Quantitative ultrasound radiomics analysis to evaluate lymph nodes in patients with cancer: a systematic review.

This systematic review aims to evaluate the role of ultrasound (US) radiomics in assessing lymphadenopathy in patients with cancer and the ability of radiomics to predict metastatic lymph node involvement. A systematic literature search was performed in the PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE (Ovid) databases up to June 13, 2023. 42 articles were included in which the lymph node mass was assessed with a US exam, and the analysis was performed using radiomics methods. From the survey of the selected articles, experimental evidence suggests that radiomics features extracted from US images can be a useful tool for predicting and characterizing lymphadenopathy in patients with breast, head and neck, and cervical cancer. This noninvasive and effective method allows the extraction of important information beyond mere morphological characteristics, extracting features that may be related to lymph node involvement. Future studies are needed to investigate the role of US-radiomics in other types of cancers, such as melanoma.

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.

Evaluation of a planar diode matrix for SRS patient-specific QA in comparison with GAFchromic films.

PURPOSE: We validate the routine use of a two-dimensional (2D) diode matrix for patient specific pre-treatment verification for Cyberknife (CK) stereotactic radiosurgery and to compare it with film dosimetry. MATERIALS AND METHOD: A total of 46 patients were selected according to the most frequent diseases treated at our institution with the CK system, that is, brain metastases, meningiomas, spine metastases, and prostate tumors. All cases were evaluated with GAFChromic EBT-3 films and SRS MapCHECK for Fixed cone, IRIS, and MLC collimators of the CK. RESULTS: The highest mean passing rate was observed for the SRS MapCHECK system compared to films. In order to assess if the two techniques provide statistically different results, a Wilcoxon Signed-Rank non-parametric test was performed (p < 0.05) and we found gamma values significantly lower for EBT-3 films with respect to the SRS MapCHECK. We noticed a moderately significant association between the two techniques using Spearman's rank correlation coefficient (rs > 0.4). We also performed the Bland-Altman statistical method: less than 5% of the differences resulted outside the range (mean ± 1.96 × SD), so the two methods can be considered interchangeable within the combined inaccuracy. CONCLUSIONS: The use of SRS MapCHECK for CK patient specific quality assurance (QA) is feasible for a variety of clinical districts and could be reliably used as a replacement for radiochromic films.

Stereotactic partial breast irradiation in primary breast cancer: A comprehensive review of the current status and future directions.

In selected low-risk breast cancer patients, accelerated partial breast irradiation (APBI) may represent an alternative option to the whole breast irradiation to reduce the volume of irradiated breast and total treatment duration. In the last few years, preliminary data from clinical trials showed that stereotactic partial breast radiotherapy may have the advantage to be less invasive compared to other APBI techniques, with preliminary good results in terms of local toxicity and cosmesis: the use of magnetic resonance, fiducial markers in the tumor bed, and new breast devices support both a precise definition of the target and radiation planning. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257856, identifier CRD42021257856.

Technical note: A wearable radiation measurement system for collection of patient-specific time-activity data in radiopharmaceutical therapy: system design and Monte Carlo simulation results.

PURPOSE: A high level of personalization in Molecular Radiotherapy (MRT) could bring advantages in terms of treatment effectiveness and toxicity reduction. Individual organ-level dosimetry is crucial to describe the radiopharmaceutical biodistribution expressed by the patient, to estimate absorbed doses to normal organs and target tissue(s). This paper presents a proof-of-concept Monte Carlo simulation study of "WIDMApp" (Wearable Individual Dose Monitoring Apparatus), a multi-channel radiation detector and data processing system for in vivo patient measurement and collection of radiopharmaceutical biokinetic data (i.e., time-activity data). Potentially, such a system can increase the amount of such data that can be collected while reducing the need to derive it via nuclear medicine imaging. METHODS: a male anthropomorphic MIRD phantom was used to simulate photons (i.e., gamma-rays) propagation in a patient undergoing a 131 I thyroid treatment. The administered activity was set to the amount usually administered for the treatment of differentiated carcinoma while its initial distribution in different organs was assigned following the ICRP indications for the 131 I biokinetics. Using this information, the simulation computes the Time-dependent Counts Curves (TCCs) that would have been measured by seven WIDMApp-like sensors placed and oriented to face each one of five emitting organs plus two thyroid lobes. A deconvolution algorithm was then applied on this simulated data set to reconstruct the Time-Activity Curve (TAC) of each organ. Deviations of the reconstructed TACs parameters from values used to generate them were studied as a function of the deconvolution algorithm initialization parameters and assuming non-Poisson fluctuation of the TCCs data points. RESULTS: This study demonstrates that it is possible, at least in the simple simulated scenario, to reconstruct the organ cumulated activity by measuring the time dependence of counts recorded by several detectors placed at selected positions on the patient's body. The ability to perform in vivo sampling more frequently than conventional biokinetic studies increases the number of time points and therefore the accuracy in TAC estimates. In this study, an accuracy on cumulated activity of 5% is obtained even with a 20% error on the TCC data points and a 50% error on the initial guess on the parameters of the deconvolution algorithm. CONCLUSIONS: the WIDMApp approach could provide an effective tool to characterize more accurately the radiopharmaceutical biokinetics in MRT patients, reducing the need of resources of nuclear medicine departments, such as technologist and scanner time, to perform individualized biokinetics studies. The relatively simple hardware for the approach proposed would allow its application to large numbers of patients. The results obtained justify development of an actual prototype system to characterize this technique under realistic conditions.

The role of dosimetry and biological effects in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study.

BACKGROUND: 223Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of α-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize 223Ra treatment. METHODS: Out of 20 mCRPC patients who underwent standard 223Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each 223Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar 223Ra images were obtained at 2-4 and 18-24 h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET/CT, PSA value and ALP while haematological parameters were evaluated weekly after 223Ra injection and 2 months after last cycle. RESULTS: 1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of 223Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics. CONCLUSIONS: This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate 223Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during 223Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose. TRIAL REGISTRATION: The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18-2111).

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.

The advantages of carbon fiber based orthopedic devices in patients who have to undergo radiotherapy.

BACKGROUND AND OBJECTIVES: The modern approach to primary and secondary muscular skeletal tumors is multidisciplinary. The right combination of chemotherapy, surgery and radiotherapy (RT) makes obtaining local and distant disease control more likely. When surgery is indicated, radiotherapy often has a fundamental role as an adjuvant treatment; however, the titanium alloy instrumentations interfere with Radiotherapy setting, decreasing its effectiveness. It is common opinion that carbon fiber-reinforced devices are convenient in case of adjuvant RT in muscular skeletal oncology. The aim of the study is to support this intuition with experimental data, verifying the more accurate estimation of the delivered dose during RT, comparing Carbon Fiber-Reinforced PEEK (CFRP) plates with titanium-alloy orthopedic devices in order to evaluate their effects on target volume identification and dose distribution for radiation treatment. METHODS: Phantoms were then irradiated with a linear accelerator Varian 2100 C/D with photon beams of 6 and 15 MV energies. Absorbed dose in the point of interest was verified by EBT3 gafchromic films above and below the two materials. Images from CT simulations were also analyzed in terms of Hounsfield numbers in patients with titanium and carbon fiber orthopedic implants in the spine or in the femur. RESULTS: For a 6 MV photon beam, the doses measured just under the titanium-alloy plate were less than approximately 20% of the value calculated by the TPS. For a 15 MV beam energy, these differences were slightly lower. Using CFRP plate, the difference between measured and calculated doses was within ±3% for both energies, which was comparable with the statistical uncertainties. In the cases of simulated treatment of humerus titanium implants, the difference varies in range ± 10% with hot spot of + 10% and cold spot of -15%. CONCLUSIONS: The use of CFRP for orthopedic devices and implants provides a valuable advantage in identifying the target due to the reduction of artifacts. Clear imaging of the soft tissues surrounding the bone is useful and reduces the discrepancies between calculated/delivered and measured doses, generating a more homogeneous dose distribution. Furthermore, there is a significant benefit in detecting the state of disease in CT imaging during the follow-up of treated patients. In-vivo studies are encouraged to verify whether a more effective radiotherapy leads to a decrease in local recurrence and local progression.

