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.

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.

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.

[Effect if 3D compared with 2D radiotherapy planning within a conventional treatment schedule of advanced lung cancer]. / Effekt der 3D- gegenüber der 2D-Bestrahlungsplanung innerhalb eines konventionellen Therapieschemas fortgeschrittener Bronchialkarzinome.

BACKGROUND: The effect of 3D radiotherapy planning (3D RTP) in comparison to 2D radiotherapy planning (2D RTP) was evaluated in a usually practiced treatment schedule (starting by v./d. opposing portals, continued with computer-planned portals) for non-small-cell lung cancer. PATIENTS AND METHODS: In 20 patients with locally advanced non-small-cell lung cancer the computer-planned part of the treatment schedule was calculated 2- and 3-dimensionally. Target volume were the primary tumor, the involved and the electively irradiated mediastinal lymph nodes. The results of the 2D RTP were recalculated 3-dimensionally and the mean doses to target volume and organs at risk were defined. Further the normal tissue complications were calculated. RESULTS: Under the prerequisite of 44 Gy maximally allowed to the spinal cord and a dose to the reference point of 50 Gy a small, but significant advantage with 2.1 Gy to the target (p = 0.004) and a reduction of 3.6 Gy to the heart (p = 0.05) was achievable for 3D RTP. The dose to the lungs did not differ significantly (19.7 Gy for 2D RTP, 20.3 Gy for 3D RTP). The dose to the heart was not estimated critical by NTCP (normal tissue complication probability). The NTCP for the ipsilateral lung was 16.1 and 18.7% for 2D RTP and 3D RTP, respectively. Regarding the simulator-planned ap/pa fields at the start of the radiotherapy the advantage of 3D RTP was further reduced but remained significant. Favorable with respect to the mean lung dose and the NTCP (18.7% NTCP ipsilateral lung for early onset of 3D planned radiotherapy vs 31.7% for late onset of 3D planned radiotherapy) but not significantly measurable is the early start of the treatment by computerized RTP. CONCLUSION: The main advantage of 3D RTP in treatment of advanced lung cancer is the better coverage of the target volume. A reduction of the mean lung dose cannot be expected. A dose escalation by 3D RTP to target volumes as described here seems not to be possible because of unchanged high lung exposure.

HDR-brachytherapy boost for residual tumour after external beam radiotherapy in patients with tracheal malignancies.

Seven inoperable patients with tracheal neoplasms received a high dose rate (HDR) brachytherapy boost (median 15 Gy, single dose 3-5 Gy) for residual tumour after external beam radiotherapy (median 50 Gy, 5 x 2 Gy/week). The median actuarial survival was 34.3 months. The 1-, 2- and 3-year actuarial survival rates were 85.7%, 85.7% and 32%. Local control was obtained in 5/7 patients. Late toxicity occurred in three patients (stenosis n = 2, hemorrhage n = 1). Our data indicate, that a HDR brachytherapy boost is effective and feasible.

[Possibilities of an open magnetic resonance scanner integration in therapy simulation and three-dimensional radiotherapy planning]. / Einsatzmöglichkeiten eines offenen Magnetresonanztomographen in der Therapiesimulation und dreidimensionalen Bestrahlungsplanung.

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.

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.

Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro.

