Implementation of a new cost efficacy method for blood irradiation using a non dedicated device

<p>Abstract</p> <p>Objectives</p> <p>To implement a new cost efficacy internal Service for blood component irradiation, we carried out specific procedures and quality assurance reports using the linear accelerators (LINACs) of the Regina Elena Institute (IRE) Radiotherapy Department instead of a dedicated device.</p> <p>Methods</p> <p>The technical aspects, quality assurance and regulatory requirements of the internal procedure to set up a local irradiated blood bank have been defined. The LINACs of the IRE Radiotherapy Department were used to deliver a mean dose of 32 Gy and dose accuracy was checked with gafchromic film. The overall time/cost of this procedure was compared with the previous procedure, out-sourcing the irradiation of blood components.</p> <p>Results</p> <p>A total of 1996 blood component units were internally irradiated in the first year. Moreover, reducing the overall procedure time by a third. Overall cost/bag of external and internal procedures was approx. 66 € and 11 €, respectively. Thus the average saving of cost/bag was higher than 80%. The use of gafchromic films in all irradiated blood component bags allowed the accuracy of the dose delivered to blood to be checked.</p> <p>Conclusions</p> <p>By utilizing LINACs installed in the Radiotherapy Department it is possible to provide an internal blood component irradiation service, capitalizing on internal resources without any inconvenience/discomfort to patients undergoing radiotherapy and satisfying governmental regulatory requirements. The internal irradiation procedures has proven to be safe and feasible, and along with the significant cost/time reduction suggests that it is more advantageous than external procedures.</p

TP53 drives abscopal effect by secretion of senescence-associated molecular signals in non small cell lung cancer

Background Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay. Results We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors

Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years

<p>Abstract</p> <p>Background</p> <p>Accelerated hypofractionation is an attractive approach for adjuvant whole breast radiotherapy. In this study we evaluated the adverse effects at least 3 years post an accelerated hypofractionated whole breast radiotherapy schedule.</p> <p>Methods</p> <p>From October 2004 to March 2006, 39 consecutive patients aged over 18 years with pTis, pT1-2, pN0-1 breast adenocarcinoma who underwent conservative surgery were treated with an adjuvant accelerated hypofractionated radiotherapy schedule consisting of 34 Gy in 10 daily fractions over 2 weeks to the whole breast, followed after 1 week by an electron boost dose of 8 Gy in a single fraction to the tumour bed. Skin and lung radiation toxicity was evaluated daily during therapy, once a week for one month after radiotherapy completion, every 3 months for the first year and from then on every six months. In particular lung toxicity was investigated in terms of CT density evaluation, pulmonary functional tests, and clinical and radiological scoring. Paired t-test, Chi-square test and non-parametric Wilcoxon test were performed.</p> <p>Results</p> <p>After a median follow-up of 43 months (range 36-52 months), all the patients are alive and disease-free. None of the patients showed any clinical signs of lung toxicity, no CT-lung toxicity was denoted by radiologist on CT lung images acquired about 1 year post-radiotherapy, no variation of pulmonary density evaluated in terms of normalised Hounsfield numbers was evident. Barely palpable increased density of the treated breast was noted in 9 out of 39 patients (in 2 patients this toxicity was limited to the boost area) and teleangectasia (<1/cm²) limited to the boost area was evident in 2 out of 39 patients. The compliance with the treatment was excellent (100%).</p> <p>Conclusion</p> <p>The radiotherapy schedule investigated in this study (i.e 34 Gy in 3.4 Gy/fr plus boost dose of 8 Gy in single fraction) is a feasible and safe treatment and does not lead to adjunctive acute and late toxicities. A longer follow up is necessary to confirm these favourable results.</p

Multiple brain metastases radiosurgery with CyberKnife Device: dosimetric comparison between fixed/Iris and multileaf collimator plans

Purpose: In our institution, stereotactic radiosurgery of multiple brain metastases is performed with the CyberKnife® (CK) device, using fixed/Iris collimators. In this study, nineteen fixed/Iris plans were recalculated with the multileaf collimator (MLC), to assess if it is possible to produce plans with comparable dosimetric overall quality. Materials and Methods: For consistent comparisons, MLC plans were re-optimized and re-normalized in order to achieve the same minimum dose for the total planning target volume (PTVtot). Conformation number (CN), homogeneity index (HI) and dose gradient index (DGI) metrics were evaluated. The dose to the brain was evaluated as the volume receiving 12 Gy (V12) and as the integral dose (ID). The normal tissue complication probability (NTCP) for brain radionecrosis was calculated as a function of V12. Results: The reoptimized plans were reviewed by the radiation oncologist and were found clinically acceptable according to the The American Association of Physicists in Medicine (AAPM) Task Group-101 protocol. However, fixed/Iris plans provided significantly higher CN (+8.6%), HI (+2.2%), and DGI (+44.0%) values, and significantly lower ID values (−35.9%). For PTVtot less than the median value of 2.58cc, fixed/Iris plans provided significantly lower NTCP values. On the other side, MLC plans provided significantly lower treatment times (−18.4%), number of monitor units (−33.3%), beams (−46.0%) and nodes (−21.3%). Conclusions: CK-MLC plans for the stereotactic treatment of brain multi metastases could provide an important advantage in terms of treatment duration. However, to contain the increased risk for brain radionecrosis, it could be useful to calculate MLC plans only for patients with large PTVtot