The effect of CELLFOODTM on radiotherapy or combined chemoradiotherapy: preclinical evidence.

BACKGROUND: Based on previous observations that the nutraceutical CELLFOOD™ (CF), the 'physiological modulator' that aimed to make oxygen available 'on demand', inhibits the growth of cancer cells, this study was designed to investigate the role of CF in the regulation of hypoxia-inducible factor 1 alpha (HIF1α) and its correlated proteins, phosphoglycerate kinase 1 and vascular endothelial growth factor. Our idea was that CF, acting on HIF1α, in combination with current anticancer therapies could improve their effectiveness. METHODS: To evaluate the effect of CF in association with radiotherapy and chemotherapy, different human cancer cell lines and mice with mesothelioma were analysed by tumour growth, clonogenic assay, western blot and immunohistochemical analysis. RESULTS: CF in combination with radiation with or without cisplatin increases the death rate of cancer cells. In vivo, 70% of mice treated with CF before the mesothelioma graft did not show any tumour growth, indicating a possible preventive effect of CF. Moreover, in mouse mesothelioma xenografts, CF improves the effect of radiotherapy also in combination with chemotherapy treatment. Immunohistochemical analysis of tumour explants showed that HIF1α expression was reduced by the combination of CF and radiotherapy treatment and even more by the combination of CF and radiotherapy and chemotherapy treatment. Mechanistically, CF increases the fraction of oxygenated cells, making the radiotherapy more effective with a greater production of reactive oxygen species (ROS) that in turn, reduce the HIF1α expression. This effect is amplified by further increase in ROS from chemotherapy. CONCLUSIONS: Collectively, results from preclinical trials suggest that CF could be a useful intervention to improve the efficacy of radiotherapy or combined treatment strategies and could be a promising treatment modality to counteract cancer.

Use of parallel-plate ionization chambers in reference dosimetry of NOVAC and LIAC® mobile electron linear accelerators for intraoperative radiotherapy: a multi-center survey.

PURPOSE: LIAC® and NOVAC are two mobile linear accelerators dedicated to intraoperative radiation therapy (IORT), generating electron beams in the energy range of 3-12 MeV. Due to high dose-per-pulse (up to 70 mGy per pulse), in 2003 the Italian National Institute of Health (ISS) stated that "for the measure of dose to water in reference conditions, ionization chambers cannot be employed and no published dosimetry protocol can be used". As a consequence, ferrous sulphate (or, alternatively alanine) dosimetry was recommended. Based on a retrospective multi-center survey, a comparison with ferrous sulphate dosimetry is now used to validate the parallel-plate ionization chambers for reference dosimetry of NOVAC and LIAC. METHODS: The IAEA TRS-398 dosimetry protocol was applied except for the reference irradiation setup and the determination of the ion-recombination correction factor ks . Moreover the depth of maximum dose (R100 ) instead of zref as measurement depth was chosen by the majority of centers, thus implying a renormalization of the beam-quality correction factor kQ,Qo , based on water-air stopping power ratios. Regarding the ks determination, a previously published method, independent of ferrous sulphate dosimetry, was adopted. All the centers participating in this study had used both ferrous sulphate dosimeters and ionization chambers in water phantoms for dosimetry under reference conditions. RESULTS: The mean percentage difference between ionization chambers and ferrous sulphate dosimetry was -0.5% with a dispersion of 3.9% (2σ). Moreover, the uncertainty analysis allowed the agreement between ionization chambers and ferrous sulphate dosimetry to be verified. These results did not show any significant dependence on electron energy, thus indirectly confirming kQ,Qo renormalization. The results from the centers using zref as the measurement depth were similar to the other data, but further focused studies could aim at investigating possible dependences of the dose differences on the chosen reference depth. CONCLUSION: The present study confirms that parallel-plate ionization chambers can properly and accurately substitute ferrous sulphate detectors in reference dosimetry of LIAC and NOVAC mobile linear accelerators. Therefore, we hope that the most commonly used protocols for reference dosimetry in external-beam radiotherapy will be updated in order to provide guidance in the calibration of electron beams from linear accelerators dedicated to IORT, so that users may benefit from specific, authoritative and up-to-date recommendations.

