31 research outputs found
BCG Induced Necrosis of the Entire Bladder Urothelium
AbstractInstillation therapy with attenuated tuberculosis bacteria (BCG) can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence
A Multi-Institutional Analysis of Prostate Cancer Patients With or Without 68Ga-PSMA PET/CT Prior to Salvage Radiotherapy of the Prostatic Fossa
Introduction: 68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only.
Material and Methods: This retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters.
Results: Median follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS †7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. â„0.5ng/ml; p<0.001) and sRT dose (<70 vs. â„70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884).
Conclusion: This analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best âdiagnostic windowâ for 68Ga-PSMA PET/CT
Detection of local recurrent prostate cancer after radical prostatectomy in terms of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal coil
Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial
Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population
Results from extended lymphadenectomies with [111In]PSMA-617 for intraoperative detection of PSMA-PET/CT-positive nodal metastatic prostate cancer
CITATION: Jilg, C. A., et al. 2020. Results from extended lymphadenectomies with [111In]PSMA-617 for intraoperative detection of PSMA-PET/CT-positive nodal metastatic prostate cancer. EJNMMI Research, 10:17, doi:10.1186/s13550-020-0598-2.The original publication is available at https://ejnmmires.springeropen.comPurpose: Identification of suspicious PSMA-PET/CT-positive lymph node (LN) metastases (LNM) from prostate
cancer (PCa) during lymphadenectomy (LA) is challenging. We evaluated an 111In-labelled PSMA ligand (DKFZ-617,
referred to as [111In]PSMA-617) as a Îł-emitting tracer for intraoperative Îł-probe application for resected tissue
samples in PCa patients. Forty-eight hours prior to LA, [111In]PSMA-617 was administered intravenously in 23
patients with suspected LNM on PSMA-PET/CT (n = 21 with biochemical relapse, n = 2 at primary therapy).
Resected tissue samples (LN, LNM and fibrofatty tissue) were measured ex situ by a Îł-probe expressed as counts
per second (CPSnorm). [111In]PSMA-617 tissue sample uptake was measured by a germanium detector for verification
and calculated as %IAlbm (percent injected activity per kilogram lean body mass at time of surgery). Based on a
clinical requirement for a specificity > 95%, thresholds for both ex situ measurements were chosen accordingly.
Correlation of the results from PET/CT, Îł-probe and germanium detector with histopathology was done.
Results: Eight hundred sixty-four LNs (197 LNM) were removed from 275 subregions in 23 patients, on average 8.6
± 14.9 LNM per patient. One hundred four of 275 tissue samples showed cancer. Median γ-probe and germanium
detector results were significantly different between tumour-affected (33.5 CPSnorm, 0.71 %IAlbm) and tumour-free
subregions (3.0 CPSnorm, 0.03 %IAlbm) (each p value 23) and
germanium detector cut-off (%IAlbm > 0.27), 64 and 74 true-positive and 158 true-negative samples for both
measurements were identified. Thirty-nine and 30 false-negative and 6 and 5 false-positive tissue samples were
identified by Îł-probe and germanium detector measurements.
Conclusion: [111In]PSMA-617 application for LA is feasible in terms of an intraoperative real-time measurement with
a Îł-probe for detection of tumour-affected tissue samples. Îł-probe results can be confirmed by precise germanium
detector measurements and were significantly different between tumour-affected and tumour-free samples.https://ejnmmires.springeropen.com/articles/10.1186/s13550-020-0598-2Publisher's versio
Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist - from mice to men
UNLABELLED
Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy.
METHODS
Biodistribution, dosimetry and tumor uptake of the GRPr antagonist â¶âŽCu-CB-TE2A-AR06 [(â¶âŽCu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEGâ-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNHâ] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7).
RESULTS
No adverse events were observed after injection of â¶âŽCu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time.
CONCLUSION
â¶âŽCu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating â¶âŽCu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary
Performance of 111In-labelled PSMA ligand in patients with nodal metastatic prostate cancer: correlation between tracer uptake and histopathology from lymphadenectomy
PURPOSE:
Intraoperative identification of lymph node (LN) metastases (LNM) detected on preoperative PSMA PET/CT may be facilitated by PSMA radioguided surgery with the use of a gamma probe. We evaluated the uptake of 111In-labelled PSMA ligand DKFZ-617 (referred to as 111In-PSMA-617) in unaffected LN and LNM at the level of single LN.
