-
Cancer Genomics & Proteomics 2024Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We,...
BACKGROUND/AIM
Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery.
MATERIALS AND METHODS
The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm) or large (700 mm) tumours were imaged, breathing air then 100% O, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.
RESULTS
Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour.
CONCLUSION
OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.
Topics: Urinary Bladder Neoplasms; Animals; Humans; Mice; Magnetic Resonance Imaging; Female; Oxygen; Pilot Projects; Mice, Nude; Genomics; Hypoxia; Tumor Hypoxia; Cell Line, Tumor; Heterografts; Xenograft Model Antitumor Assays
PubMed: 38944425
DOI: 10.21873/cgp.20455 -
The Lancet. Oncology Jul 2024The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic... (Randomized Controlled Trial)
Randomized Controlled Trial
Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group.
BACKGROUND
The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy.
METHODS
ARST1431 was a randomised, open-label, phase 3 trial conducted across 210 institutions in Australia, Canada, New Zealand, and the USA. Eligible patients were those aged 40 years or younger with non-metastatic FOXO1-positive rhabdomyosarcoma or unresected FOXO1-negative rhabdomyosarcoma disease from unfavourable sites. Two other groups of patients were also eligible: those who had FOXO1-negative disease at a favourable site (excluding orbit) that was unresected; and those who were aged younger than 10 years with stage IV FOXO1-negative disease with distant metastases. Eligible patients had to have a Lansky performance status score of 50 or higher if 16 years or younger and a Karnofsky performance status score of 50 or higher if older than 16 years; all patients were previously untreated. Patients were randomised (1:1) in blocks of four and stratified by histology, stage, and group. Patients received intravenous VAC/VI chemotherapy with a cyclophosphamide dose of 1·2 g/m per dose per cycle with or without a reducing dose of intravenous weekly temsirolimus starting at 15 mg/m or 0·5 mg/kg per dose for those who weighed less than 10 kg. The total duration of therapy was 42 weeks followed by 6 months of maintenance therapy with oral cyclophosphamide plus intravenous vinorelbine for all patients. Temsirolimus was withheld during radiotherapy and for 2 weeks before any major surgical procedure. The primary endpoint was 3-year event-free survival. Data were analysed with a revised intention-to-treat approach. The study is registered with ClinicalTrials.gov (NCT02567435) and is complete.
FINDINGS
Between May 23, 2016, and Jan 1, 2022, 325 patients were enrolled. In 297 evaluable patients (148 assigned to VAC/VI alone and 149 assigned to VAC/VI with temsirolimus), the median age was 6·3 years (IQR 3·0-11·3); 33 (11%) patients were aged 18 years or older; 179 (60%) of 297 were male. 113 (77%) of 148 patients were FOXO1 negative in the VAC/VI group, and 108 (73%) of 149 were FOXO1 negative in the VAC/VI with temsirolimus group. With a median follow-up of 3·6 years (IQR 2·8-4·5), 3-year event-free survival did not differ significantly between the two groups (64·8% [95% CI 55·5-74·1] in the VAC/VI group vs 66·8% [57·5-76·2] in the VAC/VI plus temsirolimus group (hazard ratio 0·86 [95% CI 0·58-1·26]; log-rank p=0·44). The most common grade 3-4 adverse events were anaemia (62 events in 60 [41%] of 148 patients in the VAC/VI group vs 89 events in 87 [58%] of 149 patients in the VAC/VI with temsirolimus group), lymphopenia (83 events in 65 [44%] vs 99 events in 71 [48%]), neutropenia (160 events in 99 [67%] vs 164 events in 105 [70%]), and leukopenia (121 events in 86 [58%] vs 132 events in 93 [62%]). There was one treatment-related death in the VAC/VI with temsirolimus group, categorised as not otherwise specified.
INTERPRETATION
Addition of temsirolimus to VAC/VI did not improve event-free survival in patients with intermediate-risk rhabdomyosarcoma defined by their FOXO1 translocation status and clinical factors. Novel biology-based strategies are needed to improve outcomes in this population.