BACKGROUND AND PURPOSE: Combined radiochemotherapy has gained increasing interest in clinical applications. The effects of combined exposure of ionizing radiation and 4-hydroperoxyifosfamide (4HOOIF) on cell survival were investigated in vitro. MATERIALS AND METHODS: Clonogenic survival of log phase V79, Caski (squamous carcinoma), Widr (colon carcinoma) and MRI-221 cells (human melanoma) was determined after combined exposure to 4HOOIF and radiation. Measurement of cell survival for different cell cycle phases was performed after mitotic shake-off (V79) or appropriate intervals after serum stimulation of plateau phase cells (Widr). Control of cell cycle distribution was performed using flow cytometry. RESULTS: In all cell lines tested, a combined exposure resulted in cell killing that was greater than for independent action. While this type of radiosensitization was of minor magnitude for log-phase cells or cells in G1 substantial radiosensitization was detected for S-phase cells with enhancement ratios (calculated from the respective mean inactivation doses) of up to 1.5. CONCLUSIONS: The results demonstrate the interaction of 4HOOIF and radiation-induced cell damage with marked cell cycle specificity. Since the largest combination effect was observed for the most radioresistant S-phase cells, damage interaction could be mediated by an interference of 4HOOIF with the repair/fixation pathway of radiation-induced potentially lethal damage.

Invasive thymoma: treatment with postoperative radiation therapy.

PURPOSE: To assess radiation therapy and chemotherapy in the treatment of invasive thymoma and thymic carcinoma. MATERIALS AND METHODS: In 1981-1995, 43 patients received irradiation after total (n = 23) or subtotal (n = 20) resection. Tumors were thymic carcinoma (n = 10) or invasive thymoma (n = 33). Masaoka stage was II in 10 patients, III in 14, and IV in 19. Median total dose applied was 50 Gy (range, 10-72 Gy). Seventeen patients (five with stage III and 12 with stage IV) also received chemotherapy. RESULTS: Patients with thymic carcinoma had a median survival of 9.5 months, compared with 50 months for patients with invasive thymoma (P = .008). Patients' median survival and 5-year survival rates were 97 months and 90% for stage II, 65 months and 67% for stage III, and 32.5 months and 30% for stage IV tumors (P = .024). Overall control rate within the radiation field was 81% (35 patients) and overall local control rate within the thorax was 74% (32 patients). Of the 17 patients who received chemotherapy and radiation therapy, nine had thymic carcinoma and a median survival of 12 months (range, 1.4-23.0 months). CONCLUSION: With total doses of 45-50 Gy, local control is achievable after radical resection. Whether patients with completely resected stage II thymomas should receive radiation after surgery remains uncertain, as does the role of chemotherapy in the treatment of thymoma.

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.

[Pneumonitis after radiotherapy of bronchial carcinoma: incidence and influencing factors]. / Pneumonitis nach Strahlentherapie des Bronchialkarzinoms--Inzidenz und Einflussfaktoren.

BACKGROUND: The most important side effect in radiotherapy of lung cancer is pneumonitis. The incidence of pneumonitis was evaluated in a retrospective study in the patient collective of the University of Heidelberg. Therapy related and therapy independent factors have been evaluated. PATIENTS AND METHODS: In 348 of 392 cases with lung cancer who were treated by local irradiation between January 1989 and January 1992 the patient's records were evaluable for response and toxicity. All patients were treated by megavolt equipment with a conventional fractionation in most cases. Standard target volumes were irradiated including the lymphatic drainage. From a dose of above 30 Gy a technique sparing the spinal cord was chosen. Retrospectively pneumonitis was classified into 4 grades starting from slight symptoms to respiratory insufficiency requiring O2. Grade I and II were summarized to slight, grade III and IV to severe pneumonitis. RESULTS: Regarding the treatment prior to irradiation patients with primary irradiation were affected in 26.5% (17% slight, 9.5% severe), with postoperative irradiation in 14% (9.3% slight, 4.7% severe), with radiochemotherapy of small cell lung cancer (SCLC) in 15.4% (12% slight, 3.4% severe) by this side effect. These differences were not significant (p = 0.32). The median onset of pneumonitis was 31 days after end of irradiation (severe 23 days, slight 44 days, p = 0.026). By a univariate analysis the total dose at the prescription point was the most important factor (30 to 50.5 Gy 11%, 52 to 59 Gy 15%, 60 to 74 Gy 26%, p = 0.007). High single doses (2.5 Gy) were only applied within a study of radiochemotherapy with a randomised sequential and alternating schedule. So that the increased rate of pneumonitis (42%) is not clearly separable from other influencing variables. A correlation between the applied techniques and the irradiated volume (measured by planimetric methods) was not demonstrable. Regarding the independent factors a high age, female sex and a low FeV1 were unfavourable. However, age and sex corrected FeV1 was not predictive. CONCLUSIONS: The observed incidence is within the range of literature. By a clinical point of view the total dose is an obvious factor. Also single doses above 2 Gy have to be seen critically (a total dose of 50 Gy). The results confirm the fact that patients with a low FeV1 are not suitable to a high dose irradiation of the chest. In this connection old patients and women also should be seen as patients at risk.

