FDG PET-derived parameters as prognostic tool in progressive malignant pleural mesothelioma treated patients.

PURPOSE: The value of FDG PET-derived parameters in predicting overall survival (OS), local relapse-free survival (LRFS) and distant relapse-free survival (DRFS) in treated patients with malignant pleural mesothelioma (MPM) was evaluated. METHODS: This retrospective evaluation included 55 MPM patients treated between March 2006 and February 2015 with FDG PET/CT-guided salvage helical tomotherapy (HTT) after previous surgery plus chemotherapy. Univariate Cox regression analysis was performed to assess the impact of the following FDG PET-derived parameters: biological target volume (BTV), mean and maximum standardized uptake values (SUVmean/max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured using different uptake thresholds (40%, 50% and 60%). Logistic regression was then performed to identify the best FDG PET-derived parameters for selecting patients with poorer survival. RESULTS: The median OS was 9.1 months (range 0.0 - 69.6 months) after the end of HTT; 54/55 patients were dead at the last follow-up. BTV and TLG40, TLG50 and TLG60 were the most significant predictors of OS (p < 0.005). The median OS was 4.8 months in patients with MTV60 >5 cm3 and TLG40 >334.4, compared with 13.8 months and 16.1 months in patients with smaller values, respectively. The median LRFS and DRFS were 6.2 months (range 1.2 - 39.4 months) and 6.5 months (0.0 - 66.4 months), respectively. TLG40, TLG50 and TLG60 were significantly correlated with LRFS (p < 0.015). Median DRFS was 6.4 months in patients with MTV40 >39.6 cm3 and 6.2 months in patients with TLG40 >334.4, compared with 17 months and 18.8 months in patients with smaller values. BTV, TLG40 and MTV40 were also found to be good predictors in patients with poor OS/LRFS/DRFS (median survival times less than the median values). CONCLUSION: FDG PET-derived parameters effectively discriminated patients with a poor prognosis and may be helpful in the selection of MPM patients for salvage HTT.

Could early tumour volume changes assessed on morphological MRI predict the response to chemoradiation therapy in locally-advanced rectal cancer?

AIM: To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. RESULTS: Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%). CONCLUSION: MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.

BriXS, a new X-ray inverse Compton source for medical applications.

MariX is a research infrastructure conceived for multi-disciplinary studies, based on a cutting-edge system of combined electron accelerators at the forefront of the world-wide scenario of X-ray sources. The generation of X-rays over a large photon energy range will be enabled by two unique X-ray sources: a Free Electron Laser and an inverse Compton source, called BriXS (Bright compact X-ray Source). The X-ray beam provided by BriXS is expected to have an average energy tunable in the range 20-180 keV and intensities between 1011 and 1013 photon/s within a relative bandwidth ΔE/E=1-10%. These characteristics, together with a very small source size (~20 µm) and a good transverse coherence, will enable a wide range of applications in the bio-medical field. An additional unique feature of BriXS will be the possibility to make a quick switch of the X-ray energy between two values for dual-energy and K-edge subtraction imaging. In this paper, the expected characteristics of BriXS will be presented, with a particular focus on the features of interest to its possible medical applications.

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.

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%.

Measurement and control of the air contamination generated in a medical cyclotron facility for PET radiopharmaceuticals.

The aim of this paper is to report the data concerning the contamination of the exhausted air from the hot cells dedicated to the large-scale synthesis of positron emission tomography (PET) radiopharmaceuticals. Two cyclotrons are currently operating in Ospedale San Raffaele for the routine production of C and F. They are linked with four radiochemistry laboratories by means of shielded radioisotope delivery lines. The above labs are dedicated both to the large scale preparation and to the research and development of PET radiopharmaceuticals. The department hosts four CT-PET scanners, which operate with a mean patient workload of 40 per day. Radiosyntheses are performed using automated modules located in 10 hot cells. The air outlets are monitored online by a 2-inch NaI(Tl) counter in a Marinelli geometry counting volume. Contamination values up to 10(5) Bq L(-1) have been measured at the hot cell exit point during the synthesis. The corresponding concentrations at the point of release in atmosphere are largely above the threshold of 1.29 Bq L(-1), defined by national regulations as the limit for free environmental release. A shielded gas storage system controlled by a dedicated, customized software program has thus been installed to prevent the potentially hazardous release of gaseous radioactive contaminants. The system has allowed us to maintain the effective dose to neighboring population groups below the limit of 10 muSv y(-1).

