tbuckley/cabot-search huggingface dataset:
Innovative infusion center assessments of chemotherapy-induced neurotoxicities: A pilot study supporting early and routine screenings as part of survivorship programs.
Authors: Jennessa Rooker, Matthew L. Anderson, Thomas Rutherford, Rebecca Schwarzberg, Victoria Ann Sanchez
Journal: Journal of Clinical Oncology (2024)

e24102 Background: More than 50% of patients treated with taxane and platinum chemotherapy experience neurotoxic adverse events due to treatment, including neuropathy, hearing loss or cognitive impairment. However, because risk factors and clinical trajectory of these toxicities remain poorly understood, it is not yet clear how or when patients should be screened. Innovative technology, such as tablet-based screening tools, create unique opportunities to capture patient symptoms, better understand potentially long-lasting side effects, and determine when to start either preventive or treatment/rehabilitation options. Methods: We assembled a multidisciplinary team from oncology, nursing, and audiology. IRB permission was obtained to perform a longitudinal observational pilot to assess the feasibility of performing chair-side neurotoxicity screenings in the infusion center of an urban safety net health system. Five infusion center nurses were recruited to collect data using a tablet-based application on 55 patients who met the inclusion criteria including chemotherapy-naive patients and fluent in English. Neuropathy and cognitive impairment were measured by validated standardized subjective scales (the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and the Attentional Function Index, respectively) and objective pure-tone audiometry (SHOEBOX Audiometry). Descriptive statistics were used to summarize outcome data. Results: Baseline assessments were completed on 48/55 patients with 37 completing at least one or up to 6 repeated assessments. All participants had baseline assessments before their first cycle by a chemo-certified RN in the infusion chair. Our sample included 55 adults aged 29 to 81 years, of whom 75% were females. 61% of participants were diagnosed with a gynecologic cancer, and 51% consented to receive Paclitaxel and Carboplatin chemotherapy regimen, 29% consented to receive Cisplatin chemotherapy, the remaining 20% consented to receive Oxaliplatin, Docetaxel, or Carboplatin alone. Significant changes occurred in all 3 symptoms by cycle 6 of chemotherapy with 45% of participants experiencing neuropathy, 13% experiencing a clinically significant change in hearing, and 30% experiencing self-reported cognitive concern by the 6 th cycle. Ototoxicity and neurotoxicity scores followed the same trajectory of an increase or worsening in scores over time from cycle 1 to cycle 6. Conclusions: Use of innovative, portable tablet-based screening tool can be effectively used to capture symptoms of neuropathy chair-side as patients undergo chemotherapy. These observations support the need to better assess these approaches so that they can be used to optimize clinical outcomes and patient quality of life.
Conflict and catastrophe-related severe burn injuries: A challenging setting for antimicrobial decision-making
Authors: Scott JC Pallett, Rakhee Mistry, Zoe L Lambert, Stephen D Woolley, Aula Abbara, Aodhan O Breathnach, Lucy E Lamb, Andrew Williams, Nabeela Mughal, Olena Moshynets, Stephen J Hughes, Matthew K O’Shea, Luke SP Moore
Journal: Journal of Infection (2024)
Epidemiological trends in viral meningitis in England: prospective national surveillance, 2013-2023
Authors: Seilesh Kadambari, Fariyo Abdullahi, Cristina Celma, Shamez Ladhani
Journal: Journal of Infection (2024)

In the conjugate vaccine era, viruses are the most common cause of meningitis. Here, we evaluated epidemiological trends in laboratory-confirmed viral meningitis across all age-groups over an 11-year period in England.
Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials
Authors: Matthew A Brown, Martin Rudwaleit, Floris A van Gaalen, Nigil Haroon, Lianne S Gensler, Carmen Fleurinck, Alexander Marten, Ute Massow, Natasha de Peyrecave, Thomas Vaux, Katy White, Atul Deodhar, Irene van der Horst-Bruinsma
Journal: Annals of the Rheumatic Diseases (2024)

Objectives Acute anterior uveitis (‘uveitis’) is a common axial spondyloarthritis (axSpA) extramusculoskeletal manifestation. Interleukin (IL)-17 is implicated in its pathogenesis, however, there is conflicting evidence for IL-17A inhibition in uveitis management. We report pooled analyses of uveitis incidence in patients receiving bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, from phase 2b/3 trials. Methods Data were pooled for patients receiving BKZ 160 mg or placebo in the double-blind treatment period of the phase 3 BE MOBILE 1 ( NCT03928704 ; non-radiographic axSpA) and BE MOBILE 2 ( NCT03928743 ; radiographic axSpA) trials. Data were separately pooled for patients treated with at least one BKZ dose in the BE MOBILE trials and their ongoing open-label extension (OLE; NCT04436640 ), and the phase 2b BE AGILE trial ( NCT02963506 ; radiographic axSpA) and its ongoing OLE ( NCT03355573 ). Uveitis rates and exposure-adjusted incidence rates (EAIR)/100 patient-years (PYs) are reported. Results In the BE MOBILE 1 and 2 double-blind treatment period, 0.6% (2/349) of patients receiving BKZ experienced uveitis vs 4.6% (11/237) receiving placebo (nominal p=0.001; EAIR (95% CI): 1.8/100 PYs (0.2 to 6.7) vs 15.4/100 PYs (95% CI 7.7 to 27.5)). In patients with history of uveitis, EAIR was lower in patients receiving BKZ (6.2/100 PYs (95% CI 0.2 to 34.8); 1.9%) vs placebo (70.4/100 PYs (95% CI 32.2 to 133.7); 20.0%; nominal p=0.004). In the phase 2b/3 pool (N=848; BKZ exposure: 2034.4 PYs), EAIR remained low (1.2/100 PYs (95% CI 0.8 to 1.8)). Conclusions Bimekizumab, a dual-IL-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA.
Clinical features and prognostic analysis of 247 patients with ovarian clear cell carcinoma (OCCC) and an exploration of the treatment of recurrent OCCC: A single-center study in China.
Authors: You Wu, XueYan Lyu, Kunyu Wang, Miao Ao, Haixia Luo, He Zhang, Yuanyuan Zhang, Bin Li, Yan Song
Journal: Journal of Clinical Oncology (2024)

e17548 Background: Ovarian clear cell carcinoma (OCCC) is relatively resistant to chemotherapy and has a worse prognosis than other ovary cancer. In this study, we reviewed the case files of OCCC in a single center to find its clinical characteristics and explore the treatment of recurrent cases, and the efficacy of immunotherapy. Methods: From August 2007 to August 2023 247 patients with OCCC were retrospectively involved. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors. The relapse OCCC were divided into four groups based on the different treatment who underwent chemotherapy or chemotherapy combined with surgery, bevacizumab, immune checkpoint inhibitors treatment. Kaplan–Meier curves were utilized to compare OS and DFS/PFS between the groups. Results: (1) 247 patients with OCCC were included, CA125 abnormality (&gt; 35 U/ml) 65.2%, ascites cytology positive 10.1%, and the overall satisfactory reduction of tumor was 92.7%, CR and PR were 93.1 and 6.9%, respectively. 16.2% patients received more than 6 cycles of postoperative chemotherapy.(2)Univariate Cox regression analysis identified ascites (HR=4.012, 95% CI: 1.846 - 8.720, P&lt;0.001), initial treatment effect (HR=2.714, 95% CI: 1.132 - 6.506, P=0.025), and chemotherapy cycles (HR=2.564, 95% CI: 1.402 - 4.689, P=0.002) were identified as independent prognostic factors for OS.(3)The patients who received chemotherapy cycles exceeding 6 cycles had worse prognosis(HR=3.01, 95%CI: 1.70-5.33, P&lt;0.001), the result is the first proposal in our study.(4) Kaplan-Meier survival analysis showed that the OS of the chemotherapy combined with surgery relapse OCCC group was significantly better than the other three groups (HR=0.2732, 95%CI: 10.133-0.559, P=0.001). Subgroup analysis showed that relapse patients with satisfactory tumor reduction had more significant survival benefits(HR=3.86, 95%CI: 0.79-18.93, P=0.096).(5)The PFS of the chemotherapy combined with surgery group was also better than the other three groups (median PFS 25 months vs 8.5 months in chemotherapy vs12 months in chemotherapy combined immunotherapy vs 12 months in chemotherapy combined with bevacizumab). (6)4 patients who tested positive for PD-L1 received immune maintenance therapy after chemotherapy for 6-24months. There has been no recurrence since follow-up. Conclusions: Ascites, initial treatment effect and chemotherapy cycles were identified as independent prognostic factors for OCCC OS, chemotherapy combined with surgery for recurrent OCCC was significantly improving patient prognosis. For patients who achieve CR after initial treatment, if PD-L1 expression is positive, maintenance immunotherapy can be considered, but further studies with large samples are needed.
Overall survival in patients with <i>BRCA</i>-mutated platinum-sensitive relapsed ovarian cancer (PSROC) treated with olaparib maintenance: Real-world data of the C-PATROL study.
Authors: Frederik Marmé, Felix Hilpert, Manfred Welslau, Jacek P. Grabowski, Andreas Schneeweiss, Andreas D. Hartkopf, Dirk Bauerschlag, Peter A. Fasching, Christiane Brandi, John-Kilian Rehbein, Regina Glowik, Jalid Sehouli
Journal: Journal of Clinical Oncology (2024)

