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Japanese Journal of Radiology Jun 2024Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy...
PURPOSE
Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment.
MATERIALS AND METHODS
Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39-45 Gy/13-25 fractions. and 16.5-22 Gy/2-4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined.
RESULTS
Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively.
CONCLUSION
HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy.
PubMed: 38951462
DOI: 10.1007/s11604-024-01621-4 -
Plant Foods For Human Nutrition... Jul 2024Chronic diseases like cancer and diabetes are the major public health concerns of India and worldwide. Nowadays, plant-derived products are in great demand for the...
Chronic diseases like cancer and diabetes are the major public health concerns of India and worldwide. Nowadays, plant-derived products are in great demand for the treatment of these diseases. Pumpkin seeds are traditionally implicated for their pharmacological properties, as exemplified by benign prostatic hyperplasia. Earlier, pumpkin seed proteins were extracted by the Osborne method, and their functional and nutritional qualities were evaluated. Here, the aim is to assess in vitro, the anticancer and antidiabetic properties of seed protein fractions. HepG2, MDA-MB-231, and MCF-7 cell lines were treated with water-soluble (WF) and alkali-soluble fractions (AF) to assess cytotoxicity, while pancreatic β-cells and insulin resistance (IR) - HepG2 cell lines were treated with WF to evaluate the antidiabetic potential. WF and AF showed cytotoxic effects towards HepG2 and MDA-MB-231 cell lines, suggesting apoptosis-mediated anticancerous activity. WF potentiates glucose-stimulated insulin secretion in pancreatic β-cells, in a dose-dependent manner. In IR-HepG2 cell line studies, control, metformin, and WF-treated groups showed uptake of glucose, when compared to the diabetic group, which is well-correlated with the upregulated expressions of GLUT2 and GLUT4 transporters in these groups. These results indicate that proteins from WF and AF may have anticancerous and antidiabetic properties and thus have the potential to utilize pumpkin proteins in the management of cancer and diabetes.
PubMed: 38951376
DOI: 10.1007/s11130-024-01205-7 -
Journal of Cancer Survivorship :... Jul 2024Prostate cancer survivors may benefit from a supportive social environment. We investigated associations of social integration and long-term physical and psychosocial...
PURPOSE
Prostate cancer survivors may benefit from a supportive social environment. We investigated associations of social integration and long-term physical and psychosocial quality of life among prostate cancer survivors who were participants in the Health Professionals Follow-up Study.
METHODS
We included 1,428 individuals diagnosed with non-metastatic prostate cancer between 2008 and 2016. Social integration was measured by the Berkman-Syme Social Network Index (SNI) and marital status. We fit generalized linear mixed effect models for associations of SNI and marital status with patient reported outcome measures on physical and psychosocial quality of life captured between 2008 and 2020, adjusting for age, race, employment status, body mass index, comorbidities, smoking history, and clinical factors.
RESULTS
Among those with baseline SNI (N = 1,362), 46.4% were socially integrated, 20.3% were moderately integrated, 27.4% were moderately isolated, and 5.9% were socially isolated. Among those reporting baseline marital status (N = 1,428), 89.5% were married. Socially integrated survivors (vs. socially isolated) reported fewer depressive signs and better psychosocial wellbeing. Physical quality of life did not differ by social integration. Married survivors (vs. not married) reported fewer urinary symptoms, but there were no differences in bowel, sexual, or vitality/hormonal symptoms.
CONCLUSIONS
Among prostate cancer survivors, being socially integrated was associated with fewer depressive signs and better psychosocial wellbeing, and married prostate cancer survivors had fewer urinary symptoms.
IMPLICATIONS FOR CANCER SURVIVORS
This study highlighted aspects of long-term physical and psychosocial quality of life that are more favorable among prostate cancer survivors with a supportive social environment.
PubMed: 38951371
DOI: 10.1007/s11764-024-01632-0 -
Cancer Chemotherapy and Pharmacology Jun 2024Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in...
PURPOSE
Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in clearance and toxicity. Tools for individual dose optimization are needed to maximize efficacy and avoid toxicity.
