Natascha Wachter-Gerstner

Bladder and rectum dose defined from MRI based treatment planning for cervix cancer brachytherapy: comparison of dose–volume histograms for organ contours and organ wall, comparison with ICRU rectum and bladder reference point

PURPOSE To analyze the correlation between dose-volume histograms based on organ contour and organ wall delineation for bladder and rectum, and to compare the doses to these organs with the absorbed doses at the ICRU bladder and rectum reference points. MATERIAL AND METHODS Individual MRI based brachytherapy treatment planning was performed in 15 patients as part of a prospective comparative trial. The external contours and the organ walls were delineated for the bladder and rectum in order to compute the corresponding dose-volume histograms. The minimum dose in 2 cm(3), 5 cm(3) and 10 cm(3) volumes receiving the highest dose were referred to as [D2], [D5] and [D10] and compared with the absorbed dose at the ICRU rectum and bladder reference point. RESULTS The bladder (bext) and rectal (rext) doses derived from external contours and computed for volumes of 2 cm(3) [D2], provided a good estimate for the doses computed for the organ walls (bw and rw) only (mean ratio [D2](bext)/[D2](bw)=1.1+/-0.2 and [D2](rext)/[D2](rw)=1.2+/-0.1, respectively). This correspondence was no longer true when larger volumes were considered (5 and 10 cm(3)). The dose at the ICRU rectum reference point did overestimate the dose computed for 2 cm(3) of the rectum wall (mean ratio: 1.5+/-0.4). In contrast, the dose at the ICRU bladder reference point did-in the case of inappropriate topographic location of the balloon-underestimate the dose computed for 2 cm(3) of the bladder wall (overall mean ratio: 0.9+/-0.4). CONCLUSION For clinical applications, when volumes smaller than 5 cm(3) are considered, the dose-volume histograms computed from external organ contours for the bladder and rectum can be used instead of dose-volume histograms computed for the organ walls only. External organ contours are indeed easier to obtain. The dose at the ICRU rectum reference point provides a good estimate of the rectal dose computed for volumes smaller than 2 cm(3) [D2] only for a midline position of the rectum. The ICRU bladder reference point provides a good estimate of the dose computed for the bladder wall [D2] only in cases of appropriate balloon position.

11C-Acetate Positron Emission Tomography Imaging and Image Fusion With Computed Tomography and Magnetic Resonance Imaging in Patients With Recurrent Prostate Cancer

PURPOSE To assess the clinical value of computed tomography (CT) and magnetic resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission tomography (PET) imaging for detection and exact location of clinically occult recurrences. PATIENTS AND METHODS Fifty prostate cancer patients with elevated/increasing serum prostate-specific antigen levels after radical therapy underwent whole-body AC PET. Uptake was initially interpreted as normal, abnormal, or equivocal. In case of abnormal or equivocal uptake, additional conventional imaging techniques, such as CT, MRI, and bone scans, were performed. To precisely define the anatomic location of abnormal uptake and to improve characterization of equivocal lesions, a software-assisted image fusion (CT-PET, MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n = 37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional histopathologic evaluation was available. RESULTS In five (10%), 13 (26%), and 32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as normal, equivocal, and abnormal, respectively. Image fusion changed characterization of equivocal lesions as normal in five (10%) of 51 sites and abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient management in 14 (28%) of 50 patients. CONCLUSION Retrospective fusion of AC PET and CT/MRI is feasible and seems to be essential for final diagnosis. This is particularly true in patients with AC uptake in the prostate region.

