Trends and Correlates of Mean Lung Dose in Patients Receiving Breast Radiotherapy in a Single Institution from 2014 to 2018.

AIMS: Higher mean lung dose (MLD) in breast cancer patients has been associated with pneumonitis, pulmonary fibrosis and secondary lung cancer primaries. This study examined MLD in a single institution from 2014 to 18 to assess trends in median MLD (Gy) over time and factors associated with higher MLD to determine best practices for limiting lung toxicity. MATERIALS AND METHODS: General linear regressions were analysed to determine significant change in median MLD over time in patients receiving conventional or hypofractionated schedules for whole breast/chest wall (WB) radiotherapy with or without sequential boost or simultaneous integrated boost, WB tangential radiotherapy only and WB locoregional radiotherapy. Univariate and multivariable linear regression analysed identified factors associated with MLD. RESULTS: In total, 3894 patients were included in the analysis. The total median MLD across all years was 6.8 Gy in patients treated with conventional fractionation and 3.4 Gy in patients treated with hypofractionation. A significant increase in MLD was observed between 2014 and 2018 in patients receiving conventional or hypofractionation, conventional WB treatment with locoregional radiotherapy, conventional WB radiotherapy with simultaneous integrated boost and hypofractionated WB radiotherapy with sequential boost. Increased MLD was significantly correlated with lower lung volume and larger treatment volume due to locoregional radiotherapy, inclusion of a boost, chest wall treatment and reverse decubitus or supine positioning (P < 0.0001). CONCLUSION: A significant increase in MLD was observed over the years in patients receiving conventional and hypofractionated radiotherapy. Techniques such as prone positioning should be considered to lower MLD, particularly for patients with predisposing pulmonary risk.

Results of 15 Gy HDR-BT boost plus EBRT in intermediate-risk prostate cancer: Analysis of over 500 patients.

PURPOSE/OBJECTIVE: To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. RESULTS: 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61-72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88-94)% at 5 years. Five-year FFBF was 94 (89-99)% and 89 (85-94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2-6)% at 5 years. Five-year CI of ADT was 1 (0-3)% and 5 (2-8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95-98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92-98)% in FIR and UIR patients, respectively (p = 0.020). CONCLUSION: In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.

In Vivo MR Imaging of Fibrin in a Neuroblastoma Tumor Model by Means of a Targeting Gd-Containing Peptide.

PURPOSE: A magnetic resonance imaging contrast agent based on a tetrameric Gd-DTPA-like system linked to a fibrin-targeting peptide (Gd-F) has been designed for in vivo tumor characterization. PROCEDURES: Gd-F was synthesized following Fmoc-SPPS strategy. Binding was measured using soluble fibrin DD(E) fragment and a dried fibrin assay. Contrast efficiency was tested on human and mouse clots and in vivo on Neuro2A tumor model. An anti-thrombotic drug was used to evaluate Gd-F sensitivity for changes in fibrin availability at the tumor site. RESULTS: The high relaxivity of Gd-F (42 mM(-1) s(-1), per molecule) yielded a strong signal enhancement in human and murine clots. High contrast was also measured in vivo in Neuro2A tumors, with a persistent enhancement in tumor rim and stroma. Upon treatment with an anti-thrombotic drug, the contrast uptake was significantly reduced in the tumor area confirming the specificity of the probe. CONCLUSIONS: Gd-F resulted to be an efficient probe for tumor delineation and for monitoring fibrin deposits during tumor progression and anti-thrombotic therapy.

Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel imager: zero-spatial frequency x-ray imaging properties of the solid-state SHARP sensor structure.

