bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional outcomes of bony sarcoma in adolescent and young adult patients: A systematic review.
Authors: Zheng Xuan Ong , Poon Eileen Yi Ling 
Published: August 2023

161 Background: Sarcomas are heterogeneous rare cancers, and while it affects 1% of all adult cancers, they affect 10-20% of Adolescents and Young Adults(AYAs). Sarcomas can be divided into soft tissue sarcomas(STS) and bony sarcomas(BS). The 5-year survival rates range between 50-60% but have remained stagnant. While the management of BS involves systemic treatment and morbid surgeries, functional outcomes and quality-of-life(QoL) have been largely overlooked. These changes are usually persistent and irreversible, with significant impact on mobility, function and body image. There are many facets of functional outcomes, including physical, social and psychological. These outcomes directly affect patients’ independence, self-confidence and future job endeavors, yet hardly any specific research has gone into it. Methods: A systematic review yielded 833relevant papers, but only 27was included for final analysis. Inclusion criteria included literature published in English, focused on AYAs 16-39 years, BS and papers assessing functional outcomes after treatment. We also included studies that investigated survivorship in pediatric BS, as these patients will transit into young adults who are childhood cancer survivors. Results: Outcomes of AYA are poorer in all aspects – physical function, social reintegration and psychological health. The heterogeneity among AYA patients, and large differences require individualized care based on stages of their personal development. There is greater adjustment required in AYAs due to higher physical, social and financial demands as they mature and aim to become independent. Current tools to assess HRQoL in AYAs are not standardized or validated in this age group. More research is required to identify long term outcomes post-treatment and into survivorship. Conclusions: AYAs have often been referred to as the ‘lost tribe’, with many of their needs overlooked. They are stricken with a cancer diagnosis during their prime and it is essential to manage them holistically to preserve and maximize their functional outcomes.
Effects on hematopoietic and immune system of ultra-high dose rate radiotherapy (FLASH-RT).
Authors: Yu Tosol , Choi Min-Young 
Published: August 2023

166 Background: Ultra-high dose rate radiotherapy, so-called FLASH radiotherapy (FLASH-RT) has shown to reduce radiation-induced damage including lung fibrosis, brain damage, skin fibrosis, etc. We investigated the effect of FLASH-RT compared of conventional dose rate radiotherapy (CONV-RT) at 5Gy of TBI on survival of hematopoietic system, peripheral blood cells, and immune-related responses. Methods: Mice were divided into 3 groups: control (0 Gy), FLASH-RT (109Gy/s), and CONV-RT (0.067Gy/s). FLASH-RT was performed with DIRAMS LINAC producing 6 MeV electron beams. Irradiated mice were sacrificed at 1, 2, 4, 7, 14, 21 and 28 post-TBI of 5 Gy and cellularity of peripheral blood and bone marrow, histological evaluation of immune organ such as spleen and thymus, and T and B lymphocytes in mouse spleen by flow cytometry were investigated. Results: In peripheral blood cell counts, RBC, neutrophil, lymphocyte counts were not significantly different between FLASH-RT and CONV-RT groups from day 1 to day 28 post-TBI. However, FLASH-RT initially induced more apoptosis of bone marrow cells, platelets, and eosinophils of peripheral blood compared to CONV-RT. FLASH-RT and CONV-RT groups showed similar histological changes in the thymus and spleen after 5Gy of TBI, but T lymphocytes of CONV-RT group in day 28 were less recovered compared to those of FLASH-RT group. Our results indicated that FLASH-RT affected more radiation-induced damage of hematopoietic system in early stages compared to CONV-RT, but FLASH-RT showed higher recovery of T lymphocytes after irradiation. Conclusions: These results show that FLASH-RT can induce similar damage and recovery pattern on hematopoietic system with CONV-RT in first week, but FLASH-RT might affect less T-lymphopenia in long-term than CONV-RT.
Leucocyte-hitchhiking liposomes loading gemcitabine and pyroptosis for potentiated immunotherapy of hepatocellular carcinoma.
Authors: Lu Yuejie , Du Yongzhong , Lin Bingyi , Chai Siyuan , Wu Liming 
Published: August 2023

168 Background: Hepatocellular carcinoma (HCC), as a malignant tumor with high incidence worldwide, faces the challenge of low efficacy of traditional chemotherapy drugs and immunotherapy drugs. Pyroptosis is a type of programmed cell death that can alleviate tumor immunosuppressive microenvironment and promote systemic immune response, which has great potential in improving the efficacy of immunotherapy drugs. The selection of more effective pyroptosis-inducing drugs and immunotherapy drugs, supplemented by more precise drug delivery strategies, is one of the research focuses in the treatment of HCC. Methods: In this study, Western Blot were performed to screen suitable pyroptosis-inducing drugs. A leucocyte-hitchhiking liposome nanodrug delivery system was designed to co-deliver a pyroptosis-inducing drug and a small molecule immunotherapy drug. The ability of the nanocarrier to induce pyroptosis of liver cancer cells and to activate immune cells were investigated in vitro. The targeting ability of the nanocarrier to peripheral blood leucocytes, the function of tumor inhibition and immune activation were evaluated in vivo. Results: In this study, gemcitabine was confirmed to induce pyroptosis in liver cancer cells. E-selectin modified liposomes were designed to co-deliver gemcitabine and the small molecule PD-1/PD-L1 complex inhibitor BMS-202. In vitro experiments confirmed that the nanocarrier could induce pyroptosis in liver cancer cells and activate immune cells. In vitro experiments confirmed the targeting ability of the nanocarrier to leukocytes and its ability to inhibit tumor and activate immunity. Conclusions: Leucocyte-hitchhiking liposomes loading gemcitabine and BMS-202 was successfully synthesized. After intravenous injection, liposomes effectively adhere to the surface of peripheral blood leukocytes mediated by E-selectin, thus hitchhiking with leukocytes to achieve high accumulation at the tumor site. The released gemcitabine can evoke tumor cell pyroptosis and generate anti-tumor immunity, while BMS-202 can alleviate immune suppression by inhibiting the formation of PD-1/PD-L1 complex, further enhance gemcitabine-induced anti-tumor immunity. This leucocyte-hitchhiking dual-delivery liposomal nanoplatform might provide a promising strategy for high-efficiency immunotherapy, exhibiting a great potential for clinical translation of HCC treatment.
Initial experience of robot-assisted breast conserving surgery for early breast cancer patients.
Authors: Paek Se Hyun , Lim Woosung , Moon Byung-In 
Published: August 2023

17 Background: A traditional breast conserving surgery (BCS) operation inevitably results in an external scar on breast and axilla. Various attempts including endoscopy-assisted breast surgery has been successfully and reproducibly performed for improved cosmetic outcome. In an attempt to maximize esthetic effects, we performed robot-assisted BCS through only axillary incision. Methods: From Jan. 2021 to Dec. 2021, fifteen female patients underwent robot-assisted BCS. All patients underwent robot-assisted BCS with or without sentinel lymph node biopsy (SLNBx.) through only 2.5cm axillary incision. All surgical procedures were performed in concordance with traditional BCS operation. Data on patient demographics, type of surgery, hospital stay, complications, and short-term postoperative outcomes were reviewed. Results: Mean patient age was 53.7 ± 6.35 years and mean tumor size was 1.6 ± 2.1 cm. Indications included in situ cancer in 7 cases and invasive cancer in 8 cases. Three patients underwent only BCS, and twelve patients underwent BCS + SLNBx. Two patients underwent axillary lymph node dissection. The mean operation time was 165.5±8.2 minute and the mean hospital stay was 6.4 ± 5.3 days. No open conversion case was observed. One seroma with infection occurred postoperatively and I & D performed. Two skin burn event during operation was occurred and scar revision was performed. The operative scars in axilla became inconspicuous in a few weeks. Conclusions: Our initial results show that robot-assisted BCS would be technically feasible, safe, and effective. This new technique can be a good alternative surgical option for BCS in early breast cancer patients.
The difference in efficacy of the endocrine therapy between the HER2-low and HER2-zero metastatic breast cancer: A single-center retrospective study.
Authors: Omori Reo , Nishibori Yuichiro , Nakatani Yuki , Akaishi Yuko , Tanaka Ayako , Akiyoshi Kohei , Tokunaga Shinya , Daga Haruko 
Published: August 2023

3 Background: HER2-low expression breast cancer is a new classification and began to receive attention after trastuzumab deruxtecan showed its effect on this classification. As for endocrine therapies, HER2-low expression seemed not to affect the efficacy of CDK4/6 inhibitors in a few retrospective studies. However, previous data on the effectiveness of endocrine therapies other than CDK4/6 inhibitors for HER2-low metastatic breast cancer (mBC) are still limited. This study aims to evaluate the difference in endocrine therapy between HER2-low and HER2-zero mBC. Methods: We retrospectively reviewed the clinical data of mBC patients prescribed aromatase inhibitors, tamoxifen or fulvestrant, and/or CDK4/6 inhibitors at our department between May 2012 and December 2022. Patients were excluded if they received chemotherapy before endocrine therapy, lacked data on HER2 score, or discontinued treatment before the first image evaluation. The data cutoff date was 15th March 2023. We analyzed the difference in progression-free survival (PFS) of the first-line endocrine monotherapy and the first-line CDK4/6 inhibitors between HER2-low and HER2-zero mBC by logrank analysis. Results: Of 126 patients who received the first-line endocrine monotherapy, 22 were HER2-zero, and 104 were HER2-low. In the HER2-zero group, six patients received tamoxifen, and 16 received AIs. In the HER2-low group, 29 patients received tamoxifen, 63 received AIs, and 12 received fulvestrant. The median PFS was 27.7 months with the HER2-zero group and 15.6 months with the HER2-low group. This was not statistically significant (P=0.196), but the Kaplan-Meier curve showed that PFS tended to be longer with the HER2-zero group. This trend was also observed in patients who received AIs. Of 52 patients who received CDK4/6 inhibitors as a first-line treatment, ten were HER2-zero, and 42 were HER2-low. The median PFS was NA with the HER2-zero group and 22.8 months with the HER2-low group, and no significant differences were detected. Conclusions: In this study, there were no statistically significant differences in the PFS of the first-line endocrine monotherapy and CDK4/6 inhibitors between HER2-low and HER2-zero mBC. However, the Kaplan-Meier curve showed that the PFS of endocrine therapy tended to be longer in the HER2-zero group. Further studies are warranted.
Palliative treatment for gastric outlet obstruction: A network meta-analysis.
Authors: Tran Van Khoi , Vo Nguyen-Phong , Nguyen Hung Song , Vo Nhi Thi , Thai Trang Thi Bao , Pham Vu Anh , Loh El-Wui , Tam Ka-Wai 
Published: August 2023

36 Background: The optimal palliative treatment for gastric outlet obstruction (GOO) remains inconclusive between gastrojejunostomy (G), endoscopic ultrasound-guided gastroenterostomy (E), stomach partitioning gastrojejunostomy (P), endoscopic stenting (S). This study was part of a comprehensive systematic review investigating the outcomes of the aforementioned treatments for malignant GOO. Methods: We conducted a systematic screening randomized controlled trials (RCTs) and cohort studies that compared at least two palliative procedures for GOO from Pubmed, Embase, Cochrane, Web of Science, Scopus, Clinicaltrial, WHO International Clinical Trials Registry Platform. We included full-text studies that reported at least clinical outcomes (clinical success rate, complication rate, 30-day mortality rate, and reintervention rate). We conducted this network meta-analysis using the frequentist approach, inverse variance model with a naïve combination of the treatment effects from RCTs and non-RCTs. We used P-score for treatment ranking. Certainty of evidence was evaluated following CINeMA approach. Results: This study included four RCTs and four prospective and 32 retrospective cohorts with 3417 patients. The pooled overall rates of clinical success, complication, 30-day mortality, and reintervention were 88.9% (95%CI 85.6-91.6), 20.7% (95%CI 17.2-24.7), 5.4% (95%CI 3.2-8.9), and 13.9% (95%CI 10.7-17.9), respectively. P was ranked the safest for reintervention rate (P-score: 0.90) due to obstruction and complication post-procedure (P-score: 0.88 and 0.81, respectively). E was ranked the safest for the 30-day mortality rate (P-score: 0.82). Cluster rank combined the P-score for 30-day mortality and reintervention or reintervention rate due to obstruction showed the benefit of P and E versus G and S (cophenetic correlation coefficient - c: 0.94 and 0.94, respectively). Cluster rank combined with the P-score for 30-day mortality and reintervention due to complication showed the benefit of P (c:0.99). The overall certainty of evidence was low to very low. Conclusions: P and E are recommended for malignant GOO, and P should be the first choice in centers with limited resources or cases of unfeasible or unsuccessful E.
Peri-operative predictive factors of failure to rescue after highly advanced hepatobiliary-pancreatic surgery.
Authors: Fukada Masahiro , Matsuhashi Nobuhisa , Higashi Toshiya , Yasufuku Itaru , Sato Yuta , Kiyama Shigeru , Tanaka Yoshihiro , Okumura Naoki , Murase Katsutoshi 
Published: August 2023

