Dieter Oetzel

Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients.

PURPOSE To determine the relation between the incidence of radiation pneumonitis and the three-dimensional dose distribution in the lung. METHODS AND MATERIALS In five institutions, the incidence of radiation pneumonitis was evaluated in 540 patients. The patients were divided into two groups: a Lung group, consisting of 399 patients with lung cancer and 1 esophagus cancer patient and a Lymph./Breast group with 78 patients treated for malignant lymphoma, 59 for breast cancer, and 3 for other tumor types. The dose per fraction varied between 1.0 and 2.7 Gy and the prescribed total dose between 20 and 92 Gy. Three-dimensional dose calculations were performed with tissue density inhomogeneity correction. The physical dose distribution was converted into the biologically equivalent dose distribution given in fractions of 2 Gy, the normalized total dose (NTD) distribution, by using the linear quadratic model with an alpha/beta ratio of 2.5 and 3.0 Gy. Dose-volume histograms (DVHs) were calculated considering both lungs as one organ and from these DVHs the mean (biological) lung dose, NTDmean, was obtained. Radiation pneumonitis was scored as a complication when the pneumonitis grade was grade 2 (steroids needed for medical treatment) or higher. For statistical analysis the conventional normal tissue complication probability (NTCP) model of Lyman (with n=1) was applied along with an institutional-dependent offset parameter to account for systematic differences in scoring patients at different institutions. RESULTS The mean lung dose, NTDmean, ranged from 0 to 34 Gy and 73 of the 540 patients experienced pneumonitis, grade 2 or higher. In all centers, an increasing pneumonitis rate was observed with increasing NTDmean. The data were fitted to the Lyman model with NTD50=31.8 Gy and m=0.43, assuming that for all patients the same parameter values could be used. However, in the low dose range at an NTDmean between 4 and 16 Gy, the observed pneumonitis incidence in the Lung group (10%) was significantly (p=0.02) higher than in the Lymph./Breast group (1.4%). Moreover, between the Lung groups of different institutions, also significant (p=0.04) differences were present: for centers 2, 3, and 4, the pneumonitis incidence was about 13%, whereas for center 5 only 3%. Explicitly accounting for these differences by adding center-dependent offset values for the Lung group, improved the data fit significantly (p < 10(-5)) with NTD50=30.5+/-1.4 Gy and m=0.30+/-0.02 (+/-1 SE) for all patients, and an offset of 0-11% for the Lung group, depending on the center. CONCLUSIONS The mean lung dose, NTDmean, is relatively easy to calculate, and is a useful predictor of the risk of radiation pneumonitis. The observed dose-effect relation between the NTDmean and the incidence of radiation pneumonitis, based on a large clinical data set, might be of value in dose-escalating studies for lung cancer. The validity of the obtained dose-effect relation will have to be tested in future studies, regarding the influence of confounding factors and dose distributions different from the ones in this study.

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.

Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC).

The clinical results after stereotactic single‐dose radiotherapy of nonsmall‐cell lung cancer (NSCLC) stages I and II were evaluated.

Influence of the positioning error on 3D conformal dose distributions during fractionated radiotherapy.

The influence of patient immobilization error on 3D planned conformal radiation therapy in tumors of the thorax and pelvis was studied. The mean positioning error in 43 patients with carcinomas of the thorax and pelvis undergoing 3D conformal radiotherapy (laser supported alignment, no immobilization device) was measured. A total of 194 portal films were superposed with the corresponding simulator radiographs according to anatomic landmarks and using a subtrascope. x-, y- and z-axis deviation was determined within a coordinate system. Using specialized software including Fourier transformation the mean positioning error was employed to recalculate the dose distributions of all cases under the influence of random (Gaussian) immobilization uncertainty. The mean two-dimensional positioning error using the data from all patients was 5.5 (+/- 3.7) mm. The distribution was Gaussian. Dose volume histograms (DVHs) of each patient with and without consideration of positioning uncertainty were compared on the base of tumor control probability estimations (TCP) using published DVH reduction and TCP algorithms. Inclusion of the positioning error resulted in a mean decrease in TCP (given as the difference between the TCP assuming no positioning error and the TCP modified by the positioning error) of 2% in a series of esophagus carcinomas and of 5% in the prostate carcinomas when looking at gross tumor volume (GTV), only. Planning target volume (PTV) exhibited a relative decrease in TCP of 5% and 11%, respectively.

Stereotactic single-dose radiotherapy of lung metastases.

