tbuckley/cabot-search huggingface dataset:
Dalpiciclib and chidamide in patients with HR+/HER2- advanced breast cancer and resistance to CDK4/6 inhibitors: A phase Ib trial.
Authors: Tao Wang
Journal: Journal of Clinical Oncology (2024)

e13072 Background: The combination of CDK4/6 inhibitors and endocrine therapy (ET) as first or second-line therapy could improve PFS and OS for patients with HR-positive/HER2-negative breast cancer. However, the standard treatment for patients who have failed CDK4/6 inhibitors has not been established. Histone deacetylase inhibitors (HDACi) inhibit the proliferation of tumor cells through a variety of ways, such as improving the expression level of p21 and other genes. In China, dalpiciclib (a CDK4/6 inhibitor) in combination with ET has been approved for patients with metastatic HR-positive/HER2-negative breast cancer. Chidamide (an HDAC inhibitor) has been approved for the treatment of metastatic HR-positive/HER2-negative breast cancer. The investigator's previous retrospective study has shown that chidamide combined with ET may be an optional sequential strategy for patients who have progressed on CDK4/6 Inhibitor. The aim of this study was to explore the efficacy and safety of dalpiciclib in combination with chidamide in locally advanced or metastatic HR+/HER2- breast cancer patients who have failed CDK4/6 inhibitors (NCT 05586841). Methods: This study is a single-arm, open-label, prospective, phase Ib, dose escalation clinical trial. Before entering this trial, all patients with HR-positive/HER2-negative locally recurrent or metastatic breast cancer (MBC) must have received ≤1 previous line of chemotherapy for MBC, and have failed CDK4/6 inhibitor therapy. The primary endpoint is maximum tolerated dose (MTD) of dalpiciclib in combination with chidamide. Patients were assigned to four groups to receive dalpiciclib and chidamide (Group A: dalpiciclib 125mg/d and chidamide 25mg/BIW; Group B: dalpiciclib 125mg/d and chidamide 20mg/BIW; Group C: dalpiciclib 100 mg/d and chidamide 25mg/BIW; Group D: dalpiciclib 100 mg/d and chidamide 20mg/BIW). Results: Fourteen patients were enrolled between 19/1/2023 and 30/1/2024 (Group A, N=4; Group B, N=3; Group C, N=4; Group D, N=3). All the patients were received ≥ 1 line CDK4/6 inhibitors and 11 patients (78.6%) received chemotherapy in advanced breast cancer. Two patients experienced dose-limiting toxicities (DLT, Group A, n=1; Group B, n=1). The incidence of adverse events of any grade was 100%. The most frequent grade 3-4 adverse events were neutropenia (100%) and thrombocytopenia (35.7%). The median follow-up was 251 days (range, 188.486-313.514), and median PFS was 201 days (95%CI: 158.49-243.51). 2 of 14 patients achieved partial response (PR; Group C, n=2), 10 of 14 patients achieved stable disease (SD) and 2 of 14 had progressive disease (PD; Group A, n=2). In this study, dose group C was identified as recommended phase II dose (RP2D). Conclusions: The combination of dalpiciclib and tucidinostat is an alternative treatment strategy in patients who have failed CDK4/6 inhibitors. Clinical trial information: NCT05586841 .
Acute care and overall survival results of a randomized trial of a virtual health intervention during routine cancer treatment.
