bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of BIM as a lean tool in design phase
Authors: Aziz Rania Mohsen , Nasreldin Tark Ibrahim , Hashem Omnia Mamdouh 
Published: January 2024

AbstractIn the architectural, engineering, and construction industry, poor visualization of construction processes and lack of information exchange between different work teams can lead to poor performance. To address these challenges, lean construction methodologies aim to reduce and eliminate waste in construction processes, while BIM technology aims to enhance collaboration between project team members. In general, these technologies can be used together to improve project management and cost reduction. This can be achieved through improving workflow and coordination, enhancing interaction among project members, and using available tools to analyze and improve work. Many aspects of the integration between LC and BIM have been studied, and researchers have come up with some findings and recommendations. Most studies previously demonstrated theoretically that cost reductions using BIM techniques are significant compared to the traditional approach of project management. This is what this study proved practically by applying BIM in the design of a building which is quite successful in construction as it identifies the main causes of construction waste such as reducing waiting time and reducing non-value-added work by using Dynamo to develop these designs. So, the research problem comes, which is how to keep up with development in the field of construction by applying different BIM programs, which results in reducing the time and cost used in design. BIM is a technology that aims to enhance project management and cut costs. A digital representation of the project that contains all the data required for planning, managing, and carrying out the project is created using BIM.
Prospective observational study investigating the impact of treatment sequence using regorafenib and FTD/TPI for metastatic colorectal cancer on overall survival (OSERO study).
Authors: Chida Akihiko , Kawakami Takeshi , Hamano Tetsutaro , Masuishi Toshiki , Mitani Seiichiro , Yasui Hisateru , Ishiguro Atsushi , Ando Takayuki , Sawada Kentaro , Harada Kazuaki , Takahashi Naoki , Boku Shogen , Kashiwada Tomomi , Esaki Taito , Yagisawa Masataka , Sugiyama Keiji , Yamamoto Kouji , Yuki Satoshi , Yamazaki Kentaro , Oki Eiji 
Published: January 2024

103 Background: Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BEV) are widely used as a later-line treatment for patients (pts) with metastatic colorectal cancer (mCRC). It is still unclear which is the preferable treatment strategy to start with, either REG, FTD/TPI, or FTD/TPI + BEV in clinical practice. Methods: We conducted a non–intervention, prospective, observational study in pts with mCRC at 41 sites. The key eligibility criteria were ECOG performance status (PS) 0 or 1, pts refractory to or intolerant of fluoropyrimidine, oxaliplatin, irinotecan, anti–angiogenesis, and anti–EGFR therapy if RAS status were wild type, and pts who plan to receive sequential treatment with REG and FTD/TPI BEV. Pts who starts with REG are enrolled in cohort A, FTD/TPI in cohort B, or FTD/TPI plus BEV in cohort C. The primary endpoint is overall survival (OS) of each group. Results: Between September 2020 and December 2022, a total of 501 pts were enrolled and 455 were identified as full analysis set. Pts’ characteristics of cohort A (149 pts) / B (80 pts) /C (226 pts) were as follows: median age 64.0 / 65.5 / 67.0 years, male 53.0 / 52.5 / 55.3%, ECOG PS 0 52.3 / 31.3 / 48.7%, tumor location right–sided 33.6 / 27.5 / 20.4%, RAS wild type 35.6 / 41.3 / 43.4%, and BRAF V600E mutant type 6.7 / 7.5 / 4.0 %. Pts who received subsequent with FTD/TPI BEV in cohort A / REG in cohort B / REG in cohort C were 62.4 / 37.5 / 62.8%. The median OS of cohort A / B / C was 11.8 / 7.1 / 10.2 months. Cox hazard model revealed hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01–1.94; p = 0.043) for cohort B, and HR 1.04 (95% CI 0.80–1.34; p = 0.784) for cohort C compared with cohort A. After adjusting age, ECOG PS, tumor location, the number of metastatic sites, the adjusted HR were 1.29 (95% confidence interval [CI] 0.87–1.91; p = 0.213) for cohort B, and 1.00 (95% CI 0.75–1.34; p = 0.998) for cohort C compared with cohort A. Conclusions: This study demonstrates that the OS are comparable regardless of whether REG, FTD/TPI, or FTD/TPI + BEV is administered first. Clinical trial information: UMIN000040586 .
DKN-01 plus bevacizumab and chemotherapy as second-line (2L) investigational therapy in advanced microsatellite stable (MSS) colorectal adenocarcinoma (CRC): DeFianCe trial.
Authors: Pelster Meredith , Strickler John H , Sirard Cynthia A. , Baum Jason , Haas Mike , Devoe Craig E. , Bustamante Liliana , Bubis Jeffrey Alan , Womack Mark Sanders , Chung Ki Y. , Raff Joshua P. , Wainberg Zev A. 
Published: January 2024

