PURPOSE PROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings. PATIENTS AND METHODS Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events (AWE)—namely, radiographic progression, pain progression, chemotherapy initiation, or death—at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned. RESULTS At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89; 95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients. CONCLUSION Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.
Ga-PSMA PET/CT and F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.
The expression of carbohydrate core-structures on O-linked glycoproteins was examined in fetal (n = 6), infantile (n = 2), normal adult (n = 15), and malignant (n = 22) colorectal tissue by means of monoclonal antibodies (MAbs) specific for Tn (GalNAc alpha 1-O-R), sialosyl-Tn (NeuAc alpha 2-6GalNAc alpha 1-O-R), and T (Gal beta 1-3GalNAc alpha 1-O-R) antigens. Immunolabelling of solubilized malignant tissue, separated by SDS-PAGE, showed expression of Tn and sialosyl-Tn antigens on 3 molecules of similar mw (230, 210, and 170 kDa), whereas no T antigens could be detected. Immunohistochemical techniques showed that fetal colon mucosa expressed Tn antigens but no sialosyl-Tn antigens. Infantile colon mucosa, however, expressed Tn as well as sialosyl-Tn antigens, and normal adult colon mucosa cells expressed no Tn antigens but sialosyl-Tn in 2 out of 6 biopsies from cecum, which indicates occurrence post partum of alpha-6-NeuAc-transferase. Endothelium in normal adult mucosa showed expression of both Tn and sialosyl-Tn antigens; 82% of carcinoma tissue sections expressed Tn antigens, and 73% expressed sialosyl-Tn antigens in mucin or cytoplasm, or on luminal cell membranes. T antigens could be detected neither in normal mucosa cells at any stage of development, nor in carcinomas. The possibility exists that this could be due to masking of T antigen. Mucin-type blood-group A antigens which contain an internal T-disaccharide were demonstrated in 4 out of 4 A1 tumors by means of MAb HH5. However, urea-containing SDS-PAGE analysis demonstrated an HH5 binding to molecules different from those binding anti-Tn. In remote morphologically normal and abnormal crypts in colons from carcinoma patients, both Tn and sialosyl-Tn antigens were expressed in secreted mucin in 40% of the cases. The data indicate an expression of O-linked Tn and sialosyl-Tn core structures in fetal and infantile colon and in colorectal carcinomas.
Purpose: To automatically assess the aggressiveness of prostate cancer (PCa) lesions using zonal-specific image features extracted from diffusion weighted imaging (DWI) and T2W MRI. Methods: Region of interest was extracted from DWI (peripheral zone) and T2W MRI (transitional zone and anterior fibromuscular stroma) around the center of 112 PCa lesions from 99 patients. Image histogram and texture features, 38 in total, were used together with a k-nearest neighbor classifier to classify lesions into their respective prognostic Grade Group (GG) (proposed by the International Society of Urological Pathology 2014 consensus conference). A semi-exhaustive feature search was performed (1-6 features in each feature set) and validated using threefold stratified cross validation in a one-versus-rest classification setup. Results: Classifying PCa lesions into GGs resulted in AUC of 0.87, 0.88, 0.96, 0.98, and 0.91 for GG1, GG2, GG1 + 2, GG3, and GG4 + 5 for the peripheral zone, respectively. The results for transitional zone and anterior fibromuscular stroma were AUC of 0.85, 0.89, 0.83, 0.94, and 0.86 for GG1, GG2, GG1 + 2, GG3, and GG4 + 5, respectively. Conclusion: This study showed promising results with reasonable AUC values for classification of all GG indicating that zonal-specific imaging features from DWI and T2W MRI can be used to differentiate between PCa lesions of various aggressiveness.
Background and purpose. Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefi t knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Material and methods. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n ϭ 72) had standard CT target delineation and gold markers as fi ducials. Another group of patients (n ϭ 73) had MRI target delineation and a nickel-titanium stent as fi ducial. Results. At 36 months no difference in overall survival (92% in both groups, p ϭ 0.29) or in PSA-relapse free survival was found between the groups (MRI ϭ 89% and CT ϭ 94%, p ϭ 0.67). A signifi cantly smaller CTV was found in the MRI group (p ϭ 0.02). Urinary retention and frequency were signifi cantly reduced in the MRI group (p ϭ 0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. Conclusion. MRI delineation leads to a signifi cantly reduced CTV. Signifi cantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not fi nd signifi cant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.
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