Early discontinuation (ED) in clinical trials (CTs) is frequent and deleterious for the patients, the care team, and the study duration. ED comprises screening failure or discontinuation during the first month of the treatment phase, and is often difficult to predict by clinicians. We aim at predicting ED by automatic analysis of patient's clinical record using language models (LMs). We fine-tuned a French LM on the oncology clinical reports of a French cancer center, and obtained a pretrained LM named OncoBERT. We then selected consultation reports of patients included in oncology CTs for any tumor type that we used to fine-tune OncoBERT and obtained a new model for ED prediction. We carried out a retrospective and prospective evaluation and used eXplainable Artificial Intelligence (XAI) methods to interpret the predictions. On the retrospective test cohort of 1007 reports, the model achieved a precision of 0.77, recall of 0.95, and could have decreased the ED rate from 25.3% to 21.3%. On the prospective test cohort it reached a precision of 0.75, recall of 0.75, and could have decreased the ED rate from 33.7% to 27%. Using XAI showed that the words used by the model to predict ED reflect deterioration of general condition, a well-known factor of ED. We have developed a LM that is portable, explainable, with near-human performances for ED prediction in oncology CTs. We anticipate that democratization of automatic trial matching tools should be complemented by ED prediction tools to fully optimize access to CTs and patient recruitment.
Cancer clinical trials (CCTs) are essential to advancing treatment, yet enrollment remains low. An oncologist's recommendation influences participation, but many eligible patients are never offered the option, and discussions often lack clarity or equity. CCT communication skills training can improve oncologists' confidence and patient-centered communication behaviors, yet most Hematology-Oncology fellowship programs lack structured curricula in this area. To address this gap, we implemented a CCT communication skills workshop (COMM-CCT) for Hematology-Oncology fellows. We implemented the COMM-CCT workshop at seven Hem-Onc fellowship programs in 2024. The three-hour, synchronous web-based workshop included a one-hour didactic session followed by two hours of small-group role play with cancer survivors acting as patients. We evaluated reach, acceptability, feasibility, and fidelity using post-course surveys and semi-structured interviews. Across seven sites, 72% (n = 62) of eligible fellows attended with 87% (n = 54) completing the post-workshop survey and 23% (n = 14) participating in interviews. Fellows reported high acceptability, including satisfaction with the workshop (M = 4.30, SD = 0.79) and content (M = 4.28, SD = 0.79). Feasibility was also high, with communication skills taught being viewed as compatible (M = 4.35, SD = 0.70) and useful (M = 4.33, SD = 0.73) to their clinical practice. Interview findings reinforced survey results. The COMM-CCT workshop is acceptable and feasible to implement in Hem-Onc fellowship programs. Findings will inform its refinement, broader scaling, and continued integration into graduate medical education programs. This study's innovation is in its integration of a nationwide communication-focused intervention on clinical trials into existing training structures.
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With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology.
Antimicrobial resistance is an important clinical challenge in patients with hematologic malignancies, who are highly susceptible to severe infections due to prolonged neutropenia, disrupted mucosal barriers, intensive chemotherapy, and hematopoietic stem-cell transplantation. This systematic review synthesizes available international evidence on pathogen distribution, antimicrobial resistance patterns, and clinical outcomes in hemato-oncology settings. This systematic review searched PubMed, Scopus, and Google Scholar for English-language studies published from January 2014 to 15 November 2025. Studies reporting microbiologically confirmed infections in patients with hematologic malignancies, with extractable antimicrobial susceptibility or resistance data, were included. Due to substantial clinical, microbiological, methodological, and epidemiological heterogeneity, findings were synthesized qualitatively. Seventeen studies met the inclusion criteria. Gram-negative bacteria predominated across most settings, although pathogen distribution varied by region, age group, infection type, and denominator unit. Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant Gram-negative bacteria, multidrug-resistant Gram-negative organisms, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus were reported across included studies. Where extractable study-level data were available, ESBL-related estimates ranged from 40% to 78%, while carbapenem-resistance estimates varied widely by organism group and study setting, from low carbapenem resistance among Enterobacteriaceae in one pediatric oncology cohort to 38.2% carbapenem-resistant Gram-negative bacteria in an Indian adult febrile neutropenia cohort. Mortality outcomes were heterogeneously reported and were not pooled. In comparative studies, resistant or multidrug-resistant bloodstream infections were associated with worse outcomes, including increased mortality and ICU admission, although causality cannot be inferred from the predominantly observational evidence. Antimicrobial resistance is a clinically important problem in patients with hematologic malignancies, particularly due to resistant Gram-negative pathogens. The findings support strengthened hemato-oncology-specific surveillance, local antibiogram-guided empirical therapy, antimicrobial stewardship, and standardized reporting of resistance phenotypes and clinical outcomes.
