Achievement of long-term local control in patients with craniopharyngiomas using high precision stereotactic radiotherapy.

BACKGROUND: The long-term outcome in patients with craniopharyngiomas treated with fractionated stereotactic radiotherapy (FSRT) was evaluated. METHODS: A total of 40 patients with craniopharyngiomas were treated between May 1989 and July 2006 with FSRT. Most patients were treated for tumor progression after surgery. A median target dose of 52.2 grays (Gy) (range, 50.4-56 Gy) was applied in a median conventional fractionation of 5 x 1.8 Gy per week. Follow-up examinations included thorough clinical assessment as well as contrast-enhanced magnetic resonance imaging scans. RESULTS: After a median follow-up of 98 months (range, 3-326 months), local control was 100% at both 5 years and 10 years. Overall survival rates at 5 years and 10 years were 97% and 89%, respectively. A complete response was observed in 4 patients and partial responses were noted in 25 patients. Eleven patients presented with stable disease during follow-up. Acute toxicity was mild in all patients. Long-term toxicity included enlargement of cysts requiring drainage 3 months after FSRT. No visual impairment, radionecrosis, or development of secondary malignancies were observed. CONCLUSIONS: The long-term outcome of FSRT for craniopharyngiomas is excellent with regard to local control as well as treatment-related side effects.

Local high-dose radiotherapy and sparing of normal tissue using intensity-modulated radiotherapy (IMRT) for mucosal melanoma of the nasal cavity and paranasal sinuses.

PURPOSE: To evaluate the clinical outcome of intensity-modulated radiotherapy (IMRT) in patients with mucosal melanoma (MM) of the nasal cavity and paranasal sinuses. PATIENTS AND METHODS: Between January 1999 and September 2004, eight patients with histologically proven MM of the nasal cavity and paranasal sinuses were treated with IMRT. A median dose of 66 Gy was applied to the macroscopic tumor (gross tumor volume [GTV]; range, 60-68 Gy) as an integrated boost and a median dose of 59 Gy (range, 54-64 Gy) to the clinical target volume (CTV) with IMRT. RESULTS: Treatment-related toxicity was very mild in most patients. Overall survival was 80% at 5 years. Calculated from treatment with IMRT as primary radiotherapy, survival was 100% at 1 year and 75% at 3 years. After IMRT, local progression-free survival was 71.4% at 1 year and 57.1% at 3 years, respectively. Distant progression-free survival after IMRT was 57.1% at 1 year and 28.6% at 3 years. CONCLUSION: Local dose escalation with IMRT yields good treatment results with respect to local and distant tumor control as well as survival, while treatment-related toxicity can be minimized.

Local radiotherapeutic management of ependymomas with fractionated stereotactic radiotherapy (FSRT).

BACKGROUND: To assess the role of Fractionated Stereotactic Radiotherapy (FSRT) in the management of ependymomas. METHODS: From January 1992 to July 2003, FSRT was performed in 19 patients with histologically confirmed ependymomas. The median age was 15 years, 5 patients were younger than 4 years of age. Twelve patients received FSRT as primary postoperative radiotherapy after surgical resection. In 6 patients irradiation of the posterior fossa was performed with a local boost to the tumor bed, and in 4 patients the tumor bed only was irradiated. In 7 patients FSRT was performed as re-irradiation for tumor progression. This patient group was analyzed separately. A median dose of 54 Gy was prescribed in a median fractionation of 5 x 1.8 Gy per week for primary RT using 6 MeV photons with a linear accelerator. For FSRT as re-irradiation, a median dose of 36 Gy was applied. All recurrent tumors were localized within the former RT-field. RESULTS: The 5- and 10-year overall survival rates were 77% and 64%, respectively. Patients treated with FSRT for primary irradiation showed an overall survival of 100% and 78% at 3 and 5 years after irradiation of the posterior fossa with a boost to the tumor bed, and a survival rate of 100% at 5 years with RT of the tumor bed only. After re-irradiation with FSRT, survival rates of 83% and 50% at 3-and 5 years, respectively, were obtained.Progression-free survival rates after primary RT as compared to re-irradiation were 64% and 60% at 5 years, respectively.FSRT was well tolerated by all patients and could be completed without interruptions due to side effects. No severe treatment related toxicity > CTC grade 2 for patients treated with FSRT could be observed. CONCLUSION: The present analysis shows that FSRT is well tolerated and highly effective in the management of ependymal tumors. The rate of recurrences, especially at the field border, is not increased as compared to conventional radiotherapy consisting of craniospinal irradiation and a local boost to the posterior fossa.

