Dietmar Zierhut

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.

External radiotherapy of pituitary adenomas

PURPOSE To evaluate therapeutic outcome and side effects of radiotherapy in pituitary adenomas as sole or combined treatment. METHODS AND MATERIALS Retrospective analysis of 138 patients (74 male, 64 female) irradiated for pituitary adenoma from 1972 to 1991 was performed. Mean age was 49.7 years (15-80 years). Regular follow-up (in the mean 6.53 +/- 3.99 years) included radiodiagnostical [computed tomography (CT), magnetic resonance imaging (MRI), x-ray], endocrinological, and ophthalmological examinations. Seventy patients suffered from nonfunctional pituitary adenoma, 50 patients suffered from growth-hormone producing adenomas, 11 had prolactinomas, and 7 patients had adrenocorticotropic hormone (ACTH) producing pituitary adenomas. In 99 patients surgery was followed by radiotherapy in case of suspected remaining tumor (invasive growth of the adenoma, assessment of the surgeon, pathologic CT after surgery, persisting hormonal overproduction). Twenty-three patients were treated for recurrence of disease after surgery and 16 patients received radiation as primary treatment. Total doses from 40-60 Gy (mean: 45.5 Gy) were given with single doses of 2 Gy 4 to five times a week. RESULTS Tumor control was achieved in 131 patients (94.9%). In seven patients, recurrence of disease was diagnosed in the mean 2.9 years (9-98 months) after radiotherapy and salvaged by surgery. A statistically significant dose-response relationship was found in favor of doses > or = 45 Gy. Ninety percent of the patients with hormonally active pituitary adenomas had a benefit from radiotherapy in means of complete termination (38%) or at least reduction (52%) of hormonal overproduction. Partial or complete hypopituitarism after radiotherapy developed, depending on hormonal axis, in 12 (prolactin) to 27% (follicle-stimulating hormone FSH) of patients who had not already had hypopituitarism prior to radiation. Two out of 138 patients suffered reduction of visual acuity, which was, in part, related to radiotherapy. Both therapeutic effects and side effects occurred after a latency period of 3 months up to 9 years. CONCLUSION We conclude that radiotherapy of pituitary adenomas, using modern treatment planning techniques, is effective and safe. To achieve optimal tumor control, doses of 45-48 Gy (conventionally fractionated) should be applied.

Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed beam?

PURPOSE To compare retrospectively radiotherapy with neutrons, photons, and a photon/neutron mixed beam in patients with advanced adenoid cystic carcinoma of the head and neck. Local control, survival, distant failure, and complications were analyzed. MATERIALS AND METHODS Between 1983 and 1995, 75 patients with inoperable, recurrent, or incompletely resected adenoid cystic carcinoma of the head and neck received radiotherapy that consisted of either fast 14.1 MV DT neutrons (median dose 16 neutron Gy), linac-based photon irradiation (median dose 64 photon Gy), or both (median dose 8 neutron Gy and 32 photon Gy). Follow-up ranged from 1 to 160 months (median 51 months), and the surviving patients had a minimum follow-up of 3 years at the time of analysis. RESULTS The actuarial 5-year local control was 75% for neutrons, and 32% for both mixed beam and photons (P = 0.015, log-rank). This advantage for neutrons in local control was not transferred to significant differences in survival (P > 0.1). The survival is dictated by the tumor diseases due to distant metastases occurring in 29 (39%) of the 75 patients. Positive lymph nodes were the only significant factor (P = 0.001) associated with the development of distant metastases although negative lymph nodes did not predict absence of distant metastases, but predicted a delay of occurrence. In multivariate analysis postoperative radiotherapy (P = 0.003) and small tumor size (P = 0.01) were associated with high local control, while primary therapy (P = 0.006) and negative lymph nodes (P = 0.01) were associated with longer survival. While acute toxicity was similar in all three radiotherapy groups, severe late grade 3 and 4 toxicity tended to be more prevalent (P > 0.1) with neutrons (19%) than with mixed beam (10%) and photons (4%). CONCLUSION Fast neutron radiotherapy provides higher local control rates than a mixed beam and photons in advanced, recurrent or not completely resected adenoid cystic carcinoma of the major and minor salivary glands. Neutron radiotherapy can be recommended in patients with bad prognosis with gross residual disease (R2), with unresectable tumors, or inoperable tumors. The type of radiation does not impact survival, which is dominated by the high number of distant metastases.