Authors: Robert Michael Daly, Karolina Bryl, Raymond E Baser, Angela Green, Tony Hung, Erin F. Gillespie, Katherine Panageas, Michael A. Postow, Jun J. Mao
Journal: Journal of Clinical Oncology (2024)

1503 Background: Despite rapid development of virtual health interventions, little is known of their impact on acute healthcare utilization and survival outcomes. This study aimed to evaluate the effectiveness of Integrative Medicine at Home (IM@Home), a virtual mind-body fitness program, on unplanned hospital admission and overall survival among patients undergoing systemic cancer treatment. Methods: We conducted a randomized clinical trial of IM@Home (choice of 23 weekly virtual live mind-body and fitness classes) compared with an enhanced usual care (EUC) control intervention consisting of asynchronous recordings (standard of care plus access to 17 pre-recorded online meditation resources) for patients with melanoma, thoracic, gynecological, or head/neck cancers on systemic treatment who reported moderate or greater fatigue. The study intervention lasted up to 12 weeks, and patients were followed thereafter for clinical events. Admission to a hospital over the study period was collected from patient-reported-outcomes and the electronic medical records and compared between arms. Overall survival was estimated using the Kaplan-Meier method. Results: Between October 2021 and March 2023,128 patients were randomized: (mean age 64 years) 109 (85.2%) were female, 106 (82.8 %) white, 10 (7.8%) Black, 7 (5.5%) Asian, and 118 (92.2%) non-Hispanic. 49 (38.3%) patients had thoracic, 44 (34.4%) gynecological, 25 (19.5%) head/neck, and 10 (7.8%) melanoma cancer. 58 (45.3%) were receiving chemotherapy, 45 (35.2%) immunotherapies, and 29 (22.7%) targeted therapies. Compared to EUC, patients in the IM@Home group were less likely to be hospitalized (4/64 [6.3%] vs. 12/63 [19.1%], p=0.038) and spent fewer days in the hospital (4.3 vs. 10.5 mean days per patient, p&lt;0.001) during the 12-week study period. Overall survival results were assessed in Feb 2024 after a median follow up of 20.3 months. Median overall survival was 24.3 months in the EUC arm and was not reached in the IM@Home intervention arm (p=0.06). Conclusions: Participation in the virtual IM@Home program reduced unplanned hospitalizations and number of hospitalization days among patients with cancer receiving systemic treatment. Larger studies with longer follow-up are needed to confirm the effect of virtual supportive care on improving overall survival and reducing acute healthcare utilization. Clinical trial information: NCT05053230 .
The fibula osteoseptocutaneous flap - evolution in concepts, techniques and technologies during mandibular reconstruction: a review
Authors: Curtis Hanba, Ta-Chun Lin, Fu-Chan Wei
Journal: International Journal of Surgery (2024)

The fibula-free flap has evolved from its initial description to be a reliable workhorse-free flap providing bone, soft tissue, and a reliable skin paddle. The senior author has been refining this technique since the mid-1980s and has personally performed over 950 hundred cases of the fibula-free flap. The following paragraphs detail an evolution in surgical concepts related to this technique's refinement and serves as a roadmap detailing contemporary mandibular reconstruction.
Pericardial Diseases
Authors: Allan L Klein, Tom Kai Ming Wang, Paul C Cremer, Antonio Abbate, Yehuda Adler, Craig Asher, Antonio Brucato, Michael Chetrit, Brian Hoit, Christine L Jellis, Deborah H Kwon, Martin LeWinter, David Lin, Sushil Allen Luis, Vartan Mardigyan, Jae K Oh, Karen G Ordovas, E Rene Rodriugez, Aldo L Schenone, Carmela D Tan, Brittany Weber, Massimo Imazio
Journal: JACC. Cardiovascular imaging (2024)
Clinical outcomes and short-term survival of neoadjuvant immunochemotherapy for resectable esophageal cancer: a multi-center retrospective cohort study
Authors: Ke Lan, Xiaolong Yan, Jie Lei, Xufeng Guo, Yongan Zhou, Xiaoping Wang, Honggang Liu, Feng Tian, Qiang Lu, Zhongping Gu, Jianyong Sun, Ende Yang, Daixing Zhong, Tao Wang, Lijun Huang, Jian Wang, Xu Liu, Yunfeng Ni, Tao Jiang, Jinbo Zhao
Journal: International Journal of Surgery (2024)

The present retrospective cohort study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy for resectable esophageal cancer and report the preliminary short-term survival. A multicenter, retrospective study was conducted concerning patients who received neoadjuvant PD-1 agents plus platinum-based chemotherapy between January 2019 and January 2022. The primary endpoint was the tumor pathologic complete response (pCR) rate. Two hundred and thirteen patients with initial stage cI-IVA esophageal cancer who received neoadjuvant immunochemotherapy were identified. The complete tumor resection(R0) rate was 99.1%. The pCR rate was 31.9%, and the overall major pathological response rate was 49.8%. The 2-year DFS rate was 78.9% (95% CI: 72.9-85.4%) and the 2-years OS rate was 80.9% (95% CI: 75.3-86.9%). The incidence of TRAEs and surgical complications rate were 68.5 and 35.2%, respectively. The PD-1 agents combined with chemotherapy in the neoadjuvant treatment for resectable stage I-IVA esophageal cancer had a high pCR rate as well as good short-term survival benefits and tolerable toxicity.
Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2–Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial
Authors: Akihiro Ohba, Chigusa Morizane, Yasuyuki Kawamoto, Yoshito Komatsu, Makoto Ueno, Satoshi Kobayashi, Masafumi Ikeda, Mitsuhito Sasaki, Junji Furuse, Naohiro Okano, Nobuyoshi Hiraoka, Hiroshi Yoshida, Aya Kuchiba, Ryo Sadachi, Kenichi Nakamura, Naoko Matsui, Yoshiaki Nakamura, Wataru Okamoto, Takayuki Yoshino, Takuji Okusaka
Journal: Journal of Clinical Oncology (2024)

PURPOSE Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. In addition, the significance of anti–human epidermal growth factor receptor 2 (HER2) therapy in HER2-expressing BTC has not been sufficiently investigated. METHODS In this phase II trial, participants from five institutions in Japan were enrolled. Eligible patients had pathologically confirmed unresectable or recurrent BTC with centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ or IHC2+ and in situ hybridization [ISH]+) or HER2-low (IHC2+ and ISH–, IHC1+, and IHC0 and ISH+) and were refractory or intolerant to a gemcitabine-containing regimen. The patients received 5.4 mg/kg trastuzumab deruxtecan (T-DXd) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the confirmed objective response rate (ORR) in HER2-positive BTC by an independent central review (threshold ORR, 15%; expected ORR, 40%). RESULTS A total of 32 patients were enrolled and treated. Among these patients, 22 with HER2-positive disease comprised the primary efficacy population and had a confirmed ORR of 36.4% (90% CI, 19.6 to 56.1; P = .01), meeting the primary end point. Eight with HER2-low disease comprised the exploratory population and had a confirmed ORR of 12.5%. The most common ≥grade 3 treatment-related adverse events were anemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease (ILD), including two grade 5 events. CONCLUSION T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC. Although the safety profile was generally manageable, ILD requires careful monitoring and early intervention.
Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial
Authors: Ethan B. Ludmir, Alexander D. Sherry, Bryan M. Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N. Medina-Rosales, Alexandre Reuben, Emma B. Holliday, Grace L. Smith, Sonal S. Noticewala, Sarah Nicholas, Tracy R. Price, Rachael M. Martin-Paulpeter, Luis A. Perles, Sunyoung S. Lee, Michael S. Lee, Brandon G. Smaglo, Ryan W. Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M. Taniguchi, Eugene J. Koay, Matthew H.G. Katz, Robert A. Wolff, Prajnan Das, Shubham Pant, Albert C. Koong, Chad Tang
Journal: Journal of Clinical Oncology (2024)

The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).
Directionality of HLA-DP permissive mismatches improves risk prediction in HCT for acute leukemia and MDS
Authors: Esteban Arrieta-Bolaños, Lars L. J. van der Burg, Tobias Gedde-Dahl, Marie Robin, Urpu Salmenniemi, Nicolaus Kröger, Ibrahim Yakoub-Agha, Anne Huynh, Charles Crawley, Eric Deconinck, Claude Eric Bulabois, Edouard Forcade, Eleni Tholouli, Joost G. K. van der Hem, Peter van Balen, Jorinde D. Hoogenboom, Liesbeth C. de Wreede, Florent Malard, Annalisa Ruggeri, Katharina Fleischhauer
Journal: Blood (2024)
Pyrotinib plus taxanes or vinorelbine for human epidermal growth factor receptor 2-positive metastatic breast cancer: A prospective study.
