Peter Rosenthal

IMPACT OF THE FILLING STATUS OF THE BLADDER AND RECTUM ON THEIR INTEGRAL DOSE DISTRIBUTION AND THE MOVEMENT OF THE UTERUS IN THE TREATMENT PLANNING OF GYNAECOLOGICAL CANCER

PURPOSE Determination of the impact of the filling status of the organs at risk (bladder and rectum) on the uterus mobility and on their integral dose distribution in radiotherapy of gynaecological cancer. METHODS In 29 women suffering from cervical or endometrial cancer two CT scans were carried out for treatment planning, one with an empty bladder and rectum, the second one with bladder and rectum filled. The volumes of the organs at risk were calculated and in 14 patients, receiving a definitive radiotherapy, the position of the uterus within the pelvis was shown using multiplanar reconstructions. After generation of a 3D treatment plan the dose volume histograms were compared for empty and filled organs at risk. RESULTS The mobility for the corpus uteri with/without bladder and rectum filling was in median 7 mm (95%-confidence interval: 3-15 mm) in cranial/caudal direction and 4 mm (0-9 mm) in posterior/anterior direction. Likewise, cervical mobility was observed to be 4 mm (-1-6 mm) mm in cranial/caudal direction. A full bladder led to a mean reduction in organ dose in median from 94-87% calculated for 50% of the bladder volume (P < 0.05, Wilcoxons matched-pairs signed-ranks test). For 66% of the bladder volume the dose could be reduced in median from 78 to 61% (P < 0.005) and for the whole bladder from 42 to 39% (P < 0.005), respectively. No significant contribution of the filling status of the rectum to its integral dose burden was noticed. CONCLUSIONS Due to the mobility of the uterus increased margins between CTV and PTV superiorly, inferiorly, anteriorly and posteriorly of 15, 6 and 9 mm each, respectively, should be used. A full bladder is the prerequisite for an integral dose reduction.

Computed Tomogram prior to Prostatectomy Advantage in Defining Planning Target Volumes for Postoperative Adjuvant Radiotherapy in Patients with Stage C Prostate Cancer

Purpose: To evaluate the influence of a preoperative computed tomogram (CT) on delineation of the planning target volume (PTV) for adjuvant radiation therapy of pT3 pNO prostate cancer. Patients and Methods: PTVs of ten patients who had an additional preoperative CT examination were contoured by three independent radiation oncologists. PTV included the former prostatic bed and seminal vesicles with a safety margin. First PTVs were drawn without knowledge of the preoperative CTs and in a second attempt, this procedure was repeated with these CTs available for visual comparison. Changes in PTV dimensions for every patient were analyzed. Results: In 93% of all PTVs there was a decision to increase the PTV after viewing the preoperative CT images. Mean PTV length increased from 7.3 to 8.4 cm and PTV volumes expanded 26% from 244 to 308 cm3. These differences were statistically significant for all three participating radiation oncologists. Conclusion: Planning target volume definition probably is a critical factor in adjuvant radiation therapy after radical prostatectomy. As there is a considerable incertaincy in PTV definition a preoperative CT is helpful and therefore may have beneficial influence on results.Hintergrund: Es ist bisher nicht sicher, wie das PTV bei einer postoperativen Bestrahlung nach radikaler Prostatektomie bei pT3 pNO-Prostatakarzinomen definiert werden soll. Ziel der Untersuchung war es herauszufinden, ob ein präoperativ angefertigtes CT die Wahl des PTV beeinflusst. Patienten und Methoden: Bei zehn Patienten, von denen ein präoperatives CT zur Verfügung stand, wurde von drei unterschiedlichen erfahrenen Radioonkologen unabhängig voneinander das PTV konturiert. Das PTV sollte die Prostata- und Samenblasenregion und einen Sicherheitssaum enthalten. Die PTVs wurden für jeden Patienten zweimal konturiert: zunächst ohne die präoperative CT-Untersuchung zu kennen, dann später ein weiteres Mal in Kenntnis der präoperativen Bilder. Die Änderungen der PTV-Dimensionen wurden untersucht. Ergebnisse: 93% aller PTVs wurden in Kenntnis der präoperativen Bilder größer gewählt. Die mittlere PTV-Länge wuchs von 7,3 auf 8,4 cm, das durchschnittliche PTV-Volumen wuchs um 26% von 244 auf 308 cm3. Diese Unterschiede waren für alle teilnehmenden Radioonkologen signifikant. Schlussfolgerung: Die PTV-Definition ist bei der postoperativen adjuvanten Bestrahlung nach radikaler Prostatektomie ein entscheidender Punkt. Da es erhebliche Unsicherheiten bei der PTV-Festlegung gibt, kann ein präoperatives CT hilfreich sein und hat möglicherweise einen positiven Einfluss auf das Behandlungsergebnis.

