Importance of intra-therapy single-photon emission tomographic imaging in calculating tumour dosimetry for a lymphoma patient

The dosimetry for two, similarly sized tumours in a lymphoma patient being treated with non-bone marrow ablative, monoclonal antibody therapy is reported. The 45-year-old man was infused with 2.48 GBq (67 mCi) of 131 I-labelled MB-1. Prior to therapy, a time series of diagnostic conjugate-view images and a radionuclide transmission scan were obtained and processed to obtain time-activity curves. Starting 2 days after the therapeutic infusion of radioactivity, a second conjugate-view time series was obtained. At that time, a quantitative single-photon emission tomography (SPET) acquisition was also carried out. Pre- and post-therapy X-ray computed tomography scans demonstrated a percentage reduction in volume for the right tumour which was 3.8 times that for the left tumour. In contrast, diagnostic conjugate views by themselves estimated the absorbed dose to be the same for the two tumours. Addition of therapy conjugate-view data increased the right-over-left ratio but only to 1.22. Normalizing either time-activity series by the intra-therapy SPET results increased the ratio to greater than 1.5. We assume here that a differential dose is correct according to the differential tumour shirnkage. One can further assume that the largest ratio corresponds most certainly to the most accurate dosimetric method. Other assumptions are possible. While additional study is essential, data from this patient suggest that the preferred dosimetric method is intra-therapy SPET normalization of either time series.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46832/1/259_2005_Article_BF02258433.pd

Perspective of turkish medicine students on cancer, cancer treatments, palliative care, and oncologists (ares study): A study of the palliative care working committee of the turkish oncology group (TOG)

Cancer is one of the most common causes of death all over the World (Rahib et al. in Cancer Res 74(11):2913–2921, 2014; Silbermann et al. in Ann Oncol 23(Suppl 3):iii15–iii28, 2012). It is crucial to diagnose this disease early by effective screening methods and also it is very important to acknowledge the community on various aspects of this disease such as the treatment methods and palliative care. Not only the oncologists but every medical doctor should be educated well in dealing with cancer patients. Previous studies suggested various opinions on the level of oncology education in medical schools (Pavlidis et al. in Ann Oncol 16(5):840–841, 2005). In this study, the perspectives of medical students on cancer, its treatment, palliative care, and the oncologists were analyzed in relation to their educational status. A multicenter survey analysis was performed on a total of 4224 medical school students that accepted to enter this study in Turkey. After the questions about the demographical characteristics of the students, their perspectives on the definition, diagnosis, screening, and treatment methods of cancer and their way of understanding metastatic disease as well as palliative care were analyzed. The questionnaire includes questions with answers and a scoring system of Likert type 5 (absolutely disagree = 1, completely agree = 5). In the last part of the questionnaire, there were some words to detect what the words “cancer” and “oncologist” meant for the students. The participant students were analyzed in two study groups; “group 1” (n = 1.255) were phases I and II students that had never attended an oncology lesson, and “group 2” (n = 2.969) were phases III to VI students that had attended oncology lessons in the medical school. SPSS v17 was used for the database and statistical analyses. A value of p < 0.05 was noted as statistically significant. Group 1 defined cancer as a contagious disease (p = 0.00025), they believed that early diagnosis was never possible (p = 0.042), all people with a diagnosis of cancer would certainly die (p = 0.044), and chemotherapy was not successful in a metastatic disease (p = 0.003) as compared to group 2. The rate of the students that believed gastric cancer screening was a part of the national screening policy was significantly more in group 1 than in group 2 (p = 0.00014). Group 2 had a higher anxiety level for themselves or their family members to become a cancer patient. Most of the students in both groups defined medical oncologists as warriors (57% in group 1 and 40% in group 2; p = 0.097), and cancer was reminding them of “death” (54% in group 1 and 48% in group 2; p = 0.102). This study suggested that oncology education was useful for the students’ understanding of cancer and related issues; however, the level of oncology education should be improved in medical schools in Turkey. This would be helpful for medical doctors to cope with many aspects of cancer as a major health care problem in this country. © 2018, American Association for Cancer Education

Volume reduction versus radiation dose for tumors in previously untreated lymphoma patients who received iodine-131 tositumomab therapy