e17542 Background: Maintenance monotherapy with PARP-inhibitor (PARPi), olaparib has previously shown good effectiveness and tolerability in total population of patients with PSROC who were in response to platinum-based chemotherapy (PBC) in the C-PATROL study. Here we present the overall survival (OS) data in different subgroups. Methods: The prospective German non-interventional study C-PATROL (NCT02503436) captured routine clinical data of olaparib maintenance according to label in patients with BRCA-mutated PSROC treated with PBC. The primary endpoint was PFS, relevant secondary endpoints included OS and safety. Data were analyzed by descriptive statistics. Results: Between 10/2015 and 10/2019, 277 patients were enrolled. The ITT set (study selection criteria fulfilled) comprised 267 patients (median age: 60 yrs; ECOG ≤1: 93%; ≥2 relapses: 32%; ≥3 prior PBC: 29%). Median follow-up was 23.5 months (range 0.0–80.5) and median olaparib treatment duration was 13.6 months (0.1–80.9). 10% of patients received olaparib for ≥ 5 years and 8% of patients received further PARPi also as subsequent treatment. Median OS was 35.4 months (95% CI 29.2–49.9). The longest median OS was observed in patients with a complete debulking after the surgery at current relapse, a complete response (CR) to the current PBC and a BRCA2 mutation. Adverse events (AEs) were consistent with the known tolerability profile of olaparib (safety set: n=274; any AE: 95%, AE of CTCAE grade ≥ 3: 40%, olaparib discontinuation due to AE: 11%; most common AE any CTCAE: nausea (46%), fatigue (39%), anaemia (31%), and vomiting (17%); most common AE CTCAE grade ≥ 3: anaemia (14%)). Conclusions: Olaparib is effective and safe in the real-world setting. In olaparib-treated patients with BRCA-mutated PSROC longer OS was observed mainly with respect to resection status after debulking surgery at current relapse, to tumor burden at the therapy start and BRCA mutation type. Our data underline the role of cytoreduction and platinum response in the context of PARPi maintenance therapy. Clinical trial information: NCT02503436 . [Table: see text]
Identification of tumor-marker gangliosides for early cancer detection: A multi-platform approach.
Authors: Adele Blackler, Rachel Culp-Hill, Robert A Law, Enkhtuya Radnaa, Abby Tyler, Susan Halstead, Hugh Willison
Journal: Journal of Clinical Oncology (2024)

e17551 Background: Tumor-marker gangliosides (TMGs) have enormous potential for early-stage cancer detection as diagnostic biomarkers despite being relatively understudied in this context. AOA Dx is focused on the analytical development of three separate platforms for the quantitation of TMGs in human serum. The development of these platforms for TMG quantitation may allow for the identification of diagnostic signatures for early-stage cancer detection. Methods: First, we are developing a pipeline of antibody-based assays to target TMGs. To aid in development of multiple immunoassays, we collected specificity and affinity data on commercial and proprietary antibodies targeting TMGs using glycoarrays. We are also currently using two immune-based platforms to target TMGs. We have developed an enzyme-linked immunosorbent assay (ELISA) and we have implemented high-performance thin-layer chromatography (HPTLC) to detect individual and total gangliosides. Additionally, we are applying both targeted and untargeted mass spectrometry to human serum from confirmed cancer diagnoses. Results: The specificity and affinity data from the glycoarrays confirm that our TMG antibodies have negligible cross-reactivity and are suitable for diagnostic platform development. Additionally, our developed ELISA allows for the quantification of TMGs in diverse and complex matrices including human serum and plasma, cell lines, and exosomes. HPTLC also detects individual and total gangliosides in each of these matrices, which allows for high-throughput analysis for TMG quantitation. Finally, the application of both targeted and untargeted mass spectrometry has identified multiple TMGs characterized by unique lipid tails. Notably, MS analysis shows that the serum of melanoma and ovarian cancer patients exhibited significantly increased levels of several ganglioside species compared to age-matched healthy serum, further highlighting the potential of TMGs as a promising avenue for cancer diagnosis. Further experiments will focus on refining all platforms. We will also expand the demographic representation of our human serum sample cohort to confirm the initial findings from our mass spectrometry experiments and continue to use this platform to identify additional TMGs of interest. Conclusions: AOA Dx is advancing the development of a multi-platform approach for the detection of TMGs. Our objective is the identification of a diagnostic disease signature for early-stage cancer detection. The validation of this type of diagnostic panel would allow for expedited diagnosis and treatment of cancers currently diagnosed at late stages, ultimately reducing healthcare costs and increasing survival rates. Future research will aim to validate these biomarkers in independent prospective studies.
Multiomic analysis in ovarian clear cell carcinoma to gain insight into biology and therapeutic opportunities.
Authors: Ben Kong, Jayne Stommel, Jenna Emerson, Elizabeth G. Munro, Christopher L. Corless, Gordon B. Mills, Tanja Pejovic
Journal: Journal of Clinical Oncology (2024)

