Skin DVHs predict cutaneous toxicity in Head and Neck Cancer patients treated with Tomotherapy.

PURPOSE: To explore the association between planning skin dose-volume data and acute cutaneous toxicity after Radio-chemotherapy for Head and Neck (HN) cancer patients. METHODS: Seventy HN patients were treated with Helical Tomotherapy (HT) with radical intent (SIB technique: 54/66 Gy to PTV1/PTV2 in 30fr) ±â€¯chemotherapy superficial body layer 2 mm thick (SL2) was delineated on planning CT. CTCAE v4.0 acute skin toxicity data were available. Absolute average Dose-Volume Histograms (DVH) of SL2 were calculated for patients with severe (G3) and severe/moderate (G3/G2) skin acute toxicities. Differences against patients with none/mild toxicity (G0/G1) were analyzed to define the most discriminative regions of SL2 DVH; univariable and multivariable logistic analyses were performed on DVH values, CTV volume, age, sex, chemotherapy. RESULTS: Sixty-one % of patients experienced G2/G3 toxicity (rate of G3 = 19%). Differences in skin DVHs were significant in the range 53-68Gy (p-values: 0.005-0.01). V56/V64 were the most predictive parameters for G2/G3 (OR = 1.12, 95%CI = 1.03-1.21, p = 0.001) and G3 (OR = 1.13, 95%CI = 1.01-1.26, p = 0.027) with best cut-off of 7.7cc and 2.7cc respectively. The logistic model for V56 was well calibrated being both, slope and R2, close to 1. Average V64 were 2.2cc and 6cc for the two groups (G3 vs G0-G2 toxicity); the logistic model for V64 was quite well calibrated, with a slope close to 1 and R2 equal to 0.60. CONCLUSION: SL2 DVH is associated with the risk of acute skin toxicity. Constraining V64 < 3cc (equivalent to a 4x4cm2 skin surface) should keep the risk of G3 toxicity below or around 10%.

Comprehensive Intra-Institution stepping validation of knowledge-based models for automatic plan optimization.

PURPOSE: To develop and apply a stepping approach for the validation of Knowledge-based (KB) models for planning optimization: the method was applied to the case of concomitant irradiation of pelvic nodes and prostate + seminal-vesicles bed irradiation in post-prostatectomy patients. METHODS: The clinical VMAT plans of 52 patients optimized by two reference planners were selected to generate a KB-model (RapidPlan, v.13.5 Varian). A stepping-validation approach was followed by comparing KB-generated plans (with and without planner-interaction, RP and only-RP respectively) against delivered clinical plans (RA). The validation followed three steps, gradually extending its generalization: 20 patients used to develop the model (closed-loop); 20 new patients, same planners (open-loop); 20 new patients, different planners (wide-loop). All plans were compared, in terms of relevant dose-volume parameters and generalized equivalent uniform dose (gEUD). RESULTS: KB-plans were generally better than or equivalent to clinical plans. For RPvsRA, PTVs coverage was comparable, for OARs RP was always better. Comparing only-RPvsRA, PTVs coverage was always better; bowel\bladder V50Gy and D1%, bowel\bladder\rectum Dmean, femoral heads V40Gy and penile bulb V50Gy were significantly improved. For RPvsRA gEUD reduction >1 Gy was seen in 80% of plans for rectum, bladder and bowel; for only-RPvsRA, this was found in 50% for rectum/bladder and in 70% for bowel. CONCLUSION: An extensive stepping validation approach of KB-model for planning optimization showed better or equal performances of automatically generated KB-plan compared to clinical plans. The interaction of a planner further improved planning performances.

PET textural features stability and pattern discrimination power for radiomics analysis: An "ad-hoc" phantoms study.

PURPOSE: The analysis of PET images by textural features, also known as radiomics, shows promising results in tumor characterization. However, radiomic metrics (RMs) analysis is currently not standardized and the impact of the whole processing chain still needs deep investigation. We characterized the impact on RM values of: i) two discretization methods, ii) acquisition statistics, and iii) reconstruction algorithm. The influence of tumor volume and standardized-uptake-value (SUV) on RM was also investigated. METHODS: The Chang-Gung-Image-Texture-Analysis (CGITA) software was used to calculate 39 RMs using phantom data. Thirty noise realizations were acquired to measure statistical effect size indicators for each RM. The parameter η2 (fraction of variance explained by the nuisance factor) was used to assess the effect of categorical variables, considering η2 < 20% and 20% < η2 < 40% as representative of a "negligible" and a "small" dependence respectively. The Cohen's d was used as discriminatory power to quantify the separation of two distributions. RESULTS: We found the discretization method based on fixed-bin-number (FBN) to outperform the one based on fixed-bin-size in units of SUV (FBS), as the latter shows a higher SUV dependence, with 30 RMs showing η2 > 20%. FBN was also less influenced by the acquisition and reconstruction setup:with FBN 37 RMs had η2 < 40%, only 20 with FBS. Most RMs showed a good discriminatory power among heterogeneous PET signals (for FBN: 29 out of 39 RMs with d > 3). CONCLUSIONS: For RMs analysis, FBN should be preferred. A group of 21 RMs was suggested for PET radiomics analysis.