Dose evaluation for skin and organ in hepatocellular carcinoma during angiographic procedure

Purpose: The purpose of this study is to evaluate the radiation dose in patients undergoing liver angiographic procedure and verify the usefulness of different dose measurements to prevent deterministic effects. Gafchromic film, MicroMOSFET data and DIAMENTOR device of the X-ray system were used to characterize the examined interventional radiology (IR) procedure. Materials and methods: A liver embolization procedure, the SIRT (Selective Internal Radiation Therapy), was investigated. The exposure parameters from the DIAMENTOR as well as patient and geometrical data were registered. Entrance skin dose map obtained using Gafchromic film (ESDGAF) in a standard phantom as well as in 12 patients were used to calculate the maximum skin dose (MSDGAF). MicroMOSFETs were used to assess ESD in relevant points/areas. Moreover, the maximum value of five MicroMOSFETs array, due to the extension of treated area and to the relative distance of 2–3 cm of two adjacent MicroMOSFETs, was useful to predict the MSD without interfering with the clinical practice. PCXMC vers.1.5 was used to calculate effective dose (E) and equivalent dose (H). Results: The mean dose-area product (DAPDIAMENTOR) for SIRT procedures was 166 Gycm2, although a wide range was observed. The mean MSDGAF for SIRT procedures was 1090 mGy, although a wide range was experienced. A correlation was found between the MSDGAF measured on a patient and the DAPDIAMENTOR value for liver embolizations. MOSFET and Gafchromic data were in agreement within 5% in homogeneous area and within 20% in high dose gradient regions. The mean equivalent dose in critical organs was 89.8 mSv for kidneys, 22.9 mSv for pancreas, 20.2 mSv for small intestine and 21.0 mSv for spleen. Whereas the mean E was 3.7 mSv (range: 0.5-13.7). Conclusions: Gafchromic films result useful to study patient exposure and determine localization and amplitude of high dose skin areas to better predict the skin injuries. Then, DAPDIAMENTOR or MOSFET data could offer real-time methods, as on-line dose alert, to avoid any side effects during liver embolization with prolonged duration

Toxicity and cosmesis outcomes after single fraction partial breast irradiation in early stage breast cancer

Abstract Background To report the clinical outcome after a Single Shot 3D-CRT PBI (SSPBI) in breast cancer patients after conservative surgery (ClinicalTrials.gov Identifier: NCT01316328). Methods A dose of 18Gy (in the first 4 patients) and 21Gy (in the remaining 60 patients) was prescribed in a single session and delivered to the index area (i.e. the area of breast including the primary tumor bed and the surrounding tissue) using 3D-CRT with patients in prone position. Acute and late toxicity was assessed using the National Cancer Institute's CTC for Adverse Events. Cosmesis was defined based on modified Harvard criteria. Differences between dosimetric or clinical parameters of patients with/without G2 or more late toxicity or unsatisfactory (poor or fair) cosmetic outcome were evaluated with the Mann-Whitney test. Odds ratios and 95% confidence interval were calculated for cosmesis and fibrosis. Univariate and multivariate analyses(UVA/MVA) were used to determine covariates associated with an increase in fibrosis or fat necrosis rate. Results Sixty four patients were enrolled. With a median follow-up of 3 years, G2 and G3 subcutaneous fibrosis was detected in 20(31%) and in 8(13%) patients, and ≥G2 fat necrosis was observed in 2(3%) patients. Good to excellent, fair and poor cosmesis was observed in 38(59%), 23(36%) and 3(5%) patients, respectively. Based on UVA, the breast volume receiving more than 21Gy (V21Gy) was found to be a predictor of the ≥G1 or ≥G2 fibrosis/fat necrosis. Based on MVA, V21Gy was confirmed as a predictor for ≥G1 fibrosis/fat necrosis, the results correlated as a trend for ≥G2. Cosmesis was correlated with whole breast (WB) mean dose (p = 0.030). Conclusion Our choice of a single dose of 21Gy significantly increased the treatment related toxicity. However, this should not discourage novel SSPBI approaches with lower equivalent doses.</p