The impact of sectional imaging on dose escalation in endocavitary HDR-brachytherapy of cervical cancer: results of a prospective comparative trial

PURPOSE The purpose of this comparative prospective study was to assess the effect of CT and MR based individualisation and adaptation on the dose distribution in the target volume and organs at risk compared to a radiography based procedure. MATERIAL AND METHODS In 15 patients MR scans, in 10 patients additional axial CT-scans with compatible tube-ring applicator in situ were performed and digitally transferred to the PLATO(R) planning system. Considering clinical examination and MR-scan before radiotherapy individual 3-D dose distribution was calculated and adapted based on (1) two orthogonal radiographs; (2) isodoses superimposed on the CT images; and (3) isodoses superimposed on the MR images. Adaptation was strictly limited by the dose level at 2 cm(3) bladder or rectum volume (D(2)) to allow comparison of CT and MR plans. All three individualised dose distributions were superimposed on the MR images and cumulative dose-volume histograms were calculated for comparison. RESULTS 3-D individualisation based on sectional imaging enabled higher dose to the target volume (isodose enclosing 95% of the CTV=CTV(95)) compared to individualised treatment plans based on orthogonal radiographs by a mean factor of 1.2 (1-1.7). The dose to bladder and/or rectum wall was at the same time not increased beyond the prescribed tolerance level (71% of the prescribed target dose). In a subgroup of 10 patients MRI based treatment plans were superior to CT based treatment plans allowing for a higher dose (138% vs. 124%). CONCLUSION Sectional imaging based treatment planning, in particular using MR, was superior to radiography allowing for a clinical meaningful dose escalation without increasing the dose to bladder and rectum beyond the tolerance level.

Interobserver comparison of CT and MRI-based prostate apex definition. Clinical relevance for conformal radiotherapy treatment planning.

Background: CT is widely used for conformal radiotherapy treatment planning of prostate carcinoma. Its limitations are especially at the prostatic apex which cannot be separated from the urogenital diaphragm. The aim of this study was to compare the localization of the prostatic apex in CT and axial MRI to the sagittal MRI in an interobserver analysis. Patients and Methods: 22 patients with pathologically proven prostatic carcinoma were included in the analysis. In all patients sagittal and axial T2-weighted MRI and conventional CT were performed. The position of the MRI and CT apices were localized independently by three observers in relation to the intertrochanteric line. Additional subjective judgment of the ability to define the apical border of the prostatic gland was performed by a five-scaled score. Results: The apex of the prostate could be discriminated statistically significant (p < 0.001) better in the MRI as compared to CT with best judgment for the sagittal MRI. The interobserver variation for the definition of the prostatic apex was statistically significant (p = 0.009) smaler for the sagittal MRI compared to axial MRI and CT. On the average the apex as determined by sagittal MRI, axial MRI and CT was located 29 mm, 27 mm and 24 mm above the intertrochanteric line. The apex defined by CT would have led to an additional treatment of 6–13 mm in 10/22 patients compared to the sagittal MRI, defined by axial MRI only in five patients. Conclusion: Additional MRI provides a superior anatomic information especially in the apical portion of the prostate. It should be recommended for every single patient in the treatment planning process. It helps to avoid an unnecessary irradiation of healthy tissue and could lead to a decrease of anal side effects and radiation-induced impotency due to a reduction of the extent of irradiated penile structures.Hintergrund: Die Computertomographie (CT) stellt den Standard in der konformalen Strahlentherapieplanung des Prostatakarzinoms dar. Vor allem im Bereich des Apex der Prostata stößt die CT durch die fehlende Abgrenzbarkeit vom Diaphragma urogenitale an ihre Grenzen. Ziel dieser Studie war es, die Lokalisation des Apex im konventionellen CT und im axialen MRT mit jener im sagittalen MRT zu vergleichen. Patienten und Methode: 22 Patienten mit histologisch verifiziertem Prostatakarzinom wurden in die Auswerung einbezogen. Bei allen Patienten wurde eine axiale und sagittale T2-gewichtete MRT und eine konventionelle CT unter Planungsbedingungen durchgeführt. Die Lokalisation des Apex wurde in allen drei Schnittbildmodalitäten von drei Untersuchern in Relation zur Linea intertrochanterica festgelegt. Zusätzlich wurde die subjektive Abgrenzbarkeit des Apex nach einer fünfrangigen Skala beurteilt. Ergebnisse: Die subjektive Abgrenzbarkeit des Apex wurde im MRT statistisch signifikant (p < 0,001) besser beurteilt als im CT, mit der besten Beurteilung für das sagittale MRT (Abbildung 1). Die Interobserver-Abweichung der Apexlokalisation war für das sagittale MRT statistisch signifikant (p = 0,009) kleiner im Vergleich zum axialen MRT und CT. Im Mittel wurde der Apex im sagittalen MRT, axialen MRT und CT 29 mm, 27 mm und 24 mm oberhalb der Linea intertrochanterica lokalisiert (Abbildungen 2 bis 4). Eine Apexdefinition auf Basis des CT hätte im Vergleich zum sagittalen MRT bei 10/22 Patienten zu einer zusätzlichen Bestrahlung von gesundem Gewebe geführt, auf Basis der axialen MRT nur bei fünf Patienten. Schlussfolgerung: Die Kernspintomographie bildet die Anatomie im Bereich des Prostataapex deutlich besser ab als die CT und sollte deshalb zusätzlich durchgeführt werden (Abbildung 6). Sie erlaubt eine adäquate Apexdefinition im Rahmen der konformalen Bestrahlungsplanung des Prostatakarzinoms und hilft so, eine unnötige Bestrahlung gesunder analer oder peniler Strukturen zu vermeiden. Dies kann sowohl zu einer Reduktion von radiogenen analen Nebenwirkungen als auch zu einer Verminderung von radiogenen Potenzstörungen beitragen.

