tbuckley/cabot-search huggingface dataset:
How to: assess patient suitability for unlicensed phage therapy in the United Kingdom
Authors: Joshua D. Jones, Helen J. Stacey, John W. Kennedy, Maya Merabishvilli, Melissa E.K. Haines, Oliver Blocker, Kumara Dharmasena, Andrew Gordon, Stuart A. Hamilton, Ila Aggarwal, John Nagy, Don S. Urquhart, Lesley M.L. Hall, Matthew J. Young, Gordon MacGregor, Ross J. Langley, Christine Peters, Daniela I. Munteanu
Journal: Clinical Microbiology and Infection (2024)

BackgroundBacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis.ObjectivesThis article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom.SourcesThis article builds on Health Improvement Scotland's recommendation for the consideration of phage therapy in difficult-to-treat infection and the experience of the author group who have collectively assessed the suitability of 30 patients for phage therapy.ContentIn the UK, unlicensed medicines, including phages, may be considered to meet special clinical needs. The use of unlicensed medicines is governed by national legislation and local NHS Trust policies. Phages can be used in any NHS Trust and decisions about suitability should be made via existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.
Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia
Authors: Satoshi Yoshimura, Zhenhua Li, Yoshihiro Gocho, Wenjian Yang, Kristine R. Crews, Shawn H.R. Lee, Kathryn G. Roberts, Charles G. Mullighan, Mary V. Relling, Jiyang Yu, Allen E.J. Yeoh, Mignon L. Loh, Caner Saygin, Mark R. Litzow, Sima Jeha, Seth E. Karol, Hiroto Inaba, Ching-Hon Pui, Marina Konopleva, Nitin Jain, Wendy Stock, Elisabeth Paietta, Elias Jabbour, Steven M. Kornblau, William E. Evans, Jun J. Yang
Journal: Journal of Clinical Oncology (2024)

Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.
Effect of enhanced recovery after radiotherapy (ERAR) on the quality of life in patients with nasopharyngeal carcinoma after radiotherapy: A randomized controlled trial.
Authors: Nan Lin, Xueyan Zhou, Xuelei Ma
Journal: Journal of Clinical Oncology (2024)

12128 Background: Nasopharyngeal carcinoma (NPC) is a common disease in Southern China and Southeast Asia. Radiotherapy is an essential treatment for locoregionally advanced NPC (LA-NPC). Although Enhanced Recovery After Surgery (ERAS) is widely used in surgical settings, the guidelines do not systematically address the specific roles of various disciplines involved in radiotherapy rehabilitation. Therefore, we propose the concept of Enhanced Recovery After Radiotherapy (ERAR), which is considered to be a vital complement to radiology. Methods: We enrolled patients with stage III to IVA LA-NPC in this study. Participants completed baseline surveys before random assignment. ERAR interventions were implemented during radiotherapy to develop systematic management plans in the aspects of nursing, oral care, psychology, rehabilitation, nutrition, and skin health. The control group received conventional radiotherapy. Outcomes were evaluated at the 17th and 33rd radiotherapy sessions. We used generalized estimating equations to evaluate group by time effects on the outcomes, controlling for key covariates. Results: A total of 108 LA-NPC patients with a mean age of 48.3 ± 11.0 years were enrolled in the study group from August 2021 to September 2023. Across all time points, the ERAR group showed significant improvements in Hospital Anxiety and Depression Scale (HADS) anxiety ( P &lt;.001), HADS depression ( P &lt;.001), distress thermometer ( P =.049), quality of life ( P =.014), NRS2002 ( P =.040), weight loss ( P &lt;.001), and Oral Health Impact Profile-14 (OHIP-14) ( P =.040) scores compared with the conventional care group. Conclusions: The ERAR pathway has a significant benefit on reducing acute radiation-induced toxicity in patients with LA-NPC. It is hoped that this study will provide a reference for clinicians and promote the implementation of a standardized protocol for rapid recovery from radiotherapy. Clinical trial information: ChiCTR2300075874. [Table: see text]
Preliminary results of a randomized controlled, open-label, multi-center phase II study of camrelizumab combined with chemotherapy followed by concurrent chemoradiotherapy and camrelizumab consolidation therapy versus standard chemoradiotherapy as first-line treatment for limited-disease small cell lung cancer.
Authors: Xu Yaping, Jian Ni, Shengxiang Ren, Xiaoling Xu, Min Hu, Qinghua Xu, Yun Chen, Yaoyao Zhu
Journal: Journal of Clinical Oncology (2024)