Authors: Weili Xiong, Lili Zhang, Yuan Yuan, Quan Gu, Sainan Hu, Jiayuan Huang, Min Dong, Jifeng Feng
Journal: Journal of Clinical Oncology (2024)

e13004 Background: Pyrotinib in combination with capecitabine is recommended as the second-line treatment for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) in China. The efficacy and safety of pyrotinib combined with non-capecitabine chemotherapy regimens remain unclear. Thus, we conducted this study to evaluate the efficacy and safety of pyrotinib combined with taxanes or vinorelbine in HER2-positive MBC. Methods: Patients with HER2-positive MBC were included to receive pyrotinib combined with taxanes or vinorelbine in Jiangsu Cancer Hospital. Patients received pyrotinib 400mg orally once daily plus taxanes (docetaxel 75-100 mg/m 2 on day1, or nab-paclitaxel 125 mg/m 2 on days 1 and 8, paclitaxel 80 mg/m 2 on days 1 and 8, every 3 week) or vinorelbine 25 mg/m 2 on days 1 and 8, every 3 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS) and safety. Results: Between Nov 20, 2018, and Jan 11, 2023, a total of 101 patients were assigned to pyrotinib plus taxanes group (n=83) and pyrotinib plus vinorelbine group (n=18). The median number of pyrotinib therapy lines was 2 (IQR 1-7), the first line accounted for 23.8%, the second line, and third line and above was 34.6%, 41.6%, respectively. As of May 24, 2023, the median PFS in the total was 11.5 months (95% confidence interval [CI], 8.8-15.7). The median PFS was significantly longer in the pyrotinib plus taxanes group than in the pyrotinib plus vinorelbine group, with median PFS being 12.2 months (95% CI, 9.2-18.6) and 8.4 months (95% CI, 5.5-13.7) (HR=2.2 [95% CI, 1.2-3.9]; P=0.005), respectively. The median PFS in the first-line, second-line, and third-line and above treatment was 28.6 (95% CI, 10.6-NA), 12.2 (95% CI, 8.5-16.3), and 8.3 months (95% CI, 6.3-14.5), respectively. The most common grade 3 or 4 adverse events were diarrhea (22.8%), leukopenia (19.5%), and neutropenia (18.2%). Conclusions: The median PFS of pyrotinib plus taxanes or vinorelbine, especially taxanes, was not inferior even superior to that of pyrotinib combined capecitabine. No increase treatment-related side effects was reported. Thus, the combination of pyrotinib and taxanes or vinorelbine regimen can be an option for HER2-positive MBC. Clinical trial information: ChiCTR2000041217.
Evaluation of survival outcomes in patients with solid organ cancer with brain metastasis treated with exacta encylopedic tumor analysis based treatments.