BACKGROUND A Phase II study of previously untreated patients with malignant low grade follicular lymphoma given a combination of unlabeled tositumomab and tositumomab labeled with iodine-131 has recently been completed. The responses of these patients have been characterized, and for some of them tumor dosimetry during therapy has been estimated not only by pretherapy tracer conjugate views but also by a hybrid method. METHODS Available patients were studied if they had had a pelvic or abdominal tumor evaluation by single photon emission computed tomography (SPECT) and achieved a partial response. A tumor outlined on the iodine-131 conjugate-view images was called a composite tumor. Its volume estimate came from multiple, not necessarily contiguous, regions of interest (ROI) on the pretherapy computed tomography (CT) scan. Its radiation dose was estimated from the weeklong series of pretherapy images and standard Medical Internal Radiation Dose methods. Computed tomography ROI were also grouped into smaller, contiguous volumes that defined individual tumors. Their radiation doses were estimated by the hybrid method. This method employed the activity measured for each individual tumor by a single intratherapy SPECT scan, as well as the tumor's volume, to individually normalize the composite time-activity curve as appropriate. The individual normalization factors then converted the composite radiation dose to radiation doses for individual tumors. Reduction in tumor volume was calculated for both composite and individual tumors at 12 weeks posttherapy. RESULTS For 14 composite tumors in 10 patients, the median pretherapy volume was 170 cm 3 . Application of a sigmoidal curve function to the plot of volume reduction versus radiation absorbed dose resulted in degeneration of the curve into a straight line with a negative slope. There was no statistical significance in the relationship ( P = 0.73). For 43 individual tumors, the median pretherapy tumor volume was 26 cm 3 . The plot of volume reduction versus dose was fairly well fit by a sigmoidal curve, and the relationship approached statistical significance ( P = 0.06). The representation assigned 56% of the shrinkage to the effects of unlabeled tositumomab. For the subset of individual tumors with a pretherapy volume less than 10 cm 3 from 6 patients (n = 15), the relationship was significant ( P = 0.03). The sigmoidal representation assigned only 12% of the shrinkage to unlabeled tositumomab, as contrasted with 72% for tumors with pretherapy volume greater than 10 cm 3 . CONCLUSIONS For patients who attained a partial response, analysis of individual tumors by a hybrid dosimetric method led to a dependence between volume reduction at 12 weeks and radiation dose that tended to be significant. The same was not true with dosimetry of composite tumors based on pretherapy conjugate views alone. It appeared that volume reductions from both unlabeled antibody and radiation dose were important in tositumomab therapy of lymphoma patients, with unlabeled antibody relatively more important for larger tumors. Cancer 2002;94:1258–63. © 2002 American Cancer Society. DOI 10.1002/cncr.10294Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34359/1/10294_ftp.pd

Autoradiography-based, three-dimensional calculation of dose rate for murine, human-tumor xenografts

A Fast Fourier Transform method for calculating the three-dimensional dose rate distribution for murine, human-tumor xenografts is outlined. The required input includes evenly-spaced activity slices which span the tumor. Numerical values in these slices are determined by quantitative 125I autoradiography. For the absorbed dose-rate calculation, we assume the activity from both 131I- and 90Y-labeled radiopharmaceuticals would be distributed as is measured with the 125I label. Two example cases are presented: an ovarian-carcinoma xenograft with an IgG 2ak monoclonal antibody and a neuroblastoma xenograft with meta-iodobenzylguanidine (MIBG).Considering all the volume elements in a tumor, we show, by comparison of histograms and also relative standard deviations, that the measured 125I activity and the calculated 131I dose-rate distributions, are similarly non-uniform and that they are more non-uniform than the calculated 90Y dose-rate distribution. However, the maximum-to-minimum ratio, another measure of non-uniformity, decreases by roughly an order of magnitude from one distribution to the next in the order given above.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30498/1/0000126.pd

Brixsino High-Flux Dual X-Ray and THz Radiation Source Based on Energy Recovery Linacs

We present the conceptual design of a compact light source named BriXSinO. BriXSinO was born as demonstrator of the Marix project, but it is also a dual high flux radiation source Inverse Compton Source (ICS) of X-ray and Free-Electron Laser of THz spectral range radiation conceived for medical applications and general applied research. The accelerator is a push-pull CW-SC Energy Recovery Linac (ERL) based on superconducting cavities technology and allows to sustain MW-class beam power with almost just one hundred kW active power dissipation/consumption. ICS line produces 33 keV monochromatic X-Rays via Compton scattering of the electron beam with a laser system in Fabry-Pérot cavity at a repetition rate of 100 MHz. The THz FEL oscillator is based on an undulator imbedded in optical cavity and generates THz wavelengths from 15 to 50 micron

Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts

We studied the effect of monoclonal antibody protein dose on the uniformity of radioiodinated antibody distribution within tumor masses using quantitative autoradiography. Groups ( n = 11–13/group) of athymic nude mice with subcutaneous HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an 125 I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4, using a high or a low protein dose (500 µg or 5 µg). At 6 days post-injection the macroscopic and microscopic intratumoral biodistribution of radiolabeled antibody was determined. The degree of heterogeneity of the labeled antibody distribution within each tumor was quantified and expressed as the coefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-µg protein doses had substantially lower CV values, 0.327±0.027, than did tumors from animals given 5-µg protein doses, 0.458±0.041, ( P = 0.0078), indicating that the higher protein dose resulted in more homogeneous distribution of radioactivity in tumors than did the lower dose. While the percentage of the injected dose reaching the tumor was comparable between groups, injecting the higher dose of protein resulted in significantly lower tumor to non-tumor uptake ratios than those obtained for the lower protein dose. These data indicate, in this system, that to achieve more uniform intratumoral antibody (and radiation for radioimmunotherapy) delivery, a relatively high protein dose must be administered. However, to obtain this increased uniformity, a substantial drop in tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation of human tumor xenografts is a useful method to assess the intratumoral distribution of antibodies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46859/1/262_2005_Article_BF01789014.pd

SAUDI MEDICAL JOURNAL

Objective: Subclinical hypothyroidism is an elevation in serum thyroid-stimulating hormone (TSH) while having normal serum free thyroxine (FT4) and triiodothyronine (FT3) levels. The purpose of this prospective observational study was to evaluate the pulmonary function of patients diagnosed with subclinical hypothyroidism, both before and after treatment with thyroid hormone. Methods: This study took place at the Medical Faculty, Celal Bayar University, Manisa, Turkey between February 2003 and June 2004. Thirty-eight patients (37 females, one male) with subclinical hypothyroidism between 20 and 65 years of age were included in the study. Most were mildly obese. Arterial blood gases and pulmonary function tests were performed before treatment with thyroid hormone, and afterwards, the TSH value reached the normal range (indicating euthyroidism). Results: Oxygen saturation, but not partial oxygen pressure or partial carbon dioxide pressure, was statistically, but not clinically significantly higher after treatment with thyroid hormone (p=0.01). Pulmonary function tests were not significantly different before and after treatment with thyroid hormone. Conclusion: In our subclinical hypothyroidism patients, pulmonary function tests were normal and did not significantly change with thyroid hormone replacement. The advantages of thyroid hormone replacement therapy, at least regarding respiratory function, seem to be clearly present in patients with overt, clinical hypothyroidism but not in patients with subclinical hypothyroidism

SNAP: Stateful network-wide abstractions for packet processing

Early programming languages for software-defined networking (SDN) were built on top of the simple match-action paradigm offered by OpenFlow 1.0. However, emerging hardware and software switches offer much more sophisticated support for persistent state in the data plane, without involving a central controller. Nevertheless, managing stateful, distributed systems efficiently and correctly is known to be one of the most challenging programming problems. To simplify this new SDN problem, we introduce SNAP. SNAP offers a simpler "centralized" stateful programming model, by allowing programmers to develop programs on top of one big switch rather than many. These programs may contain reads and writes to global, persistent arrays, and as a result, programmers can implement a broad range of applications, from stateful firewalls to fine-grained traffic monitoring. The SNAP compiler relieves programmers of having to worry about how to distribute, place, and optimize access to these stateful arrays by doing it all for them. More specifically, the compiler discovers read/write dependencies between arrays and translates one-big-switch programs into an efficient internal representation based on a novel variant of binary decision diagrams. This internal representation is used to construct a mixed-integer linear program, which jointly optimizes the placement of state and the routing of traffic across the underlying physical topology. We have implemented a prototype compiler and applied it to about 20 SNAP programs over various topologies to demonstrate our techniques' scalability