Low-grade Cancer Research Articles

What is the Standard of Care For Multifocal Low-Grade Bladder Cancer?

What is the Standard of Care For Multifocal Low-Grade Bladder Cancer?

Abstract A070: Diagnostic accuracy of Oncuria®-Detect in the detection of upper tract urothelial tumors

Abstract Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with upper tract urothelial carcinoma. The robust urine-based multiplex assay for diagnosis of upper tract urothelial carcinoma has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis.We previously developedOncuria®-Detect, a multiplex immunoassay capable of detecting bladder cancer using a single voided urine. In this study, its application to upper tract urothelial cancer was evaluated in a multi-institutional cohort of 61 prospectively collected subjects presenting for evaluation of upper tract mass along with 61 prospective collected matched controls. The ability of the test to identify patients harboring upper tract urothelial carcinoma was assessed. Cancer status was confirmed by endoscopy and tissue biopsy or definitive surgery. Oncuria®-Detect provided an AUC of 0.868 (95% CI: 0.802- 0.933) with an overall sensitivity of 96.7%, specificity of 59.0%, NPV 94.7% and PPV 70.2%. Sensitivity values of Oncuria®-Detect for low-grade, high-grade, non-invasive and invasive upper tract urothelial cancer were 100%, 89.7%, 93.3% and 96.2%, respectively. Voided urine cytology showed an overall sensitivity of 54.5%, specificity of 100%, NPV 31.0% and PPV 100%. As a non-invasive test, Oncuria®-Detect outperformed both voided urinary cytology and selective cytology (sensitivities 96.7% vs. 54.5% vs. 81.8%, respectively). Oncuria®-Detect enabled the accurate discrimination of upper tract urothelial carcinoma and controls non-tumor bearing individuals. The Oncuria®-Detect test can achieve the efficient and accurate detection of upper tract urothelial carcinoma in a non-invasive patient setting. Citation Format: Kazutoshi Fujita, Makito Miyake, Takuto Shimizu, Jennifer Linehan, Joshua Gottlieb, Ian Pagano, Sergei Tikhonenkov, Kaoru Murakami, Riko Lee, Toru Sakatani, Sunao Tanaka, Charles J Rosser, Hideki Furuya. Diagnostic accuracy of Oncuria®-Detect in the detection of upper tract urothelial tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A070.

Glucose chemical exchange saturation transfer MRI for predicting the histological grade of rectal cancer: a comparative study with amide proton transfer-weighted and diffusion-weighted imaging.

To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer. This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis. Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p < 0.01). The AUCs of MTRasym (1.2 ppm), MTRasym (3.5 ppm), and ADC for differentiating between low- and high-grade rectal cancer cases were 0.792, 0.839, and 0.855, respectively. The diagnostic performance of the combination of the three indexes was improved (AUC, 0.969; sensitivity, 95.24%; specificity, 87.18%). The good consistency and reliability of the combination of independent predictors were demonstrated by calibration curve analysis and DCA. The glucoCEST MRI without contrast injection, APTWI, and DWI all facilitate the assessment of histological grade in rectal cancer, and the combination of the three can effectively discriminate between high- and low-grade rectal cancer, which is expected to be a promising imaging marker. The glucose chemical exchange saturation transfer MRI method facilitates the assessment of histological grade in rectal cancer and offers additional information to improve the diagnostic performance of amide proton transfer-weighted imaging, and diffusion-weighted imaging. Glucose chemical exchange saturation transfer imaging could differentiate histological grade. Amide proton transfer-weighted and diffusion-weighted were associated with histological grade. The combination of different parameters showed the best diagnostic performance.