Background:Stereotactic treatment approaches lead to a significant reduction of irradiated volumes, which should make pulmonary targets more accessible to radiotherapy.Patients and Methods:Between May 1997 and December 2005, 61 patients received stereotactic single-dose dose treatment for 71 pulmonary metastases. Doses to the isocenter ranged from 12 to 30 Gy. Survival and local tumor control rates were evaluated prospectively.Results:After a median follow-up period of 14 months the actuarial overall survival was 78.4%, 65.1%, and 47.8% 12, 24, and 36 months after therapy, respectively. There was a significantly better survival (p = 0.023) for patients not developing further metastases during follow-up. The actuarial local progression-free rate was 88.6%, 73.7%, and 63.1% 12, 24, and 36 months after therapy. Although the majority of patients (70.4%) developed perifocal normal-tissue changes, these were not related to clinically relevant toxicities.Conclusion:Stereotactic single-dose radiotherapy is a feasible, safe and effective local treatment option for solitary pulmonary metastases in patients with contraindications to surgery or for palliation of symptomatic pulmonary metastases.Hintergrund:Stereotaktische Bestrahlungsansätze führen zu einer signifikanten Reduktion der bestrahlten Volumina, was intrapulmonale Zielstrukturen der Strahlentherapie zugänglicher machen sollte.Patienten und Methodik:Zwischen Mai 1995 und Dezember 2005 erhielten 61 Patienten eine stereotaktische Einzeitbestrahlung von 71 Lungenmetastasen (Tabelle 1) unter Verwendung von Strahlendosen von 12–30 Gy (Tabellen 1 und 2). Überleben und lokale Tumorkontrollraten wurden prospektiv evaluiert.Ergebnisse:Nach einer medianen Nachbeobachtungszeit von 14 Monaten betrug das aktuarische Gesamtüberleben 12, 24 und 36 Monate nach Therapie 78,4%, 65,1% und 47,8% (Abbildung 1). Das Überleben war bei Patienten, welche keine weiteren Metastasen während der Nachbeobachtung entwickelten, signifikant verlängert (Abbildung 2). Die aktuarische lokale Progressionsfreiheit betrug 12, 24 und 36 Monate nach Therapie 88,6%, 73,7% und 63,1% (Abbildungen 3 und 4). Obwohl die Mehrzahl der Patienten (70,4%) perifokale Normalgewebsveränderungen entwickelte, korrelierten diese nicht mit klinisch relevanten Toxizitäten (Tabelle 3).Schlussfolgerung:Die stereotaktische Einzeitbestrahlung ist eine praktikable, sichere und effektive lokale Behandlungsoption für solitäre Lungenmetastasen bei Patienten mit Kontraindikationen für eine Operation oder zur Palliation symptomatischer Lungenmetastasen.

Conservative treatment of breast cancer: modified irradiation technique for women with large breasts

Seven patients with large, pendulous breasts received external beam irradiation to the whole breast (50 Gy in 25 fractions plus boost) after lumpectomy. A special breast holding mask was shaped for each patient. Three-dimensional treatment plans and dose-volume histograms of the same patient with and without a mask were compared. Day-to-day variance was checked. This technique provides improvements in dose homogeneity, reproducibility, and sparing of normal tissues. Cosmetic outcome at present is good.

Five-year experience with setup and implementation of an integrated database system for clinical documentation and research

In radiation oncology, where treatment concepts are elaborated in interdisciplinary collaborations, handling distributed, large heterogeneous amounts of data efficiently is very important, yet challenging, for an optimal treatment of the patient as well as for research itself. This becomes a strong focus, as we step into the era of modern personalized medicine, relying on various quantitative data information, thus involving the active contribution of multiple medical specialties. Hence, combining patient data from all involved information systems is inevitable for analyses. Therefore, we introduced a documentation and data management system integrated in the clinical environment for electronic data capture. We discuss our concept and five-year experience of a precise electronic documentation system, with special focus on the challenges we encountered. We specify how such a system can be designed and implemented to plan, tailor and conduct (multicenter) clinical trials, ultimately reaching the best clinical performance, and enhancing interdisciplinary and clinical research.

The impact of 3-D radiotherapy planning after a pneumonectomy compared to a conventional treatment set-up.

Three-dimensional radiotherapy planning (3-D RTP) is becoming more available in clinical practice, although so far there is little data showing its clinical advantage. The goal of this study was to compare 3-D RTP and dose delivery with conventional treatment planning in pneumonected lung cancer patients, receiving postoperative irradiation. Adjuvant radiotherapy in 20 pneumonected patients was planned with a 3-D system and patients were irradiated according to this plan. The resulting dose distribution was compared with the combination of a simulator and 2-D planned treatment to the same target volume. Dose volume histograms of the target, the lung and the heart of both treatment plans were analysed. A biophysical model was added to estimate the differences in the biological effect. 3-D RTP significantly reduced the mean dose to the lung in 14/20 patients and to the heart in 20/20 patients. The mean dose delivered to the target was equal in both planning methods. The early clinical results do not differ from published results in postoperatively treated lung cancer patients.

Connection of European particle therapy centers and generation of a common particle database system within the European ULICE-framework

BackgroundTo establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology.MethodsWe developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation.ResultsIt is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs.ConclusionsThe described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy.