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Plant stress diagnosis is essential for efficient crop management and productivity increase. Under stress, plants undergo physiological and compositional changes. Vegetation indices obtained from leaf reflectance spectra and bioimpedance spectroscopy provide information about the external and internal aspects of plant responses, respectively. In this study, bioimpedance and vegetation indices were noninvasively acquired from sweet basil (Ocimum basilicum L.) leaves exposed to three types of stress (drought, salinity, and chilling). Integrating the vegetation index, a novel approach, contains information about the surface of plants and bioimpedance data, which indicates the internal changes of plants. The fusion of these two datasets was examined to classify the types and severity of stress. Among the eight supervised machine learning models (three linear and five non-linear), the support vector machine (SVM) exhibited the highest accuracy in classifying stress types. Bioimpedance spectroscopy alone exhibited an accuracy of 0.86 and improved to 0.90 when fused with vegetation indices. Additionally, for drought and salinity stresses, it was possible to classify the early stage of stress with accuracies of 0.95 and 0.93, respectively. This study will allow us to classify the different types and severity of plant stress, prescribe appropriate treatment methods for efficient cost and time management of crop production, and potentially apply them to low-cost field measurement systems.
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Técnicas Biossensoriais , Aprendizado de Máquina , Ocimum basilicum , Folhas de Planta , Estresse Fisiológico , Ocimum basilicum/química , Folhas de Planta/química , Técnicas Biossensoriais/métodos , Espectroscopia Dielétrica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Secas , Máquina de Vetores de Suporte , SalinidadeRESUMO
This study presents a novel, ultralow-power single-sensor-based electronic nose (e-nose) system for real-time gas identification, distinguishing itself from conventional sensor-array-based e-nose systems, whose power consumption and cost increase with the number of sensors. Our system employs a single metal oxide semiconductor (MOS) sensor built on a suspended 1D nanoheater, driven by duty cyclingâcharacterized by repeated pulsed power inputs. The sensor's ultrafast thermal response, enabled by its small size, effectively decouples the effects of temperature and surface charge exchange on the MOS nanomaterial's conductivity. This provides distinct sensing signals that alternate between responses coupled with and decoupled from the thermally enhanced conductivity, all within a single time domain during duty cycling. The magnitude and ratio of these dual responses vary depending on the gas type and concentration, facilitating the early stage gas identification of five gas types within 30 s via a convolutional neural network (classification accuracy = 93.9%, concentration regression error = 19.8%). Additionally, the duty-cycling mode significantly reduces power consumption by up to 90%, lowering it to 160 µW to heat the sensor to 250 °C. Manufactured using only wafer-level batch microfabrication processes, this innovative e-nose system promises the facile implementation of battery-driven, long-term, and cost-effective IoT monitoring systems.
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Aprendizado Profundo , Nariz Eletrônico , Gases , Semicondutores , Gases/química , Gases/análise , Fontes de Energia ElétricaRESUMO
As semiconductor devices shrink and their manufacturing processes advance, accurately measuring in-cell critical dimensions (CD) becomes increasingly crucial. Traditional test element group (TEG) measurements are becoming inadequate for representing the fine, repetitive patterns in cell blocks. Conventional non-destructive metrology technologies like optical critical dimension (OCD) are limited due to their large spot diameter of approximately 25 µm, which impedes their efficacy for detailed in-cell structural analysis. Consequently, there is a pressing need for small-spot and non-destructive metrology methods. To address this limitation, we demonstrate a microsphere-assisted hyperspectral imaging (MAHSI) system, specifically designed for small spot optical metrology with super-resolution. Utilizing microsphere-assisted super-resolution imaging, this system achieves an optical resolution of 66 nm within a field of view of 5.6 µm × 5.6 µm. This approach effectively breaks the diffraction limit, significantly enhancing the magnification of the system. The MAHSI system incorporating hyperspectral imaging with a wavelength range of 400-790 nm, enables the capture of the reflection spectrum at each camera pixel. The achieved pixel resolution, which is equivalent to the measuring spot size, is 14.4 nm/pixel and the magnification is 450X. The MAHSI system enables measurement of local uniformity in critical areas like corners and edges of DRAM cell blocks, areas previously challenging to inspect with conventional OCD methods. To our knowledge, this approach represents the first global implementation of microsphere-assisted hyperspectral imaging to address the metrology challenges in complex 3D structures of semiconductor devices.
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The demand for gas sensing systems that enable fast and precise gas recognition is growing rapidly. However, substantial challenges arise from the complex fabrication process of sensor arrays, time-consuming data transmission to an external processor, and high energy consumption in multi-stage data processing. In this study, a gas sensing system using on-chip annealing for fast and power-efficient gas detection is proposed. By utilizing a micro-heater embedded in the gas sensor, the sensing material of adjacent sensors in the same substrate can be easily varied without further fabrication steps. The response to oxidizing gas is constrained in metal oxide (MOX) sensing material with small grain sizes, as the depletion width of grain cannot extend beyond the grain size during the gas reaction. On the other hand, the response to reducing gases and humidity, which decrease the depletion width, is less affected by grain sizes. A readout circuit integrating a differential amplifier and dual FET-type gas sensors effectively emphasizes the response to oxidizing gases by canceling the response to reducing gases and humidity. The selective on-chip annealing method is applicable to various MOX sensing materials, demonstrating its potential for application in commercial fields due to its simplicity and expandability.
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The pursuit of sub-1-nm field-effect transistor (FET) channels within 3D semiconducting crystals faces challenges due to diminished gate electrostatics and increased charge carrier scattering. 2D semiconductors, exemplified by transition metal dichalcogenides, provide a promising alternative. However, the non-idealities, such as excess low-frequency noise (LFN) in 2D FETs, present substantial hurdles to their realization and commercialization. In this study, ideal LFN characteristics in monolayer MoS2 FETs are attained by engineering the metal-2D semiconductor contact and the subgap density of states (DOS). By probing non-ideal contact resistance effects using CuS and Au electrodes, it is uncovered that excess contact noise in the high drain current (ID) region can be substantially reduced by forming a van der Waals junction with CuS electrodes. Furthermore, thermal annealing effectively mitigates sulfur vacancy-induced subgap density of states (DOS), diminishing excess noise in the low ID region. Through meticulous optimization of metal-2D semiconductor contacts and subgap DOS, alignment of 1/f noise with the pure carrier number fluctuation model is achieved, ultimately achieving the sought-after ideal LFN behavior in monolayer MoS2 FETs. This study underscores the necessity of refining excess noise, heralding improved performance and reliability of 2D electronic devices.
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BACKGROUND: Ketamine has been used to control refractory cancer pain as an adjuvant to opioids. We conducted a prospective phase II study to investigate the efficacy and safety of 5-day continuous intravenous infusion (CIVI) of Ketamine in terminally ill cancer patients with refractory cancer pain. METHODS: Hospitalized terminally ill cancer patients with refractory cancer pain were enrolled. Refractory cancer pain was indicated by requirements for 4 or more rescue opioids or pain intensity using numerical rating scale > personalized pain goal (PPG) despite of intravenous morphine equivalent daily dose (IV MEDD) ≥ 120 mg/day. The CIVI of ketamine was increased from .05 mg/kg/hour to .5 mg/kg/hour by .05 every 8 hours if pain intensity exceeded PPG or if number of rescue opioids ≥2 during prior 8 hours was required. The primary end-point was overall pain response rate, which indicates complete response (both rescue opioid ≤3/day and pain intensity ≤ PPG) plus partial response (rescue opioid ≤3/day), without unacceptable toxicities. RESULTS: Among 21 eligible patients enrolled between September 2019 and January 2023, 20 were analyzed. Most pain mechanisms were mixed type (n = 15, 75%), with neuropathic component (n = 17, 85%). The baseline background opioids were IV MEDD 186 mg/24hour (range, 124-592), number of rescue opioids was 6 (IQR, 5-9), and median PPG was 4 (IQR, 3-4). The overall pain response rate was 50% (n = 10) including 40% (n = 8) for complete pain response and 10% (n = 2) for partial pain response. CONCLUSION: This study showed efficacy of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. CIVI of ketamine could be a useful tool in these patients considering the limited treatment options. (NCT03362073, Initial Release: November 15, 2017).
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Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.
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To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.
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BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).
