Ulf W. Tunn

3-D conformal HDR brachytherapy as monotherapy for localized prostate cancer. A pilot study.

Purpose:Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning.Patients and Methods:Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) ≤ 10 ng/ml, Gleason score ≤ 7 and clinical stage ≤ T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT® was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (Dref) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D90, D10 urethra, and D10 rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales.Results:Median D90 was 106% of Dref (range: 93–115%), median D10 urethra 159% of Dref (range: 127–192%), and median D10 rectum 55% of Dref (range: 35–68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred.Conclusion:3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.Ziel:Pilotstudie zur Evaluation der Praktikabilität, Akuttoxizität und konformalen Qualität der konformalen dreidimensionalen (3-D) High-Dose-Rate-(HDR-)Brachytherapie als Monotherapie beim lokal begrenzten Prostatakarzinom unter Einsatz intraoperativer Real-Time-Planung.Patienten und Methodik:Zwischen 05/2002 und 05/2003 wurden 52 Patienten mit einem Prostatakarzinom, PSA-Wert (prostataspezifisches Antigen) ≤ 10 ng/ml, Gleason-Score ≤ 7 und klinischem Stadium ≤ T2a behandelt. Der mediane PSA-Wert betrug 6,4 ng/ml und der mediane Gleason-Score 5. 24/52 Patienten waren im Stadium T1c und 28/52 im Stadium T2a. Für die TRUS-gesteuerte (transrektaler Ultraschall) transperineale Implantation von flexiblen Plastiknadeln in die Prostata kam das Real-Time- HDR-Planungssystem SWIFT® zum Einsatz. Nach der Implantation wurde ein CT-basiertes 3-D-Postplanning durchgeführt. Alle Patienten erhielten ein Implantat für vier Fraktionen HDR-Brachytherapie in 48 h mit einer Referenzdosis (Dref) von 9,5 Gy bis zu einer Gesamtdosis von 38,0 Gy. Dosis-Volumen-Histogramme (DVH) wurden analysiert, um die konformale Qualität der Implantate mit Berechnung der D90, D10 Urethra und D10 Rektum zu bestimmen. Akuttoxizitäten wurden unter Verwendung der CTC-Skalen (Common Toxicity Criteria) evaluiert.Ergebnisse:Die mediane D90 betrug 106% von Dref (Range: 93–115%), die mediane D10 Urethra 159% von Dref (Range: 127–192%), die mediane D10 Rektum 55% von Dref (Range: 35–68%). Die mediane Nachbeobachtungszeit beträgt gegenwärtig 8 Monate. Bei 2/52 Patienten wurden akute urogenitale Grad-3-Toxizitäten beobachtet. Gastrointestinale Toxizitäten > Grad 1 traten nicht auf.Schlussfolgerung:Die konformale 3-D-HDR-Brachytherapie als Monotherapie unter Einsatz intraoperativer Real-Time-Planung erweist sich als praktikable und hochkonformale Behandlung mit minimalen akuten Nebenwirkungen beim lokal begrenzten Prostatakarzinom. Eine längere Nachbeobachtungszeit ist zur Beurteilung von Spättoxizitäten und biochemischer Kontrolle notwendig.

High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

PURPOSE To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. METHODS AND MATERIALS Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. RESULTS The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. CONCLUSION Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

Purpose:Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning.Patients and Methods:Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) ≤ 10 ng/ml, Gleason score ≤ 7 and clinical stage ≤ T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT® was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (Dref) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D90, D10 urethra, and D10 rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales.Results:Median D90 was 106% of Dref (range: 93–115%), median D10 urethra 159% of Dref (range: 127–192%), and median D10 rectum 55% of Dref (range: 35–68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred.Conclusion:3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.Ziel:Pilotstudie zur Evaluation der Praktikabilität, Akuttoxizität und konformalen Qualität der konformalen dreidimensionalen (3-D) High-Dose-Rate-(HDR-)Brachytherapie als Monotherapie beim lokal begrenzten Prostatakarzinom unter Einsatz intraoperativer Real-Time-Planung.Patienten und Methodik:Zwischen 05/2002 und 05/2003 wurden 52 Patienten mit einem Prostatakarzinom, PSA-Wert (prostataspezifisches Antigen) ≤ 10 ng/ml, Gleason-Score ≤ 7 und klinischem Stadium ≤ T2a behandelt. Der mediane PSA-Wert betrug 6,4 ng/ml und der mediane Gleason-Score 5. 24/52 Patienten waren im Stadium T1c und 28/52 im Stadium T2a. Für die TRUS-gesteuerte (transrektaler Ultraschall) transperineale Implantation von flexiblen Plastiknadeln in die Prostata kam das Real-Time- HDR-Planungssystem SWIFT® zum Einsatz. Nach der Implantation wurde ein CT-basiertes 3-D-Postplanning durchgeführt. Alle Patienten erhielten ein Implantat für vier Fraktionen HDR-Brachytherapie in 48 h mit einer Referenzdosis (Dref) von 9,5 Gy bis zu einer Gesamtdosis von 38,0 Gy. Dosis-Volumen-Histogramme (DVH) wurden analysiert, um die konformale Qualität der Implantate mit Berechnung der D90, D10 Urethra und D10 Rektum zu bestimmen. Akuttoxizitäten wurden unter Verwendung der CTC-Skalen (Common Toxicity Criteria) evaluiert.Ergebnisse:Die mediane D90 betrug 106% von Dref (Range: 93–115%), die mediane D10 Urethra 159% von Dref (Range: 127–192%), die mediane D10 Rektum 55% von Dref (Range: 35–68%). Die mediane Nachbeobachtungszeit beträgt gegenwärtig 8 Monate. Bei 2/52 Patienten wurden akute urogenitale Grad-3-Toxizitäten beobachtet. Gastrointestinale Toxizitäten > Grad 1 traten nicht auf.Schlussfolgerung:Die konformale 3-D-HDR-Brachytherapie als Monotherapie unter Einsatz intraoperativer Real-Time-Planung erweist sich als praktikable und hochkonformale Behandlung mit minimalen akuten Nebenwirkungen beim lokal begrenzten Prostatakarzinom. Eine längere Nachbeobachtungszeit ist zur Beurteilung von Spättoxizitäten und biochemischer Kontrolle notwendig.

The significance of serum levels of insulin‐like growth factor‐1 in patients with prostate cancer

Objectives To compare the serum levels of insulin‐like growth factor‐1 (IGF‐1) in patients with prostate cancer and in control patients with no malignancy, and to evaluate any possible influence of testicular androgen withdrawal on the level of IGF‐1 in patients with prostate cancer.

Prognostic value of combined triple-reverse transcription-PCR analysis for prostate-specific antigen, human kallikrein 2, and prostate-specific membrane antigen mRNA in Peripheral blood and lymph nodes of prostate cancer patients

Purpose: We present the largest study of both peripheral blood and lymph node samples examining the utility of reverse transcription-polymerase chain reaction (RT-PCR) for established molecular markers as a diagnostic tool in the molecular staging of prostate cancer patients undergoing radical prostatectomy. Experimental Design: Peripheral blood from 358 patients was obtained before radical prostatectomy. Corresponding obturatory lymph node samples were collected from 153 of these patients. Nested RT-PCR for prostate-specific antigen (PSA), human kallikrein 2 (hK2), and prostate-specific membrane antigen (PSMA) were performed on cDNA from peripheral blood. The lymph node cDNA was analyzed for PSA und hK2 expression. Results: RT-PCR in peripheral blood was positive in 124 (34.6%) of 358 samples for PSA, 215 (60.1%) of 358 for PSMA, and 97 (27.1%) of 358 for hK2. Comparison of positive RT-PCR rates of pT2 and pT3 tumors in corresponding peripheral blood for PSA, PSMA, and hK2 were 31.9 and 40.0%, 58.8 and 62.5%, and 26.9 and 27.5%, respectively. Histopathologically, cancer-free lymph node samples were positive in RT-PCR for PSA and hK2 in 70 (49.6%) of 141 and 89 (63.2%) of 141 of cases. All histologically positive lymph node samples (n = 12, pN+) were positive for PSA RT-PCR. PSA RT-PCR alone, as well as combined PSA/PSMA RT-PCR evaluation, in peripheral blood showed a significant association with grading. PSA RT-PCR lymph node-negative samples were significantly less likely positive in their corresponding peripheral blood RT-PCR sample. Conclusions Although the preoperative PSA RT-PCR in peripheral blood correlated with the grading of prostate cancer, no combination of RT-PCR results using “triple” markers (PSA, hK2, PSMA) in peripheral blood and/or lymph nodes yielded additional preoperative staging information.

