Peter Schraube

Estimation of pneumonitis risk in three-dimensional treatment planning using dose-volume histogram analysis

PURPOSE Investigations to study correlations between the estimations of biophysical models in three dimensional (3D) treatment planning and clinical observations are scarce. The development of clinically symptomatic pneumonitis in the radiotherapy of thoracic malignomas was chosen to test the predictive power of Lymans normal tissue complication probability (NTCP) model for the assessment of side effects for nonuniform irradiation. METHODS AND MATERIALS In a retrospective analysis individual computed-tomography-based 3D dose distributions of a random sample of 46/20 patients with lung/esophageal cancer were reconstructed. All patients received tumor doses between 50 and 60 Gy in a conventional treatment schedule. Biological isoeffective dose-volume histograms (DVHs) were used for the calculation of complication probabilities after applying Lymans and Kutchers DVH-reduction algorithm. Lung dose statistics were performed for single lung (involved ipsilateral and contralateral) and for the lung as a paired organ. RESULTS In the lung cancer group, about 20% of the patients (9 out of 46) developed pneumonitis 3-12 (median 7.5) weeks after completion of radiotherapy. For the majority of these lung cancer patients, the involved ipsilateral lung received a much higher dose than the contralateral lung, and the pneumonitis patients had on average a higher lung exposure with a doubling of the predicted complication risk (38% vs. 20%). The lower lung exposure for the esophagus patients resulted in a mean lung dose of 13.2 Gy (lung cancer: 20.5 Gy) averaged over all patients in correlation with an almost zero complication risk and only one observed case of pneumonitis (1 out of 20). To compare the pneumonitis risk estimations with observed complication rates, the patients were ranked into bins of mean ipsilateral lung dose. Particularly, in the bins with the highest patient numbers, a good correlation was achieved. Agreement was not reached for the lung functioning as a paired organ. CONCLUSIONS Realistic assessments for the prediction of radiation-induced pneumonitis seem to be possible. In this respect, the implementation of DVH-analysis in 3D planning could be a helpful tool for the evaluation of treatment plans.

Combined error of patient positioning variability and prostate motion uncertainty in 3D conformal radiotherapy of localized prostate cancer

PURPOSE To measure the patient positioning and prostate motion variability and to estimate its influence on the calculated 3D dose distribution in 3D conformal radiotherapy of patients with localized prostate carcinoma. METHODS AND MATERIALS Patient positioning variability was determined retrospectively by comparing 54 orthogonal simulator films with 125 corresponding portal films from 27 patients. Prostate motion variability was determined by 107 computed tomography (CT) examinations with a CT simulator in 28 patients during radiotherapy. RESULTS In each observed direction, the patient positioning variability and prostate motion showed a normal distribution. This observation enabled the calculation of a combined error of both components. The standard deviation (1 SD) of the patient positioning error in three directions ranged from 3.1 to 5.4 mm; the prostate motion variability was significantly greater in the anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior-posterior direction 6.1 mm and in mediolateral direction 3.6 mm. CONCLUSION The range of patient positioning variability and prostate motion were statistically predictable under the patient setup conditions used. Dose-volume histograms demonstrating the influence of the combined error of both components on the calculated dose distribution are presented.

Combined external beam radiotherapy and intraluminal high dose rate brachytherapy on bile duct carcinomas.

PURPOSE The aim of this study was to investigate the effectiveness and complications of combined external beam and intraluminal high dose rate irradiation and various adjuvant biliary drainage techniques on patients with bile duct carcinomas. METHODS AND MATERIALS Eighteen patients with carcinomas of the hepatic duct bifurcation and 12 patients with carcinomas of the choledochus duct or the common hepatic duct were treated with combined external beam radiotherapy and intraluminal high-dose rate brachytherapy. Nine patients received radiotherapy after palliative tumor resection and 21 patients were primarily irradiated. Twenty-five patients completed the full course of radiotherapy. On these patients, the reference doses for the external beam varied from 30 to 45 Gy and for brachytherapy from 20 to 45 Gy. Biliary drainage after radiotherapy was achieved either with percutaneous catheters, endoprosthesis, or stents. RESULTS The median survival for the entire group was 10 months. The actuarial survival was 34% after 1 year, 18% after 2 and 3 years, and 8% after 5 years. The subgroup with palliative tumor resection exhibit a significantly better survival (median: 12.1 months vs. 7.9 months). Three patients are still living without evidence of disease since 35 to 69 months. Major complications like bacterial cholangitis could be lowered from 37% to 28% through exchange of percutaneous transhepatic catheters to endoprosthesis or stents. The longest lasting drainages were achieved through stents. The frequency of radiogenic ulcera were lowered from 23% to presently 7.6% after the total dose of the high dose rate afterloading boost was reduced to 20 Gy. CONCLUSIONS The present standard treatment schedule 40 Gy for the external beam and 20 Gy (fourfold 5 Gy) for the afterloading boost seems to be appropriate and well tolerated. After radiotherapy, a permanent supply of drainage should be made with a stent.