Vergleich unterschiedlicher dreidimensionaler Bestrahlungstechniken bei der lokalen Strahlentherapie des Prostatakarzinoms

ZielVier verschiedene SD-Bestrahlungstechniken wurden hinsichtlich der Dosishomogenität im Targetvolumen und der Dosis-Volumen-Belastung der Risikoorgane in AbhÄngigkeit vom Tumorstadium untersucht.Patienten und MethodeBei 17 Patienten wurden eine 3D-Rotations-, Vier-Felder-, Fünf-Felder- und Sechs-Felder-Technik erstellt. Sechs Patienten wiesen ein Stadium T1N0M0, sieben Patienten ein Stadium T2N0M0 und vier Patienten ein Stadium T3N0M0 auf. Dosiert wurde auf den Referenzpunkt im Isozentrum (100%). Die 95%-Isodose mu\te das Planungszielvolumen umschlie\en. Es wurden bei allen Techniken Multileaf-Kollimatoren verwendet und Dosis-Volumen-Histogramme für das Planungszielvolumen und die Risikoorgane (Blase, Rektum, Hüftköpfe) erstellt und miteinander verglichen. Der Vergleich erfolgte jeweils bei 33%, 50% und 66% Volumen des jeweiligen Risikoorgans.ErgebnisseHinsichtlich der Dosishomogenität im Targetvolumen zeigte sich kein Unterschied. Eine signifikante Differenz wurde bei der Blasenbelastung zwischen der Sechs-Felder- und der Vier-Felder-Technik nur bei 50% Volumenanteil (p = 0,034), zwischen Sechs-Felder- und Rotationstechnik sowie zwischen Fünf-Felder- und Rotationstechnik bei allen Volumenanteilen gesehen. Bei der Belastung des Rektums ergab sich eine signifikante Differenz zwischen der Sechs- und der Vier-Felder-Technik bei T1- und T2-Tumoren sowohl bei 50% (p = 0,033) als auch bei 66% (p = 0,011). Bei den T3-Tumoren ergaben sich hinsichtlich der Rektumbelastung keine signifikanten Unterschiede. Die beste Schonung der Hüftköpfe wurde durch die Rotationstechnik erzielt.Schlu\folgerungBei der kleinvolumigen Bestrahlung der Prostata ist bei T1/2-Tumoren durch die Sechs-Felder-Technik die beste Schonung von Rektum und Blase zu erzielen, bei grö\erem Planungszielvolumen und bei Einschlu\ der SamenblÄschen sollten andere Techniken, wie zum Beispiel eine dreidimensional geplante Vier-Felder-Technik, zur besseren Schonung der Risikoorgane angewendet werden.AbstractPurposeFour different three-dimensional planning techniques for localized radiotherapy of prostate cancer were compared with regard to dose homogeneity within the target volume and dose to organs at risk, dependent upon tumor stage.Patients and MethodsSix patients with stage T1, 7 patients with stage T2 and 4 patients with stage T3 were included in this study. Four different 3D treatment plans (rotation, 4-field, 5-field and 6-field technique) were calculated for each patient. Dose was calculated with the reference point at the isocenter (100%). The planning target volume was encompassed within the 95% isodose surface. All the techniques used different shaped portal for each beam. Dose volume histograms were created and compared for the planning target volume and the organs at risk (33%, 50%, 66% volume level) in all techniques.ResultsThe 4 different three-dimensional planning techniques revealed no differences concerning dose homogeneity within the planning target volume. The dose volume distribution at organs at risk show differences between the calculated techniques. In our study the best protection for bladder and rectum in stage T1 and T2 was achieved by the 6-field technique. A significant difference was achieved between 6-field and 4-field technique only in the 50% volume of the bladder (p = 0.034), between the 6-field and rotation technique (all volume levels) and between 5-field and rotation technique (all volume levels). In stage T1, T2 6-field and 4-field technique in 50% (p = 0.033) and 66% (p = 0.011) of the rectum volume. In stage T3 a significant difference was not observed between the 4 techniques. The best protection of head of the femur was achieved by the rotation technique.ConclusionIn the localized radiotherapy of prostate cancer in stage T1 or T2 the best protection for bladder and rectum was achieved by a 3D-planned conformai 6-field technique. If the seminal vesicles have been included in the target volume and in the case of large planning target volume other techniques should be taken for a better protection for organs at risk e. g. a 3D-planned 4-field technique box technique.PURPOSE Four different three-dimensional planning techniques for localized radiotherapy of prostate cancer were compared with regard to dose homogeneity within the target volume and dose to organs at risk, dependent upon tumor stage. PATIENTS AND METHODS Six patients with stage T1, 7 patients with stage T2 and 4 patients with stage T3 were included in this study. Four different 3D treatment plans (rotation, 4-field, 5-field and 6-field technique) were calculated for each patient. Dose was calculated with the reference point at the isocenter (100%). The planning target volume was encompassed within the 95% isodose surface. All the techniques used different shaped portal for each beam. Dose volume histograms were created and compared for the planning target volume and the organs at risk (33%, 50%, 66% volume level) in all techniques. RESULTS The 4 different three-dimensional planning techniques revealed no differences concerning dose homogeneity within the planning target volume. The dose volume distribution at organs at risk show differences between the calculated techniques. In our study the best protection for bladder and rectum in stage T1 and T2 was achieved by the 6-field technique. A significant difference was achieved between 6-field and 4-field technique only in the 50% volume of the bladder (p = 0.034), between the 6-field and rotation technique (all volume levels) and between 5-field and rotation technique (all volume levels). In stage T1, T2 6-field and 4-field technique in 50% (p = 0.033) and 66% (p = 0.011) of the rectum volume. In stage T3 a significant difference was not observed between the 4 techniques. The best protection of head of the femur was achieved by the rotation technique. CONCLUSION In the localized radiotherapy of prostate cancer in stage T1 or T2 the best protection for bladder and rectum was achieved by a 3D-planned conformal 6-field technique. If the seminal vesicles have been included in the target volume and in the case of large planning target volume other techniques should be taken for a better protection for organs at risk e. g. a 3D-planned 4-field technique box technique.

Long‐term clopidogrel administration following severe coronary injury reduces proliferation and inflammation via inhibition of nuclear factor‐kappaB and activator protein 1 activation in pigs

Background  The optimal duration of clopidogrel treatment following percutaneous coronary intervention (PCI) and the patient population that would benefit most are still unknown. In a porcine coronary injury model, we tested two different durations of clopidogrel treatment on severely or moderately injured arteries and examined the arterial response to injury. To understand the molecular mechanism, we also investigated the effects on transcription factors nuclear factor‐kappaB (NF‐κB) and activator protein 1 (AP‐1).

Virtuelle Simulation@@@Virtual simulation — First clinical results in patients with prostate cancer: Erste klinische Ergebnisse bei Patienten mit Prostatakarzinom

AIM Investigation of options of virtual simulation in patients with localized prostate cancer. PATIENTS AND METHODS Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patients skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning. RESULTS Mean differences of the patients mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs. CONCLUSIONS The precise patients mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarily of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning.ZusammenfassungZielUntersuchung von Optionen der virtuellen Simulation bei Patienten mit lokal begrenztem Prostatakarzinom.Patienten und Methode24 Patienten mit einem lokal begrenzten Prostatakarzinom wurden virtuell simuliert. Nach dem Bestrahlungsplanungs-CT erfolgte die Konturierung des Klinischen Zielvolumens und des Planungszielvolumens sowie die Bestimmung des geometrischen Isozentrums, das auf der Haut markiert wurde. Nach Erstellung des Bestrahlungsplanes wurde die Genauigkeit der Markierung des Isozentrums am konventionellen Simulator überprüft.ErgebnisseDie Markierung des Isozentrums an den Patienten erfolgte mit einer mittleren Abweichung von 1 mm in allen drei Ebenen. Auf den digital rekonstruierten Simulationsaufnahmen werden alle vorher konturierten Strukturen wie Zielvolumina und Risikoorgane dargestellt.SchlußfolgerungenAufgrund der Präzision der Markierung des Isozentrums kann bei Einsatz der virtuellen Simulation bei Patienten mit einem lokal begrenzten Prostatakarzinom auf die konventionelle Simulation verzichtet werden. Die Darstellung der Risikoorgane in den digital rekonstruierten Simulationsaufnahmen ermöglicht den Verzicht auf die Kontrastmittelapplikation bei der Simulation und führt zu einer weiteren Entlastung für den Patienten. Der personelle Aufwand ist im Vergleich zur konventionellen CT-gestützten Bestrahlungsplanung nicht höher.AbstractAimInvestigation of options of virtual simulation in patients with localized prostate cancer.Patients and MethodsTwenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient’s skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning.ResultsMean differences of the patient’s mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs.ConclusionThe precise patient’s mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarity of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning.

Cytoprotective effects of opioids on irradiated oral epithelial cells

Oral mucositis is a common side effect of chemotherapy and radiation therapy accompanied with acute inflammation and ulceration of the oral mucosa. Opioids can improve the wound healing of dermal and oral tissue when applied locally. The aim of this study was to investigate if morphine exhibits cytoprotective effects on oral epithelial cells postirradiation. Hence, oral epithelial cells were exposed to increasing doses (3–30 Gy) of ionization radiation. We assessed the effects of the radiation on cell viability, proinflammatory cytokine release (interleukin [IL]‐1α, IL‐6), and matrix metalloproteinase (MMP‐1, ‐8, and ‐9) expression. As expected, radiation significantly impaired cell viability and morphology and resulted in enhanced IL release. However, morphine‐treated cells consistently showed higher cell viability postirradiation: 9.19 ± 1.16% after 24 hours and 7.45 ± 0.93% after 48 hours compared with the control. In terms of proinflammatory cytokines, the release of IL‐1α and IL‐6 was significantly reduced, too, being most pronounced at 48 hours postradiation. Additionally, we observed a significant reduction of MMP‐1 and especially MMP‐9 expression in morphine‐treated cells. The results clearly indicate anti‐inflammatory as well as cytoprotective effects of morphine on irradiated oral epithelial cells. Interestingly, the protective effects of morphine are not related to a decrease in cell apoptosis or necrosis. Before final conclusions can be drawn, further studies in more complex systems in vitro and in vivo are required. Nevertheless, these findings further underline the high potential of opioids for the treatment of topical wounds and inflammatory conditions.