Definitive radiotherapy is a standard larynx-preserving treatment for early-stage glottic squamous cell carcinoma. This study evaluated recurrence patterns and freedom from recurrence after definitive radiotherapy in Panama; explored baseline clinical, pathological, and treatment-related factors associated with recurrence; and analyzed initial post-treatment response as an early marker of subsequent recurrence risk. We conducted a retrospective cohort study of adults diagnosed between 2013 and 2022 with T1-T2 N0 M0 glottic squamous cell carcinoma and treated with definitive radiotherapy at the National Oncology Institute of Panama. Time to recurrence, event-free survival, overall survival, and laryngeal preservation with oncologic control were evaluated. Freedom from recurrence was estimated using the Kaplan-Meier method, with deaths without prior recurrence censored. Survival outcomes were compared using log-rank tests and Cox proportional hazards models. Ninety-four patients were included: 79.8% had T1a, 13.8% had T1b, and 6.4% had T2 disease; 94.7% received three-dimensional conformal radiotherapy. An initial complete response was achieved in 86/93 patients (92.5%). With a median observed follow-up of 65.9 months (38.6-96.6), 17/94 patients (18.1%) developed recurrence: local recurrence occurred in 13.8% and regional recurrence in 4.3%, with no distant metastases. Freedom from recurrence at two and five years was 87.0% and 80.2%, respectively; five-year event-free survival was 70.4%, and five-year overall survival was 81.7%. Laryngeal preservation with oncologic control was achieved in 77/94 patients (81.9%). Partial response was associated with lower five-year freedom from recurrence compared with complete response (28.6% vs. 84.2%; p < 0.001). Five-year freedom from recurrence was 85.4% with hypofractionation and 78.5% with conventional fractionation (p = 0.483). In this retrospective cohort with a median observed follow-up of 65.9 months, definitive radiotherapy achieved a high initial complete response rate, predominantly local recurrence patterns, and a five-year freedom from recurrence of 80.2%, with deaths without prior recurrence censored. Partial response identified a high-risk subgroup as an early post-treatment response marker. Hypofractionation showed a non-significant numerical trend toward higher five-year freedom from recurrence, but the study did not demonstrate superiority, equivalence, or non-inferiority between fractionation schedules.
