Franca Foppiano

Rectal dose–volume constraints in high-dose radiotherapy of localized prostate cancer

PURPOSE To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. METHODS In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. RESULTS Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. CONCLUSIONS The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.

THE IMPACT OF CONTOURING UNCERTAINTY ON RECTAL 3D DOSE- VOLUME DATA: RESULTS OF A DUMMY RUN IN A MULTICENTER TRIAL (AIROPROS01- 02)

PURPOSE To estimate the impact of the uncertainty in contouring the rectum on rectal dose-volume parameters and normal tissue complication probability (NTCP) in a prospective (AIROPROS01-02) investigation about rectal toxicity. METHODS AND MATERIALS The participants in a prospective trial (18 observers) were asked to draw the external contour of the rectum of 4 sample patients (3 patients undergoing radical conformal radiotherapy, 1 patient undergoing post-prostatectomy) on CT images (0.5 cm spacing) using a 3D treatment planning system. A previously accepted definition of cranial and caudal borders of the rectum was applied. For each patient, four- and six-field 3D-conformal techniques (70-76 Gy, ICRU dose) were planned and DVH/dose statistics of the rectum were calculated. The impact of interobserver variability on rectal volume, cranial and caudal borders, mean, maximum, and median rectal dose, percentage of rectum receiving more than 40, 45, 50, 55, 60, 65, 70, and 75 Gy (V(40)-V(75)), and NTCP were investigated. RESULTS Concerning DVHs, 9/18 observers tended to have some systematic deviation. However, deviations from the mean values greater than 5% were found only in 1/9 because of a systematic discrepancy in the caudal limit assessment (mean deviation from the most frequently chosen slice: 8 mm). No other observers showed a mean deviation in the cranial or the caudal limit definition greater than 5.8 mm. For another observer, it was possible to clearly assess the cause of a relatively large systematic deviation for DVH parameters. In both cases, the observers were contacted to avoid these systematic deviations. When considering the remaining 16/18 observers, the average values of SD for V(40)-V(75) ranged between 1% and 4% and were found to be lower (<3%) for the 3 nonoperated patients. The average values of the SD were around 1.5-2 Gy and less than 1.5% for mean/median dose and NTCPs, respectively. CONCLUSIONS Concerning the uncertainty in rectum definition, the collection of rectal dose-volume data in multicenter investigations seems to be feasible after a clear and previously accepted definition of rectum is assessed. However, even with a general agreement on rectum definition, contouring appears to be a quite significant source of uncertainty. A dummy run procedure is useful in identifying possible discrepancies among single observers and in assessing reliable confidence levels on dose-volume constraints because of contouring uncertainty, making the dummy run mandatory in multicenter trials evaluating 3D dose-volume data.

Does treatment of the pelvic nodes with IMRT increase late rectal toxicity over conformal prostate-only radiotherapy to 76 Gy?