e17540 Background: Ovarian clear cell carcinoma (OCCC) is a rare subtype with distinct histologic and molecular features. The prognosis of advanced/recurrent OCCC treated with standard of care surgery and platinum-based chemotherapy remains poor due to inherent chemoresistance. Therefore, there is an urgent need to identify novel biological insights and personalized treatment approaches to improve outcomes. Methods: Participants were referred to the SMMART Program at the OHSU Knight Cancer Institute. Archival or fresh tissue was obtained from metastatic sites and processed through a multiomics platform that included immunohistochemistry (Ki67, HER2, CD4, CD8, PD-L1), fluorescent in-situ hybridization, targeted next-generation sequencing panel (225 genes), whole transcriptomic sequencing, chromosomal microarray, and multiplexed analysis of 67 key cancer proteins and phosphoproteins on the Nanostring GeoMx Digital Spatial Profiler. Results: 5 participants were enrolled with an average age of 62 years (range 52-72). Therapeutically relevant findings included detectable HER2 expression by IHC (2+, N=2; 3+, N=2), HER2 amplification by FISH (N=2), and high HER2 and phospho-HER2 protein expression compared to a breast cancer cohort (phospho-HER2 supports active HER2 signaling in the tumor cells). Additional findings include TMB &lt;10 muts/Mb (N=5), microsatellite stable (N=5), Ki67 40-60% (N=4), mild to moderate CD4 and/or CD8 infiltration (N=4), PD-L1 &gt;1% (N=3), low homologous recombination deficiency score (N=4), chromosomal losses including ATM, SMAD4, RB1, and TP53, and single nucleotide variations in ARID1A (N=4). Two participants with HER2 expression were treated with off-label trastuzumab deruxtecan for 6 or 7 cycles yielding significant clinical benefit. Participant A (HER2 = 3+, FISH negative) had an exceptional response while Participant B (HER2 = 2+, FISH amplified) had stable disease. The toxicity profile was consistent with literature. Conclusions: Our OCCC cohort revealed elevated HER2 expression with or without genomic amplification in 4/5 cases. Two participants experienced clinical benefit when treated with trastuzumab deruxtecan, supporting further exploration of HER2 antibody drug conjugates in this aggressive disease. More study is needed to determine the frequency of HER2 overexpression and amplification in OCCC, the importance of HER2 on OCCC pathophysiology, and the therapeutic benefit of targeting HER2 in this population.
Weekly BH009 in patients with squamous cell carcinoma of the head and neck (SCCHN) and ovarian cancer: Interim phase I results.
Authors: Jing Wang, Yaqian Han, Ruoyu Wang, Xiang Li, Yu Kang, Xiaobo Cheng, Ranran Chai, Guanqin Jin, Xiaohua Wei, Qun Sun
Journal: Journal of Clinical Oncology (2024)

e17545 Background: BH009 is a novel polysorbate 80-free formulation of docetaxel that will eliminate hypersensitivity reactions associated with polysorbate 80. BH009 has completed a bioavailability study compared to Taxotere and was found to have a better safety profile to Taxotere with the potential for higher doses. As a result, we conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), and the safety profile of a weekly BH009 regimen in the treatment of patients with advanced SCCHN and Ovarian cancer. Methods: This phase I study assessed safety of BH009 in patients with advanced SCCHN and Ovarian cancer. BH009 was administered at escalating doses (starting dose 40 mg/m 2 ) as a 1-h i.v. infusion for three consecutive weeks every 28 days without dexamethasone premedication. Results: Up to January 2024, 11 patients were treated with BH009 (4 at 40 mg/m 2 , 7 at 50 mg/m 2 ). 2 patients with SCCHN, and 9 patients with ovarian cancer. 100% of ovarian cancer patients were recurrent platinum-resistant ovarian cancer (PROC) patients. 82% (9/11) of patients had received prior taxanes, of whom 33% (3/9) had received prior docetaxel. There were no DLT observed in 40 mg/m 2 dose groups, and one DLT was observed in the 50 mg/m 2 group (grade 3 febrile neutropenia). The MTD for BH009 is expected to exceed 50 mg/m 2 , which would be higher than that of Taxotere under the same dosing regimen (≥50mg/m 2 vs 42mg/m 2 *), and the overall tolerability was better than Taxotere. In this study, treatment-related adverse events (TRAEs) occurred in 100% (11/11) patients. The most common grade 3/4 TRAEs were Leukopenia (36%, n=4), Anaemia (36%, n=4), and Neutropenia (55%, n=6). Non-hematologic toxicities were generally mild with no grade 4 toxicity observed. No AEs that led to death were related to BH009. Up to January 2024, the DCR is 50% (3/6) after 2 courses of treatment. The ORR in 6 evaluable patients was 33% (2/6, 1 patient with SCCHN at 40 mg/m 2 , 1 patient with ovarian cancer at 50 mg/m 2 ). One patient (17%, 1/6) with ovarian cancer at 50 mg/m 2 dose group received a complete response to the target lesion and the non-target lesion was partially responded after 2 courses of BH009, and this patient had been previously treated with docetaxel, carboplatin, and bevacizumab. Conclusions: The weekly BH009 for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity profile, and the overall tolerability is better than Taxotere. BH009 has the potential to increase the dose of administration and improve the clinical efficacy. Dose escalation is ongoing. Clinical trial information: NCT06232863 . [Table: see text]
A phase I/II study of maplirpacept in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (OC): Phase 1 results.
Authors: Daron G. Street, Luke Kuttschreuter, David Starks, Haider Mahdi, Carlos Linn, Dmitri Pavlov, Julio Antonio Peguero, Sant P. Chawla, Ingmar Bruns, Steven E. Waggoner
Journal: Journal of Clinical Oncology (2024)

e17546 Background: CD47, an overexpressed factor correlated with poor clinical characteristics and prognosis in OC, is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a signal to suppress macrophage phagocytosis. Maplirpacept (PF-07901801) is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4, enhancing phagocytosis by blocking CD47. Blockade of CD47, both alone and combined with doxorubicin, has shown anti-tumor activity in vitro and in vivo in xenograft animal models. PLD 40mg/m 2 conveyed poor efficacy (PFS 4 months; ORR 8%), as did bevacizumab + PLD (PFS 5 months; ORR 14%) (AURELIA), highlighting the need for new treatments for platinum-resistant OC. C4971002 [NCT05261490] is an open label, multicenter dose-escalation and expansion study evaluating the safety, preliminary anti-tumor activity, pharmacokinetics and -dynamics of maplirpacept in combination with PLD in patients with platinum-resistant recurrent OC. Methods: The study included adults with platinum-resistant recurrent epithelial OC (PD ≤6 months after platinum-based therapy or unable/unwilling to receive platinum-based therapy). PLD while platinum-resistant or directly prior to study was not permitted. Patients received maplirpacept (12mg/kg Dose Level [DL] 1; 24mg/kg DL2; 48mg/kg DL3) weekly in Cycle 1 and every 2 weeks in Cycle 2+, and PLD (40mg/m 2 ) on Day 1 of each 4-week cycle. Assessments of adverse events (AEs) were based on CTCAE v5.0. Response assessments (RECIST v1.1) were performed every 8 weeks. Results of the Phase I portion, aiming to evaluate the DLTs, the MTD and the RP2D, are presented as of 18 December 2023, after all patients completed the 28-day DLT assessment period. Results: 10 patients were treated (DL1 n=3; DL2 n=3; DL3 n=4) with a median (min, max) age of 69 (53, 77) years, 80% ECOG 1, 60% serous adenocarcinoma. Median (min, max) treatment duration was 14 (8, 32) weeks. Most common adverse events are shown in the table. No DLTs occurred in the assessment period. 1 serious AE (gait disturbance &amp; muscle weakness) related to maplirpacept was reported (DL3). 2 deaths occurred &gt;120 days after 1 st dose, both due to disease. 5 (50%) patients had a best response of stable disease, 2 of which were treated into at least Cycle 6. Conclusions: Despite immature anti-tumor activity, maplirpacept + PLD was tolerable at all dose levels, not reaching the MTD. The encouragingly tolerable dose of 48mg/kg thus represents the RP2D which could support further development for this population. Clinical trial information: NCT05261490 . [Table: see text]