PURPOSE: The authors are investigating the feasibility of a new type of solid-state x-ray imaging sensor with programmable avalanche gain: scintillator high-gain avalanche rushing photoconductor active matrix flat panel imager (SHARP-AMFPI). The purpose of the present work is to investigate the inherent x-ray detection properties of SHARP and demonstrate its wide dynamic range through programmable gain. METHODS: A distributed resistive layer (DRL) was developed to maintain stable avalanche gain operation in a solid-state HARP. The signal and noise properties of the HARP-DRL for optical photon detection were investigated as a function of avalanche gain both theoretically and experimentally, and the results were compared with HARP tube (with electron beam readout) used in previous investigations of zero spatial frequency performance of SHARP. For this new investigation, a solid-state SHARP x-ray image sensor was formed by direct optical coupling of the HARP-DRL with a structured cesium iodide (CsI) scintillator. The x-ray sensitivity of this sensor was measured as a function of avalanche gain and the results were compared with the sensitivity of HARP-DRL measured optically. The dynamic range of HARP-DRL with variable avalanche gain was investigated for the entire exposure range encountered in radiography∕fluoroscopy (R∕F) applications. RESULTS: The signal from HARP-DRL as a function of electric field showed stable avalanche gain, and the noise associated with the avalanche process agrees well with theory and previous measurements from a HARP tube. This result indicates that when coupled with CsI for x-ray detection, the additional noise associated with avalanche gain in HARP-DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor produced identical avalanche gain dependence on electric field as the optical measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP-DRL enabled a very wide dynamic range which encompassed all clinically relevant medical x-ray exposures. CONCLUSIONS: This work demonstrates that the HARP-DRL sensor enables the practical implementation of a SHARP solid-state x-ray sensor capable of quantum noise limited operation throughout the entire range of clinically relevant x-ray exposures. This is an important step toward the realization of a SHARP-AMFPI x-ray flat-panel imager.

Validation of the Joensuu risk criteria for primary resectable gastrointestinal stromal tumour - the impact of tumour rupture on patient outcomes.

BACKGROUND: Approval of imatinib for adjuvant treatment of gastrointestinal stromal tumours (GIST) raised discussion about accuracy of prognostic factors in GIST and the clinical significance of the available risk stratification criteria. METHODS: We studied the influence of a new modification of the NIH Consensus Criteria (the Joensuu risk criteria), NCCN-AFIP criteria, and several clinicopathological factors, including tumour rupture, on relapse-free survival (RFS) in a prospectively collected tumour registry series consisting of 640 consecutive patients with primary, resectable, CD117-immunopositive GIST. The median follow-up time after tumour resection was 39 months. None of the patients received adjuvant imatinib. RESULTS: The median RFS time after surgery was 50 months. In univariable analyses, high Joensuu risk group, tumour mitotic count >5/50 HPF, size >5 cm, non-gastric location, tumour rupture (7% of cases; P = 0.0014) and male gender had adverse influence on RFS. In a multivariable analysis mitotic count >5/50HPF, tumour size >5 cm and non-gastric location were independent adverse prognostic factors. Forty, 151, 86 and 348 patients were assigned according to the Joensuu criteria to very low, low, intermediate and high risk groups and had 5-year RFS of 94%, 94%, 86% and 29%, respectively. CONCLUSION: The Joensuu criteria, which include 4 prognostic factors (tumour size, site, mitotic count and rupture) and 3 categories for the mitotic count, were found to be a reliable tool for assessing prognosis of operable GIST. The Joensuu criteria identified particularly well high risk patients, who are likely the proper candidates for adjuvant therapy.

A solid-state amorphous selenium avalanche technology for low photon flux imaging applications.

PURPOSE: The feasibility of a practical solid-state technology for low photon flux imaging applications was investigated. The technology is based on an amorphous selenium photoreceptor with a voltage-controlled avalanche multiplication gain. If this photoreceptor can provide sufficient internal gain, it will be useful for an extensive range of diagnostic imaging systems. METHODS: The avalanche photoreceptor under investigation is referred to as HARP-DRL. This is a novel concept in which a high-gain avalanche rushing photoconductor (HARP) is integrated with a distributed resistance layer (DRL) and sandwiched between two electrodes. The avalanche gain and leakage current characteristics of this photoreceptor were measured. RESULTS: HARP-DRL has been found to sustain very high electric field strengths without electrical breakdown. It has shown avalanche multiplication gains as high as 10(4) and a very low leakage current (< or = 20 pA/mm2). CONCLUSIONS: This is the first experimental demonstration of a solid-state amorphous photoreceptor which provides sufficient internal avalanche gain for photon counting and photon starved imaging applications.

A phospholipid-PEG2000 conjugate of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeting heterodimer peptide for contrast-enhanced ultrasound imaging of angiogenesis.

The transition of a targeted ultrasound contrast agent from animal imaging to testing in clinical studies requires considerable chemical development. The nature of the construct changes from an agent that is chemically attached to microbubbles to one where the targeting group is coupled to a phospholipid, for direct incorporation to the bubble surface. We provide an efficient method to attach a heterodimeric peptide to a pegylated phospholipid and show that the resulting construct retains nanomolar affinity for its target, vascular endothelial growth factor receptor 2 (VEGFR2), for both the human (kinase insert domain-containing receptor - KDR) and the mouse (fetal liver kinase 1 - Flk-1) receptors. The purified phospholipid-PEG-peptide isolated from TFA-based eluents is not stable with respect to hydrolysis of the fatty ester moieties. This leads to the time-dependent formation of the lysophospholipid and the phosphoglycerylamide derived from the degradation of the product. Purification of the product using neutral eluent systems provides a stable product. Methods to prepare the lysophospholipid (hydrolysis product) are also included. Biacore binding data demonstrated the retention of binding of the lipopeptide to the KDR receptor. The phospholipid-PEG2000-peptide is smoothly incorporated into gas-filled microbubbles and provides imaging of angiogenesis in a rat tumor model.

Direct-conversion flat-panel imager with avalanche gain: feasibility investigation for HARP-AMFPI.

The authors are investigating the concept of a direct-conversion flat-panel imager with avalanche gain for low-dose x-ray imaging. It consists of an amorphous selenium (a-Se) photoconductor partitioned into a thick drift region for x-ray-to-charge conversion and a relatively thin region called high-gain avalanche rushing photoconductor (HARP) in which the charge undergoes avalanche multiplication. An active matrix of thin film transistors is used to read out the electronic image. The authors call the proposed imager HARP active matrix flat panel imager (HARP-AMFPI). The key advantages of HARP-AMFPI are its high spatial resolution, owing to the direct-conversion a-Se layer, and its programmable avalanche gain, which can be enabled during low dose fluoroscopy to overcome electronic noise and disabled during high dose radiography to prevent saturation of the detector elements. This article investigates key design considerations for HARP-AMFPI. The effects of electronic noise on the imaging performance of HARP-AMFPI were modeled theoretically and system parameters were optimized for radiography and fluoroscopy. The following imager properties were determined as a function of avalanche gain: (1) the spatial frequency dependent detective quantum efficiency; (2) fill factor; (3) dynamic range and linearity; and (4) gain nonuniformities resulting from electric field strength nonuniformities. The authors results showed that avalanche gains of 5 and 20 enable x-ray quantum noise limited performance throughout the entire exposure range in radiography and fluoroscopy, respectively. It was shown that HARP-AMFPI can provide the required gain while maintaining a 100% effective fill factor and a piecewise dynamic range over five orders of magnitude (10(-7)-10(-2) R/frame). The authors have also shown that imaging performance is not significantly affected by the following: electric field strength nonuniformities, avalanche noise for x-ray energies above 1 keV and direct interaction of x rays in the gain region. Thus, HARP-AMFPI is a promising flat-panel imager structure that enables high-resolution fully quantum noise limited x-ray imaging over a wide exposure range.

Sci-Fri AM: YIS-10: Development of a flat panel detector with avalanche gain for low-dose x-ray imaging.

