included 2,000 patients (1,156 males and 844 females) who underwent primary ACLR with hamstring autografts between 2007 to 2017. This included 1,063 patients who received pre-soaked saline hamstring grafts for ACLR followed by 937 patients who received pre-soaked gentamicin hamstring grafts for ACLR. All operative procedures were completed by a single surgeon using a standardized surgical technique. Medical notes were reviewed and data relating to the following outcomes recorded: postoperative infection, clinical progress, causative organisms, management received, and outcomes.

Results

Superficial wound infection developed in 14 patients (1.31 %) receiving pre-saline soaked hamstring grafts compared to 13 patients (1.38 %) receiving pre-gentamicin soaked hamstring grafts, and this finding was not statistically significant (p = 0.692). All superficial wound infections were treated with oral antibiotics with no further complications. There were no recorded cases of septic arthritis in patients receiving pre-gentamicin soaked grafts compared to nine patients (0.85%) receiving pre-saline soaked grafts, which was statistically significant (p = 0.004).

Conclusion

Pre-soaking hamstring autographs in gentamicin does not affect superficial infection rates but does reduce deep intra-articular infection rates compared to pre-soaking hamstring grafts in saline alone. These findings suggest that pre-soaking hamstring autografts in gentamicin provides an effective surgical technique for reducing intra-articular infection rates following ACLR. Cite this article: Bone Jt Open 2021;2(1):66–71.
Defining brokers, intermediaries, and boundary spanners: a systematic review
Authors: Neal Jennifer Watling , Neal Zachary P. , Brutzman Brian
Published: January 2021

Background:

A growing literature focuses on the roles of brokers, intermediaries, and boundary spanners (BIBS) in addressing the challenges of transferring research evidence between the research and practice or policy communities.

Aims and objectives:

In this systematic review, we examined two research questions: (1) where, how, and when are different BIBS terms (broker, intermediary, and boundary spanner) used? and (2) which BIBS terms get defined, and when these terms are defined, who are BIBS and what do they do?

Methods:

We conducted literature searches designed to capture articles on BIBS and the transfer of research evidence. We extracted information about eligible articles’ characteristics, use of BIBS terms, and definitions of BIBS terms.

Findings:

The search revealed an initial pool of 667 results, of which 277 articles were included after screening. Although we coded 430 separate uses of BIBS terms, only 37.2% of these uses provided explicit definitions. The terms, ‘broker’ and ‘brokerage’, were commonly applied in the health sector to describe a person engaged in multiple functions. The term, ‘intermediary’, was commonly applied in the education sector to describe an organisation engaged in dissemination. Finally, the terms ‘boundary spanner’ and ‘boundary spanning’ were commonly applied in the environment sector to describe people or organisations that engage in relationship building.

Discussion and conclusions:

Results demonstrated that when BIBS were defined, there were important (albeit implicit) distinctions between terms. Based on these results, we identify archetypal definitions for brokers, intermediaries, and boundary spanners and offer recommendations for future research.
Paid parental leave and fathers’ involvement: capturing fathers’ gender beliefs and fathering perceptions
Authors: Streckenbach Luisa A. , Castiglioni Laura , Schober Pia S.
Published: January 2021

This study examines how multidimensional gender and fathering beliefs of fathers may explain their relative involvement in childcare after considering paid leave uptake. We draw on cross-sectional survey data from one German state, which allow us to distinguish three belief dimensions: (1) gender traditionalism and essentialism, (2) fathering attitudes, and (3) fathering self-concepts and self-efficacy. By means of multiple linear regression models we investigate how the different dimensions of gender and fatherhood beliefs relate to fathers’ relative involvement in basic and indirect childcare tasks. Our results show that gender (essentialist) ideologies and fatherhood attitudes were strongly associated with fathers’ relative involvement in both childcare domains. The higher fathers perceived self-efficacy in fathering, the more involved they were in basic but not indirect care. All belief dimensions mediated the positive association of fathers’ uptake of paid leave with their involvement in basic childcare.
Normalization of underwater laser-induced breakdown spectroscopy using acoustic signals measured by a hydrophone
Authors: Huang Fuzhen , Tian Ye , Li Ying , Ye Wangquan , Lu Yuan , Guo Jinjia , Zheng Ronger
Published: January 2021

Laser-induced breakdown spectroscopy (LIBS) signals in water always suffer strong pulse-to-pulse fluctuations that result in poor stability of the spectrum. In this work, a spectrum normalization method based on acoustic signals measured by a hydrophone immersed in water was developed and compared with laser energy normalization. The characteristics of the acoustic signals were studied first, and the correlations between the acoustic signals and LIBS spectra were analyzed. It showed that the spectral line intensity has a better linear relationship with the acoustic energy than with the laser energy. Consequently, the acoustic normalization exhibited better performance on the reduction of LIBS spectral fluctuation versus laser energy normalization. Calibration curves of Mn, Sr, and Li were then built to assess the analytical performance of the proposed acoustic normalization method. Compared with the original spectral data, the average RSD_C values of all analyte elements were significantly reduced from 5.00% to 3.18%, and the average RSD_P values were reduced from 5.09% to 3.28%, by using the acoustic normalization method. These results suggest that the stability of underwater LIBS can be clearly improved by using acoustic signals for normalization, and acoustic normalization works more efficiently than laser energy normalization. This work provides a simple and cost-effective external acoustic normalization method for underwater LIBS applications.
Deep neural network for coded mask cryptographical imaging
Authors: Lee Ya-Ti Chang , Fang Yi-Chun , Tien Chung-Hao
Published: January 2021

