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Translational Oncology Aug 2024Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer...
BACKGROUND
Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection.
METHODS
The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms.
RESULTS
A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS.
CONCLUSIONS
Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.
PubMed: 38805774
DOI: 10.1016/j.tranon.2024.101985 -
Autopsy & Case Reports 2024Primary cardiac tumors are rare. The cardiac sarcomas are the most common malignant cardiac tumors. These tumors have a dismal prognosis with an overall median survival...
Primary cardiac tumors are rare. The cardiac sarcomas are the most common malignant cardiac tumors. These tumors have a dismal prognosis with an overall median survival of 25 months. Clinical features include dyspnea, arrhythmias, pericardial effusions, heart failure, and sudden cardiac death. The diagnosis is often challenging. Therefore, the cardiac imaging workup plays a central role in addition to a high clinical suspicion in the setting of atypical presentations that do not respond to standard therapies. The echocardiography, computed tomography, and cardiac MRI are crucial in clinching the diagnosis. Multimodal treatment with surgery, chemotherapy, and radiotherapy has been shown to improve outcomes, as opposed to using either of these modalities alone. We describe the case of a 30-year-old gentleman with COVID-19 infection who developed recurrent hemorrhagic pericardial effusions refractory to standard treatment and was eventually diagnosed as a case of pericardial angiosarcoma after his biopsy revealed the diagnosis and staging was performed using PET-CT-FDG scan. Our case re-emphasizes the importance of considering a malignant etiology early in the course of the disease presentation, especially in recurrent hemorrhagic effusions despite an inflammatory cytologic diagnosis of fluid. It also highlights the place for cardiac CT and MRI to ascertain the location and spread and to plan the further course of treatment. If diagnosed early, the estimated survival time can be prolonged by instituting a multimodal approach.
PubMed: 38803483
DOI: 10.4322/acr.2024.488 -
Contemporary Oncology (Poznan, Poland) 2024The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC)...
INTRODUCTION
The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC) in rural Nordland County, Norway. Prognostic factors related to treatment and other variables were evaluated.
MATERIAL AND METHODS
Overall, 132 pa- tients were included in this retrospective study covering the years 2009-2022. Uni- and multivariate survival analyses were performed.
RESULTS
In this elderly cohort (median age 72 years), weekly low-dose docetaxel was the preferred regimen (44%). Seventy-three percent were treated in the first line. Only 11 patients (8%) were pre-exposed to docetaxel in the hormone-sensitive phase. Median survival was 14.3 months. Prognostic factors for longer survival included higher hemoglobin, lower lactate dehydrogenase, administration of docetaxel as first-line MCRPC treatment, and use of fewer prescription drugs for comorbidity. Pre-exposure to docetaxel did not play a major role, p = 0.76.
CONCLUSIONS
In this rural health care setting, survival after docetaxel was shorter than reported by other groups. Blood test results were confirmed as important prognostic factors. In the present era of evolving treatment sequences, we recommend monitoring of real-world treatment results.
PubMed: 38800536
DOI: 10.5114/wo.2024.138842 -
Acta Biochimica Et Biophysica Sinica May 2024A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug...
A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.
PubMed: 38798241
DOI: 10.3724/abbs.2024082 -
Pharmaceutics Apr 2024Docetaxel, a taxane used in the treatment of solid tumours, exerts pharmacological activity when in its unbound form. We report a sensitive assay to quantify unbound...
INTRODUCTION
Docetaxel, a taxane used in the treatment of solid tumours, exerts pharmacological activity when in its unbound form. We report a sensitive assay to quantify unbound docetaxel after oral administration of docetaxel plus encequidar (oDox+E). Unbound drug quantification is important due to its direct correlation with drug-related toxicity and therapeutic efficacy. We improve on the sensitivity of current assay methods and demonstrate the utility of the assay on a novel formulation of oral docetaxel.
METHODS
Ultrafiltration followed by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) was utilized. Long-term stability, precision, accuracy, and recovery experiments were conducted to validate the assay. Additionally, patient samples from a Phase I dose-escalation pharmacokinetic study were analyzed using the developed assay.
RESULTS
The assay method exhibited long-term stability with an observed change between 0.8 and 6.9% after 131 days of storage at -60 °C. Precision and accuracy quality controls met the FDA acceptance criteria. An average recovery of 88% was obtained. Patient sample analysis demonstrated successful implementation of the assay.
CONCLUSION
A validated sensitive assay was developed with an LLOQ of 0.084 ng/mL using 485 µL of human plasma. The sensitivity of the assay allowed quantification of unbound docetaxel concentrations in an early-phase oDox+E clinical study to compare it against IV docetaxel using pharmacokinetic modelling. Successful development of oDox+E represents an opportunity to replace the current IV docetaxel regimen with an oral regimen with lower cost, decreased side effects, and improve patient quality of life and experience.