Intensity modulated radiotherapy (IMRT) in patients with carcinomas of the paranasal sinuses: clinical benefit for complex shaped target volumes.

INTRODUCTION: The aim of the study was to evaluate the clinical outcome of intensity modulated radiotherapy (IMRT) in 46 patients with paranasal sinus tumors with special respect to treatment-related toxicity. PATIENTS AND METHODS: We treated 46 patients with histologically proven tumors of the paranasal sinuses with IMRT. Histological classification included squamous cell carcinoma in 6, adenocarcinoma in 8, adenoidcystic carcinoma in 20 and melanoma in 8 patients, respectively. Six patients had been treated with RT during initial therapy after primary diagnosis, and IMRT was performed for the treatment of tumor progression as re-irradiation. RESULTS: Overall survival rates were 96% at 1 year, 90% at 3 years. Calculated from the initiation of IMRT as primary radiotherapy, survival rates at 1 and 3 years were 95% and 80%. In six patients IMRT was performed as re-irradiation, and survival rate calculated from re-irradiation was 63% at 1 year. Local control rates were 85% at 1, 81% at 2 and 49% at 3 years after primary RT and 50% at 1 year after re-irradiation. Distant metastases-free survival in patients treated with IMRT as primary RT was 83% after 1 and 64% after 3 years. For patients treated as primary irradiation with IMRT, the distant control rate was 83% at 1 year and 0% at 2 years. No severe radiation-induced side-effects could be observed. CONCLUSION: IMRT for tumors of the paranasal sinuses is associated with very good tumor control rates. Treatment-related acute and long-term toxicity can be minimized as compared to historical results with conventional RT.

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

BACKGROUND: The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy. PATIENTS AND METHODS: For 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 DISCUSSION: Bony 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. CONCLUSION: The 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.

Linac-integrated kV-cone beam CT: technical features and first applications.

One of the most prominent imaging techniques in image-guided radiotherapy (IGRT) is the acquisition of cone beam computed tomographies (CBCTs) at the linac with the patient in treatment position. CBCTs provide accurate 3-dimensional (3D) knowledge about the patient's anatomy for every treatment fraction and are therefore well suited for all adaptive corrections of errors related to interfractional uncertainties of the treatment process. In this paper, we first describe the technical development and implementation of this new imaging technique at our linac, i.e., the hardware components and their operating parameters are discussed in detail for a standard image acquisition of CBCTs. Then, an extension of this approach for the acquisition of complete images for extended field of views--the "shifted detector" technique--is presented followed by a first investigation of how CBCTs can be reliably used for adaptive dose calculations. Finally, a first clinical application, the process of automatic patient positioning based on CBCT images, is discussed. From our investigations, we conclude that the technical development of linac-integrated CBCTs bears an enormous potential for the correction of interfractional treatment errors. However, image quality and reconstruction speed of the images leave room for improvement. The development of clinical strategies for the optimal application of this new image modality in a clinical environment is one the major tasks for the future.

The influence of breathing motion on intensity modulated radiotherapy in the step-and-shoot technique: phantom measurements for irradiation of superficial target volumes.