Digital flat panel detectors are increasingly being used in radiography and fluoroscopy. The imaging performance of current systems, however, is compromised by electronic noise at the low X-ray exposures employed in fluoroscopy and low-dose radiography. In other words, current flat panel detectors are not quantum noise limited at these low radiation exposures. There is thus a need to develop an imaging detector with the high sensitivity of an X-ray image intensifier and the inherent advantages of a solid-state flat panel detector. Towards this end, we have developed and characterized a novel solid-state device capable of providing very high avalanche gains and an excellent temporal response. The device which is based on the amorphous photoconductor a-Se, is scalable (i.e. can be manufactured in large areas), can overcome electronic noise even at the lowest X-ray exposures used in diagnostic imaging (0.1 µR/frame at the detector) and has a very low level of dark current. Here, we investigate the gain and temporal characteristics of this device and discuss its applicability for low exposure X-ray imaging as well as the effects of avalanche gain on the detective quantum efficiency. Coupled to a high-resolution structured CsI X-ray scintillator and a thin film transistor array, this device should provide a true solid-state alternative to the X-ray image intensifier, which is both robust and cost-effective. This should open the door to dose-efficient flat panel imagers for radiography and fluoroscopy as well as a number of other demanding medical imaging applications.

A distinct strategy to generate high-affinity peptide binders to receptor tyrosine kinases.

We describe a novel and general way of generating high affinity peptide (HAP) binders to receptor tyrosine kinases (RTKs), using a multi-step process comprising phage-display selection, identification of peptide pairs suitable for hetero-dimerization (non-competitive and synergistic) and chemical synthesis of heterodimers. Using this strategy, we generated HAPs with K(D)s below 1 nM for VEGF receptor-2 (VEGFR-2) and c-Met. VEGFR-2 HAPs bound significantly better (6- to 500-fold) than either of the individual peptides that were used for heterodimer synthesis. Most significantly, HAPs were much better (150- to 800-fold) competitors than monomers of the natural ligand (VEGF) in various competitive binding and functional assays. In addition, we also found the binding of HAPs to be less sensitive to serum than their component peptides. We believe that this method may be applied to any protein for generating high affinity peptide (HAP) binders.

Fractionated radiosurgery for brain metastases in 43 patients with breast carcinoma.

About 15% of metastatic breast carcinoma patients are diagnosed with brain metastases. Historically, the majority are treated with palliative external whole-brain radiation with a median survival of 4 months. We examined stereotactic radiosurgery's effect on treatment outcome in such patients. Four hundred and fifty four consecutive patients with brain metastases were treated with stereotactic radiosurgery at Staten Island University Hospital, NY, between 1991 and 1999. The medical records of 60 women with histologically confirmed breast cancer were retrospectively reviewed. Forty-three patients (71%) received fractionated radiosurgery (4 x 600 cGy) and form the core of this report. Sixty five percentage had been previously unsuccessfully treated by whole-brain radiation or had recurrence after craniotomy. Survival was calculated by the Kaplan-Meier method. The median age at diagnosis of brain metastases was 52 years, with median interval of 49 months following the diagnosis of tumor primary. Median survival from brain diagnosis reached 13.6 months. Overall median survival from radiosurgery treatment was 7.5 months. Fifteen patients with one or two brain lesions survived a median of 11.5 months. For the fractionated cohort of patients 1- and 2-year actuarial survival was 28.2% and 12.8%, respectively. Three patients are alive at 32, 34 and 64 months, respectively. We conclude that fractionated radiosurgery improves survival of patients with brain metastases from breast cancer, especially those with small lesions, good functional status and no other metastatic disease. These patients should be encouraged to consider radiosurgery, possibly before WBRT. Considering our 7.5 months overall survival including patients with multiple metastases, and patients with progressive brain metastases despite extensive standard therapy and often systemic disease, these results suggest that radiosurgery could benefit breast cancer patients with brain metastases and extend life.

Surgical treatment of brain metastases from melanoma: a retrospective study of 91 patients.

OBJECT: Reports on the surgical treatment of brain metastases from melanoma in a large group of patients are sparse. The goal of this paper is to review the surgical experience in a series of 91 patients with brain metastases from primary melanoma treated at a single institution. METHODS: Seven hundred eighty patients underwent resection of brain metastases at Memorial Sloan-Kettering Cancer Center between 1974 and 1994. The records of 91 (11.7%) of these patients who had melanoma were retrospectively reviewed. The median time from diagnosis of the primary melanoma to diagnosis of the brain lesion was 14.1 months. The overall median length of survival following craniotomy was 6.7 months. Fifteen patients with resected multiple metastases had shorter median survival times than 76 patients with a single lesion (5.4 months compared with 7.8 months, p = 0.12). In eight patients with cerebellar metastases the median length of survival was significantly shorter than that found in patients with supratentorial lesions (2 compared with 7 months, p = 0.03). There was no difference in length of survival between 49 patients who underwent postoperative whole-brain radiation therapy (WBRT) and 29 patients who did not (9.5 compared with 8.3 months, p = 0.67). The incidence of brain metastasis recurrences in WBRT-treated and untreated patients was similar (56% and 45.7%, respectively). Only the presence of infratentorial metastases (p = 0.0013) and unresected recurrence of brain metastases (p = 0.0003) had an impact on outcome according to a Cox regression analysis. Five patients (5.5%) died within 31 days of surgery. Overall survival rates at 1, 2, 3, and 5 years were 36.3, 18.7, 13.2, and 6.6%, respectively. CONCLUSIONS: Although melanoma metastatic to the brain carries a foreboding prognosis, patients who do not display preoperative neurological deficits, harbor a single lesion situated supratentorially, and have no lung or visceral metastases may derive significant palliative benefit from surgical resection of brain metastases.

Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel.

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.

Apolipoprotein B mRNA editing and apolipoprotein gene expression in the liver of hyperinsulinemic fatty Zucker rats: relationship to very low density lipoprotein composition.

We previously demonstrated increased apolipoprotein B (apoB) mRNA editing, elevated levels of mRNA for the catalytic component of the apoB mRNA editing complex, apobec-1, and increased secretion of the product of the edited mRNA, apoB48, in very low density lipoproteins (VLDL) in primary cultures of Sprague-Dawley rat hepatocytes following insulin treatment. In order to determine the effect of in vivo hyperinsulinemia on these processes, we determined apoB mRNA editing, apobec-1 expression, hepatic expression of mRNA for apoB and other VLDL apoproteins, and the quantity and composition of plasma VLDL in the hyperinsulinemic fatty Zucker rat. Total apoB mRNA content of the livers of the fatty rats and lean littermates did not differ; however, edited apoB message coding for hepatic apo B48, and abundance of mRNA for the catalytic subunit of the apoB mRNA editing complex, apobec-1, was increased by 1.7- and 3.3-fold, respectively, in fatty rats. ApoCIII mRNA abundance was increased in livers of fatty rats as well, but the abundance of hepatic apoE mRNA in the fatty animal was not different from that of the lean rat. Hepatic apoAI mRNA abundance was also increased in the fatty rats. Associated with increased apoB mRNA editing, was the 1.7-fold increase in the fraction of apoB in plasma as apoB48 in fatty rats. VLDL-triglyceride and -apoB in plasma were 15- and 3-fold higher, respectively, in fatty Zucker rats compared to lean littermates, indicating both enrichment of VLDL with triglycerides and increased accumulation of VLDL particles. Increased hepatic expression of mRNA for apoCIII and apoAI was associated with increased content of apoC (and relative depletion of apoE) in VLDL of fatty rats, and plasma apoAI was increased in fatty Zucker rats, primarily in the HDL fraction. The current study provides further evidence that chronic exposure to high levels of insulin influences both the quantity of and lipid/apoprotein composition of VLDL in plasma. The increased apoC and decreased apoE (as well as increased triglyceride) content of VLDL in the fatty Zucker rat observed in the current study may affect VLDL clearance and therefore may be a factor in the observed accumulation of VLDL in the plasma of the fatty hyperinsulinemic Zucker rats.

