An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer); that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes; (2) association between endogenous testosterone density and the tumor load; and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature's results.
Humans ; Male ; Prostatic Neoplasms/metabolism* ; Testosterone/metabolism* ; Risk Factors ; Neoplasm Grading ; Tumor Burden

Objective: Solid and micropapillary pattern are highly invasive histologic subtypes in lung adenocarcinoma and are associated with poor prognosis while the biopsy sample is not enough for the accurate histological diagnosis. This study aims to assess the correlation and predictive efficacy between metabolic parameters in (18)F-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET-CT), including the maximum SUV (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and solid and micropapillary histological subtypes in lung adenocarcinoma. Methods: A total of 145 resected lung adenocarcinomas were included. The clinical data and preoperative (18)F-FDG PET-CT data were retrospectively analyzed. Mann-Whitney U test was used for the comparison of the metabolic parameters between solid and micropapillary subtype group and other subtypes group. Receiver operating characteristic (ROC) curve and areas under curve (AUC) were used for evaluating the prediction efficacy of metabolic parameters for solid or micropapillary patterns. Univariate and multivariate analyses were conducted to determine the prediction factors of the presence of solid or micropapillary subtypes. Results: Median SUV(max) and TLG in solid and papillary predominant subtypes group (15.07 and 34.98, respectively) were significantly higher than those in other subtypes predominant group (6.03 and 10.16, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for prediction of solid and micropapillary predominant subtypes [AUC=0.811(95% CI: 0.715~0.907) and 0.725(95% CI: 0.610~0.840), P<0.05]. Median SUV(max) and TLG in lung adenocarcinoma with the solid or micropapillary patterns (11.58 and 22.81, respectively) were significantly higher than those in tumors without solid and micropapillary patterns (4.27 and 6.33, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for predicting the presence of solid or micropapillary patterns [AUC=0.757(95% CI: 0.679~0.834) and 0.681(95% CI: 0.595~0.768), P<0.005]. Multivariate logistic analysis showed that the clinical stage (Stage Ⅲ-Ⅳ), SUV(max) ≥10.27 and TLG≥7.12 were the independent predictive factors of the presence of solid or micropapillary patterns (P<0.05). Conclusions: Preoperative SUV(max) and TLG of lung adenocarcinoma have good prediction efficacy for the presence of solid or micropapillary patterns, especially for the solid and micropapillary predominant subtypes and are independent factors of the presence of solid or micropapillary patterns.
Adenocarcinoma of Lung/diagnostic imaging* ; Fluorodeoxyglucose F18/metabolism* ; Humans ; Lung Neoplasms/pathology* ; Multimodal Imaging/methods* ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography/methods* ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tomography, X-Ray Computed/methods* ; Tumor Burden

OBJECTIVE: To investigate the value of ⁶⁸Ga-labeled prostate specific membrane antigen (PSMA) PET/CT for assessing tumor load in primary lesions for risk stratification and predicting metastasis of newly diagnosed prostate cancer (PCa). METHODS: We retrospectively analyzed the data of 36 patients (mean age 71.3 ± 8.6 years, range 56 to 89 years) with newly diagnosed PCa undergoing ⁶⁸Ga-PSMA-I&T PET/CT from June 2018 to July 2019. SUVmax and SUVmean of the primary lesions were measured, and the primary PSMA tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were automatically measured and calculated in all the patients. The correlations of primary SUVmax, PSMA-TV, and TL-PSMA with PSA and Gleason score (GS) were analyzed, and SUVmax, PSMA-TV and TL-PSMA of the primary lesions were compared among different PCa subgroups. RESULTS: SUVmax, PSMA-TV and TL-PSMA of the primary lesions were all correlated with PSA and GS (P < 0.05). PCa subgroup analysis showed that SUVmax, PSMA-TV and TL-PSMA were all significantly higher in patients with PSA >20 ng/mL than in those with PSA ≤20 ng/mL (P < 0.001), and were higher in patients with a GS ≥8 than in those with a GS ≤7 (P < 0.001). PSMA-TV and TL-PSMA were significantly higher in patients with tumor metastasis than in those without metastasis (P < 0.001), while SUVmax did not differ significantly with tumor metastasis. SUVmax (P=0.002), PSMA-TV (P < 0.001), and TL-PSMA (P < 0.001) were all significantly higher in high-risk group than in low-to moderate-risk group. CONCLUSION PSMA-TV and TL-PSMA of ⁶⁸Ga-PSMA-I&T PET/CT have potential value in predicting risk stratification and metastasis of newly diagnosed PCa.
Aged ; Aged, 80 and over ; Edetic Acid ; Gallium Isotopes ; Gallium Radioisotopes ; Humans ; Male ; Middle Aged ; Oligopeptides ; Positron Emission Tomography Computed Tomography ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology* ; Retrospective Studies ; Tumor Burden

Background: PSMA-targeted radiopharmaceuticals have been widely studied for their theragnostic role in prostate cancer and were introduced in the Philippines in 2018. The optimal administered activity of 177Lu-PSMA for targeted endoradiotherapy has not yet been established and is thought to be influenced by several factors, including tumor burden. This study investigates the effect of tumor burden on the normal tissue PSMA uptake among Filipino patients with prostate cancer using its diagnostic counterpart, 68Ga-PSMA I&T Methods: One hundred four patients imaged with 68Ga-PSMA I&T PET/CT in our institution from January 2018 to May 2020 were included. Patients were visually classified into low, medium, and high tumor burden groups. Maximum and mean standardized uptake values (SUVmax and SUVmean) of the lacrimal glands, parotid glands, submandibular glands, kidneys, liver, spleen, and bone were measured and compared among tumor burden groups. Results and Conclusions 68Ga-PSMA I&T uptake in the kidneys, the salivary glands, and the liver, were significantly reduced by approximately 25-50% in patients with high tumor burden. This finding supports the hypothesis that patients with higher tumor load can tolerate higher activity doses of 177Lu-PSMA for endoradiotherapy before developing significant damage to the critical organs. This may serve as a guide towards optimizing and personalizing 177Lu-PSMA I&T administered activity dose for radionuclide therapy
Positron-Emission Tomography ; Prostatic Neoplasms ; Tumor Burden

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*

tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma.METHODS: We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients.RESULTS: CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 cm³ and 64.8 cm³, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis).CONCLUSION: Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.]]>
Adenocarcinoma ; Humans ; Linear Models ; Lung Neoplasms ; Lung ; Methods ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis ; Propensity Score ; Tumor Burden

OBJECTIVE: To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from ¹⁸F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics. METHODS: Data of 84 lung adenocarcinoma patients pre-treated, who underwent ¹⁸F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve. RESULTS: The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm³), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis. CONCLUSION High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.
Adenocarcinoma of Lung/genetics* ; Anaplastic Lymphoma Kinase/genetics* ; ErbB Receptors/genetics* ; Fluorodeoxyglucose F18 ; Genes, erbB-1 ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Positron Emission Tomography Computed Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tumor Burden

OBJECTIVES: In our institutional experience, involved-field radiation therapy (IFRT) yields favorable outcomes in patients with recurrent epithelial ovarian cancer (EOC). This retrospective study aimed to investigate the clinical benefits of IFRT in this patient population. METHODS: Among patients treated with IFRT for recurrent EOC between 2010 and 2017, 61 patients with 90 treatments were included. IFRT encompassed all treatable lesions identified via imaging studies with 10–15-mm margins. Prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). RESULTS: Patients were followed up for a median of 19.0 (Interquartile range, 8.6–34.9) months after IFRT. The 2-year in-field control, progression-free survival, and overall survival (OS) rates were 42.7%, 24.2%, and 78.9%, respectively. Fifty-three IFRT sessions (58.9%) were followed by systemic chemotherapy, and the median chemotherapy-free interval (CFI) was 10.5 (95% confidence interval=7.3–13.7) months. A higher carbohydrate antigen-125 (CA-125) level correlated with a worse 2-year OS (69.2% vs. 91.0%; p=0.001) and shorter median CFI (4.7 vs. 11.9 months; p<0.001). Twenty-eight (31.1%) of 90 treatments yielded a long-term CFI >12 months. For patients with a normal CA-125 level and/or platinum-sensitive tumor, IFRT prolonged CFI regardless of pre-existing carcinomatosis, gross tumor volume, and number of treatment sites. CONCLUSION: Our early experience demonstrates the safety and feasibility of IFRT as an effective salvage therapy and enables a “chemotherapy holiday” in selected recurrent EOC settings. The CA-125 value before IFRT (within normal range) and/or platinum sensitivity could be used as selection criteria for IFRT.
CA-125 Antigen ; Carcinoma ; Disease-Free Survival ; Drug Therapy ; Humans ; Ovarian Neoplasms ; Patient Selection ; Platinum ; Retrospective Studies ; Salvage Therapy ; Tumor Burden

OBJECTIVE: To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), measured by preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), in risk stratification of patients with endometrial carcinoma (EC). METHODS: The patients with pathological diagnosis of EC who underwent preoperative ¹⁸F-FDG PET/CT imaging were retrospectively selected for analysis of the prognostic values of PET parameters in risk classification and lymph node metastases (LNMs). Receiver-operating-characteristic analysis was used to analyze the correlation of PET parameters cutoff values with deep myometrial invasion (MI), lymphovascular space involvement and LNM for prognostic values in risk stratification. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of LNM are 83.3%, 99.7%, 90.9%, 99.5% and 99.2%, respectively. The MTV and TLG of primary lesion of EC in the patients with LNM are notably higher than those in patients without LNM, p<0.010. The MTV and TLG of the EC primary lesions in high-risk patients are significantly higher than those in low-risk patients (p<0.010), but the maximum standardized uptake value (SUVmax) is not. The MTV and TLG of primary lesions were superior to SUVmax for predicting of deep MI, LNM and high-risk of EC (p<0.005). CONCLUSION: MTV and TLG of primary lesions are more valuable in predicting risk stratification of EC patients. Preoperative ¹⁸F-FDG PET/CT imaging is useful in predicting the LNM of EC and may help guide pelvic lymphadenectomy to avoid unnecessary pelvic lymphadenectomy in EC patients with low-risk stratification.
Classification ; Diagnosis ; Electrons ; Endometrial Neoplasms ; Female ; Glycolysis ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Metabolism ; Neoplasm Metastasis ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; Risk Assessment ; Sensitivity and Specificity ; Tumor Burden

BACKGROUND: Recently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors. METHODS: Fifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days. RESULTS: The mean duration of clinical follow-up was 12 months (range, 4–24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images. CONCLUSION: Daily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.
Brain Neoplasms ; Brain ; Cohort Studies ; Follow-Up Studies ; Humans ; Immobilization ; Masks ; Necrosis ; Neoplasm Metastasis ; Prospective Studies ; Radiosurgery ; Survival Rate ; Tumor Burden