e20132 Background: Immune checkpoint inhibitors combined with chemotherapy have significant clinical benefits in extensive-stage small cell lung cancer (SCLC). However, for patients with limited-disease SCLC (LD-SCLC), the data on immunotherapy combined with chemoradiotherapy is insufficient. Methods: In this open-label, multi-center, phase 2 trial, we randomly 1:1 assigned patients with previously untreated LD-SCLC to receive camrelizumab combined with chemotherapy followed by concurrent chemoradiotherapy (CCRT) and camrelizumab consolidation therapy or standard chemoradiotherapy. Patients with ECOG performance status of 0 to 1, and adequate organ function were eligible. For thoracic radiation, 45 Gy in 3 weeks (1.5 Gy, BID) was given on the first day of the third cycle of chemotherapy. An etoposide plus platinum-based regimen was given 4 cycles in total. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 1-year progression-free survival rate. We assumed that the 1-year PFS rate in the experimental group was expected to reach 65% compared to chemoradiotherapy alone group 45%, and planned to enroll 112 patients with 56 in each group. Results: Up to date, we have enrolled 40 patients. The median follow-up was 10.6 months. Safety was evaluated in all treated patients. No Grade 5 adverse event was observed. Grade 3 or 4 treatment-related adverse events occurred in 58.8% of the patients in the camrelizumab plus chemoradiotherapy and in 52.9% of those in the chemoradiotherapy alone group. The most frequent grade 3 or 4 adverse events were hematologic toxicities (70.6% vs. 58.8%). Acute esophagitis and pneumonitis of grade 3 occurred in both groups were 1/17 (5.9%) and 1/17 (5.9%), respectively. In the experimental group, only one patient was developed grade 3 immune pneumonia 1/17 (5.9%). The 1-year PFS rate was 54.5% (95% confidence interval [CI] 19.5%-89.6%) with camrelizumab plus chemoradiotherapy and 44.4% (95% CI 3.9%-88.0%) with chemoradiotherapy alone. Among the 17 patients who received camrelizumab, the median PFS time was not reached, as compared with 14.35 (95% CI, 8.15-20.91) months among the 17 patients with chemoradiotherapy alone. Conclusions: In patients with LD-SCLC, the addition of camrelizumab to chemoradiotherapy did not increase the incidence of adverse events. Camrelizumab plus chemoradiotherapy resulted in an encouraging 1-year PFS rate. Larger sample sizes and longer follow-up times are required to validate our preliminary results. Clinical trial information: ChiCTR2000032275.
Omega-3 Fatty Acids and Arrhythmias
Authors: Mason D. Marcus, Mark S. Link
Journal: Circulation (2024)

The pro- and antiarrhythmic effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been extensively studied in preclinical and human trials. Despite early evidence of an antiarrhythmic role of n-3 PUFA in the prevention of sudden cardiac death and postoperative and persistent atrial fibrillation (AF), subsequent well-designed randomized trials have largely not shown an antiarrhythmic benefit. Two trials that tested moderate and high-dose n-3 PUFA demonstrated a reduction in sudden cardiac death, but these findings have not been widely replicated, and the potential of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to reduce arrhythmic death in combination, or as monotherapy, remains uncertain. The accumulated clinical evidence does not support supplementation of n-3 PUFA for postoperative AF or secondary prevention of AF. Several large, contemporary, randomized controlled trials of high-dose n-3 PUFA for primary or secondary cardiovascular prevention have demonstrated a small, significant, dose-dependent increased risk of incident AF compared with mineral oil or corn oil comparator. These findings were reproduced with both icosapent ethyl monotherapy and a mixed EPA+DHA formulation. The proarrhythmic mechanism of increased AF in contemporary cohorts exposed to high-dose n-3 PUFA is unknown. EPA and DHA and their metabolites have pleiotropic cardiometabolic and pro- and antiarrhythmic effects, including modification of the lipid raft microenvironment; alteration of cell membrane structure and fluidity; modulation of sodium, potassium, and calcium currents; and regulation of gene transcription, cell proliferation, and inflammation. Further characterization of the complex association between EPA, EPA+DHA, and DHA and AF is needed. Which formulations, dose ranges, and patient subgroups are at highest risk, remain unclear.
Stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) versus TACE and TKIs alone for unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombus (PVTT): A randomized controlled trial.
Authors: Jiayu Duan, Jitao Zhou, Chang Liu, Hanyu Jiang, Jin Zhou, Kunlin Xie, Hong Wu, Yong Zeng, Xin Wang
Journal: Journal of Clinical Oncology (2024)

4102 Background: TKIs-based systemic therapy is a primary treatment option for uHCC. Clinical studies have established the effectiveness and safety of radiotherapy (RT) in patients with PVTT, who typically have a poor prognosis. Previous research has shown that combining TACE and RT can extend survival in HCC patients with PVTT compared to sorafenib treatment. This study aimed to explore the efficacy and safety of combined local therapy (TACE plus SBRT) and TKIs in HCC patients with PVTT. Methods: This single-center, randomized controlled study enrolled patients aged ≥18 years with HCC and PVTT. Additional eligible criteria included ECOG PS 0-1, Child-Pugh score ≤B7, no extrahepatic metastasis on CT scan, and normal liver volume ≥700cc. Patients were randomly assigned to either the SBRT+TACE+TKIs group (Group A) or the TACE+TKIs group (Group B). SBRT was administered at 35-45 Gy in 5 fractions, 3 fractions per week. TKIs (sorafenib 0.4g bid; donafenib 0.2g bid; or lenvatinib 8mg/12mg qd, depending on body weight) were paused during the perioperative period of TACE (up to 4 times). The primary endpoint was the 6-month progression-free survival (PFS) rate, with secondary endpoints including objective response rate (ORR), overall survival (OS), disease control rate (DCR) and treatment-related adverse events (TRAEs). Treatment response was evaluated using mRECIST. Results: A total of 90 patients with uHCC were enrolled from June 2019 to October 2023 in this trial, with baseline characteristics presented in the Table. As of January 5th 2024, the median follow-up time was 14.5 months [IQR, 2.43-55]. The 6-month PFS rate was significantly higher in Group A (78%) compared to Group B (36%, P=0.0245). Group A also showed prolonged median PFS (9.75 vs. 4.89 months, HR=1.703 [95%CI, 1.045-2.777], P=0.0245) and OS (17.93 vs. 9.61 months, HR=1.869 [95%CI, 1.059-3.266], P=0.017). Improved ORR was observed in the SBRT group (74.4% vs. 40.5%, P=0.0015). DCR was 81.4% in Group A and 66.7% in Group B ( P=0.1211). The most common grade 3/4 TRAEs were hypertension (Group A: 17.8%, Group B: 13.3%, P=0.5608), ALT elevation (Group A: 26.7%, Group B: 22.2%, P=0.6237), and AST elevation (Group A: 22.2%, Group B: 15.6%, P=0.4191). There was one treatment-related death in Group B due to liver failure. Conclusions: In uHCC patients with PVTT, the combination of SBRT and TACE-TKIs showed significant survival benefit without the identification of any severe safety concerns. Clinical trial information: ChiCTR1900025300. [Table: see text]
Preliminary results of phase I/II study to evaluate safety and efficacy of combination pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in patients with EGFR positive solid tumors.
Authors: Dan-yun Ruan, Fei Han, Yujuan Zhou, Fenghua Wang, Lin-Quan Tang, Zhiming Li, Qiu-Yan Chen, Chunyan Chen, Jinguan Lin, Fu-Rong Liu, Feng Xiao, Yingrui Shi, Rui-Hua Xu
Journal: Journal of Clinical Oncology (2024)

