Papers by Andrea Pirzkall
A combined anatomic and metabolic region of interest (MRI/S) consisting of T2-weighted hyperinten... more A combined anatomic and metabolic region of interest (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement (CE), resection cavity, and CNI2 (CNI > 2) based on the pre-RT imaging was compared to the extent of CNI2 and the RT dose distribution. The spatial relationship of the pre-RT MRI/S and the RT dose volume was compared with the extent of CE at each follow-up. Results: Nine patients showed new or increased CE during follow-up, and 14 patients were either stable or had decreased CE. New or increased areas of CE occurred within CNI2 that was covered by 60 Gy in 6 patients and within the CNI2 that was not entirely covered by 60 Gy in 3 patients. New or increased CE resided within the pre-RT MRI/S lesion in 89% (8/9) of the patients with new or increased CE. Conclusion: These data indicate that the definition of RT target volumes according to the combined morphologic and metabolic abnormality may be sufficient for RT targeting.
Strahlentherapie Und Onkologie, 2003
Purpose: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the mana... more Purpose: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors.Patients and Methods: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed
Clinical cancer research : an official journal of the American Association for Cancer Research, 2015
The novel dual-action humanized IgG1 antibody MEHD7945A targeting HER3 and EGFR inhibits ligand-d... more The novel dual-action humanized IgG1 antibody MEHD7945A targeting HER3 and EGFR inhibits ligand-dependent HER dimer signaling. This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of MEHD7945A. Patients with locally advanced or metastatic epithelial tumors received escalating doses of MEHD7945A (1-30 mg/kg) every 2 weeks (q2w) until disease progression or intolerable toxicity. An expansion cohort was enrolled at the recommended phase II dose (14 mg/kg, q2w). Plasma samples, tumor biopsies, FDG-PET were obtained for assessment of pharmacokinetics, and pharmacodynamic modulation downstream of EGFR and HER3. No dose-limiting toxicities or MEHD7945A-related grade ≥ 4 adverse events (AE) were reported in dose-escalation (n = 30) or expansion (n = 36) cohorts. Related grade 3 AEs were limited to diarrhea and nausea in the same patient (30 mg/kg). Related AEs in ≥20% of patients ≤24 hours after the first infusion included grade 1/2 headache, f...
Purpose: The role of radiotherapy (RT) seems established for patients with low-grade gliomas with... more Purpose: The role of radiotherapy (RT) seems established for patients with low-grade gliomas with poor prognostic factors. Three-dimensional (3D) magnetic resonance spectroscopy imaging (MRSI) has been reported to be of value in defining the extent of glioma infiltration. We performed a study examining the impact MRSI would have on the routine addition of 2-3-cm margins around MRI T2-weighted hyperintensity to generate the treatment planning clinical target volume (CTV) for low-grade gliomas. Methods and Materials: Twenty patients with supratentorial gliomas WHO Grade II (7 astrocytomas, 6 oligoastrocytomas, 7 oligodendrogliomas) underwent MRI and MRSI before surgery. The MRI was contoured manually; the regions of interest included T2 hyperintensity and, if present, regions of contrast enhancement on T1-weighted images. The 3D-MRSI peak parameters for choline and N-acetyl-aspartate, acquired voxel-by-voxel, were categorized using a choline/N-acetyl-aspartate index (CNI), a tool for quantitative assessment of tissue metabolite levels, with CNI 2 being the lowest value corresponding to tumor. CNI data were aligned to MRI and displayed as 3D contours. The relationship between the anatomic and metabolic information on tumor extent was assessed by comparing the CNI contours and other MRSI-derived metabolites to the MRI T2 volume. Results: The limitations in the size of the region "excited" meant that MRSI could be used to evaluate only a median 68% of the T2 volume (range 38 -100%), leaving the volume T2c. The CNI 2 volume (median 29 cm 3 , range 10 -73) was contained totally within the T2c in 55% of patients. In the remaining patients, the volume of CNI 2 extending beyond the T2c was quite small (median 2.3 cm 3 , range 1.4 -5.2), but was not distributed uniformly about the T2c, extending up to 22 mm beyond it. Two patients demonstrated small regions of contrast enhancement corresponding to the regions of highest CNI. Other metabolites, such as creatine and lactate, seem useful for determining less and more radioresistant areas, respectively. Conclusion: Metabolically active tumor, as detected by MRSI, is restricted mainly to the T2 hyperintensity in low-grade gliomas, but can extend outside it in a limited and nonuniform fashion up to 2 cm. Therefore, a CTV including T2 and areas of CNI extension beyond the T2 hyperintensity would result in a reduction in the size and a change in the shape of the standard clinical target volumes generated by adding uniform margins of 2-3 cm to the T2 hyperintensity.
Functional/metabolic information provided by MR-spectroscopy (MRSI) suggests MRI may not be a rel... more Functional/metabolic information provided by MR-spectroscopy (MRSI) suggests MRI may not be a reliable indicator of active and microscopic disease in malignant brain tumors. We assessed the impact MRSI might have on the target volumes used for radiation therapy treatment planning for high-grade gliomas. Thirty-four patients (22 Grade III; 12 Grade IV astrocytomas) were evaluated; each had undergone MRI and MRSI studies before surgery. MRI data sets were contoured for T1 region of contrast enhancement (T1), region of necrosis, and T2 region of hyperintensity (T2). The three-dimensional MRSI peak parameters for choline (Cho) and N-acetylaspartate (NAA), acquired by a multivoxel technique, were categorized based on an abnormality index (AI), a quantitative assessment of tissue metabolite levels. The AI data were aligned to the MRI and displayed as three-dimensional contours. AI vs. T conjoint and disjoint volumes were compared. For both grades, although T2 estimated the region at risk of microscopic disease as being as much as 50% greater than by MRSI, metabolically active tumor still extended outside the T2 region in 88% of patients by as many as 28 mm. In addition, T1 suggested a lesser volume and different location of active disease compared to MRSI. The use of MRSI to define target volumes for RT treatment planning would increase, and change the location of, the volume receiving a boost dose as well as reduce the volume receiving a standard dose. Incorporation of MRSI into the treatment-planning process may have the potential to improve control while reducing complications.
International Journal of Radiation Oncology Biology Physics, 2005
Transplantation Proceedings, 2003
A MONG a variety of surgical procedures for simultaneous pancreas-kidney transplantation (SPK) fo... more A MONG a variety of surgical procedures for simultaneous pancreas-kidney transplantation (SPK) for patients with insulin-dependent diabetes mellitus and endstage kidney failure, portal venous enteric exocrine drainage (PVED) has been established as a standard technique. One advantage is physiologic glycemic control based upon normal first-pass effect through the recipient liver. We report our single-center experience with 70 consecutive PVED transplant recipients.
Radiotherapy and Oncology, 2000
Tumors in the nasal cavity and paranasal sinus are difficult to treat with radiotherapy. Usually,... more Tumors in the nasal cavity and paranasal sinus are difficult to treat with radiotherapy. Usually, in addition to a two- or three-field photon technique, an interorbital electron field is required. This may result, however, in severe over- or underdosage, the latter being especially detrimental when occurring in the main tumor bulk. We present a conformal three-dimensional treatment technique that provides sufficient interorbital dose with photons only while sparing the eyes, optic nerves and chiasm, and may be considered for selected tumors in this region.
Medical Physics, 2001
The incorporation of multiple imaging modalities into radiotherapy treatment planning offers the ... more The incorporation of multiple imaging modalities into radiotherapy treatment planning offers the potential to improve identification of regions of pathology. This work outlines and evaluates a methodology for registration of magnetic resonance images (MRI) and spectroscopic images (MRSI) to computed tomography (CT) images, and visualization of the multimodality data on the treatment planning workstation. Volumetric magnetic resonance images were acquired during an examination prior to the initiation of radiotherapy. Registration between these images and the treatment planning computed tomography images was performed using an automated alignment routine, and was improved manually using an interactive registration tool. The parameters of the alignment were then used to transform the spectroscopic images into the same reference frame. The spectroscopy data were represented in terms of a statistical measure of abnormality, and embedded within the MRI data as overlaid contours. These images were sent via DICOM transfer to the treatment planning workstation. An analysis of the reproducibility of the
Seminars in Surgical Oncology, 2001
With an incidence of 15/10(5) in the general population, brain metastases constitute a serious, d... more With an incidence of 15/10(5) in the general population, brain metastases constitute a serious, debilitating complication in cancer patients. The majority of those patients suffer from more than one metastasis, but up to 30% to 40% present with a solitary lesion. Whole-brain radiotherapy (WBRT) extends median survival from 1 to 2 months for treatment with steroids only, to 4 to 6 months in most series. However, long-term survival (>1-2 years) is observed in up to 10% of patients with favorable prognostic factors, such as solitary lesions, good Karnofsky performance status, and absence of extracranial disease. For those patients, individually optimized treatment is worthwhile. For good-prognosis patients with controlled extracranial disease, surgery in combination with postoperative WBRT should be considered, especially when fast relief of symptoms is mandated. For surgically inaccessible solitary lesions below a size threshold of approximately 30 ccm, stereotactic radiosurgery (RS), although never compared to surgery in a randomized fashion, seems to yield comparable results and is the treatment of choice for more than one lesion in appropriately selected patients. Nevertheless, a number of questions concerning the optimal treatment regimens for brain metastases remain. These mainly concern the radiation dose, need for a combination of RS and WBRT, relative timing of different treatment modalities, and maximum number of brain metastases that can reasonably be treated with RS when long-term progression-free survival is the goal. However, RS is definitely an excellent option for salvage and palliation in patients with short life expectancy, as it is simultaneously noninvasive and cost-effective, with short hospitalization times.
Journal of Neurosurgery, 2004
The objective of this study was to investigate cerebellar metabolism in patients with autosomal d... more The objective of this study was to investigate cerebellar metabolism in patients with autosomal dominant cerebellar ataxia type 1 (ADCA-I) carrying two distinct mutations of spinocerebellar ataxia (SCA). Non-invasive image-guided proton magnetic resonance spectroscopy imaging (1H-MRSI) was performed in 4 patients with SCA2, and 3 patients carrying the SCA6 mutation. For MRSI, we employed a spinecho sequence (TR ؍ 1500 msec, TE ؍ 135 msec, slice thickness ؍ 15 mm, FOV ؍ 240 mm) and a stimulated-echo sequence (TR ؍ 1500 msec, TE ؍ 20 msec, slice thickness ؍ 15 mm, FOV ؍ 240 mm). Measures included the peak integral ratios of neuronal and glial markers [N-acetylaspartate (NA) to creatine (Cr), choline-containing compounds (CHO) to Cr, and lactate (LAC) to Cr]. We found NA:Cr ratios were significantly lower in patients with SCA2 (40.4% lower) compared to patients carrying the SCA6 mutation. CHO:Cr ratios differed between the two mutations using short echo time (30.8% lower in SCA2), but not when applying long echo time 1H-MRSI. Measurements using long echo time revealed LAC peaks in all SCA2 patients. 1H-MRSI revealed metabolic differences between SCA2 and SCA6 patients. NA:Cr ratios were significantly lower in patients with the SCA2 mutation compared to the SCA6 mutation, and LAC signals were obtained in the cerebella of SCA2 patients. In addition, CHO:Cr ratios showed different behavior using short and long TE, indicating differences in relaxation times of choline compounds in SCA2. J. Magn. Reson. Imaging 2001;13:553-559.
Journal of Neurosurgery, 2002
Journal of Neuro-Oncology, 2009
GBM) are heterogeneous lesions, both in terms of their appearance on anatomic images and their re... more GBM) are heterogeneous lesions, both in terms of their appearance on anatomic images and their response to therapy. The goal of this study was to evaluate the prognostic value of parameters derived from physiological and metabolic images of these lesions. Fifty-six patients with GBM were scanned immediately before surgical resection using conventional anatomical MR imaging and, where possible, perfusion-weighted imaging, diffusionweighted imaging, and proton MR spectroscopic imaging. The median survival time was 517 days, with 15 patients censored. Absolute anatomic lesion volumes were not associated with survival but patients for whom the combined volume of contrast enhancement and necrosis was a large percentage of the T2 hyperintense lesion had relatively poor survival. Other volumetric parameters linked with less favorable survival were the volume of the region with elevated choline to N-acetylaspartate index (CNI) and the volume within the T2 lesion that had apparent diffusion coefficient (ADC) less than 1.5 times that in white matter. Intensity parameters associated with survival were the maximum and the sum of levels of lactate and of lipid within the CNI lesion, as well as the magnitude of the 10th percentile of the normalized ADC within the contrast-enhancing lesion. Patients whose imaging parameters indicating that lesions with a relatively large percentage with breakdown of the blood brain barrier or necrosis, large regions with abnormal metabolism or areas with restricted diffusion have relatively poor survival. These parameters may provide useful information for predicting outcome and for the stratification of patients into high or low risk groups for clinical trials.