Deformable registration-based segmentation of the bowel on Megavoltage CT during pelvic radiotherapy.

During pelvic radiotherapy bowel loops (BL) are subject to inter-fraction changes. MVCT images have the potential to provide daily bowel segmentation. We assess the feasibility of deformable registration and contour propagation in replacing manual BL segmentation on MVCT. Four observers delineated BL on the planning kVCT and on one therapy MVCT in eight patients. Inter-observer variations in BLs contouring were quantified using DICE index. BLs were then automatically propagated onto MVCT by a commercial software for image deformation and subsequently manually corrected. The agreement between propagated BL/propagated+manually corrected BL vs manual were quantified using the DICE. Contouring times were also compared. The impact on DVH of using the deformable-registration method was assessed. The same procedures were repeated on high-resolution planning-kVCT and therapy-kVCT. MVCTs are adequate to visualize BL (average DICE: 0.815), although worse than kVCT (average DICE:0.889). When comparing propagated vs manual BL, a poor agreement was found (average DICE: 0.564/0.646 for MVCT/KVCT). After manual correction, average DICE indexes increased to 0.810/0.897. The contouring time was reduced to 15min with the semi-automatic approach from 30min with manual contouring. DVH parameters of propagated BL were significantly different from manual BL (p<0.0001); after manual correction, no significant differences were seen. MVCT are suitable for BL visualization. The use of a software to segment BL on MVCT starting from BL-kVCT contours was feasible if followed by manual correction. The method resulted in a substantial reduction of contouring time without detrimental effect on the quality of bowel segmentation and DVH estimates.

PET guidance in prostate cancer radiotherapy: Quantitative imaging to predict response and guide treatment.

Positron emission tomography (PET) allows a monitoring and recording of the spatial and temporal distribution of molecular/cellular processes for diagnostic and therapeutic applications. The aim of this review is to describe the current applications and to explore the role of PET in prostate cancer management, mainly in the radiation therapy (RT) scenario. The state-of-the art of PET for prostate cancer will be presented together with the impact of new specific PET tracers and technological developments aiming at obtaining better imaging quality, increased tumor detectability and more accurate volume delineation. An increased number of studies have been focusing on PET quantification methods as predictive biomarkers capable of guiding individualized treatment and improving patient outcome; the sophisticated advanced intensity modulated and imaged guided radiation therapy techniques (IMRT/IGRT) are capable of boosting more radioresistant tumor (sub)volumes. The use of advanced feature analyses of PET images is an approach that holds great promise with regard to several oncological diseases, but needs further validation in managing prostate diseases.

The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for Head and Neck Cancers.

The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman's test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this "dose volume grouping" parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor.

Quality assurance of rapid arc treatments: performances and pre-clinical verifications of a planar detector (MapCHECK2).

The purpose of this study is to evaluate the use of MapCHECK2 in a patient-specific quality assurance (QA) procedure for Rapid Arc (RA) radiotherapy and to obtain reference values of gamma index (γ) for different irradiation geometries. Dose distributions of 386 patients, optimized with Eclipse treatment planning system for RA on Varian Clinac 2300IX were exported and measured with MapCHECK2 detector array inserted in a MapPHAN dedicated phantom. Gamma index analysis was used to evaluate differences between calculated and delivered doses; collected data were analysed on the basis of complexity of plans and type of disease. Angular dependence and dose drift of detectors were estimated. The overall mean passing rate (percentage of points with γ < 1) was equal to 97.0% ± 3.1%; plan-specific evaluation of %γ < 1 showed significant differences among different treatment protocols (pancreas 98.6% ± 1.5%, prostate 96.6% ± 2.8% and rectum 92.8% ± 5.7%). MapCHECK2 demonstrated a strong angular dependence over a restricted range of angles (90° ± 5° and 270° ± 5°); this condition affected the result of pre-treatment QA only for plans with intense lateral fluence. The drift of diode array response due to the accumulated dose was found to be comparable with the manufacturer's declaration (0.5% per 1000 Gy). MapCHECK2 proved to be a useful and accurate tool in the process of patient-specific QA for RA treatment. Excluding the irradiation geometries with a high contribution of lateral fluence, the mean percentage of cases with γ-index > 95% equal to 90.3% was obtained instead of 81.7% including all plans.