Open low-field magnetic resonance imaging in radiation therapy treatment planning

PURPOSE To evaluate the possibilities of an open low-field magnetic resonance imaging (MRI) scanner in external beam radiotherapy treatment (RT) planning. METHODS AND MATERIALS A custom-made flat tabletop was constructed for the open MR, which was compatible with standard therapy positioning devices. To assess and correct image distortion in low-field MRI, a custom-made phantom was constructed and a software algorithm was developed. A total of 243 patients (43 patients with non-small-cell lung cancer, 155 patients with prostate cancer, and 45 patients with brain tumors) received low-field MR imaging in addition to computed tomographic (CT) planning imaging between January 1998 and September 2001 before the start of the irradiation. RESULTS Open low-field MRI provided adequate images for RT planning in nearly 95% of the examined patients. The mean and the maximal distortions 15 cm around the isocenter were reduced from 2.5 mm to 0.9 mm and from 6.1 mm to 2.1 mm respectively. The MRI-assisted planning led to better discrimination of tumor extent in two-thirds of the patients and to an optimization in lung cancer RT planning in one-third of the patients. In prostate cancer planning, low-field MRI resulted in significant reduction (40%) of organ volume and clinical target volume (CTV) compared with CT and to a reduction of the mean percentage of rectal dose of 15%. In brain tumors, low-field MR image quality was superior compared with CT in 39/45 patients for planning purposes. CONCLUSIONS The data presented here show that low-field MRI is feasible in RT treatment planning when image correction regarding system-induced distortions is performed and by selecting MR imaging protocol parameters with the emphasis on adequate images for RT planning.

Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients.

Purpose: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors. Patients and Methods: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at that time. The median dose to the 80% isodose line, prescribed to encompass the tumor margin, was 20 Gy (range, 15–22 Gy). Results: Neurologic symptoms improved in five of twelve symptomatic patients. 41 patients remained asymptomatic or unchanged in their neurologic symptoms. Only five patients (8%) temporarily worsened neurologically after therapy despite no signs of tumor progression. With a mean follow-up time of 9.4 months, actuarial local control was 81% after 1 year. There was a statistically significant dose and size dependency of local tumor control. Median actuarial survival after treatment was 10.6 months. Patients without extracerebral tumor manifestation showed a superior survival (p = 0.04). Conclusions: Despite high local tumor control rates, the prognosis of patients with cerebral metastases of malignant melanoma remains poor. Stereotactic radiosurgery has the potential of stabilizing or improving neurologic symptoms in these patients in a palliative setting.Ziel: Die stereotaktische Radiochirurgie hat sich als Alternative zur neurochirurgischen Exzision bei der Behandlung zerebraler Metastasen erwiesen. Wir analysierten retrospektiv den Verlauf und prognostische Faktoren bei Patienten, die wegen Hirnmetastasen bei malignem Melanom in Heidelberg stereotaktisch behandelt wurden. Patienten und Methodik: Zwischen 1986 und 2000 wurden insgesamt 122 Hirnmetastasen bei 64 Patienten mit metastasiertem malignem Melanom mit einer stereotaktischen Einzeitbestrahlung behandelt. Zwölf Patienten (19%) zeigten zum Zeitpunkt der Therapie neurologische Symptome. 46 Patienten hatten zum Therapiezeitpunkt extrazerebrale Tumormanifestationen. Die mediane Dosis, die auf die tumorumschließende 80%-Isodose appliziert wurde, betrug 20 Gy (Spannweite 15–22 Gy). Ergebnisse: Die neurologischen Symptome besserten sich bei fünf der zwölf symptomatischen Patienten. 41 Patienten blieben während der weiteren Nachbeobachtung neurologisch asymptomatisch oder stabil. Eine vorübergehende neurologische Symptomverschlechterung ohne Tumorprogression zeigte sich bei fünf Patienten (8%). Die aktuarische lokale Tumorkontrolle lag, mit einer mittleren Nachbeobachtungszeit von 9,4 Monaten, nach 1 Jahr bei 81%. Die lokale Tumorkontrolle zeigte sich statistisch signifikant abhängig von der Höhe der applizierten Dosis und der Größe der Metastasen. Das mediane Überleben nach Therapie lag bei 10,6 Monaten. Das Fehlen einer extrazerebralen Tumormanifestation war mit einem verlängerten Überleben assoziiert (p = 0,04). Schlussfolgerungen: Patienten mit zerebral metastasiertem malignem Melanom haben trotz hoher zerebraler lokaler Tumorkontrollwahrscheinlichkeit eine schlechte Prognose, insbesondere bei zusätzlicher extrazerebraler Tumorlast. In palliativer Zielsetzung bietet die stereotaktische Einzeitbestrahlung die Möglichkeit, neurologische Symptome positiv zu beeinflussen.

