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.

Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis.

Altered glomerular metabolism of arachidonic acid (AA) has already been demonstrated in experimental nephrotoxic nephritis. The enhanced synthesis of thromboxane A2 (TxA2) in isolated glomeruli that has been found may mediate changes in renal hemodynamics. The objectives of this investigation were: to check whether glomerular AA metabolism is also altered in a model of glomerulopathy in which no leukocyte infiltration or platelet deposition could be demonstrated; to establish a correlation between the altered AA metabolism and proteinuria; and to explore whether the alteration of the prostaglandin (PG) pathway found in isolated glomeruli is an in vitro artifact or reflects a modification in vivo. We used a model of glomerular damage characterized by heavy and persistent proteinuria, which was induced in the rat by a single intravenous injection of adriamycin. At light microscopy, minimal glomerular abnormalities were found in this model. Electron microscopy showed profound alterations of glomerular epithelial cells with extensive fusion of foot processes and signs of epithelial cell activation. Electron microscopy of numerous glomeruli showed no platelet deposition or macrophage and leukocyte infiltration in this model. Isolated glomeruli from nephrotic rats studied 14 or 30 d after a single intravenous injection of adriamycin (7.5 mg/kg) when animals were heavily proteinuric generated significantly more TxB2, the stable breakdown product of TxA2, than normal glomeruli. No significant changes were found in the other major AA metabolites formed through cyclooxygenase. Urinary excretion of immunoreactive TxB2 was also significantly higher in nephrotic than in normal animals. Administration of a selective Tx synthetase inhibitor, UK-38,485, from day 14 to day 18 after adriamycin resulted in a significant reduction of proteinuria compared with pretreatment values. Glomerular synthesis and urinary excretion of TxB2 were normal during the UK-38,485 treatment. Additional experiments showed that elevated glomerular synthesis and urinary excretion of TxB2 were not a consequence of increased substrate availability. Maximal stimulation of the renin-angiotensin axis with furosemide increased glomerular TxB2 synthesis in normal rats, which was significantly lower than in nephrotic animals. Finally, experiments using a unilateral model of adriamycin nephrosis indicated that the enhancement of glomerular TxB2 synthesis is not simply a consequence of the nephrotic syndrome. We conclude that: there is an abnormality of glomerular AA metabolism in nephritic syndrome, which leads to increased TxA2 production; the increased Tx generation correlates with protein excretion and might be responsible for altering the glomerular basement membrane permeability to protein; and the alteration found in isolated glomeruli probably reflects a modification in vivo, in that urinary excretion of immunoreactive TxB2 is also consistently increased in adriamycin nephrosis.

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.

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.

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.

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.

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.

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.

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.

Detection of systematic errors in external radiotherapy before treatment delivery.

The execution of an independent control of monitor units (MU) and dose distribution calculation, together with a check of the data reported in the treatment chart is an effective tool in strongly reducing the occurrence of systematic errors before treatment delivery. In this paper we report the results of the analysis of 6272 controls (about 5000 patients) registered over more than 5 years; 70 serious errors (producing a deviation larger than 5% from the prescribed daily dose) and 147 minor errors were detected and corrected before the start of the treatment. The error rate was found to be strongly operator-dependent (serious error rate ranging from 0.3 to 2.5% when considering different operators). A time-trend analysis showed a significant reduction of serious errors, i.e. 1.5% in the period from September 1991 to April 1994 compared to 0.9% in the period from April 1994 to November 1996. However, even if the double check was highly effective in revealing human errors, three serious systematic errors (errors occurring during the calculation/planning/transcription phases) escaped the control and were detected by diode in vivo dosimetry during the period October 1994 to November 1996 (in 650 patients controlled).

Variations of tumor control and rectum complication probabilities due to random set-up errors during conformal radiation therapy of prostate cancer.

BACKGROUND AND PURPOSE: The effect of random set-up errors on tumor control probability (TCP) and rectum complication probability (NTCP) on 3D conformal treatment planning of prostate cancer has been investigated by applying the convolution method originally proposed by Leong (Leong, J. Implementation of random positioning error in computerized radiation treatment planning systems as a result of fractionation. Phys. Med. Biol. 32: 327-334, 1987). MATERIALS AND METHODS: The combined influence of the standard deviation of the random shifts probability distribution (sigma) of the dose and of the Beam's-eye-view margin (M) between the clinical target volume (CTV) and the edge of the blocks have been investigated in two patients. RESULTS AND CONCLUSIONS: Random set-up error has been found to decrease TCP (for a typical 70 Gy CTV mean dose) by up to 6% for a 1 cm margin (sigma = 7 mm). When M is equal to or larger than 1.5 cm, no relevant effects on TCP are obtained. Maximum acceptable TCP values (corresponding to a rectum NTCP equal to 5%) have been derived and the dependence on sigma and M has been investigated.

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.

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.

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.