Bernhard Isaak

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PURPOSE To determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy. METHODS AND MATERIALS Between October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5Gy within 48h for a total prescribed dose (PD) of 38Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4-4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria. RESULTS Acute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V(100) (% PTV receiving > or =100% of the PD; p=0.036), D(90) (dose delivered to 90% of the PTV; p=0.02), and the urethral V(120) (urethral volume receiving > or =120% of the PD; p=0.043). The urethral V(120) was associated with increased PTV V(100) (p<0.001) and D(90) (p=0.003). CONCLUSIONS After HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V(120) and the V(100) and D(90) of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

INTRODUCTION To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving > or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

High Dose-Rate Versus Low Dose-Rate Brachytherapy for Lip Cancer

PURPOSE To analyze the outcome after low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy for lip cancer. METHODS AND MATERIALS One hundred and three patients with newly diagnosed squamous cell carcinoma of the lip were treated between March 1985 and June 2009 either by HDR (n = 33) or LDR brachytherapy (n = 70). Sixty-eight patients received brachytherapy alone, and 35 received tumor excision followed by brachytherapy because of positive resection margins. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events 3.0. RESULTS Median follow-up was 3.1 years (range, 0.3-23 years). Clinical and pathological variables did not differ significantly between groups. At 5 years, local recurrence-free survival, regional recurrence-free survival, and overall survival rates were 93%, 90%, and 77%. There was no significant difference for these endpoints when HDR was compared with LDR brachytherapy. Forty-two of 103 patients (41%) experienced acute Grade 2 and 57 of 103 patients (55%) experienced acute Grade 3 toxicity. Late Grade 1 toxicity was experienced by 34 of 103 patients (33%), and 5 of 103 patients (5%) experienced late Grade 2 toxicity; no Grade 3 late toxicity was observed. Acute and late toxicity rates were not significantly different between HDR and LDR brachytherapy. CONCLUSIONS As treatment for lip cancer, HDR and LDR brachytherapy have comparable locoregional control and acute and late toxicity rates. HDR brachytherapy for lip cancer seems to be an effective treatment with acceptable toxicity.

Applicability and dosimetric impact of ultrasound-based preplanning in high-dose-rate brachytherapy of prostate cancer

Background and Purpose:Analyses of permanent brachytherapy seed implants of the prostate have demonstrated that the use of a preplan may lead to a considerable decrease of dosimetric implant quality. The authors aimed to determine whether the same drawbacks of preplanning also apply to high-dose-rate (HDR) brachytherapy.Patients and Methods:15 patients who underwent two separate HDR brachytherapy implants in addition to external-beam radiation therapy for advanced prostate cancer were analyzed. A pretherapeutic transrectal ultrasound was performed in all patients to generate a preplan for the first brachytherapy implant. For the second brachytherapy, a subset of patients were treated by preplans based on the ultrasound from the first brachytherapy implant. Preplans were compared with the respective postplans assessing the following parameters: coverage index, minimum target dose, homogeneity index, and dose exposure of organs at risk. The prostate geometries (volume, width, height, length) were compared as well.Results:At the first brachytherapy, the matching between the preplan and actual implant geometry was sufficient in 47% of the patients, and the preplan could be applied. The dosimetric implant quality decreased considerably: the mean coverage differed by –0.11, the mean minimum target dose by –0.15, the mean homogeneity index by –0.09. The exposure of organs at risk was not substantially altered. At the second brachytherapy, all patients could be treated by the preplan; the differences between the implant quality parameters were less pronounced. The changes of prostate geometry between preplans and postplans were considerable, the differences in volume ranging from –8.0 to 13.8 cm3 and in dimensions (width, height, length) from –1.1 to 1.0 cm.Conclusion:Preplanning in HDR brachytherapy of the prostate is associated with a substantial decrease of dosimetric implant quality, when the preplan is based on a pretherapeutic ultrasound. The implant quality is less impaired in subsequent implants of fractionated brachytherapy.Hintergrund und Ziel:Die Anwendung eines Preplan bei der Prostata-Brachytherapie mit radioaktiven Seeds geht häufig mit einer relevanten Abnahme der dosimetrischen Qualität des Implantats einher. Es wird untersucht, ob bei der High-Dose-Rate- (HDR-)Brachytherapie dieselben Nachteile des Preplannings auftreten.Patienten und Methodik:Die Studie stützt sich auf 15 Patienten mit einem fortgeschrittenen Prostatakarzinom, die mit externer Strahlentherapie und zwei HDR-Brachytherapie-Sitzungen behandelt wurden. Alle Patienten wurden mit prätherapeutischem transrektalem Ultraschall als Basis zur Erstellung eines Preplan für die erste Brachytherapie untersucht. Die zweite Brachytherapie wurde in einer Subgruppe (n = 6) mittels Preplan appliziert, der auf dem Ultraschall der ersten Brachytherapie basierte (Abbildung 1). Die Preplans wurden mit den entsprechenden Postplans auf folgende Parameter hin verglichen: Coverage-Index, minimale Target-Dosis, Homogenitätsindex und Dosisbelastung der Risikoorgane. Ebenso wurden die geometrischen Maße der Prostata verglichen (Volumen, Breite, Höhe, Länge).Ergebnisse:Bei 47% der Patienten wurde die Übereinstimmung der Implantatgeometrie von Preplan und erster Brachytherapiesitzung als ausreichend erachtet, und der Preplan konnte nachfolgend angewendet werden. Die Implantatqualität nahm deutlich ab (Tabelle 1): Der mittlere Coverage-Index sank um –0,11, die mittlere Target-Dosis um –0,15, der mittlere Homogenitätsindex um –0,09. Die Strahlenbelastung der Risikoorgane erhöhte sich nicht wesentlich (Tabelle 2). Die Unterschiede der geometrischen Parameter waren beträchtlich (–8,0 bis 13,8 cm3 betreffend Volumen; –1,1 bis 1,0 cm betreffend Breite, Höhe und Länge; Abbildung 2 und Tabelle 3).Schlussfolgerung:Die Verwendung eines Preplan in der HDR-Brachytherapie der Prostata resultiert in einer wesentlichen Abnahme der Implantatqualität, wenn der Preplan auf einem prätherapeutischen Ultraschall basiert. Diese Abnahme ist bei fraktionierter Behandlung in nachfolgenden Brachytherapiesitzungen weniger ausgeprägt.

