Christoph Thilmann

Efficacy of Fractionated Stereotactic Reirradiation in Recurrent Gliomas: Long-Term Results in 172 Patients Treated in a Single Institution

PURPOSE To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) performed as reirradiation in 172 patients with recurrent low- and high-grade gliomas. PATIENTS AND METHODS Between 1990 and 2004, 172 patients with recurrent gliomas were treated with FSRT as reirradiation in a single institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO grade 3 gliomas were diagnosed in 42 patients, and 59 patients were diagnosed with glioblastoma multiforme (GBM). The median time between primary radiotherapy and reirradiation was 10 months for GBM, 32 months for WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was performed with a median dose of 36 Gy in a median fractionation of 5 x 2 Gy/wk. RESULTS Median overall survival after primary diagnosis was 21 months for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and 111 months for patients with WHO grade 2 gliomas. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection and age at primary diagnosis. Median survival after reirradiation was 8 months for patients with GBM, 16 months for patients with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only time to progression and histology were significant in influencing survival after reirradiation. Progression-free survival after FSRT was 5 months for GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas. CONCLUSION FSRT is well tolerated and may be effective in patients with recurrent gliomas. Prospective studies are warranted for further evaluation.

Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM).

This article describes the results of a study of stereotactic radiosurgery (SRS) in the treatment of patients with recurrent malignant glioma.

CLINICAL RESULTS OF RETREATMENT OF VERTEBRAL BONE METASTASES BY STEREOTACTIC CONFORMAL RADIOTHERAPY AND INTENSITY-MODULATED RADIOTHERAPY

PURPOSE Reirradiation of spinal tumors is limited by the tolerance of the spinal cord. We evaluated local control, pain relief, neurologic improvement, side effects, and survival rates after fractionated conformal radiotherapy (FCRT) and intensity-modulated RT (IMRT) of recurrent spinal metastases. METHODS AND MATERIALS Eighteen patients with 19 radiologic manifestations were retreated for recurrent spinal metastases using FCRT (n = 5) or IMRT (n = 14). All patients had previously undergone conventional RT (median dose 38 Gy). The indication for reirradiation was tumor progression associated with pain (n = 16) or neurologic symptoms (n = 12). The median time to recurrence was 17.7 months. The median total dose for reirradiation was 39.6 Gy. RESULTS The overall local control rate was 94.7% after a median follow-up of 12.3 months. Of 16 patients with pain, 13 experienced significant relief after reirradiation. Neurologic improvement was obtained in 5 of 12 patients. Tumor size remained unchanged in 84.2%. A partial response was seen in 2 of 19 patients. One patient had local tumor progression 9.5 months after reirradiation. Six patients received chemotherapy after reirradiation because of progressive distant metastases. Twelve patients died 10.5 months median after reirradiation. No clinically significant late toxicity was seen after FCRT or IMRT. CONCLUSION These data demonstrate that FCRT and IMRT are effective and safe in recurrent spinal tumors and can be offered to patients to achieve local control, as well as pain relief.

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.

Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with carbon ions

PURPOSE Compared to photon irradiation, carbon ions provide physical and biologic advantages that may be exploited in chordomas and chondrosarcomas. METHODS AND MATERIALS Between August 1998 and December 2000, 37 patients with chordomas (n = 24) and chondrosarcomas (n = 13) were treated with carbon ion radiotherapy within a Phase I/II trial. Tumor conformal application of carbon ion beams was realized by intensity-controlled raster scanning with pulse-to-pulse energy variation. Three-dimensional treatment planning included biologic plan optimization. The median tumor dose was 60 GyE (GyE = Gy x relative biologic effectiveness). RESULTS The mean follow-up was 13 months. The local control rate after 1 and 2 years was 96% and 90%, respectively. We observed 2 recurrences outside the gross tumor volume in patients with chordomas. Progression-free survival was 100% for chondrosarcomas and 83% for chordomas at 2 years. Partial remission after carbon ion radiotherapy was observed in 6 patients. Treatment toxicity was mild. CONCLUSION These are the first data demonstrating the clinical feasibility, safety, and effectiveness of scanning beam delivery of ion beams in patients with skull base tumors. The preliminary results in patients with skull base chordomas and low-grade chondrosarcomas are encouraging, although the follow-up was too short to draw definite conclusions concerning outcome. In the absence of major toxicity, dose escalation might be considered.

Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences

BackgroundThe purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy.Patients and methodsFor evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used.Results and discussionBony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10–12 minutes, which can be further reduced by streamlining the different steps.ConclusionThe cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable.

Assessment of irradiated brain metastases by means of arterial spin-labeling and dynamic susceptibility-weighted contrast-enhanced perfusion MRI: Initial results

Rationale and Objectives:To assess if preradiation and early follow-up measurements of relative regional cerebral blood flow (rrCBF) can predict treatment outcome in patients with cerebral metastases and to evaluate rrCBF changes in tumor and normal tissue after stereotactic radiosurgery using arterial spin-labeling (ASL) and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MRI. Methods:In 25 patients with a total of 28 brain metastases, DSC MRI and ASL perfusion MRI using the Q2TIPS sequence were performed with a 1.5-T unit. Measurements were performed prior to and at 6 weeks, 12 weeks, and 24 weeks after stereotactic radiosurgery. Follow-up examinations were completely available in 25 patients for Q2TIPS and 17 patients with 18 metastases for DSC MRI. The rrCBF of the metastases and the normal brain tissue was determined by a region-of-interest analysis. rrCBF values were correlated with the treatment outcome that was classified according to tumor volume changes at 6 months. Results:The alteration of the rrCBF at the 6-week follow-up was highly predictive for treatment outcome. A decrease of the rrCBF value predicted tumor response correctly in all metastases for Q2TIPS and in 13 of 16 metastases for DSC MRI. The pretherapeutic rrCBF was not able to predict treatment outcome. The rrCBF values in normal brain tissue affected by radiation doses less than 0.5 Gy remained unchanged after therapy. Conclusion:These preliminary results suggest that ASL and DSC MRI techniques determining rrCBF changes in brain metastases after stereotactic radiosurgery allow the prediction of treatment outcome.

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients.

Purpose:To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas.Patients and Methods:Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the “Gesellschaft für Schwerionenforschung” (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction.Results:Median follow-up was 15 months (range 3–46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC°III have been observed.Conclusions:These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.Ziel:Prospektive Evaluation von Therapieergebnissen und Toxizität bei Chordomen und niedriggradigen Chondrosarkomen nach Kohlenstoffionentherapie.Patienten und Methodik:Von September 1998 bis Dezember 2001 wurden 74 Patienten mit Chordomen und Chondrosarkomen bei der Gesellschaft für Schwerionenforschung (GSI) mit Kohlenstoffionen bestrahlt. Sieben mit konventioneller Radiotherapie vorbestrahlte Patienten, die eine Rebestrahlung mit reduzierter Kohlenstoffionendosis erhielten, wurden von der Analyse ausgeschlossen. Die Analyse umfasst 67 Patienten (44 Chordome und 23 Chondrosarkome), die eine voll fraktionierte Kohlenstoffionentherapie erhielten. Die tumorkonforme Kohlenstoffionenapplikation erfolgte mittels intensitätsgesteuerten Rasterscanverfahrens mit aktiver Energievariation. Die dreidimensionale Bestrahlungsplanung beinhaltete eine Intensitätsmodulation sowie eine biologische Planoptimierung. Die mediane Dosis betrug 60 GyE im Zielvolumen und wurde an 20 aufeinander folgenden Tagen bei einer täglichen Fraktionierung von 3,0 GyE appliziert.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 15 Monate (3–46 Monate). Die aktuarische lokale Kontrollrate nach 3 Jahren lag bei 100% für Chondrosarkome und bei 87% für Chordome. Eine partielle Tumorremission wurde bei 14/44 (31%) Chordompatienten und bei 4/23 (17%) Chondrosarkompatienten beobachtet. Die aktuarische Gesamtüberlebensrate lag nach 3 Jahren bei 100% für Chondrosarkome und bei 89% für Chordome. Schwere Nebenwirkungen > CTC°III wurden nicht beobachtet.Schlussfolgerungen:Die Daten belegen die klinische Effektivität und Sicherheit der Kohlenstoffionentherapie mit einem gescannten Kohlenstoffionenstrahl bei Patienten mit Chordomen und Chondrosarkomen der Schädelbasis. Die Beobachtung von Tumorregressionen bei einer Dosis von 60 GyE weist darauf hin, dass die biologische Wirksamkeit der Kohlenstoffionen bei Chordomen und Chondrosarkomen höher sein könnte als ursprünglich angenommen.

Treatment of Cerebral Metastases from Breast Cancer with Stereotactic Radiosurgery