Authors: Razelle Kurzrock, Sewanti Limaye, Farzad Massoudi, Rajan Datar, Ajay Srinivasan, Rahul Ashok Gosavi, Vineet Datta, Nelofer Syed, Tim Crook
Journal: Journal of Clinical Oncology (2024)

2033 Background: Brain metastasis in solid organ cancers presents a challenging scenario with an adverse prognosis and limited systemic treatment options. Treatment of such patients becomes more challenging because most drugs can't cross the blood-brain barrier, besides the treatment being too harsh for sensitive brain parenchyma. Moreover, these patients are frequently excluded from clinical trials, reflecting concerns about their poor prognosis influencing trial outcomes and potentially distorting efficacy data. While almost all cancers metastasize to the brain, cancers of the breast, lungs, kidney and melanoma carry a higher risk. Methods: The Resilient Study, a Phase-II, single-arm, open-label interventional trial, focused on evaluating the efficacy of Exacta Encyclopedic Tumor Analysis (ETA)-guided treatment for a range of solid organ cancers in patients who had failed multiple lines of treatment and were broadly refractory. 143 patients were recruited out of whom 126 patients were evaluable. Prior to treatment initiation, all patients underwent PET-CT and MRI scans to assess the extent of the disease. 9 out of 126 patients (7.1%) were found to have metastatic deposits of the brain comprising 6/21 patients (29%) of breast cancer, 2/5 patients (40%) of lung cancer, and 1/15 patient (7%) of colorectal cancer. Utilizing freshly biopsied tumor tissue (primary/lymph node/liver) and peripheral blood, Exacta ETA was performed, encompassing gene mutations, gene expression, and in vitro chemosensitivity profiling of viable tumor cells. Exacta ETA-derived personalized therapy recommendations were administered to patients. Follow-up data for OS was collated. Results: Median overall survival (OS) was not reached at the time of analysis. By considering the OS values censored at the interim (most recent follow-up), the median OS was 9.7 months (95% CI 7.06 - 12.3 months; range: 1 month – not reached) among patients without brain metastases (n = 117, 92.8%) and 10 months (95% CI 2.6 - 15.9 months; range: 2.6 months – not reached) among patients with brain metastases. Conclusions: Our data shows that personalized Exacta ETA-guided treatments resulted in almost similar OS for patients with brain metastases as seen in patients or without brain metastases. These findings stand out as significant considering the poor outcomes with Standard of Care treatments in patients with brain metastases. Clinical trial information: CTRI/2018/02/011808.
Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors.
Authors: Sajeve Samuel Thomas, Brian Pico, Brian S. Henick, Rom Leidner, Yazan Samhouri, James Isaacs, Jared Weiss, Michael E. Hurwitz, Jaspreet Singh Grewal, Jason J. Luke, Shrikanta Chattopadhyay, Yun Wang, Marlyane Motta, Jim Murray, Debora Barton, Dawn Pinchasik, Gavin MacBeath, Justin C Moser
Journal: Journal of Clinical Oncology (2024)

2542 Background: Solid tumors are notoriously heterogenous with highly variable antigen expression and an immunosuppressive microenvironment. HLA loss of heterozygosity (LOH) has also been identified in up to 40% of solid tumors, allowing tumor cells to evade T cell attack. To overcome these issues and a lack of potent endogenous antitumor T cells in cancer patients, TScan has developed T-Plex, a multiplexed cell therapy comprising two to three different TCR-Ts, chosen from a collection of TCR-Ts called the ImmunoBank. Product and study design details were presented at ASCO 2023 (Abstract #2554). Methods: A screening protocol (NCT05812027) pre-identifies patients with solid tumors any time during clinical care, enabling rapid enrollment into the treatment protocol (NCT05973487) upon disease progression. TCR-Ts currently in the master protocol target PRAME on HLA-A*02:01; HPV16 on HLA-A*02:01; MAGE-A1 on HLA-A*02:01, HLA-A*01:01, or HLA-C*07:02; or MAGE-C2 on HLA-B*07:02. All TCR-Ts in the ImmunoBank and master protocol are first tested as single therapies in dose levels 1 and 2 before becoming available for multiplexing in dose levels 3 and 4. Results: From September 2023 to the time of abstract submission, 140 participants with a variety of solid tumors were enrolled in the screening protocol and are in different stages of screening. To date, 65% have ≥1 HLA match, and 20% and 6% have 2 and 3 HLA matches, respectively, highlighting the advantage of including TCR-Ts targeting multiple different HLA types within the same master protocol. Of those who have completed target screening, 92% express at least one target and 65% qualify for at least one TCR-T. Intratumoral heterogeneity of target expression was observed even with the most prevalently expressed target, PRAME, supporting the rationale for multiplexed TCR-T treatment. Although HLA-LOH affects only half of HLA genes and the remaining intact HLA alleles in tumors can still be recognized by TCR-Ts, about 13% of participants had LOH of the targeted HLA allele, excluding them from TCR-T treatment. Conclusions: Initial data indicate that the combination of HLAs and targets in the ImmunoBank results in ≥1 TCR-T match for the majority of solid tumor patients evaluated to date, and many patients qualify for multiplexed TCR-T treatment. LOH testing can prevent selection and treatment with a TCR-T that would not confer benefit. The proportion of patients eligible for multiplexing is expected to increase as the ImmunoBank grows. Updated data on screened and treated patients will be presented at the meeting. Clinical trial information: NCT05973487 ; NCT05812027 .
Asciminib Monotherapy as Frontline Treatment of Chronic-Phase Chronic Myeloid Leukemia: Results from the ASCEND Study
Authors: David T. Yeung, Naranie Shanmuganathan, John Reynolds, Susan Branford, Mannu Walia, Agnes SM Yong, Jake Shortt, Lynette Chee, Nicholas Viiala, Ilona Cunningham, David M Ross, Alwyn Bernard D'Souza, Matthew Wright, Rosemary Anne Harrup, Cecily Jane Forsyth, Robin Filshie, Steven W Lane, Peter J Browett, Carolyn S Grove, Andrew A Grigg, Timothy P Hughes
Journal: Blood (2024)
Tislelizumab combined with gemcitabine and albumin paclitaxel as preoperative therapy for patients with borderline resectable pancreatic cancer: A prospective, single-arm, phase II trial.
Authors: Yonggang Gang He, Xiaobing Huang, Lu Zheng, Jing Li, Chongyu Zhao, Ying Li, Guohua Zuo
Journal: Journal of Clinical Oncology (2024)

4162 Background: Pancreatic cancer is a highly aggressive disease with low resection rate and poor prognosis. Neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) is increasing in acceptability, but no standard treatment has been established. Herein, we aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with BRPC. Methods: This is a single arm, exploratory phase II clinical trial. Gemcitabine (1000 mg/m 2 ) and albumin paclitaxel (125 mg/m 2 ; AG) were administered to patients with BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Surgical intervention was assessed after two cycles of treatment. Primary endpoint was adverse events (AE) and R0 resection rate. Secondary endpoints were objective response rate (ORR) and progression free survival (PFS) by mRECIST, relapse-free survival (RFS) and overall survival (OS). Results: Between October 2022 and December 2023, 21 patients were enrolled in the study. At the end of the last follow-up (January 27, 2024), 15 patients had a best response of partial response, the ORR was 71.4% according to mRECIST. The disease control rate (DCR) was 85.7%. The 12-months PFS rate, and 12-months OS rate were 68.2% (95% CI: 38.0%–86.0%), and 63.8% (95% CI: 33.2%–88.3%), respectively. After the two cycles of neoadjuvant therapy, 14 patients underwent resection (66.7%,14/21) and the R0 resection rate was 100%. For those patients who did not undergo surgery, 3 of them achieved PR but refused surgery, 3 patients developed disease progression and lost the chance of surgery. 1 patient died of severe pneumonia caused by H1N1 infection. So far the safety of neoadjuvant treatment was satisfied, no grade 4 or above treatment-related-adverse events (TRAEs) were observed. Grade 3 TRAEs were reported in 3(14.29%) patients. Frequently occurring adverse events were grade 1-2, including myelosuppression (90.47%), albuminuria (80.95%), nausea (61.90%), elevated aspartate aminotransferase (47.62%) and elevated alanine aminotransferase (38.10%). Grade 3 or higher adverse events were pneumonia (4.76%), elevated AST (4.76%), elevated ALT (4.76%) and myelosuppression (4.76%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy displayed promising antitumor activity and acceptable safety profile for patients with BRPC. Clinical trial information: ChiCTR2200063680.