Voices of women with low-grade serous ovarian cancer: Results from a multinational survey

Voices of women with low-grade serous ovarian cancer: Results from a multinational survey

Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer

Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer

A phase III, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of therapy among patients with recurrent low-grade serous ovarian cancer: GOG-3097/ENGOT-OV81/NCRI/RAMP 301

A phase III, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of therapy among patients with recurrent low-grade serous ovarian cancer: GOG-3097/ENGOT-OV81/NCRI/RAMP 301

P225 ENLIGHTED Phase 3 study: Efficacy and safety of Padeliporfin Vascular Targeted Photodynamic Therapy (VTP) for Treatment of Low-grade Upper Tract Urothelial Cancer (LG UTUC)

P225 ENLIGHTED Phase 3 study: Efficacy and safety of Padeliporfin Vascular Targeted Photodynamic Therapy (VTP) for Treatment of Low-grade Upper Tract Urothelial Cancer (LG UTUC)

Folate receptor positivity in low-grade serous ovarian cancer: Exploring new therapeutic possibilities

Folate receptor positivity in low-grade serous ovarian cancer: Exploring new therapeutic possibilities

Cause of death following conservative, non-surgical treatment for seasoned patients with early-stage, low-grade endometrial cancer

Cause of death following conservative, non-surgical treatment for seasoned patients with early-stage, low-grade endometrial cancer

Avutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A

Avutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A

Low-grade endometrial cancer histology at diagnosis does not improve survival in the TP53 molecular subtype regardless of stage: A large, retrospective cohort validated by the Cancer Genome Atlas dataset

Low-grade endometrial cancer histology at diagnosis does not improve survival in the TP53 molecular subtype regardless of stage: A large, retrospective cohort validated by the Cancer Genome Atlas dataset

Quality of life and survivorship in patients with low-grade ovarian cancer

ObjectiveHigh-grade (HGOC) and low-grade ovarian carcinoma (LGOC) are distinct malignancies with different biological features, treatment paradigms, and life expectancies. However, differences in quality of life (QOL), sleep, and depressive symptoms have not been examined by grade, and neither have inflammatory profiles associated with these symptoms. We aim to characterize QOL and biomarkers by OC grade. MethodsParticipants included patients with HGOC (N = 578) or LGOC (N = 85). Participants completed baseline assessments of psychosocial factors prior to primary surgery or neoadjuvant chemotherapy and contributed saliva for cortisol and blood for interleukin-6 (IL-6) quantification. Samples were collected intraoperatively to quantify tumor cortisol. General linear models were used to examine differences in biological and psychological variables by grade. ResultsAt baseline, patients with LGOC reported less depression (p = 0.018) and sleep disturbances (p = 0.014), but no significant difference in depressive mood (p = 0.11) or QOL (p = 0.51) compared to patients with HGOC, adjusting for age and disease stage. There were trends towards lower tumor cortisol levels (p = 0.078) in LGOC compared to HGOC. One-year post-diagnosis, we found a significant improvement in QOL and fatigue, and a decrease in vegetative depression and IL-6 levels irrespective of grade. ConclusionsWe present the first characterization of psychosocial experiences of patients with LGOC. Despite having a better disease prognosis, patients with LGOC were just as likely to have mood disturbances as those with HGOC. There was a trend towards differences in tumor cortisol by grade. Our findings highlight the need to address well-being in patients with both low- and high-grade ovarian malignancies.

Conservative, non-surgical treatment for young patients with early-stage, low-grade endometrial cancer: Population-level trends and oncologic outcomes

Conservative, non-surgical treatment for young patients with early-stage, low-grade endometrial cancer: Population-level trends and oncologic outcomes

A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer.

To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC). A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included. Patients were assigned 1:1:1, to receive intra-vesical chemo-hyperthermia (C-HT), mitomycin-C (MMC) or BCG therapy. There was no treatment crossover. Patients were followed up with check cystoscopy every 3 months for histopathological recurrence. The three arms were comparable in terms of age, gender, tumor size, number of tumors and clinical stage or grade of tumors. Mean tumor size was 2.58 (± 0.88) cm and the mean number of tumors resected was 2.04 (± 1.02) (Range 1-5). There was no significant difference between the various groups for tumor recurrence (χ2 = 1.96, p = 0.375) or time to recurrence (13.6 vs. 10.8 vs. 9.8 months, p = 0.844)though incidence of non-healing necrotic area was higher with C-HT (22.2% vs. 11.1% and 4.8%, χ2 = 6.093, p = 0.048). Median (IQR) follow up period was 26 (12-52) months. Treatment discontinuation or drug intolerance was significantly higher in BCG arm (p = 0.03). Intravesical C-HT with MMC, conventional MMC and BCG are equally effective and comparable alternatives for intravesical therapy in low-grade intermediate-risk NMIBC. Higher incidence of non-healing resection site with C-HT and higher local symptoms with BCG are a concern.

Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION).

To evaluate the efficacy and safety of UGN-102 chemoablation for the primary treatment of patients with recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer. ENVISION is an ongoing, multinational, single-arm, Phase 3 study in patients with a biopsy-proven recurrence of untreated low-grade intermediate-risk nonmuscle-invasive bladder cancer. Patients received 6 weekly intravesical instillations of UGN-102 (mitomycin; outpatient setting) and were evaluated at 3 months. Patients achieving complete response (CR) (negative cystoscopic examination, cytology, and for-cause biopsy) were surveilled regularly until recurrence, progression, or death. Patients who remain disease-free will be followed up to 5 years, and further results will be reported in the future. Of 240 patients enrolled, 228 (95%) received all 6 planned doses; 191 (79.6%; 95% CI: 73.9, 84.5) achieved CR at 3 months, with an 82.3% (95% CI: 75.9, 87.1) probability of response 12 months later. Median duration of response was not estimable over a median 13.9-month follow-up period. The most common adverse events (≥5.0% of patients) were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention; generally mild/moderate and resolved/resolving. Serious adverse events were observed in 29/240 (12.1%), 2 were treatment-related (urinary retention/urethral stenosis), both resolved. Primary chemoablation with UGN-102 in patients with recurrent low-grade-intermediate-risk-nonmuscle-invasive bladder cancer resulted in a 79.6% CR rate. Patients achieving a CR had an 82.3% likelihood of remaining disease-free 1 year later. The benefit-risk profile was favorable, supporting UGN-102 as a non-surgical alternative for transurethral resection of bladder tumors in this patient population. Limitations of this study included lack of tumor sizing after the diagnostic biopsy. ClinicalTrials.gov Identifier: NCT05243550.

The Diversity of Methylation Patterns in Serous Borderline Ovarian Tumors and Serous Ovarian Carcinomas.

Background: Changes in DNA methylation patterns are a pivotal mechanism of carcinogenesis. In some tumors, aberrant methylation precedes genetic changes, while gene expression may be more frequently modified due to methylation alterations than by mutations. Methods: Herein, 128 serous ovarian tumors were analyzed, including borderline ovarian tumors (BOTS) with (BOT.V600E) and without (BOT) the BRAF V600E mutation, low-grade (lg), and high-grade (hg) ovarian cancers (OvCa). The methylome of the samples was profiled with Infinium MethylationEPIC microarrays. Results: The biggest number of differentially methylated (DM) CpGs and regions (DMRs) was found between lgOvCa and hgOvCa. By contrast, the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups and, in relation to BOT, their genome was strongly downmethylated. Remarkably, the ten most significant DMRs, discriminating BOT from lgOvCa, encompassed the MHC region on chromosome 6. We also identified hundreds of DMRs, being of potential use as predictive biomarkers in BOTS and hgOvCa. DMRs with the best discriminative capabilities overlapped the following genes: BAIAP3, IL34, WNT10A, NEU1, SLC44A4, and HMOX1, TCN2, PES1, RP1-56J10.8, ABR, NCAM1, RP11-629G13.1, AC006372.4, NPTXR in BOTS and hgOvCa, respectively. Conclusions: The global genome-wide hypomethylation positively correlates with the increasing aggressiveness of ovarian tumors. We also assume that the immune system may play a pivotal role in the transition from BOTS to lgOvCa. Given that the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups, when methylome is considered, such tumors might be placed in-between BOT and OvCa.

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.

An Analysis of Genetic Polymorphisms in 76 Genes Related to the Development of Ovarian Tumors of Different Aggressiveness.