Background and Purpose:The role of stereotactic radiosurgery (SRS) alone or in combination with whole brain radiotherapy (WBRT) in the treatment of cerebral metastases from breast carcinoma is discussed controversially. To elucidate the role of SRS in this context, a retrospective study evaluating the benefit of SRS and prognostic factors for survival was performed.Patients and Methods:From 1986 to 2003, 62 patients with cerebral metastases from breast cancer were treated for 103 lesions. Ten patients received SRS alone (group 1), 13 patients were treated with WBRT and SRS as a focal boost (group 2), and 39 patients received WBRT and salvage SRS (group 3) for recurrent metastases at a later time point.Results:Survival was increased in patients receiving SRS only compared to WBRT and SRS as a focal boost. Patients < 40 years of age had a favorable outcome (p > 0.04). However, no other prognostic factors could be identified. Overall tolerance of radiation was acceptable. Median local control intervals were 9 months for all patients, 6.5 months in group 1, 4 months in group 2, and 9 months in group 3, respectively. There were no significant intergroup differences.Conclusion:SRS alone is an effective treatment for patients with one to three brain metastases from breast cancer. A randomized trial should be performed to evaluate whether WBRT is a necessary component in the primary treatment of these patients. Salvage SRS is an effective therapy option after WBRT.Hintergrund und Ziel:Die Behandlung zerebraler Metastasen des Mammakarzinoms mit stereotaktischer Radiochirurgie (SRS) allein oder in Kombination mit einer Ganzhirnbestrahlung (WBRT) wird derzeit kontrovers diskutiert. Um die Vorteile der SRS in diesem Kontext und den Einfluss von prognostischen Faktoren auf das Gesamtüberleben zu evaluieren, wurde eine retrospektive Analyse durchgeführt.Patienten und Methodik:Zwischen 1986 und 2003 wurden 62 Patientinnen mit 103 Hirnmetastasen bei Brustkrebs behandelt. Zehn Patientinnen erhielten eine alleinige SRS (Gruppe 1), 13 Patientinnen wurden mit WBRT und SRS (fokaler Boost) behandelt (Gruppe 2), und 39 Patientinnen erhielten eine WBRT und eine Salvage-SRS (Gruppe 3) bei Progredienz der Metastasen zu einem späteren Zeitpunkt.Ergebnisse:Das mediane Gesamtüberleben war in der Gruppe, die mit alleiniger SRS behandelt wurde, tendenziell erhöht im Vergleich zu der Gruppe, die eine WBRT mit SRS als fokalem Boost erhalten hatte. Bei Patientinnen < 40 Jahren war das Gesamtüberleben signifikant besser (p > 0,04). Es konnten keine weiteren prognostischen Faktoren identifiziert werden. Die Strahlentherapie wurde von allen Patientinnen gut toleriert. Die mediane lokale Kontrolle lag bei 9 Monaten für alle Patientinnen, 6,5 Monaten in Gruppe 1, 4 Monaten in Gruppe 2 and 9 Monaten in Gruppe 3. Es gab keine signifikanten Unterschiede zwischen den einzelnen Gruppen.Schlussfolgerung:Die alleinige SRS ist eine effektive Behandlungsmethode für Patientinnen mit ein bis drei Hirnmetastasen bei Mammakarzinom. Eine randomisierte Studie zur weiteren Evaluation der Notwendigkeit einer WBRT bei diesen Patientinnen sollte durchgeführt werden. Die Salvage-SRS ist eine effektive Therapieoption bei progredienten Hirnmetastasen nach einer WBRT.

Carbon Ion Radiotherapy for Chordomas and Low-Grade Chondrosarcomas of the Skull Base

Purpose:To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas.Patients and Methods:Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the “Gesellschaft für Schwerionenforschung” (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction.Results:Median follow-up was 15 months (range 3–46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC°III have been observed.Conclusions:These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.Ziel:Prospektive Evaluation von Therapieergebnissen und Toxizität bei Chordomen und niedriggradigen Chondrosarkomen nach Kohlenstoffionentherapie.Patienten und Methodik:Von September 1998 bis Dezember 2001 wurden 74 Patienten mit Chordomen und Chondrosarkomen bei der Gesellschaft für Schwerionenforschung (GSI) mit Kohlenstoffionen bestrahlt. Sieben mit konventioneller Radiotherapie vorbestrahlte Patienten, die eine Rebestrahlung mit reduzierter Kohlenstoffionendosis erhielten, wurden von der Analyse ausgeschlossen. Die Analyse umfasst 67 Patienten (44 Chordome und 23 Chondrosarkome), die eine voll fraktionierte Kohlenstoffionentherapie erhielten. Die tumorkonforme Kohlenstoffionenapplikation erfolgte mittels intensitätsgesteuerten Rasterscanverfahrens mit aktiver Energievariation. Die dreidimensionale Bestrahlungsplanung beinhaltete eine Intensitätsmodulation sowie eine biologische Planoptimierung. Die mediane Dosis betrug 60 GyE im Zielvolumen und wurde an 20 aufeinander folgenden Tagen bei einer täglichen Fraktionierung von 3,0 GyE appliziert.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 15 Monate (3–46 Monate). Die aktuarische lokale Kontrollrate nach 3 Jahren lag bei 100% für Chondrosarkome und bei 87% für Chordome. Eine partielle Tumorremission wurde bei 14/44 (31%) Chordompatienten und bei 4/23 (17%) Chondrosarkompatienten beobachtet. Die aktuarische Gesamtüberlebensrate lag nach 3 Jahren bei 100% für Chondrosarkome und bei 89% für Chordome. Schwere Nebenwirkungen > CTC°III wurden nicht beobachtet.Schlussfolgerungen:Die Daten belegen die klinische Effektivität und Sicherheit der Kohlenstoffionentherapie mit einem gescannten Kohlenstoffionenstrahl bei Patienten mit Chordomen und Chondrosarkomen der Schädelbasis. Die Beobachtung von Tumorregressionen bei einer Dosis von 60 GyE weist darauf hin, dass die biologische Wirksamkeit der Kohlenstoffionen bei Chordomen und Chondrosarkomen höher sein könnte als ursprünglich angenommen.