Gastric cancer (GC) remains a leading cause of mortality in Vietnam, where distant metastasis is frequently present at diagnosis. Since accessible biomarkers are scarce, we evaluated the association of Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) with distant metastasis in a Vietnamese cohort to develop a model for patient stratification. This retrospective study analyzed 114 patients, categorizing into metastatic (Stage IV) and non-metastatic groups per AJCC 8th criteria. The optimal cutoffs were determined using receiver operating characteristic (ROC) curve analysis. The diagnostic efficacy between models was compared by DeLong's test. LASSO regression was employed to identify stable indicators. A multivariable logistic regression model was constructed, and its performance was evaluated using 1,000 bootstrap resamples. Clinical utility was assessed via Decision Curve Analysis (DCA). Distant metastasis was 44.7% of cases. Optimal cutoffs of 2.0 for NLR and 181.5 for PLR were identified. Both markers were significantly higher in metastatic group and positively correlated with disease progression. LASSO identified PLR, NLR, and tumor location as the most robust determinants. In multivariable analysis, only multiple tumor location and high PLR remained independent prognostic factors. The combined model integrating clinical factors with NLR and PLR significantly outperformed clinical features alone (AUC: 0.766 vs. 0.619, p=0.0036), with an optimism-corrected C-index of 0.708. At a 0.586 threshold, the model achieved 82.5% specificity and 62.7% sensitivity, supporting a conservative "rule-out" strategy. Calibration slope was 0.659. DCA demonstrated superior net benefit across a 15%-90% risk range; specifically, at a 40% threshold, model spared 19 per 100 patients from unnecessary intervention. This study establishes the first baseline for NLR and PLR in the Vietnamese cohort, showing an association of these biomarkers with GC distant metastasis. A model integrating PLR, NLR and tumor location optimizes patient stratification and resource allocation in resource-constrained healthcare environments. Gastric cancer (stomach cancer) is a leading cause of cancer-related deaths worldwide. In Vietnam, many patients are diagnosed only after the cancer has already spread to distant parts of the body (metastasis). When cancer spreads, it becomes much harder to treat. Doctors need affordable and reliable ways to identify which patients are at a higher risk of metastasis to improve how they manage the disease. Researchers studied 114 gastric cancer patients at the Ho Chi Minh City Oncology Hospital. They looked at two specific markers found in routine, inexpensive blood tests: the Neutrophil-to-Lymphocyte Ratio (NLR) and the Platelet-to-Lymphocyte Ratio (PLR). These markers measure the balance of different white blood cells and platelets, which partially reflect the body’s “inflammation” levels in response to a tumor. The study found that patients with advanced, metastatic cancer had significantly higher NLR and PLR levels compared to those in earlier stages. By combining these blood markers with other clinical information—such as the patient’s and tumor’s data —the researchers created a diagnostic model. This combined model was much more accurate at identifying patients with distant metastasis than using clinical information alone. Because these blood tests are simple, low-cost, and already widely available in hospitals, they offer a practical way for doctors to monitor cancer progression. Using the NLR and PLR ratios can help healthcare providers in Vietnam and elsewhere better identify high-risk patients and personalize their treatment plans more effectively.
The increasing incidence of cancer and the fact that the family is an important factor in cancer care; attention to the positive mental health of cancer patients should be sought to provide solutions to improve the mental health of these caregivers. The present study aimed to investigate the effect of web-based education on positive mental health of family caregivers of breast cancer patients undergoing chemotherapy in educational and treatment centers of Zahedan University of Medical Sciences. This study is a semi-experimental study. The statistical population of the study included all family members of breast cancer patients undergoing chemotherapy who referred to Imam Ali Hospital in Zahedan in 1402. The samples included 70 people who were randomly assigned to two groups: the intervention group and the control group. Caregivers in the intervention group received the necessary training and education for 20 days through a website prepared by the researcher. Data collection was carried out using the demographic information formula and the 9-question positive mental health questionnaire of Lockett before the intervention and 30 days after the intervention. The data were analyzed using descriptive and analytical tests using SPSS 27 statistical software and independent t-tests, paired t-tests, and chi-square tests. Before the intervention, there was no significant difference between the two groups in terms of positive mental health (p = 0.43). However, after web-based training, the results of the analysis of covariance (ANCOVA) with adjustment for pre-test scores showed that the positive mental health score in the intervention group was 19.02 ± 3.05, compared to 15.94 ± 2.61 in the control group (p = 0.0001). The findings of this study suggest that web-based educational programs can enhance the positive mental health of family caregivers of breast cancer patients undergoing chemotherapy. Accordingly, such interventions may be considered an effective supportive approach for family caregivers in oncology care settings.
Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review summarizes recent advances in RES-loaded nanoformulations, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, inorganic nanocarriers, protein-based systems, and biomimetic vesicles. Their therapeutic performance is evaluated across prostate, lung, colorectal, breast, and other cancers, with attention to tumor targeting, controlled release, combination therapy, multidrug-resistance reversal, and modulation of cancer-relevant pathways such as NF-κB, p53, and PI3K/Akt/mTOR. Current oncology-related clinical evidence for RES is still largely based on conventional oral or micronized formulations. Translation of engineered RES nanocarriers therefore requires stronger evidence on scalable manufacturing, carrier-specific safety, heterogeneous tumor delivery, and biomarker-guided trial design. This review also introduces a semi-quantitative prioritization framework based on model-readiness, translational priority, and safety-alert scoring for future PBPK, PK-PD, nano-QSAR, and machine-learning analyses.
