Gerd Becker

Geometric accuracy of field alignment in fractionated stereotactic conformal radiotherapy of brain tumors

PURPOSEnTo assess the accuracy of field alignment in patients undergoing three-dimensional (3D) conformal radiotherapy of brain tumors, and to evaluate the impact on the definition of planning target volume and control procedures.nnnMETHODS AND MATERIALSnGeometric accuracy was analyzed in 20 patients undergoing fractionated stereotactic conformal radiotherapy for brain tumors. Rigid head fixation was achieved by using cast material. Transfer of stereotactic coordinates was performed by an external positioning device. The accuracy during treatment planning was quantitatively assessed by using repeated computed tomography (CT) examinations in treatment position (reproducibility of isocenter). Linear discrepancies were measured between treatment plan and CT examination. In addition, for each patient, a series of 20 verifications were taken in orthogonal projections. Linear discrepancies were measured between first and all subsequent verifications (accuracy during treatment delivery).nnnRESULTSnFor the total group of patients, the distribution of deviations during treatment setup showed mean values between -0.3-1.2 mm, with standard deviations (SD) of 1.3-2.0 mm. During treatment delivery, the distribution of deviations revealed mean values between 0.7-0.8 mm, with SDs of 0.5-0.6 mm, respectively. For all patients, deviations for the transition to the treatment machine were similar to deviations during subsequent treatment delivery, with 95% of all absolute deviations between less than 2.8 and 4.6 mm.nnnCONCLUSIONnRandom fluctuations of field displacements during treatment planning and delivery prevail. Therefore, our quantitative data should be considered when prescribing the safety margins of the planning target volume. Repeated CT examination are useful to detect operator errors and large random or systematic deviations before start of treatment. Control procedures during treatment delivery appear to be of limited importance. In addition, our findings should help to determine cut-off points for corrective actions in stereotactic conformal radiotherapy of brain tumors.

Clinical indications and biological mechanisms of splenic irradiation in chronic leukaemias and myeloproliferative disorders.

Splenic irradiation (SI) was the first efficient treatment for chronic leukaemia, but with the emergence of effective drugs its use has been more and more restricted to advanced cases presenting with splenomegaly. But in selected patients who are not responsive or not suitable to drug treatment, SI may offer still an effective, low toxic and cost-effective palliative modality. Eight studies of SI in chronic lymphatic leukaemia (CLL) including 198 patients, six reports about SI in prolymphocytic leukaemia (PLL), including 18 patients, one study and six case reports about SI in hairy cell leukaemia (HCL) and nine studies about SI in myeloproliferative disorders has been analyzed. In CLL, symptoms of splenomegaly have been improved in 50-87% of all patients with overall doses between 4 and 10 Gy in mostly 1-Gy fractions. PLL seems to be more resistant to SI with a median response rate of 66%. Casuistic reports described also efficacy of SI in HCL patients using similar radiation schedules. Symptomatic relief is also provided by SI in myeloproliferative disorders using lower overall doses between 1 and 9 Gy with small single fractions of 0.25 Gy (median). Acute toxicity was low in lymphoid disorders, but higher in myeloproliferative disorders with severe cytopenia in 10-30% of all cases, indicating the need for a cautious fractionation schedule. Interestingly, even complete systemic remissions after SI in all types of lymphoproliferative disorders have been described. Different mechanisms underlying SI such as direct cell kill, immune modulation via changes in lymphocyte subsets or cytokine induction or radiotherapeutic splenectomy with high doses are discussed.

Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide

Purpose: Despite the progress made in neurosurgery and radiotherapy, the prognosis of glioblastoma multiforme (GB) is poor, due to the lack of an effective salvage therapy. In vitro analysis revealed activity for ifosfamide and temozolomide. The usefulness of these agents in recurrent disease was investigated. Methods: Six adult patients with recurrent GB received one to four courses of 1,500u2009mg/m2 ifosfamide given over 5 days intravenously. Furthermore, temozolomide (100–200u2009mg/m2) was given orally over 5 days to 14 patients. Results: After ifosfamide treatment, one partial response and two cases of stable disease were observed. The median survival time was 24 weeks (range of 9–52 weeks). Toxicity analysis revealed one paranoid reaction, three grade III leukocytopenia, and one grade I–II nausea, anemia, and hematuria. Temozolomide therapy resulted in three partial responses and four cases of stable disease. The median survival time (Kaplan-Meier) was 21 weeks (range 4–64 weeks). The major toxicities were grade I–II nausea and hematological side effects (one case of grade IV leuko- and thrombocytopenia). Conclusions: Ifosfamide treatment might be a feasible approach, but it necessitates hospitalization. Temozolomide showed promising results. Due to its oral application, the patients quality of life (time out of hospital) is favorable. Subgroups with improved survival were observed.