For intensity modulated radiotherapy (IMRT) of deep-seated tumours, dosimetric variations of the original static dose profiles due to breathing motion can be primarily considered as blurring effects known from conventional radiotherapy. The purpose of this dosimetric study was to clarify whether these results are transferable to superficial targets and to quantify the additional effect of fractionation. A solid polystyrene phantom and an anthropomorphic phantom were used for film and ion chamber dose measurements. The phantoms were installed on an electric driven device and moved with a frequency of 6 or 12 cycles per minute and an amplitude of 4 mm or 10 mm. A split beam geometry of two adjacent asymmetric fields and an IMRT treatment plan with 12 fields for irradiation of the breast were investigated. For the split beam geometry the dose modifications due to unintended superposition of partial fields were reduced by fractionation and completely smoothed out after 20 fractions. IMRT applied to the moving phantom led to a more homogeneous dose distribution compared to the static phantom. The standard deviation of the target dose which is a measure of the dose homogeneity was 10.3 cGy for the static phantom and 7.7 cGy for a 10 mm amplitude. The absolute dose values, measured with ionization chambers, remained unaffected. Irradiation of superficial targets by IMRT in the step-and-shoot technique did not result in unexpected dose perturbations due to breathing motion. We conclude that regular breathing motion does not jeopardize IMRT of superficial target volumes.

Long-term outcome of stereotactic radiosurgery (SRS) in patients with acoustic neuromas.

PURPOSE: To evaluate the effectiveness and long-term outcome of stereotactic radiosurgery (SRS) for acoustic neuromas (AN). PATIENTS AND METHODS: Between 1990 and 2001, we treated 26 patients with 27 AN with SRS. Two patients suffered from neurofibromatosis type 2. Before SRS, a subtotal or total resection had been performed in 3 and in 5 patients, respectively. For SRS, a median single dose of 13 Gy/80% isodose was applied. RESULTS: The overall actuarial 5-year and 10-year tumor control probability in all patients was 91%. Two patients developed tumor progression after SRS at 36 and 48 months. Nineteen patients (73%) were at risk of treatment-related facial nerve toxicity; of these, 1 patient developed a complete facial nerve palsy after SRS (5%). A total of 93% of the lesions treated were at risk of radiation-induced trigeminal neuralgia. Two patients (8%) developed mild dysesthesia of the trigeminal nerve after SRS. The hearing preservation rate in patients with useful hearing before SRS was 55% at 9 years. CONCLUSION: Stereotactic radiosurgery results in good local control rates of AN and the risk of cranial nerve toxicities is acceptable. As toxicity is lower with fractionated stereotactic radiotherapy, SRS should be reserved for smaller lesions.

Reirradiation of recurrent WHO grade III astrocytomas using fractionated stereotactic radiotherapy (FSRT).

PURPOSE: To assess the effect of reirradiation in recurrent WHO grade III astrocytomas. PATIENTS AND METHODS: From January 1995 to July 2003, 40 patients with grade III gliomas were treated with fractionated stereotactic reirradiation at the time point of recurrence. Median size of planning target volume for reirradiation was 56.2 ml (range 25.1-296.2 ml). A median target total dose of 36 Gy (range 20-57.6 Gy) was applied using a median fractionation of 5 x 2 Gy/week with a 6-MeV linear accelerator. RESULTS: Radiotherapy was well tolerated by all patients. No toxicities > CTC grade 2 developed. Median overall survival calculated from the time point of primary diagnosis was 48 months (range 7-180 months). The 5- and 10-year overall survival rates were 49.5% and 24.7%, respectively. From the time point of reirradiation, median survival was 16 months (range 1-98 months). Median progression-free survival from the time point of reirradiation was 8 months (range 1-72 months). No prognosticators for survival or progression-free survival after reirradiation could be identified. CONCLUSION: Fractionated stereotactic radiotherapy is well tolerated and effective in patients with recurrent grade III astrocytomas.

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).

