Stefanie Milker-Zabel

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.

Fractionated stereotactic radiation therapy in the management of benign cavernous sinus meningiomas : Long-term experience and review of the literature

Purpose:To analyze own long-term results with fractionated stereotactic radiotherapy (FSRT) in patients with benign meningiomas of the cavernous sinus and to review the literature on these rare lesions.Patients and Methods:57 patients were treated with FSRT for benign meningiomas of the cavernous sinus between 01/1990 and 12/2003 at the authors’ institution. Histology was WHO grade I in 28/57 lesions, and undetermined in 29/57 lesions. 29 patients received radiotherapy as primary treatment, ten following surgery, and 18 patients were irradiated for recurrent disease. Median target volume was 35.2 cm3. Median total dose was 57.6 Gy with 1.8 Gy per fraction. 51/57 patients showed clinical symptoms before radiotherapy like reduced vision (n = 19), diplopia (n = 25), or trigeminal hyp-/dysesthesia (n = 17).Results:Median follow-up period was 6.5 years. 50/57 patients were followed for > 36 months. Overall local tumor control was 100%. 39/57 patients had stable disease based on CT/MRI, while 18/57 had a partial remission of tumor volume. Overall survival for patients with WHO grade I meningiomas was 95.5% after 5 and 10 years. Two patients died 2.8 and 4.1 years after radiotherapy due to cardiac failure. In 11/57 patients, preexisting neurologic deficits improved. There was one patient with recurrent hyperlacrimation of one eye on the side of the irradiated meningioma. Three patients complained about subjective visual deterioration after FSRT without any objective findings in an ophthalmologic examination. No late toxicity RTOG ≥ °III was seen.Conclusion:These data demonstrate that FSRT is an effective and safe treatment modality for local control of benign cavernous sinus meningiomas with a minimal risk of significant late toxicity.Ziel:Darstellung der Langzeitergebnisse nach fraktionierter stereotaktischer Strahlentherapie (FSRT) von benignen Sinus-cavernosus-Meningeomen und Literaturübersicht dieser seltenen Befunde.Patienten und Methodik:Zwischen 01/1990 und 12/2003 wurden 57 Patienten mittels FSRT an einem benignen Sinus-cavernosus-Meningeom in der Abteilung der Autoren behandelt. Histopathologisch entsprachen 28/57 Befunde WHO-Grad I, und 29/57 Befunde waren ausschließlich bildmorphologisch eindeutig als Meningeom diagnostiziert worden. 29 Patienten wurden primär, zehn postoperativ und 18 in einer Rezidivsituation bestrahlt. Die mediane Zielvolumengröße betrug 35,2 cm3. Die mediane applizierte Gesamtdosis betrug 57,6 Gy bei einer wöchentlichen Fraktionierung von 5 × 1,8 Gy. Initial zeigten 51/57 Patienten neurologische Symptome, wie Sehverschlechterung (n = 19), Doppelbilder (n = 25) oder Trigeminushyp-/-dysästhesie (n = 17).Ergebnisse:Die lokale Tumorkontrollrate betrug 100% nach einer medianen Nachbeobachtungszeit von 6,5 Jahren. Bei 50/57 Patienten war der Nachbeobachtungszeitraum > 36 Monate. 39 Meningeome zeigten eine Größenkonstanz im CT/MRT, 18 Befunde eine Größenreduktion. Das Gesamtüberleben betrug 95,5% nach 5 und 10 Jahren. Zwei Patienten verstarben 2,8 und 4,1 Jahre nach Strahlentherapie an kardialer Ursache. Bei 11/57 Patienten zeigte sich nach Strahlentherapie eine deutliche Besserung der vorbestehenden neurologischen Symptomatik. Ein Patient entwickelte im Verlauf rezidivierendes Augentränen auf der Seite des bestrahlten Meningeoms. Drei Patienten berichteten über rezidivierende subjektive Sehverschlechterung ohne ophthalmologisches Korrelat. Es traten keine Spättoxizitäten RTOG ≥ °III auf.Schlussfolgerung:Die FSRT ist sicher anwendbar und erreicht gute lokale Tumorkontrollraten bei geringem Risiko für radiogene Spätkomplikationen.