Validation of a method for "dose of the day" calculation in head-neck tomotherapy by using planning ct-to-MVCT deformable image registration.

PURPOSE: The aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT). METHODS: For each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences <2% of the prescribed dose (DD2%) and 2D/3D gamma-index values (2%-2mm) were assessed respectively with Mapcheck SNC Patient software (Sun Nuclear) and with 3D-Slicer. RESULTS: On average, 87.9%±1.2% of voxels were found for DD2% (on average 27 slices available for each patient) and 94.6%±0.8% of points passed the 2D gamma analysis test while the 3D gamma test was satisfied in 94.8%±0.8% of body's voxels. CONCLUSIONS: This study represents the first demonstration of the dosimetric accuracy of kVCT-to-MVCT DIR for dose of the day computations. The suggested method is sufficiently fast and reliable to be used for daily delivered dose evaluations in clinical strategies for adaptive Tomotherapy of HN cancer.

Decommissioning procedures for an 11 MeV self-shielded medical cyclotron after 16 years of working time.

The present article describes the decommissioning of a compact, self-shielded, 11 MeV medical cyclotron. A Monte Carlo simulation of the possible nuclear reactions was performed in order to plan the decommissioning activities. In the course of the cyclotron dismantling, cyclotron components, shields, and floor concrete samples were measured. Residual activities were analyzed with a Ge(Li) detector and compared with simulation data. Doses to staff involved in the decommissioning procedure were monitored by individual TL dosimeters. The simulations identified five radioactive nuclides in shields and floor concrete: 55Fe and 45Ca (beta emitters, total specific activity: 2.29 x 10(4) Bq kg) and 152Eu, 154Eu, 60Co (gamma emitters, total specific activity: 1.62 x 10(3) Bq kg-1). Gamma-ray spectrometry confirmed the presence of gamma emitters, corresponding to a total specific activity of 3.40 x 10(2) Bq kg-1. The presence of the radioisotope 124Sb in the lead contained in the shield structure, corresponding to a simulated specific activity of 9.38 x 10(3) Bq kg-1, was experimentally confirmed. The measured dose from external exposure of the involved staff was <20 muSv, in accordance with the expected range of values between 10 and 20 muSv. The measured dose from intake was negligible. Finally, the decommissioning of the 11 MeV cyclotron does not represent a risk for the involved staff, but due to the presence of long-lived radioisotopes, the cyclotron components are to be treated as low level radioactive waste and stored in an authorized storage area.

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.

Moderate Hypofractionation with Simultaneous Integrated Boost in Prostate Cancer: Long-term Results of a Phase I-II Study.

AIMS: To report 5 year outcome and late toxicity in prostate cancer patients treated with image-guided tomotherapy with a moderate hypofractionated simultaneous integrated boost approach. MATERIALS AND METHODS: In total, 211 prostate cancer patients, 78 low risk, 53 intermediate risk and 80 high risk were treated between 2005 and 2011. Intermediate- and high-risk patients received 51.8 Gy to pelvic lymph nodes and concomitant simultaneous integrated boost to prostate up to 74.2 Gy/28 fractions, whereas low-risk patients were treated to the prostate only with 71.4 Gy/28 fractions. Daily megavoltage computed tomography (MVCT) image guidance was applied. Androgen deprivation was prescribed for a median duration of 6 months for low-risk patients (for downsizing), 12 months for intermediate-risk and 36 months for high-risk patients. The 5 year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), overall survival and late gastrointestinal and genitourinary CTCAE.v3 toxicity were assessed. The effect of several clinical variables on both outcome and gastrointestinal/genitourinary toxicity was tested by uni- and multivariate Cox regression analyses. RESULTS: After a median follow-up of 5 years, the late toxicity actuarial incidence was: genitourinary ≥ grade 2: 20.2%; genitourinary ≥ grade 3: 5.9%; gastrointestinal ≥ grade 2: 17%; gastrointestinal ≥ grade 3: 6.3% with lower prevalence at the last follow-up visit (≥ grade 3: genitourinary: 1.9%; gastrointestinal: 1.9%). Major predictors of ≥ grade 3 genitourinary and gastrointestinal late toxicity were genitourinary acute toxicity ≥ grade 2 (hazard ratio: 4.9) and previous surgery (hazard ratio: 3.4). The overall 5 year bRFS was 93.7% (low risk: 94.6%; intermediate risk: 96.2%; high risk: 91.1%), overall survival and CSS were 88.6% (low risk: 90.5%; intermediate risk: 87.4%; high risk: 87%) and 97.5% (low risk: 98.7%; intermediate risk: 95%; high risk: 94.3%), respectively. Risk classes and androgen deprivation were not significantly correlated with either bRFS, overall survival or CSS. Twelve patients experienced a biochemical relapse but none experienced clinically proven local and/or pelvic recurrence. CONCLUSION: A satisfactory 5 year outcome with an acceptable toxicity profile was observed. The combination of image-guided radiotherapy-intensity-modulated radiotherapy, high equivalent 2 Gy dose (EQD2) with a moderate hypofractionated approach and extensive prophylactic lymph node irradiation also leads to very good outcome in high-risk patients.

