Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation.

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.

A real-time system to report abnormal events involving staff in a nuclear medicine therapy unit.

A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient's room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.

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.

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.

Refinement & validation of rectal wall dose volume objectives for prostate hypofractionation in 20 fractions.

BACKGROUND AND PURPOSE: Dose-volume objectives for the rectum have been proposed to limit long term toxicity after moderately hypofractionated radiotherapy (MHRT) for localized prostate cancer. The purpose of the present study is to validate and possibly refine dose volume objective for the rectal wall after 20-fraction MHRT. MATERIALS AND METHODS: All patients treated by 20-fraction MHRT at a single Institution were identified and relative rectal wall (%RW) DVH retrieved. The endpoint of the study is the development of grade 2+ late rectal bleeding (LRB) according to a modified RTOG scale. Clinical and dosimetric predictors of LRB were investigated at both uni- and multi-variable analysis. RESULTS: 293 patients were identified and analyzed. Of them, 35 (12%) developed the endpoint. At univariable analysis, antithrombotic drug usage (yes vs no), technique (3DCRT vs IMRT/VMAT) and several %RW DVH cut-points were significantly correlated with LRB. However, within patients treated by 3DCRT (N = 106), a bi-variable model including anti-thrombotic drug usage and selected %RW dose/volume metrics failed to identify independent dosimetric predictors of LRB. Conversely, within patients treated with intensity modulation (N = 187), the same model showed a progressively higher impact of the percent of RW receiving doses above 40 Gy. Based on this model, we were able to confirm (V32), refine (V60) and identify a novel (V50) cut-point for the %RW. CONCLUSION: We recommend the following dose volume objectives for the %RW in order to minimize the risk of LRB after 20-fraction MHRT: V32 ≤ 50%; V50 ≤ 25.8% and V60 ≤ 10%.

Absorbed dose measurements from a 90Y radionuclide liquid solution using LiF:Mg,Cu,P thermoluminescent dosimeters.

In the last few years there has been an increasing interest in the measurement of the absorbed dose from radionuclides, with special attention devoted to molecular radiotherapy treatments. In particular, the determination of the absorbed dose from beta emitting radionuclides in liquid solution poses a number of issues when dose measurements are performed using thermoluminescent dosimeters (TLD). Finite volume effect, i.e. the exclusion of radioactivity from the volume occupied by the TLD is one of these. Furthermore, TLDs need to be encapsulated into some kind of waterproof envelope that unavoidably contributes to beta particle attenuation during the measurement. The purpose of this study is twofold: I) to measure the absorbed dose to water, Dw, using LiF:Mg,Cu,P chips inside a PMMA cylindrical phantom filled with a homogenous 90YCl3 aqueous solution II) to assess the uncertainty budget related to Dw measurements. To this purpose, six cylindrical PMMA phantoms were manufactured at ENEA. Each phantom can host a waterproof PMMA stick containing 3 TLD chips encapsulated by a polystyrene envelope. The cylindrical phantoms were manufactured so that the radioactive liquid environment surrounds the whole stick. Finally, Dw measurements were compared with Monte Carlo (MC) calculations. The measurement of absorbed dose to water from 90YCl3 radionuclide solution using LiF:Mg,Cu,P TLDs turned out to be a viable technique, provided that all necessary correction factors are applied. Using this method, a relative combined standard uncertainty in the range 3.1-3.7% was obtained on each Dw measurement. The major source of uncertainty was shown to be TLDs calibration, with associated uncertainties in the range 0.7-2.2%. Comparison of measured and MC-calculated absorbed dose per emitted beta particle provided good results, with the two quantities being in the ratio 1.08.

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.

Short course hypofractionated whole breast irradiation after conservative surgery: a single institution phase II study.

BACKGROUND: To assess the oncologic outcomes of hypofractionated whole breast irradiation (Hypo-WBI). METHODS: Eligible patients had undergone breast conservative surgery for early breast cancer (pTis-2) and none/limited nodal involvement. Hypo-WBI consisted of 34 Gy in 10 daily fractions over 2 weeks to the whole breast three-dimensional conformal radiotherapy (3DCRT), followed by a single fraction of 8 Gy to the tumor bed after 1 week (electrons). Primary endpoint is freedom from ipsilateral breast tumor recurrence (IBTR). Minimum follow up for living & event-free patients is 3 yrs.; median follow up time of the whole analyzed patient population is 5.4 yrs. (range: 1.8-11.4 yrs). RESULTS: Two hundred fifty-one patients were accrued from 2004 to 2013. All patients underwent local excision of the primary tumor to negative margins. Four patients failed in the ipsilateral breast after a median time of 3.2 years (range: 1.7-5.7 yrs) for a 5-year IBTR-free survival of 98.7% (95%CI: 97.3%-100%). IBTR-free survival was significantly higher for patients with invasive cancer than for patients with intraductal carcinoma (p = 0.036). Within patients with invasive tumors, no clear trends or associations were detected between IBTR and age, grading, molecular subtype, pT or pN stage. At 5 years, the actuarial rates of GR2 fibrosis and GR2+ teleangectasia are 2.4% (95%CI: 0-6.5%) and 7.1% (95%CI: 0.4-13.7%), respectively. Cosmesis was scored as excellent/good by ≈95% of patients and ≈60% of clinicians. CONCLUSIONS: Hypo-WBI in 3 weeks allows excellent oncologic outcomes for invasive breast cancer after conservative surgery. Patients with intraductal carcinoma should be treated with Hypo-WBI only within a controlled study. TRIAL REGISTRATION: IRE-IFO Ethical and Scientific Committee (cod. RS61/04).

Phantom validation of quantitative Y-90 PET/CT-based dosimetry in liver radioembolization.