Elastic registration based on particle filter in radiotherapy images with brain deformations.

This paper presents the evaluation of the accuracy of an elastic registration algorithm, based on the particle filter and an optical flow process. The algorithm is applied in brain CT and MRI simulated image datasets, and MRI images from a real clinical radiotherapy case. To validate registration accuracy, standard indices for registration accuracy assessment were calculated: the dice similarity coefficient (DICE), the average symmetric distance (ASD) and the maximal distance between pixels (Dmax). The results showed that this registration process has good accuracy, both qualitatively and quantitatively, suggesting that this method may be considered as a good new option for radiotherapy applications like patient's follow up treatment.

Automatic registration of PET and CT studies for clinical use in thoracic and abdominal conformal radiotherapy.

AIM: Implementation and validation of an automatic registration method based on mutual information (MI) for the integration of thoracic and abdominal positron emission tomography (PET)/computed tomography (CT) studies, with the purpose to facilitate in a clinical context the inclusion of PET metabolic information in conformal radiotherapy (RT). METHODS: Registration was obtained by modeling a rigid spatial transformation between CT and PET transmission studies. The registration method was based on Normalized Mutual Information (NMI), by iteratively transforming the PET volume, until its optimal alignment to the CT study is achieved, in correspondence of the maximum of NMI. To avoid entrapment in local maxima and to improve convergence speed we introduced a multiresolution scheme. Accuracy of the proposed approach was investigated in experimental data, relative to phantom and patient studies, acquired in conditions similar to clinical situations. RESULTS: In phantom studies the mean error in the 3D space is 3.6 mm (range 3-4 mm) in thoracic region and 3.2 mm (range 2.9-3.7 mm) in abdominal region, considerably less than PET spatial resolution. In patient studies the spatial mean error increases with respect to phantom studies (5.4 mm and 5.2 mm for thorax and abdomen, respectively) but remains comparable to the PET spatial resolution. The accuracy of spatial realignment was thus found adequate for the registration of PET/CT registration, if good patient repositioning was adopted. CONCLUSIONS: The proposed registration method, based on MI, was validated for the integration of PET/CT studies of patients candidate for thoracic and abdominal conformal RT. The method is automatic and provided with a user interface, thus suitable for clinical use.

Multi-modal medical image integration to optimize radiotherapy planning in lung cancer treatment.

This work presents a method for CT and PET image registration, and multi-modal analysis, to optimize radiotherapy planning in lung cancer treatment. The method relies on an image registration technique based on fiducial external markers to realign, spatially, PET images with the CT spatial reference system. The method was set up for clinical use in radiotherapy, allowing minimal modifications to be introduced in the management of patients undergoing radiation treatment. The accuracy of the registration technique was evaluated on patient studies in terms of Target Registration Error and was found to be less than 6.40 mm. The method was applied in the treatment planning of five patients affected by non-small-cell lung cancer, revealing the usefulness of PET/CT integration in delineating the extension of both the tumor mass and the tissues involved in the neoplastic process. Moreover, the functional information provided by PET often led to alterations in the treatment planning, changing the size and/or direction of radiation portals. The proposed method for PET/CT integration has been confirmed as being useful for optimizing radiotherapy planning in lung cancer treatment.

Fitting late rectal bleeding data using different NTCP models: results from an Italian multi-centric study (AIROPROS0101).