METHODS
We performed a proof-of-concept study (EudraCT 2016-003785-77) to evaluate whether pharmacokinetics after a sub-pharmacological test dose of 1000 µg docetaxel (millidose) could be used to predict therapeutic dose exposure. Thirty prostate cancer patients eligible for treatment with docetaxel as part of routine clinical care were included. An intravenous docetaxel millidose was administered 1-7 days prior to therapeutic docetaxel. After both doses plasma docetaxel concentrations were measured by ultra- high performance liquid chromatography-tandem mass spectrometry. The docetaxel clearance was estimated with non-linear mixed effects modeling.
RESULTS
Geometric mean docetaxel clearance was 57.9 L/h (GCV 78.6%) after admission of a millidose and 40.3 L/h (GCV 60.7%) after admission of a therapeutic dose. The millidose and therapeutic dose in a single patient were not significantly correlated (Spearman's rho R = 0.02, P = 0.92).
CONCLUSION
Docetaxel pharmacokinetics at milli- and therapeutic dose level showed insufficient correlation for individual dose optimization. However, the clearance of a docetaxel millidose and full dose are within the same order of magnitude. Therefore, docetaxel millidose pharmacokinetics could potentially facilitate prediction of docetaxel pharmacokinetics at a population level in situations where therapeutic dose levels are impractical, such as pharmacokinetic drug-drug interaction studies or pediatric studies.
PubMed: 38951305
DOI: 10.1007/s00280-024-04684-2 -
Abdominal Radiology (New York) Jul 2024The broad range of disease aggressiveness together with imperfect screening, diagnostic, and treatment options in prostate cancer (PCa) makes medical decision-making...
The broad range of disease aggressiveness together with imperfect screening, diagnostic, and treatment options in prostate cancer (PCa) makes medical decision-making complex. The primary goal of a multidisciplinary conference is to improve patient outcomes by combining evidence-based data and expert opinion to discuss optimal management, including for those patients with challenging presentations. The primary purpose of the genitourinary imaging specialist in the prostate cancer multidisciplinary conference is to use imaging findings to reduce uncertainty by answering clinical questions. In this review, we discuss the role and the opportunities for an imaging specialist to add value in the care of men with prostate cancer discussed at multidisciplinary conferences.
PubMed: 38951230
DOI: 10.1007/s00261-024-04433-2 -
Nucleic Acids Research Jul 2024CCCTC-binding factor (CTCF) is an insulator protein that binds to a highly conserved DNA motif and facilitates regulation of three-dimensional (3D) nuclear architecture...
CCCTC-binding factor (CTCF) is an insulator protein that binds to a highly conserved DNA motif and facilitates regulation of three-dimensional (3D) nuclear architecture and transcription. CTCF binding sites (CTCF-BSs) reside in non-coding DNA and are frequently mutated in cancer. Our previous study identified a small subclass of CTCF-BSs that are resistant to CTCF knock down, termed persistent CTCF binding sites (P-CTCF-BSs). P-CTCF-BSs show high binding conservation and potentially regulate cell-type constitutive 3D chromatin architecture. Here, using ICGC sequencing data we made the striking observation that P-CTCF-BSs display a highly elevated mutation rate in breast and prostate cancer when compared to all CTCF-BSs. To address whether P-CTCF-BS mutations are also enriched in other cell-types, we developed CTCF-INSITE-a tool utilising machine learning to predict persistence based on genetic and epigenetic features of experimentally-determined P-CTCF-BSs. Notably, predicted P-CTCF-BSs also show a significantly elevated mutational burden in all 12 cancer-types tested. Enrichment was even stronger for P-CTCF-BS mutations with predicted functional impact to CTCF binding and chromatin looping. Using in vitro binding assays we validated that P-CTCF-BS cancer mutations, predicted to be disruptive, indeed reduced CTCF binding. Together this study reveals a new subclass of cancer specific CTCF-BS DNA mutations and provides insights into their importance in genome organization in a pan-cancer setting.
PubMed: 38950902
DOI: 10.1093/nar/gkae530 -
The Lancet. Oncology Jun 2024Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and...
