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Cureus May 2024Background The pathological response rate in operable breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC) is postulated to be related to body...
Background The pathological response rate in operable breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC) is postulated to be related to body composition. The success of complete pathological response (pCR) is a known prognostic factor in BC patients treated with NAC. We aimed to accurately measure body composition through BMI and skeletal muscle mass and observe their effects on pCR. Materials and methods Patients diagnosed with operable BC who had a positron emission tomography-computed tomography (PET-CT) or chest/abdominal CT taken at the time of diagnosis were retrospectively screened and enrolled in this study. Muscle mass was defined by third lumbar vertebra (L3) level transverse CT images, and data, including weight and height, were collected from the chemotherapy records. All these data were evaluated together with the postoperative pathological results. Results Sixty-nine operable BC patients with a median age of 46 (range: 29-72) years were included in the study. In all patients, regardless of sarcopenia, 23% (n = 16) achieved pCR to NAC. The pCR rate was 37.5% (n=6) in sarcopenic patients and 62.5% (n=10) in non-sarcopenic patients (p = 0.530). Overweight (n=4; 25%) and obese (n=2; 12.5%) patients also had a lower pathological response than normal-weight (n=10; 62.5%) BC patients (p=0.261). Conclusion Both sarcopenia and obesity independently and synergistically contribute to poorer pathological responses after NAC. Addressing these conditions through tailored interventions, such as nutritional support, exercise programs, and careful monitoring of body composition, could improve treatment outcomes. Further research with larger patient populations and comprehensive body measurements is essential to fully understand these relationships and develop effective strategies to mitigate their impact.
PubMed: 38933645
DOI: 10.7759/cureus.61145 -
Chemistry of Materials : a Publication... Nov 2023Immunotherapies have become the standard treatment for melanoma. To further improve patient responses, combinations of immunotherapies and radiotherapy (RT) are being...
Immunotherapies have become the standard treatment for melanoma. To further improve patient responses, combinations of immunotherapies and radiotherapy (RT) are being studied, since radiotherapies can potentially provide additional immune stimulation, in addition to direct antitumor effects. FLASH-RT is a novel, ultrahigh dose rate, radiation delivery approach, with the potential of at least equivalent tumor control efficacy and reduced damage to healthy tissue. However, the effects of combining FLASH-RT and immunotherapy have not been extensively studied in melanoma. Toll-like receptor (TLR) agonists, such as imiquimod (IMQ), are potent immunostimulatory agents, although their utility is limited due to poor solubility and systemic side effects. We therefore developed a novel combination therapy for melanoma consisting of IMQ delivered to the tumor via a radiopaque and radiation responsive hydrogel combined with FLASH-RT. We found that FLASH was able to effectively stimulate IMQ release from the hydrogel. In addition, we found that the combination of FLASH and released IMQ resulted in synergistic melanoma cell killing . The combination therapy reduced tumor growth compared to controls, enhanced survival, and resulted in remarkable enhancements in certain tumor cytokine levels. CT imaging allowed the hydrogel to be monitored . In addition, no adverse effects of the treatment were observed. Overall, this IMQ-gel and FLASH-RT combination may have potential as an improved treatment for melanoma and indicates that the interactions of FLASH-RT and TLR agonists merit further study.
PubMed: 38933522
DOI: 10.1021/acs.chemmater.3c01390 -
Policy Insights From the Behavioral and... Mar 2024Sensory systems continuously recalibrate their responses according to the current stimulus environment. As a result, perception is strongly affected by the current and...
Sensory systems continuously recalibrate their responses according to the current stimulus environment. As a result, perception is strongly affected by the current and recent context. These adaptative changes affect both sensitivity (e.g., habituating to noise, seeing better in the dark) and appearance (e.g. how things look, what catches attention) and adjust to many perceptual properties (e.g. from light level to the characteristics of someone's face). They therefore have a profound effect on most perceptual experiences, and on how and how well the senses work in different settings. Characterizing the properties of adaptation, how it manifests, and when it influences perception in modern environments can provide . Adaptation could also be (e.g. in visual inspection tasks like radiology) and to (e.g. exposure to potentially unhealthy stimulus environments).
PubMed: 38933347
DOI: 10.1177/23727322231220494 -
Frontiers in Immunology 2024To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC)...
OBJECTIVES
To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image.
METHODS
This retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV).
RESULTS
In the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686.
CONCLUSION
The quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Male; Female; Neoadjuvant Therapy; Middle Aged; Retrospective Studies; Aged; Tomography, X-Ray Computed; Treatment Outcome; Machine Learning; Immunotherapy; Adult; Pathologic Complete Response
PubMed: 38933281
DOI: 10.3389/fimmu.2024.1414954 -
World Journal of Nuclear Medicine Jun 2024Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in...
Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.
PubMed: 38933067
DOI: 10.1055/s-0044-1785461 -
Nuclear Medicine and Molecular Imaging Jun 2024Neuroinflammation is associated with the pathophysiologies of neurodegenerative and psychiatric disorders. Evaluating neuroinflammation using positron emission... (Review)
Review
Neuroinflammation is associated with the pathophysiologies of neurodegenerative and psychiatric disorders. Evaluating neuroinflammation using positron emission tomography (PET) plays an important role in the early diagnosis and determination of proper treatment of brain diseases. To quantify neuroinflammatory responses in vivo, many PET tracers have been developed using translocator proteins, imidazole-2 binding site, cyclooxygenase, monoamine oxidase-B, adenosine, cannabinoid, purinergic P2X7, and CSF-1 receptors as biomarkers. In this review, we introduce the latest developments in PET tracers that can image neuroinflammation, focusing on clinical trials, and further consider their current implications.
PubMed: 38932754
DOI: 10.1007/s13139-023-00831-4 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic...
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1β, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.
PubMed: 38931456
DOI: 10.3390/ph17060789 -
Journal of Clinical Medicine Jun 2024: Understanding the behavioral and neural underpinnings of the post-concussion recovery of working memory function is critically important for improving clinical...
: Understanding the behavioral and neural underpinnings of the post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points. We aimed to examine working memory recovery during the first 6 months post-concussion in adolescents. : We used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONCs] at baseline (<10 days post-concussion) and at 6 months post-concussion. Healthy control adolescents [HCs; n = 32] without a history of concussion were scanned once. During the scans, participants performed one-back and two-back working memory tasks with letters as the stimuli and angry, happy, neutral, and sad faces as distractors. : All affected adolescents were asymptomatic and cleared to return to activity 6 months after concussion. Working memory recovery was associated with faster and more accurate responses at 6 months vs. baseline (-values < 0.05). It was also characterized by significant difficulty-related activation increases in the left inferior frontal gyrus (LIFG) and the left orbitofrontal cortex (LOFC) at 6 months vs. baseline. Although the activation differences between one-back and two-back were comparable between HCs and CONCs at 6 months, HCs had more pronounced activation in the LIFG than concussed adolescents. : Post-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as the normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.
PubMed: 38930114
DOI: 10.3390/jcm13123585 -
Journal of Clinical Medicine Jun 2024Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper... (Review)
Review
Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional "PARP enzyme-inhibitor complex" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as (). Hence, identifying HR-deficiencies by genomic analysis-for instance, used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available analysis. In this review, we discuss [F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.
PubMed: 38929955
DOI: 10.3390/jcm13123426 -
Journal of Personalized Medicine May 2024In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients...
The Immunomodulatory Potential of Concurrent High-Dose Radiotherapy and Immune Checkpoint Inhibitor Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Initial Results.
In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported.
PubMed: 38929802
DOI: 10.3390/jpm14060581