104 Background: CRC is characterized by hyperactivation of the Wnt pathway where DKK1 plays a critical regulatory role. DKN-01 is an IgG4 monoclonal antibody that potently neutralizes DKK1. DKN-01 has immunomodulatory activity and stimulates a pro-inflammatory tumor microenvironment. Elevated DKK1 expression has been shown to correlate with fluorouracil (5FU) resistance in CRC tumors. 5FU-based combination therapies have demonstrated promising clinical activity in combination with DKN-01 in gastric cancer. In pre-clinical models of 5FU-resistant CRC, DKN-01 showed potent anti-tumor effects. Methods: DeFianCe (NCT05480306) is a Phase 2 randomized, open-label, two-part, multicenter study to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as 2L treatment of advanced MSS CRC patients (pts). The primary endpoint of the single arm Part A (DKN-01 + SOC) was safety and tolerability with secondary endpoints including overall response rate (ORR), progression-free survival (PFS) and overall survival. Retrospective analysis of tumoral DKK1 mRNA expression was measured centrally by in situ hybridization. Results: Thirty-three pts enrolled in Part A between Sept 2022-April 2023. As of 21 Aug 2023, median age 56 years (35, 84); 20 males. 29 pts had tumors with evaluable baseline DKK1 expression; 55% were DKK1-expressing (≥1% tumor cells). All patients had received prior 5FU-based therapies, 30 pts (91%) with oxaliplatin in combination and 17 pts (52%) had prior bevacizumab. 24 pts (73%) had RAS mutations (22 KRAS, 2 NRAS) and 23 pts (70%) had liver metastasis. 30 pts (91%) received DKN-01 + bevacizumab + FOLFIRI. 17 pts (52%) had ≥grade 3 treatment related adverse events (TRAE) with neutrophil count decreased, anemia and fatigue representing the most common. No pt discontinued DKN-01 due to a TRAE. Of the 27 response evaluable pts the ORR was 30% and the DCR was 93%: 8 PR, 17 SD and 2 PD. The median PFS has not been reached. Conclusions: DKN-01 in combination with SOC was well tolerated with promising preliminary activity (ORR 30% and DCR 93%) in the single arm Part A. PFS has not been reached and survival follow up is ongoing. Part B randomized expansion phase has begun and is enrolling an additional 130 pts. Tumoral DKK1 expression and correlation with clinical outcomes will be evaluated as an exploratory efficacy endpoint. Clinical trial information: NCT05480306 .
Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Updated results from multi-cohort, multi-center phase II trial ALTER-G-001-cohort A.
Authors: Wu Junwei , Zhu Lingjun , Zhou Chenfei , Shi Min , Chen Jun , Zhao Liqin , Han Zhengxiang , Wang Chunbing , Jiang Jinling , Yan Jun , Wang Chun , Wei Xiaowei , Mao Yong , Cui Donghai , Yang Xiuli , Qin Zhiquan , Tang Xinyu , Zhang Jun 
Published: January 2024

