Gregor Goldner

Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors.

PURPOSE To identify clinically relevant parameters predictive of late rectal bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum after conformal radiotherapy of prostate cancer. MATERIALS AND METHODS One hundred and nine patients treated with 3D conformal radiotherapy between 1/1994 and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction (specified at the International Commission on Radiation Units and Measurements ICRU reference point). DVHs of the contoured rectum were analyzed by defining the absolute (aV) and relative (rV) rectum volume that received more than 30% (V30), 50% (V50), 70% (V70), 80% (V80), 90% (V90) and 100% (V100) of the prescribed dose. Additionally, a new aspect of DVH analysis was investigated by calculation of the area under the DVH-curve between several dose levels (area under the curve (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated in 3-6 months intervals and graded according to the EORTC/RTOG score. The median follow-up was 30 months (12-60 months). RESULTS Univariate and multivariate stepwise Cox-Regression analysis including age, PTV, rectum size, rV100, rV90, rV80, rV70, rV50 rV30 and aV30 to aV100 were calculated. Late rectal bleeding (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum volume receiving > or = 90% of the prescribed dose (rV90) (P = 0.007) and inversely correlated in a significant way with the size of contoured rectum (P = 0.006) in multivariate analysis. In our series, a proportion of the rectum volume > or = 57% were included in the 90%-isodose (rV90 > or = 57%) in one half of the patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years. In the other half of the patients, when rV90 < 57%, the 3-year actuarial incidence was 11% (P < 0.03). CONCLUSION Our data demonstrate a dose-volume relationship at the reference dose of 60 Gy ( approximately 90% of the prescribed dose) with respect to late rectal toxicity. The rV90 seems to be the most useful and easily obtained parameter when comparing treatment plans to evaluate the risk of rectal morbidity.

Endoscopic scoring of late rectal mucosal damage after conformal radiotherapy for prostatic carcinoma

PURPOSE To describe rectal mucosal damage in an endoscopic study after conformal radiotherapy of prostate cancer and to correlate this with clinical outcome. MATERIALS AND METHODS Flexible rectosigmoidoscopy was performed on 44 patients who voluntarily accepted the examination. The median follow-up was 29 months (20-41 months) after 3-D-planned conformal radiotherapy of prostate cancer (66 Gy at the ICRU Reference point, 2 Gy per fraction). To enable a systematic topographic description of endoscopic findings the rectum was divided into four sections. Additionally we differentiated between anterior, posterior, right and left lateral rectal wall. Due to the lack of an existing valid graduation system for radiation induced proctitis, we introduced a six-scaled rectoscopy score for describing and reporting endoscopic findings based on the standardization of the endoscopic terminology published by the ESGE (European Society for Gastrointestinal Endoscopy). Endoscopic findings were compared to the EORTC/RTOG morbidity score. In addition, since 3-D dose distribution of organs at risks was available, a correlation could be made between the location of the rectal lesions and the absorbed dose at that level. RESULTS In general, endoscopic findings increased from the proximal rectum to the anorectal transition, as well as from the posterior to the anterior rectum wall. Telangiectasia grade 1 and 2 were observed at the whole circumference, only telangiectasia grade 3 were limited to the high dose region at the anterior rectum wall. Similar results were found for congested mucosa (reddening and edematous mucosa). Correlation with symptoms, 7/9 patients who suffered from intermittent rectal bleeding (EORTC/RTOG grade 2) had multiple telangiectasia grade 2-3 and/or congested mucosa grade 3 and microulcerations. However, the same extent of mucosal damage (rectoscopy score 2-3) was found in seven out of 35 patients who have never developed a period of macroscopic rectal bleeding. CONCLUSION Rectoscopy offers the possibility of detecting signs of tissue dysfunction below the level of subjective symptoms. Systematic analytic examinations such as rectoscopy, in addition to clinical examinations, as already foreseen in the LENT-SOMA-score, will be necessary due to the fact that even telangiectatic lesions have been observed for asymptomatic patients. For the opportunity of sharing and comparing data collected from endoscopy after radiotherapy a graduation system as proposed based on a standardisation of the endoscopic terminology will be necessary.