Simulation of 3D-treatment plans in head and neck tumors aided by matching of digitally reconstructed radiographs (DRR) and on-line distortion corrected simulator images.

BACKGROUND AND PURPOSE: Simulation of 3D-treatment plans for head and neck malignancy is difficult due to complex anatomy. Therefore, CT-simulation and stereotactic techniques are becoming more common in the treatment preparation, overcoming the need for simulation. However, if simulation is still performed, it is an important step in the treatment preparation/execution chain, since simulation errors, if not detected immediately, can compromise the success of treatment. A recently developed PC-based system for on-line image matching and comparison of digitally reconstructed radiographs (DRR) and distortion corrected simulator monitor images that enables instant correction of field placement errors during the simulation process was evaluated. The range of field placement errors with non-computer aided simulation is reported. MATERIALS AND METHODS: For 14 patients either a primary 3D-treatment plan or a 3D-boost plan after initial treatment with opposing laterals for head and neck malignancy with a coplanar or non-coplanar two- or three-field technique was simulated. After determining the robustness of the matching process and the accuracy of field placement error detection with phantom measurements, DRRs were generated from the treatment planning CT-dataset of each patient and were interactively matched with on-line simulator images that had undergone correction for geometrical distortion, using a landmark algorithm. Translational field placement errors in all three planes as well as in-plane rotational errors were studied and were corrected immediately. RESULTS: The interactive matching process is very robust with a tolerance of <2 mm when suitable anatomical landmarks are chosen. The accuracy for detection of translational errors in phantom measurements was <1 mm and for in-plane rotational errors the accuracy had a maximum of only 1.5 degrees. For patient simulation, the mean absolute distance of the planned versus simulated isocenter was 6.4 +/- 3.9 mm. The in-plane rotational error in both planes was <3 degrees with one exception. Three large field placement errors (two patients with 11.5 and 16.0 mm distances of the planned versus simulated isocenter, respectively and one patient with a 7 degree rotational error) were detected and, as with the smaller errors, were immediately corrected. CONCLUSION: On-line image matching of treatment planning CT-derived DRRs and distortion corrected treatment simulator images is a precise and reliable method to reduce field placement errors in the simulation of complex 3D-treatment plans for head and neck malignancy and thus enhances accuracy in the first step of the treatment preparation/execution chain. However, out-of-plane rotational errors could not be assessed and assumedly they are comparatively small since due to rigid fixation, detected in-plane errors were small.

[Acute tolerance in hyperfractionated accelerated whole-body irradiation]. / Akuttoleranz bei der hyperfraktionierten akzelerierten Ganzkörperbestrahlung.