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.

A simple and robust method for in vivo midline dose map estimations using diodes and portal detectors.

INTRODUCTION: This work investigates the possibility of using a pair of diodes on the beam axis in conjunction with a portal imaging detector to estimate in vivo midline dose distributions, without any additional patient information, related to the external body contour. MATERIALS AND METHODS: In the proposed method, the patient is considered equivalent to a parallelepiped phantom with a thickness z equal to the patient's physical thickness on the field axis with a variable electronic density rho, depending on the water-equivalent thickness. Based on this assumption, if the air gap between portal detector and patient is kept small (within 10-15 cm), the relative exit dose map may be assumed to be equal to the corresponding map measured at the portal detector level by geometrical back projection to the corresponding exit points. The relative exit dose map is then normalized at the on-axis value measured by the exit diode. The entrance dose map is derived by correcting the absolute dose value measured with the diode at the entrance surface by the off-axis ratios. For each pair of entrance and exit doses, the midline dose may be estimated by applying algorithms reported in literature. The method was tested in 6 MV beams using portal film as detector and the Huyskens and Rizzotti algorithms for midline dose estimation. Tests on homogeneous cubic phantoms, homogeneous phantoms with varying thickness symmetrically (simulating head and neck regions) and asymmetrically (simulating abdomen/pelvis region), and a half-sphere phantom with simulating the breast, were performed. Midline doses estimated with the proposed method have been compared with corresponding ones measured by ionisation chamber. RESULTS AND DISCUSSION: Results confirm that the proposed method can be used to estimate midplane dose maps within 2-3% for most clinically suitable situations. For homogeneous symmetrical phantoms the agreement between estimated and measured midline doses decreases with the phantom-portal film distance, the field sizes and the thickness. For homogeneous asymmetrical phantoms the percentage deviations are generally within 3%. Discrepancies larger than 3% (up to 5-6%) are found only for "stressed" irradiation geometries which are not linked with any clinical condition. CONCLUSIONS: The obtained results not only show the accuracy of the proposed method but, due to its simplicity, suggest a rapid clinical implementation of this method in relevant clinical situations such as head-neck, breast and abdomen/pelvis irradiation. Previous investigations which confirmed the possibility of using portal detectors for transit dosimetry in inhomogeneous regions suggest the further exploration of the accuracy and the limits of the proposed method in such cases.

Dose calculation and dosimetry tests for clinical implementation of 1D tissue-deficit compensation by a single dynamic absorber.