6013 Background: Pucotenlimab (HX008) is a recombinant humanized PD-1 inhibitor approved for marketing in China, and MRG003 is an EGFR-ADC which has shown promising anti-tumor activity in squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC) in multiple clinical studies. In the preclinical studies, the combination of them has demonstrated a synergistic antitumor effect. This study was aimed to assess the safety and efficacy of the combination therapy in patients (pts) with locally advanced or metastatic solid tumors known to express EGFR. Methods: In this Phase I/II dose escalation and expansion study, eligible pts were treated with 3.0 mg/kg HX008 combined with MRG003 every 3 weeks, with an escalated dosing ranging from 1.5 mg/kg to 2.3 mg/kg. The primary endpoints were maximum tolerated dose (MTD), recommended Phase II dose (RP2D) of combination and objective response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS). Results: As of 30 January 2024 (cut-off date), 33 pts (9 NPC, 1 SCCHN and 3 other solid tumors pts in Phase I, 14 NPC and 6 SCCHN pts in Phase II) were enrolled in this study with a median age of 52 (31,65), and 25 pts (76%) were male. 11 (33%) pts were ECOG PS 0. The most commonly reported treatment-related adverse events (TRAEs) included pruritus (46%), rash (33%), AST increased (30%), anemia (30%). Grade 3-4 TRAEs occurred in 4 pts (12%), and mainly was white blood cell count decreased (9%) and hypokalemia (6%). The only DLT event occurred in the 2.3mg/kg dose group, and the RP2D of MRG003 determined was 2.0mg/kg by SMC. Out of the 27 evaluable pts, 17 pts achieved PR and 7 pts achieved SD, thus the ORR and DCR were 63.0% (95%CI: 42.4, 80.6) and 88.9% (95%CI: 70.8, 97.7), respectively. In the Phase II, among 9 evaluable EGFR-positive NPC pts progression after first-line treatment of PD-1 plus platinum-based chemotherapy, 2 CR, 5 PR and 2 SD were observed, ORR and DCR were 77.8% (95%CI:40.0, 97.2) and 100% (95%CI:66.4, 100), respectively. Five evaluable systemic treatment naïve SCCHN pts with EGFR-positive, 3 PR and 1 SD were observed, ORR and DCR were 60% (95%CI:14.7, 94.7) and 80% (95%CI:28.4, 99.5), respectively. The DOR and PFS in the study were immature. The longest patient treated has had a DOR for more than 17 months and still ongoing. Conclusions: The Phase I/II study pts treated with HX008 in combination with MRG003 demonstrated good tolerability and encouraging antitumor activity in NPC and SCCHN, especially in PD-1 treatment failed NPC pts. The Phase II study is currently ongoing. Research Sponsor: Shanghai Miracogen Inc. Clinical trial information: NCT05688605.
Conditional survival analysis between primary squamous cell carcinoma of the thyroid and anaplastic thyroid carcinoma
Authors: Jingzhe Xiang, Ziyao Zhang, Liang He, Hao Zhang
Journal: International Journal of Surgery (2024)

Jingzhe Xiang, Liang He, Hao Zhang: Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, P.R. China Ziyao Zhang: The First Hospital of China Medical University, Shenyang, P.R. China Jingzhe Xiang, Ziyao Zhang These authors contributed equally to this work. All data included in this study are available upon request by contact with the corresponding author. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding authors. Address: Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, P.R. China. E-mail: [email protected] (H. Zhang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Bevacizumab Erlotinib Switch Maintenance in Chemo-Responsive Advanced Gallbladder and Cholangiocarcinoma (BEER BTC): A Multicenter, Open-Label, Randomized, Phase II Trial
Authors: Anant Ramaswamy, Prabhat Bhargava, Sujay Srinivas, Akhil Kapoor, Bal Krishna Mishra, Anuj Gupta, Sarika Mandavkar, Sadhana Kannan, Deepali Chaugule, Rajshree Patil, Manali Parulekar, Chaitali Nashikkar, Suman Kumar Ankathi, Rajiv Kumar Kaushal, Deepali Naughane, Anuprita Daddi, Neha Mer, Nitin Shetty, Vikas Ostwal
Journal: Journal of Clinical Oncology (2024)

