Abstract Background Despite adjuvant intravesical therapy, recurrences in non–muscle-invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of ...chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data. Objective To compare CHT using mitomycin C (MMC) with bacillus Calmette-Guérin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC. Design, setting, and participants Between 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1-yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov ( NCT00384891 ). Outcome measurements and statistical analysis The primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients ( n = 147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided. Results and limitations The 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group ( p = 0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group ( p = 0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias. Conclusions CHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC. Patient summary Recurrences in non–muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guérin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy.
To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer.
Between May ...2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence P, 4 patients reirradiated for anastomosis recurrence A, 16 patients treated for single lymph node recurrence LN, and 3 patients treated for single metastasis M). In all but 4 patients, (11)Ccholine positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months).
The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease.
CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation is warranted to identify the patients who benefit most from this treatment modality. The optimal combination with androgen deprivation should also be defined.
Prostate cancer (PCa) is the most common worldwide diagnosed malignancy in male population. The diagnosis, the identification of aggressive disease, and the post-treatment follow-up needs a more ...comprehensive and holistic approach. Radiomics is the extraction and interpretation of images phenotypes in a quantitative manner. Radiomics may give an advantage through advancements in imaging modalities and through the potential power of artificial intelligence techniques by translating those features into clinical outcome prediction. This article gives an overview on the current evidence of methodology and reviews the available literature on radiomics in PCa patients, highlighting its potential for personalized treatment and future applications.
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Although both docetaxel and androgen-receptor-axis-targeted (ARAT) agents have yielded survival improvements in combination with androgen deprivation therapy (ADT) compared to ADT ...alone in metastatic castration-sensitive prostate cancer (mCSPC) patients, the optimal therapeutic choice remains to be established. We analyzed estimates of the hazard ratios for death (OS-HRs) in patients treated in the first-line setting enrolled in the GETUG-AFU15, CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN trials. Overall, men with mCSPC receiving ADT with vs. without either an ARAT agent or docetaxel as first-line systemic therapy showed a pooled OS-HR of 0.69 (95 % CI: 0.61−0.78), with significant heterogeneity (p = 0.045, I2 = 52.5 %). Network meta-analysis showed an OS-HR in patients receiving an ARAT agent vs. docetaxel of 0.78 (95 %CI: 0.67−0.91). In conclusion, the evidence analysed indicates that an ARAT agent may provide improved OS outcomes compared to docetaxel. Prospective randomized trials are warranted.
Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC ...and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase(SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.
Radiomics and artificial intelligence (AI) may increase the differentiation of benign from malignant kidney lesions, differentiation of angiomyolipoma (AML) from renal cell carcinoma (RCC), ...differentiation of oncocytoma from RCC, differentiation of different subtypes of RCC, to predict Fuhrman grade, to predict gene mutation through molecular biomarkers and to predict treatment response in metastatic RCC undergoing immunotherapy. Neural networks analyze imaging data. Statistical, geometrical, textural features derived are giving quantitative data of contour, internal heterogeneity and gray zone features of lesions. A comprehensive literature review was performed, until July 2022. Studies investigating the diagnostic value of radiomics in differentiation of renal lesions, grade prediction, gene alterations, molecular biomarkers and ongoing clinical trials have been analyzed. The application of AI and radiomics could lead to improved sensitivity, specificity, accuracy in detecting and differentiating between renal lesions. Standardization of scanner protocols will improve preoperative differentiation between benign, low-risk cancers and clinically significant renal cancers and holds the premises to enhance the diagnostic ability of imaging tools to characterize renal lesions.
Objective: Accurate visual classification of bladder tissue during Trans-Urethral Resection of Bladder Tumor (TURBT) procedures is essential to improve early cancer diagnosis and treatment. During ...TURBT interventions, White Light Imaging (WLI) and Narrow Band Imaging (NBI) techniques are used for lesion detection. Each imaging technique provides diverse visual information that allows clinicians to identify and classify cancerous lesions. Computer vision methods that use both imaging techniques could improve endoscopic diagnosis. We address the challenge of tissue classification when annotations are available only in one domain, in our case WLI, and the endoscopic images correspond to an unpaired dataset, i.e. there is no exact equivalent for every image in both NBI and WLI domains. Method: We propose a semi-surprised Generative Adversarial Network (GAN)-based method composed of three main components: a teacher network trained on the labeled WLI data; a cycle-consistency GAN to perform unpaired image-to-image translation, and a multi-input student network. To ensure the quality of the synthetic images generated by the proposed GAN we perform a detailed quantitative, and qualitative analysis with the help of specialists. Conclusion: The overall average classification accuracy, precision, and recall obtained with the proposed method for tissue classification are 0.90, 0.88, and 0.89 respectively, while the same metrics obtained in the unlabeled domain (NBI) are 0.92, 0.64, and 0.94 respectively. The quality of the generated images is reliable enough to deceive specialists. Significance: This study shows the potential of using semi-supervised GAN-based bladder tissue classification when annotations are limited in multi-domain data. The dataset is available at https://zenodo.org/record/7741476#.ZBQUK7TMJ6k
Objectives
Radiomic involves testing the associations of a large number of quantitative imaging features with clinical characteristics. Our aim was to extract a radiomic signature from axial ...T2-weighted (T2-W) magnetic resonance imaging (MRI) of the whole prostate able to predict oncological and radiological scores in prostate cancer (PCa).
Methods
This study included 65 patients with localized PCa treated with radiotherapy (RT) between 2014 and 2018. For each patient, the T2-W MRI images were normalized with the histogram intensity scale standardization method. Features were extracted with the IBEX software. The association of each radiomic feature with risk class, T-stage, Gleason score (GS), extracapsular extension (ECE) score, and Prostate Imaging Reporting and Data System (PI-RADS v2) score was assessed by univariate and multivariate analysis.
Results
Forty-nine out of 65 patients were eligible. Among the 1702 features extracted, 3 to 6 features with the highest predictive power were selected for each outcome. This analysis showed that texture features were the most predictive for GS, PI-RADS v2 score, and risk class; intensity features were highly associated with T-stage, ECE score, and risk class, with areas under the receiver operating characteristic curve (ROC AUC) ranging from 0.74 to 0.94.
Conclusions
MRI-based radiomics is a promising tool for prediction of PCa characteristics. Although a significant association was found between the selected features and all the mentioned clinical/radiological scores, further validations on larger cohorts are needed before these findings can be applied in the clinical practice.
Key Points
• A radiomic model was used to classify PCa aggressiveness.
• Radiomic analysis was performed on T2-W magnetic resonance images of the whole prostate gland.
• The most predictive features belong to the texture (57%) and intensity (43%) domains.
Objectives
To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to ...compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low‐risk classification, and (iv) EAU low‐risk or low‐volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification.
Patients and Methods
We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa csPCa) at RP, defined as: ISUP GG ≥3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low‐risk, and EAU low‐risk or low‐volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate‐specific antigen density (PSA‐D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging‐Reporting and Data System (PI‐RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI‐RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used.
Results
Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low‐risk, EAU low‐risk or low‐volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low‐risk, EAU low‐risk or low‐volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA‐D, ISUP GG, PI‐RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS‐eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: −14.3%), JH (Δ: −5.9%), EAU low‐risk (Δ: −17.2%), and EAU low‐risk or low‐volume ISUP GG2 classifications (Δ: −18.0%).
Conclusion
The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low‐risk, and EAU low‐risk or low‐volume ISUP GG2 classifications.
Abstract Purpose To evaluate the PSA response, local control, progression free survival (PFS) and toxicity of stereotactic body radiotherapy (SBRT) for nodal (LN) oligorecurrent prostate cancer. ...Material and Methods Between 05/2012 and 10/2015, 124 lesions were treated in 94 patients with a median dose of 24Gy/3 fractions. 70 patients were treated for a single lesion, 25 for >1 lesion. In 34 patients androgen deprivation (AD) was added to SBRT. We evaluated biochemical response with PSA dosage every three months after SBRT: a three months’ PSA decreased pre-SBRT PSA of more than 10% identified responder patient. In case of PSA increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6-9 months after SBRT. Results Median follow-up was 18.5 months. In 13 patients (14%) grade 1-2 toxicity were reported without any grade 3-4. Biochemical response, stabilization and progression were observed in 64 (68%), 10 (11%) and 20 (21%) out of 94 evaluable patients. Clinical progression was observed in 31 (33%) patients after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). 2-year local control and PFS rates were 84% and 30%, respectively. Age>75years correlated with better biochemical response rate. Age>75years, concomitant AD administered up to 12 months and pelvic LN involvement correlated with longer PFS. Conclusions SBRT is safe and offers good in-field control. At two years after SBRT, 1 out of 3 patients is progression-free. Further investigation is warranted to identify patients that benefit most from SBRT and to define the optimal combination with AD.
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