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Niacinamida/análogos & derivados , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Irinotecano , Neoplasias Gástricas/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Antígeno B7-H1 , Camptotecina , Estudos Retrospectivos , Neoplasias Peritoneais/tratamento farmacológico , Fluoruracila , Leucovorina , República da Coreia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
PURPOSE: Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy. MATERIALS AND METHODS: We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response. RESULTS: Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group. CONCLUSION: Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Terapia Neoadjuvante , Microambiente Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , PrognósticoRESUMO
Hardware neuromorphic systems are crucial for the energy-efficient processing of massive amounts of data. Among various candidates, hafnium oxide ferroelectric tunnel junctions (FTJs) are highly promising for artificial synaptic devices. However, FTJs exhibit non-ideal characteristics that introduce variations in synaptic weights, presenting a considerable challenge in achieving high-performance neuromorphic systems. The primary objective of this study is to analyze the origin and impact of these variations in neuromorphic systems. The analysis reveals that the major bottleneck in achieving a high-performance neuromorphic system is the dynamic variation, primarily caused by the intrinsic 1/f noise of the device. As the device area is reduced and the read bias (VRead ) is lowered, the intrinsic noise of the FTJs increases, presenting an inherent limitation for implementing area- and power-efficient neuromorphic systems. To overcome this limitation, an adaptive read-biasing (ARB) scheme is proposed that applies a different VRead to each layer of the neuromorphic system. By exploiting the different noise sensitivities of each layer, the ARB method demonstrates significant power savings of 61.3% and a scaling effect of 91.9% compared with conventional biasing methods. These findings contribute significantly to the development of more accurate, efficient, and scalable neuromorphic systems.
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γ-Hydroxybutyrate (GHB), a date-rape drug, causes certain symptoms, such as amnesia, confusion, ataxia, and unconsciousness, when dissolved in beverages and consumed by a victim. Commonly, assailants use GHB in secret for the crime of drug-facilitated sexual assault because it is tasteless, odorless, and colorless when dissolved in beverages. Generally, GHB detection methods are difficult to use promptly and secretly in situ and in real life because of the necessary detection equipment and low selectivity. To overcome this problem, we have developed a fast, simple, and easy-to-use second skin platform as a confidential self-protection platform that can detect GHB in situ or in real life without equipment. The second skin platform for naked-eye detection of GHB is fabricated with poly(vinyl alcohol) (PVA), polyurethane (PU), and polyacrylonitrile (PAN) included in the chemical receptor 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI). PAN conjugated with BHEI nanofibers (PB NFs) has various characteristics, such as ease of use, high sensitivity, and fast color change. PB NFs rapidly detected GHB at 0.01 mg/mL. Furthermore, the second-skin platform attached to the fingertip and wrist detected both 1 and 0.1 mg/mL GHB in solution within 50 s. The color changes caused by the interaction of GHB and the second skin platform cannot be stopped due to strong chemical reactions. In addition, a second skin platform can be secretly utilized in real life because it can recognize fingerprints and object temperatures. Therefore, the second skin platform can be used to aid daily life and prevent drug-facilitated sexual assault crime when attached to the skin because it can be exposed anytime and anywhere.
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Estupro , Oxibato de Sódio , EtanolRESUMO
Background and Purpose: Growing evidence has shown that cognitive interventions can mitigate cognitive decline in patients with mild cognitive impairment (MCI). However, most previous cognitive interventions have been group-based programs. Due to their intrinsic limitations, group-based programs are not widely used in clinical practice. Therefore, we have developed a tablet-based cognitive intervention program. This preliminary study investigated the feasibility and effects of a 12-week structured tablet-based program on cognitive function in patients with MCI. Methods: We performed a single-arm study on 24 patients with MCI. The participants underwent a tablet-based cognitive intervention program 5 times a week over a 12-week period. The primary outcome was changes in cognitive function, measured using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K). Outcomes were evaluated at baseline, within two weeks of the last program (post-intervention), and at the six-month follow-up session. Results: The completion rate of the tablet-based program was 83.3% in patients with MCI. The program improved cognitive function based on the CERAD-K total score (p=0.026), which was maintained for at least three months (p=0.004). There was also an improvement in the depression scale score (p=0.002), which persisted for three months (p=0.027). Conclusions: Our 12-week structured tablet-based program is feasible for patients with MCI. Furthermore, although further studies with a double-arm design are required, the program appears to be an effective strategy to prevent cognitive decline in patients with MCI.
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Multipoint 3-axis tactile pressure sensing by a high-resolution and sensitive optical system provides rich information on surface pressure distribution and plays an important role in a variety of human interaction-related and robotics applications. However, the optical system usually has a bulky profile, which brings difficulties to sensor mounting and system integration. Here, we show a construction of thin-film and flexible multipoint 3-axis pressure sensor by optical methods. The sensor can detect the distribution of 3-axis pressure on an area of 3 centimeter by 4 centimeter, with a high-accuracy normal and tangential pressure sensing up to 360 and 100 kilopascal, respectively. A porous rubber is used as a 3-axis pressure-sensitive optical modulator to omit the thick and rigid focusing system without sacrificing the sensitivity. In addition, by integrating thin and flexible backlight and imager, the sensor has a total thickness of 1.5 milimeter, making it function properly even when bent to a radius of 18 milimeter.