BACKGROUND: Acute side effects of total body irradiation lead to intense molestations of the patients. Therefore, it is desirable to take measures to reduce these side effects. In a retrospective study the frequency of acute side effects of a hyperfractionated accelerated total body irradiation was assessed and compared to frequencies of other exposure schedules published in the literature. Additionally the influence of ondansetron on the frequency of nausea and vomiting was investigated. PATIENTS AND METHOD: From 1989 to 1992, 76 patients (47 male, 29 female; median age 38 years) underwent total body irradiation before autologous bone marrow transplantation. They received 3 daily doses of 1.20 Gy each every 4 h on 4 successive days to a total dose of 14.40 Gy. Thirty-nine patients received 3 x 8 mg (daily, intravenous or per os) ondansetron during the whole course of irradiation. RESULTS: The most relevant side effects were nausea and vomiting. Patients, who did not receive ondansetron (n = 37) showed a nausea and emesis rate of 73%. With ondansetron (n = 39) nausea and emesis were reduced to 38%. Also the grade of severity of these side effects was reduced. CONCLUSIONS: Ondansetron proved to be an effective medicament for relieving nausea and vomiting during total body irradiation. The results obtained are in concordance with those published in the literature.

First experiences with superfractionated skin irradiations using large afterloading molds.

PURPOSE: Radiotherapy of cutaneous metastases of breast cancer requires large radiation fields and high doses. This report examines the effectiveness and sequelae of superfractionated irradiation of cutaneous metastases of breast cancer with afterloading molds on preirradiated and nonirradiated skin. METHODS AND MATERIALS: A flexible reusable skin mold was developed for use with a pulsed (PDR) afterloader. An array of 18 parallel catheters was sewn between two foam rubber slabs 5 mm in thickness to provide a defined constant distance to the skin. By selection of appropriate dwell positions, arbitrarily shaped skin areas can be irradiated up to a maximal field size of 17 x 23.5 cm2. Irradiations are performed with a nominal 37 GBq 192Ir stepping source in pulses of 1 Gy/h at the skin surface. The dose distribution is geometrically optimized. The 80 and 50% dose levels lie 5 and 27 mm below the skin surface. Sixteen patients suffering from metastases at the thoracic wall were treated with 18 fields (78-798 cm2) and total doses of 40-50 Gy applying two PDR split courses with a pause of 4-6 weeks. Eleven of the fields had been previously irradiated with external beam therapy to doses of 50-60 Gy at 7-22 months in advance. RESULTS: For preirradiated fields (n = 10) the results were as follows: follow-up 4.5-28.5 months (median 17); local control (LC): 8 of 10; acute skin reactions: Grade 2 (moist desquamation) 2 of 10; intermediate/late skin reactions after minimum follow-up of 3 months: Grade 1 (atrophy/pigmentation): 2 of 10, Grade 2-3a (minimal/marked teleangiectasia): 7 of 10, Grade 4 (ulcer): 1 of 10; recurrencies: 2 of 10. For newly irradiated fields (n = 7) results were: follow-up: 2-20 months (median 5); LC: 6 of 7; acute reactions: Grade 1: 4 of 7, Grade 2: 3 of 7; intermediate/late skin reactions after minimum follow-up of 3 months (n = 5): Grade 2-3a: 2 of 5; recurrencies: 0 of 7. Local control could be achieved in 82% of the mold fields. Geometric optimization was mandatory to achieve a homogeneous dose distribution on the skin. CONCLUSION: Superfractionated brachytherapy with skin molds is an effective alternative for the treatment of skin metastases of breast cancer even if the skin is preirradiated. This method is economically advantageous compared to external beam therapy, which would require several weeks. At the curved chest wall, optimized molds can provide better dose homogeneity than abutted electron fields. Skin reactions are comparable to the sequelae of orthovolt irradiation. In preirradiated areas, PDR doses should be restricted to 40-45 Gy. PDR doses of 50 Gy seem to be the limit for tolerance even in previously unirradiated fields.

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.

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.

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 Lyman's 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 Lyman's and Kutcher's 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.

Treatment of primary squamous cell carcinoma of the trachea: the role of radiation therapy.

Eleven patients with SCC of the trachea were treated (ten primarily, one postoperatively) with megavolt irradiation (four in combination with brachytherapy). A median survival of 31 and a median disease free survival of 7.5 months was observed. Factors favourable for survival were the achievement of complete remission, the absence of mediastinal lymphnode involvement, and the use of additional brachytherapy.

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.