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Scientific Reports Apr 2021Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide...
Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (r = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (r = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.
Topics: Adult; Aged; Bevacizumab; Biomarkers, Pharmacological; Brain Neoplasms; Cerebral Blood Volume; Drug Resistance, Neoplasm; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Misonidazole; Neoplasm Recurrence, Local; Positron-Emission Tomography; Progression-Free Survival; Tumor Hypoxia; Young Adult
PubMed: 33828310
DOI: 10.1038/s41598-021-84331-5 -
Journal of Nuclear Medicine : Official... Jun 2003During the past decade the clinical value of PET imaging has been investigated for many different tumors. As knowledge of the advantages and limitations of this modality... (Review)
Review
During the past decade the clinical value of PET imaging has been investigated for many different tumors. As knowledge of the advantages and limitations of this modality increased, PET has gained acceptance in tumor imaging. (18)F-FDG PET is now successfully used and approved for procedure reimbursement in many types of cancer-for example, lung cancer, melanoma, lymphoma, head and neck tumors, brain tumors, esophageal cancer, and colorectal cancer. In osteosarcoma, the introduction of neoadjuvant chemotherapy has dramatically improved survival rates, thus changing the demands for state-of-the-art imaging to provide detailed information on tumor staging and grading, evaluating treatment, and detecting recurrences. In this review, the available literature on PET imaging in osteosarcoma patients is critically summarized with respect to diagnosis, staging, therapy monitoring, and follow-up focusing on the clinically used tracers (18)F-FDG and (18)F-fluoride ion. Potential and probable indications are outlined. Because of the relatively small number of patients enrolled in clinical trials published to date, further research needs to be done in larger, prospective patient series to determine the full utility of PET in osteosarcoma.
Topics: Bone Neoplasms; Fluorodeoxyglucose F18; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Osteosarcoma; Radiopharmaceuticals; Tomography, Emission-Computed
PubMed: 12791822
DOI: No ID Found -
Frontiers in Cell and Developmental... 2021Head and Neck cancer survival has continued to remain around 50% despite treatment advances. It is thought that cancer stem cells play a key role in promoting tumor... (Review)
Review
Head and Neck cancer survival has continued to remain around 50% despite treatment advances. It is thought that cancer stem cells play a key role in promoting tumor heterogeneity, treatment resistance, metastasis, and recurrence in solid malignancies including head and neck cancer. Initial studies identified cancer stem cell markers including CD44 and ALDH in head and neck malignancies and found that these cells show aggressive features in both and studies. Recent evidence has now revealed a key role of the tumor microenvironment in maintaining a cancer stem cell niche and promoting cancer stem cell plasticity. There is an increasing focus on identifying and targeting the crosstalk between cancer stem cells and surrounding cells within the tumor microenvironment (TME) as new therapeutic potential, however understanding how CSC maintain a stem-like state is critical to understanding how to therapeutically alter their function. Here we review the current evidence for cancer stem cell plasticity and discuss how interactions with the TME promote the cancer stem cell niche, increase tumor heterogeneity, and play a role in treatment resistance.
PubMed: 35047489
DOI: 10.3389/fcell.2021.660210 -
International Journal of Surgery Case... Mar 2022Different groups of neoplastic and non-neoplastic conditions can involve the ovaries and the epithelial tumors such as mucinous and Brenner tumors are the most common...
INTRODUCTION
Different groups of neoplastic and non-neoplastic conditions can involve the ovaries and the epithelial tumors such as mucinous and Brenner tumors are the most common neoplastic category.
PRESENTATION OF CASE
This is a case report of a huge mucinous cystadenoma associated with benign Brenner tumor in 56 years old postmenopausal woman, who presented with a fast-growing abdominopelvic mass, and also review the reported articles about this rare occurrence.
DISCUSSION
Mucinous neoplasms of the ovary represent 10%-15% of ovarian neoplasms and about 80% of them are benign. Brenner tumors are a relatively rare epithelial neoplasm of the ovary that usually affect postmenopausal women and most of them are benign. Coexistence of Mucinous cystadenoma with Brenner tumor is a rare mixed epithelial tumor of the ovary.