PubMed: 38794263
DOI: 10.3390/pharmaceutics16050602 -
Tislelizumab combined with GT chemotherapy for intimal sarcoma of inferior vena cava: A case report.Medicine May 2024Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack...
RATIONALE
Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods.
PATIENT CONCERNS
A 54-year-old female patient presented to Fenghua District People's Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital.
DIAGNOSES
The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG.
INTERVENTIONS
The patient initially received GT chemotherapy (gemcitabine injection + docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation).
OUTCOMES
The disease was stabilized after receiving the treatment.
LESSONS
Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.
Topics: Humans; Female; Middle Aged; Vena Cava, Inferior; Sarcoma; Antibodies, Monoclonal, Humanized; Vascular Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Gemcitabine; Deoxycytidine; Lung Neoplasms
PubMed: 38788046
DOI: 10.1097/MD.0000000000038056 -
Gels (Basel, Switzerland) May 2024Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of...
Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.
PubMed: 38786224
DOI: 10.3390/gels10050307 -
Current Oncology (Toronto, Ont.) Apr 2024This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer-mixed adenosquamous...
This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer-mixed adenosquamous cell carcinoma of the prostate. Prostate cancers of this nature pose distinctive diagnostic and therapeutic dilemmas due to their rarity and complex histological composition. We present a case of a 63-year-old man with metastatic prostate cancer, featuring adenocarcinoma with squamous cell differentiation, who underwent a multimodal treatment approach. The patient responded to first-line carboplatin, docetaxel, and androgen deprivation therapy, followed by androgen receptor pathway inhibitor (ARPI) maintenance. However, disease progression led to radiation therapy and a subsequent switch to Lutetium (177Lu) vipivotide tetraxetan after chemotherapy challenges. Comprehensive genetic profiling revealed shared mutations in the prostate and liver lesions, emphasizing the role of targeted therapies. Prostate-specific membrane antigen (PSMA)-targeted therapy resulted in a notable PSA decline. This case highlights the evolving treatment landscape for rare prostate cancers, integrating genetic insights for tailored interventions. In conclusion, squamous cell carcinoma (SCC) of the prostate is rare, emphasizing the imperative for enhanced comprehension in diagnosis and management. Our case suggests the potential efficacy of ARPI and PSMA-targeted therapies. Our findings advocate for a more nuanced approach to the management of this rare prostate cancer variant, leveraging genomic insights for personalized treatment strategies. This exploration serves as a foundation for further research and clinical considerations in addressing the challenges posed by mixed adenosquamous cell carcinoma of the prostate.
Topics: Humans; Male; Liver Neoplasms; Middle Aged; Prostatic Neoplasms; Carcinoma, Adenosquamous
PubMed: 38785459
DOI: 10.3390/curroncol31050178 -
American Society of Clinical Oncology... Jun 2024Chemoimmunotherapy is currently the preferred first-line treatment option for the majority of patients with advanced non-small cell lung cancer without driver genetic... (Review)
Review
Chemoimmunotherapy is currently the preferred first-line treatment option for the majority of patients with advanced non-small cell lung cancer without driver genetic alterations. Most of these patients, however, will experience disease progression within the first year after treatment initiation and both patients and their physicians will be confronted with the dilemma of the optimal second-line treatment. Identification of molecular targets, such as , , , and human epidermal growth factor receptor 2 mutations, and RET rearrangements offer therapeutic opportunities in pretreated patients with corresponding alterations. For those tumors that do not harbor oncogenic drivers, second-line treatment with docetaxel remains the current standard of care despite modest efficacy. Strategies to challenge docetaxel include the combination of immune checkpoint inhibitors (ICIs) with tyrosine inhibitors of multiple kinases or with DNA damage response inhibitors, antibody-drug conjugates, and locoregional treatments for oligoprogressive disease. Next-generation immunotherapy strategies, such as T-cell engagers, immune-mobilizing monoclonal T-cell receptors, chimeric antigen receptor cell therapy, tumor infiltrating lymphocytes, and T-cell receptor cell therapy are being currently investigated in the quest to reverse resistance to ICIs. Importantly, the advent of these new agents heralds a novel spectrum of toxicities that require both the physician's and the patient's education. Herein, we review current and future strategies aiming to outperform docetaxel after chemoimmunotherapy failure, and we provide practical information on how to best communicate to our patients the unique toxicity aspects associated with immunotherapy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immunotherapy; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Molecular Targeted Therapy
PubMed: 38781566
DOI: 10.1200/EDBK_432526 -
BMC Cardiovascular Disorders May 2024Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis...
INTRODUCTION
Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients' long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy.
CASE PRESENTATION
The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components.
CONCLUSIONS
Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.
Topics: Humans; Male; Thymus Neoplasms; Middle Aged; Treatment Outcome; Time Factors; Thymoma; Coronary Angiography; Vascular System Injuries; Coronary Vessels; Chemoradiotherapy
PubMed: 38778265
DOI: 10.1186/s12872-024-03948-2