Resection of brain metastases from colorectal carcinoma in 73 patients.

BACKGROUND: At the time of diagnosis of colorectal carcinoma, 2-3% of patients are likely to be harboring brain metastases, and another 10% of patients will develop brain lesions during the course of their disease. The purpose of this study was to examine the clinical course of a group of patients with metastatic brain disease who underwent surgical resection in a single institution. The authors believe this information will be useful for establishing prognostic factors and for clinical decision making. METHODS: Between 1974 and 1993, 709 consecutive patients underwent surgical resection of brain metastases at Memorial Sloan-Kettering Cancer Center. Seventy-three patients had histologically confirmed colorectal carcinoma. The medical records of these patients were reviewed retrospectively, and the data were analyzed by univariate and multivariate analysis. RESULTS: The median age of the 43 women and 30 men was 61.5 years. The median interval from the time of diagnosis of the primary tumor and the development of brain metastases was 27.6 months. The primary colorectal tumor was resected in all patients, and the median survival from the day of surgery was 38 months. The median survival from the time of craniotomy was 8.3 months. The 1-year and 2-year survival rates were 31.5% and 6.8%, respectively. Postoperative mortality was 4%. Gender, presence of multiple metastases, presence of lung lesions, and adjuvant brain radiation after craniotomy appeared to have no impact on survival as determined by multivariate Cox analysis. Only the presence of cerebellar brain metastases was associated with decreased survival. CONCLUSIONS: The results of this series, which the authors believe is the largest series of resected brain metastases from colorectal carcinoma published to date, indicate that surgical resection may increase the survival of these patients. Analysis of prognostic factors shows that infratentorial tumor location is associated with a poorer survival compared with supratentorial tumor location (5.1 months vs. 9.1 months; P < 0.002). In patients with recurrent brain disease, repeated resection is a worthwhile consideration because it may prolong survival compared with patients who do not undergo re-resection.

Insulin increases expression of apobec-1, the catalytic subunit of the apolipoprotein B mRNA editing complex in rat hepatocytes.

We have previously shown that chronic insulin treatment of rat hepatocytes increases the fraction of edited apolipoprotein B (apoB) mRNA from approximately 50% to as much as 90%. We have now examined the effect of insulin on apobec-1 mRNA abundance and demonstrate that increased editing of apoB mRNA following insulin treatment is accompanied by elevated apobec-1 mRNA levels in primary rat hepatocytes. Time-course measurements of the effects of insulin on apoB mRNA editing and apobec-1 mRNA abundance showed that both were elevated almost maximally within 48 hours and sustained for at least 5 days of insulin treatment.

Fractionated stereotactic radiosurgery and concurrent taxol in recurrent glioblastoma multiforme: a preliminary report.

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.

[Plagiarism in publications by Dr. Andrzej Jendryczko]. / Plagiaty w publikacjach dr hab. Andrzeja Jendryczko.

The paper reviews the formal action taken by the Silesian Medical University (SMU) in Katowice, against a professor who mass-produced plagiarized papers over many years. Plagiarized publications were based on articles of other authors, published in the European and American medical journals. Over 40 papers written by Andrzej Jendryczko, PhD, a former professor of biochemistry at SMU were declared to be plagiarized. Most of these publications have been retracted from Polish and international medical databases (Medline) by the editors of the journals involved. Dr. Jendryczko resigned in March 1998 from the Czestochowa Polytechnic, where he was a professor and Deputy Director of the Institute. Disciplinary action against him has still not been taken, because he is on sick leave. Criticizing some formal steps taken by SMU, the author proposes to establish a national committee for scientific misconduct. This independent committee, should be able by law to supervise the investigation in all Polish cases in academia which are suspected of scientific fraud. The committee also should have the power to initiate and conduct the investigation.