Journal of Neuro-Oncology, 2009
Purpose-Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults... more Purpose-Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults. The goal of this study was to test the predictive value of MR parameters in relation to the survival of patients with newly diagnosed GBM who were scanned prior to receiving adjuvant radiation and chemotherapy.
Journal of Magnetic Resonance Imaging, 2004
Purpose: To identify radiation-induced changes in healthy white-matter spectra in the first six m... more Purpose: To identify radiation-induced changes in healthy white-matter spectra in the first six months following radiotherapy, and assess the impact of these changes on an automated algorithm for detecting spectral abnormalities.
Journal of Magnetic Resonance Imaging, 2002
To evaluate the role of 3D MR spectroscopic imaging (MRSI) as a tool for characterizing heterogen... more To evaluate the role of 3D MR spectroscopic imaging (MRSI) as a tool for characterizing heterogeneity within a lesion in glioma patients.
Journal of Magnetic Resonance Imaging, 2004
To investigate the potential value of pre-external-beam radiation therapy (XRT) choline-to-NAA (N... more To investigate the potential value of pre-external-beam radiation therapy (XRT) choline-to-NAA (N-acetylaspartate) index (CNI), apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV) for predicting survival in newly diagnosed patients with glioblastoma multiforme (GBM). Twenty-eight patients with GBM were studied using in vivo proton magnetic resonance spectroscopic imaging (1H MRSI) and diffusion- and perfusion-weighted imaging after surgery but prior to XRT. Patients were categorized on the basis of their volumes of morphologic and metabolic abnormalities (volume of CNI > or = 2 and CNI values), normalized ADC (nADC), or rCBV values within the T1 contrast-enhancing and T2 regions. The median survival time was compared. A significantly shorter median survival time was observed for patients with a large volume of metabolic abnormality than for those with a small abnormality (12.0 and 17.1 months, respectively, P = 0.002). A similar pattern was observed for patients with a low mean nADC value compared to those with high mean nADC value within the T2 region (11.2 and 21.7 months, respectively, P = 0.004). A shorter median survival time was also observed for patients with contrast-enhancing residual disease than for those without the presence of contrast enhancement with marginal significance. The pre-XRT volume of the metabolic abnormality and the nADC value within the T2 region may be valuable in predicting outcome for patients with GBM.
International Journal of Radiation Oncology*Biology*Physics, 2000
Target volumes that wrap around the spinal cord are difficult to treat. We present and evaluate a... more Target volumes that wrap around the spinal cord are difficult to treat. We present and evaluate a refined multiple arc segment (MAS) technique that is applicable with standard three-dimensional (3D) radiotherapy equipment and may be a solution for facilities that do not yet have full access to intensity-modulated radiotherapy (IMRT). The presented technique consisted of 13 isocentric coplanar beam's eye view shaped fields, delivered as 20 degrees or 10 degrees arc segments with an integrated multileaf collimator (MLC) using automatic sequential field delivery. Dose-volume histograms (DVH) for this technique were compared to a modified bar-arc technique (MBA) modeled as 30 static fields and to an inverse planned IMRT technique using 7 coplanar, equispaced beams delivered with the same MLC. Compared to the MBA technique, maximum dose and target coverage were similar when using 80% of the maximum dose as the reference dose. However, the MAS technique reduced the maximum doses (to > or = 1% of the organs at risk [OAR]) by 9% for the spinal cord, 17% for the esophagus, and 25% for the trachea, as well as the mean doses. Although inverse planned IMRT could further reduce exposure of OAR except for the spinal cord and improve target coverage, our forward planned MAS technique seems to achieve clinically comparable results. Substituting a series of small split-field arc segments for large static fields and using additional narrow paraspinal segments significantly improves the sparing of organs at risk for paraspinal targets. Although these results are not quite as good as those achieved with IMRT, for facilities not yet equipped with inverse treatment planning capability, the presented technique enables dose escalation for primary paraspinal tumors and retreatment of recurrent lesions.
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Papers by Andrea Pirzkall