The Carbofix™ "Piccolo Proximal femur nail": A new perspective for treating proximal femur lesion. A technique report.

Metastases to proximal femur are common and surgery is often suggested to prevent fractures; otherwise it is necessary in cases where this has already occurred. Adjuvant radiotherapy is necessary to reduce the risk of local progression. Nevertheless, the success or failure of radiation therapy treatments depends upon the accuracy in which target identification is correct and dose prescription is fulfilled. Unfortunately, the use of titanium nails consistently limits radiation dose; indeed, the presence of ferromagnetic artifacts interferes with target identification. We present the technique for implant a new carbon fiber nail useful to reduce the ferromagnetic artifacts which allows a better adjuvant radiotherapy.

Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status.

PURPOSE: This study investigates whether the abscopal effect induced by radiation-therapy (RT) is able to sterilize non-irradiated tumour cells through bystander signals. MATERIAL AND METHODS: Wild-type (wt)-p53 or p53-null HCT116 human colon cancer cells were xenografted into both flanks of athymic female nude mice. When tumours reached a volume of 0.2 cm(3), irradiation was performed, under strict dose monitoring, with a dedicated mobile accelerator designed for intra-Operative-RT (IORT). A dose of 10 or 20 Gy (IR groups), delivered by a 10 MeV electron beam, was delivered to a tumour established in one side flank, leaving the other non-irradiated (NIR groups). A subset of mice were sacrificed early on to carry out short-term molecular analyses. RESULTS: All directly-irradiated tumours, showed a dose-dependent delayed and reduced regrowth, independent of the p53 status. Importantly, a significant effect on tumour-growth inhibition was also demonstrated in NIR wt-p53 tumours in the 20 Gy-irradiation group, with a moderate effect also evident after 10 Gy-irradiation. In contrast, no significant difference was observed in the NIR p53-null tumours, independent of the dose delivered. Molecular analyses indicate that p53-dependent signals might be responsible for the abscopal effect in our model system, via a pro-apoptotic pathway. CONCLUSIONS: We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells.

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.

Dosimetric and clinical advantages of deep inspiration breath-hold (DIBH) during radiotherapy of breast cancer.

BACKGROUND: To investigate the potential dosimetric and clinical benefits of Deep Inspiration Breath-Hold (DIBH) technique during radiotherapy of breast cancer compared with Free Breathing (FB). METHODS: Eight 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. RESULTS: For 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. CONCLUSION: Delivering 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.

Development and optimization of a beam shaper device for a mobile dedicated IOERT accelerator.

PURPOSE: The aim of this study was to design and build a prototype beam shaper to be used on a dedicated mobile accelerator that protects organs at risk within the radiation field and conforms the beam to the target geometry during intraoperative electron radiotherapy (IOERT). A dosimetric characterization of the beam shaper device was performed based on Monte Carlo (MC) simulations, as well as experimental data, at different energies, field sizes, and source to skin distances. METHODS: A mobile light intraoperative accelerator (LIAC(®), Sordina, Italy) was used. The design of the beam shaper prototype was based on MC simulations (BEAMnrc∕OMEGA and DOSXYZnrc code) for a selection of materials and thicknesses, as well as for dosimetric characterization. Percentage depth dose (PDD) and profile measurements were performed using a p-type silicon diode and a commercial water phantom, while output factors were measured using a PinPoint ion chamber in a PMMA phantom. Planar doses in planes of interest were carried out using radiochromic films (Gafchromic(TM) EBT and EBT2) in PMMA and in a Solid Water(®) phantom. Several experimental set-ups were investigated with the beam shaper device fixed on the top of the phantom, varying both the short side of the rectangular field and the air gap between the device and the phantom surface, simulating the clinical situation. The output factors (OFs) were determined using different geometrical set-ups and energies. RESULTS: The beam shaper prototype consists of four blades sliding alongside each other and mounted on a special support at the end of the 10 cm diameter PMMA circular applicator. Each blade is made of an upper layer of 2.6 cm of Teflon(®) and a lower layer of 8 mm of stainless steel. All rectangles inscribed in a 5 cm diameter can be achieved in addition to any "squircle-shaped" field. When one side of the rectangular field is held constant and the second side is reduced, both R(50) and R(max) move towards the phantom surface. Comparing the PDDs obtained with the 5 cm circular applicator and with a 4.4 × 4.4 cm(2) square field (that is the equivalent square of the 5 cm circular field) obtained with the beam shaper, a different behavior was observed in the region extending from the surface to a depth of 50% of the maximum dose. Isodoses measured for rectangular fields used for clinical cases (i.e., 4 × 9 cm(2) 8 MeV) are shown, with different air gaps. For each energy investigated, the normalized OFs slowly increase, when the length of the side decreases down to about 4 cm, and then rapidly decreases for smaller field widths. MC simulation showed an excellent agreement with experimental data (<2%). CONCLUSIONS: The beam shaper device is able to provide square∕rectangular∕squircle fields with adequate dose homogeneity for mobile dedicated accelerators, thus allowing conformal treatment with IOERT. Monte Carlo simulation can be a very useful tool to simulate any clinical set up and can be used to create a data set to calculate MUs, thereby increasing the accuracy of the delivered dose during IOERT procedures.