BACKGROUND AND PURPOSE: Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer. PATIENTS AND METHODS: Rectal dose-volume histograms of the rectum (DVH) and clinical records of 547 prostate cancer patients (pts) pooled from five institutions previously collected and analyzed were considered. All patients were treated in supine position with 3 or 4-field techniques: 123 patients received an ICRU dose between 64 and 70 Gy, 255 patients between 70 and 74 Gy and 169 patients between 74 and 79.2 Gy; 457/547 patients were treated with conformal RT and 203/547 underwent radical prostatectomy before RT. Minimum follow-up was 18 months. Patients were considered as bleeders if showing grade 2/3 late bleeding (slightly modified RTOG/EORTC scoring system) within 18 months after the end of RT. Four NTCP models were considered: (a) the Lyman model with DVH reduced to the equivalent uniform dose (LEUD, coincident with the classical Lyman-Kutcher-Burman, LKB, model), (b) logistic with DVH reduced to EUD (LOGEUD), (c) Poisson coupled to EUD reduction scheme and (d) relative seriality (RS). The parameters for the different models were fit to the patient data using a maximum likelihood analysis. The 68% confidence intervals (CI) of each parameter were also derived. RESULTS: Forty six out of five hundred and forty seven patients experienced grade 2/3 late bleeding: 38/46 developed rectal bleeding within 18 months and were then considered as bleeders The risk of rectal bleeding can be well calculated with a 'smooth' function of EUD (with a seriality parameter n equal to 0.23 (CI 0.05), best fit result). Using LEUD the relationship between EUD and NTCP can be described with a TD50 of 81.9 Gy (CI 1.8 Gy) and a steepness parameter m of 0.19 (CI 0.01); when using LOGEUD, TD50 is 82.2 Gy and k is 7.85. Best fit parameters for RS are s=0.49, gamma=1.69, TD50=83.1 Gy. Qualitative as well as quantitative comparisons (chi-squared statistics, P=0.005) show that the models fit the observed complication rates very well. The results found in the overall population were substantially confirmed in the subgroup of radically treated patients (LEUD: n=0.24 m=0.14 TD50=75.8 Gy). If considering just the grade 3 bleeders (n=9) the best fit is found in correspondence of a n-value around 0.06, suggesting that for severe bleeding the rectum is more serial. CONCLUSIONS: Different NTCP models fit quite accurately the considered clinical data. The results are consistent with a rectum 'less serial' than previously reported investigations when considering grade 2 bleeding while a more serial behaviour was found for severe bleeding. EUD may be considered as a robust and simple parameter correlated with the risk of late rectal bleeding.

Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma.

PURPOSE: To assess the impact on local control and survival of intraoperative radiotherapy (IORT) in resectable pancreatic adenocarcinoma. METHODS AND MATERIALS: The outcome of 127 patients surgically treated with curative intent combined with IORT was compared with the therapeutic results of 76 patients treated with surgery as exclusive treatment. RESULTS: Operative mortality and morbidity were similar in IORT and no-IORT patients. In 49 patients with locally limited disease (Stage I-II; LLD), IORT (n = 30) reduced the local failure rate and significantly prolonged time to local failure (TTLF), time to failure (TTF), and overall survival (OS) with respect to surgery alone (n = 19). The multivariate analyses, stratifying patients by age, tumor grade, resection margins, chemotherapy, and external-beam radiotherapy use, confirmed the independent impact of IORT on outcome. In patients with locally advanced disease (Stage III-IVA; LAD), IORT had an impact on local failure rate and on TTLF when combined with beam energies of greater than 6 MeV, whereas no effect on TTF and OS was observed. CONCLUSION: IORT did not increase operative mortality and morbidity and achieved a significant improvement in local control and outcome in patients with LLD. In patients with LAD, beam energies greater than 6 MeV prolonged TTLF.

Polarity effects of ionization chambers used in tbi dosimetry due to cable irradiation.

This paper presents the results of an investigation on polarity effects in total-body irradiation (TBI) dosimetry. Thimble (NE2571, 0.6 cc) and plane-parallel (Markus NE2534 0.055 cc) chambers were investigated in a 30 x 30 x 30-cm3 acrylic phantom in TBI conditions (6-MV x-rays). The thimble chamber was positioned at the midline and at the entrance and exit Dmax (1.5 cm from the phantom surface) levels. The Markus chamber, which is generally used for skin dose estimations, was positioned at various depths from the entrance surface of the phantom (from 0- to 2-cm depth). The polarity factor (Ppol) was defined as (Q+ + Q-)/2Q-, where Q+ and Q- were the collected charges at positive and negative bias voltage, respectively. The variations of Ppol with many parameters (absorbed dose, dose rate, the presence or absence of a 1-cm acrylic spoiler, irradiated cable length) were investigated. Results show that Ppol is quite small (within 1.002 for on-axis measurements and 1.005 for off-axis measurements) for the NE2571 chamber when the beam spoiler is placed. Ppol was significantly higher without the beam spoiler (within 1.008 for on-axis measurements, up to 1.02 for off-axis measurements). Concerning the Markus chamber, for on-axis skin dose measurements, Ppol was found to be less than unity (around 0.988) or more than unity (around 1.0035), respectively, with and without the beam spoiler. Possible "directional effects" of the currents generated in the cable were investigated for both chambers and found to be insignificant. This shows that the application of Ppol correction has to be considered a reliable procedure in minimizing these effects. When the beam spoiler is placed, the cable has to be drawn to minimize the portion of cable just outside the beam; if this is not the case, Ppol may significantly vary (for the NE2571 chamber values up to 1.0035 were found for on-axis measurements).

