Intraoperative Radiation Therapy

Intraoperative radiation therapy is a developing technology that is being explored at least 60 centers around the world. lt is nota procedure to be undertaken lightly because of high initial startup costs (shielding, modification/adaptation of machine head, operating table modifications, remote monitoring equipment, etc.). It demands dose cooperation between surgeons, physicists, anesthesiologists, radiotherapists, nurses, and other personnel76. IOPT is not without its complications77. Only recently has the ROTG begun to collect data in a prospective fashion forpatients treated with lORT Much investigative work remains to be done, and, at this time, IORT is a modality best suited for facilities that not only have the technological capacity to embark on such a program, but that also can cooperatively collect meaningful data in a prospective fashion and interpret sarne

Examination of criticality accident alarm coverage on the operating floors of Buildings X-333, X-330, and X-326 at the Portsmouth Gaseous Diffusion Plant. Revision 1

The diffusion cascade processing equipment at the Portsmouth Gaseous Diffusion Plant (PORTS) is located in Buildings X-333, X-330, and X-326. These buildings were referred to as the cascade buildings. Because enriched uranium operations are performed within the cascade buildings, the potential for a criticality accident in these buildings exists. A Criticality Accident Alarm System (CAAS) is in place to alarm in the event of a criticality accident. The CAAS is required to be designed to immediately detect the minimum accident-of-concern. A minimum accident-of-concern in an area with nominal shielding delivers the equivalent of an absorbed dose rate in free air of 20 rads per minute at a distance of 2 meters from the reacting material [Am86]. This report summarizes the analysis that was performed to evaluate the CAAS response to selected minimum accidents-of-concern on the operating floor of the cascade buildings. Selection of potential accident locations was based, in part, on the maximum distance to the closest CAAS detector. The other factor in selecting potential accident locations for analysis was the amount of intervening shielding between the accident location and CAAS detector. If the CAAS was predicted to alarm under conditions of significant shielding, then the system presumably would alarm in response to all accidents greater than the minimum accident-of-concern, at closer distances, and with less shielding

Determination of the response function for the Portsmouth Gaseous Diffusion Plant criticality accident alarm system neutron detectors

Neutron-sensitive radiation detectors are used in the Portsmouth Gaseous Diffusion Plant`s (PORTS) criticality accident alarm system (CAAS). The CAAS is composed of numerous detectors, electronics, and logic units. It uses a telemetry system to sound building evacuation horns and to provide remote alarm status in a central control facility. The ANSI Standard for a CAAS uses a free-in-air dose rate to define the detection criteria for a minimum accident-of-concern. Previously, the free-in-air absorbed dose rate from neutrons was used for determining the areal coverge of criticality detection within PORTS buildings handling fissile materials. However, the free-in-air dose rate does not accurately reflect the response of the neutron detectors in use at PORTS. Because the cost of placing additional CAAS detectors in areas of questionable coverage (based on a free-in-air absorbed dose rate) is high, the actual response function for the CAAS neutron detectors was determined. This report, which is organized into three major sections, discusses how the actual response function for the PORTS CAAS neutron detectors was determined. The CAAS neutron detectors are described in Section 2. The model of the detector system developed to facilitate calculation of the response function is discussed in Section 3. The results of the calculations, including confirmatory measurements with neutron sources, are given in Section 4

Expression Signature of IFN/STAT1 Signaling Genes Predicts Poor Survival Outcome in Glioblastoma Multiforme in a Subtype-Specific Manner

Previous reports have implicated an induction of genes in IFN/STAT1 (Interferon/STAT1) signaling in radiation resistant and prosurvival tumor phenotypes in a number of cancer cell lines, and we have hypothesized that upregulation of these genes may be predictive of poor survival outcome and/or treatment response in Glioblastoma Multiforme (GBM) patients. We have developed a list of 8 genes related to IFN/STAT1 that we hypothesize to be predictive of poor survival in GBM patients. Our working hypothesis that over-expression of this gene signature predicts poor survival outcome in GBM patients was confirmed, and in addition, it was demonstrated that the survival model was highly subtype-dependent, with strong dependence in the Proneural subtype and no detected dependence in the Classical and Mesenchymal subtypes. We developed a specific multi-gene survival model for the Proneural subtype in the TCGA (the Cancer Genome Atlas) discovery set which we have validated in the TCGA validation set. In addition, we have performed network analysis in the form of Bayesian Network discovery and Ingenuity Pathway Analysis to further dissect the underlying biology of this gene signature in the etiology of GBM. We theorize that the strong predictive value of the IFN/STAT1 gene signature in the Proneural subtype may be due to chemotherapy and/or radiation resistance induced through prolonged constitutive signaling of these genes during the course of the illness. The results of this study have implications both for better prediction models for survival outcome in GBM and for improved understanding of the underlying subtype-specific molecular mechanisms for GBM tumor progression and treatment response

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer

Molecular fingerprinting of radiation resistant tumors: Can we apprehend and rehabilitate the suspects?

Radiation therapy continues to be one of the more popular treatment options for localized prostate cancer. One major obstacle to radiation therapy is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors. Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA) may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2. In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer

Pancreatic tumours in patients with previous malignancy.

One hundred and ten patients were seen in the Department of Radiation Therapy at Thomas Jefferson University Hospital for pancreatic tumours between January 1975 and June 1980. Twelve patients had previously been treated for a non-pancreatic malignancy. Pancreatic biopsies were performed in nine patients and were interpreted as pancreatic carcinoma. When the previous pathological material was compared to the pancreatic biopsy, the diagnosis was changed in five of the 12 patients to recurrent non-pancreatic malignancy. We emphasise the importance of the distinction between primary pancreatic malignancy and metastatic disease in the pancreas