Neurobehavioral toxicity of total body irradiation: a follow-up in long-term survivors

PURPOSE Total body irradiation (TBI) in preparation for bone marrow transplantation (BMT) is a routine treatment of hematological malignancy. A retrospective and a prospective group study of long-term cerebral side effects was performed, with a special emphasis on neurobehavioral toxicity effects. METHODS AND MATERIALS Twenty disease-free patients treated with hyperfractionated TBI (14.4 Gy, 12 x 1.2 Gy, 4 days), 50 mg/kg cyclophosphamide, and autologous BMT (mean age 38 years, range 17-52 years; age at TBI 35 years, 16-50 years; follow-up time 32 months, 9-65 months) participated in a neuropsychological, neuroradiological, and neurological examination. Data were compared to 14 patients who were investigated prior to TBI. Eleven patients with renal insufficiencies matched for sex and age (38 years, 20-52 years) served as controls. In a longitudinal approach, neuropsychological follow-up data were assessed in 12 long-term survivors (45 years, 23-59 years; follow-up time 8.8 years, 7-10.8 years; time since diagnosis 10.1 years, 7.5-14.2 years). RESULTS No evidence of neurological deficits was found in post-TBI patients except one case of peripheral movement disorder of unknown origin. Some patients showed moderate brain atrophy. Neuropsychological assessment showed a subtle reduction of memory performance of about one standard deviation. Cognitive decline in individual patients appeared to be associated with pretreatment (brain irradiation, intrathecal methotrexate). Ten-years post disease onset, survivors without pretreatment showed behavioral improvement up to the premorbid level. CONCLUSION The incidence of long-term neurobehavioral toxicity was very low for the present TBI/BMT regimen.

Cataract incidence after total-body irradiation

PURPOSE The aim of this retrospective study was to evaluate cataract incidence in a homogeneously-treated group of patients after total-body irradiation (TBI) followed by autologous bone marrow transplantation or peripheral blood stem cell transplantation. METHODS AND MATERIALS Between 1982 and 1994, a total of 260 patients received either autologous bone marrow or blood stem cell transplantation for hematological malignancy at the University of Heidelberg. Two hundred nine of these patients received TBI in our hospital. Radiotherapy was applied as hyperfractionated TBI, with a median dose of 14.4 Gy in 12 fractions over 4 days. Minimum time between fractions was 4 h. Photons with an energy of 23 MeV were used with a dose rate of 7-18 cGy/min. Ninety-six of the 209 irradiated patients were still alive in 1996; 86 of these patients (52 men, 33 women) answered a questionnaire and could be examined ophthalmologically. The median age at time of TBI was 38.5 years, with a range of 15-59 years. RESULTS The median follow-up is now 5.8 years, with a range of 1.7-13 years. Cataract occurred in 28/85 patients (32.9%) after a median of 47 months (1-104 months). In 6 of 28 patients who developed a cataract, surgery of the cataract was performed. Whole-brain irradiation prior to TBI had been performed more often in the group of patients developing cataract (14.3%) versus 10.7% in the group of patients without cataract. However, there was no statistical difference (Chi-square, p>0.05). CONCLUSION Cataract is a common side effect of TBI. Cataract incidence found in our patients is comparable to results of other centers using a fractionated regimen for TBI. To assess the incidence of cataract after TBI, a long-term follow-up is required.

A new applicator, positionable to the center of tracheobronchial lumen for HDR-IR-192-afterloading of tracheobronchial tumors

A new bronchial applicator for afterloading irradiation is introduced which can be positioned to the center of the tracheobronchial lumen. The central position in the lumen leads to a clear improvement of dose distribution. The applicator is built on the principle of a coaxial tube. Parts of the outer cover can be expanded to baskets and effect a distance of the radiation source from the bronchial mucosa or tumor surface, and at the same time, expend a relief of extreme contact doses. No obstruction of the respiratory system through the positioning device will be caused. The positionable bronchial applicator seems to be suitable for reducing complications caused through high contact doses and irregular dose distributions and may be able to improve the results of endoluminal radiotherapy.

LETHAL PULMONARY TOXICITY AFTER AUTOLOGOUS BONE MARROW TRANSPLANTATION/ PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FOR HEMATOLOGICAL MALIGNANCIES

BACKGROUND AND PURPOSE Retrospective evaluation of the incidence of lethal pulmonary complications (LPC) with special emphasis on interstitial pneumonia (IP) in a large group of patients homogeneously treated with hyperfractionated total body irradiation (HTBI) before autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) for hematological malignancy. The factors influencing IP are discussed. MATERIALS AND METHODS Of 260 patients (maximum follow-up 137 months) that were treated with ABMT or PBSCT for hematological neoplasms between 1982 and 1994, 209 patients received HTBI and could be evaluated with respect to lethal pulmonary complications and especially lethal interstitial pneumonia. For most patients (n = 155), the HTBI dose was 14.4 Gy (lung dose 9-9.5 Gy) given in 12 fractions over 4 days. Twenty-one patients received a total dose of > or =15 Gy with pulmonary doses of 9-10.5 Gy. RESULTS The actuarial overall 5-year survival for all 209 patients evaluated was 44 +/- 4%, enabling valid evaluation with respect to lethal pulmonary toxicity. The actuarial incidence of all LPC during the first year was calculated as being 8 +/- 2%. The actuarial incidence of lethal IP is certainly lower and was estimated to be between 3 and 5% for all patients. The overall treatment-related mortality was 12% in 188 patients that received a total dose of <15 Gy and 24% among the patients treated with a total dose of > or =15 Gy. CONCLUSION ABMT/PBSCT, like other transplant modalities without significant graft versus host disease (GvHD), has a low transplant-related mortality, a very small rate of overall LPC and a low incidence of lethal IP after HTBI. Doses up to 14.4 Gy with lung doses of 9-9.5 Gy can be administered safely. For total doses of > or =15 Gy with lung doses of 9-10.5 Gy, the risk of serious transplant-related complications cannot yet be finally assessed but such higher doses should be considered with caution because of the possibility of increasing toxicity in organs other than the lung.

Effect and toxicity of endoluminal high-dose-rate (HDR) brachytherapy in centrally located tumors of the upper respiratory tract

Aim: To assess effect and toxicity of high-dose-rate afterloading (HDR) alone or in combination with external beam radiotherapy (EBRT) in centrally located tumors of the upper respiratory tract. Patients and Methods: From 1987 to 1996, 55 patients were treated. Twenty-one patients (group A1: 17 non-small-cell lung cancer [NSCLC], A2: 4 metastases from other malignancies) were treated using HDR alone due to a relapse after external beam irradiation. In 34 previously untreated and inoperable patients (group B1: 27 NSCLC, B2: 7 metastases from other malignancies) HDR was given as a boost after EBRT (30 to 60 Gy, median 50). HDR was carried out with a 192Ir source (370 GBq). The brachytherapy dose (group A: 5 to 27 Gy, median 20; B: 10 to 20 Gy, median 15) was prescribed to 1 cm distance from the source axis. A distanciable applicator was used in 39/55 patients. Results: In group A1, a response rate (CR, PR) of 53% (group B1: 77%) was reached. The median survival (Kaplan-Meier) was 5 months in group A1 (B1: 20 months). The 1-, 3- and 5-year local progression free survival rates (Kaplan-Meier) were 66% (15%), 52% (0%), and 37% (0%) in group B1 (group A1). Prognostic favorable factors in group B1 were a tumor diameter < 20 mm, the lack of radiological mediastinal involvement, a complete remission, and a Karnofsky performance status > 70. Grade-1 or 2 toxicity (RTOG/EORTC) occurred in 0% in group A and in 6% in group B. We observed no Grade-3 or 4 toxicity. Complications caused by persistent or progressive local disease occurred in 3 patients in group A (fatal hemorrhage, tracheomediastinal fistula, hemoptysis) and in 2 patients in group B (fatal hemorrhage, hemoptysis). Conclusions: HDR brachytherapy is an effective treatment with moderate side effects. In combination with external beam irradiation long-term remissions can be reached in one third of the patients.Ziel: Evaluierung von Effektivität und Toxizität der endoluminalen High-dose-rate-(HDR-)Brachytherapie als alleinige oder kombinierte (EBRT) Therapie bei zentral sitzenden Tumoren der oberen Atemwege. Patienten und Methode: Von 1987 bis 1996 wurden 55 Patienten behandelt. 21 Patienten (Gruppe A1: 17 Patienten mit nichtkleinzelligem Bronchialkarzinom [NSCLC], A2: vier Patienten mit Metastasen anderer Tumoren) wurden bei Lokalrezidiven nach vorheriger perkutaner Bestrahlung ausschließlich endoluminal bestrahlt. Bei 34 inoperablen und vorher unbehandelten Patienten (Gruppe B1: 27 NSCLC, B2: sieben Metastasen anderer Tumoren) wurde die Brachytheranie als Boost nach externer Bestrahlung (30 bis 60 Gy, Median 50) appliziert. Die endoluminale Bestrahlung wurde mit einer 192Ir-Quelle (370 GBq) durchgeführt. Dosiert wurde auf 1 cm Quellenabstand (Gruppe A: 5 bis 27 Gy, Median 20; B: 10 bis 20 Gy, Median 15). Ein distanzierbarer Spreizkorbapplikator wurde bei 39/55 Patienten verwendet. Ergebnisse: In Gruppe A1 wurde ein Therapieansprechen (CR, PR) in 53% erzielt (Gruppe B1: 77%). Das mediane Überleben (Kaplan-Meier) betrug fünf Monate in Gruppe A1 (B1: 20 Monate). Das lokalrezidivfreie Ein-, Drei- und Füf-Jahres-Überleben (Kaplan-Meier) betrug in Gruppe B1 ((A1) 66% (15%), 52% (0%) und 37% (0%). Als prognostisch günstige Faktoren konnten in Gruppe B1 ein Tumordurchmesser < 20 mm, radiologisch fehlende mediastinale Beteiligung, eine komplette Remission und ein Karnofsky-Index > 70 ermittelt werden. Grad-1- oder -2-Toxizität (RTOG/EORTC) trat in keinem Fall in Gruppe A und in 6% in Gruppe B auf. Wir beobachteten keine Grad-3- oder -4-Toxizität Tumorassoziierte Komplikationen kamen in drei Fällen in Gruppe A (Blutung, tracheomediastinale Fistelung, Hämoptysen) und in zwei Fällen in Gruppe B vor (Blutung, Hämoptysen). Schlußfolgerungen: Die endoluminale HDR-Brachytherapie ist eine effektive Therapie mit moderaten Nebenwirkungen. In Kombination mit externer Radiotherapie können Langzeitremissionen bei einem Drittel der Patienten erzielt werden.

Einsatzmöglichkeiten eines offenen magnetresonanztomographen in der therapiesimulation und dreidimensionalen bestrahlungsplanung

HintergrundEs wird ein Verfahren zur rein digitalen Einbindung der diagnostischen Information aus einem offenen Niederfeld-MR-Tomographen (0,23 T) in die Therapiesimulation und die CT-gestützte dreidimensionale Bestrahlungsplanung vorgestellt.MethodikDie Bilder der Magnetresonanztomographie (MRT) wurden unter Verwendung spezieller Lagerungs- und Positionierungshilfen mit der Körperspule akquiriert. Standardmäßig wurde eine Gradientenechosequenz mit einer Repetitionszeit von 320 ms und einer Echozeit von 24 ms verwendet, um transversale und koronare Datensätze aufzunehmen. Eventuell auftretende Verzeichnungen der Bilder wurden bestimmt und mittels Phantommessungen und spezieller Software korrigiert.ErgebnisseDie Bildverzeichnungen konnten durch die Verzeichnungskorrektur von maximal 19 mm auf maximal 8,2 mm und durchschnittlich von 2,7 mm auf 0,7 mm korrigiert werden. Für den Einsatz am Therapiesimulator wurden koronare Aufnahmen verwendet und gemäß Strahlensatz in die Fächerstrahlprojektion umgerechnet. Ein Landmark-Matching-Algorithmus ermöglichte es, die aus der MRT erhaltene Tumorausdehnung in das zuvor digital eingelesene und korrigierte Simulatorbild zu übertragen. An einem Bestrahlungsplanungssystem (TMS, Helax) wurde, ebenfalls mittels Landmark-Matching mit CT-Schichten, die diagnostische MRT-Information aus den transversalen Schichten zur Kontrolle des Zielvolumens eingesetzt. Verschiedene Einsatzmöglichkeiten werden an repräsentativen Patientenbeispielen aufgezeigt.SchlußfolgerungMit dem vorgestellten System kann die Bildinformation aus einem offenen MR-System in die Therapiesimulation und die dreidimensionale Bestrahlungsplanung eingebunden werden. Das Niederfeld-MRT stellt für die Radioonkologie aufgrund der offenen Bauweise und der geringen Kosten eine attraktive Erweiterung der Planungsmöglichkeiten dar.AbstractPurposeA system for digital integration of an open MR scanner (0.23 T, Figure 1) in therapy simulation and 3D radiation treatment planning is described.MethodMR images were acquired using the body coil and various positioning and immobilization aids. A gradient echo sequence (TRITE 320 ms/24 ms) was used to create axial and coronal data sets. Image distortions were measured and corrected using phantom measurements (Figure 2) and specially developed software.ResultsMaximal and mean distortions of the MR images could be reduced from 19 mm to 8.2 mm and from 2.7 mm to 0.7 mm, respectively (Figure 3 to 5, Table 1). Coronal MR images were recalculated in fan beam projection for use at the therapy simulator. Tumor and organ conturs were transferred from the MR image to the digitally acquired and corrected simulator image using a landmark matching algorithm (Figure 6 and 7). For 3D treatment planning, image fusion of axial MR images with standard CT planning images was performed using a landmark matching algorithm, as well (Figure 8). Representative cases are shown to demonstrate potential applications of the system.ConclusionThe described system enables the integration of the imaging information from an open MR system in therapy simulation and 3D treatment planning. The low-field MR scanner is an attractive adjunct for the radiooncologist because of the open design and the low costs.PURPOSE A system for digital integration of an open MR scanner (0.23 T, Figure 1) in therapy simulation and 3D radiation treatment planning is described. METHOD MR images were acquired using the body coil and various positioning and immobilization aids. A gradient echo sequence (TR/TE 320 ms/24 ms) was used to create axial and coronal data sets. Image distortions were measured and corrected using phantom measurements (Figure 2) and specially developed software. RESULTS Maximal and mean distortions of the MR images could be reduced from 19 mm to 8.2 mm and from 2.7 mm to 0.7 mm, respectively (Figure 3 to 5, Table 1). Coronal MR images were recalculated in fan beam projection for use at the therapy simulator. Tumor and organ contours were transferred from the MR image to the digitally acquired and corrected simulator image using a landmark matching algorithm (Figure 6 and 7). For 3D treatment planning, image fusion of axial MR images with standard CT planning images was performed using a landmark matching algorithm, as well (Figure 8). Representative cases are shown to demonstrate potential applications of the system. CONCLUSION The described system enables the integration of the imaging information from an open MR system in therapy simulation and 3D treatment planning. The low-field MR scanner is an attractive adjunct for the radio-oncologist because of the open design and the low costs.