Purpose:To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate.Patients and Methods:68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months).Results:At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6% ± 4% for WP-IMRT/PB and 21.2% ± 6% for P-3D-CRT (p = 0.06). The difference became significant (HR [hazard ratio] = 0.1, 95% CI [confidence interval]: 0.0–0.6; p = 0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity.Conclusion:Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.Ziel:Vergleich der rektalen Spättoxizität nach alleiniger dreidimensionaler konformaler Strahlentherapie der Prostata (P-3D-CRT) und nach intensitätsmodulierter Radiotherapie des gesamten Beckens mit Prostataradiochirurgie (WP-IMRT/PB) bei gleicher Gesamtdosis.Patienten und Methodik:Die erste Gruppe bestand aus 68 Patienten, die eine alleinige konformale Strahlentherapie der Prostata bis 76 Gy am National Institute for Cancer Research in Genua, Italien, erhielten (P-3D-CRT). Die zweite Gruppe umfasste 45 Patienten, welche am University of Texas Medical Branch (UTMB), Galveston, TX, USA, mit IMRT der Beckenlymphknoten und der Samenbläschen bis 54 Gy zu 1,8 Gy pro Fraktion und der Prostata bis 60 Gy, ebenfalls in 30 Fraktionen, behandelt wurden. Die Radiochirurgie der Prostata erfolgte separat bis 76 Gy (WP-IMRT/PB). Die Hauptaspekte bei der Planung waren an beiden Einrichtungen bemerkenswert ähnlich, so dass lediglich die Frage des Einschlusses der Beckenlymphknoten als Hauptunterschied bei der Behandlung der beiden Gruppen übrig blieb. Die rektale Spättoxizität wurde anhand der RTOG-Skala bewertet. Alle Patienten erhalten eine mindestens 12-monatige Nachsorge; die durchschnittliche Nachsorgedauer beträgt bei beiden Gruppen 25,9 Monate (SD [Standardabweichung]: 8,4 Monate).Ergebnisse:Nach 2 Jahren liegt die geschätzte kumulative Inzidenz der rektalen Spättoxizität Grad 2 bei 6% ± 4% für WP-IMRT/PB und 21,2% ± 6% für P-3D-CRT (p = 0,06). Der Unterschied wurde bei der Multivarianzanalyse signifikant (HR [Hazard-Ratio] = 0,1, 95%-CI [Konfidenzintervall]: 0,0–0,6; p = 0,01). Kein Patient entwickelte eine rektale Spättoxizität Grad 3+.Schlussfolgerung:Trotz des größeren Behandlungsumfangs ermöglicht die WP-IMRT/PB eine schonendere Behandlung des Rektalbereichs als die P-3D-CRT.

Sucralfate versus mesalazine versus hydrocortisone in the prevention of acute radiation proctitis during conformal radiotherapy for prostate carcinoma: A randomized study

Purpose: To assess whether the topical use of steroids or 5-aminosalicylic acid (5-ASA) is superior to sucralfate in preventing acute rectal toxicity during three-dimensional conformal radiotherapy (3DCRT) to 76 Gy. Patients and Methods: Patients undergoing 3DCRT for prostate carcinoma at our institution were offered to be randomized to sucralfate 3 g in 15 ml suspension enema (Antepsin®), mesalazine 4 g gel enema (Enterasyn®), or hydrocortisone 100 mg foam enema (Colifoam®). Randomization was blind to the treating physician but not to the patient. Sucralfate was chosen as control arm. Topical treatment had to be performed once