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.

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.

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.

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.

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.

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.

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.

Radiation protection measurements around a 12 MeV mobile dedicated IORT accelerator.

PURPOSE: The aim of this study is to investigate radioprotection issues that must be addressed when dedicated accelerators for intraoperative radiotherapy (IORT) are used in operating rooms. Recently, a new version of a mobile IORT accelerator (LIAC Sordina SpA, Italy) with 12 MeV electron beam has been implemented. This energy is necessary in some specific pathology treatments to allow a better coverage of thick lesions. At an electron energy of 10 MeV, leakage and scattered x-ray radiation (stray radiation) coming from the accelerator device and patient must be considered. If the energy is greater than 10 MeV, the x-ray component will increase; however, the most meaningful change should be the addition of neutron background. Therefore, radiation exposure of personnel during the IORT procedure needs to be carefully evaluated. METHODS: In this study, stray x-ray radiation was measured and characterized in a series of spherical projections by means of an ion chamber survey meter. To simulate the patient during all measurements, a polymethylmethacrylate (PMMA) slab phantom with volume 30 x 30 x 15 cm3 and density 1.19 g / cm3 was used. The PMMA phantom was placed along the central axis of the beam in order to absorb the electron beams and the tenth value layer (TVL) and half value layer (HVL) of scattered radiation (at 0 degrees, 90 degrees, and 180 degrees scattering angles) were also measured at 1 m of distance from the phantom center. Neutron measurements were performed using passive bubble dosimeters and a neutron probe, specially designed to evaluate ambient dose equivalent H*(10). RESULTS: The x-ray equivalent dose measured at 1 m along the beam axis at 12 MeV was 260 microSv/Gy. The value measured at 1 m at 90 degrees scattering angle was 25 microSv/Gy. The HVL and TVL values were 1.1 and 3.5 cm of lead at 0 degrees, and 0.4 and 1 cm at 90 degrees, respectively. The highest equivalent dose of fast neutrons was found to be at the surface of the phantom on the central beam axis (2.9 +/- 0.6 microSv/Gy), while a lower value was observed below the phantom (1.6 +/- 0.3 microSv/Gy). The neutron dose equivalent at 90 degrees scattering angle and on the floor plane on the beam axis below the beam stopper was negligible. CONCLUSIONS: Our data confirm that neutron exposure levels around the new dedicated IORT accelerator are very low. Mobile shielding panels can be used to reduce x-ray levels to below regulatory levels without necessarily providing permanent shielding in the operating room.

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.

Phase I-II study of intraoperative radiation therapy (IORT) after radical prostatectomy for prostate cancer.

PURPOSE: Recent studies have suggested an alpha/beta ratio in prostate cancer of 1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues. Therefore the administration of a single, intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer. MATERIALS AND METHODS: Between February 2002 and June 2004, 34 patients with localized prostate cancer with only one risk factor (Gleason score > or =7, Clinical Stage [cT] > or =2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without clinical evidence of lymph node metastases were treated with radical prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose-finding procedure based on the Fibonacci method was employed. Dose levels of 16, 18, and 20 Gy were selected, which are biologically equivalent to total doses of about 60-80 Gy administered with conventional fractionation, using an alpha/beta ratio value of 3. RESULTS: At a median follow-up of 41 months, 24 (71%) patients were alive with an undetectable PSA value. No patients died from disease, whereas 2 patients died from other malignancies. Locoregional failures were detected in 3 (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field. A PSA rise without local or distant disease was observed in 7 (21%) cases. The overall 3-year biochemical progression-free survival rate was 77.3%. CONCLUSIONS: Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose.

DVHs evaluation in brain metastases stereotactic radiotherapy treatment plans.

PURPOSE: The aim of this work is to report a retrospective study of radiobiological indicators based on Dose-Volume Histograms analysis obtained by stereotactic radiotherapy treatments. METHODS AND MATERIALS: Fifty-five patients for a total of sixty-seven brain metastases with a mean target volume of 8.49 cc were treated by Dynamic Conformal Arc Therapy (DCAT) and Intensity-Modulated Stereotactic Radiotherapy (IMRST). The Delivered prescription dose was chosen on the basis of tumor size and location so as to ensure a 100% isodose coverage to the target volume. RESULTS: The treatment plans reported a mean value of 10% and 2.19% for the inhomogeneity and conformal index, respectively. The F factor showed we overdosed sixty-three patients delivering an additional 7% dose more than calculated values. The radiobiological parameters: TCP and NTCP showed a complete tumor control limiting the organs at risk damage. CONCLUSION: One goal of stereotactic radiotherapy is to design a treatment plan in which the steep dose gradient achievable minimizes the amount of radiation delivered outside the tumor region. This technique allows to deliver a much larger dose to the target without exceeding the radiation-related tolerance of normal tissues and improving patients' quality of life.

Relationships between rectal wall dose-volume constraints and radiobiologic indices of toxicity for patients with prostate cancer.

