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British Journal of Clinical Pharmacology Jul 2024Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this...
AIMS
Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations.
METHODS
A total of 1469 abiraterone plasma levels from 83 healthy volunteers collected in a bioequivalence study were analysed using a nonlinear mixed-effects model. Monte Carlo simulation was used to describe the theoretical distribution of abiraterone pharmacokinetic profiles at a dose of 1000 mg once daily. Adherence of 36 prostate cancer patients treated with abiraterone was then evaluated by comparing the real abiraterone concentration measured in each patient during follow-up visit with the theoretical distribution of profiles based on simulations. Patients whose abiraterone levels were ˂5th or ˃95th percentile of the distribution of simulated profiles were considered to be non-adherent.
RESULTS
Based on this evaluation, 13 patients (36%) have been classified as non-adherent. We observed significant association (P = .0361) between richness of the breakfast and rate of non-adherence. Adherent patients reported significantly better overall condition in self-assessments (P = .0384). A trend towards a higher occurrence of adverse effects in non-adherent patients was observed.
CONCLUSIONS
We developed an abiraterone population pharmacokinetic model and proposed an advanced approach to medical adherence evaluation. Due to the need for administration under fasting conditions, abiraterone therapy is associated with a relatively high rate of non-adherence.
PubMed: 38958217
DOI: 10.1111/bcp.16155 -
Asia-Pacific Journal of Clinical... Jul 2024To evaluate the efficacy and safety of triptorelin after radical prostatectomy (RP) in patients with negative lymph nodes.
AIM
To evaluate the efficacy and safety of triptorelin after radical prostatectomy (RP) in patients with negative lymph nodes.
METHODS
PRIORITI (NCT01753297) was a prospective, open-label, randomized, controlled, phase 4 study conducted in China and Russia. Patients with high-risk (Gleason score ≥ 8 and/or pre-RP prostate-specific antigen [PSA] ≥ 20 ng/mL and/or primary tumor stage 3a) prostate adenocarcinoma without evidence of lymph node or distant metastases were randomized to receive triptorelin 11.25 mg at baseline (≤ 8 weeks after RP) and at 3 and 6 months, or active surveillance. The primary endpoint was biochemical relapse-free survival (BRFS), defined as the time from randomization to biochemical relapse (BR; increased PSA > 0.2 ng/mL). Patients were monitored every 3 months for at least 36 months; the study ended when 61 BRs were observed.
RESULTS
The intention-to-treat population comprised 226 patients (mean [standard deviation] age, 65.3 [6.4] years), of whom 109 and 117 were randomized to triptorelin or surveillance, respectively. The median BRFS was not reached. The 25th percentile time to BRFS (95% confidence interval) was 39.1 (29.9-not estimated) months with triptorelin and 30.0 (18.6-42.1) months with surveillance (p = 0.16). There was evidence of a lower risk of BR with triptorelin versus surveillance but this was not statistically significant at the 5% level (p = 0.10). Chemical castration was maintained at month 9 in 93.9% of patients who had received triptorelin. Overall, triptorelin was well tolerated and had an acceptable safety profile.
CONCLUSION
BRFS was observed to be longer with triptorelin than surveillance, but the difference was not statistically significant.
PubMed: 38958195
DOI: 10.1111/ajco.14101 -
Clinical Chemistry Jul 2024Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications...
BACKGROUND
Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications from the European Committee for Standardization (CEN/TS) standardized workflows exist, their implementation in clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS standards in a real-world clinical setting, with a particular focus on evaluating the impact of preanalytical parameters and hemolysis on liquid biopsy analysis.
METHODS
We evaluated 659 peripheral blood samples from advanced prostate cancer patients against ISO and CEN/TS standards and documented all essential criteria, including tube draw order, filling level, temperature, and time tracking from blood draw to storage. We assessed hemolysis and its effect on circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analysis.
RESULTS
Our results demonstrated a high compliance rate, with 96.2% (634/659) of samples meeting essential ISO and CEN/TS criteria. We did not observe a significant impact on ctDNA or CTC detection rates between hemolytic and nonhemolytic samples. Hemolysis was identified in 12.9% (40/311) of plasma samples from our advanced prostate cancer cohort, and within the draw order of 5 blood collection tubes, hemolysis did not significantly increase from tube 1 to 5. In total, 83.8% (552/659) of blood collection tubes had high fill levels above 80% of nominal filling level.
CONCLUSIONS
Our study demonstrates the feasibility and benefits of adhering to ISO and CEN/TS standards in a clinical liquid biopsy study. The standards revealed that hemolysis occurred frequently but did not impair downstream ctDNA and CTC analysis in our cohort of advanced prostate cancer patients.
PubMed: 38958115
DOI: 10.1093/clinchem/hvae079 -
Cureus Apr 2024Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where...
Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where solid tumors metastasize. Complications involved in spinal metastasis include root or spinal cord compression, progressing to a declining quality of life as patient autonomy reduces and pain increases. The main objective of this study is to report the incidence of patients and typology of spinal metastases in three reference centers in Mexico. Methodology Retrospective cohorts of patients diagnosed with spinal metastases from January 2010 to February 2017 at the National Cancer Institute, National Rehabilitation Institute, and the Traumatology and Orthopedics Hospital "Lomas Verdes" in Mexico City were analyzed. Results A total of 326 patients (56% males) with spinal metastases were reported. The mean age was 58.06 ± 14.05 years. The main sources of spinal metastases were tumors of unknown origin in 53 (16.25%) cases, breast cancer in 67 (20.5%) cases, prostate cancer in 59 (18%) cases, myeloma in 24 (7.4%) cases, and lung cancer in 23 (7.1%) cases. Conclusions The data obtained in this analysis delivers an updated standpoint on Mexico, providing the opportunity to distinguish the current data from global references. Collecting more epidemiological information for better recording of cancer and its associated complications, as well as further studies on them, is necessary.
PubMed: 38957823
DOI: 10.7759/cureus.58546 -
Ghana Medical Journal Sep 2023To explore the prevalence of prostate cancer screening among Ghanaian men and interrogate why some individuals screen for the disease and others do not.
OBJECTIVE
To explore the prevalence of prostate cancer screening among Ghanaian men and interrogate why some individuals screen for the disease and others do not.
DESIGN
A cross-sectional questionnaire survey based on the Health Belief Model was used to collect data from 356 men aged 40 years and above. Data were collected between February and March 2021.
SETTING
The study was conducted in the Accra metropolitan area of the Greater Accra region of Ghana.
PARTICIPANTS
Convenience sampling was used to recruit participants for the study.
RESULTS
Although 86% of the respondents had heard about prostate cancer, only 23% had ever screened for it. Logistic regression analysis suggested that knowledge of the disease (OR = 1.19, CI 95% = 1.03 -1.38) and barriers to screening (OR = .87, CI 95% = .83 -.91) were statistically significant predictors of screening behaviour.
CONCLUSION
HBM has limited predictive power as far as our study is concerned. We suggest increasing public education on prostate cancer and its screening methods. The cost of screening should also be made more affordable so as not to become a barrier.
FUNDING
None declared.
Topics: Humans; Male; Prostatic Neoplasms; Ghana; Middle Aged; Cross-Sectional Studies; Early Detection of Cancer; Adult; Health Belief Model; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; Aged; Mass Screening; Logistic Models; Patient Acceptance of Health Care
PubMed: 38957671
DOI: 10.4314/gmj.v57i3.10 -
Dermatology Reports Jun 2024
PubMed: 38957639
DOI: 10.4081/dr.2023.9734 -
Frontiers in Pharmacology 2024The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer... (Review)
Review
The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data and studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.
PubMed: 38957397
DOI: 10.3389/fphar.2024.1406619 -
Frontiers in Pharmacology 2024One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its...
BACKGROUND
One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated.
METHODS
Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub).
RESULTS
113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa.
CONCLUSION
We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.
PubMed: 38957390
DOI: 10.3389/fphar.2024.1383304 -
Frontiers in Oncology 2024Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel...
INTRODUCTION
Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer.
MATERIALS AND METHODS
Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared.
RESULTS
140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators.
CONCLUSIONS
For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.
PubMed: 38957327
DOI: 10.3389/fonc.2024.1386058 -
Cureus Jun 2024Adenocarcinoma, while constituting the predominant variant among small bowel cancers, is a component of the broader category of primary small bowel malignancies, which...
An Unexpected Challenge: Marked Small Bowel Obstruction Arising From a Poorly Differentiated Metastatic Mucinous Adenocarcinoma of the Distal Ileum in a Risk-Free Healthy Patient.
Adenocarcinoma, while constituting the predominant variant among small bowel cancers, is a component of the broader category of primary small bowel malignancies, which are notably infrequent in occurrence. The diagnosis of such malignancies is often markedly delayed, a consequence of their insidious onset and the nonspecific nature of the abdominal symptoms presented. A 69-year-old Caucasian male presented to the emergency department manifesting acute, sharp, and colicky abdominal pain accompanied by a single episode of vomiting, all developing over one day. His medical history was notable for gastroesophageal reflux disease (GERD) and regionally confined prostate adenocarcinoma, which was under meticulous surveillance by the urological team. The patient's lifestyle was characterized by abstention from alcohol and tobacco, adherence to a nutritious diet, and a commitment to regular physical activity. Subsequent examination and surgical excision of an abnormal mass, as delineated on computed tomography (CT), culminated in the diagnosis of a stage IV, poorly differentiated adenocarcinoma. We have reported this case to spark research regarding early diagnostic techniques for small bowel adenocarcinoma (SBA). In this case, a healthy individual presented with vague abdominal pain and a single episode of vomiting. Diagnosis required the surgical resection of the tumor, where metastasis was also visualized. Due to the rare nature of SBA, we believe different diagnostic measures and adjuvant therapy should be researched for earlier diagnosis and subsequently better patient outcomes.
PubMed: 38957234
DOI: 10.7759/cureus.61528