daily, starting on day 1 of 3DCRT. Acute rectal toxicity was scored weekly according to RTOG criteria. Time to occurrence of grade 2+ acute rectal toxicity was taken as endpoint. Results: The trial was opened in August 1999, and after the first 24 patients had been treated, arm 2 was discontinued because of eight patients receiving mesalazine, seven actually developed acute rectal toxicity (five patients grade 3 and two patients grade 2).Until May 2001, 134 consecutive patients were randomly assigned to sucralfate (63 patients), mesalazine (eight patients) or hydrocortisone (63 patients). The cumulative incidence of acute rectal toxicity at the end of treatment by arm is 61.9 ± 6.1%, 87.5 ± 11.7%, and 52.4 ± 6.2% for arms 1, 2, and 3, respectively. The difference between the mesalazine group and the sucralfate group is highly significant (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.1–5.7; p = 0.03). At both uni- and multivariate analysis taking into account several patients and treatment covariates, the difference between hydrocortisone and sucralfate is not significant (HR 0.7, 95% CI 0.5–1.2; p = 0.2). Conclusion: Topical mesalazine is contraindicated during radiotherapy. Hydrocortisone enema is not superior to sucralfate in preventing acute rectal toxicity.Fragestellung: Randomisierter Vergleich der lokalen Anwendung von Steroiden oder 5-ASA oder Sucralfat zur Prävention einer akuten Strahlenproktitis unter 3-D-konformaler Radiotherapie (3DCRT) bis 76 Gy. Patienten und Methodik: Patienten, die sich in unserer Klinik wegen eines Prostatakarzinoms einer 3DCRT unterzogen, wurde randomisiert angeboten eine Vorbehandlung 1) mit Sucralfat (3 g suspendiert im 15-ml-Klysma), 2) Mesalazin als 4-g-Gelklysma) oder 3) Hydrocortison: 100 mg als Schaumklysma). Die Randomisierung zu einem dieser drei Studienarme war dem behandelnden Arzt unbekannt, nicht aber dem Patienten. Sucralfat wurde als Kontrollarm gewählt. Die jeweilige topische Therapie musste ab dem 1. Tag der 3DCRT einmal täglich durchgeführt werden. Auf akute Strahlenproktitis wurde jede Woche nach RTOG-Kriterien geprüft. Als Endpunkt wurde das Auftreten einer akuten Strahlenproktitis Grad 2 festgelegt. Ergebnisse: Die Studie begann im August 1999. Nachdem die ersten 24 Patienten aufgenommen worden waren, wurde Arm 2 abgebrochen, da sieben Patienten unter Mesalazin eine akute Strahlenproktitis (Grad 3 bei fünf Patienten und Grad 2 bei zwei Patienten) entwickelten.Bis zum Mai 2001 wurden 134 Patienten der lokalen Anwendung von Sucralfat (63 Patienten), Mesalazin (acht Patienten) oder Hydrocortison (63 Patienten) zugeführt. Die kumulative Inzidenz akuter Strahlenproktitis betrug jeweils 61,9 ± 6,1%, 87,5 ± 11,7% und 52,4 ± 6,2%. Der Unterschied zwischen Mesalazin- und Sucralfat-Gruppe ist hoch signifikant (HR: 2,5; 95%-CI: 1,1–5,7; p = 0,03), der zwischen Hydrocortison und Sucralfat nicht (HR = 0,7; 95%-CI: 0,5–1,2; p = 0,2). Schlussfolgerung: Topisches Mesalazin ist unter Radiotherapie kontraindiziert. Hydrocortison-Klysmen und Sucralfat sind zur Prophylaxe einer akuten Strahlenproktitis gleichwertig.