112 Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs). The prognosis of CRC with unresectable LMs is poor, with a 5-year survival rate of less than 5%. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, etc.). In cohort A, CRC patients received induction therapy (6 cycles, q3w): anlotinib (12 mg, PO, QD, days 1-14), oxaliplatin (130 mg/m2, IV, day 1), capecitabine (850 mg/m2, PO, BID, days 1-14). Patients without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 45 patients were enrolled in cohort A, the median age was 67 years (35-75), 66.7% male, 91.1% ECOG-PS 1 and 60% had LMs only. After induction therapy, 8 patients received surgical resection. Currently, 13 patients are receiving induction therapy and 10 are undergoing maintenance therapy, with a maximum duration of treatment (DOT) of 13.7 months. Of 39 evaluable patients in cohort A, ORR and DCR were 48.7% and 97.4% (PR, n=19; SD, n=19, 16 SD had reduced tumor size). The median PFS was not reached. 36 patients had TEAEs and ≥ grade 3 TEAEs (33.3%) mainly included neutropenia (11.1%), hypertension (6.7%), and white blood cell decreased (6.7%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs CRC tumors. Clinical trial information: NCT05262335 .
HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer (mCRC) refractory to anti-EGFR antibodies.
Authors: Ishiguro Atsushi , Nakatsumi Hiroshi , Harada Kazuaki , Yuki Satoshi , Sawada Kentaro , Sogabe Susumu , Ando Takayuki , Sasaki Yusuke , Yoshikawa Ayumu , Nakamura Michio , Dazai Masayoshi , Tateyama Miki , Muto Osamu , Kotaka Masahito , Sagawa Tamotsu , Hatanaka Kazuteru , Takagi Ryo , Sakata Yuh , Komatsu Yoshito 
Published: January 2024

113 Background: Aflibercept (AFL) combined with FOLFIRI prolongs overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) who failed a prior oxaliplatin-based regimen. However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI in RAS / BRAF wild type pts previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese pts with mCRC failing a prior oxaliplatin-based chemotherapy combined with an anti-EGFR agent. Methods: This was a prospective open-label phase II trial. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-FU 400 mg/m2 and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months; secondary endpoints included OS, PFS, overall response rate (ORR), disease control rate (DCR), adverse events, and relative dose intensity (RDI) for each drug. Given a PFS rate threshold at 6 months of 38.9% and an expected PFS rate of 58.4% with AFL plus FOLFIRI, a sample size of 41 pts was required (two-sided alpha, 0.1; beta, 0.2). Analyses were conducted in the full analysis set (FAS) of pts satisfying eligibility criteria. Results: Forty-three patients were enrolled between November 2019 and October 2022, and 43 were analyzed (median age 68 years (range 27-80); male, 69.8%; ECOG PS 0/1, 72.1%/27.9%; left sided primary tumor, 90.7%). The primary endpoint was met: 6-month PFS rate was 58.7% (90%CI, 45.5%-71.9%). Median PFS and OS were 7.3 months (95%CI, 5.5-11.0 months) and 18.8 months (95%CI, 12.9-26.6 months), respectively. The ORR was 23.3 % (95%CI, 11.8-38.6%) and DCR was 88.4% (95%CI, 74.9- 96.1%). Mean RDI of AFL, irinotecan, bolus 5-FU and infusional 5-FU were 75.3% (SD, 26.2), 50.6% (SD, 12.5), 31.6% (SD, 26.6), and 58.7% (SD, 7.21), respectively. The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%) and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. Conclusions: Results of this prospective phase II study suggest that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese pts with mCRC who failed a first-line oxaliplatin-based plus anti-EGFR regimen. Clinical trial information: jRCTs011190006 .
Prognostic factors of patients (pts) with salvage-line metastatic colorectal cancer (mCRC).
Authors: Bando Hideaki , Oki Eiji , Takeda Yuriko , Misumi Toshihiro , Suzuki Motoko , Wakabayashi Masashi , Yamazaki Kentaro , Grothey Axel , Mayer Robert J. , Li Jin , Andre Thierry , Shi Qian , De Gramont Aimery , Yoshino Takayuki 
Published: January 2024