Borderline ovarian tumors (BOTS) are rare neoplasms of intermediate aggressiveness between cystadenomas and low-grade ovarian cancers (lgOvCa), which they share some molecular resemblances with. In contrast to the most frequent and well-described high-grade ovarian carcinomas (hgOvCa), the molecular background of BOTS and lgOvCa is less thoroughly characterized. Here, we aimed to analyze genetic variants in crucial tumor suppressors and oncogenes in BOTS (with or without the BRAF V600E mutation), lgOvCa, and hgOvCa in two gene panels using next-generation sequencing. Then, we verified the existence of selected polymorphisms by Sanger sequencing. Finally, Western blot analyses were carried out to check the impact of the selected polymorphisms on the expression of the corresponding proteins. Our study contributes to the molecular characterization of ovarian neoplasms, demonstrating divergent polymorphic patterns pointing to distinct signaling pathways engaged in their development. Certain mutations seem to play an important role in BOTS without the BRAF V600E variant (KRAS) and in lgOvCa (KRAS and NRAS), but not in hgOvCa. Additionally, based on multivariable regression analyses, potential biomarkers in BOTS (PARP1) and hgOvCa (FANCI, BRCA2, TSC2, FANCF) were identified. Noteworthy, for some of the analyzed genes, such as FANCI, FANCD2, and FANCI, FANCF, TSC2, the status of BRCA1/2 and TP53, respectively, turned out to be crucial. Our results shed new light on the similarities and differences in the polymorphic patterns between ovarian tumors of diverse aggressiveness. Furthermore, the biomarkers identified herein are of potential use as predictors of the prognosis and/or response to therapy.

Profiling mRNA and miRNA expression variations associated with cyclin-dependent kinase pathway in the low-grade luminal early breast cancer.

Luminal A and B subtypes of breast tumors have fluctuated in proliferation rates, which arise from cell cycle dysregulation in cancer. Besides, microRNAs can regulate various cell processes through integration with mRNA. miRNAs that target the cell cycle are significant because of their prediction capability of prognosis. The objective of this study is to discover the integration between miRNA-mRNA and miRNA-miRNA related to cyclin-dependent kinase. Thirty-four pairs of human primary breast cancer and tumor margin samples from luminal breast cancer patients were investigated to assess the expression levels of CCND1, E2F1, miR-124, miR-503, miR-449a, and miR-449b. Afterward, the expression levels of mRNAs and miRNAs were investigated by real-time PCR. Statistical analysis was conducted to compare the expression levels between breast cancer and corresponding normal tissues. The protein expressions of E2F1 and CCND1 were verified by western blotting. Further, the correlation between mRNAs and miRNAs was calculated. E2F1 was significantly increased in both luminal A and B patients, while CCND1 was upregulated only in luminal B. Significant differences in all miRNAs were detected in both luminal A and B biopsy specimens (p < 0.0001). The correlation analysis revealed a positive strong correlation between miR-124 and E2F1 in luminal A patient. Moreover, the correlation test confirmed the ability of miR-449a to increase the CCND1 gene in luminal B subtypes. Also, miRNA correlation exhibited the miRNA-miRNA interaction in luminal breast cancer. This study demonstrated the novel miRNA-mRNA and miRNA-miRNA interactions, providing new insights into the molecular integration in luminal A and B patients. The authors propose that this research could contribute to introducing valuable biomarkers for luminal cancerous cells.

Comparative Immunohistochemistry Study Of Expression Of E- Cadherin In Benign Prostatic Hyperplasia And Prostate Cancer

Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PC ) are the most common diseases in men, especially in older men than 50 years old, BPH is a non-cancerous enlargement of the prostate as a result of the increased number of smooth muscle cells. Tumors can be benign (not cancerous), or malignant (cancerous), prostate cancer is the abnormal and random growth of cells in the prostate gland to the extent that it loses its shape and function. this study involved 120 samples of tissues taken from men suffering from benign and malignant tumours with ages ranging between (40- 85) years. For detection of the expression of E-cadherin in BPH and PC using immunohistochemistry (IHC) method. The results obtained after microscopic examination showed that protein expression of E-cadherin was highly positive in BPH comparison with the expression of E-cadherin was weakly positive in low-grade cancer and negative in high-grade cancer (advanced prostate cancer).