39 Background: Failure to rescue (FTR), defined as postoperative complications leading to mortality, is a recently described outcome metric to evaluate the quality of treatment. However, predictive factors of FTR, particularly after highly advanced hepatobiliary-pancreatic surgery (HBPS), have not been adequately investigated. Thus, it remains unclear. The object of this study is to identify the perioperative predictive factors of FTR after highly advanced HBPS. Methods: This single-institution retrospective study included 177 patients who developed severe postoperative complications (Clavien-Dindo classification≧grade3a) after highly advanced HBPS from 2010 to 2022 at Gifu University Hospital. We statistically analyzed pre-, intra-, and post-operative risks for FTR using logistic regression. Results: Nine postoperative mortalities occurred, for overall mortality rate of 1.3% (9 / 686) and FTR rate of 5.1% (9 /177). In univariate analysis, liver disease comorbidity, intra-operative blood loss, intra-operative blood transfusion, post-operative liver failure, post-operative respiratory failure, and post-operative bleeding were significantly correlated with FTR. A multivariate analysis revealed that intra-operative blood loss (>1600ml; odds ratio [OR] 77255486; 95% confidence interval [CI] 18.26–; p <0.0001) and post-operative respiratory failure (OR 43422062; 95% CI 9.83–; p <0.0005) were independently associated with FTR. Conclusions: FTR have been shown to be associated with hospital factors. This study showed that FTR may be also associated with peri-operative factors. Prevention of massive intra-operative blood loss and postoperative respiratory failure may be able to decrease FTR.
Breast self-examination practice and its determinants among women in Indonesia: A systematic review, meta-analysis, and meta-regression.
Authors: Azhar Yohana , Halim Freda , Hanafi Ricarhdo Valentino 
Published: August 2023

4 Background: Breast cancer (BC) is the most diagnosed cancer in Indonesia, according to the World Health Organization in 2020. Economic centralization in Java Island worsens the accessibility and inequality of healthcare facilities. The limited standard BC screening, such as mammography and ultrasound, generates breast self-examination (BSE) as the practical and effortless method to detect the earliest sign of breast cancer. Early detection and prompt management of BC improve survival rate and quality of life. Hence, we aimed to synthesize the pooled prevalence data, identify the determinants, and compare BSE practice between Java Island and non-Java Islands in Indonesia. Methods: This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). We conducted intensive searches in Cochrane Library, PubMed, Google Scholar, and SINTA (Science and Technology Index) - Indonesian web-based research information from September 2017 – 2022. For a critical appraisal of the studies, we employed the Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data. We utilized Review Manager 5.4 for conducting the meta-analysis. The pooled analysis was reported as a prevalence and odds ratio (OR) with a 95% confidence interval (CI). Results: Total samples (n = 6,361) from 41 full-text publications were included. The overall national prevalence of BSE practice was 43.14% [95% CI: 36.08, 50.20, P <0.001, I2 = 100%]. BSE practice in Java Island was 44.58% [95% CI: 35.42, 53.75] and significantly higher than that of Non-Java Island at 41.62% [95% CI: 29.83, 53.41]. University students reported the highest prevalence of BSE practice with 49.90 [95% CI: 40.27, 59.33]. Good knowledge, good attitude toward BSE, family history of BC, family support, and BC information exposure were all statistically associated with a higher determinant of BSE practice among women in Indonesia. Conclusions: Only less than 50% of fertile women in Indonesia practiced BSE, with the lowest percentage on non-Java Islands and community-group. Integrative and collaborative programs should be established with the government, health policymakers, and community health groups to promote BSE as routine screening for breast cancer.
First-line (1L) panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with HER2 amplification (HER2amp+), RAS wild type (WT) metastatic colorectal cancer (mCRC) according to tumor sidedness.
Authors: Oki Eiji , Muro Kei , Watanabe Jun , Shitara Kohei , Yamazaki Kentaro , Ohori Hisatsugu , Shiozawa Manabu , Yasui Hirofumi , Sato Takeo , Naito Takeshi , Komatsu Yoshito , Kato Takeshi , Soeda Junpei , Yamamoto Kouji , Yamashita Riu , Akagi Kiwamu , Ochiai Atsushi , Uetake Hiroyuki , Tsuchihara Katsuya , Yoshino Takayuki 
Published: August 2023