FUNDING
The Children's Oncology Group (supported by the US National Cancer Institute, US National Institutes of Health).
Topics: Humans; Male; Female; Child; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Sirolimus; Rhabdomyosarcoma; Child, Preschool; Vincristine; Young Adult; Cyclophosphamide; Adult; Dactinomycin; Irinotecan; Infant; Progression-Free Survival; Forkhead Box Protein O1
PubMed: 38936378
DOI: 10.1016/S1470-2045(24)00255-9 -
The Lancet. Oncology Jul 2024
Topics: Humans; Rhabdomyosarcoma; Child; Randomized Controlled Trials as Topic
PubMed: 38936374
DOI: 10.1016/S1470-2045(24)00287-0 -
Tidsskrift For Den Norske Laegeforening... Jun 2024Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts,...
Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts, fibromas, fibroadenomas, lipomas and hamartomas. Adenoma was the tentative diagnosis is this case history, but the histology showed a benign leiomyoma.
Topics: Humans; Female; Vulvar Neoplasms; Leiomyoma; Adult; Middle Aged; Diagnosis, Differential
PubMed: 38934324
DOI: 10.4045/tidsskr.23.0818 -
Nutrients Jun 2024This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients...
This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients.
Topics: Humans; Pancreatic Neoplasms; Body Composition; Male; Female; Aged; Sarcopenia; Middle Aged; Adipose Tissue; Tomography, X-Ray Computed; Prognosis
PubMed: 38931189
DOI: 10.3390/nu16121834 -
Journal of Clinical Medicine Jun 2024: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than... (Review)
Review
: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than 50 documented cases in English medical literature, the diagnosis and management of adrenal LMS remain challenging. The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers and report our specific case. : A systematic review of the literature was conducted using PubMed, Web of Science, Google Scholar, and Scopus databases, up to December 2020. The search utilized MeSH terms such as "Adrenal Gland Neoplasms," "Leiomyosarcoma," "Adrenalectomy," and "Smooth Muscle Tumor." The inclusion criteria focused on studies reporting patients with a histopathological diagnosis of adrenal leiomyosarcoma. The PRISMA guidelines were followed to ensure a comprehensive analysis. : Out of 63 identified studies, 43 met the inclusion criteria and were reviewed. These studies highlighted the rarity and aggressive behavior of adrenal leiomyosarcoma. Surgical excision remains the cornerstone of treatment, often complemented by adjuvant therapies. The reviewed case involved a 52-year-old woman who underwent a right laparoscopic adrenalectomy for a 9 × 7 × 6 cm grade 3 leiomyosarcoma. Despite subsequent adjuvant chemotherapy, hepatic metastases were detected, illustrating the aggressive nature of the disease. The literature underscores the importance of histopathological analysis and long-term surveillance for managing disease progression. : Optimal management of adrenal leiomyosarcoma requires a multidisciplinary approach and meticulous follow-up. The rarity of the disease poses challenges for standardizing treatment, but surgical excision and tailored adjuvant therapies show promise. Further research is essential to refine treatment strategies and improve prognosis for this rare malignancy.
