Intensity modulated radiotherapy with simultaneously integrated dose escalation in the clinical target volume as primary therapy for localised and locally advanced prostate cancer

Die perkutane Strahlentherapie ist neben der radikalen Prostatektomie die Therapiealternative zur Behandlung des lokalisierten und lokal fortgeschrittenen Prostatakarzinoms. Die vorliegende Arbeit untersuchte die onkologischen Ergebnisse und Nebenwirkungen von 307 Patienten mit Prostatakarzinom, die in den Jahren 2000 bis 2007 an der Charité in intensitätsmodulierter Technik mit simultaner integrierter Dosiseskalation im klinischen Zielvolumen bestrahlt wurden. Alle Patienten erhielten ein risikoadaptiertes Bestrahlungskonzept mit 72 Gy bis 75,6 Gy auf das PTV und mit 80 Gy bis 84 Gy auf das CTV in simultaner integrierter Dosiseskalation. Bei allen Patienten war die Bestrahlung die Primärbehandlung der Erkrankung, bei einigen Patienten wur-de zusätzlich eine neoadjuvante, begleitende und/oder eine adjuvante hormonablative Therapie durchgeführt. Die Nebenwirkungen wurden anhand der internationalen Common Terminology Criteria for Adverse Events CTCAE in der Version 3.0 ausgewertet. Die Rate des biochemisch-rezidivfreien Überlebens beträgt 84,5 % für alle Patienten und 70 %, 90 % und 87 % für Patien-ten der hohen, intermediären und niedrigen Risikogruppe. Urogenitale sowie gastrointestinale Nebenwirkungen Grad 2 oder höher traten bei 21,5 % und 4,3 % der Patienten auf, Nebenwir-kungen vierten und fünften Grades traten nicht auf. Urogenitale Grad 3 Spätnebenwirkungen (besonders häufig Pollakisurie) traten lediglich bei 5,2 % der Patienten auf. Gastrointestinale Grad 3 Spätnebenwirkungen wurden nicht beobachtet. Es existieren keine randomisierten Stu-dien, die den Stellenwert der intensitätsmodulierten Strahlentherapie gegenüber der 3D-konformalen Therapie darlegen. In dieser Arbeit kann gezeigt werden, dass die intensitätsmodu- lierte Strahlentherapie mit simultaner integrierter Dosiseskalation eine wirksame und nebenwir-kungsarme Therapieoption des lokalisierten und lokal fortgeschrittenen Prostatakarzinoms dar-stellt und mit anderen dosiseskalierten Serien vergleichbare Ergebnisse liefert. Insbesondere im Vergleich zur radikalen Prostatektomie ist die IMRT eine effektive und nebenwirkungsarme The-rapie. Allerdings ist das Kollektiv in der vorliegenden Arbeit nicht randomisiert, so dass ein Vor-teil dieser Methode nicht direkt mit einer Standardmethode unter identischen Voraussetzungen verglichen werden kann. Weitere Untersuchungen müssen zeigen, ob durch die neuen bildge-führten und rotationsmodulierten Strahlentherapietechniken die Rate an urogenitalen Nebenwir-kungen weiter gesenkt werden kann.External beam radiotherapy is the standard radiation therapy option for the treatment of prostate cancer. In this study we the analyzed the oncologic outcome and long term side effects of 307 patients with prostate cancer. Every patient in this group underwent a risk-adapted intensity modulated radiotherapy with simultaneous integrated dose escalation on the clinical target vol-ume. The planning target volume received a dose of 72-75.6 Gy, the clinical target volume re-ceived a dose of 80-84 Gy. For all patients the radiotherapy was the primary treatment of pros-tate cancer, some patients underwent an androgen deprivation before, during or after the irra-diation. For toxicity assessment the CTCAE v3.0 was used. The median follow up was 54 month, progression free survival was 84.5 % over all patients, 70 %, 90 % and 87 % for low- intermedi-ate- and high-risk group, respectively. 21.5 % and 4.3 % of the patients showed genitourinary and gastrointestinal late toxicity grade 2 or higher. There were no grade 4 and 5 side effects. Genitourinary grade 3 toxicity (very often pollakisuria) ocurred at 5.2 % of the patients. Gastrointestinal grade 3 side effects did not occur. Up to now no randomized study showed the superiority of intensity modulated radiotherapy for prostate cancer over 3 dimensional conformal radiotherapy. This study demonstrates that intensity modu-lated radiotherapy is a safe and effective treatment option for prostate cancer. The results are comparable to other published IMRT series. Direct comparison with standard 3D conformal ther-apy is not possible due to lack of randomisation

Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

PURPOSE: To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. MATERIAL AND METHODS: Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. RESULTS: Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. CONCLUSION: Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall

Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

Abstract Purpose To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. Material and methods Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. Results Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. Conclusion Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall.</p