BACKGROUND: PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment. RESULTS: Our results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach. Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties. CONCLUSIONS: Patient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y-PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation.

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.

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.

Dose escalation using ultra-high dose IMRT in intermediate risk prostate cancer without androgen deprivation therapy: preliminary results of toxicity and biochemical control.

BACKGROUND: To investigate the feasibility of dose escalation (86 Gy at 2 Gy/fraction) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer without androgen deprivation therapy. METHODS: Patients with histologically proven adenocarcinoma of the prostate, intermediate prognostic category, were enrolled in this study. Early and late toxicity were scored according to the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0. Treatment outcome was stated in terms of biochemical failure, biopsy result and clinical failure. RESULTS: 39 patients with a median follow-up of 71 months were analyzed. No patient experienced G3 or G4 acute gastrointestinal (GI) or genitourinary (GU) toxicity. G2 acute GI and GU toxicity were observed in 17 (44%) and 20 (51%) patients, respectively. Fourteen patients (36%) did not experience acute GI toxicity and 4 patients (10%) did not experience acute GU toxicity. G2 late GI bleeding occurred in 7 of 39 patients (18%). Both G3 and G4 late GI toxicity were seen only in one patient (2.5%). Two patients (5%) experienced G2 late GU toxicity, while G3 late GU toxicity occurred in 3 patients (8%). The 5-year actuarial freedom from biochemical failure (FFBF) was 87%. Thirty-four patients (87%) did not show biochemical relapse. Seventeen patients (44%) underwent biopsy two year after radiotherapy; of these only two were non-negative and both did not show evidence of biochemical disease. CONCLUSIONS: IMRT treatment of patients with localized intermediate-risk prostate cancer at high dose levels without using androgen deprivation therapy (ADT) seems to give good disease control. Nevertheless, future trials should aim at further decreasing toxicity by exploiting image guidance techniques and by reducing the dose delivered at the interface between organs at risk and prostate.

Tissue heterogeneity in IMRT dose calculation for lung cancer.

The aim of this study was to evaluate the differences in accuracy of dose calculation between 3 commonly used algorithms, the Pencil Beam algorithm (PB), the Anisotropic Analytical Algorithm (AAA), and the Collapsed Cone Convolution Superposition (CCCS) for intensity-modulated radiation therapy (IMRT). The 2D dose distributions obtained with the 3 algorithms were compared on each CT slice pixel by pixel, using the MATLAB code (The MathWorks, Natick, MA) and the agreement was assessed with the γ function. The effect of the differences on dose-volume histograms (DVHs), tumor control, and normal tissue complication probability (TCP and NTCP) were also evaluated, and its significance was quantified by using a nonparametric test. In general PB generates regions of over-dosage both in the lung and in the tumor area. These differences are not always in DVH of the lung, although the Wilcoxon test indicated significant differences in 2 of 4 patients. Disagreement in the lung region was also found when the Γ analysis was performed. The effect on TCP is less important than for NTCP because of the slope of the curve at the level of the dose of interest. The effect of dose calculation inaccuracy is patient-dependent and strongly related to beam geometry and to the localization of the tumor. When multiple intensity-modulated beams are used, the effect of the presence of the heterogeneity on dose distribution may not always be easily predictable.

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.

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.

Analysis of salivary flow and dose-volume modeling of complication incidence in patients with head-and-neck cancer receiving intensity-modulated radiotherapy.

PURPOSE: To investigate dose-volume effects of salivary flow and the functional recovery over time, using salivary function data and different models of normal tissue complication probability (NTCP). METHODS AND MATERIALS: A total of 59 patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT) were analyzed in the present study. The toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale and salivary flows, both unstimulated (USF) and stimulated (SSF). The assessments were done before radiotherapy (RT) and at 3, 6, 12, 18, and 24 months after RT. Grade 3 toxicity was the primary endpoint. Analyses of toxicity incidence at 3, 6, and 12 months after RT were performed by both the Lyman-Kutcher-Burman (LKB) and relative seriality (S) models. RESULTS: A significant correlation was found between the incidence of Grade 3 toxicity and the incidence of patients with a reduction in SSF to <25% of the pre-RT value. Better correlations resulted between the RTOG toxicity score and the dosimetric parameters, compared with USF/SSF. The TD(50), assessed by the LKB model, was 21.4, 27.8, and 41.6 Gy at 3, 6, and 12 months after RT, respectively. The TD(50), assessed by the S model, was 20.0, 26.3, and 40.0 Gy at 3, 6, and 12 months after RT, respectively. CONCLUSION: Recovery of salivary gland function vs. time after RT took place mostly within 1 year after RT. The RTOG Grade 3 was a reliable score to perform the NTCP modeling. The choice of NTCP model had no influence on the accuracy of predictions.

Intraoperative radiation therapy as an "early boost" in locally advanced head and neck cancer: preliminary results of a feasibility study.

BACKGROUND: The acute toxicity of intraoperative radiation therapy (IORT) delivered as an "early boost" after tumor resection in patients with locally advanced head and neck cancer was evaluated. METHODS: Twenty-five patients were enrolled in the study. All patients underwent surgery with radical intent, and 17 had microvascular flap reconstruction. The IORT was delivered in the operating room. Twenty patients received adjuvant external beam radiation therapy (EBRT). RESULTS: Five patients experienced various degrees of complications in the postoperative period, all of which were treated conservatively. One patient had a partial flap necrosis after EBRT that was treated with flap removal. Six deaths were recorded during the mean follow-up period of 8 months; none of the deaths were related to radiation treatment. CONCLUSION: This feasibility study shows that the use of IORT as an early boost is feasible with no increase in acute toxicity directly attributable to radiation.