Combined endoluminal and external irradiation of inoperable oesophageal carcinoma

PURPOSE Higher radiation doses to oesophageal cancer might be possible by the steep dose gradient of an afterloading source. Structures at risk are not impaired by endoesophageal brachytherapy. Our experiences with endoesophageal afterloading in combination with external beam treatment are reported. METHODS AND MATERIALS Fifty-four patients were treated by this technique. All patients suffered from an inoperable oesophageal carcinoma (7 adenocarcinoma, 47 squamous-cell carcinoma). Patients were scheduled by tumour stage and medical condition into a curative group (21 patients) and into a palliative group (33 patients). Mean sum doses of 60.3 Gy (range 58-70 Gy) percutaneously and an additional endoluminal dose of 13.6 Gy (range 10-20 Gy) were applied endoluminally in the curative group and 44.9 Gy (range 14-53 Gy) plus 17.5 Gy (range 5-30 Gy), respectively, in the palliative group. Overall treatment time was 10 weeks (range 4.6-14.3 weeks) for the curative group and 9.3 weeks (range 4.1-13.9 weeks) for the palliative group. RESULTS Six weeks after the end of therapy a radiological remission could be observed in 32/33 of the palliatively treated patients (10 complete, 22 partial, 1 none). In 13 patients of this group a local progression was observed after a median time of 7.1 months. Median survival of this group was 9 months. A radiological remission occurred in 18/21 of the curatively treated patients (11 complete, 7 partial, 3 none). Median time to local progression (12 patients) was 4.5 months in this group and median survival was 7.7 months. The difference in time to progression reached a significant level (P = 0.05). The only favourable factors for survival were an incomplete or complete radiological remission (median survival 7.5 versus 11.4 months, P = 0.003) and stage I/II or III/IV (median survival 7.4 versus 12.6 months, P = 0.0024). The prior estimation of the treatment goal was not confirmed by survival data (curative, 7.7 months versus palliative, 9.0 months (not significant)). Eight of 54 minor and 8/54 (15%) major adverse events were observed. In four of these patients major complications were caused by progressive tumour. CONCLUSIONS Endoesophageal afterloading combination with percutaneous irradiation is a feasible save treatment in inoperable cases. A good local tumour regression and functional results can be reached. The data suggest that higher endoluminal doses extend the time to local progression. In comparison with the literature survival can not be increased by this treatment technique. The best way to combine both treatment modalities has not yet been found.