Sucralfate versus Mesalazine versus Hydrocortisone in the Prevention of Acute Radiation Proctitis during Conformal Radiotherapy for Prostate Carcinoma

Purpose: To assess whether the topical use of steroids or 5-aminosalicylic acid (5-ASA) is superior to sucralfate in preventing acute rectal toxicity during three-dimensional conformal radiotherapy (3DCRT) to 76 Gy. Patients and Methods: Patients undergoing 3DCRT for prostate carcinoma at our institution were offered to be randomized to sucralfate 3 g in 15 ml suspension enema (Antepsin®), mesalazine 4 g gel enema (Enterasyn®), or hydrocortisone 100 mg foam enema (Colifoam®). Randomization was blind to the treating physician but not to the patient. Sucralfate was chosen as control arm. Topical treatment had to be performed once daily, starting on day 1 of 3DCRT. Acute rectal toxicity was scored weekly according to RTOG criteria. Time to occurrence of grade 2+ acute rectal toxicity was taken as endpoint. Results: The trial was opened in August 1999, and after the first 24 patients had been treated, arm 2 was discontinued because of eight patients receiving mesalazine, seven actually developed acute rectal toxicity (five patients grade 3 and two patients grade 2).Until May 2001, 134 consecutive patients were randomly assigned to sucralfate (63 patients), mesalazine (eight patients) or hydrocortisone (63 patients). The cumulative incidence of acute rectal toxicity at the end of treatment by arm is 61.9 ± 6.1%, 87.5 ± 11.7%, and 52.4 ± 6.2% for arms 1, 2, and 3, respectively. The difference between the mesalazine group and the sucralfate group is highly significant (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.1–5.7; p = 0.03). At both uni- and multivariate analysis taking into account several patients and treatment covariates, the difference between hydrocortisone and sucralfate is not significant (HR 0.7, 95% CI 0.5–1.2; p = 0.2). Conclusion: Topical mesalazine is contraindicated during radiotherapy. Hydrocortisone enema is not superior to sucralfate in preventing acute rectal toxicity.Fragestellung: Randomisierter Vergleich der lokalen Anwendung von Steroiden oder 5-ASA oder Sucralfat zur Prävention einer akuten Strahlenproktitis unter 3-D-konformaler Radiotherapie (3DCRT) bis 76 Gy. Patienten und Methodik: Patienten, die sich in unserer Klinik wegen eines Prostatakarzinoms einer 3DCRT unterzogen, wurde randomisiert angeboten eine Vorbehandlung 1) mit Sucralfat (3 g suspendiert im 15-ml-Klysma), 2) Mesalazin als 4-g-Gelklysma) oder 3) Hydrocortison: 100 mg als Schaumklysma). Die Randomisierung zu einem dieser drei Studienarme war dem behandelnden Arzt unbekannt, nicht aber dem Patienten. Sucralfat wurde als Kontrollarm gewählt. Die jeweilige topische Therapie musste ab dem 1. Tag der 3DCRT einmal täglich durchgeführt werden. Auf akute Strahlenproktitis wurde jede Woche nach RTOG-Kriterien geprüft. Als Endpunkt wurde das Auftreten einer akuten Strahlenproktitis Grad 2 festgelegt. Ergebnisse: Die Studie begann im August 1999. Nachdem die ersten 24 Patienten aufgenommen worden waren, wurde Arm 2 abgebrochen, da sieben Patienten unter Mesalazin eine akute Strahlenproktitis (Grad 3 bei fünf Patienten und Grad 2 bei zwei Patienten) entwickelten.Bis zum Mai 2001 wurden 134 Patienten der lokalen Anwendung von Sucralfat (63 Patienten), Mesalazin (acht Patienten) oder Hydrocortison (63 Patienten) zugeführt. Die kumulative Inzidenz akuter Strahlenproktitis betrug jeweils 61,9 ± 6,1%, 87,5 ± 11,7% und 52,4 ± 6,2%. Der Unterschied zwischen Mesalazin- und Sucralfat-Gruppe ist hoch signifikant (HR: 2,5; 95%-CI: 1,1–5,7; p = 0,03), der zwischen Hydrocortison und Sucralfat nicht (HR = 0,7; 95%-CI: 0,5–1,2; p = 0,2). Schlussfolgerung: Topisches Mesalazin ist unter Radiotherapie kontraindiziert. Hydrocortison-Klysmen und Sucralfat sind zur Prophylaxe einer akuten Strahlenproktitis gleichwertig.

Anatomic variations due to radical prostatectomy. Impact on target volume definition and dose-volume parameters of rectum and bladder.

Background and Purpose:A quantitative estimate of the impact of prostatectomy on pelvic anatomy is unavailable, even if it would be an important prerequisite for a precise definition of clinical target volume (CTV) in post-prostatectomy radiotherapy. The purpose of this study was to investigate the impact of prostatectomy on the definition of CTV, on the position of bladder and rectum and their implications for three-dimensional conformal radiotherapy (3-D CRT).Patients and Methods:Six patients eligible for radical retropubic prostatectomy were considered. Each patient underwent a planning CT between 1 week and 1 month before surgery (CTpre), and then CT was repeated in the same positioning 1–2 months after surgery (CTpost). For each patient the CTpre/post scans were matched; rectum, bladder and CTV were contoured on both CT scans for each patient by one observer. Two different CTVs were contoured: CTV1: prostate + seminal vesicles in CTpre; prostate + seminal vesicles surgical bed in CTpost; CTV2: prostate in CTpre; prostate surgical bed in CTpost. After image registration, the contours of rectum, bladder and CTV1/2 drawn on CTpost were transferred on CTpre. The corresponding planning target volumes (PTVs) were generated, and for each PTV, a conformal four field technique using 18-MV X-rays was planned. The volumes of CTV1, CTV2, PTV1, PTV2, rectum and bladder pre- and post-surgery were compared. Differences in 3-D position of these structures before and after surgery were analyzed by beam’s eye view (BEV) images. Pre- and post-surgery dose-volume histograms (DVHs) of rectum and bladder were compared together with the fraction of rectum/bladder receiving at least 95% of the ICRU dose (V95), the treated volume (TV, body included in the 95% isodose) and the irradiated volume (IV, body included in the 50% isodose).Results:For both CTV1 and CTV2, the volumes were significantly reduced after prostatectomy (average reduction around 30 cm3 for both; range 0–60 cm3). This reduction was mainly due to a more caudal definition of the cranial edge of CTV after prostatectomy (average difference for CTV2: 1.5 cm; range 0–2.5 cm). Concerning the bladder, a systematic posterior shift of the bladder base (average: 1.5 cm) was found and was correlated with a significant reduction of V95 for bladder (around 10 cm3; p = 0.03). V95 of the rectum, TV and IV also resulted to be significantly lower after surgery. The average reduction of V95 for the rectum was relatively small (2.5 cm3 of rectal wall).Conclusion:The impact of prostatectomy on CTV definition is high. A significant reduction of CTV, PTV, TV and IV may be expected after surgery with a consequent reduction of the portions of rectum/bladder irradiated with adjuvant radiotherapy.Hintergrund und Ziel:Eine Methode zur quantitativen Bestimmung der Auswirkungen einer Prostatektomie auf die Anatomie des Beckenraums gibt es nicht, obwohl dies eine wichtige Voraussetzung für eine genaue Festlegung des klinischen Zielvolumens (CTV) für die postoperative Radiotherapie wäre. Ziel dieser Studie war, die Auswirkungen der Prostatektomie auf die Zielvolumendefinition, auf die anatomische Lage von Blase und Rektum und die Folgen für die dreidimensionale konformale Radiotherapie (3-D CRT) zu untersuchen.Patienten und Methodik:Sechs Patienten, bei denen eine radikale retropubische Prostatektomie indiziert war, unterzogen sich einer Planungs-CT 1 Woche bis 1 Monat präoperativ (CTpre); die CT wurde in der gleichen Positionierung 1-2 Monate postoperativ wiederholt (CTpost). Für jeden Patienten wurden die CTpre- und CTpost-Aufnahmen verglichen sowie Rektum, Blase und CTV auf beiden CTs für jeden Patienten vom selben Untersucher eingetragen. Es wurden unterschiedliche CTVs eingetragen: CTV1: Prostata + Samenbläschen in CTpre; Operationsfeld von Prostata + Samenbläschen in CTpost; CTV2: Prostata in CTpre; Prostataoperationsfeld in CTpost. Nach der Bildaufzeichnung wurden die Umrisse von Rektum, Blase und CTV1/2 von CTpost auf CTpre übertragen. Die entsprechenden Planungszielvolumina (PTV) wurden ermittelt und für jedes PTV wurde eine konformale Vier-Felder-Technik mit 18-MV-Röntgenstrahlung geplant. Die Werte von CTV1, CTV2, PTV1, PTV2, Rektum und Blase jeweils prä- und postoperativ wurden verglichen. Die Unterschiede in der dreidimensionalen Position dieser Volumina wurden prä- und postoperativ mittels BEV-(Beam’s-Eye-View-)Darstellung verglichen. Prä- und postoperative Dosis-Volumen-Histogramme (DVHs) von Rektum und Blase wurden verglichen und der Anteil von Rektum und Blase, die mindestens 95% der ICRU-Dosis (V95) erhielten, sowie das Behandlungsvolumen (TV, innerhalb der 95%-Isodose) und das Bestrahlungsvolumen (IV, innerhalb der 50%-Isodose).Ergebnisse:Für CTV1 wie auch CTV2 waren die Werte nach Prostatektomie signifikant geringer (durchschnittliche Abnahme ca. 30 cm3 für beide Werte; Range 0-60 cm3). Diese Reduktion war im Wesentlichen einer weiter kaudalen Lage des kranialen CTV-Randes nach Prostatektomie (durchschnittliche Abweichung für CTV2: 1,5 cm; Spannweite 0-2,5 cm) zuzuschreiben. Für die Blase wurde regelmäßig eine posteriore Verschiebung des Blasenbodens (Durchschnitt: 1,5 cm) festgestellt, die mit einer signifikanten Verminderung von V95 der Blase (ca. 10 cm3; p = 0,03) korrelierte. V95 des Rektums, TV and IV waren postoperativ ebenfalls signifikant kleiner. Die durchschnittliche Abnahme von V95 des Rektums war relativ klein (2,5 cm3 der Rektumwand).Schlussfolgerung:Die Auswirkungen der Prostatektomie auf die CTV-Definition sind bedeutend. Postoperativ ist eine signifikante Abnahme von CTV, PTV, TV und IV zu erwarten mit der Folge einer Verminderung der bei der adjuvanten Radiotherapie von Strahlung erfassten Anteile von Rektum und Blase.