Brown adipose tissue (BAT) activity has been suggested to play a role in cancer progression. Previous studies have shown that BAT activity is higher in patients with cancer, and that BAT volume is a predictor of tumour recurrence and mortality in patients with cancer, but the data on melanoma are limited. Here, we re-analysed 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG-PET-CT) images from 135 patients with cutaneous melanoma treated at Turku University Hospital between 2012 and 2021 to assess associations among BAT, melanoma progression, patient survival, and patient weight. We applied a three-stage universal BAT threshold definition using predetermined standardised uptake value thresholds of 0.8, 1.0, and 1.2 g/ml, given the retrospective nature of our study. Of the 135 patients (81 men and 54 women; median age 61 years, interquartile range 54-71), 40 (29.6%), 24 (17.8%), and 19 (14.1%) were BAT-positive at the 0.8, 1.0, and 1.2 g/ml thresholds, respectively. Our results showed that patients with active melanoma on FDG-PET-CT imaging were more frequently BAT-positive at the 0.8 threshold (P = 0.026) and 1.0 threshold (P = 0.016). We also found a significantly higher BAT volume among patients who survived the observation period (0.8, 1.0, and 1.2 g/ml thresholds; P = 0.018, P = 0.038, and P = 0.571, respectively) and those who did not relapse (0.8, 1.0, and 1.2 g/ml thresholds; P = 0.631, P = 0.012, and P = 0.030, respectively). No association between BAT positivity and relapse-free survival or overall survival was observed at any threshold. Although higher BAT volumes were observed in subgroups of patients who survived or did not relapse, these findings were not supported by survival analyses and should be considered exploratory.
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To assess the rate and timing of spontaneous regression of high-grade cervical intraepithelial lesions (CIN2/HSIL and CIN3/HSIL) in young women and to identify associated factors. This retrospective cohort study included patients aged ≤ 30 years diagnosed with HSIL (CIN2 or CIN3) at the certified dysplasia unit of the Department of Gynecology, University Hospital Erlangen, between April 2014 and November 2025 who underwent observational management. Regression was defined as partial regression (low-grade squamous intraepithelial lesion; LSIL) or complete regression (less than LSIL), with histology as the reference standard. 45 patients with CIN3/HSIL and 38 with CIN2/HSIL were included. In the CIN3/HSIL cohort, regression was observed in 21 of 45 patients (46.7%), including regression to LSIL in 6 (13.3%) and complete regression in 15 (33.3%) cases. The median time to regression (≤ LSIL) was 236 days (IQR, 126-308 days). The CIN2/HSIL cohort showed even higher regression rates, with partial or complete regression in 24 of 38 cases (63.2%). Regression was associated with HPV clearance in both groups and with HPV16 negativity and HPV vaccination in the CIN2/HSIL cohort. No cases of progression to (micro)invasive disease were observed in either group. The probability of regression did not differ between patients aged ≤ 24 and > 24 years. In this selected cohort of women aged ≤ 30 years managed conservatively, spontaneous regression of CIN2/HSIL and CIN3/HSIL occurred frequently, particularly during the first year of follow-up, without progression to invasive disease. HPV clearance, HPV16 and vaccination status may help guide patient selection for observational management.
