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

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

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

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

BACKGROUND/AIMS: This study was conducted to identify risk factors that predict vulnerability to cancer therapy on the basis of the clinical, geriatric, and quality of life assessment before starting treatment in elderly patients. METHODS: Seventy-five patients aged 65 years and over with newly diagnosed stage IV solid cancer receiving chemotherapy were analyzed. Clinical and laboratory data were collected. The geriatric assessment was performed using the Korean versions of the Modified Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, and Geriatric Depression Scale. The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC-QLQ-C30) was also performed. RESULTS: Forty-one patients stopped cancer treatment during or after the end of first-line therapy and were classified as the treatment interruption group. By univariate analysis, treatment interruption was associated with metastases to ≥ 2 distant sites, lower albumin level, lower EORTC-QLQ-C30 physical and role functioning scores, and higher EORTC-QLQ-C30 fatigue and appetite loss symptom scores. By multivariate analysis, treatment interruption was significantly associated with low score for the EORTC-QLQ-C30 physical functioning scale (odds ratio [OR], 1.020; 95% confidence interval [CI], 1.002 to 1.039; p = 0.030), and ≥ 2 sites of distant metastases (OR, 2.965; 95% CI, 1.012 to 8.681; p = 0.047). CONCLUSIONS: The EORTC-QLQ-C30 physical functioning score and metastases to ≥ 2 organs, which indicate a poor physical functional status and metastatic high tumor burden, were significantly associated with interruption of first-line treatment in elderly patients with cancer.
Activities of Daily Living ; Aged* ; Appetite ; Depression ; Drug Therapy ; Fatigue ; Geriatric Assessment ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Quality of Life ; Risk Factors ; Tumor Burden

OBJECTIVES: We conducted a protocol-based cohort study to evaluate the outcomes of interval debulking surgery (IDS) followed by paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of advanced-stage ovarian cancer. METHODS: From October 2015 to May 2018, 65 patients with stages IIIC–IV ovarian cancer were treated according to the study protocol. HIPEC was performed with paclitaxel (175 mg/m2) for 90 minutes, only in cases of optimal cytoreduction. RESULTS: Of 65 patients, 40 (61.5%) patients underwent neoadjuvant chemotherapy (NAC), 34 (52.3%) patients had a high tumor burden with a Fagotti score ≥8 at diagnostic laparoscopy, and 6 (9.2%) had definite stage IV metastasis and/or poor performance status before NAC. Twenty-seven (41.5%) patients underwent IDS followed by HIPEC. The mean duration of IDS with HIPEC was 543.8 (range, 277.0–915.0) minutes. Grade III/IV perioperative complications occurred in 7.4% (n=2)/3.7% (n=1) of patients and no cases of mortality were reported within 30 days postoperatively. The median progression-free survival was 21.3 months, and the median overall survival was not reached for those who received HIPEC. CONCLUSIONS: According to our study protocol, IDS followed by paclitaxel-based HIPEC as a first-line treatment appears to be feasible and safe for the treatment of advanced-stage ovarian cancer. Further evaluations of this procedure are required to assess its survival benefits.
Cohort Studies ; Disease-Free Survival ; Drug Therapy* ; Humans ; Laparoscopy ; Mortality ; Neoplasm Metastasis ; Ovarian Neoplasms* ; Paclitaxel ; Pilot Projects* ; Tumor Burden

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. METHODS: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. RESULTS: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were independent predictors of PFS. ECOG PS 0–1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. CONCLUSION: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.
Adenocarcinoma* ; Biomarkers ; Disease-Free Survival ; Female ; Genes, erbB-1 ; Humans ; In Situ Hybridization ; Lung Neoplasms ; Lung* ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Silver ; Tumor Burden