Correlation of dose–volume parameters, endoscopic and clinical rectal side effects in cervix cancer patients treated with definitive radiotherapy including MRI-based brachytherapy

PURPOSE Correlation of dosimetric parameters for MRI-based 3D treatment planning with rectoscopic findings and clinical rectal side effects. METHODS AND MATERIALS Rectosigmoidoscopy and rectal morbidity assessment were performed on 35 cervical cancer patients treated with external beam radiotherapy (EBRT) and HDR-intracavitary brachytherapy (ICB). The total doses, normalised to 2 Gy fractions (EQD2, alpha/beta=3 Gy), in 0.1, 1.0 and 2.0 cm(3) (D(0.1 cc), D(1 cc), D(2 cc)) of rectum were determined by summation of EBRT and ICB plans. Correlation analysis between clinical symptoms (LENT/SOMA) and rectoscopic changes (Vienna Rectoscopy Score, VRS) was performed. For dose-response analyses, the logit model was applied. RESULTS Mean follow-up was 18 months. LENT/SOMA score was 1 in 4 patients, 2 in 8 patients, 4 in 1 patient. Telangiectasia was found in 26 patients (74%), five of them had ulceration corresponding to the 0.1 cm(3) volume (anterior wall). Mean values D(0.1 cc), D(1 cc), and D(2 cc) were 81+/-13, 70+/-9 and 66+/-8 Gy, respectively. The ED50 values for VRS > or = 3 and for LENT/SOMA > or = 2 significantly increased with decreasing volumes. D(2 cc) was higher in patients with VRS > or = 3 compared to VRS<3 (72+/-6 vs 62+/-7 Gy; p<0.001) and in symptomatic vs asymptomatic patients (72+/-6 vs 63+/-8 Gy; p<0.001). VRS correlated with the LENT/SOMA score. CONCLUSIONS Rectosigmoidoscopy is sensitive in detecting mucosal changes, independent of clinical symptoms. The localization of these changes corresponds to the high dose volumes as defined by imaging. The development of mucosal and clinical changes in the rectum follows a clear dose-effect and volume-effect. DVH parameters could be established.

Feasibility of CBCT-based target and normal structure delineation in prostate cancer radiotherapy: Multi-observer and image multi-modality study

BACKGROUND AND PURPOSE In-room cone-beam CT (CBCT) imaging and adaptive treatment strategies are promising methods to decrease target volumes and to spare organs at risk. The aim of this work was to analyze the inter-observer contouring uncertainties of target volumes and organs at risks (oars) in localized prostate cancer radiotherapy using CBCT images. Furthermore, CBCT contouring was benchmarked against other image modalities (CT, MR) and the influence of subjective image quality perception on inter-observer variability was assessed. METHODS AND MATERIALS Eight prostate cancer patients were selected. Seven radiation oncologists contoured target volumes and oars on CT, MRI and CBCT. Volumes, coefficient of variation (COV), conformity index (cigen), and coordinates of center-of-mass (COM) were calculated for each patient and image modality. Reliability analysis was performed for the support of the reported findings. Subjective perception of image quality was assessed via a ten-scored visual analog scale (VAS). RESULTS The median volume for prostate was larger on CT compared to MRI and CBCT images. The inter-observer variation for prostate was larger on CBCT (CIgen=0.57±0.09, 0.61 reliability) compared to CT (CIgen=0.72±0.07, 0.83 reliability) and MRI (CIgen=0.66±0.12, 0.87 reliability). On all image modalities values of the intra-observer reliability coefficient (0.97 for CT, 0.99 for MR and 0.94 for CBCT) indicated high reproducibility of results. For all patients the root mean square (RMS) of the inter-observer standard deviation (σ) of the COM was largest on CBCT with σ(x)=0.4 mm, σ(y)=1.1 mm, and σ(z)=1.7 mm. The concordance in delineating OARs was much stronger than for target volumes, with average CIgen>0.70 for rectum and CIgen>0.80 for bladder. Positive correlations between CIgen and VAS score of the image quality were observed for the prostate, seminal vesicles and rectum. CONCLUSIONS Inter-observer variability for target volume delineation in prostate cancer is larger for CBCT-based contouring compared to CT and MRI. This factor of influence needs to be considered when defining safety margins for CBCT-based Adaptive Radiotherapy (ART).