PURPOSE Patients with chemotherapy-responsive advanced biliary tract cancers (BTCs) are usually observed after 6 months of gemcitabine-based therapy. There is limited prospective evidence for maintenance strategies after chemotherapy. METHODS This investigator-initiated, open-label, randomized, integrated phase II-III study enrolled adult patients with advanced BTC from two cancer centers in India. Patients with histologically confirmed advanced biliary tract adenocarcinoma who had at least disease stabilization after 6 months of gemcitabine-based chemotherapy were randomly assigned (1:1) to either active surveillance or switch maintenance, which was a combination of bevacizumab 5 mg/kg intravenous once every 21 days plus erlotinib 100 mg once daily. Both arms were continued until disease progression, unacceptable toxicity, or patient decision to withdraw. The primary end point of the phase II component of the trial was investigator-evaluated progression-free survival. This trial is registered with Clinical Trials Registry of India (CTRI/2019/05/019323I). RESULTS From May 2021 to November 2022, 98 patients were randomly assigned to active surveillance (n = 49) or bevacizumab-erlotinib (n = 49). A majority of patients had gallbladder cancer (80%). The median follow-up was 13.4 months. The median progression-free survival was 3.1 months (95% CI, 2.47 to 3.64) in the active surveillance group versus 5.3 months (95% CI, 3.53 to 7.04) in the bevacizumab-erlotinib group (hazard ratio, 0.51 [95% CI, 0.33 to 0·74]; P = .0013). The most common grade 3 class-specific adverse events associated with bevacizumab-erlotinib were acneiform rash 1 (2%) and oral stomatitis 1 (2%) with erlotinib and bleeding 1 (2%) with bevacizumab. CONCLUSION The combination of bevacizumab and erlotinib as switch maintenance improves progression-free survival with an acceptable safety profile compared with active surveillance in patients with advanced BTCs in this phase II study. The trial moves on to the phase III component to evaluate improvement in overall survival.
Hepatic artery infusion chemotherapy (HAIC) combined with tislelizumab and lenvatinib for initial unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus: A prospective, single-arm phase II trial.
Authors: Long Pan, Ruirui Sun, Qiang He, Yin Zhou, Jiachu Li, Yang Gou, Chenrui Wu, Zixuan Fu, Yaowu Zhao, Qin He, Ping Huang
Journal: Journal of Clinical Oncology (2024)

4103 Background: The combination of immune checkpoint blockade and multikinase inhibitor has been proven to improve clinical outcomes of advanced HCC. Hepatic arterial infusion chemotherapy is an intra-arterial procedure that has been widely used in Asia, with high response rate. The aim of this trial was to evaluate the efficacy and safety of HAIC combined with tislelizumab and lenvatinib for initial unresectable HCC with portal vein tumor thrombus (PVTT). Methods: This is a prospective, single-arm phase II study. Patients with histologically or cytologically diagnosed or clinically confirmed hepatocellular carcinoma and accompanied by PVTT, no previous systemic treatment were eligible for inclusion. Patients received HAIC(FOLOFOX), combined with intravenous tislelizumab (200mg, q3w) and lenvatinib (8/12mg, qd) for six cycles, followed by maintenance therapy with tislelizumab and lenvatinib until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1 and mRECIST. Results: Between Sep, 2021 to Nov, 2023, a total of 29 eligible patients were enrolled and evaluable for efficacy analyses: median age 54 years (M/F:25/4; CNLC stage IIIa/IIIb: 24/ 5). Portal vein tumor thrombus PVTT Ⅰ-Ⅱ/PVTT Ⅲ-Ⅳ:19/10. An average of 4.35 times of HAIC were underwent in these patients. With a median follow-up of 11 months (interquartile range [IQR] 7.5-21.5), the confirmed ORR was 68.97% (95%CI 49.19-84.72)and 58.62%(95%CI 38.94-76.48)per mRECIST and RECIST v1.1, respectively. The disease control rate (DCR) according to mRECIST and RECIST v1.1 were both 93.10% (95%CI 77.23-99.15). Median progression-free survival (PFS) was 15 months (95%CI 10-22). Median overall survival (OS) was not reached. 7(24.1%) patients became eligible for surgical resection. 1 of them received surgical resection and was confirmed as pathological CR; 6 of them refused surgical treatment and received tislelizumab and lenvatinib treatment continuously. 27(93.1%) patients had mild treatment related adverse events (TRAEs) (grade 0-2). Common TRAEs included hypoproteinemia (93.10%), abdominal pain (72.41%), nausea (68.97%) and leukopenia (65.52%). There were no deaths due to TRAEs. Conclusions: HAIC (FOLOFOX) combined with tislelizumab and lenvatinib afforded promising efficacy and safety in tumor control in patients with advanced HCC with PVTT in short-term observation and an eligible surgical conversion rate was observed. Clinical trial information: CHiCTR2100051717.