PURPOSE: The purpose of this article was to investigate how exceeding specified rectal wall dose-volume constraints impacts on the risk of late rectal bleeding by using radiobiologic calculations. METHODS AND MATERIALS: Dose-volume histograms (DVH) of the rectal wall of 250 patients with prostate cancer were analyzed. All patients were treated by three-dimensional conformal radiation therapy, receiving mean target doses of 80 Gy. To study the main features of the patient population, the average and the standard deviation of the distribution of DVHs were generated. The mean dose , generalized equivalent uniform dose formulation (gEUD), modified equivalent uniform dose formulation (mEUD)(0), and normal tissue complication probability (NTCP) distributions were also produced. The DVHs set was then binned into eight classes on the basis of the exceeding or the fulfilling of three dose-volume constraints: V(40) = 60%, V(50) = 50%, and V(70) = 25%. Comparisons were made between them by , gEUD, mEUD(0), and NTCP. RESULTS: The radiobiologic calculations suggest that late rectal toxicity is mostly influenced by V(70). The gEUD and mEUD(0) are risk factors of toxicity always concordant with NTCP, inside each DVH class. The mean dose, although a reliable index, may be misleading in critical situations. CONCLUSIONS: Both in three-dimensional conformal radiation therapy and particularly in intensity-modulated radiation therapy, it should be known what the relative importance of each specified dose-volume constraint is for each organ at risk. This requires a greater awareness of radiobiologic properties of tissues and radiobiologic indices may help to gradually become aware of this issue.

Setup verification and in vivo dosimetry during intraoperative radiation therapy (IORT) for prostate cancer.

The purpose of this study was to check the setup and dose delivered to the patients during intraoperative electron beam radiation therapy (IORT) for prostate cancer. Twenty eight patients underwent IORT after radical prostatectomy for prostate cancer by means of a dedicated mobile accelerator, Novac7 (by Hitesys, SpA, Italy). A 9 MeV electron beam at high dose per pulse was used. Eighteen patients received IORT at escalating doses of 16, 18, and 20 Gy at 85% isodose, six patients for each dose level. Further, ten patients received 20 Gy at 85% isodose. The electron applicator position was checked in all cases by means of two orthogonal images obtained with brilliance intensifier. Target and organ at risk doses were measured in vivo by a MOSFETs dosimetry system. MOSFETs and microMOSFET dosimeters were inserted into sterile catheters and directly positioned into the rectal lumen, for ten patients, and into the bladder to urethra anastomosis, in the last 14 cases. Verification at 0 degree led to very few adjustments of setup while verifications at 90 degrees often suggested to bring the applicator closer to the target. In vivo dosimetry showed an absorbed dose into the rectum wall < or =1% of the total dose. The average dose value inside the anastomosis, for the 12 patients analyzed, was 23.7 Gy with a standard deviation of +/-7.6%, when the prescription was 20 Gy at 85% isodose. Using a C-arm mobile image intensifier, it is possible to assess if the positioning is correct and safe. Radio-opaque clips and liquid were necessary to obtain good visible images. In vivo MOSFETs dosimetry is feasible and reliable. A satisfactory agreement between measured and expected doses was found.

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.

A study of the effect of setup errors and organ motion on prostate cancer treatment with IMRT.

PURPOSE: To assess the influence of setup errors and organ motion in terms of the probability of tumor control and normal-tissue complications by tumor control probability and normal-tissue complication probability. METHODS AND MATERIALS: Twelve patients were treated for prostate cancer with intensity-modulated radiation therapy. Two orthogonal portal images were taken daily. All patients underwent three computed tomography scans during the 8-week treatment time (i.e., baseline, intermediate, and final). The original treatment plans were re-evaluated, taking into account setup errors and organ motion. RESULTS: The mean shifts +/- standard deviation of the whole patient population in the lateral, anterior-posterior, and craniocaudal direction were 1.0 +/- 1.5 mm, 0.9 +/- 2.1 mm, and 1.9 +/- 2.1 mm, respectively. In most of the recalculated dose-volume histograms, the coverage of clinical target volume was granted despite organ motion, whereas the rectal wall histograms were often very different from the planned ones. CONCLUSION: We have studied the impact of prostate and rectum motion, as well as setup errors, on dose-volume histograms. The estimate of these effects may have implications for predictive indications when planning intensity-modulated radiation therapy treatments on prostate.

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.

In vivo dosimetry with MOSFETs: dosimetric characterization and first clinical results in intraoperative radiotherapy.

PURPOSE: To investigate the use of metal oxide silicon field effect transistors (MOSFETs) as in vivo dosimetry detectors during electron beams at high dose-per-pulse intraoperative radiotherapy. METHODS AND MATERIALS: The MOSFET system response in terms of reproducibility, energy, dose rate and temperature dependence, dose-linearity from 1 to 25 Gy, angular response, and dose perturbation was analyzed in the 6-9-MeV electron beam energy range produced by an intraoperative radiotherapy-dedicated mobile accelerator. We compared these with the 6- and 9-MeV electron beams produced by a conventional accelerator. MOSFETs were also used in clinical dosimetry. RESULTS: In experimental conditions, the overall uncertainty of the MOSFET response was within 3.5% (+/-SD). The investigated electron energies and the dose rate did not significantly influence the MOSFET calibration factors. The dose perturbation was negligible. In vivo dosimetry results were in accordance with the predicted values within +/-5%. A discordance occurred either for an incorrect position of the dosimeter on the patient or when a great difference existed between the clinical and calibration setup, particularly when performing exit dose measurements. CONCLUSION: Metal oxide silicon field effect transistors are suitable for in vivo dosimetry during intraoperative radiotherapy because their overall uncertainty is comparable to the accuracy required in target dose delivery.