Die bedeutung eines rektumballons als interne immobilisation bei der konformalen strahlentherapie des prostatakarzinoms

BACKGROUND As known from the literature, prostate motion depends on different bladder and/or rectum fillings. The aim of this study was to analyze the influence of a rectum balloon catheter, used as an internal immobilization device, on prostate and rectum motion during the treatment course. Moreover we have analyzed if the balloon enables an increase of the distance between the prostate and the posterior rectum wall. PATIENTS AND METHODS Ten patients with localized prostate cancer (T1 to T3) underwent computed tomographic examinations with and without rectal balloon (filled with 40 ml air) at 3 times during treatment course (at the start, middle and end of treatment). Edges of prostate, rectum and bladder were measured in relation to bony reference structures and compared for both examination series (with and without balloon). RESULTS An increase of the distance between the prostate and the posterior rectal wall of 8 mm was observed at the base of the prostate when using the rectum balloon (Figures 1a,b and 2). Moreover prostate motion in the ventrodorsal direction > or = 4 mm (1 SD) was reduced from 6/10 patients (60%) to 1/10 patients (10%) using the rectal balloon (Table 3, Figure 3). In general, deviations in the latero-lateral and cranio-caudal directions were less (mean < or = 2 mm, 1 SD), no difference between both examination series (with and without balloon) was observed. CONCLUSION Rectal balloon catheter offers a possibility to reduce prostate motion and rectum filling variations during treatment course. In addition it enables an increase in the distance between prostate and posterior rectal wall, which could enable an improved protection of the posterior rectal wall.HintergrundDie Lageveränderung der Prostata, bedingt durch unterschiedliche Harnblasen- und Rektumfüllungen, wurde bereits in einigen Studien untersucht. Ziel dieser Studie war es, zu prüfen, ob durch die Anwendung eines Rektumballonkatheters als interne Immobilisation der Prostata eine Reduktion der Prostataeigenbeweglichkeit möglich ist. Darüber hinaus wurde untersucht, inwieweit durch den Rektumballon der Abstand zwischen Prostata und Rektumhinterwand vergrößert werden kann.Patienten und MethodeDrei konsekutive Planungscomputertomographien (Therapiebeginn, Therapiemitte, Therapieende) von zehn Patienten mit lokal begrenztem Prostatakarzinom (Tl bis T3) wurden jeweils mit und ohne Rektumballon (gefüllt mit 40 ml Luft) angefertigt. Die Lage von Prostata und Rektum im Therapieverlauf beider Untersuchungsserien (mit und ohne Rektumballon) wurde in Relation zu knöchernen Referenzstrukturen vermessen und miteinander verglichen.ErgebnisseDurch die Anwendung des Rektumballons konnte der Abstand zwischen Prostata und Rektumhinterwand an der Prostatabasis im Mittel um 8 mm vergrößert werden. Insgesamt konnte durch den Rektumballon die Prostatabewegung in ventrodorsaler Richtung deutlich reduziert werden. Die Anzahl jener Patienten, bei denen eine ventrodorsale Bewegung der zentralen Prostata im Therapieverlauf ≥ 4 mm (1 SD) beobachtet wurde, konnte durch die Anwendung des Rektumballons von 6/10 Patienten (60%) auf 1/10 Patienten (10%) reduziert werden. Die Lageveränderungen der Prostata in laterolateraler und kraniokaudaler Richtung waren deutlich geringer als jene in ventrodorsaler Richtung (im Mittel ≤ 2 mm, 1 SD) und wurden durch den Rektumballon nicht beeinflußt.SchlußfolgerungDie Anwendung des Rektumballons ermöglicht eine Reduktion der Prostataeigenbeweglichkeit in ventrodorsaler Richtung im Sinne einer internen Immobilisation. Zusätzlich wird eine Vergrößerung des Abstands zwischen Prostata und Rektumhinterwand erreicht, wodurch eine bessere Schonung der Rektumhinterwand möglich scheint.AbstractBackgroundAs known from the literature, prostate motion depends on different bladder and/or rectum fillings. The aim of this study was to analyze the influence of a rectum balloon catheter, used as an internal immobilization device, on prostate and rectum motion during the treatment course. Moreover we have analyzed if the balloon enables an increase of the distance between the prostate and the posterior rectum wall.Patients and MethodsTen patients with localized prostate cancer (Tl to T3) underwent computed tomographic examinations with and without rectal balloon (filled with 40 ml air) at 3 times during treatment course (at the start, middle and end of treatment). Edges of prostate, rectum and bladder were measured in relation to bony reference structures and compared for both examination series (with and without balloon).ResultsAn increase of the distance between the prostate and the posterior rectal wall of 8 mm was observed at the base of the prostate when using the rectum balloon (Figures la,b and 2). Moreover prostate motion in the ventrodorsal direction ≥ 4 mm (1 SD) was reduced from 6/10 patients (60%) to 1/10 patients (10%) using the rectal balloon (Table 3, Figure 3). In general, deviations in the latero-lateral and cranio-caudal directions were less (mean ≤ 2 mm, 1 SD), no difference between both examination series (with and without balloon) was observed.ConclusionRectal balloon catheter offers a possibility to reduce prostate motion and rectum filling variations during treatment course. In addition it enables an increase in the distance between prostate and posterior rectal wall, which could enable an improved protection of the posterior rectal wall.