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peripherally inserted central catheters (PICCs) and totally implantable ports (Ports) are used for chemotherapy administration. This study aimed to compare their morbidity, mortality, and complication rates. a prospective, randomised, comparative single-centre study with 6 months of follow-up included adult patients with non-hematological malignancies eligible for chemotherapy (palliative, curative, or adjuvant intent). Primary endpoints were the frequency of adverse events (minor/major), impact on quality of life (EORTC QLQ-C30), and medico-economic cost. out of 206 randomised patients, 192 were analysed (Port: 102; PICC: 90). The overall complication rate was 12.5% (n=24). Major complications were significantly more frequent with PICCs (17.8%; 16/90) than with Ports (4.9%; 5/102), with a relative risk of 3.6 (95% CI 1.3-9.9; p=0.041). For chemotherapy lasting less than 6 months, the mean total cost was significantly higher for Ports (160,123.41 DA) than for PICCs (43,259.69 DA) (p<0.001). No significant difference was observed in overall quality of life, with a modest trend favoring Ports for global health and pain at three months. Ports, although costlier, are associated with a significantly lower risk of major complications. They may be preferred as a safe and effective access for long-term chemotherapy. The optimal choice should integrate treatment duration, patient risk profile, and economic constraints. les cathéters centraux à insertion périphérique (PICC) et les chambres implantables (Ports) sont utilisés pour la chimiothérapie. Cette étude vise à comparer leur morbi-mortalité et l'incidence des complications. une étude prospective, comparative randomisée et monocentrique, avec un suivi de 6 mois, a inclus des patients adultes atteints de tumeurs non hématologiques, éligibles à une chimiothérapie (intention palliative, curative ou adjuvante). Les critères d'évaluation principaux étaient la fréquence des événements indésirables (mineurs/majeurs), l'impact sur la qualité de vie (EORTC QLQ-C30) et le coût médico-économique. sur 206 patients randomisés, 192 ont été analysés (Port: 102; PICC: 90). L'incidence globale des complications était de 12,5% (n=24). Les complications majeures étaient significativement plus fréquentes avec les PICC (17,8%; 16/90) qu'avec les Ports (4,9%; 5/102), avec un risque relatif de 3,6 (IC95% 1,3-9,9; p=0,041). Pour une chimiothérapie de moins de 6 mois, le coût total moyen était significativement plus élevé pour les Ports (160 123,41 DA) que pour les PICC (43 259,69 DA) (p<0,001). Aucune différence significative n'a été observée sur la qualité de vie globale, avec une tendance modeste en faveur des Ports pour la santé globale et la douleur à trois mois. les Ports, bien que plus coûteux, sont associés à un risque significativement plus faible de complications majeures. Ils pourraient être préférés comme accès sûr et efficace pour les chimiothérapies de longue durée. Le choix optimal doit intégrer la durée du traitement, le profil de risque du patient et les contraintes économiques.
Adult T cell leukemia/lymphoma (ATL) is an aggressive T cell malignancy with poor prognosis. Recurrent genetic alterations in T cell receptor (TCR) signaling components, including PLCG1, PRKCB, and CARD11, highlight the biological relevance of this pathway in ATL. We focused on mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), a key regulator of TCR signaling that functions through complex formation with CARD11 and BCL10, and developed a potent and selective MALT1 protease inhibitor, CRD-1441551. CRD-1441551 exhibited variable antitumor effects across ATL models both in vitro and in vivo. Among three ATL cell lines and five patient-derived xenograft models, two demonstrated marked sensitivity, three showed modest responses, and three were unresponsive. Notably, therapeutic responses were more frequently observed in models with constitutive MALT1 activation accompanied by enhanced MALT1-NF-κB signaling. These findings suggest that CRD-1441551 preferentially targets a subset of ATL, in which tumor growth is dependent on the MALT1-driven NF-κB pathway.
Opioid-induced constipation is a practical bowel-management issue when opioids are started for cancer pain, but real-world naldemedine timing and subsequent laxative needs remain variable. To describe naldemedine initiation timing/context after oxycodone start and early additional laxative adjustment among adults with cancer. Single-center retrospective cohort study using routine clinical records. Adults with cancer pain in a single-center Japanese cancer-care setting who started oxycodone between June 1, 2017, and December 31, 2018, and subsequently received naldemedine. Concurrent initiation was naldemedine prescribed as part of the same oxycodone-start prescribing decision; reactive initiation was naldemedine added as a separate prescribing decision after physician-recognized constipation during ongoing oxycodone therapy. The primary outcome was prescription-record-based additional laxative initiation or dose escalation of existing laxatives within 7 days after naldemedine initiation. Secondary outcomes were oxycodone-to-naldemedine interval and diarrhea-related discontinuation within 28 days. Among 101 patients, the primary outcome occurred in 6/31 (19.4%) concurrent and 2/70 (2.9%) reactive cases (p = 0.010). The reactive group had a median oxycodone-to-naldemedine interval of 15 days (interquartile range, 5-83); diarrhea-related discontinuation occurred in 2/31 (6.5%) versus 6/70 (8.6%). Concurrent naldemedine at oxycodone start did not eliminate early additional laxative initiation or escalation. Naldemedine timing should be understood within individualized bowel-management planning, with conventional or rescue laxatives considered when clinically appropriate.