BACKGROUND
Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.56 conjugated to p-SCN-Bn-deferoxamine [DFO] serving as a chelator for zirconium-89) in patients with neuroendocrine-derived cancer.
METHODS
We conducted an open-label, first-in-human study of immunoPET-CT imaging with [Zr]Zr-DFO-SC16.56. The study was done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Patients aged 18 years or older with a histologically verified neuroendocrine-derived malignancy and an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. An initial cohort of patients with SCLC (cohort 1) received 37-74 MBq [Zr]Zr-DFO-SC16.56 as a single intravenous infusion at a total mass dose of 2·5 mg and had serial PET-CT scans at 1 h, day 1, day 3, and day 7 post-injection. The primary outcomes of phase 1 of the study (cohort 1) were to estimate terminal clearance half-time, determine whole organ time-integrated activity coefficients, and assess the safety of [Zr]Zr-DFO-SC16.56. An expansion cohort of additional patients (with SCLC, neuroendocrine prostate cancer, atypical carcinoid tumours, and non-small-cell lung cancer; cohort 2) received a single infusion of [Zr]Zr-DFO-SC16.56 at the same activity and mass dose as in the initial cohort followed by a single PET-CT scan 3-6 days later. Retrospectively collected tumour biopsy samples were assessed for DLL3 by immunohistochemistry. The primary outcome of phase 2 of the study in cohort 2 was to determine the potential association between tumour uptake of the tracer and intratumoural DLL3 protein expression, as determined by immunohistochemistry. This study is ongoing and is registered with ClinicalTrials.gov, NCT04199741.
FINDINGS
Between Feb 11, 2020, and Jan 30, 2023, 12 (67%) men and six (33%) women were enrolled, with a median age of 64 years (range 23-81). Cohort 1 included three patients and cohort 2 included 15 additional patients. Imaging of the three patients with SCLC in cohort 1 showed strong tumour-specific uptake of [Zr]Zr-DFO-SC16.56 at day 3 and day 7 post-injection. Serum clearance was biphasic with an estimated terminal clearance half-time of 119 h (SD 31). The highest mean absorbed dose was observed in the liver (1·83 mGy/MBq [SD 0·36]), and the mean effective dose was 0·49 mSv/MBq (SD 0·10). In cohort 2, a single immunoPET-CT scan on day 3-6 post-administration could delineate DLL3-avid tumours in 12 (80%) of 15 patients. Tumoural uptake varied between and within patients, and across anatomical sites, with a wide range in maximum standardised uptake value (from 3·3 to 66·7). Tumour uptake by [Zr]Zr-DFO-SC16.56 was congruent with DLL3 immunohistochemistry in 15 (94%) of 16 patients with evaluable tissue. Two patients with non-avid DLL3 SCLC and neuroendocrine prostate cancer by PET scan showed the lowest DLL3 expression by tumour immunohistochemistry. One (6%) of 18 patients had a grade 1 allergic reaction; no grade 2 or worse adverse events were noted in either cohort.
INTERPRETATION
DLL3 PET-CT imaging of patients with neuroendocrine cancers is safe and feasible. These results show the potential utility of [Zr]Zr-DFO-SC16.56 for non-invasive in-vivo detection of DLL3-expressing malignancies.
FUNDING
National Institutes of Health, Prostate Cancer Foundation, and Scannell Foundation.
PubMed: 38950555
DOI: 10.1016/S1470-2045(24)00249-3 -
Journal of Radiation Research Jul 2024Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers that affect the head and neck region. Recent researches have confirmed that long...
Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers that affect the head and neck region. Recent researches have confirmed that long non-coding RNAs (lncRNAs) present an emerging role in diversiform diseases including cancers. Prostate cancer-associated ncRNA transcript 6 (PCAT6) is an oncogene in lung cancer, cervical cancer, colon cancer and gastric cancer, but its role in LSCC is still unknown. In the current study, we attempted to figure out the role of PCAT6 in LSCC. RT-qPCR was to analyze PCAT6 expression in LSCC cells. Functional assays were to uncover the role of PCAT6 in LSCC. Mechanism assays were to explore the regulatory mechanism behind PCAT6 in LSCC. PCAT6 exhibited higher expression in LSCC cells and PCAT6 strengthened cell proliferation and inhibited cell apoptosis. Furthermore, lncRNA PCAT6 modulated notch receptor 3 expression and activated NOTCH signaling pathway via serving as a sponge for miR-4731-5p. Taken together, lncRNA PCAT6 was identified as an oncogene in LSCC, which revealed that PCAT6 might be used as potential therapeutic target for LSCC.