115 Background: Randomized clinical trials provide the best evidence for the effects of a new treatment. However, the use of a placebo control arm may present practical and ethical concerns for enrolled patients and treating providers. The CRC ARCAD global database includes a total of 1,673 individual patient data (IPD) treated with placebo plus best supportive care in a salvage-line setting for refractory mCRC. By using placebo IPD, we have proposed to construct a synthetic control arm for clinical trials (Yoshino T. et al., Nature Medicine 2023). Methods: From 40,889 IPD from 59 studies in ARCAD mCRC database, 723 placebo pts were selected from 4 placebo-controlled randomized studies in a salvage-line setting (CORRECT, RECOURSE, CONCUR and TERRA). We analyzed the impact of baseline patient characteristics and various prognostic factors on outcome in the placebo control. Results: The adjusted hazard ratios (HRs) (95% confidence interval [CI]) were 0.52 (0.40-0.67) for the number of metastatic sites (1 vs 2+), 0.71 (0.59-0.84) for ECOG performance status (PS) (0 vs 1), 0.54 (0.45-0.66) for liver metastases (No vs Yes), 0.54 (0.40-0.71) for peritoneal metastases (No vs Yes), and 0.51 (0.38-0.70) for Royal Marsden Hospital (RMH) Score (consisting of albumin level, number of metastatic sites, and LDH level) (0-1 vs 2-3). Conclusions: Number of metastatic sites, ECOG PS, liver metastasis, peritoneal metastasis and RMH Score were significant prognostic factors in patients with mCRC receiving placebo in a salvage-line setting. Further prognostic factors should be investigated to increase the accuracy of the proposed synthetic control arm. [Table: see text]
Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial.
Authors: Stintzing Sebastian , Tabernero Josep , Satoh Taroh , Dasari Arvind , Lonardi Sara , Eng Cathy , Garcia-Carbonero Rocio , Elez Elena , Yoshino Takayuki , Sobrero Alberto F. , Yao James C. , Kasper Stefan , Arnold Dirk , Basic Edin , Granold Matthias , Petschulies Marco , Wu Liwen , Chen Lucy , Yang Zhao , Van Cutsem Eric 
Published: January 2024

116 Background: As mCRC and its treatment can adversely impact quality of life (QoL), maintaining QoL is an important treatment goal in addition to improving survival outcomes, particularly as patients progress through lines of therapy. In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + BSC vs placebo (P) + BSC demonstrated significantly improved overall survival (OS) (median 7.4 months vs 4.8 months; HR 0.66, 95% confidence interval [CI] 0.55–0.80) and progression-free survival, with a manageable safety profile and without deterioration of QoL in heavily pretreated patients with refractory mCRC. The objective of this post-hoc Q-TWiST analysis was to assess the quality-adjusted survival benefit of F + BSC in the context of the FRESCO-2 trial. Methods: The Q-TWiST analysis was applied to all 691 randomized patients from FRESCO-2 (F + BSC n=461 vs P + BSC n=230). Survival time of each patient was partitioned into 3 health states: time spent with treatment-emergent adverse events of CTCAE grade 3 or 4 before disease progression (TOX), time before disease progression without toxicity (TWiST), and time between disease progression and death or censoring (REL). Assuming utility coefficients of 1 for TWIST and 0.5 for TOX and REL, Q-TWiST was calculated as the utility-weighted sum of the time spent in each health state. The mean time spent in each of the 3 health states was calculated for each treatment group using Kaplan-Meier analysis, and a 95% CI for the difference between treatment was calculated using the nonparametric bootstrap method. Results: Q-TWiST was 6.25 months for F + BSC and 4.21 months for P + BSC, a difference of 2.04 (95% CI 1.51–2.57) months longer with F + BSC vs P + BSC. This difference in Q-TWiST was mainly driven by the difference in the TWiST component (2.14 months [95% CI 1.78–2.49]; F + BSC 4.06 months vs P + BSC 1.92 months). The relative Q-TWiST gain, calculated as the difference in Q-TWiST divided by the mean OS time of the P + BSC group, was 31.4% in favor of F + BSC. Conclusions: In the FRESCO-2 trial, F + BSC demonstrated a clinically meaningful quality-adjusted survival benefit compared with P + BSC in heavily pretreated patients with refractory mCRC. Clinical trial information: NCT04322539 .
Subgroup analyses of the phase 3 CAIRO3 trial: Association of number and total volume of metastases on survival in patients with metastatic colorectal cancer based on a deep-learning automatic segmentation model.
Authors: Zwart Koen , Zeeuw Michiel J. , Stehouwer Bertine L. , Al-Toma Dania , Kurk Sophie , Braat Manon N.G.J.A. , de Jong Pim A. , Lagendijk Jan J.W. , May Anne M. , Koopman Miriam , Punt Cornelis J. A. , Kazemier Geert , Bol Guus 
Published: January 2024