Prostate specific membrane antigen (PSM) is expressed in various human tissues: implication for the use of PSM reverse transcription polymerase chain reaction to detect hematogenous prostate cancer spread

Abstract Detection of prostate-specific membrane antigen (PSM)-mRNA expression in blood samples using reverse transcription polymerase chain reaction (RT-PCR) is discussed as a new diagnostic marker of circulating micrometastases in prostate cancer patients. We applied the RT-PCR technique to different human tissues and obtained positive signals for PSM transcripts in human genital and multiple extra-genital tissue sites. The cDNAs were prepared from different human tissues and prostatic cell lines. RT-PCR and nested RT-PCR for PSM was performed with primers derived from the published PSM cDNA. The RT-PCR fragments obtained were cloned and showed 100% sequence homology to PSM. Southern blot hybridization with labeled probes was used to confirm the specificity of the amplicons. In addition to the known PSM expression in the human brain, PSM-mRNA was detected in cDNA isolated from human testis, epididymis and seminal vesicles and in the PC-3 prostatic cancer cell line. Furthermore, we found PSM-mRNA in heart, liver, lung, kidney, spleen, and thyroid gland. The results indicate that PSM expression is not restricted to the prostate gland, but represents a more general component of genital and extra-genital human tissues. This must be considered when RT-PCR and nested RT-PCR screening for PSM expression is performed as a diagnostic measure in blood from prostate cancer patients.

New interstitial HDR brachytherapy technique for prostate cancer: CT based 3D planning after transrectal implantation

We have developed a new interstitial HDR brachytherapy technique for the treatment of prostate cancer using CT based 3D planning after transrectal implantation of four non-parallel needles. CT based needle reconstruction, target definition, evaluation and documentation, including DVHs and 3D imaging, is a feasible, safe and well tolerated treatment concept.

3D Interstitial HDR Brachytherapy Combined with 3D External Beam Radiotherapy and Androgen Deprivation for Prostate Cancer Preliminary Results

Background: Evaluation of feasibility, tolerance and efficiency for a new 3D interstitial HDR brachytherapy technique combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Patients and Methods: Between January 1997 and August 1998 we treated 35 patients with Stage cT1–3 N0 M0 prostate cancer. Thirty-two patients with a follow-up of 12 to 28 months (median: 18 months) were evaluated. After ultrasound-guided transrectal implantation of 4 non-parallel needles, CT based 3D brachytherapy treatment planning (“Offenbach system”) was performed. All patients received 4 fractions brachytherapy using a fractional dose of 5 or 7 Gy. Time between each fraction was 14 days. After brachytherapy 3D external irradiation followed up to 39.6 or 45.0 Gy. All patients received androgen deprivation, starting 2 to 19 months before brachytherapy, ending 3 months after 3D external radiotherapy. Results: Posttreatment PSA levels dropped to < 1.5 ng/ml in 29/32 patients (91%). In 25 patients PSA levels were < 0.5 ng/ml, in 4 patients 0.5 to 1.5 ng/ml. In 2 patients we noted biochemical relapse. Transrectal implantation was very well tolerated. Grade 3 acute urinary toxicity occurred in 1 patient. We noted no Grade 2 or higher acute gastrointestinal toxicity. One patient developed a Grade 3 late urinary toxicity. No patient showed late gastrointestinal side effects. All 140 dose-volume histograms for 3D HDR brachytherapy were analyzed. Conclusions: The new 3D HDR brachytherapy technique, combined with 3D external irradiation and androgen deprivation, is a feasible, so far well tolerated and effective treatment in the short-time follow-up of median 18 months.Hintergrund: Auswertung der Praktikabilität, Verträglichkeit und Effektivität einer neuen interstitiellen 3D-HDR-Brachytherapie-Technik, kombiniert mit externer 3D-Radiotherapie und Androgendeprivation beim Prostatakarzinom. Patienten und Methoden: Von Januar 1997 bis August 1998 behandelten wir 35 Patienten mit Prostatakarzinomen im Stadium cT1–3 N0 M0. Die Daten von 32 Patienten mit einer Nachbeobachtungszeit von zwölf bis 28 Monaten (median: 18 Monate) wurden ausgewertet. Nach ultraschallgesteuerter transrektaler Implantation von vier nicht parallelen Nadeln erfolgte die CT-gestützte 3D-Brachytherapie-Planung (“Offenbach-System”). Alle Patienten erhielten vier Fraktionen der 3D-Brachytherapie mit einer Einzeldosis von 5 oder 7 Gy im Abstand von jeweils 14 Tagen. Anschließend erfolgte die externe 3D-Radiotherapie bis 39,6 oder 45,0 Gy. Alle Patienten erhielten zusätzlich eine Androgendeprivation, die zwei bis 19 Monate vor der Brachytherapie eingeleitet und drei Monate nach Abschluss der externen Radiotherapie abgesetzt wurde. Ergebnisse: Bei 29/32 Patienten (91%) sank der posttherapeutische PSA-Wert unter 1,5 ng/ml, davon bei 25 Patienten auf unter 0,5 ng/ml, bei vier Patienten auf 0,5 bis 1,5 ng/ml. Zwei Patienten entwickelten ein biochemisches Rezidiv. Die transrektale Implantation wurde sehr gut toleriert. Ein Patient entwickelte akute Grad-3-Toxizitäten des Harntraktes, kein Patient akute gastrointestinale Nebenwirkungen größer als Grad 1. Eine Grad-3-Spättoxizität des Harntraktes zeigte ein Patient, gastrointestinale Spättoxizitäten entwickelte kein Patient. Alle 140 Dosis-Volumen-Histogramme der 3D-HDR-Brachytherapie wurden ausgewertet. Schlussfolgerung: Die neue 3D-HDR-Brachytherapie-Technik, kombiniert mit externer 3D-Radiotherapie und Androgendeprivation, stellt eine praktikable, bisher gut verträgliche und effektive Therapiemodalität nach Kurzzeitnachbeobachtung von median 18 Monaten dar.

