Quantifying cell kill and cell survival
Michael C. Joiner, Albert J. van der Kogel in Basic Clinical Radiobiology, 2018
This is a non-cloning assay that was used in early radiation cell survival studies and which for some experimental tumours has the advantage of high sensitivity. The principle of the method is to prepare a suspension of tumour cells and to make a large number of subcutaneous implants into syngeneic animals, covering a range of inoculum sizes and if possible spanning the level of 50% tumour takes. The animals, usually mice, are then observed for a long enough period to record nearly every tumour that can grow from a single-cell implant. Take-rate is plotted against inoculum size and the point of 50% takes is interpolated; this is usually called the ‘TD50’ cell number. The experiment is performed simultaneously on treated cells and control cells and the surviving fraction is given by the ratio of the TD50 values. The addition of an excess of lethally irradiated cells improves the take-rate; using this manoeuvre Steel and Adams (25) found a TD50 of one to three cells for the Lewis lung tumour and were thus able to measure cell survival down to 10−6. The method only works well in the absence of an immune response against the tumour grafts, a relatively uncommon situation especially with chemically and virally induced tumours.
MRCPsych Paper A1 Mock Examination 1: Answers
Melvyn WB Zhang, Cyrus SH Ho, Roger Ho, Ian H Treasaden, Basant K Puri in Get Through, 2016
Explanation: Therapeutic index is the relative measure of the toxicity or safety of a drug and is usually defined as the ratio of the median toxic dose to the median effective dose. The median toxic dose is defined as the dose at which 50% of the patients would experience specific toxic effects. The median effective dose is defined as the dose at which 50% of the patients would have a specified therapeutic effect. A drug with a high therapeutic index implies that a wide range of dosages of the drug could be prescribed. Conversely, if the therapeutic index is low, closer monitoring of the prescribed medication would be essential.
ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
The therapeutic index (TI) of a DRUG is the TD50 divided by the ED50: that is, the toxic dose 50 divided by the effective dose 50. If the TD50 and the ED50 are the same dose one would have a TI of 1, which would not be good. If the TD50 was very high (that is, toxic effects required administration of massive doses) while the ED50 was very low (that is, tiny amounts of drug were very effective in producing a desired effect) then the TI would be very much greater than 1, which would be good.
One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant
Published in Expert Review of Hematology, 2019
Jan Philipp Bewersdorf, Maximilian Stahl, Amer M. Zeidan
As common for such studies, the trial had strict eligibility criteria. Patients with active acute or chronic graft-versus-host disease (GVHD) or any previous GVHD of grade ≥3 as well as patients with impaired renal or hepatic function were excluded from this trial. Of the 31 recruited patients, 29 patients were evaluable for a response with a median follow-up of 23 months. The median toxic dose of LEN determined by the CRM model used by the authors for the combination with AZA was 25 mg. The authors reported a 47% (7 out of 15 patients) response rate (defined as complete remission (CR) [n = 3], CR with incomplete cell count recovery [n = 3], or partial remission [n = 1]) in patients who received at least three cycles of treatment with only 3 patients experiencing GVHD. In the entire cohort of 29 patients, the response rate was 24% (7 out of 29 patients) with a median duration from transplant to relapse in responders of 11 months. The median overall survival (OS) for responders was 27 months, which was statistically significantly superior to the 10 months median OS observed in non-responders (p = 0.004)[13].
Dosimetric comparison between carbon, proton and photon radiation for renal retroperitoneal soft tissue sarcoma recurrence or metastasis after radical nephrectomy
Published in International Journal of Radiation Biology, 2022
Xue Ming, Weiwei Wang, Kambiz Shahnazi, Jiayao Sun, Qing Zhang, Ping Li, Zhengshan Hong, Yinxiangzi Sheng
All the patients in this study underwent radical nephrectomy before radiotherapy. The renal function of the contralateral kidney would play a vital role in the prognosis and life quality of the patients. The renal RSTS patients who received radical resection of their lesions and the ipsilateral kidney were recommended to take a renal function test before the surgery (Luo chenghua et al. 2016). In this study, the doses in the contralateral kidney were compressed hard in treatment planning. With the use of particle radiotherapy, the volume and doses of the contralateral kidney could be further spared from radiation. A total of four cases with a distance <5 mm (range: 0–3 mm) between CTV and the contralateral kidney were enrolled in this study. For these patients, the mean doses of the contralateral kidney were 0.61 ± 0.45 Gy (RBE) and 0.74 ± 0.41 Gy (RBE), which were 4.71 Gy (RBE) and 4.58 Gy (RBE) lower than the photon plans. The incidence of radiation nephritis was all lower than 0.001 in the four techniques by NTCP modeling. The phenomenon could be attributed to the parameters in this LKB model (Burman et al. 1991), which was regressed based on the patients with both normal kidneys and used 28 Gy as TD50/5 estimation.
Knowledge-based planning for oesophageal cancers using a model trained with plans from a different treatment planning system
Published in Acta Oncologica, 2020
Yoshihiro Ueda, Masayoshi Miyazaki, Iori Sumida, Shingo Ohira, Mikoto Tamura, Hajime Monzen, Haruhi Tsuru, Shoki Inui, Masaru Isono, Kazuhiko Ogawa, Teruki Teshima
For calculating normal tissue complication probability (NTCP) for lung, the formula with the Lyman–Kutcher–Burman model were used with biological evaluation in Eclipse. End point of this formula is pneumonitis (G ≥ 2). The TD50, m, n, and α/β were following values 26.8 Gy, 0.37, 0.999, and 3.0. The NTCP calculation for the lungs was influenced by the dose calculation algorithm used for inhomogeneity correction. For the lungs, we used a refitted TD50 estimation based on the CCC algorithm as per Hedin et al. [21].
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