Paola Franzone

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.

Development of a set of nomograms to predict acute lower gastrointestinal toxicity for prostate cancer 3D-CRT.

PURPOSE To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. METHODS AND MATERIALS Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. RESULTS Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p = 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR = 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR = 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p = 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR = 1.029). CONCLUSIONS To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.

Randomized study comparing chemotherapy plus radiotherapy versus radiotherapy alone in FIGO stage IIB-III cervical carcinoma

Between January 1989 and December 1991, 64 patients with advanced cervical carcinoma FIGO stage IIb-III were randomized to receive radiotherapy (RT) alone or the sequential combination of chemotherapy (CT) and RT. RT consisted of external RT (40 Gy fractionated over 4 weeks) + brachytherapy (40 Gy to point A) + an additional boost to the parameters (15–20 Gy) in arm RT; CT consisted of cisplatin 60 mg/m2 i.v. day 1 q 15 days administered for 2 cycles before the start of RT and for 4 cycles after the end of radiation treatment in CT + RT arm. Among the 58 evaluable patients objective response rate was as follows: in RT arm, CR in 40.7% of patients, PR in 40.7%, and SD in 18.6%; in CT+RT arm, CR in 42% of patients, PR in 35.5%, and SD in 22.5%. The median duration of response was 12 months (range: 3–38 + months). At a median follow-up of 36 months survival (S) and progression-free survival (PFS) were 83% and 72.4% in RT arm, 72% and 59.3% in CT + RT arm, respectively. No significant difference was observed between the 2 treatment arms, neither in terms of objective response nor in terms of S and PFS. Both treatments were generally well tolerated. In our experience the addition of chemotherapy to standard radiotherapy does not enhance morbidity and does not interfere with the correct delivery of the planned treatment. However, results of this combined modality regimen remain unsatisfactory, since no improvement in pelvic control and survival of patients with advanced cervical carcinoma was observed.

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.

Alternating chemo-radiotherapy in bladder cancer: A conservative approach

PURPOSE The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. METHODS AND MATERIALS Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). RESULTS A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. CONCLUSION Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy.

High-Risk Early-Stage Ovarian Cancer Randomized Clinical Trial Comparing Cisplatin Plus Cyclophosphamide versus Whole Abdominal Radiotherapy

From 1985 to 1989 70 patients with high-risk FIGO Stage I-II ovarian carcinoma entered a randomized trial comparing chemotherapy (CT: cisplatin 50 mg/m2 + cyclophosphamide 600 mg/nr day 1 every 28 days for 6 courses) versus whole abdominal radiotherapy (WAR) given according to the open-field technique (43.2 Gy/24 fractions to the pelvis and 30.2 Gy to the upper abdomen). Protocol violations occurred in 8 patients randomized to WAR who received CT because of their own and/or physicians decision. Since protocol compliance was poor and accrual low the study was prematurely closed. Treatment-related toxicity for patients receiving CT was mild and tolerable, consisting chiefly of controllable grade 3 emesis (71%). Grade 3–4 diarrhea was experienced by 28% of patients treated with WAR: severe enteritis requiring hospitalization was observed in 2 patients. Late bowel obstruction requiring surgery was observed in I patient. At a median follow-up of 60 months, 21 patients died and 23 relapsed. Five-year survival was 71% and 53% (p =.16), while relapse- free survival was 14% and 50% (p =.07) for CT and WAR, respectively. Although no firm conclusion can be drawn from the present study, a short-term CT. including cisplatin, appears a safe treatment in comparison to WAR.

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.

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant

PURPOSE To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). METHODS AND MATERIALS Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. RESULTS At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p = 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first remission (p = 0.05). At multivariate analysis, TBI dose was an independent factor affecting overall survival (p = 0.05) as well as chronic GvHd (p = 0.001) and age (p = 0.04). CONCLUSIONS This retrospective analysis showed that different variables involved in TBI delivery may influence the occurrence of cGvHd and affect prognosis of patients with ALL receiving allogeneic BMT. The total dose of 12 Gy, administered in six fractions over 3 days, appears to be an effective and low toxic regimen for ALL patients transplanted in first remission.