Fractionated Stereotactic Radiation Therapy in the Management of Benign Cavernous Sinus Meningiomas

Purpose:To analyze own long-term results with fractionated stereotactic radiotherapy (FSRT) in patients with benign meningiomas of the cavernous sinus and to review the literature on these rare lesions.Patients and Methods:57 patients were treated with FSRT for benign meningiomas of the cavernous sinus between 01/1990 and 12/2003 at the authors’ institution. Histology was WHO grade I in 28/57 lesions, and undetermined in 29/57 lesions. 29 patients received radiotherapy as primary treatment, ten following surgery, and 18 patients were irradiated for recurrent disease. Median target volume was 35.2 cm3. Median total dose was 57.6 Gy with 1.8 Gy per fraction. 51/57 patients showed clinical symptoms before radiotherapy like reduced vision (n = 19), diplopia (n = 25), or trigeminal hyp-/dysesthesia (n = 17).Results:Median follow-up period was 6.5 years. 50/57 patients were followed for > 36 months. Overall local tumor control was 100%. 39/57 patients had stable disease based on CT/MRI, while 18/57 had a partial remission of tumor volume. Overall survival for patients with WHO grade I meningiomas was 95.5% after 5 and 10 years. Two patients died 2.8 and 4.1 years after radiotherapy due to cardiac failure. In 11/57 patients, preexisting neurologic deficits improved. There was one patient with recurrent hyperlacrimation of one eye on the side of the irradiated meningioma. Three patients complained about subjective visual deterioration after FSRT without any objective findings in an ophthalmologic examination. No late toxicity RTOG ≥ °III was seen.Conclusion:These data demonstrate that FSRT is an effective and safe treatment modality for local control of benign cavernous sinus meningiomas with a minimal risk of significant late toxicity.Ziel:Darstellung der Langzeitergebnisse nach fraktionierter stereotaktischer Strahlentherapie (FSRT) von benignen Sinus-cavernosus-Meningeomen und Literaturübersicht dieser seltenen Befunde.Patienten und Methodik:Zwischen 01/1990 und 12/2003 wurden 57 Patienten mittels FSRT an einem benignen Sinus-cavernosus-Meningeom in der Abteilung der Autoren behandelt. Histopathologisch entsprachen 28/57 Befunde WHO-Grad I, und 29/57 Befunde waren ausschließlich bildmorphologisch eindeutig als Meningeom diagnostiziert worden. 29 Patienten wurden primär, zehn postoperativ und 18 in einer Rezidivsituation bestrahlt. Die mediane Zielvolumengröße betrug 35,2 cm3. Die mediane applizierte Gesamtdosis betrug 57,6 Gy bei einer wöchentlichen Fraktionierung von 5 × 1,8 Gy. Initial zeigten 51/57 Patienten neurologische Symptome, wie Sehverschlechterung (n = 19), Doppelbilder (n = 25) oder Trigeminushyp-/-dysästhesie (n = 17).Ergebnisse:Die lokale Tumorkontrollrate betrug 100% nach einer medianen Nachbeobachtungszeit von 6,5 Jahren. Bei 50/57 Patienten war der Nachbeobachtungszeitraum > 36 Monate. 39 Meningeome zeigten eine Größenkonstanz im CT/MRT, 18 Befunde eine Größenreduktion. Das Gesamtüberleben betrug 95,5% nach 5 und 10 Jahren. Zwei Patienten verstarben 2,8 und 4,1 Jahre nach Strahlentherapie an kardialer Ursache. Bei 11/57 Patienten zeigte sich nach Strahlentherapie eine deutliche Besserung der vorbestehenden neurologischen Symptomatik. Ein Patient entwickelte im Verlauf rezidivierendes Augentränen auf der Seite des bestrahlten Meningeoms. Drei Patienten berichteten über rezidivierende subjektive Sehverschlechterung ohne ophthalmologisches Korrelat. Es traten keine Spättoxizitäten RTOG ≥ °III auf.Schlussfolgerung:Die FSRT ist sicher anwendbar und erreicht gute lokale Tumorkontrollraten bei geringem Risiko für radiogene Spätkomplikationen.

Treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) by stereotactic linac-based radiosurgery: prognostic factors

A restrospective study of patients with brain metastases from non-small cell lung cancer (NSCLC) is performed to identify patients who benefit from radiosurgery and to determine prognostic factors for survival. Eighty-six consecutive patients with a total of 110 brain metastases from NSCLC were treated with linac-based radiosurgery. Six patients with eight brain metastases who received radiosurgery as a focal boost to whole brain radiotherapy where excluded. Median age at treatment was 60 years. Median dose was 20 Gy/80%-isodose. A chi(2)-test was used to identify potential prognostic factors for local control of brain metastases and survival of the patients. Median follow-up was 6 months (range 1 1/2-77 months) with 17/80 patients still alive. Median actuarial survival was significantly longer (P<0.004) in patients with metachronous onset of brain metastases in comparison to synchronous onset (8.3 vs. 3.3 months). Survival was significantly increased after radiosurgery in the absence of extracranial tumor progression (P<0.03). Eleven patients (14%) developed new brain metastases after radiosurgery after a latency of median 5 months. Actuarial local control rate was 96% after 3 months. Local control was significantly increased with a prescribed dose > or=18 Gy/80%-isodose (P<0.01). We conclude that especially patients with poor prognostic factors and a limited number of brain metastases may be palliatively treated with radiosurgery alone. This approach allows to effectively control CNS manifestation of the disease and can be integrated into chemotherapeutic protocols.

INTENSITY-MODULATED RADIOTHERAPY OF THE FEMALE BREAST

Current methods for intensity-modulated radiotherapy (IMRT) in breast cancer use forward planning based on equivalent radiological path length to design intensity modulated tangential beams. Compared to conventional tangential techniques, dose reduction of organs at risk is limited using these techniques. We developed a method for intensity modulation of multiple beams for adjuvant radiotherapy of breast cancer by application of a virtual bolus defined on CT for inverse optimization. This method enables multibeam IMRT, which provides improved sparing of lung and heart tissue. In this paper, we present the general aspects of this approach and an evaluation of the optimum beam configuration for IMRT based on inverse treatment planning. We compared this method to conventional techniques. Different clinical examples illustrate the possible indications and feasibility of this new approach. This method is superior to conventional techniques because of the reduction of high-dose area of a substantial cardiac volume in those cases where the parasternal lymph nodes are part of the target volume.

Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease

PURPOSE To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease. MATERIAL/METHODS We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n=13) or with IMRT alone (n=4). Seventeen patients were treated in recurrent disease after surgery (n=11) or with radiotherapy alone (n=6). Median total dose to the boost volume (PTV2) was 66 Gy (range, 72-54) with 2 Gy per fraction using an integrated boost concept. Median dose to target volume (PTV1) was 54 Gy in 1.8 Gy. RESULTS Local control was 35% (12/34) and overall survival 74% (25/34) after a median follow-up of 4.5 years. Actuarial local control was 79%, 55% and 27% after 1, 2 and 5 years, respectively. Local control was significantly higher in patients treated for primary tumors (p<0.03) and in total doses >60 Gy (p<0.01). Actuarial overall survival was 97%, 91% and 70% after 1, 2 and 5 years, respectively. CONCLUSION These data demonstrate that local control after IMRT is higher in patients treated for primary tumors and using higher radiation doses. Therefore, we recommend radiotherapy as part of initial treatment in sacral chordoma.

Multidisciplinary pain management based on a computerized clinical decision support system in cancer pain patients