CONCLUSION
This case report and review of article create awareness among the surgeons and pathologists about rare occurrence of combination of ovarian mucinous cystadenoma and benign Brenner tumor.
PubMed: 35245850
DOI: 10.1016/j.ijscr.2022.106859 -
Cancers Mar 2024Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the... (Review)
Review
BACKGROUND
Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors.
METHODS
We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023.
RESULTS
After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature.
CONCLUSIONS
We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.
PubMed: 38539441
DOI: 10.3390/cancers16061106 -
Diagnostic Pathology Mar 2020Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of... (Review)
Review
BACKGROUND
Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors.
CASE PRESENTATION
A 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34βE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence.
CONCLUSIONS
We report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.
Topics: Brenner Tumor; Female; Humans; Middle Aged; Uterine Neoplasms
PubMed: 32164751
DOI: 10.1186/s13000-019-0906-1 -
Ginekologia Polska 2018To describe the ultrasound features of benign Brenner tumor in the background of complex clinical and histopathological pictures.
OBJECTIVES
To describe the ultrasound features of benign Brenner tumor in the background of complex clinical and histopathological pictures.
MATERIAL AND METHODS
We retrospectively identified patients with histologically confirmed benign Brenner tumor of the ovary who were treated in our institution in 2003-2016, and for whom complete imaging, clinical, perioperative and histopathological data were available in the database. Ultrasound findings were drawn from images and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied.
RESULTS
Twenty-three patients were identified, most postmenopausal and asymptomatic. On ultrasound, 19/23 tumors were found unilaterally, 4/23 bilaterally, and 82% of tumors were detected in the left ovary. Most Brenner tumors (16/23) contained solid components and revealed no or minimal blood flow by subjective color score upon Doppler examination (19/23, 83%). Calcifications with shadowing were observed in 57% of all Brenner tumors and in 81% of tumors containing solid components. The complex appearance of the tumor misled the sonographers to describe the mass as malignant in 9 cases (39%), and frozen section was performed perioperatively. Surgery was performed via laparoscopy in 11 (48%) and via laparotomy in 12 (52%) cases.
CONCLUSIONS
The complexity of the ultrasound picture, consisting of features like calcifications with acoustic shadowing, a poorly vascularized solid mass, and a left-sided localization could be signs of a benign Brenner tumor and could preop-eratively help to differentiate between benign and malignant tumor.
Topics: Adult; Brenner Tumor; Disease Management; Female; Humans; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Ultrasonography, Doppler, Color
PubMed: 30091444
DOI: 10.5603/GP.a2018.0061 -
Modern Pathology : An Official Journal... May 2021Malignant Brenner tumor is a rare primary ovarian carcinoma subtype that may present diagnostic and therapeutic conundrums. Here, we characterize the genomics of 11...
Malignant Brenner tumor is a rare primary ovarian carcinoma subtype that may present diagnostic and therapeutic conundrums. Here, we characterize the genomics of 11 malignant Brenner tumors, which represented 0.1% of 14,153 clinically advanced ovarian carcinomas submitted for genomic profiling during the course of clinical care. At the time of molecular profiling, there was no evidence of a primary urothelial carcinoma of the urinary tract in any case. Cases with transitional-like morphologic features in the setting of variant ovarian serous or endometrioid carcinoma morphology were excluded from the final cohort. Malignant Brenner tumors exhibited CDKN2A/2B loss and oncogenic FGFR1/3 genomic alterations in 55% of cases, respectively; including recurrent FGFR3 S249C or FGFR3-TACC3 fusion in 45% of cases. FGFR3-mutated cases had an associated benign or borderline Brenner tumor pre-cursor components, further confirming the diagnosis and the ovarian site of origin. Malignant Brenner tumors were microsatellite stable, had low tumor mutational burden and exhibited no evidence of homologous recombination deficiency. PIK3CA mutations were enriched with FGFR3 alterations, while FGFR3 wild-type cases featured MDM2 amplification or TP53 mutations. The FGFR3 S249C short variant mutation was absent in 14,142 non-Brenner, ovarian carcinomas subtypes. In contrast to malignant Brenner tumors, FGFR1/2/3 alterations were present in ~5% of non-Brenner, ovarian serous, clear cell and endometrioid carcinoma subtypes, most often as FGFR1 amplification in serous carcinoma or FGFR2 short variant alterations in clear cell or endometrioid carcinomas, respectively. Finally, malignant Brenner tumors had overall distinct genomic signatures compared to FGFR-mutated ovarian serous, endometrioid, and clear cell carcinoma subtypes. This study provides insights into the molecular pathogenesis of malignant Brenner tumors, contrasts the extent of FGFR1/2/3 alterations in ovarian serous, clear cell and endometrioid carcinomas and emphasizes the potential value of novel and FDA-approved, anti-FGFR inhibitors, such as erdafitinib and pemigatinib, in refractory, FGFR3-mutated malignant Brenner tumors.
