Giovanni Mauro Cattaneo

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.

Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study.

PURPOSE To evaluate clinical and lung dose-volume histogram based factors as predictors of radiation pneumonitis (RP) in lung cancer patients (PTs) treated with thoracic irradiation. METHODS AND MATERIALS Records of all lung cancer PTs irradiated at our Institution between 1994 and 2000 were retrospectively reviewed. Eighty-four PTs with small or non-small-cell lung cancer, irradiated at >40 Gy, with full 3D dosimetry data and a follow-up time of >6 months from start of treatment, were analysed for RP. Pneumonitis was scored on the basis of SWOG toxicity criteria and was considered a complication when grade> or =II. The following clinical parameters were considered: gender, age, surgery, chemotherapy agents, presence of chronic obstructive pulmonary disease (COPD), performance status. Dosimetric factors including prescribed dose (Diso), presence of final conformal boost, mean lung dose (Dmean), % of lung receiving > or =20, 25, 30, 35, 40, and 45 Gy (respectively V20-->V45), and normal tissue complication probability (NTCP) values were analysed. DVHs data and NTCP values were collected for both lungs considered as a paired organ. Median and quartile values were taken as cut-off for statistical analysis. Factors that influenced RP were assessed by univariate (log-rank) and multivariate analyses (Cox hazard model). RESULTS There were 14 PTs (16.6%) who had > or =grade II pulmonary toxicity. In the entire population, the univariate analysis revealed that many dosimetric parameters (Diso, V20, V30, V40, V45) were significantly associated with RP. No significant correlation was found between the incidence of RP and Dmean or NTCP values. Multivariate analysis revealed that the use of mitomycin (MMC) (P=0.005) and the presence of COPD (P=0.026) were the most important risk factor for RP. In the group without COPD (55 PTs, seven RP) a few dosimetric factors (Dmean, V20, V45) and NTCP values (all models) were associated with RP in the univariate analysis (P< or =0.06). According to the multivariate analysis, the use of MMC was independently associated with RP (P=0.007), while Dmean approached statistical significance (P=0.082). CONCLUSIONS In this study the use of mitomycin or the presence of COPD is associated with a higher risk of RP. In the entire population NTCP values were not significantly correlated with the incidence of RP. Mean lung dose shows a clear trend toward statistical significance in the patient group without COPD.

Significant correlation between rectal DVH and late bleeding in patients treated after radical prostatectomy with conformal or conventional radiotherapy (66.6 –70.2 Gy

PURPOSE Investigating the correlation between dosimetric/clinical parameters and late rectal bleeding in patients treated with adjuvant or salvage radiotherapy after radical prostatectomy. METHODS AND MATERIALS Data of 154 consecutive patients, including three-dimensional treatment planning and dose-volume histograms (DVHs) of the rectum (including filling), were retrospectively analyzed. Twenty-six of 154 patients presenting a (full) rectal volume >100 cc were excluded from the analysis. All patients considered for the analysis (n = 128) were treated at a nominal dose equal to 66.6-70.2 Gy (ICRU dose 68-72.5 Gy; median 70 Gy) with conformal (n = 76) or conventional (n = 52) four-field technique (1.8 Gy/fr). Clinical parameters such as diabetes mellitus, acute rectal bleeding, hypertension, age, and hormonal therapy were considered. Late rectal bleeding was scored using a modified Radiation Therapy Oncology Group scale, and patients experiencing >or=Grade 2 were considered bleeders. Median follow-up was 36 months (range 12-72). Mean and median rectal dose were considered, together with rectal volume and the % fraction of rectum receiving more than 50, 55, 60, and 65 Gy (V50, V55, V60, V65, respectively). Median and quartile values of all parameters were taken as cutoff for statistical analysis. Univariate (log-rank) and multivariate (Cox hazard model) analyses were performed. RESULTS Fourteen of 128 patients experienced >or=Grade 2 late bleeding (3-year actuarial incidence 10.5%). A significant correlation between a number of cutoff values and late rectal bleeding was found. In particular, a mean dose >or=54 Gy, V50 >or=63%, V55 >or=57%, and V60 >or=50% was highly predictive of late bleeding (p <or= 0.01). A rectal volume <60 cc and type of treatment (conventional vs. conformal) were also significantly predictive of late bleeding (p = 0.05). Concerning clinical variables, acute bleeding (p < 0.001) was significantly related to late bleeding, and a trend was found for hypertension (p = 0.11). After patients were grouped into those with V50 >or=63% and those with V50 <63% (DVH grouping), data were fitted with a Cox regression hazard model using DVH grouping, rectal volume, and the main clinical parameters as independent variables. Results of the analysis showed that DVH grouping (relative risk 3.3; p = 0.04) and acute bleeding (relative risk 7.1; p = 0.001) are independently predictive of late bleeding. CONCLUSIONS DVHs of the rectum are significantly correlated with late bleeding for patients irradiated at 66.6-70.2 Gy after radical prostatectomy.

IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients treated with post-operative adjuvant or salvage radiotherapy after radical prostatectomy

PURPOSE To investigate the role of IMRT in reducing the risk of acute genito-urinary (GU), upper gastrointestinal (uGI) and lower gastrointestinal (lGI) toxicity following whole-pelvis irradiation (WPRT) after radical prostatectomy. PATIENTS AND METHODS 172 consecutive patients with prostate cancer were post-operatively irradiated to the prostatic bed (PB) and pelvic lymph-nodal area with adjuvant (n=100) or salvage (n=72) intent. Eighty-one patients underwent three-dimensional conformal (3DCRT) WPRT, while the remaining 91 underwent IMRT (54/91 with helical tomotherapy (HTT); 37/91 with Linac intensity-modulated RT (LinacIMRT)). RESULTS Patients treated with IMRT experienced a decreased risk of acute toxicity. The crude incidence of grade > or =2 toxicity was GU 12.3% vs. 6.6% (p=0.19); lGI 8.6% vs. 3.2% (p=0.14); uGI 22.2% vs. 6.6% (p=0.004), for 3DCRT and IMRT, respectively. With respect to uGI and lGI, the acute toxicity profile of the HTT patients was even better when compared to that of 3DCRT patients (crude incidence:1.8% and 0.0%, respectively). Treatment interruptions due to uGI toxicity were 11/81 in the 3DCRT group vs. 2/91 in the IMRT group (p=0.006). CONCLUSIONS The risk of acute toxicity following post-operative WPRT delivered by means of IMRT was reduced compared to that of 3DCRT. The most significant reduction concerned uGI, mainly owing to better bowel sparing with IMRT.

Rectum contouring variability in patients treated for prostate cancer: impact on rectum dose–volume histograms and normal tissue complication probability

BACKGROUND Recent investigations showed some correlation between three-dimensional (3D) treatment planning dose-volume data (dose-volume histograms: DVH, dose statistics) and rectal toxicity for patients treated for prostate cancer. However, no data are available about the possible impact of inter-institute variability in contouring the rectum, so that the possibility of reliably using information from single-centre studies remains doubtful. PURPOSE Within a retrospective three-institutes study on correlation between dose-volume treatment planning data and rectum bleeding in patients treated for prostate cancer, an investigation about the impact of inter- and intra-observer variability in contouring the rectum was performed. MATERIALS AND METHODS Ten patients were considered for a dummy run exercise and three observers (one per Institute) contoured the rectum (including filling). An anatomically based definition of rectum extension was previously accepted by the three observers. Six of the ten patients were randomly chosen in the subgroup of patients (large spacing, LS) with a distance between computed tomography (CT) slices (outside the prostate region) equal to 10 mm; for the remaining four patients the distance between CT slices was 5 mm over the whole rectum volume (small spacing, SS). The original 3D treatment planning was recovered on the Cadplan treatment planning system for each patient and rectum dose statistics (mean, median and maximum rectum dose), volume, DVH and NTCP values were calculated for each observer. For DVH analysis, the values of V(50), V(55), V(60), V(65) and V(70) (defined as the % of rectum volume receiving at least 50, 55, 60, 65, 70 Gy) were considered. Normal tissue complication probabilities (NTCPs) were calculated for the original ICRU dose and for a 75.6 Gy ICRU dose (NTCP and NTCP(75.6), respectively). Intra-observer variability was investigated by asking the observers to redraw the same rectum contours 6 months later and comparing the two contouring sessions. RESULTS In general, a good agreement was found for most patients and, in particular, for all SS patients. The impact of inter-observer variability was quite significant on dose statistics and DVH in two of six LS patients. Looking at the patient population, some systematic deviations, even if quite small, were demonstrated between institute B and institute C (volume, P = 0.02) and between institute A and institute B (mean/median dose, V(50)-V(65), NTCP(75.6); P < 0.05). Four of six LS patients (0/4 in the SS group) presented a maximum difference among observers at the cranial and/or caudal limit of the rectum equal to 1 cm. For these patients, inter-observer variability was significantly higher than for the others (P < 0.03). When inter-observer variability was expressed in terms of standard deviations (SD), values around 2-3 Gy and 0.5 Gy for LS and SS patients, respectively, were found for mean/median dose; values around 3-4% and 0.5-2% for LS and SS patients, respectively, were found for V(50)-V(70). The average SD for NTCP and NTCP(75.6) were 0.4 and 0.6%, respectively (0.5 and 0.9% for LS patients; 0.2 and 0.3% for SS patients). Intra-observer variability was found to be lower than inter-observer variability even if the impact on dose statistics and DVH was visible. CONCLUSIONS Once a robust definition of rectum is assessed, inter- and intra-institute variability in contouring the rectum appear relatively modest. However, the results suggest that the number of LS patients in DVH correlation studies should be as low as possible; the low number of these patients in the multi-centric trial involving our institutions should not have significant impact on the results of the study.