PubMed: 38950346
DOI: 10.1093/jrr/rrae042 -
Journal of Managed Care & Specialty... Jul 2024The advent of next-generation imaging will likely reduce nonmetastatic prostate cancer (PC) prevalence and increase identification of metastatic prostate cancer cases,...
Real-world economic burden associated with disease progression from metastatic castration-sensitive to castration-resistant prostate cancer on treatment in the United States.
BACKGROUND
The advent of next-generation imaging will likely reduce nonmetastatic prostate cancer (PC) prevalence and increase identification of metastatic prostate cancer cases, resulting in two predominant advanced stages in the metastatic setting. There is a need to characterize changes in health care resource utilization (HRU) and costs when metastatic castration-sensitive PC (mCSPC) progresses to metastatic castration-resistant PC (mCRPC) to identify value drivers from current and new treatments.
OBJECTIVE
To describe treatment patterns, HRU, and total health care costs among patients with mCSPC, before and after progression to mCRPC.
METHODS
Clinical data from the Flatiron Metastatic PC Core Registry (January 1, 2013, to December 1, 2021) and linked claims from Komodo Health (January 1, 2014, to December 1, 2021) were used to identify patients with progression from mCSPC to mCRPC (date of progression was the index date) and subsequently initiated first-line mCRPC therapy on/after January 1, 2017. Treatment patterns and all-cause/PC-related HRU and health care costs were described per-patient-per-month (PPPM), separately for no more than 12 months pre-index (mCSPC disease state) and post-index (mCRPC disease state). Costs (payer's perspective) included those for services/procedures from medical claims and costs from pharmacy claims. Continuous HRU and costs were compared between the mCSPC and mCRPC disease states using Wilcoxon signed rank tests.
RESULTS
Among 296 patients with mCSPC progressing to mCRPC (median age 69.0 years, 60.5% White, 15.9% Black), use of systemic therapies with androgen deprivation therapy increased dramatically from 35.1% in the mCSPC disease state to 92.9% in the mCRPC disease state, and use of androgen deprivation therapy monotherapy decreased from 25.7% to 2.4%, respectively. Although 39.2% received none of these therapies in the mCSPC disease state, this proportion decreased to 4.7% after transition to mCRPC. The mean number of days with PC-related outpatient visits increased from 1.57 to 2.16 PPPM in the mCSPC and mCRPC disease states ( < 0.001). From the mCSPC to mCRPC disease states, mean all-cause total health care costs PPPM increased from $4,424 (medical costs: $2,846) to $9,717 (medical costs: $4,654), and mean PC-related total health care costs PPPM increased from $2,859 (medical costs: $1,626) to $8,012 (medical costs: $3,285; all < 0.001).
CONCLUSIONS
In this real-world study of patients with disease progression from mCSPC to mCRPC in US clinical practice, nearly 2-in-3 patients did not receive treatment with additional systemic therapies before progression to castration resistance. Post-progression, mean PC-related total costs increased nearly 3-fold, with a more than 2-fold increase in PC-related medical costs. Use of additional systemic therapies may delay the time and cost associated with disease progression to castration resistance.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Disease Progression; United States; Aged; Health Care Costs; Middle Aged; Cost of Illness; Retrospective Studies; Aged, 80 and over; Neoplasm Metastasis; Registries
PubMed: 38950154
DOI: 10.18553/jmcp.2024.30.7.684 -
Cancer Jul 2024This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate...
BACKGROUND
This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System.
METHODS
In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status.
RESULTS
Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively.
CONCLUSIONS
Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies.
PubMed: 38950063
DOI: 10.1002/cncr.35466