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.

Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

PURPOSE To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. METHODS AND MATERIALS Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior-posterior) and 8 mm (superior-inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT ((192)Ir) and LDR-BT ((125)I) were D(90%) ≥34 Gy in 8.5 Gy per fraction and D(90%) ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose-volume parameters were extracted. RESULTS Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose-volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra D(mean) around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. CONCLUSION Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques were clearly superior in terms of BW, RW, and normal tissue sparing, with lowest values for HDR-BT.

Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series ☆

BACKGROUND Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). OBJECTIVE To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. DESIGN, SETTING, AND PARTICIPANTS Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml. INTERVENTION We compared aRT versus observation followed by esRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). RESULTS AND LIMITATIONS Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. CONCLUSIONS At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. PATIENT SUMMARY At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT.

Moderate dose escalation in three-dimensional conformal localized prostate cancer radiotherapy: single-institutional experience in 398 patients comparing 66 Gy versus 70 Gy versus 74 Gy.

Purpose:To evaluate the clinical outcome in prostate cancer patients treated at one single institution by the implementation of moderate dose escalation.Patients and Methods:A total of 398 patients with histologically verified localized prostate cancer (T1–3 Nx0 Mx0) were treated by three-dimensional conformal radiotherapy with/without additional hormonal therapy. Risk group distribution was as follows: 106 low-risk (27%), 164 intermediate-risk (41%), and 128 high-risk (32%) patients. Total local dose was increased from 66 Gy (1994–1998) to 70 Gy (1998–2003) and 74 Gy (1998–2005). Biochemical no evidence of disease (bNED: ASTRO/Phoenix definition) and late gastrointestinal/urogenital side effects (EORTC/RTOG) were assessed.Results:Median follow-up was 64 months. The 5-year bNED rates according to 66 Gy, 70 Gy and 74 Gy were 37%, 64% and 63% (ASTRO), and 54%, 74% and 69% (Phoenix), respectively. In multivariate analysis, age and T-stage were significant in predicting bNED. The 5-year bNED rates (ASTRO) according to 66 Gy, 70 Gy and 74 Gy were 40%, 78% and 73% in the low-risk group, 41%, 55% and 85% in the intermediate-risk group, and 30%, 53% and 52% in the high-risk group. Intermediate-risk patients showed a significant improvement of bNED by increasing the dose up to 74 Gy. The 5-year actuarial rates of gastrointestinal/urogenital side effects grade ≥ 2 were 18%/16% (66 Gy), 20%/24% (70 Gy), and 27%/28% (74 Gy).Conclusion:A benefit of local doses at a level of ≥ 70 Gy could be detected showing the highest increase of prostate-specific antigen control in the intermediate-risk group. The amount of patients reporting of severe late side effects is small.Ziel:Evaluation der klinischen Ergebnisse zur moderaten Dosiseskalation bei Patienten mit Prostatakarzinom.Patienten und Methodik:Bei 398 Patienten mit histologisch verifiziertem Prostatakarzinom (T1–3 Nx0 Mx0) wurde eine dreidimensionale konformale Teletherapie mit/ohne begleitende Hormontherapie durchgeführt. Es fanden sich 106 Patienten (27%) mit niedrigem Risiko, 164 (41%) mit intermediärem Risiko und 128 (32%) mit hohem Risiko (Tabelle 1). Die applizierte Dosis wurde von 66 Gy (1994–1998) auf 70 Gy (1998–2003) bzw. 74 Gy (1998–2005) gesteigert. Biochemische Kontrollraten (bNED: ASTRO/Phoenix-Definition) sowie späte gastrointestinale/urogenitale Nebenwirkungen (EORTC/RTOG) wurden ermittelt.Ergebnisse:Der mediane Nachbeobachtungszeitraum betrug 64 Monate. Die 5-Jahres-bNED-Raten entsprechend der 66-Gy-, 70-Gy- und 74-Gy-Dosis betrugen 37%, 64% und 63% (ASTRO, Abbildung 1) bzw. 54%, 74% und 69% (Phoenix, Abbildung 2). In der multivariaten Analyse zeigten sich das Alter und das T-Stadium als signifikant hinsichtlich der bNED-Raten (Tabelle 2). Die 5-Jahres-bNED-Raten (ASTRO) entsprechend der 66-Gy-, 70-Gy- und 74-Gy-Dosis betrugen in der Niedrigrisikogruppe 40%, 78% und 73%, in der Gruppe mit intermediärem Risiko 41%, 55% und 85% und in der Hochrisikogruppe 30%, 53% und 52%. Bei Patienten mit intermediärem Risiko zeigte sich ein signifikanter Vorteil durch die Dosissteigerung auf 74 Gy (Abbildungen 3a bis 3c). Die 5-Jahres-Raten an gastrointestinalen/urogenitalen Nebenwirkungen Grad ≥ 2 lagen bei 18%/16% (66 Gy), 20%/24% (70 Gy) und 27%/28% (74 Gy; Abbildungen 4 und 5).Schlussfolgerung:Die dreidimensionale konformale Bestrahlung mit einer Dosis ≥ 70 Gy zeigt verbesserte bNED-Raten vor allem für Patienten der intermediären Risikogruppe. Die Rate an schweren Spätnebenwirkungen ist dabei gering.