Topics: Adult; Aged; Biomarkers, Tumor; Brenner Tumor; Carcinoma, Endometrioid; Cystadenocarcinoma, Serous; Female; Gene Expression Profiling; Humans; Middle Aged; Mutation; Ovarian Neoplasms; Ovary; Receptor, Fibroblast Growth Factor, Type 3
PubMed: 33077920
DOI: 10.1038/s41379-020-00699-1 -
Gynecologic Oncology Reports Nov 2017Ovarian neoplasms are a heterogeneous group of tumors with varying incidence in the general population. The most common are the surface epithelial tumors which include...
Ovarian neoplasms are a heterogeneous group of tumors with varying incidence in the general population. The most common are the surface epithelial tumors which include transitional cell tumors. Transitional cell tumors include both transitional cell carcinoma and Brenner tumor. The vast majority of Brenner tumors are benign, often incidental findings; however, malignant Brenner tumors (MBT) do occasionally occur. MBT present similarly to other ovarian neoplasms with abdominal pain and bulk symptoms. On imaging, these tumors demonstrate nonspecific findings. Microscopically, they demonstrate areas of conventional benign Brenner tumor juxtaposed with regions of frank malignancy showing marked cytologic atypia and infiltration. There is no consistent tumor marker for these tumors, but CA-125, CA 72-4 and SCC have been reported in singular instances. Tumors express several immunohistochemical markers of urothelial differentiation including uroplakin III, thrombomodulin, GATA3, p63, as well as cytokeratin 7. The primary treatment modality is surgical excision. Due to their rarity, the precise role and regimen of adjuvant chemo-radiation therapy for MBT has not been established. We herein review a case of MBT with emphasis on primary treatment and treatment of recurrent disease, including the use of adjuvant pelvic radiation, discuss the current state of the literature and standards of practice regarding this malignancy.
PubMed: 28971141
DOI: 10.1016/j.gore.2017.07.001 -
Frontiers in Bioscience (Scholar... Jan 2011Glioblastoma multiforme (GBM) represents the most devastating adult brain tumor. GBM follows a hierarchical development in oncogenesis, with a sub-population of cells -... (Review)
Review
Glioblastoma multiforme (GBM) represents the most devastating adult brain tumor. GBM follows a hierarchical development in oncogenesis, with a sub-population of cells - brain tumor stem cells (BTSCs), exhibiting tumor-initiating potential. BTSCs possess extensive self-renewal capability and can repopulate the entire tumor mass. They are resistant to conventional therapies, suggesting that they are the likely candidates of tumor recurrence. Their eradication is thus important for an effective cure. Previous works showed that human-derived BTSCs could be stably maintained for 10-15 passages in serum-free condition, and gene expression and karyotypic hallmarks similar to the primary tumors were preserved. However, primary cells have been shown to sustain additional karyotypic aberrations owing to the harsh conditions of extended in vitro serial passage. Several investigators have proposed passaging these cells in xenograft models. A limitation of such an approach is the inability to return to identical passages for experimental repetitions, or the unavailability of suitably-aged mice for implantation. We have devised a method to cryopreserve BTSCs and that important characteristics were maintained, establishing a repository for drug screening endeavors.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cryopreservation; Drug Screening Assays, Antitumor; Glioblastoma; Humans; Mice; Neoplastic Stem Cells
PubMed: 21196406
DOI: 10.2741/s181