53 Background: HER2 gene alterations occur in 3%–5% of pts with mCRC and may be associated with aggressive tumor behavior. Gene amplification is a frequent HER2 alteration in mCRC, often leading to HER2 protein overexpression. Preclinical and retrospective studies suggest HER2 alterations may predict anti–epidermal growth factor receptor (EGFR) therapy resistance in mCRC; however, there is limited information regarding the efficacy of 1L anti-EGFR therapy in mCRC pts with HER2 alterations. The PARADIGM trial demonstrated longer median OS with 1L PAN (anti-EGFR) vs BEV (anti–vascular endothelial growth factor), with mFOLFOX6, in RAS WT mCRC (NCT02394795). We evaluated the efficacy of PAN vs BEV in pts with HER2amp + and HER2amp−, RAS WT mCRC from PARADIGM, taking into account primary tumor sidedness. Methods: Baseline plasma ctDNA was obtained from pts with RAS WT mCRC enrolled in PARADIGM; pts with evaluable pretreatment ctDNA were included in the biomarker analysis (NCT02394834). A custom panel (PlasmaSELECT-R 91, PGDx) was used to detect HER2amp+ and HER2amp− samples. OS, PFS, and response rate (RR) were compared in pts with HER2amp+ vs pts with HER2amp−. Results: Of 802 pts with RAS WT mCRC, 733 (91%) had evaluable pretreatment samples; 32 (4%) had HER2amp + (PAN, n=19; BEV, n=13). A lack of a survival benefit with PAN vs BEV was suggested in pts with HER2amp+, regardless of tumor-sidedness (median OS: overall population, PAN, 23.0 mo; BEV, 26.7 mo; HR, 0.96; 95% CI: 0.45–2.04; left-sided population, PAN, 25.1 mo; BEV, 26.7 mo; HR, 0.89; 95% CI: 0.39–2.04]). Data in the right-sided population are not shown for pts with HER2amp+ due to the small sample size. In the overall population, there was a trend toward shorter OS for HER2amp + vs HER2amp− pts (PAN: 23.0 vs 36.3 mo; HR, 1.57; 95% CI: 0.96–2.57; BEV: 26.7 vs 31.6 mo; HR, 1.41; 95% CI: 0.79–2.52). Median PFS and RR were similar between pts with HER2amp + and HER2amp− in PAN or BEV arms (Table). Conclusions: HER2 amplification appears to be prognostic in pts with RAS WT mCRC but may not be predictive of a survival benefit of 1L PAN treatment over BEV. Clinical trial information: NCT02394834 . [Table: see text]
Efficacy of fibroblast growth factor receptor (FGFR) inhibitors therapy in advanced cholangiocarcinoma with FGFR genes alterations: A meta-analysis of phase II clinical trials.
Authors: Patel Rushin , Chitkara Akshit , Patel Zalak , Patel Femina , Patel Mrunal , Anamika Fnu , Kavani Himanshu , Thawani Rajat 
Published: August 2023

54 Background: Fibroblast growth factor receptor ( FGFR) gene fusions and rearrangements are involved in the pathogenesis of approximately 10 to 16 percent of patients with cholangiocarcinoma. There is no meta-analysis available of phase 2 clinical trials of FGFR inhibitors in these patients. In this article, we analyze the efficacy of FGFR inhibitors in advanced cholangiocarcinoma with FGFR gene fusions or other rearrangements. Methods: Systemic searches of PubMed, Embase, the Cochrane Library, Google Scholar, and ClinicalTrials.gov were conducted with prespecified terms. The outcomes studied in our analysis were Objective response rate (ORR), Disease control rate (DCR), Progression-free survival (PFS), and Overall survival (OS). We calculated the pooled ORR for these studies by using weighted average ORR = Σ (ORR_i * weight_i). Calculate the standard error using the formula SE = √(Σ (wi x (1 - ORRi) x ORRi) / Σ (wi x ni)) and the 95% confidence interval using the formula CI = ORR ± (1.96 x SE). However, it is important to note that the pooled ORR is only as reliable as the individual ORR estimates from each study and may be subject to bias or confounding factors. This method was used to calculate the pooled DCR, PFS, and OS for our study as well. All data extraction and calculations were verified by three reviewers. Results: Eight phase II clinical trials met the inclusion criteria (1-8). Outcome data were available for all eight studies, comprising 562 patients with FGFR-positive advanced cholangiocarcinoma who received FGFR-targeted treatment regimens. The pooled objective response rate (ORR) and disease control rate (DCR) were 32.6% (95% CI 28.1-37.1) and 81.86% (95% CI 74.96-88.76), respectively. The pooled weighted progression-free survival (PFS) was 7.5 months, and pooled overall survival (OS) was 17.4 months. These findings suggest that FGFR-targeted treatment regimens have a promising ORR, DCR, PFS, and OS. Conclusions: FGFR inhibitors as a class in patients with advanced or metastatic cholangiocarcinoma with FGFR gene alterations showed clinically meaningful efficacy with durable objective responses. [Table: see text]