Radioactive 90 Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normaltissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively. Methods: Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of 99m Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the 90 Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood. Results: Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6-78 Gy), the $grade 2 (G2), $grade 3 (G3), and $grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the $G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44-61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18-0.60), assuming n 5 1. Conclusion: The radiobiologic approach, based on patient-specific dosimetry, could improve the 90 Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.

BackgroundTo investigate the potential dosimetric and clinical benefits of Deep Inspiration Breath-Hold (DIBH) technique during radiotherapy of breast cancer compared with Free Breathing (FB).MethodsEight left-sided breast cancer patients underwent a supervised breath hold during treatment. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for conventional tangential fields, utilizing 6 or 15 MV photon fields. The resulting dose–volume histograms were calculated, and the volumes of heart/lung irradiated to given doses were assessed. The left anterior descending coronary artery (LAD) mean and maximum doses were calculated, together with tumour control probability (TCP) and normal tissue complication probabilities (NTCP) for lung and heart.ResultsFor all patients a reduction of at least 16% in lung mean dose and at least 20% in irradiated pulmonary volumes was observed when DIBH was applied. Heart and LAD maximum doses were decreased by more than 78% with DIBH. The NTCP values for pneumonitis and long term cardiac mortality were also reduced by about 11% with DIBH. The NTCP values for pericarditis were zero for both DIBH and FB.ConclusionDelivering radiation in DIBH conditions the dose to the surrounding normal structures could be reduced, in particular heart, LAD and lung, due to increased distance between target and heart, and to reduced lung density.

The use of plane parallel ionization chambers with electron beams with high dose per pulse entails dose uncertainties due to the overestimation of the ion recombination factor, k, up to 20% if conventional dosimetric protocols are used. In this work MD-55-2 radiochromic films have been used as reference dosimeters to obtain dose to water per pulse DGAF(w) values for three Novac7 (Hitesys) electron beams of E0 = 5.8 MeV. However, the beam calibration by MD-55-2 films is time consuming and the use of plane parallel chambers is fundamental for a periodic quality control procedure. Three plane parallel chambers have been used and the general formula for the k determination has been tested using the calibration doses, DGAF(w). In particular, consistent ion recombination factors ksat(V0) (with the ion chamber polarized at V0), that follow the Boag theory, have been estimated at different dose per pulse values for the three plane parallel ionization chambers. This means that at present any ion chamber needs a specific ksat (V0) determination by using a reference dosimeter for which the response is independent of the dose rate. An accurate determination of ksat(V0), using a reference quality beam, can be used to determine the dose to water per pulse for electron beams of different quality and geometrical configuration.

No abstract

We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells.