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BackgroundWhole pelvis intensity modulated radiotherapy (IMRT) is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB) to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach.PurposeTo evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB) regression and motion during chemo-radiotherapy (CRT) for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met.Methods and materialsTen patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR) were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM) was used to evaluate the degree of motion. The Dice’s similarity coefficient (DSC) was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses.ResultsThe CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction between CTV-SIB reduction and OAR dose increase.ConclusionsThe CTV-SIB had important regression and motion during CRT, receiving lower therapeutic doses than expected. The OAR had unpredictable shifts and received higher doses. The use of SIB without frequent adaptation of the treatment plan exposes cervical cancer patients to an unpredictable risk of under-dosing the target and/or overdosing adjacent critical structures. In that scenario, brachytherapy continues to be the gold standard approach.

The lethal effects of mustard gas, di(2-chloroethyl) sulphide, in the albino rat have been counteracted by Thiocit, a mixture of sodium thiosulphate and trisodium citrate in the ratio 10: 1, administered intraperitoneally in a dose of 2.75 g./kg. Thiocit afforded complete protection against greater than the median lethal dose of mustard gas whether given 10 min. before or 10 min. after mustard gas and raised the LD50 of mustard gas by approximately three times. The protection appeared whether the total dose of Thiocit was given in one injection or serially over 30 min. The effective doses of sodium thiosulphate and of Thiocit in rats were of the order of 3.0 g./kg. Sodium thiosulphate alone and Thiocit have been administered in single doses by slow infusion, by stomach tube and in drinking water. Both have shown activity by all routes of administration, but activity was greatest by intraperitoneal injection. The use of Thiocit in conjunction with mustard gas therapy is suggested.Many attempts have been made to find a substance which offers effective protection against the systemic effects and death produced by poisoning with mustard gas, di(2-chloroethyl) sulphide. Numerous authors have demonstrated some alleviation of the local or systemic effects of mustard gas by cysteine and glutathione. Paulet and Chappet (1956) have discussed the more recent work and showed that phenylallylthiourea was as active as cysteine, but somewhat more effective than glutathione in reducing the severity of the leucopenia produced by sublethal injections of mustard gas into albino rats.In spite of this extensive search, however, little success has been achieved in protecting against lethal doses of mustard gas. A large number of thio compounds has been tested on the basis of theoretical bonding with, and high competition factor for, mustard gas (Ogston, 1948). Sodium thiosulphate has a high competition factor (2.7x 104), and has probably a relatively high permeability through the cell membrane; it is nontoxic in very high doses and theoretically could combine with mustard gas. Citrates also have a high competition factor (1.7 x 102) (Callaway and Pearce, unpublished observations) for mustard gas; they are natural constituents of body fluids and probably possess a fairly high permeability at the cellular level.These two compounds were therefore investigated for possible prophylactic or therapeutic effects against poisoning by mustard gas. Each was tried separately and also in combination as Thiocit by several routes against lethal doses of the mustard gas. METHODSSodium thiosulphate 500 mg./ml. and sodium citrate 100 mg./ml. were used in aqueous solution both for injection and for drinking purposes. Thiocit consisted of Na2S203,5H20 (50 g.) and NaC6HFO07,5H20 (5 g.) made up to 100 ml. with distilled water to give a total concentration of 550 mg./ml.Male albino rats of the Wistar strain weighing 190 to 215 g. were used. Mustard gas solution in propylene glycol was freshly prepared for each experiment, such that the volume injected in m...

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