BACKGROUND AND PURPOSE: In this study the possibilities for implementing 1D tissue-deficit compensation techniques by a dynamic single absorber were investigated. This research firstly involved a preliminary examination on the accuracy of a pencil beam-based algorithm, implemented for irregularly shaped photon beams in our 3D treatment planning system (TPS) (Cadplan 2.7, Varian-Dosetek Oy), in calculating dose distributions delivered in ID non-uniform fields. Once the reliability of the pencil beam (PB) algorithm for dose calculations in non-uniform beams was verified, we proceeded to test the feasibility of tissue-deficit compensation using our single absorber modulator. As an example, we considered a mantle field technique. MATERIALS AND METHODS: To evaluate the accuracy of the method employed in calculating dose distributions delivered in 1D non-uniform fields, three different fluence profiles, which could be considered as a small sample representative of clinically relevant applications, were selected. The incident non-uniform fluences were simulated by the sum of simple blocked fields (i.e. with rectangular 'strip' blocks, one per beam) properly weighed by the 'modulation factors' Fi, defined in each interval of the subdivided profile as the ratio between the desired fluence and the open field fluence. Depth dose distributions in a cubic phantom were then calculated by the TPS and compared with the corresponding doses (at 5 and 10 cm acrylic depths) delivered by the single absorber modulation system. In the present application, the absorber speed profile able to compensate for the tissue deficit along the cranio-caudal direction and then homogenizing the dose distribution on a 'midline' isocentric plane with sufficient accuracy can be directly derived from anatomic data, such as the SSDs (source-skin distances) along the patient contour. The compensation can be verified through portal dosimetry techniques (using a traditional port film system). RESULTS: The technique was tested in isocentric conditions on the humanoid RANDO phantom in a clinically suitable situation. The agreement between expected/calculated and measured incident/exit dose profiles was found to be within 4%, with deviations generally around 1-2%. As for the PB accuracy investigation for dose calculations in non-uniform fields, calculated versus measured dose profiles were found to be in good agreement, indicating a satisfactory accuracy of the method employed for dose calculation in 1D non-uniform photon beams. A better performance should be expected if the incident fluences could be directly inserted in the TPS. CONCLUSIONS: The results show that the proposed technique should be sufficiently reliable for clinical application. The main advantages are its simplicity and the possibility of application on Linacs which have no complex options for dynamic control of collimators.

Intra- and inter-observer variability in contouring prostate and seminal vesicles: implications for conformal treatment planning.

BACKGROUND AND PURPOSE: Accurate contouring of the clinical target volume (CTV) is a fundamental prerequisite for successful conformal radiotherapy of prostate cancer. The purpose of this study was to investigate intra- and inter-observer variability in contouring prostate (P) and seminal vesicles (SV) and its impact on conformal treatment planning in our working conditions. MATERIALS AND METHODS: Inter-observer variability was investigated by asking five well-trained radiotherapists of contouring on CT images the P and the SV of six supine-positioned patients previously treated with conformal techniques. Short-term intra-observer variability was assessed by asking the radiotherapists to contour the P and SV of one patient for a second time, just after the first contouring. The differences among the inserted volumes were considered for both intra- and inter-observer variability. Regarding intra-observer variability, the differences between the two inserted contours were estimated by taking the relative differences in correspondence to the CT slices on BEV plots (antero-posterior and left-right beams). Concerning inter-observer variability, the distances between the internal and external envelopes of the inserted contours (named projected diagnostic uncertainties or PDUs) and the distances from the mean inserted contours (named mean contour distances or MCDs) were measured from BEV plots (i.e. parallel to the CT slices). RESULTS: Intra-observer variability was relatively small (the average percentage variation of the volume was approximately 5%; SD of the differences measured on BEV plots within 1.8 mm). Concerning inter-observer variability, the percentage SD of the inserted volumes ranged from 10 to 18%. Differences equal to 1 cm in the cranio-caudal extension of P + SV were found in four out of six patients. The largest inter-observer variability was found when considering the anterior margin in the left-right beam of P top (MCD = 7.1 mm, 1 SD). Relatively high values for MCDs were also found for P bottom, for the posterior and lateral margins of P top (2.6 and 3.1 mm, respectively, I SD) and for the anterior margin of SV (2.8 mm, 1 SD). Relatively small values were found for P central (from 1.4 to 2.0 mm, 1 SD) and the posterior margin of SV (1.5 mm, 1 SD). CONCLUSIONS: The application of larger margins taking inter-observer variability into account should be taken into consideration for the anterior and the lateral margins of SV and P top and for the lateral margin of P. The impact of short-term intra-observer variability does not seem to be relevant.