We proposed a novel cryptographic imaging scheme that is the combination of optical encryption and computational decryption. To prevent personal privacy from being spied upon amid the imaging formation process, in this study we applied a coded mask to optically encrypt the scene and utilized the deep neural network for computational decryption. For encryption, the sensor recorded a new representation of the original signal, not being distinguishable by humans on purpose. For decryption, we successfully reconstructed the image with the mean squared error equal to 0.028, and 100% for the classification through the Japanese Female Facial Expression dataset. By means of the feature visualization, we found that the coded mask served as a linear operator to synthesize the spatial fidelity of the original scene, but kept the features for the post-recognition process. We believe the proposed framework can inspire more possibilities for the unconventional imaging system.
Twyman effect in thin curved optics: effects of variable thickness and curvature
Authors: Lakshmanan Sanjay N. , Lambropoulos John C.
Published: January 2021

Grinding or finishing of thin curved optics introduces surface-localized stresses that may result in bending deformations, thus affecting optical performance (Twyman effect). The Twyman effect depends on local thickness of the optic as well as its curvature. We use numerical and analytical techniques to assess the effects of these variables for shallow and deeply curved axisymmetric optics. A useful metric of comparison, valid for shallow optics, is the deformation of a similar flat optic (window). This comparison is inadequate for more curved optics, which demonstrate a smaller deformation that is now localized in a boundary layer near the optic-free edge. The effects of thickness variation are also presented. Normal deflection and slope for a positive optic (thickness at the center greater than the tip) are well approximated by a constant thickness optic. This is not the case for a negative optic, where deformations near the apex are more pronounced, thus extending significant deformations through the full optic aperture.
Megahertz repetition rate satellite laser ranging demonstration at Graz observatory
Authors: Wang Peiyuan , Steindorfer Michael A. , Koidl Franz , Kirchner Georg , Leitgeb Erich
Published: January 2021

Using ultra-high repetition rate lasers (

≥

100

k
H
z

) is one of the most promising strategies for the next generation of satellite laser ranging (SLR) systems. We present successful 1 MHz repetition rate SLR to targets up to inclined geosynchronous orbits at nighttime. Among those, a maximum return rate of up to 53% was achieved, equivalent to 265 k returns per second for the satellite Swarm-B. In addition, daytime megahertz (MHz) SLR was realized by utilizing a propagated MHz range gate to reduce the massive background noise. In the future, MHz SLR will greatly improve current technology with respect to data amount and data precision, shorter acquisition time, target signature detection, and attitude determination.
Asymmetric-ration optical power couplers based on nano-pixel structure
Authors: Han Yu , Chen Zanhui , Wang Leiyun , Li Wenying , Jiang Haisong , Hamamoto Kiichi
Published: January 2021

An optical power coupler is one of the most well-used components in integrated photonics. Although couplers with an output power ratio 1:1 have been widely studied in the past, constructing asymmetric-ration optical power couplers is still an issue that is difficult to be addressed by using traditional Y-branch waveguides. Artificial intelligence (AI) assisted design is an effective technique for realizing complex optical structures. In this work, we have designed asymmetric-ration optical power couplers by using AI assisted design. Two couplers with the targeted splitting power ratio as 1:9 and 1:99 have been designed, respectively. In the AI assisted design, the coupler area was divided into discrete nano-pixels in the shape of circular holes with the same dimension. The AI controlled each pixel to be occupied by waveguide or air and trialed the occupation of each pixel one by one. In a 3.4 × 3.2 µm2 area, it took 1452 trials to obtain one optimized coupler. As a result, a splitting power ratio of 1:9.007 and 1:99.004 for the two couplers has been confirmed by using the finite-difference time-domain method. In addition, the waveguide configuration was further modified as the excess loss of the AI-designed coupler was a bit high, more than 3.50 dB. The way to reduce the loss is as follows: 1) positioning optimization of the output waveguide to avoid light scattering at the boundary between the coupler and the output waveguide, and 2) widening the output waveguide width to avoid insufficient light coupling. As a result, a scattering loss reduction of 1.7 dB by position optimization, and a coupling loss reduction of 1.6 dB by width widening were confirmed. The achieved design also exhibited a wide operation wavelength ranging from 1500–1600 nm in addition to sufficient fabrication tolerance of ±10 nm (± 11%).