130 Background: Maintenance treatment with capecitabine and bevacizumab after capecitabine, oxaliplatin, and bevacizumab therapy in metastatic colorectal cancer (mCRC) is shown to be effective with observation as an acceptable alternative. Metastatic burden might aid in shared decision-making and the aim of this exploratory analysis is to assess the prognostic and predictive value of number and total volume of metastases in mCRC patients included in the CAIRO3 study. Methods: Patients in the CAIRO3 study with liver and/or lung metastases were included. Every individual liver and lung metastasis was counted and volumes were assessed using deep-learning automatic segmentation software (SAS analytical platform and Philips IntelliSpace). Lymph node metastases were counted manually. Each scan was supervised by a dedicated radiologist. Kaplan-Meier analyses were used to estimate progression-free survival (PFS) and overall survival (OS) using log-rank testing for statistical comparison. Hazard ratios (HR) were estimated using Cox regression models. Results: A total of 156 patients were included with 154 OS events, in which 8198 metastases were identified: 5179 were liver metastases, 2835 lung metastases, and 184 lymph node metastases. Patients had a mean age of 63 years and 67% were male. At randomization, the median number of metastases was 9 and mean total metastatic volume was 116 cm3. Median OS for patients with ≤10 versus >10 metastases was 22.0 months (95%CI: 19.3-29.3) and 14.3 months (95% CI: 11.6-20.9, p-value <0.01), with similar differences for low/high tumor volume. In multivariable analysis number and total volume were independent prognostic markers for PFS and OS, respectively, after adjustment for age, sex, WHO performance score, treatment arm, serum lactate dehydrogenase (LDH) level, site of primary tumor, time to metastases, and treatment response. Benefit of maintenance therapy was most pronounced in patients with ≤10 compared to >10 metastases with a PFS HR of 0.24 (0.12-0.46) compared to 0.52 (0.28-0.96) and OS HR of 0.75 (0.42-1.34) compared to 1.17 (0.66-2.08), demonstrating potential predictive value. Conclusions: Metastatic burden is associated with a poor prognosis in patients with mCRC. Furthermore, patients with limited metastatic disease (1-10 metastases) benefit most from maintenance treatment and this could potentially be a predictive biomarker. [Table: see text]
Patterns of presentation and delivery of care of appendiceal neoplasms in the largest municipal health care delivery system in the United States.
Authors: Ahmed Armaan , Whittington Jennifer , Shafaee Zahra 
Published: January 2024

14 Background: Appendiceal neoplasms (AN) are rare tumors with a broad spectrum of referral and treatment patterns. NYC Health+Hospital (HHC) is the largest municipal health care system in the United States. Here, we study patterns of presentation and management of AN in this safety-net setting. Methods: We identified 92 patients in HHC with AN between 01/01/2017 to 07/01/2023. Statistical analyses were performed in Python. Results: There were 38 (41.3%) mucinous neoplasms, 24 (26.1%) adenocarcinomas, 23 (25.0%) neuroendocrine, and 7 (7.6%) ex-goblet cell adenocarcinomas. 16 cases of pseudomyxoma peritonei were identified. The median age at diagnosis was 55 (IQR: 45-65). 49% were Hispanic, and African Americans were the largest racial block (28%). 50% of cases presented as appendicitis. Appendectomy and a second surgical intervention were more common in this group (p<0.001 and p=0.044, respectively). Other surgical interventions included colon resections and cytoreduction ± Hyperthermic intraperitoneal chemotherapy. Among the patients with mucinous neoplasm or adenocarcinoma, 35 had multidisciplinary tumor board discussion (15 mucinous neoplasm and 20 adenocarcinomas). The median follow-up period was 22.0 months (95% CI: 11.5-30.7 months). Surveillance modalities included CT (75%), CEA (74%), and colonoscopy (35%). 85% remained within HHC during treatment. 16 patients were planned to have chemotherapy, including 9 pseudomyxoma peritonei cases. 5 patients did not follow through, and the other cases had a median of 10 cycles. The following adjuvant chemotherapy regimens were employed: 50% FOLFOX, 20% FOLFIRI, 20% XELODA, and 10% CapeOX and FOLFIRI. There were 2 cancer-related deaths (pseudomyxomas). Excluding pseudomyxomas, none had evidence of disease at the last follow-up. Conclusions: Minorities and immigrants constitute the majority of the population of HHC. 50% of AN presented as appendicitis emphasizing the need for a robust system to identify these cases. Despite challenges encountered in providing long-term oncological care, HHC has treated and provided vigorous follow-up for this underserved population. [Table: see text]