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.

Comparing 3-, 4- and 6-fields techniques for conformal irradiation of prostate and seminal vesicles using dose-volume histograms.

BACKGROUND AND PURPOSE: Comparing some isocentric coplanar techniques for conformal irradiation of prostate and seminal vesicles. MATERIALS AND METHODS: Five conformal techniques have been considered: (A) a 3-fields technique with an antero-posterior (AP) field and two lateral (LAT-LAT) 30 degrees wedged fields; (B) a 3-fields technique with an AP field and two oblique posterior (OBL) 15 degrees wedged fields with relative weights of 0.8, 1 and 1, respectively; (C) a 4-fields technique (AP-PA and LAT-LAT); (D) a 6-fields technique (LAT-LAT and four OBL at gantry angles 45 degrees, 135 degrees, 235 degrees and 315 degrees) with all the fields having the same weight; (E) the same 6-fields technique with lateral fields double-weighted with respect to the oblique fields. The conformal plans have been simulated on 12 consecutive patients (stages B and C) by using our 3D treatment planning system (Cadplan 2.7). The contours of the rectum, the bladder and the left femoral head were outlined together with the clinical target volume (CTV) which included the prostate and the seminal vesicles. A margin of 10 mm was added to define the planning target volume (PTV) through automatic volume expansion. Then a 7 mm margin between the PTV and block edges was added to take the beam penumbra into account. Dose distributions were normalised to the isocentre and the reference dose was considered to be 95% of the isocentre dose. Dose-volume histograms and dose statistics of the rectum, the bladder and the left femoral head were collected for all plans. For the rectum and the bladder the mean dose (Dm) and the fraction of volume receiving a dose higher than the reference dose (V95) were compared. For the femoral head, the mean dose together with the fraction of volume receiving a dose higher than 50% (V50) were compared. RESULTS: Differences among the techniques have been found for all three considered organs at risk. When considering the rectum, technique A is better than the others both when considering Dm and V95 (P = 0.002), while technique D is the worst when considering Dm (P < 0.002) and is also worse than techniques A, E (P = 0.002) and C (P = 0.003) when considering V95. Technique E is the best when considering the bladder mean dose (P = 0.002 against A and D, P < 0.01 against B and C) and technique C is the worst (P < 0.012). No relevant differences were found for the bladder V95. In the femoral heads, techniques A and E are worse than B, C and D (P < 0.003) when considering Dm and V50. Moreover, techniques B and D are better than C (P < 0.004) when considering V50. CONCLUSIONS: There is no technique that is absolutely better than the others. Technique A gives the best sparing of the rectum; the bladder is better spared with technique E. These results are reached with a worse sparing of the femoral heads which should be carefully taken into account.

Human errors in the calculation of monitor units in clinical radiotherapy practice.

Human mistakes are an important source of error in all steps of radiotherapy planning and their incidence should be investigated. As has been recognized by different authors and by the ICRU [4], the human error rate in the calculation of monitor units (MU) is relatively high. At our institute, we measured the human error rate in the calculation of MU by an independent check of the calculation. From September 1991 to June 1992 we identified and corrected 17 serious errors (deviation from the prescribed dose > or = 5%) over 890 controls (1.9%) (daily dose errors). We also found a serious global dose error rate (i.e. the errors induced on the total reference dose for the complete course of the treatment) of 1.3% (9/685) during the period November 1991-June 1992. These values suggest the importance of human errors in the calculation of MU and also confirm the validity of the independent check of MU calculation as one of the simplest ways of avoiding erroneous dose delivery by incorrect calculation of MU.

Exit dose measurements by portal film dosimetry.

Portal in vivo dosimetry is a very attractive tool for patient dose measurements because of the large amount of information that portal film systems can easily collect, once positioned at the exit surface of the patient. The first step in the verification of the reliability of portal films as in vivo dosimeters is the evaluation of the agreement between exit patient dose profiles and optical density profiles measured on the portal film. We checked the possibilities for exit dose measurements of a commercial portal film system (Film Kodak X-Omat V and Localization Kodak Cassette) verifying the agreement between relative exit doses (measured by ionization chamber and film dosimetry, calculated by our treatment planning system (Cadplan Dosetek)) and relative optical densities on portal films in cubic homogeneous and inhomogeneous, cylindrical and humanoid phantoms. In particular, a good agreement (mean difference in absolute value: 2%) between optical densities and calculated exit doses for the Rando phantom were found, once the optical densities values are corrected for an inverse square correction factor, taking into account the variation of the profile of the phantom.

Skin-sparing reduction effects of thermoplastics used for patient immobilization in head and neck radiotherapy.

Skin-sparing benefits derived from the use of megavoltage photon beams can be strongly reduced when filters are inserted between the source and the patient. The use of plastic masks for immobilizing the patient is the most important cause of this reduction in head and neck treatments. The influence of thermoplastics, commercially available for patient immobilization systems (Orfit Raycast (Luxilon Ind. Co.), Posicast (Sinmed bv) and Optimold (WFR Aquaplast Corp.)), on the patient skin dose value has been investigated by using an NE2534 'Markus' chamber. Indicative measurements with moulded masks (carried out with 2-mm Orfit and 3.2-mm Optimold layers) show significant differences between masks moulded with the two thermoplastics.

Set-up error in supine-positioned patients immobilized with two different modalities during conformal radiotherapy of prostate cancer.

BACKGROUND: Conformal radiotherapy requires reduced margins around the clinical target volume (CTV) with respect to traditional radiotherapy techniques. Therefore, high set-up accuracy and reproducibility are mandatory. PURPOSE: To investigate the effectiveness of two different immobilization techniques during conformal radiotherapy of prostate cancer with small fields. MATERIALS AND METHODS: 52 patients with prostate cancer were treated by conformal three- or four-field techniques with radical or adjuvant intent between November 1996 and March 1998. In total, 539 portal images were collected on a weekly basis for at least the first 4 weeks of the treatment on lateral and anterior 18 MV X-ray fields. The average number of sessions monitored per patient was 5.7 (range 4-10). All patients were immobilized with an alpha-cradle system; 25 of them were immobilized at the pelvis level (group A) and the remaining 27 patients were immobilized in the legs (group B). The shifts with respect to the simulation condition were assessed by measuring the distances between the same bony landmarks and the field edges. The global distributions of cranio-caudal (CC), posterior-anterior (PA) and left-right (LR) shifts were considered; for each patient random and systematic error components were assessed by following the procedure suggested by Bijhold et al. (Bijhold J, Lebesque JV, Hart AAM, Vijlbrief RE. Maximising set-up accuracy using portal images as applied to a conformal boost technique for prostatic cancer. Radiother. Oncol. 1992;24:261-271). For each patient the average isocentre (3D) shift was assessed as the quadratic sum of the average shifts in the three directions. RESULTS: Group B showed a better accuracy and reproducibility than group A for PA shifts (2.6 versus 4.4 mm, 1 SD), LR shifts (2.4 versus 3.6 mm, 1 SD) and CC shifts (2.7 versus 3.3 mm, 1 SD). Furthermore, group B showed a rate of large PA shifts (>5 mm) equal to 4.4% with respect to the 21.6% of group A (P<0.0001). This value was also better than the corresponding value found in a previously investigated group of 21 non-immobilized patients (Italia C, Fiorino C, Ciocca M, et al. Quality control by portal film analysis of the conformal radiotherapy of prostate cancer: comparison between two different institutions and treatment techniques (abstract). Radiother. Oncol. 1997;43(Suppl. 2):S16, 16.8%, P = 0.001). For both groups there was no clear prevalence of one component (systematic or random) with respect to the other. The average isocentre shifts (averaged on all patients) were 3.0 mm (+/-1.4 mm, 1 SD) for group B and 5.0 mm (+/-2.8 mm, 1 SD) for group A against a value of 4.4 mm (+/-2.4 mm, 1 SD) for the previously investigated non-immobilized patient group. CONCLUSIONS: Immobilization of the legs with an alpha-cradle system seems to improve both the accuracy and reproducibility of the positioning of patients treated for prostate cancer with respect to alpha-cradle pelvic-abdomen immobilization. Based on these data, we decided to use the legs immobilization system and to reduce the margin around the CTV (from 10 to 8 mm) in the PA direction.