BACKGROUND: This article describes the results of a study of stereotactic radiosurgery (SRS) in the treatment of patients with recurrent malignant glioma. METHODS: Thirty-two patients with recurrent glioblastoma multiforme (GBM) were treated for 36 lesions with SRS from 1993 to 2001. Nineteen patients were male and 13 were female. The median age at primary diagnosis of the tumor was 56 years (range, 33-76 yrs). At the time of initial diagnosis a total neurosurgical resection was performed in 7, a subtotal resection in 21, and a biopsy in 4 patients. Histology evaluations revealed glioblastoma multiforme (WHO Grade IV) in all 32 patients. In all patients radiotherapy was performed as the first-line therapy, applied as fractionated external beam radiotherapy. The median interval between primary irradiation and reirradiation was 10 months. The median dose applied was 15 Gy (range, 10-20 Gy) prescribed to the 80% isodose line that encompassed the target volume. No concomitant chemotherapy was applied. RESULTS: Treatment was well tolerated by all patients. No acute toxicities > CTC Grade II occurred. No severe long-term toxicities including radionecrosis were observed. The median follow-up time was 13 months (range, 1-89 mo). All patients died of tumor progression during follow-up. The median overall survival from primary diagnosis of the tumor was 22 months (range, 9-133 mo). The survival rate at 1 year was 90%, and 49% and 26% at 2 and 3 years, respectively. Median overall survival after SRS was 10 months. At 6 and 12 months after SRS, survival rates were 72% and 28%, respectively. Median progression-free survival after SRS was 7 months. CONCLUSIONS: SRS offers effective treatment as a salvage therapy for a subgroup of patients with smaller lesions of recurrent GBM.

Precision radiotherapy for hemangiopericytomas of the central nervous system.

BACKGROUND: Radiotherapy (RT) plays a major role in the management of hemangiopericytomas (HAP). The present analysis evaluates the role of precision RT in the management of HAP of the central nervous system (CNS) and represents one of the largest series of HAP treated with RT that can be found in the literature. METHODS: Of 37 consecutive patients with histologically confirmed HAP who were treated at the institution between 1984 and 2004, the majority, 25 tumors, was localized within the skull base (n = 25) and 4 tumors were localized at the spine. In 25 patients, high-precision RT was delivered as fractionated stereotactic RT or intensity modulated RT. Median age at primary diagnosis was 40.5 years (range, 10-77 yrs). After primary diagnosis, surgical resection was performed in 23 patients. A median total dose of 54 Gy was delivered in a fractionation of 5 x 1.8-2 Gy per week. The median planning target volume was 58.2 mL (range, 10-412 mL). The median follow-up time was 34 months (range, 3-166 mos). RESULTS: Radiotherapy was well tolerated by all patients. Seventeen patients of this series remain alive. Overall survival rates at 5 and 10 years are 100% and 64%, respectively. Actuarial survival rates after RT were 85% and 69% at 3 and 5 years, respectively. Progression-free survival after RT 80% and 61% at 3 and 5 years, respectively. CONCLUSION: High-precision RT is an effective and safe treatment modality for patients with HAP of the CNS and the spine and achieves highly acceptable tumor control, while sparing normal tissue.

Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution.