Urethral toxicity vs. cancer control—Lessons to be learned from high–dose rate brachytherapy combined with intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

PURPOSE To describe biochemical relapse-free survival (BRFS) and late toxicity after combined high-dose rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT) in intermediate- and high-risk prostate cancer patients. METHODS AND MATERIALS From March 2003 to September 2005, 64 men were treated by 3×7Gy HDR-B using one implant followed by 50Gy IMRT. Median age was 66.1 years; risk of recurrence was intermediate in 30 (47%) or high in 34 (53%) patients. Forty-four (69%) patients received hormonal therapy. Patients were treated with a median of 13 HDR-B applicators (range, 8-17). Biochemical relapse was defined according to Phoenix criteria. Toxicity was scored according to the Common Toxicity Criteria scale version 3.0. RESULTS Median followup was 5.1 years. The 3-year BRFS was 100% and 91% for intermediate- and high-risk patients. Late Grade 2 gastrointestinal (GI) toxicity occurred in 3 (4.7%) patients, late Grade 3 GI toxicity was absent. Late Grade 3 and 4 genitourinary (GU) toxicity was observed in 7 (10.9%) and 2 (3.1%) patients. The 5-year Grade 3 or higher late GU toxicity-free survival was associated with a higher number of HDR-B applicators (p=0.049). CONCLUSIONS The 3-year BRFS was excellent and late GI toxicity was negligible. However, the late Grade 3 and 4 GU toxicity was unacceptably high.

610 poster ACCELERATED PARTIAL BREAST IRRADIATION: A DOSIMETRIC COMPARISON OF PERI- AND POSTOPERATIVE IMPLANTS

the lumpectomy cavity is comprised at least 0.5 cm in radial direction by the balloon pressure. Although breast tissue is essentially uncompressible, i.e. density is nearby constant, it can be stretched. Let us consider CTV as a spherical crown of 1.5 cm width around a theoretical spherical lumpectomy cavity with radius RCAV. If the cavity radius were expanded by the balloon, CTV would be contained into a spherical crown of 1 cm width at some balloon radius, RBALLOON > RCAV. In this way, the minimum balloon volume required to cover up CTV by the prescription dose can be calculated as a cavity volume function. Results: An approximate solution is (volume unit in cc): VBALLOON 0.52(1.46VCAV 0.33 + 1.59) [eq. 1]. If we consider also air or seroma inside the CTV up to 10% in volume, uniformly distributed on a ring fitted to the balloon, we obtain: VBALLOON 0.52(1.42VCAV 0.33 + 1.26) [eq 2]. Exact calculations (points) and approximations (continuous curves) for both cases are showed in the graph. Horizontal lines indicate the available diameter range of spherical mammosite balloons: 4-5 cm and 5-6 cm.