Quality assurance by systematic in vivo dosimetry: results on a large cohort of patients.

BACKGROUND: In vivo dosimetry is widely considered to be an important tool for quality assurance in external radiotherapy. INTRODUCTION: In this study we report on our experience over more than 4 years in systematic in vivo dosimetry with diodes. MATERIALS AND METHODS: From November '94 an in vivo entrance dosimetry check was performed for every new patient irradiated at one of our treatment units (Linac 6/100, 6 MV X-rays). Diodes were calibrated in terms of entrance dose; appropriate correction factors had been previously assessed (taking SSDs, field width, wedge, oblique incidence and blocking tray into account) and were individually applied to in vivo diode readings. The in vivo measured entrance dose was compared with the expected one, with a 5% action level; if a larger deviation was found, all treatment parameters were verified, and the in vivo dosimetry check was repeated. During the period November '94-May '99, 2824 measurements on 1433 patients were collected. RESULTS: Nine out of 1433 (0.63%) serious systematic errors (leading to a 5% or more on the delivered dose to the PTV) were detected by in vivo dosimetry; four out of nine would produce a 10% or more error if not detected. The rate of serious systematic errors detected by an independent check of treatment chart and MU calculation was found to be 1.5%, showing that less than 1/3 of the errors escapes this check. One hundred and twelve out of 1433 (7.8%) patients had more than one check: the rate of second checks was significantly higher for breast patients (31/250, 12.4%) against non-breast patients (81/1183, 6.8%, P=0.003). A number of patients demonstrated a persistent relatively large error even after two or more checks. For almost all patients the cause of the deviation was assessed; the most frequent cause was the difficulty in correctly positioning the patient and/or the diode. When analyzing the distribution of the deviations between measured and expected entrance doses (excluding first checks in the case of repetition of the in vivo dosimetry control) the mean deviation was 0.4% with a standard deviation equal to 3.0%. The rates of deviations larger than 5 and 7% were 9.9 and 2.6%, respectively. When considering the same data taking the average deviation in the case of opposed beams, the SD became 2.6% and the rates of deviations larger than 5 and 7%, respectively, 5.2 and 0.8%. When dividing the beams according to their orientation, significantly higher rates of large deviations (>5 and 7%) were found for oblique and posterior-anterior (PA) fields against lateral and anterior-posterior (AP) fields (P<0.05). Similarly, higher rates of large deviations were found for wedged fields against unwedged fields (P<0.03) and for blocked fields against unblocked fields (P<0.01). When dividing the data according to the anatomical district, accuracy was worse for breast (mean deviation 0.1%, 1 SD: 3.5%) and neck AP-PA fields (mean deviation 1%, 1 SD: 3,4%). Better accuracy was found for vertebrae (0.1%, 1 SD 2. 1%) and brain patients (-0.7%, 1 SD: 2.6%). During the considered period, in vivo dosimetry was also able to promptly detect a systematic error caused by a wrong resetting of the simulator height couch indicator, with a consequent error in the estimate of patient thickness of about 4 cm. CONCLUSIONS: In our experience, systematic in vivo dosimetry demonstrated to be a valid tool for quality assurance, both in detecting systematic errors which may escape the data transfer/MU calculation check and in giving an effective way of estimating the accuracy of treatment delivery.

Conformal irradiation of concave-shaped PTVs in the treatment of prostate cancer by simple 1D intensity-modulated beams.

BACKGROUND: In the case of concave-shaped PTVs including prostate (P) and seminal vesicles (SV), intensity-modulated radiation therapy (IMRT) should improve the therapeutic ratio of the treatment of prostate cancer. PURPOSE: Comparing IMRT by simple 1D modulations with conventional 3D conformal therapy (i.e. non-IMRT) in the treatment of concave-shaped PTVs including P+SV. MATERIALS AND METHODS: For five patients having a concave-shaped PTV (P+SV) previously treated at our Institute with conformal radiotherapy, conventional 3- and 4-fields conformal plans were compared with IMRT plans in terms of biological indices. IMRT plans were generated by using five equi-spaced beams with a partial shielding of the rectum obtainable with our single-absorber modulation technique (Fiorino C, Lev A, Fusca M, Cattaneo GM, Rudello F, Calandrino R. Dynamic beam modulation by using a single dynamic absorber. Phys. Med. Biol. 1995;40:221-240). The modulation was one-dimensional and the shape of the beams was at single minimum in correspondence with the 'core' of the rectum; the beam intensity in the minimum was set equal to 20 or 40% of the open beam intensity. All plans were simulated on the CADPLAN TPS using a pencil-beam based algorithm (with 18 MV X-rays). Tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) (for rectum, bladder and femoral head) were calculated for all situations when varying the isocentre dose from 60 to 90 Gy. Dose distributions were corrected taking dose fractionation into account through the linear-quadratic model; for the TCP/NTCP estimations the Webb-Nahum and the Lyman-Kutcher models were respectively applied. Three different scores were considered: (a) increase of TCP while keeping rectum NTCP equal to 5% (TCP(5%)); (b) increase of the uncomplicated tumour control probability (P+); (c) increase of the biological-based scoring function (S+), developed by Mohan et al. (Mohan R, Mageras GS, Baldwin B, Clinically relevant optimization of 3D conformal treatments. Med. Phys. 1992;19:933-944). The impact of the uncertainty in the knowledge of the parameters of the biological models was investigated for TCP(5%). RESULTS: (a) The average gain in TCP(5%) when considering IMRT against non-IMRT conformal plans was 7.3% (range 5.0-13.5%); (b) the average increase of P+ was 3.4% (range: 1. 0-8.5%); and (c) the average increase of S+ was 5.4% (range 2.9-12. 4%). The largest gain was found for one patient (patient 5) showing a significantly larger overlapping between PTV and rectum. CONCLUSIONS: Simple 1D-IMRT may clearly improve the therapeutic ratio in the treatment of concave-shaped PTVs including P and SV. In the range of clinically suitable values, the impact of the uncertainty of the parameters n and sigma(alpha) does not significantly alter the main results concerning the gain in TCP(5%). The reported gain in terms of P+ and S+ should be considered with great caution because of the intrinsic uncertainties of the model's parameters and, for bladder, because the 'true' DVH (considering variations of the shape and dimension due to variable filling) may be very different from the DVH calculated on a single CT scan. Further investigations should consider inversely-optimised 1D and 2D-IMRT plan in order to compare them in terms of cost-benefit.

In-vivo dosimetry by diode semiconductors in combination with portal films during TBI: reporting a 5-year clinical experience.

BACKGROUND AND PURPOSE: In-vivo dosimetry is vital to assure an accurate delivery of total body irradiation (TBI). In-vivo lung dosimetry is strongly recommended because of the risk of radiation-induced interstitial pneumonia (IP). Here we report on our 5-year experience with in-vivo dosimetry using diodes in combination with portal films and assessing the effectiveness of in-vivo dosimetry in improving the accuracy of the treatment. Moreover, we wished to investigate in detail the possibility of in-vivo portal dosimetry to yield individual information on the lung dose and to evaluate the impact of CT planning on the correspondence between stated and in-vivo measured doses. MATERIALS AND METHODS: From March 1994 to March 1999, 229 supine-positioned patients were treated at our Institute with TBI, using a 6 MV X-rays opposed lateral beam technique. 146 patients received 10 Gy given in three fractions, once a day (FTBI), shielding the lungs by the arms; 70 received 12-13.2 Gy, given in 6-11 fractions, 2-3 fractions per day (HFTBI): in this case about 2/3 of the lungs were shielded by moulded blocks (mean shielded lung dose equal to 9 or 9.5 Gy). Thirteen patients received 8 Gy given in a single fraction (SFTBI, lung dose: 7 Gy). For all HFTBI and FTBI patients, midline in-vivo dosimetry was performed at the first fraction by positioning two diodes pairs (one at entrance and one at the exit side) at the waist (umbilicus) and at the pelvis (ankles). If at least one of the two diodes doses (waist-pelvis) was outside +/-5% from the prescribed dose, actions could be initiated, together with possible checks on the following fractions. Transit dosimetry by portal films was performed for most patients; for 165 of them (117 and 48, respectively for FTBI and HFTBI) the midline in-vivo dose distribution of the chest region was derived and mean lung dose assessed. As a CT plan was performed for all HFTBI patients, for these patients, the lung dose measured by portal in-vivo dosimetry was compared with the expected value. RESULTS: Concerning all diodes data, 528 measurements were available: when excluding the data of the first fraction(s) of the patients undergoing corrections (n = 392), mean and SD were respectively 0.0% and 4.5% (FTBI: -0.3 +/- 4.8%; HFTBI: 0.4 +/- 3.9%). In total 105/229 patients had a change after the first fraction and 66/229 were controlled by in-vivo dosimetry for more than one fraction. Since January 1998 a CT plan is performed for FTBI patients too: when comparing the diodes data before and after this date, a significant improvement was found (i.e. rate of deviations larger than 5% respectively equal to 30.7% and 13.1%, P = 0.007). When considering only the patients with a CT plan, the global SD reduced to 3.5%. Concerning transit dosimetry data, for FTBI, the mean (midline) lung dose was found to vary significantly from patient to patient (Average 9.13 +/- 0.81 Gy; range 7.4-11.4 Gy); for the HFTBI patients the mean deviation between measured and expected lung dose was 0.0% (1 SD = 3.8%). CONCLUSIONS: In vivo dosimetry is an effective tool to improve the accuracy of TBI. The impact of CT planning for FTBI significantly improved the accuracy of the treatment delivery. Transit dosimetry data revealed a significant inter-patient variation of the mean lung dose among patients undergoing the same irradiation technique. For patients with partial lung shielding (HFTBI), an excellent agreement between measured and expected lung dose was verified.