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.

Radiation therapy of stage I and II non-small cell lung cancer (NSCLC)

Surgery is the preferred and standard treatment for patients with resectable stage I and II non-small cell lung cancer (NSCLC). Survival rates of local surgery are unbeaten by other treatment modalities. Up to 70% of these patients survive 5 years or longer. However, there is a subset of patients who either are inoperable due to the presence of severe associated diseases, or who refuse surgery. In these patients radical radiotherapy with curative intent is an effective alternative. In our department we retrospectively analysed survival and freedom from treatment failure in those patients treated in our hospital with primary irradiation for stage I and II NSCLC (T1-2 N0-1 M0) during the last 20 years. In total 60 patients with a median age of 69 years could be evaluated. 35% had stage I and 65% had stage II NSCLC. All patients received 2- or 3-dimensionally planned megavoltage radiotherapy with a median dose of 60 Gy with normally fractionated single doses of 2.0 Gy five times a week. Pneumonitis WHO Grade III was found in 5 out of the 60 patients (8.3%). Locoregional recurrence was observed in 53% of the patients resulting in a median progression-free survival of 18 months and a median overall survival of 20.5 months. However, there is a need for further improvement of treatment outcome of radiotherapy for medically inoperable patients with early-stage NSCLC. One possibility might be radiation dose escalation or alteration in fractionation of radiotherapy, such as continuous hyperfractionated accelerated radiotherapy CHART or a modification thereof CHARTWEL. These new fractionation schemes might be beneficial for a subset of patients in terms of improved local control, reduced incidence of metastasis and improved long term survival. The combination of chemotherapy and radiotherapy might be another option for treatment of early-stage NSCLC. In advanced disease combined modality treatment turned out to be superior to radiotherapy alone, concerning local control and survival. If this is true also for early-stage NSCLC, it has to be shown in further investigations.

Linac-Based Radiosurgery of Cerebral Melanoma Metastases

Purpose: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors. Patients and Methods: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at that time. The median dose to the 80% isodose line, prescribed to encompass the tumor margin, was 20 Gy (range, 15–22 Gy). Results: Neurologic symptoms improved in five of twelve symptomatic patients. 41 patients remained asymptomatic or unchanged in their neurologic symptoms. Only five patients (8%) temporarily worsened neurologically after therapy despite no signs of tumor progression. With a mean follow-up time of 9.4 months, actuarial local control was 81% after 1 year. There was a statistically significant dose and size dependency of local tumor control. Median actuarial survival after treatment was 10.6 months. Patients without extracerebral tumor manifestation showed a superior survival (p = 0.04). Conclusions: Despite high local tumor control rates, the prognosis of patients with cerebral metastases of malignant melanoma remains poor. Stereotactic radiosurgery has the potential of stabilizing or improving neurologic symptoms in these patients in a palliative setting.Ziel: Die stereotaktische Radiochirurgie hat sich als Alternative zur neurochirurgischen Exzision bei der Behandlung zerebraler Metastasen erwiesen. Wir analysierten retrospektiv den Verlauf und prognostische Faktoren bei Patienten, die wegen Hirnmetastasen bei malignem Melanom in Heidelberg stereotaktisch behandelt wurden. Patienten und Methodik: Zwischen 1986 und 2000 wurden insgesamt 122 Hirnmetastasen bei 64 Patienten mit metastasiertem malignem Melanom mit einer stereotaktischen Einzeitbestrahlung behandelt. Zwölf Patienten (19%) zeigten zum Zeitpunkt der Therapie neurologische Symptome. 46 Patienten hatten zum Therapiezeitpunkt extrazerebrale Tumormanifestationen. Die mediane Dosis, die auf die tumorumschließende 80%-Isodose appliziert wurde, betrug 20 Gy (Spannweite 15–22 Gy). Ergebnisse: Die neurologischen Symptome besserten sich bei fünf der zwölf symptomatischen Patienten. 41 Patienten blieben während der weiteren Nachbeobachtung neurologisch asymptomatisch oder stabil. Eine vorübergehende neurologische Symptomverschlechterung ohne Tumorprogression zeigte sich bei fünf Patienten (8%). Die aktuarische lokale Tumorkontrolle lag, mit einer mittleren Nachbeobachtungszeit von 9,4 Monaten, nach 1 Jahr bei 81%. Die lokale Tumorkontrolle zeigte sich statistisch signifikant abhängig von der Höhe der applizierten Dosis und der Größe der Metastasen. Das mediane Überleben nach Therapie lag bei 10,6 Monaten. Das Fehlen einer extrazerebralen Tumormanifestation war mit einem verlängerten Überleben assoziiert (p = 0,04). Schlussfolgerungen: Patienten mit zerebral metastasiertem malignem Melanom haben trotz hoher zerebraler lokaler Tumorkontrollwahrscheinlichkeit eine schlechte Prognose, insbesondere bei zusätzlicher extrazerebraler Tumorlast. In palliativer Zielsetzung bietet die stereotaktische Einzeitbestrahlung die Möglichkeit, neurologische Symptome positiv zu beeinflussen.