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

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 18 Gy (in the first 4 patients) and 21 Gy (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 21 Gy (V21 Gy) was found to be a predictor of the ≥G1 or ≥G2 fibrosis/fat necrosis. Based on MVA, V21 Gy 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 21 Gy significantly increased the treatment related toxicity. However, this should not discourage novel SSPBI approaches with lower equivalent doses.

Dose and polymorphic genes xrcc1, xrcc3, gst play a role in the risk of articledeveloping erythema in breast cancer patients following single shot partial breast irradiation after conservative surgery.

BACKGROUND: To evaluate the association between polymorphisms involved in DNA repair and oxidative stress genes and mean dose to whole breast on acute skin reactions (erythema) in breast cancer (BC) patients following single shot partial breast irradiation (SSPBI) after breast conservative surgery. MATERIALS AND METHODS: Acute toxicity was assessed using vers.3 criteria. single nucleotides polymorphisms(SNPs) in genes: XRCC1(Arg399Gln/Arg194Trp), XRCC3 (A4541G-5'UTR/Thr241Met), GSTP1(Ile105Val), GSTA1 and RAD51(untranslated region). SNPs were determined in 57 BC patients by the Pyrosequencing analysis. Univariate(ORs and 95% CI) and logistic multivariate analyses (MVA) were performed to correlate polymorphic genes with the risk of developing acute skin reactions to radiotherapy. RESULTS: After SSPBI on the tumour bed following conservative surgery, grade 1 or 2 acute erythema was observed in 19 pts(33%). Univariate analysis indicated a higher significant risk of developing erythema in patients with polymorphic variant wt XRCC1Arg194Trp, mut/het XRCC3Thr241Met, wt/het XRCC3A4541G-5'UTR. Similarly a higher erythema rate was also found in the presence of mut/het of XRCC1Arg194Trp or wt of GSTA1. Whereas, a lower erythema rate was observed in patients with mut/het of XRCC1Arg194Trp or wt of XRCC1Arg399Gln. The mean dose to whole breast(p = 0.002), the presence of either mut/het XRCC1Arg194Trp or wt XRCC3Thr241Met (p = 0.006) and the presence of either mut/het XRCC1Arg194Trp or wt GSTA1(p = 0.031) were confirmed as predictors of radiotherapy-induced erythema by MVA. CONCLUSIONS: The Whole breast mean dose together with the presence of some polymorphic genes involved in DNA repair or oxidative stress could explain the erythema observed after SSPBI, but further studies are needed to confirm these results in a larger cohort.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy and toxicity related to treatment of hepatocellular carcinoma with 90Y-SIR spheres: radiobiologic considerations.

UNLABELLED: 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 normal-tissue 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 >or=grade 2 (G2), >or=grade 3 (G3), and >or=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 >or=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 = 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.