Dosimetric evaluation of a commercial 3-D treatment planning system using Report 55 by AAPM Task Group 23.

BACKGROUND AND PURPOSE: A relevant part of radiotherapy treatment planning system QA concerns dose calculation verification. Report 55 by AAPM TG-23 is an instrument for performing dosimetric evaluation of treatment planning systems in case of external photon beams. It was employed by different groups in three radiotherapy departments for controlling performances of RTPS CadPlan Varian-Dosetek, versions 2.7.9, 3.0.6 and 3.1.1. MATERIALS AND METHODS: Once the basic data of the AAPM 4 MV and 18 MV X-ray units had been converted into the CadPlan format and the AAPM units configured, the whole set of TG23 tests were carried out on three different systems. According to Report 55, comparisons between values measured by TG-23 and calculated by RTPS were made in terms of dose at selected points and radiological field width at different depths. RESULTS: As far as dose is concerned, 266 data were compared for 4 MV and 297 for 18 MV. Ninety-five-point-nine percent of dose deviations for 4 MV and 92.6% for 18 MV are less than 2%. Most of the relevant discrepancies for both energies occur in a test case where dose has to be calculated under a long narrow block centred on the beam axis. Deviations as much as 6.1% for 4 MV and -7.5% for 18 MV were observed in points at 1 cm depth under the block. Poor results were also observed in the rectangular field 25 x 5, in points outside the field edges under collimators. As regards radiological field width, 58 out of 64 comparisons for 4 MV occurred in the range +/- 2 mm. For 18 MV the biggest deviation was -2.2 mm. CONCLUSIONS: The TG-23 tests demonstrated that the accuracy of the RTPS in dose calculation is good in most of the typical radiotherapy applications. Our results are better than those recently published for other RTPS. The TG-23 package turned out to be an effective instrument for QA and calculation verification, as well as being a powerful method for training purpose in configuring and using a RTPS.

Use of dose-volume histograms and biophysical models to compare 2D and 3D irradiation techniques for non-small cell lung cancer.

For non-small cell lung cancer (NSCLC), unsatisfactory local control (LC) still remains an important cause of failure. It has been suggested that improved LC can be achieved with both higher radiation dosage and adequate target coverage. Modern three-dimensional treatment planning systems (3D-TPSs) offer many tools for planning optimization. Biophysical models, which estimate the normal tissue complication probability (NTCP), are gaining in importance in comparing plans. This study compares conventional two-dimensional (2D) with 3D irradiation techniques using parameters related to volumetric dose distribution and two different biophysical models predicting normal tissue tolerance to radiotherapy (RT). Nine patients with inoperable locally advanced NSCLC were treated with a beam's eye view-based 3D technique. For the same patients, a conventional treatment was simulated; the irradiation geometry and beam contour were fully defined at the simulator and then transferred to the 3D-TPS to calculate the dose distribution. Both techniques gave the same prescribed dose at the reference point. Dose-volume histograms (DVHs) and dose statistics of organs at risk (OARs) (heart, lung(s), parenchyma lung, spinal cord and oesophagus) were analysed. The probability of side effects was estimated using two different biophysical models: the integrated normal ("empirical") model and the relative seriality model. Apart from contralateral lung, the 3D irradiation technique significantly reduced the average mean doses to all OARs. The current analysis suggests that in the treatment of locally advanced NSCLC, the use of 3D irradiation techniques allows a large sparing of OARs; this advantage is confirmed by both dose statistics analysis and NTCP values.

[Integration of computerized tomography imaging with single photon emission in a commercial system for developing radiotherapy fields: application to conformational irradiation for lung carcinoma]. / Integrazione delle immagini della Tomografia Computerizzata con emissione di fotone singolo in un sistema commerciale per l'elaborazione dei piani di radioterapia: applicazione all'irradiazione conformazionale del carcinoma polmonare.