ABSTRACT A prospective controlled intervention cohort study in cancer pain patients (n = 50 per group) admitted to radiation oncology wards (62 beds, 3 wards) was conducted in a 1621‐bed university hospital. We investigated the effect of an intervention consisting of daily pain assessment using the numeric visual analog scale (NVAS) and pain therapy counseling to clinicians based on a computerized clinical decision support system (CDSS) to correct deviations from pain therapy guidelines. Effects on guideline adherence (primary outcome), pain relief (NVAS) at rest and during physical activity (both groups: cross‐sectional assessment on day 5; intervention group: every day assessment), co‐analgesic prescription, and acceptance rates of recommendations (secondary outcomes) were assessed. The number of patients with at least one deviation from guidelines at discharge was decreased by the intervention from 37 (74%) in controls to 7 (14%, p < 0.001). In the intervention group, pain (NVAS) decreased during hospital stay at rest from 3.0 (Δ0.5 (Q75% − Q25%) = 3.0) on admission to 1.5 (Δ0.5 = 1.0) at discharge (p < 0.01) and during physical activity from 7.0 (Δ0.5 = 4.0) on admission to 2.5 (Δ0.5 = 3.8) at discharge (p < 0.001). At discharge, the number of patients treated with co‐analgesics increased from 23 (46%) in controls to 33 (66%) in the intervention group (p = 0.04). From 279 recommendations issued in the intervention 85% were fully accepted by the physicians. Deviations from well‐established guidelines are frequent in pain therapy. A multidisciplinary pain management increased adherence to pain management guidelines.

Results of Three-dimensional Stereotactically-guided Radiotherapy in Recurrent Medulloblastoma

AbstractPurpose: To evaluate survival rates and side effects after stereotactically-guided radiotherapy (SRT) in patients with recurrent medulloblastoma of the brain. Methods and materials: Between 1992 and 2000, 20 patients with 29 radiological manifestations were treated with fractionated SRT (n=21) or radiosurgery (n=8). Median age was 16 years with 6 patients ≤14 years. All patients had prior cranio-spinal radiotherapy plus boost to the posterior fossa with a total dose of 54 Gy. Time to recurrence was 33 months mean. Eighteen of the 29 lesions were located within the boost volume. Chemotherapy was given according to current international study protocols (HIT) in all patients. Mean total dose for re-irradiation was 24 Gy for fractionated stereotactically-guided radiotherapy, and 15 Gy for radiosurgery. Mean follow-up was 88.5 months. Results: Overall local control was 89.7%. Thirteen recurrences showed partial or complete response in CT/MR-imaging, 13 showed stable disease. Local tumor progression was seen 5 months mean after radiotherapy in three cases. A multifocal intracranial progression was seen in 9 patients, 5 patients developed additional spinal metastases. Thirteen patients died with disseminated cranio-spinal progression, after 72.6 months median. No late toxicity >CTC II∘ especially no brain radionecrosis was seen after radiotherapy. Conclusion: SRT is effective and safe in the treatment of recurrent medulloblastoma to improve local control without evident side effects. The main problem remains the control of subclinical cranio-spinal dissemination.

The role of stereotactically guided conformal radiotherapy for Local tumor control of esthesioneuroblastoma