High dose rate brachytherapy as monotherapy for localised prostate cancer: a hypofractionated two-implant approach in 351 consecutive patients

BackgroundTo report the clinical outcome of high dose rate brachytherapy as sole treatment for clinically localised prostate cancer.MethodsBetween March 2004 and January 2008, a total of 351 consecutive patients with clinically localised prostate cancer were treated with transrectal ultrasound guided high dose rate brachytherapy. The prescribed dose was 38.0 Gy in four fractions (two implants of two fractions each of 9.5 Gy with an interval of 14 days between the implants) delivered to an intraoperative transrectal ultrasound real-time defined planning treatment volume. Biochemical failure was defined according to the Phoenix Consensus and toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.ResultsThe median follow-up time was 59.3 months. The 36 and 60 month biochemical control and metastasis-free survival rates were respectively 98%, 94% and 99%, 98%. Toxicity was scored per event with 4.8% acute Grade 3 genitourinary and no acute Grade 3 gastrointestinal toxicity. Late Grade 3 genitourinary and gastrointestinal toxicity were respectively 3.4% and 1.4%. No instances of Grade 4 or greater acute or late adverse events were reported.ConclusionsOur results confirm high dose rate brachytherapy as safe and effective monotherapy for clinically organ-confined prostate cancer.

Fine structure of the canine prostatic complex

SummaryThe canine prostatic complex, including the prostatic urethra, the urethral openings of the prostatic gland ducts, the prostate gland proper and the ejaculatory ducts has been studied with the transmission and scanning electron microscopes. The urethral epithelium was found to be a modified transitional epithelium; it extended a short distance from the urethra into the orifices of the ducts where it gradually lost height. The columnar cells were replaced by cuboidal superficial cells in the terminal ducts of the gland. With increasing distance from the urethral openings of the ducts, the superficial cuboidal cells developed secretory activity and finally were indistinguish-able from regular prostatic secretory cells. The latter formed typical prostatic acini, consisting of secretory cells which were merocrine in nature, and flat lentilate basal cells. In addition to exocrine cells, three different types of presumptive endocrine cells occurred, predominantly in the periurethral ducts of the prostate gland. It has been concluded from this study that, firstly, fluid absorption and spermatophagy are the main functions of the epithelia of the ejaculatory ducts and the ampulla of the vas deferens. Secondly, it has been concluded that the different functions of the various structures of the prostatic complex can be related to their different embryological origins.