METHODS:
Six patients with prostate cancer (PCa) with suspicion of LNM on preoperative PSMA PET/CT underwent 111In-PSMA-617-guided lymphadenectomy (LA; four salvage LA and two primary LA). 111In-PSMA-617 (109â±â5 MBq). was injected Intravenously 48 h prior to surgery Template LAs were performed in small subregions: common, external, obturator and internal iliac vessels, and presacral and retroperitoneal subregions (n =â4). Samples from each subregion were isolated aiming at the level of single LN. Uptake was measured ex situ using a germanium detector. Receiver operating characteristic (ROC) analysis was performed based on 111In-PSMA-617 uptake expressed as standardized uptake values normalized to lean body mass (SUL).
RESULTS:
Overall 310 LN (mean 52â±â19.7) were removed from 74 subregions (mean 12â±â3.7). Of the 310 LN, 35 turned out to be LNM on histopathology. Separation of the samples from all subregions resulted in 318 single specimens: 182 PCa-negative LN samples with 275 LN, 35 single LNM samples, 3 non-nodal PCa tissue samples and 98 fibrofatty tissue samples. The median SULs of nonaffected LN (0.16) and affected LN (13.2) were significantly different (p <â0.0001). Based on 38 tumour-containing and 182 tumour-free specimens, ROC analysis revealed an area under the curve of 0.976 (95% CI 0.95-1.00, p <â0.0001). Using a SUL cut-off value of 1.136, sensitivity, specificity, positive predictive value, negative predictive value and accuracy in discriminating affected from nonaffected LN were 92.1% (35/38), 98.9% (180/182), 94.6% (35/37), 98.4% (180/183) and 97.7% (215/220), respectively.
CONCLUSION:
Ex situ analysis at the level of single LN showed that 111In-PSMA-617 had excellent ability to discriminate between affected and nonaffected LN in our patients with PCa. This tracer characteristic is a prerequisite for in vivo real-time measurements during surgery
Stereotactic Body Radiotherapy for Renal Cell Carcinoma in Patients with Von HippelâLindau DiseaseâResults of a Prospective Trial
Von HippelâLindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade â„ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m2, which decreased to 76.6 ± 8.0 mL/min/1.73 m2 after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts
99mTc-labelled PSMA ligand for radio-guided surgery in nodal metastatic prostate cancer: proof of principle
Purpose!#!Intraoperative identification of prostate cancer (PCa) lymph node (LN) metastases (LNM) detected by preoperative PSMA PET/CT may be facilitated by PSMA radio-guided surgery (RGS) with use of a Îł-probe. Earlier we demonstrated excellent performance of the !##!Methods!#!Six patients with PCa with the suspicion of LNM on preoperative PSMA-PET/CT underwent [!##!Results!#!Separation of the tissue samples from 73 subregions resulted in 498 single samples. After final histopathology 356 LN, 160 LNM und 11 non-nodal PCa samples were identified. Median SUL of tumor-free samples (0.26) and samples with cancer (3.5) was significantly different (pâ&lt;â0.0001). ROC analysis revealed an area under the curve (AUC) of 0.917 (95% CI 0.89-0.95). Using a SUL cutoff of 1.1, sensitivity, specificity, positive predictive value, and negative predictive values were 76.6%, 94.4%, 89.4% and 86.9%.!##!Conclusion!#!Ex situ analysis of
Diagnostic Accuracy of Robot-Guided, Software Based Transperineal MRI/TRUS Fusion Biopsy of the Prostate in a High Risk Population of Previously Biopsy Negative Men
Objective. In this study, we compared prostate cancer detection rates between MRI-TRUS fusion targeted and systematic biopsies using a robot-guided, software based transperineal approach. Methods and Patients. 52 patients received a MRIT/TRUS fusion followed by a systematic volume adapted biopsy using the same robot-guided transperineal approach. The primary outcome was the detection rate of clinically significant disease (Gleason grade â„ 4). Secondary outcomes were detection rate of all cancers, sampling efficiency and utility, and serious adverse event rate. Patients received no antibiotic prophylaxis. Results. From 52 patients, 519 targeted biopsies from 135 lesions and 1561 random biopsies were generated (total = 2080). Overall detection rate of clinically significant PCa was 44.2% (23/52) and 50.0% (26/52) for target and random biopsy, respectively. Sampling efficiency as the median number of cores needed to detect clinically significant prostate cancer was 9 for target (IQR: 6-14.0) and 32 (IQR: 24-32) for random biopsy. The utility as the number of additionally detected clinically significant PCa cases by either strategy was 0% (0/52) for target and 3.9% (2/52) for random biopsy. Conclusions. MRI/TRUS fusion based target biopsy did not show an advantage in the overall detection rate of clinically significant prostate cancer