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.

The Role of Radiation Therapy in the Management of Desmoid Tumors

Purpose: To investigate the role of radiation therapy (RT) in the management of desmoid tumors. Patients and Methods: Retrospective analysis was performed on 28 patients with desmoid tumors treated with radiation therapy between March 1989 and March 1999. Tumor site was intraabdominal in three, abdominal wall in three and extraabdominal in 22 patients. Median tumor dose was 48 Gy (range 36–60 Gy). Radiation therapy was delivered postoperatively in 26 of 28 patients, two patients received radiation therapy for unresectable recurrent tumors. Results: Median follow-up was 46 months (range 13–108 months). Actuarial 5-year control rate was 73%. We observed six recurrences, located within the radiation field in one patient, out of field in two and at the field margin in three patients. All patients with intraabdominal tumors have been controlled without severe side effects. Conclusions: Radiation therapy is an effective treatment after incomplete resection of desmoid tumors. We did not observe a benefit for tumor doses exceeding 50 Gy. In some patients with circumscribed intraabdominal desmoid tumors, radiation therapy might be a treatment option with low toxicity, if 3-D treatment planning is utilized.Hintergrund: Der Stellenwert der Strahlentherapie (RT) bei der Behandlung von Desmoiden soll untersucht werden. Patienten und Methode: Die Untersuchung umfasste 28 Patienten mit Desmoiden, die zwischen März 1989 und März 1999 eine Strahlentherapie erhielten. Die Tumorlokalisation war bei drei Patienten intraabdominell und bei 22 Patienten extraabdominell. Bei drei Patienten war die Bauchwand betroffen. Die mediane Tumordosis lag bei 48 Gy (36–60 Gy). Die Strahlentherapie erfolte bei 26 von 28 Patienten postoperativ, zwei Patienten erhielten eine Bestrahlung aufgrund inoperabler Rezidive. Ergebnisse: Die mediane Nachbeobachtungszeit lag bei 46 Monaten (13–108 Monate). Die aktuarische Kontrollrate nach 5 Jahren betrug 73%. Wir haben sechs Rezidive beobachtet, davon waren eines innerhalb und zwei außerhalb des ehemaligen Bestrahlungsvolumens gelegen. Drei Patienten entwickelten ein Feldrandrezidiv. Alle drei intraabdominellen Desmoide konnten ohne schwere Nebenwirkungen durch die Bestrahlung kontrolliert werden. Schlussfolgerungen: Die Strahlentherapie ist effektiv bei der Behandlung von inkomplett resezierten Desmoiden. Wir konnten keinen Vorteil für eine Dosiseskalation auf Tumordosen > 50 Gy nachweisen. Bei ausgewählten Patienten mit umschriebenen intraabdominellen Desmoidtumoren stellt die Strahlentherapie eine Behandlungsoption mit geringer Toxizität dar, sofern eine dreidimensionale Bestrahlungsplanung erfolgt.