Michela Marcenaro

Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma

To evaluate whether androgen deprivation impacts late rectal toxicity in patients with localised prostate carcinoma treated with three-dimensional conformal radiotherapy. One hundred and eighty-two consecutive patients treated with 3DCRT between 1995 and 1999 at our Institution and with at least 12 months follow-up were analysed. three-dimensional conformal radiotherapy consisted in 70–76 Gy delivered with a conformal 3-field arrangement to the prostate±seminal vesicles. As part of treatment, 117 patients (64%) received neo-adjuvant and concomitant androgen deprivation while 88 (48.4%) patients were continued on androgen deprivation at the end of three-dimensional conformal radiotherapy as well. Late rectal toxicity was graded according to the RTOG morbidity scoring scale. Median follow up is 25.8 (range: 12–70.2 months). The 2-year actuarial likelihood of grade 2–4 rectal toxicity was 21.8±3.2%. A multivariate analysis identified the use of adjuvant androgen deprivation (P=0.0196) along with the dose to the posterior wall of the rectum on the central axis (P=0.0055) and the grade of acute rectal toxicity (P=0.0172) as independent predictors of grade 2–4 late rectal toxicity. The 2-year estimates of grade 2–4 late rectal toxicity for patients receiving or not adjuvant hormonal treatment were 30.3±5.2% and 14.1±3.8%, respectively. Rectal tolerance is reduced in presence of adjuvant androgen deprivation.

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.

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.

Feasibility of helical tomotherapy for radical dose retreatment in pelvic area: a report of 4 cases

AIMS AND BACKGROUND To retrospectively determine acute toxicity and local control in patients with recurrence after definitive radiotherapy for prostate, bladder and rectal carcinoma. METHODS Between September 2009 and March 2010, 4 patients with a prior history of pelvic radiotherapy were treated with helical tomotherapy. The prior course of radiotherapy was given for prostate cancer in 2 patients, bladder carcinoma in 1 patient and rectal carcinoma in 1 patient. The median prescribed dose of the prior course of radiotherapy was 6320 cGy (range, 5000-7600), and the median elapsed time between the first and second course was 17 months (range, 4-73). The total prescribed dose for tomotherapy retreatment was 60 Gy in 3 patients and 50 Gy in 1 patient. Hormone therapy was administered to 2 patients before and during radiation. No patient underwent surgical resection. RESULTS The cumulative mean dose to the rectum ranged from 3813 to 6058 cGy; cumulative rectal maximum dose to 1 cc ranged from 6475 to 8780 cGy. Regarding the bladder, the cumulative mean dose was between 4384 and 7612 cGy; cumulative maximum dose to 1 cc ranged from 7560 to 9790 cGy. All patients completed the re-irradiation course. Acute genitourinary toxicity (RTOG scale) was grade 0 in 3 patients and grade 1 in 1 patient; acute gastrointestinal toxicity was grade 0 in 3 patients and grade 1 in 1 patient. With a median follow-up of 9 months (range, 7-12), late toxicity was G0 in all patients. Three patients showed partial response with computed tomography or magnetic resonance imaging, and 1 had a PSA decrease. CONCLUSIONS Re-irradiation with helical tomotherapy was well tolerated, with low rates of acute and late toxicity. It can be therefore considered a useful tool to improve local control in patients previously treated with radiotherapy. However, a larger number of patients and a longer follow-up are required to assess retreatment safety.

A phase II trial of low-dose gemcitabine and radiation alternated to cisplatin and 5-fluorouracil: An active and manageable regimen for stage IV squamous cell carcinoma of the head and neck

BACKGROUND The addition of gemcitabine may be a reasonable way to enhance the activity of the alternating cisplatin/5-fluorouracil and radiation regimen considered the referring approach for patients with advanced squamous cell carcinoma (SCC) of the head and neck at the National Institute for Cancer Research of Genoa. METHODS Three courses of cisplatin, 20mg/m(2)/day and 5-fluorouracil, 200mg/m(2)/day, days 1-5 (weeks 1, 4, and 7) alternated to 3 courses of radiotherapy at standard fractionation (weeks 2-3, 5-6, 8-9) up to 60Gy, and gemcitabine, 50mg/m(2) on monday of each week of radiation, were administered to 47 patients with stage IV (42 patients) or relapsed after surgery (5 patients), SCC of the oral cavity, pharynx or larynx. RESULTS Eighty-five percent of the patients completed the planned treatment. Main grade 3-4 acute toxicities were: mucositis (40%), neutropenia (26%) and thrombocytopenia (30%). Twenty-seven patients reached a complete response (57%). Seven partial responders were rendered disease-free by surgery (final complete response rate: 72%). At a median follow-up of 37 months, 3-year overall survival, progression-free survival and loco-regional control are 50%, 43% and 54%, respectively. CONCLUSIONS The addition of gemcitabine at low dose to our referring alternating regimen is feasible and very active. It may improve the long-term outcomes despite an acceptable increase of acute mucoseal toxicity.

Late local treatment morbidity after accelerated radiotherapy or alternating chemoradiotherapy for advanced head and neck carcinoma.

Background To report local long-term morbidity after concomitant boost radiotherapy (AFRT) or alternating chemoradiotherapy (CTRT), we analyzed the toxicity data recorded in 168 patients with advanced head and neck squamous cell carcinoma treated at our institution within phase II-III studies. Patients and Methods All patients enrolled in three consecutive phase II-III studies and followed for a minimum of three months after the end of treatment were included in the present analysis. Local late reactions were scored prospectively. The actuarial incidence of grade 2 or more (2-4) late local toxicity according to RTOG/EORTC was taken as endpoint. The median follow-up is 32.0 months (range, 3.3-138.1 months). For living patients the minimum and median follow-up are 12.1 and 69.3 months, respectively. Results The five-year actuarial incidence of grade 2+ and grade 3+ toxicity are 56.7 ± 5% and 21 ± 4%, respectively. At multivariate analysis, acute mucositis grade, complementary surgery, primary site and performance status proved to be independent predictive factors of grade 2+ late toxicity with P values of <0.001, 0.009, 0.022 and 0.033, respectively. No effect was found for treatment itself on the incidence of late toxicity, although patients treated with accelerated radiotherapy had a higher probability of confluent mucositis than patients treated with alternating chemoradiotherapy (68% vs 32%, P <0.01). Conclusions A substantial proportion of surviving patients develops late complications, although severe irreversible reactions occur in a minority of patients. Acute local toxicity can be used to predict local late toxicity that arises within five years of the end of treatment.