This study aims to evaluate the demographic characteristics, anatomical distribution, diagnostic and treatment patterns, postoperative complications, recurrence rates, and recurrence-associated factors in patients diagnosed with tenosynovial giant cell tumors (TGCTs). A total of 246 patients diagnosed with TGCT and treated between January 2010 and March 2021, were retrospectively analyzed. Pre- and postoperative data of the patients were recorded. Histopathological diagnosis was reviewed, and tumors were classified as localized TGCT and diffuse-type TGCT. Recurrence was defined as the reappearance of a lesion at the same location following an initially complete surgical excision. Survival time was defined as the time elapsed since surgery. Recurrence-free survival was calculated from the date of the surgical procedure to the date of recurrence or the last follow-up. Of a total of 246 patients included in the study, 87 were male and 159 were female with a mean age of 44.3 ± 16.3 (range, 18 to 75) years. The lesions were most commonly located in the hand (62.6%), predominantly at the phalangeal level (89.6%). Foot involvement was mainly at the ankle region (40.8%), while the knee was the third most frequently affected site (15%), with 64.8% of knee lesions being intra-articular. Multiple lesions were observed in 3.3% of patients. Small joints were involved in 63% of cases. Excisional biopsy was the most common diagnostic approach (63.8%), followed by Tru-Cut biopsy (23.2%) and incisional biopsy (8.5%), while macroscopically complete marginal resection was performed in 4.5% of cases. Postoperative complications occurred in 15.4% of patients, including infection, sensory deficits, hematoma, motion restriction, and vascular complications. The median follow-up was 43 months, and recurrence occurred in 15.4% of patients, of whom 76.3% required reoperation. Our study results suggest that TGCT is associated with a notable recurrence rate and postoperative morbidity. Accurate diagnosis, complete surgical excision, and long-term follow-up are essential for optimal management. Recurrence may be associated with factors such as pain at presentation, presence of multiple lesions, delayed treatment, and postoperative infection. Adequate surgical excision with sufficient margins is of utmost importance in reducing the risk of recurrence.
In this chapter, we describe a general sample preparation workflow for small extracellular vesicles (sEVs) from breast cancer cell lines using techniques such as protein solubilization, enzymatic digestion, and Fe3+-immobilized metal affinity chromatography (IMAC) and titanium dioxide (TiO2) enrichment prior to mass spectrometry-based proteomic analysis. This workflow can be used to perform global phosphoproteomics of sEVs enabling the study of tumor biology and the discovery of biomarkers for cancer diagnosis and treatment.
Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.
Here, we describe the covalent modification of cell surfaces with antibodies through bioconjugation to the self-labeling SNAP-tag enzyme. We apply this approach to the reprogramming of T cell signaling through the universal chimeric antigen receptor (CAR), "SNAP-CAR." Universal CARs are a highly programmable class of engineered receptors that interact with co-administered "adaptor" antibodies to recognize one or more antigens of interest to trigger receptor signaling. Universal CARs have promise for use in cell therapeutics and as research tools. SNAP-CAR covalently attaches to adaptor antibodies containing a benzyl guanine (BG) motif. The protocols presented here include methods for SNAP-CAR T cell and antibody adaptor generation using gamma retroviral transduction and BG-NHS ester conjugation, respectively. The chapter also describes methods to evaluate cell surface bioconjugate formation, including quantification of BG motifs on antibodies and co-incubation experiments to assay for antigen-directed SNAP-CAR T cell functions of target cell killing and SNAP-CAR T cell activation.