Anatomic Variations Due to Radical Prostatectomy

Background and Purpose:A quantitative estimate of the impact of prostatectomy on pelvic anatomy is unavailable, even if it would be an important prerequisite for a precise definition of clinical target volume (CTV) in post-prostatectomy radiotherapy. The purpose of this study was to investigate the impact of prostatectomy on the definition of CTV, on the position of bladder and rectum and their implications for three-dimensional conformal radiotherapy (3-D CRT).Patients and Methods:Six patients eligible for radical retropubic prostatectomy were considered. Each patient underwent a planning CT between 1 week and 1 month before surgery (CTpre), and then CT was repeated in the same positioning 1–2 months after surgery (CTpost). For each patient the CTpre/post scans were matched; rectum, bladder and CTV were contoured on both CT scans for each patient by one observer. Two different CTVs were contoured: CTV1: prostate + seminal vesicles in CTpre; prostate + seminal vesicles surgical bed in CTpost; CTV2: prostate in CTpre; prostate surgical bed in CTpost. After image registration, the contours of rectum, bladder and CTV1/2 drawn on CTpost were transferred on CTpre. The corresponding planning target volumes (PTVs) were generated, and for each PTV, a conformal four field technique using 18-MV X-rays was planned. The volumes of CTV1, CTV2, PTV1, PTV2, rectum and bladder pre- and post-surgery were compared. Differences in 3-D position of these structures before and after surgery were analyzed by beam’s eye view (BEV) images. Pre- and post-surgery dose-volume histograms (DVHs) of rectum and bladder were compared together with the fraction of rectum/bladder receiving at least 95% of the ICRU dose (V95), the treated volume (TV, body included in the 95% isodose) and the irradiated volume (IV, body included in the 50% isodose).Results:For both CTV1 and CTV2, the volumes were significantly reduced after prostatectomy (average reduction around 30 cm3 for both; range 0–60 cm3). This reduction was mainly due to a more caudal definition of the cranial edge of CTV after prostatectomy (average difference for CTV2: 1.5 cm; range 0–2.5 cm). Concerning the bladder, a systematic posterior shift of the bladder base (average: 1.5 cm) was found and was correlated with a significant reduction of V95 for bladder (around 10 cm3; p = 0.03). V95 of the rectum, TV and IV also resulted to be significantly lower after surgery. The average reduction of V95 for the rectum was relatively small (2.5 cm3 of rectal wall).Conclusion:The impact of prostatectomy on CTV definition is high. A significant reduction of CTV, PTV, TV and IV may be expected after surgery with a consequent reduction of the portions of rectum/bladder irradiated with adjuvant radiotherapy.Hintergrund und Ziel:Eine Methode zur quantitativen Bestimmung der Auswirkungen einer Prostatektomie auf die Anatomie des Beckenraums gibt es nicht, obwohl dies eine wichtige Voraussetzung für eine genaue Festlegung des klinischen Zielvolumens (CTV) für die postoperative Radiotherapie wäre. Ziel dieser Studie war, die Auswirkungen der Prostatektomie auf die Zielvolumendefinition, auf die anatomische Lage von Blase und Rektum und die Folgen für die dreidimensionale konformale Radiotherapie (3-D CRT) zu untersuchen.Patienten und Methodik:Sechs Patienten, bei denen eine radikale retropubische Prostatektomie indiziert war, unterzogen sich einer Planungs-CT 1 Woche bis 1 Monat präoperativ (CTpre); die CT wurde in der gleichen Positionierung 1-2 Monate postoperativ wiederholt (CTpost). Für jeden Patienten wurden die CTpre- und CTpost-Aufnahmen verglichen sowie Rektum, Blase und CTV auf beiden CTs für jeden Patienten vom selben Untersucher eingetragen. Es wurden unterschiedliche CTVs eingetragen: CTV1: Prostata + Samenbläschen in CTpre; Operationsfeld von Prostata + Samenbläschen in CTpost; CTV2: Prostata in CTpre; Prostataoperationsfeld in CTpost. Nach der Bildaufzeichnung wurden die Umrisse von Rektum, Blase und CTV1/2 von CTpost auf CTpre übertragen. Die entsprechenden Planungszielvolumina (PTV) wurden ermittelt und für jedes PTV wurde eine konformale Vier-Felder-Technik mit 18-MV-Röntgenstrahlung geplant. Die Werte von CTV1, CTV2, PTV1, PTV2, Rektum und Blase jeweils prä- und postoperativ wurden verglichen. Die Unterschiede in der dreidimensionalen Position dieser Volumina wurden prä- und postoperativ mittels BEV-(Beam’s-Eye-View-)Darstellung verglichen. Prä- und postoperative Dosis-Volumen-Histogramme (DVHs) von Rektum und Blase wurden verglichen und der Anteil von Rektum und Blase, die mindestens 95% der ICRU-Dosis (V95) erhielten, sowie das Behandlungsvolumen (TV, innerhalb der 95%-Isodose) und das Bestrahlungsvolumen (IV, innerhalb der 50%-Isodose).Ergebnisse:Für CTV1 wie auch CTV2 waren die Werte nach Prostatektomie signifikant geringer (durchschnittliche Abnahme ca. 30 cm3 für beide Werte; Range 0-60 cm3). Diese Reduktion war im Wesentlichen einer weiter kaudalen Lage des kranialen CTV-Randes nach Prostatektomie (durchschnittliche Abweichung für CTV2: 1,5 cm; Spannweite 0-2,5 cm) zuzuschreiben. Für die Blase wurde regelmäßig eine posteriore Verschiebung des Blasenbodens (Durchschnitt: 1,5 cm) festgestellt, die mit einer signifikanten Verminderung von V95 der Blase (ca. 10 cm3; p = 0,03) korrelierte. V95 des Rektums, TV and IV waren postoperativ ebenfalls signifikant kleiner. Die durchschnittliche Abnahme von V95 des Rektums war relativ klein (2,5 cm3 der Rektumwand).Schlussfolgerung:Die Auswirkungen der Prostatektomie auf die CTV-Definition sind bedeutend. Postoperativ ist eine signifikante Abnahme von CTV, PTV, TV und IV zu erwarten mit der Folge einer Verminderung der bei der adjuvanten Radiotherapie von Strahlung erfassten Anteile von Rektum und Blase.

Postoperative radiotherapy for head and neck squamous cell carcinomas: Feasibility of a biphasic accelerated treatment schedule

PURPOSE It has been suggested that postoperative tumor cell proliferation may influence the outcome of advanced head and neck squamous cell carcinomas treated by surgery and postoperative radiotherapy. This Phase I pilot study was undertaken to determine the feasibility of a biphasic accelerated radiotherapy regimen with early and late concomitant boost delivery for postoperative treatment of patients with advanced head and neck cancers. METHODS AND MATERIALS From April 1993 to April 1994, 29 patients with advanced head and neck cancers were enrolled in this study after they underwent complete surgical resection. The basic radiation course delivered a median dose of 49 Gy in 25 fractions over 5 weeks at 1.8-2 Gy/fraction. The concomitant boost was delivered to the high-risk areas as a second daily fraction during the first (1.4 Gy/fraction) and fifth weeks (1.6 Gy/fraction). The total dose to the high-risk areas was 64 Gy in 35 fractions over 5 weeks. RESULTS Twenty-seven patients (93%) completed the treatment without interruptions. Only two patients experienced severe acute toxicity requiring treatment breaks of 6 and 8 days, respectively. All patients developed confluent mucositis; in 69% of the cases it covered >50% of the treated surface. No patient developed Grade 5 (ulceration/bleeding) mucosal reaction. Mucositis required a median time of 7 weeks for complete healing (range 3-43). Two patients developed transient bone exposure. The median weight loss was 5.5% of pretreatment body weight (range 1.2-17.1%), and four patients required nutritional assistance with nasogastric feeding tube. CONCLUSION The results of this study show that this biphasic acceleration regimen is feasible with acceptable acute toxicity.

Kidney-sparing radiotherapy by multiple-field three-dimensional technique in the postoperative management of patients with gastric cancer: Comparison with standard two-field conformal technique

Aims and Background The opposed two-field technique is the standard approach for delivering adjuvant radiotherapy to patients with resected gastric cancer. Since a considerable radiation dose may reach both kidneys with this beam arrangement, with a potential risk of late effects, we investigated whether the CT-based multiple-field (M-F) approach was superior in terms of sparing critical organs at risk. Methods From March 2001 to March 2004, 19 patients with radically resected gastric cancer entered the study. They were treated with adjuvant chemoradiotherapy according to the INT 0116 protocol. For each patient dose-volume histograms were calculated and the volume values of both kidneys and liver receiving 25 Gy (V25), 30 Gy (V30) and 40 Gy (V40) individually estimated with the M-F and two-field techniques were compared in detail. Results Right kidney median V25, V30 and V40 values for the two-field and M-F techniques were 1.50%, 0%, 0% and 0%, 0% and 0%, respectively (P <0.005, P <0.01, P <0.05). Left kidney median V25, V30 and V40 values for the M-F and two-field technique were 16%, 9.80%, 0.90% and 33.20%, 30.20%, 21.40% (P <0.001, P <0.0005, P <0.0005). Liver median V25, V30 and V40 values for the M-F and two-field techniques were 51.30%, 22.30%, 8.90% and 13.30%, 11.60%, 8.10%, respectively (P <0.0001, P <0.0005 and P = 0.18). Conclusions Our comparison revealed that with the multiple-field technique the right kidney may be largely spared from irradiation; with respect to the two-field technique, the left kidney may receive a significantly reduced dose; however, the liver receives an increased dose that warrants careful long-term monitoring of hepatic function.

On the delineation of the gross tumor volume and clinical target volume for head and neck squamous cell carcinomas.

Gross tumor volume (GTV) and clinical target volume (CTV) delineation on planning computed tomography (pICT) for head and neck squamous cell carcinomas can be troublesome. We highlight the factors which can be crucial for the radiation oncologist in delineating GTV and CTV on pICT and provide some pratical solutions. Regarding GTV, uncertainties are correlated with transfer of information collected by physical examination and diagnostic radiology to pICT. Moreover, reproducibility of delineation can also be highly variable, particularly when diagnostic imaging quality and pICT quality are poor. Once the prescription has been made, clinical target volume identification on pICT is rarely straightforward. Whereas there are some data about the location of major lymph node stations of the neck, there are no reported guidelines on how to draw subclinical extention of primary head and neck tumors on pICT. Such volumes can be derived from those currently included in simulator films or from those addressed by the surgeon. Some examples are provided. A particular situation is represented by the adjuvant setting, when the primary tumor is removed (by surgery) or reduced (by chemotherapy). In conclusion, this paper shows some major problems associated with identification of GTV and CTV on pICT. Apart from selected cases, the use of pICT for target volume delineation (and thus for field shaping) for head and neck squamous cell carcinoma is still to be considered investigational.