To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic ...mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC.
This article aims to expand on the existing literature regarding the incidence of withdrawal pain following discontinuation of Trk inhibitors and to explore strategies that mitigate this withdrawal ...pain.OBJECTIVEThis article aims to expand on the existing literature regarding the incidence of withdrawal pain following discontinuation of Trk inhibitors and to explore strategies that mitigate this withdrawal pain.A retrospective observational study was conducted among patients who were at least 18 years-old or older and had documentation of starting larotrectinib or entrectinib at University of California, San Francisco (UCSF) between November 2018 and November 2022. Data were collected from electronic records and pharmacy databases and a total of 21 patients were identified in this study.DATA SOURCEA retrospective observational study was conducted among patients who were at least 18 years-old or older and had documentation of starting larotrectinib or entrectinib at University of California, San Francisco (UCSF) between November 2018 and November 2022. Data were collected from electronic records and pharmacy databases and a total of 21 patients were identified in this study.Of the 21 patients included in this study, five patients (24%) experienced pain during temporary or permanent discontinuation of Trk inhibitor with the onset of withdrawal pain ranging from a few hours to three days following discontinuation. Various strategies were implemented to manage this pain including restarting of Trk inhibitor, tapering of Trk inhibitor on discontinuation, minimizing dose interruptions and use of prescription pain medications.DATA SUMMARYOf the 21 patients included in this study, five patients (24%) experienced pain during temporary or permanent discontinuation of Trk inhibitor with the onset of withdrawal pain ranging from a few hours to three days following discontinuation. Various strategies were implemented to manage this pain including restarting of Trk inhibitor, tapering of Trk inhibitor on discontinuation, minimizing dose interruptions and use of prescription pain medications.This article illustrates the presence of withdrawal pain syndrome in patients stopping a Trk inhibitor treatment and highlight the need for patient education to avoid missing any doses and for development of a guideline for Trk inhibitor discontinuation.CONCLUSIONThis article illustrates the presence of withdrawal pain syndrome in patients stopping a Trk inhibitor treatment and highlight the need for patient education to avoid missing any doses and for development of a guideline for Trk inhibitor discontinuation.
MXenes, an emerging class of 2D transition metal carbides and nitrides with the general formula M
X
T
(n = 1-4), have potential for application as floating gates in memory devices because of their ...intrinsic properties of a 2D structure, high density-of-states, and high work function. In this study, a series of MXene-TiO
core-shell nanosheets are synthesized by deterministic control of the surface oxidation of MXene. The floating gate (multilayer MXene) and tunneling layer (TiO
) in a nano-floating-gate transistor memory (NFGTM) device are prepared simultaneously by a facile, low-cost, and water-based process. The memory performance is optimized via adjustment of the thickness of the oxidation layer formed on the MXene surface. The fabricated MXene NFGTMs exhibit excellent nonvolatile memory characteristics, including a large memory window (>35.2 V), high programming/erasing current ratio (≈10
), low off-current (<1 pA), long retention (>10
s), and cyclic endurance (300 cycles). Furthermore, synaptic functions, including the excitatory postsynaptic current/inhibitory postsynaptic current, paired-pulse facilitation, and synaptic plasticity (long-term potentiation/depression), are successfully emulated using the MXene NFGTMs. The successful control of MXene oxidation and its application to NFGTMs are expected to inspire the application of MXene as a data-storage medium in future memory devices.
The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC.
Patients with locally ...advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety.
Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 83.3%) and those who received prior AR- (6 of 13 46.2%) or human epidermal growth factor receptor 2-targeted therapies (5 of 8 62.5%). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide.
Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.
Stem-cell therapy provided significant reductions in myocardial infarct size and better recovery rates of regional systolic function after 4 months of follow-up, but no significant benefit in terms ...of left-ventricular ejection fraction, myocardial perfusion, and cardiac metabolism.
This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic ...(R/M) adenoid cystic carcinoma (ACC).
Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC).
Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% 95% confidence interval (95% CI), 7.9-25.7 and 9.7% (95% CI, 4.0-19.0); median duration of response was 14.9 months (95% CI, 4.9-17.3) and 7.2 months (95% CI, 3.5-8.4); and median progression-free survival was 9.0 months (95% CI, 7.3-11.5) and 9.0 months (95% CI, 7.7-11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity.
In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs.
In this paper we describe an application called peFinder for document-level classification of CT pulmonary angiography reports. peFinder is based on a generalized version of the ConText algorithm, a ...simple text processing algorithm for identifying features in clinical report documents. peFinder was used to answer questions about the disease state (pulmonary emboli present or absent), the certainty state of the diagnosis (uncertainty present or absent), the temporal state of an identified pulmonary embolus (acute or chronic), and the technical quality state of the exam (diagnostic or not diagnostic). Gold standard answers for each question were determined from the consensus classifications of three human annotators. peFinder results were compared to naive Bayes’ classifiers using unigrams and bigrams. The sensitivities (and positive predictive values) for peFinder were 0.98(0.83), 0.86(0.96), 0.94(0.93), and 0.60(0.90) for disease state, quality state, certainty state, and temporal state respectively, compared to 0.68(0.77), 0.67(0.87), 0.62(0.82), and 0.04(0.25) for the naive Bayes’ classifier using unigrams, and 0.75(0.79), 0.52(0.69), 0.59(0.84), and 0.04(0.25) for the naive Bayes’ classifier using bigrams.
Integrase interactor 1 (INI‐1)‐deficient carcinoma is a rare cancer characterized by the loss of the SWItch/Sucrose Non‐Fermentable‐related matrix‐associated actin‐dependent regulator of chromatin ...subfamily B member 1 gene (SMARCB1) and tends to follow an aggressive clinical course. There is no currently available standard therapy option, although a few promising treatment strategies, including enhancer of zeste homolog 2 (EZH2) inhibition, are under active investigation. This report describes a 30‐year‐old woman with INI‐1‐deficient carcinoma who progressed on combination chemotherapy and an EZH2 inhibitor. Next‐generation‐sequencing‐based targeted cancer‐related gene assay confirmed SMARCB1 loss and revealed other mutations in breast cancer 1 gene and checkpoint kinase 2 gene, which may have impacted her clinical course. After discussion at the molecular tumor board, she was offered alisertib, an aurora A kinase inhibitor, on a single‐patient expanded‐use program and achieved prolonged disease stabilization. Aurora A kinase inhibition may have an important role in the management of patients with INI‐1‐deficient tumors, warranting further evaluation in clinical studies.
Key Points
Loss of the SWItch/Sucrose Non‐Fermentable‐related matrix‐associated actin‐dependent regulator of chromatin subfamily B member 1 gene (SMARCB1), which encodes integrase interactor 1 (INI‐1), is associated with various mesenchymal malignancies, but a few carcinomas with rhabdoid features have been recently described as a distinct entity.
INI‐1‐deficient carcinoma can be very aggressive, and there is no known treatment option available.
There are encouraging preliminary data with an enhancer of zeste homolog 2 inhibitor, tazematostat, in INI‐1‐deficient malignancies, including INI‐1‐deficient carcinomas.
Loss of INI‐1 can activate aurora A kinase (AurkA), and inhibition of AurkA by alisertib could be a viable option and warrants further investigation in this cancer.
Clinical genomic profiling can confirm diagnosis of molecularly defined malignancy and provide insights on therapeutic options.
INI‐1 deficient carcinoma is characterized by loss of the SMARCB1 gene. Standard treatments options are currently unavailable for this rare and aggressive cancer. This report describes the case of a patient with INI‐1 deficient carcinoma and the course of treatment resulting in disease stabilization.
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