Biochemical Response after 3-D Conformal Radiotherapy of Localized Prostate Cancer to a Total Dose of 66 Gy

Background: Since the introduction of 3-D conformal radiotherapy (CRT) doses of ≤ 70 Gy have been used in many European countries. In this analysis, the impact of a short-term neoadjuvant hormonal treatment in combination with CRT to a moderate dose level of 66 Gy was examined. Patients and Methods: From January 1994 to February 1999 397 patients were treated for carcinoma of the prostate. In 279 patietns a definitive curative treatment (T1 = 38, T2 = 165, T3 = 50, Tx = 11) with or without androgen deprivation was performed. 164 patients with radiotherapy of the prostate ± seminal vesicles to a total dose of 66 Gy (n = 109) alone or in combination with a short-term hormonal treatment (n = 55) were included in this analysis. Biochemical relapse was defined as three rising PSA values or reintroduction of hormonal treatment. A low-risk subgroup was defined for patients with maximum serum PSA level ≤ 10 and cT≤2 and G≤2, all other patients were summarized as high-risk patients. Results: The median follow-up of alive patients was 40 months (12–72 months). There was a total of 29/164 deaths, two were cause-specific and 27 were considered unrelated to prostate cancer. The 4-year rates of no biochemical evidence of disease for all patients was 58%. For the high-risk group the 4-year rates could be improved with borderline significance from 35% to 66% (p = 0.057) by additional neoadjuvant hormonal treatment. In contrast for the low-risk group no significant improvement was observed: 73% and 82%, respectively (p = 0.5). Conclusion: Especially in high-risk patients doses ≤ 70 Gy for radiotherapy alone seem not to be sufficient for curative treatment. Additional hormonal treatment and doses ≥ 70 Gy should be considered. As a consequence of our earlier analysis a prospective multicenter treatment optimization protocol has been initiated in 1999. The protocol includes a risk-adapted dose increase from 70 Gy in low-risk patients to 74 Gy in high-risk patients including short-term androgen ablation.Hintergrund: Seit Einführung der dreidimensionalen (3-D) konformalen Radiatio wurden in vielen europäischen Zentren Dosen ≤ 70 Gy bei der primären Bestrahlung des Prostatakarzinoms angewandt. Ziel dieser Arbeit war es, den Einfluss einer Kurzzeithormontherapie für Patienten mit unterschiedlichem Risikoprofil bei einer Dosis von 66 Gy zu evaluieren. Patienten und Methode: 397 Patienten wurden von Januar 1994 bis Februar 1999 wegen eines Prostatakarzinoms behandelt. Bei 279 Patienten wurde eine definitive kurative Radiatio eines lokal begrenzten Prostatakarzinoms (T1 = 38, T2 = 165, T3 = 50, Tx = 11) mit oder ohne Hormontherapie durchgeführt. 164 Patienten, bei denen eine alleinige Radiatio (n = 109) der Prostata ± Samenblasen bis zu einer GHD von 66 Gy (ICRU-Referenzpunkt) oder eine Kombination mit neoadjuvanter Hormontherapie (n = 55) durchgeführt wurde, wurden ausgewertet (Tabele 1). Das biochemische Rezidiv wurde mit drei steigenden Serum-PSA-Werten oder der Wiederaufnahme einer Hormontherapie definiert. Die Patienten wurden in eine Niedrigrisikogruppe (PSA ≤ 10 ng/ml, G≤2, T≤3) und eine Hochrisikogruppe (PSA > 10 ng/ml oder G3 oder T3) eingeteilt. Ergebnisse: Die mediane Nachbeobachtungszeit betrug bei den überlebenden Patienten 40 Monate (12–72 Monate). Insgesamt verstarben 29/164 Patienten (27 Patienten interkurrent, zwei Patienten am Tumor). Für alle Patienten betrug die biochemische Rezidivfreiheit nach 4 Jahren 58% nach Kaplan-Meier (Abbildung 1). Durch die neoadjuvante Hormontherapie konnte eine grenzwertig signifikante Verbesserung von 35% (alleinige Radiatio) of 66% (neoadjuvante Hormontherapie) für die Hochrisikogrupe erzielt werden (p = 0,057) (Abbildungen 2 und 3). Für die Niedrigrisikogruppe konnte keine signifikante Verbesserung (73% vs. 82%) beobachtet werden (p = 0,5) (Abbildung 4). Schlussfolgerung: Vor allem bei Patienten mit hohem Risikoprofil ist eine alleinige lokale Radiatio mit < 70 Gy nicht ausreichend. Eine (neo-)adjuvante Hormontherapie und/oder Dosissteigerung > 70 Gy ist notwendig, um die lokale Kontrolle zu erhöhen. Als Konsequenz aus unserer früheren Analyse wurde 1999 eine risikoadaptierte multizentrische Therapieoptimierungsstudie mit Dosissteigerung von 70 Gy auf 74 Gy und neoadjuvanter Hormontherapie für Hochrisikopatienten initiiert.

Neoadjuvant Hormonal Treatment and Radiotherapy for Prostate Cancer

Adjuvant hormone treatment with radiotherapy has been demonstrated in two studies (Bolla and RTOG 8531) to be beneficial in patients with locally advanced prostate cancer. However, the vast majority of patients with early prostate cancer can be cured with radiotherapy alone. Subset analysis combining RTOG 8610 and RTOG 8531 has demonstrated a survival benefit only for patients with a biopsy Gleason score ≤6 after short-term neoadjuvant hormonal therapy. The results of ongoing research will further clarify the use of hormone treatment with radiotherapy in patients with low and intermediate risk.

Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy@@@Dreidimensionale konformale risikoadaptierte Radiotherapie des lokalisierten Prostatakarzinoms mit moderater Dosiseskalation von 70 auf 74 Gy. 5-Jahres-Resultate der prospektiven österreichisch-deutschen Phase-II-Multicenterstudie: First report on 5-year morbidity and biochemical control from a prospective Austrian-German multicenter phase II trial

Purpose:Evaluation of late side effects and biochemical control (bNED) 5 years after three-dimensional radiotherapy with moderate, risk-adapted dose escalation.Patients and Methods:From 03/1999 to 07/2002, 486 patients have been registered in the prospective Austrian-German multicenter phase II trial (AUGE). 399 (82%) localized prostate cancer patients (T1–3 Nx/N0 M0) were evaluated. The low- and intermediate-risk groups were treated with 70 Gy, the high-risk group with 74 Gy, respectively. Additional hormonal therapy (HT) was recommended for intermediate- and high-risk group patients. Late toxicity (EORTC/RTOG) and bNED (ASTRO and Phoenix) were prospectively assessed.Results:Median follow-up was 65 months. Distribution concerning risk groups (low-, intermediate-, high-risk group) showed 29%, 50% and 21% of patients, respectively. HT was given in 87% of patients. The 5-year actuarial rates of late side effects grade ≥ 2 for 70 Gy/74 Gy were 28%/30% (gastrointestinal; p = 0.73) and 19%/34% (urogenital; p = 0,06). The 5-year actuarial bNED rate stratified by risk groups (low-, intermediate-, high-risk group) was 74%, 66% and 50% (ASTRO), and 81%, 80% and 60% (Phoenix), respectively. Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED (ASTRO) whereas Gleason Score and duration of HT were not.Conclusion:Dose escalation within standard three-dimensional conformal radiotherapy (3D-CRT) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects, whereas urogenital side effects showed an increase close to significance. However, the total number of patients with severe toxicity was low. To achieve high tumor control rates with acceptable treatment-related morbidity, local doses of at least 74 Gy should be considered, in particular for intermediate- or high-risk patients applying 3D-CRT.Ziel:Bestimmung von Spätnebenwirkungen und biochemischer Kontrolle (bNED) nach risikoadaptierter Dosiseskalation im Rahmen einer prospektiven österreichisch-deutschen Phase-II-Multicenterstudie.Patienten und Methodik:Von 03/1999 bis 07/2002 wurden 486 Patienten mit Prostatakarzinom (T1–3 Nx/N0 M0) gemeldet, und 399 (82%) kamen zur Auswertung. Patienten der Niedrig- und Intermediärrisikogruppe wurden mit 70 Gy, die Hochrisikogruppe mit 74 Gy bestrahlt (Tabelle 1). Eine begleitende Hormontherapie wurde für Patienten der Intermediär- und Hochrisikogruppe empfohlen. Spätnebenwirkungen (EORTC/RTOG) und bNED (ASTRO/Phoenix) wurden ermittelt.Ergebnisse:Der mittlere Nachbeobachtungszeitraum betrug 65 Monate. Hinsichtlich der Risikogruppen (Niedrig-, Intermediär-, Hochrisikogruppe) fanden sich 29%, 50%, und 21% Patienten. Eine begleitende Hormontherapie erhielten 87% der Patienten. Detaillierte Patientendaten sind in Tabelle 2 aufgeführt. Die 5-Jahres-Raten an Spätnebenwirkungen Grad ≥ 2 für 70 Gy/74 Gy lagen bei 28%/30% (gastrointestinal; p = 0,73) und 19%/34% (urogenital; p = 0,06; Abbildungen 1 und 2). Die 5-Jahres-bNED-Raten entsprechend den Risikogruppen (Niedrig-, Intermediär-, Hochrisikogruppe) lagen bei 74%, 66% und 50% (ASTRO; Abbildung 3) bzw. 81%, 80% und 60% (Phoenix; Abbildung 4). In der multivariaten Analyse zeigten sich T-Stadium und initiales prostataspezifisches Antigen als signifikant bezüglich bNED (ASTRO) und Gleason-Score sowie die Dauer der Hormontherapie als nicht signifikant (Tabelle 4).Schlussfolgerung:Die Dosissteigerung auf 74 Gy führt zu keinen signifikant erhöhten Raten an gastrointestinalen Spätnebenwirkungen. Die Rate an urogenitalen Spätnebenwirkungen ist hingegen erhöht. Insgesamt finden sich jedoch nur wenige schwere Grad-3-Spätnebenwirkungen (Tabelle 3). Um respektable Tumorkontrollraten (Abbildung 5) zu erreichen, sollte, vor allem für Patienten der Intermediär- und Hochrisikogruppe, eine lokale Dosis von zumindest 74 Gy appliziert werden.