PURPOSE: To assess the long-term outcome and toxicity of fractionated stereotactic radiotherapy for acoustic neuromas in 106 patients treated in a single institution. PATIENTS AND METHODS: Between October 1989 and January 2004, fractionated stereotactic radiotherapy (FSRT) was performed in 106 patients with acoustic neuroma (AN). The median total dose applied was 57.6 Gy in median single fractions of 1.8 Gy in five fractions per week. The median irradiated tumor volume was 3.9 mL (range, 2.7-30.7 mL). The median follow-up time was 48.5 months (range, 3-172 months). RESULTS: Fractionated stereotactic radiotherapy was well tolerated in all patients. Actuarial local tumor control rates at 3- and 5- years after FSRT were 94.3% and 93%, respectively. Actuarial useful hearing preservation was 94% at 5 years. The presence of neurofibromatosis (NF-2) significantly adversely influenced hearing preservation in patients that presented with useful hearing at the initiation of RT (p = 0.00062). Actuarial hearing preservation without the diagnosis of NF-2 was 98%. In cases with NF-2, the hearing preservation rate was 64%. Cranial nerve toxicity other than hearing impairment was rare. The rate of radiation induced toxicity to the trigeminal and facial nerve was 3.4% and 2.3%, respectively. CONCLUSION: Fractionated stereotactic radiotherapy is safe and efficacious for the treatment of AN, with mild toxicity with regard to hearing loss and cranial nerve function. FSRT might be considered as an equieffective treatment modality compared to neurosurgery and therefore represents an interesting alternative therapy for patients with AN.

Fractionated stereotactic radiation therapy in the management of primary oligodendroglioma and oligoastrocytoma.

PURPOSE: To retrospectively analyze the outcomes and benefits from radiation therapy (RT) as a component of multimodal treatment for oligodendroglioma and oligoastrocytoma, assessing local control and survival rates and evaluating prognostic factors. METHODS AND MATERIALS: We retrospectively reviewed 56 adult patients with supratentorial oligodendroglioma or oligoastrocytoma treated at our institution from January 1990 to December 2003 with fractionated stereotactic RT (FSRT). RESULTS: Fractionated stereotactic RT was well tolerated in all patients, without side effects. Median survival and progression-free survival calculated from the initiation of radiotherapy were 48 months (range, 2-133 months) and 38 months (range, 2-132 months), respectively. Progression-free survival rates after radiation were 89% at 1 year and 52% at 5 years. Of 26 recurrences, 92% developed in field. With regard to histology, overall survival rates in the World Health Organization (WHO) Grade II group were 89% and 74% at 5 and 10 years, respectively. In patients with WHO Grade III tumors, overall survival rates at 5 and 10 years were 69% and 46%, respectively. No prognosticators could be identified for median survival and progression-free survival after radiotherapy. Median overall survival calculated from primary diagnosis was 77.5 months (range, 3-214 months). The Cox regression multivariate analysis for age and neurologic symptoms showed a significance of p = 0.003 for age and p = 0.037 for the presence of neurologic symptoms on overall survival since primary diagnosis. CONCLUSIONS: Commonly, conventional conformal RT is applied in the treatment of brain tumors. In FSRT, the tumor volume can be irradiated with high doses, sparing volume of normal brain tissue. Our data are in accordance with survival times found in the literature. Ninety-two percent of all recurrences occurred within the defined target volume, confirming that reduction of the RT portals by the use of FSRT does not lead to an increased rate of recurrences at the field border or out of field. Fractionated stereotactic RT can therefore be implemented as an effective and safe modality in the therapy of primary oligodendroglioma and oligoastrocytoma.

Fractionated stereotactic radiotherapy of optic pathway gliomas: tolerance and long-term outcome.

PURPOSE: To evaluate the effectiveness and toxicity of fractionated stereotactically guided radiotherapy (FSRT) in the management of optic glioma. METHODS AND MATERIALS: Fifteen patients with optic pathway gliomas were treated with FSRT at our institution between 1990 and 2003. A median target dose of 52.2 Gy (range, 45.2-57.6 Gy) was applied using a median fractionation of 5 fractions of 1.8 Gy weekly using a linear accelerator. RESULTS: The median follow-up time was 97 months (range, 8-151 months). Of the 15 patients, 1 died of tumor progression during the follow-up period. The progression-free survival rate at 3 and 5 years was 92% and 72%, respectively. The median overall survival after FSRT was 90 months (range, 8-151 months). The 5-year survival rate after FSRT was 90%. We did not observe secondary malignancies. CONCLUSION: Fractionated stereotactic radiotherapy was safe and well tolerated in all patients. The good tumor control and the potential of sparing normal brain tissue, especially the pituitary gland in lesions involving the optic chiasm, permit effective treatment of patients with optic nerve gliomas. Longer follow-up is needed to assess the incidence of late effects fully.

Temozolomide combined with irradiation as postoperative treatment of primary glioblastoma multiforme. Phase I/II study.

BACKGROUND AND PURPOSE: The role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/m(2) temozolomide in patients with primary malignant glioma, this phase I/II study was conducted. PATIENTS AND METHODS: 53 Patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/m(2). RESULTS: Prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity > grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival. CONCLUSION: The combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy alone. The application of 50 mg/m(2) of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity.

Radiobiological investigation of dose-rate effects in intensity-modulated radiation therapy.

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) has proven extraordinary capability in physical terms such as target conformity, dose escalation in the target volume, and sparing of neighboring organs at risk. The radiobiological consequences of the protracted dose delivery for cell survival and cell cycle progression are still unclear and shall be examined in this study. MATERIAL AND METHODS: Human lymphoblasts (TK6) and human melanoma cells (MeWo) were irradiated with protocols of increasing dose protraction. In addition, a new biophysical phantom was developed and used to transfer clinical IMRT plans to experimental cell irradiation. Clonogenic cell survival and cell cycle analysis were performed after various irradiation experiments. RESULTS: In a first series of experiments, melanoma cells showed a highly significant increase of survival of 6.0% after protracted dose delivery of 2 Gy compared to conventional fast application with the same dose. Lymphoblastoid cells also showed a significant increase of survival of 2.2%. Experiments with patient plans in the phantom confirmed the trend of increased cell survival after protracted dose delivery. Cells were irradiated at 13 points in four different IMRT plans. In comparison to irradiation with application of the same dose in a classic four-field box, a significantly increased survival of 5.1% (mean value) was determined. CONCLUSION: Even at fraction times of 15-30 min the protracted dose delivery increases the survival rates in cell culture. The altered survival rates indicate the importance of the dose rate in the effectivity of IMRT. Besides physical parameters the consideration of biological factors might contribute to the optimization of IMRT in the future.

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.

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.

Inversely planned intensity modulated radiotherapy of the breast including the internal mammary chain: a plan comparison study.

The aim of this paper is to evaluate the benefit of inversely planned intensity modulated radiotherapy (IMRT) in the adjuvant irradiation of breast cancer when internal mammary lymph nodes are included in the treatment volume. 20 patients treated with 3D-planned conventional radiotherapy (CRT) following breast conserving surgery were included in the study. We chose 10 patients with left-sided and 10 patients with right-sided tumors. All treatment volumes included the internal mammary chain. For plan comparison to the applied CRT plan an inverse IMRT-plan in, step-and-shoot'-technique was calculated. For all patients IMRT resulted in an improved conformity of dose distribution to the target volume compared to CRT (mean COIN95: 0.798 vs. 0.514 with COIN95 = C1 * C2 (C1= fraction of CTV that is covered by > 95% of the prescribed dose and C2 = volume of CTV that is covered by > 95% of the prescribed dose/total volume that is covered by > 95% of the prescribed dose). In all cases with matching adjacent beams, the homogeneity in the target volume was improved. The volume of the ipsilateral lung irradiated with a dose higher than 20 Gy was reduced with IMRT from 24.6% to 13.1% compared to CRT. For left-sided target volume the heart volume with a dose higher than 30 Gy was reduced from 6.2% to 0.2%. The presented plan comparison study for irradiation of the breast and the parasternal lymph nodes showed a substantial improvement of the dose distribution by inversely planned IMRT compared to CRT. This is visible for the target volume, the ipsilateral lung and, in case of left-sided target volume, the heart. Despite an increase in integral dose to the entire normal tissue, the application of IMRT might be clinically advantageous in cases where no satisfying dose distribution can be obtained by CRT.