Background: In a retrospective analysis we compared conventional radiotherapy and stereotactically guided conformal radiotherapy (SCRT) in patients with esthesioneuroblastoma. Patients and Methods: Between 1991 and 1999 14 patients with esthesioneuroblastoma underwent radiotherapy at our institution. Median follow-up was 30 months (range 12–107 months). Treatment included adjuvant radiotherapy (9), adjuvant radiochemotherapy (3) or radiotherapy alone (2). Eight patients received SCRT with 3-D treatment planning. For comparison a standard three-field plan for these patients and dose-volume histogram analyses were performed. Median total dose was 64 Gy using SCRT and 56 Gy with standard technique. Results: Local tumor control rate was 50% with conventional radiotherapy and 75% with SCRT. Overall survival was 33.3% and 62.5%, respectively. Target coverage could be improved statistically significant (p < 0.05) and dose to critical structures was reduced using SCRT. Greatest differences were seen regarding volume above the 30%-isodose as well as mean dose of brain stem (p < 0.05). A reduction of maximum dose was seen using SCRT as consequence of a more homogeneous treatment. Conclusions: SCRT improves target coverage and sparing of organs at risk. Our clinical data although with low patient numbers suggest that the technical advantage translates into a clinical advantage. The use of SCRT appears to facilitate higher dose prescriptions without risking major acute and late side effects. Thus the risk of complications in this area is minimized. Adjuvant radiotherapy is a save and effective treatment modality for local control of esthesioneuroblastoma.Hintergrund: Ziel der vorliegenden Untersuchung war ein retrospektiver Vergleich der konventionellen Strahlentherapie und stereotaktischer Konformationsbestrahlung (SCRT) bei Patienten mit einem Ästhesioneuroblastom. Patienten und Methode: Im Zeitraum von 1991 bis 1999 wurden 14 Patienten mit histologisch gesichertem Ästhesioneuroblastom in unserer Abteilung strahlentherapiert. Die mediane Nachbeobachtungszeit lag bei 30 Monaten (12–107 Monate). Die Behandlungsmodalitäten umfassten adjuvante Strahlentherapie (9), adjuvante Radiochemotherapie (3) oder primäre Strahlentherapie (2). Acht Patienten wurden stereotaktisch konformierend geplant und bestrahlt. Zum Vergleich wurden für diese Patienten ein konventioneller Drei- Felder-Plan erstellt und Dosis-Volumen-Histogramm-Analysen durchgeführt. Die mediane Gesamtdosis betrug 64 Gy bei SCRT und 56 Gy mit konventioneller Technik. Ergebnisse: Mit konventioneller Technik lag die lokale Tumorkontrollrate bei 50% im Vergleich zu 75% mit SCRT. Das Gesamtüberleben lag bei 33,3% bzw. 62,5%. Die Zielvolumenauslastung ließ sich mit SCRT signifikant verbessern (p < 0,05) und die Dosisbelastung der Risikostrukturen reduzieren. Der größte Unterschied fand sich bezüglich des Volumens oberhalb der 30%-Isodose und der mittleren Dosisbelastung des Hirnstamms (p < 0.05). Des Weiteren fand sich eine Reduktion der Maximaldosis als Folge einer homogeneren Dosisverteilung bei SCRT. Schlussfolgerungen: SCRT verbessert die Zielvolumenauslastung und Schonung der Risikostrukturen. Unsere klinischen Daten lassen trotz niedriger Patientenzahlen vermuten, dass der technische Vorteil zu einem klinischen Vorteil führt. Mittels SCRT scheint eine Dosiseskalation ohne Erhöhung des Risikos therapiebedingter lokaler Nebenwirkungen und Spätkomplikationen möglich zu sein. Mit modernen Techniken stellt die adjuvante Strahlentherapie eine sichere und effektive Behandlungsmodalität zur lokalen Kontrolle beim Ästhesioneuroblastom dar.

Proposal for a new prognostic score for linac-based radiosurgery in cerebral arteriovenous malformations.

PURPOSE We evaluate patient-, angioma-, and treatment-specific factors for successful obliteration of cerebral arteriovenous malformations (AVM) to develop a new appropriate score to predict patient outcome after linac-based radiosurgery (RS). METHODS AND MATERIALS This analysis in based on 293 patients with cerebral AVM. Mean age at treatment was 38.8 years (4-73 years). AVM classification according Spetzler-Martin was 55 patients Grade I (20.5%), 114 Grade II (42.5%), 79 Grade III (29.5%), 19 Grade IV (7.1%), and 1 Grade V (0.4%). Median maximum AVM diameter was 3.0 cm (range, 0.3-10 cm). Median dose prescribed to the 80% isodose was 18 Gy (range, 12-22 Gy). Eighty-five patients (29.1%) had prior partial embolization; 141 patients (51.9%) experienced intracranial hemorrhage before RS. Median follow-up was 4.2 years. RESULTS Age at treatment, maximum diameter, nidus volume, and applied dose were significant factors for successful obliteration. Under presumption of proportional hazard in the dose range between 12 and 22 Gy/80% isodose, an increase of obliteration rate of approximately 25% per Gy was seen. On the basis of multivariate analysis, a prediction score was calculated including AVM maximum diameter and age at treatment. The prediction error up to the time point 8 years was 0.173 for the Heidelberg score compared with the Kaplan-Meier value of 0.192. An increase of the score of 1 point results in a decrease of obliteration chance by a factor of 0.447. CONCLUSION The proposed score is linac-based radiosurgery-specific and easy to handle to predict patient outcome. Further validation on an independent patient cohort is necessary.