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Neuromorphic computing (NC) architecture inspired by biological nervous systems has been actively studied to overcome the limitations of conventional von Neumann architectures. In this work, we propose a reconfigurable NC block using a flash-type synapse array, emerging positive feedback (PF) neuron devices, and CMOS peripheral circuits, and integrate them on the same substrate to experimentally demonstrate the operations of the proposed NC block. Conductance modulation in the flash memory enables the NC block to be easily calibrated for output signals. In addition, the proposed NC block uses a reduced number of devices for analog-to-digital conversions due to the super-steep switching characteristics of the PF neuron device, substantially reducing the area overhead of NC block. Our NC block shows high energy efficiency (37.9 TOPS/W) with high accuracy for CIFAR-10 image classification (91.80%), outperforming prior works. This work shows the high engineering potential of integrating synapses and neurons in terms of system efficiency and high performance.
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Redes Neurais de Computação , Sinapses , Sinapses/fisiologia , Neurônios/fisiologiaRESUMO
An energy-efficient power management interface (PMI) with adaptive high-voltage (HV) stimulation capability is presented for patch-type healthcare devices where power management and sensor readout circuits are integrated. For efficient power supply, it proposes a multimode buck converter with an adaptive mode controller, delivering 95.6% peak power conversion efficiency and over 90% efficiency across a wide 4-440 mA output current range. For energy-efficient stimulation, a HV stimulation system is designed to perform mode-adaptive on/off control, where the charge pump (CP) is adopted for periodic power saving. The CP output is adaptively tuned to minimize the stimulator's power waste by utilizing a bio-impedance path in the sensor circuit. The stimulation core supports multimode functionality of current-/voltage-controlled stimulations with monopolar and bipolar modes, providing ten kinds of various stimulation waveform shape. For efficient system operation, battery interface circuits are included to monitor state-of-charge (SOC) conditions, and a device power adjustment scheme is proposed to provide SOC-based maximum 28% power reduced optimal operation of high-resolution and low-power. The power-sensor integrated circuits were fabricated in a 0.18-µm CMOS process, and the proposed schemes were experimentally verified. For system-level feasibility, a patch-type device prototype was manufactured, and both power and bio-signal interfaces were functionally demonstrated.
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Fontes de Energia Elétrica , Desenho de EquipamentoRESUMO
BACKGROUND AND PURPOSE: Administration of pegylated granulocyte-colony-stimulating factor (peg-GCSF) 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of grade (Gr) 4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day method in preventing CIN, especially in chemotherapy regimens that include day 1 myelosuppressive agents. Thus, we aim to verify the hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. METHODS: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or first-line palliative chemotherapy comprising intensively myelosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. The randomizations are stratified according to number of patient CIN risk factors (1 vs ≥2), chemotherapy setting (perioperative vs palliative), and interval (2-week vs 3-week). In the same-day arm, pegteograstim 6 mg is subcutaneously injected within 4 hours after completion of chemotherapy. In the next-day arm, pegetograstim is injected at 24 to 36 hours post-chemotherapy. A complete blood count test is performed daily from day 5 to 9 during the cycle 1. The primary endpoint is duration of Gr4 CIN (cycle 1), and secondary endpoints include incidence of Gr 3 to 4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery absolute neutrophil count 1000/µL (cycle 1), incidence of febrile neutropenia, incidence of CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each group.
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Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Fator Estimulador de Colônias de Granulócitos , Neutropenia , Humanos , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Carcinoma Neuroendócrino/tratamento farmacológico , Esquema de MedicaçãoRESUMO
This corrects the article on p. 3 in vol. 23, PMID: 36750993.
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BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.
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Neoplasias da Mama , Carcinoma Ductal , Humanos , Feminino , Docetaxel/uso terapêutico , Micelas , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trastuzumab/uso terapêutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Glândulas Salivares/metabolismo , Neoplasias da Mama/tratamento farmacológicoRESUMO
Peritoneal metastasis, also known as peritoneal carcinomatosis (PC), is a refractory cancer that is typically resistant to conventional therapies. The typical treatment for PC is a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recently, research in this area has seen significant advances, particularly in immunotherapy as an alternative therapy for PC, which is very encouraging. Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM. Intraperitoneal (IP) immunotherapy breaks immunological tolerance to treat peritoneal illness. Increasing T-cell responses and vaccination against tumor-associated antigens are two methods of treatment. CAR-T cells, vaccine-based therapeutics, dendritic cells (DCs) in combination with pro-inflammatory cytokines and NKs, adoptive cell transfer, and immune checkpoint inhibitors are promising treatments for PC. Carcinoembryonic antigen-expressing tumors are suppressed by IP administration of CAR-T cells. This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body.