Credentialing of stereotactic radiosurgery and stereotactic body radiation therapy programs for quality and safety: The Novalis Certified Program.

The expectation of quality and safety is a fundamental tenet in all areas of healthcare, and a cornerstone of best practice is a process of continuous learning and continuous improvement. Independent audits and peer review of radiotherapy programs are an important mechanism for identifying process or technology gaps, for highlighting areas for improvement, and for incorporating within continuous improvement processes. In the field of radiotherapy, independent certification programs exist within various national and/or professional spheres, yet few focus specifically on specialty procedures such as radiosurgery or brachytherapy, despite several recommendations for such programs.

Elimination of refractory ventricular tachycardia storm and fibrillation using stereotactic radiotherapy.

Ventricular tachycardia storm is a potentially lethal condition with limited treatment options. Failed ablation is associated with a fourfold mortality increase in this population. Stereotactic body radiotherapy was proposed in these cases.

Linac-based stereotactic radiotherapy and radiosurgery in patients with meningioma.

Background: It was our purpose to analyze long-term clinical outcome and to identify prognostic factors after Linac-based fractionated stereotactic radiotherapy (Linac-based FSRT) and stereotactic radiosurgery (SRS) in patients with intracranial meningiomas.

Materials And Methods: Between 10/1995 and 03/2009, 297 patients with a median age of 59 years were treated with FSRT for intracranial meningioma. 50 patients had a Grade I meningioma, 20 patients had a Grade II meningioma, 12 patients suffered from a Grade III tumor, and in 215 cases no histology was obtained (Grade 0).

Contribution of (18)F-Fluoro-ethyl-tyrosine Positron Emission Tomography to Target Volume Delineation in Stereotactic Radiotherapy of Malignant Cranial Base Tumours: First Clinical Experience.

Increased amino acid uptake has been demonstrated in intracerebral tumours and head and neck carcinomas of squamous cell origin. We investigated the potential impact of using (18)F-fluoro-ethyl-tyrosine ((18)F-FET)-PET/CT in addition to conventional imaging for gross tumour volume (GTV) delineation in stereotactic radiotherapy of skull base tumours. The study population consisted of 14 consecutive patients with cranial base tumours (10 with squamous cell histology, 4 others).

Contribution of 68Ga-DOTATOC PET/CT to target volume delineation of skull base meningiomas treated with stereotactic radiation therapy.

Purpose: To investigate the potential impact of 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) for retrospectively assessing the gross tumor volume (GTV) delineation of meningiomas of the skull base in patients treated with fractionated stereotactic radiation therapy (FSRT).

Methods And Materials: The study population consisted of 48 patients with 54 skull base meningiomas, previously treated with FSRT. After scans were coregistered, the GTVs were first delineated with MRI and CT data (GTVMRI/CT) and then by PET (GTVPET) data.

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy--a case series.

Introduction: Magnetic resonance imaging (MRI) and computed tomography (CT) with (68)Ga-DOTATOC positron emission tomography ((68)Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.

Methods: Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and (68)Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) or PET, and were evaluated further.

The inhibitor of growth 1 (ING1) is involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells.

Prognosis for patients with glioblastoma multiforme (GBM) is poor. Inhibitors of histone deacetylases (HDACi) like trichostatin A (TSA) are promising alternatives to conventional treatment. Deficient tumor suppressor functions, such as TP53 mutations and p14(ARF)/p16(INK4a) deletions, are characteristic for GBM and can cause resistance to DNA damaging agents such as cisplatin and to HDACi like TSA.

Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas.

Purpose: Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with (68)Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of (68)Ga-DOTATOC-PET/CT on the definition of the "gross tumour volume" (GTV) in meningiomas, in order to assess the potential value of this method.

Methods: Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and (68)Ga-DOTATOC-PET/CT examinations.

Novalis frameless image-guided noninvasive radiosurgery: initial experience.

Objective: To evaluate our initial experience with Novalis (BrainLAB, Heimstetten, Germany) frameless image-guided noninvasive radiosurgery.

Methods: The system combines the dedicated Novalis linear accelerator with ExacTrac X-Ray 6D, an infrared camera and a kilovolt stereoscopic x-ray imaging system, a noninvasive mask system, and ExacTrac robotics for patient positioning in six degrees of freedom. Reference cranial skeletal structures are radiographically imaged and automatically fused to digital reconstructed radiographs calculated from the treatment planning computed tomographic scan to find the target position and accomplish automatic real-time tracking before and during radiosurgery.

Down-regulation of the inhibitor of growth 1 (ING1) tumor suppressor sensitizes p53-deficient glioblastoma cells to cisplatin-induced cell death.

Impaired tumor suppressor functions, such as deficient p53, are characteristic for glioblastoma multiforme (GBM) and can cause resistance to DNA-damaging agents like cisplatin. We have recently shown that the INhibitor of Growth 1 (ING1) tumor suppressor is down-regulated in malignant gliomas and that the decrease of ING1 expression correlates with histological grade of malignancy, suggesting a role for ING1 in the pathogenesis and progression of malignant gliomas. Based on this background, the purpose of our current study was to examine the potential impact of ING1 protein levels on DNA-damage response in GBM.

Prognostic factors and impact of treatment in melanoma brain metastases: better prognosis for women?

Background: Brain metastases are a common consequence in patients with stage IV melanoma associated with a grim prognosis.

Objective: The objective of this study was the examination of prognostic factors and the evaluation of different treatment options.

Methods: A consecutive series of 133 patients with melanoma brain metastases with regard to prognostic factors and the impact on survival were analyzed.

Diagnostic value of 123I-IMT SPECT in the follow-up of head and neck cancer.

Background: Nuclear medicine imaging is increasingly used in the evaluation of tumors of the head and neck. In the current study, we assess the value of single-photon emission tomography (SPECT) using the amino acid tracer L-3-[123I]iodine-alpha-methyl-tyrosine (IMT) for the detection of recurrent head and neck cancer.

Patients And Methods: 45 consecutive patients with suspected recurrence of previously treated head and neck cancer were examined by IMT-SPECT using a dual head system with integrated low-dose computed tomography (CT).

Relevance of image fusion with MRI for the interpretation of I-123 iodo-methyl-tyrosine scans in patients with suspected recurrent or residual brain tumor.

Purpose: The aim of the study was to investigate the impact of MR/SPECT image fusion on the interpretation of I-123 iodo-methyl-tyrosine (IMT) SPECT examinations in patients with pretreated brain tumors.

Material And Methods: In this retrospective study, 45 consecutive patients with suspected recurrent/residual gliomas (n = 41) or cerebral metastases (n = 4) were included. SPECT studies were performed using a triple-head gamma-camera system 10 minutes after injection of 300 to 370 MBq (8.

Quantitative measurement of leakage volume and permeability in gliomas, meningiomas and brain metastases with dynamic contrast-enhanced MRI.

The spatial properties and function of the tumor vasculature differ with the tumor type and grade. T1-weighted dynamic contrast-enhanced imaging technique enables the simultaneous quantification of some functional parameters of the vasculature. These are the fractional contrast-enhancing volumes of the tissue compartments (blood volume and leakage/extravascular extracellular volume) and the exchange parameters (perfusion and permeability).

Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases.

Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m2 temozolomide on days 1 to 5 every 28 days as first or second-line therapy.

Combined SPECT/CT imaging using 123I-IMT in the detection of recurrent or persistent head and neck cancer.

The aim of the study was to assess the clinical value of combined SPECT/CT imaging using L: -3-[123I]iodine-alpha-methyl tyrosine (IMT) for the differential diagnosis of recurrences in patients pre-treated for head and neck cancer. Thirty-four consecutive patients with biopsy-proven carcinomas, who had previously been treated by surgery and/or radio/chemotherapy, were examined at our clinic by IMT-SPECT using a dual-head system with integrated low-dose CT. SPECT results were correlated with histopathology, clinical and CT/MRI follow-up data.

Value of 123I-IMT SPECT for diagnosis of recurrent non-astrocytic intracranial tumours.

The value of single-photon emission tomography (SPECT) using iodine-123-alpha-methyl-tyrosine (IMT) for the diagnosis of recurrent or residual gliomas is well established. In the current study we investigated whether IMT-SPECT could also be useful in the follow-up of brain metastases and other intracranial tumours of non-astrocytic origin. The study included 22 patients with suspected recurrent intracranial tumours of non-astrocytic origin (12 brain metastases, one supratentorial primitive neuroendocrine tumour (PNET), one rhabdoid tumour, two clivus chordomas, three ependymomas, two pituitary tumours, one anaplastic meningioma) who had previously been treated by surgery and/or radio/chemotherapy.

Stereotactic radiation treatment planning and follow-up studies involving fused multimodality imaging.

Object: Innovative new software solutions may enable image fusion to produce the desired data superposition for precise target definition and follow-up studies in radiosurgery/stereotactic radiotherapy in patients with intracranial lesions. The aim is to integrate the anatomical and functional information completely into the radiation treatment planning and to achieve an exact comparison for follow-up examinations. Special conditions and advantages of BrainLAB's fully automatic image fusion system are evaluated and described for this purpose.

123I-IMT SPECT and 1H MR-spectroscopy at 3.0 T in the differential diagnosis of recurrent or residual gliomas: a comparative study.

The aim of this investigation was to compare two current non-invasive modalities, single photon emission tomography (SPECT) using 123-iodine-alpha-methyl tyrosine (123I-IMT) and single-voxel proton magnetic resonance spectroscopy (1H-MRS) at 3.0 T, with regard to their ability to differentiate between residual/ recurrent tumors and treatment-related changes in patients pretreated for glioma. The patient population comprised 25 patients in whom recurrent glioma was suspected based on MR imaging.

Increased radiation-induced apoptosis and altered cell cycle progression of human lung cancer cell lines by antisense oligodeoxynucleotides targeting p53 and p21(WAF1/CIP1).

Lung cancer is difficult to control locally by radiotherapy and is known to have frequently p53 mutations. Previous results have shown that non-small-cell lung cancer (NSCLC) cell lines with nonfunctional p53 have a higher fraction of radiation-induced apoptosis and that apoptosis follows after the release from the G2/M arrest. The aim of the present work was to study whether inhibition of the p53 response in NSCLC cell lines can modulate the G2/M arrest and the induction of apoptosis after ionizing radiation.

[Improved patient repositioning accuracy by integrating an additional jaw fixation into a high precision face mask system in stereotactic radiotherapy of the head].

Background: For high precision radiotherapy of the neurocranium a precise, reproducible positioning technique is the basic prerequisite. The aim of this study was to assess the influence of a modification of the commercially available stereotactical BrainLab-head mask system on accuracy in patient positioning during fractionated radiotherapy.

Material And Methods: 29 patients were treated with stereotactic radiotherapy of the head.

Chemo- and radiation sensitivity of xenografted acute lymphoblastic leukemias--correlation to the expression of multidrug resistance proteins.

The aim of our study was to characterise, for the first time, the chemo- and radiation sensitivity of seven pediatric acute lymphoblastic leukemias xenotransplanted into immunodeficient NOD/SCID mice and to correlate the findings with the expression of three drug resistance proteins, P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1) and lung resistance protein (LRP). Mice were treated with single drugs used in clinical protocols: daunorubicin, doxorubicin, cyclophosphamide, vincristine, cytarabine, asparaginase and methotrexate. Two ALL samples, established from primarily diagnosed patients, responded to 5 or 6 of the tested cytostatics, respectively, while 3 out of 5 ALLs from relapse patients were only sensitive towards 2-4 drugs tested.

Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis.

Deregulation of cell-cycle G(1)-restriction point control by disruption of Rb-pathway components is a frequent event in cancer. In concert with the inactivation of cell death pathways, such events not only contribute to tumor development but also determine the intrinsic and acquired resistance to cancer therapy and, ultimately, disease prognosis. We previously observed that the cyclin-dependent kinase inhibitor p16(INK4a) and the proapoptotic Bcl-2 homolog Bax are positive prognostic factors and identify patients with good prognosis in esophageal squamous cell carcinoma (SCC).

Selective inactivation of DNA-dependent protein kinase with antisense oligodeoxynucleotides: consequences for the rejoining of radiation-induced DNA double-strand breaks and radiosensitivity of human cancer cell lines.

The inhibition of DNA-dependent protein kinase activity with antisense-oligodeoxynucleotide (As-ODN) and its consequences for the rejoining of DNA-double-strand breaks (Dsbs) and radiation sensitivity was studied in human non-small cell lung cancer (NSCLC) cell lines. Cells were transfected with As-ODNs specific for the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). In comparison, cells were treated with Wortmannin, a potent but nonspecific inhibitor of DNA-PK activity.

Intraindividual comparison of conventional three-dimensional radiotherapy and intensity modulated radiotherapy in the therapy of locally advanced non-small cell lung cancer a planning study.

Background: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs.

Patients And Methods: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D(max)) to spinal cord < 48 Gy, mean lung dose 70 Gy in not more than 5 cm of the total length.