PubMed: 38930027
DOI: 10.3390/jcm13123499 -
Medicina (Kaunas, Lithuania) Jun 2024: As brain lesions present complex diagnostic challenges, accurate tissue sampling via biopsy is critical for effective treatment planning. Traditional frame-based... (Comparative Study)
Comparative Study
: As brain lesions present complex diagnostic challenges, accurate tissue sampling via biopsy is critical for effective treatment planning. Traditional frame-based stereotactic biopsy has been complemented by navigated biopsy techniques, leveraging advancements in imaging and navigation technology. This study aims to compare the navigated and frame-based stereotactic biopsy methods in a clinical setting, evaluating their efficacy, safety, and diagnostic outcomes to determine the optimal approach for precise brain lesion targeting. : retrospective analysis was conducted on patients who underwent brain biopsies between January 2017 and August 2023 at an academic medical center. Data on patient demographics, clinical characteristics, biopsy technique (navigated vs. frame-based), and outcomes including accuracy, complications, and hospital stay duration were analyzed. : The cohort comprised 112 patients, with no significant age or gender differences between groups. Symptoms leading to biopsy were predominantly diminished muscle strength (42.0%), cognitive issues (28.6%), and aphasia (24.1%). Tumors were most common in the deep hemisphere (24.1%). The median hospital stay was 5 days, with a rehospitalization rate of 27.7%. Complications occurred in 4.47% of patients, showing no significant difference between biopsy methods. However, navigated biopsies resulted in fewer samples ( < 0.001) but with comparable diagnostic accuracy as frame-based biopsies. : Navigated and frame-based stereotactic biopsies are both effective and safe, with comparable accuracy and complication rates. The choice of technique should consider lesion specifics, surgeon preference, and technological availability. The findings highlight the importance of advanced neurosurgical techniques in enhancing patient care and outcomes.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Stereotaxic Techniques; Adult; Aged; Cohort Studies; Biopsy; Brain Neoplasms
PubMed: 38929566
DOI: 10.3390/medicina60060949 -
Medicina (Kaunas, Lithuania) May 2024Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing... (Review)
Review
UNLABELLED
Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms.
OBJECTIVES
In this review we present all currently available treatment modalities for uterine fibroids.
METHODS
An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted.
REVIEW
Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient's age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results.
CONCLUSIONS
Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient's desire for definitive treatment or fertility preservation.
Topics: Humans; Leiomyoma; Female; Uterine Neoplasms; Hysterectomy; Uterine Artery Embolization; Uterine Myomectomy
PubMed: 38929485
DOI: 10.3390/medicina60060868 -
International Journal of Molecular... Jun 2024Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications,...
Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, prognostic and predictive markers for tumor cells and immune cells are still needed. Using a tissue microarray, we analyzed the expression of the chemokine CC motif ligand 5 (CCL5) by immunohistochemistry (IHC) in 175 muscle-invasive BC samples. The application of a single cutoff for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; positive vs. negative) revealed 75 patients (42.9%) and 123 patients (70.3%) with CCL5-positive TCs or ICs, respectively. IHC results were associated with prognostic and predictive data. Multivariate Cox regression analysis revealed that positive CCL5 staining in TCs was associated with significantly shorter disease-specific survival (DSS; RR = 1.51; = 0.047), but CCL5-negative ICs were associated with significantly shorter overall survival (OS; RR = 1.66; = 0.005), DSS (RR = 2.02; = 0.001) and recurrence-free survival (RFS; RR = 1.94; = 0.002). Adjuvant chemotherapy was favorable for patients with CCL5-negative ICs for OS (RR = 0.30; = 0.006), DSS (RR = 0.36; = 0.022) and RFS (RR = 0.41; = 0.046) but not for patients with CCL5-positive ICs, except in the subgroup of N1 + N2 patients, where it was associated with better OS. We suggest that CCL5 expression can be a prognostic and predictive marker for muscle-invasive bladder cancer patients.
Topics: Humans; Urinary Bladder Neoplasms; Chemokine CCL5; Male; Female; Aged; Prognosis; Middle Aged; Biomarkers, Tumor; Neoplasm Invasiveness; Aged, 80 and over; Adult; Immunohistochemistry
PubMed: 38928033
DOI: 10.3390/ijms25126325 -
Genes Jun 2024Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not... (Comparative Study)
Comparative Study
Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.
Topics: Female; Humans; Transcriptome; Endometriosis; Leiomyoma; Gene Expression Profiling; Endometrial Neoplasms; Uterine Neoplasms; Uterine Diseases; Algorithms
PubMed: 38927658
DOI: 10.3390/genes15060723