Stereotactic Convergent Beam Radiosurgery Versus Stereotactic Conformation Beam Radiotherapy

By means of preliminary results in the treatment of patients with acoustic neurinoma the achievable accuracies, dose distributions and time consumption of stereotactic LINAC-based convergent beam radiosurgery are compared to those achieved with fractionated stereotactic conformation beam radiotherapy. Characteristics of both techniques are described. With the Tübingen radiosurgery system a good adaptation of the dose distribution to spherical or oval target volumes with a steep dose gradient was achieved, whereas homogeneity and adaptation of the dose distribution to irregularly shaped targets were better with the Heidelberg conformation technique. The mechanical accuracy of the Tübingen floorstand system was 0.3 mm +/- 0.2 mm, and that of the Heidelberg mask fixation system < 1 mm. Both methods require similar total treatment times. Nine patients were treated by the Tübingen radiosurgery system. The results are compared with 12 patients treated by conformation radiotherapy in Heidelberg. In both patient groups no further tumour growth occurred. Four of 9 single dose treated patients developed side-effects, such as temporary trigeminal and facial paraesthesia hearing deterioration and oedema. In contrast, patients treated by fractionated radiotherapy showed no side-effects. Relating to the short follow-up the results indicate that single dose application has certain drawbacks for special indications. Further studies have to work out which method gives the best treatment results.

Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases.

Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients.nn Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia.nn Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate.nn Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality.Hintergrund: Die Bestrahlung der Milz zur Behandlung von hämatologischen Autoimmunerkrankungen wie den autoimmun hämolytischen Anäein (AIHA) oder den autoimmun vermittelten Thrombozytopenien (AIT) ist eine wenig bekannte Therapieoption. Die klinische Erfahrung und das Wissen um die zugrunde liegenden biologischen Mechanismen sind begrenzt. Trotzdem profitieren Patienten in bestimmten klinischen Konstellationen von der Milzbestrahlung.nn Patienten und Methode: Diese Übersichtsarbeit fasst die bisherigen Erfahrungen zur Milzbestrahlung bei der autoimmun vermittelten Thrombozytopenie – sieben Studien und zwei Fallberichte mit insgesamt 71 Patienten – zusammen und berichtet über die bisher eher anekdotischen Erfahrungen zur Milzbestrahlung im Falle einer autoimmun hämolytischen Anämie.nn Ergebnisse: Zwischen 40 und 90% aller Patienten mit autoimmun vermittelten Thrombozytopenien sprachen auf die Bestrahlung der Milz an, wobei allerdings die meisten kurz nach Ende der Therapie wieder einen Abfall der Thrombozytenzahl erlitten (Tabelle 1). Etwa 10 bis 20% aller Patienten profitierten langfristiger von der Behandlung, wobei Patienten mit einer HIV-assoziierten Thrombozytopenie möglicherweise etwas schlechter ansprechen. Einzelne Fallberichte schildern auch erfolgreiche Behandlungen von autoimmun hämolytischen Anämien durch Bestrahlung der Milz. Die Nebenwirkungen der Milzbestrahlung waren in allen ausgewerteten Studien sehr moderat.nn Schlussfolgerungen: In Risikokonstellationen für eine Splenektomie oder bei Resistenz gegenüber medikamentösen Ansätzen kann die Milzbestrahlung bei ausgewählten Patienten eine wertvolle Alternative bei der Therapie der Autoimmunthrombopenie darstellen. Eine viel versprechende neue Anwendung könnte möglicherweise die präoperative, akzelerierte Milzbestrahlung vor Splenektomie bei Patienten darstellen, die auf immunsuppressive Medikamente schlecht oder gar nicht ansprechen. Ein Verständnis der immunsuppressiven Effekte der Milzbestrahlung könnte in Zukunft die Grundlage optimierter Dosiskonzepte und einer besseren Patientenselektion für diese Behandlungsform darstellen und gleichzeitig das Verständnis über Strahlentherapie als immunmodulatorische Behandlung im Allgemeinen fördern.

Time requirements in conformal radiotherapy treatment planning

To investigate the influence of implementing three-dimensional treatment planning on staffing needs, valid questionnaire responses from 22 radiotherapy institutions have been evaluated. Average time requirements per plan rise from 213 to 439 min upon implementation, but with experience decrease to 317 min. No institution reports additional staff positions according to estimated requirements.

Radiochirurgie von Hirnmetastasen

Die Tatsache, daB die Fernmetastasierungsrate in beiden Behandlungsarmen gleich hoch war, zeigt die Insuffizienz der gegebenen Chemotherapiedosis bei der Beherrsehung der systemischen Tumorausbreitung. Da die h/~matogene Metastasierung mit einer Inzidenz von 60 bis 80% ein Hauptproblem bei de r Behandlung des niehtkleinzelligen Bronchialkarzinotas im Stadium III darstellt, muB neben der Verbesserung des Gesamt a durch verbesserte lokale Kontrol le nach Radioehemotherapie auch der Einsatz der adjuvanten oder neoadjuvanten hochdosierten Chemotherap ie in mul t imodalen Therapiekonzepten weiter verfolgt werden.

Treatment planning for bicentric stereotactic irradiation.

We have investigated a bicentric stereotactic convergent beam irradiation technique for the treatment of irregularly shaped, especially elongated, target volumes. Depending on the size and shape of the target volume optimum values for the isocenter distance, collimator apertures and dose inhomogeneity have been determined which serve as starting parameters for the interactive optimization of dose distribution. The treatment planning system of the stereotactic unit SRS-200 (Philips) has been used to calculate the parameter tables. However, the presented results are also applicable to other stereotactic systems.