Prostate and Patient Intrafraction Motion: Impact on Treatment Time-Dependent Planning Margins for Patients With Endorectal Balloon

PURPOSE To investigate intrafraction prostate and patient motion during different radiation therapy treatments as a function of treatment time; included were prostate patients with an endorectal balloon (ERB). Margins accounting for setup uncertainties and intrafraction motion were determined. METHODS AND MATERIALS The study included 17 patients undergoing prostate cancer radiation therapy. All patients received 3 fiducial gold markers implanted in the prostate and were then immobilized in the supine position with a knee support and treated with an ERB. Twelve patients with intermediate risk for pelvic lymph node metastases received intensity modulated radiation therapy (IMRT), and 5 patients at low risk received a 4-field box treatment. After setup based on skin marks, patients were imaged with a stereoscopic imaging system. If the marker displacement exceeded a 3-mm tolerance relative to planning computed tomography, patients were shifted and verification images were taken. All patients underwent additional imaging after treatment; IMRT patients also received additional imaging at halftime of treatment. Prostate and bone drifts were evaluated as a function of treatment time for more than 600 fractions, and margins were extracted. RESULTS Patient motion evaluated by bone match was strongly patient dependent but in general was smallest in the superior-inferior (SI) direction. Prostate drifts were less patient dependent, showing an increase with treatment time in the SI and anterior-posterior (AP) directions. In the lateral (LAT) direction, the prostate stayed rather stable. Mean treatment times were 5.5 minutes for 4-field box, 10 minutes for 5-field boost IMRT, and 15 minutes or more for 9-field boost and 9-field pelvic IMRT treatments. Margins resulted in 2.2 mm, 3.9 mm, and 4.3 mm for 4-field box; 3.7 mm, 2.6 mm, and 3.6 mm for 5-field boost IMRT; 2.3 mm, 3.9 mm, and 6.2 mm for 9-field boost IMRT; and 4.2 mm, 5.1 mm, and 6.6 mm for 9-field pelvic IMRT in the LAT, SI, and AP directions, respectively. CONCLUSION Intrafraction prostate and patient displacement increased with treatment time, showing different behaviors for the single directions of movement. Repositioning of the patients during long treatments or shorter treatment times will be necessary to further reduce the treatment margin.