PURPOSE: Single photon emission computed tomography (SPECT) of lung perfusion permits to map functioning lung parenchyma with higher sensitivity than CT. Delivering higher radiation doses is used to increase local control in lung carcinoma; this strategy is based on radiobiological and clinical studies. Lung parenchyma is a dose-limiting tissue in patients irradiated for lung cancer. Functional mapping based on SPECT and CT findings permits to design radiation beams such as to minimize irradiation of functioning lung. MATERIAL AND METHODS: CT and SPECT were used to examine a patient with non small cell lung carcinoma (stage IIIB, T4N0, left lung) candidate to conformal irradiation. Images were spatially correlated based on lung contours and using CT findings as reference. SPECT images were normalized to mean right lung value and expressed as perfusion (functional) contours. CT images and perfusion contours were transferred to the treatment planning system (Cadplan V 2.79, Varian-Dosetek Oy): in this way both functional (SPECT) and anatomical (CT) data were available for planning. A comparison was made between two irradiation techniques defined at TPS with (technique B) or without (technique A) SPECT contour information. The prescribed dose was 70.2 Gy. Rival plans were compared using dose volume histograms of target and risk organs. Both functional and anatomical regions were considered in the lung, together with single lung(s) and lung parenchyma. A second perfusion SPECT was obtained 5 months after irradiation and correlated with pretreatment CT images. RESULTS: SPECT lung scans showed marked heterogeneity in the left lung, which was found neither at CT nor at classic lung function tests. The lung volume with perfusion exceeding 80% of average corresponds to about 70% of the anatomical volume. Mean doses to anatomical and to functional lung parenchyma were 24 Gy and 19 Gy, respectively, with technique A and 23 Gy and 18 Gy, respectively, with technique B. Thirty-five percent and 20%, respectively of anatomical and functional lung parenchyma received > or = 25 Gy (V25) with technique B. The figure for functional lung parenchyma was reduced by 5% with technique B. Optimal design of irradiation field geometry decreased the area of functional parenchyma given high doses, which sparing was greater with smaller irradiation volumes. CONCLUSIONS: We have integrated the functional data provided by SPECT lung perfusion into a commercial irradiation planning system. Lung function mapping permits to design irradiation portals sparing larger areas of functional lung parenchyma.

Dosimetry of Gamma Knife and linac-based radiosurgery using radiochromic and diode detectors.

In stereotactic radiosurgery the choice of appropriate detectors, whether for absolute or relative dosimetry, is very important due to the steep dose gradient and the incomplete lateral electronic equilibrium. For both linac-based and Leksell Gamma Knife radiosurgery units, we tested the use of calibrated radiochromic film to measure absolute doses and relative dose distributions. In addition a small diode was used to estimate the relative output factors. The data obtained using radiochromic and diode detectors were compared with measurements performed with other conventional methods of dosimetry, with calculated values by treatment planning systems and with data prestored in the treatment planning system supplied by the Leksell Gamma Knife (LGK) vendor. Two stereotactic radiosurgery techniques were considered: Leksell Gamma Knife (using gamma-rays from 60Co) and linac-based radiosurgery (LR) (6 MV x-rays). Different detectors were used for both relative and absolute dosimetry: relative output factors (OFs) were estimated by using radiochromic and radiographic films and a small diode; relative dose distributions in the axial and coronal planes of a spherical polystyrene phantom were measured using radiochromic film and calculated by two different treatment planning systems (TPSs). The absolute dose at the sphere centre was measured by radiochromic film and a small ionization chamber. An accurate selection of radiochromic film was made: samples of unexposed film showing a percentage standard deviation of less than 3% were used for relative dose profiles, and for absolute dose and OF evaluations this value was reduced to 1.5%. Moreover a proper calibration curve was made for each set of measurements. With regard to absolute doses, the results obtained with the ionization chamber are in good correlation with radiochromic film-generated data, for both LGK and LR, showing a dose difference of less than 1%. The output factor evaluations, performed using different methods, are in good agreement with a maximum difference of 1.5% for all field sizes considered (LGK and LR) except the 4 mm helmet used in the LGK unit. In this case, differences exist between diode and radiochromic film measurements and both detectors show data values larger than the prestored OF value of 0.80. Dose profiles measured by radiochromic film and calculated are in excellent agreement for both LGK and LR with a maximum deviation of less than 1.0 mm, when full widths of the dose profiles at 20%, 50%, 80% levels are considered. When external photon beams are used in stereotactic radiosurgery, the 'well selected' radiochromic films are very accurate detectors both for relative and absolute dosimetry. The experimental results, obtained using both radiochromic and diode detectors, show that the 4 mm helmet relative output factor could be underestimated.