Simultaneous integrated boost (SIB) for nasopharynx cancer with helical tomotherapy. A planning study.

Purpose:To explore the potential of helical tomotherapy (HT) in the treatment of nasopharynx cancer.Patients and Methods:Six T1–4 N1–3 patients were considered. A simultaneous integrated boost (SIB) technique was planned with inversely optimized conventional intensity-modulated radiotherapy (IMRT; dynamic multileaf collimator using the Eclipse-Helios Varian system) and HT. The prescribed (median) doses were 54 Gy, 61.5 Gy, and 64.5 Gy delivered in 30 fractions to PTV1 (planning target volume), PTV2, and PTV3, respectively. The same constraints for PTV coverage and for parotids, spinal cord, mandible, optic structures, and brain stem were followed in both modalities. The planner also tried to reduce the dose to other structures (mucosae outside PTV1, larynx, esophagus, inner ear, thyroid, brain, lungs, submental connective tissue, bony structures) as much as possible.Results:The fraction of PTV receiving > 95% of the prescribed dose (V95%) increased from 97.6% and 94.3% (IMRT) to 99.6% and 97% (HT) for PTV1 and PTV3, respectively (p < 0.05); median dose to parotids decreased from 30.1 Gy for IMRT to 25.0 Gy for HT (p < 0.05). Significant gains (p < 0.05) were found for most organs at risk (OARs): mucosae (V30 decreased from 44 cm3 [IMRT] to 18 cm3 [HT]); larynx (V30: 25 cm3 vs. 11 cm3); thyroid (mean dose: 48.7 Gy vs. 41.5 Gy); esophagus (V45: 4 cm3 vs. 1 cm3); brain stem (D1%: 45.1 Gy vs. 37.7 Gy).Conclusion:HT improves the homogeneity of dose distribution within PTV and PTV coverage together with a significantly greater sparing of OARs compared to linac five-field IMRT.Ziele:Untersuchung des Potentials der helikalen Tomotherapie (HT) beim Nasopharynxkarzinom.Patienten und Methodik:Sechs T1–4 N1–3-Patienten wurden einbezogen. Eine Technik des simultanen integrierten Boost (SIB) wurde geplant mit invers optimierter konventioneller intensitätsmodulierter Radiotherapie (IMRT; dynamischer Multileaf-Kollimator des Eclipse-Helios Varian-Systems) und mit HT. Die verschriebenen (medianen) Strahlungsdosen waren 54 Gy, 61,5 Gy und 64,5 Gy, die in 30 Fraktionen auf die Planungszielvolumina PTV1, PTV2 bzw. PTV3 gegeben wurden. Bei beiden Modalitäten, HT und IMRT, wurden für die PTV-Erfassung sowie für Parotiden, Rückenmark, Kiefer, optischen Apparat und Stammhirn dieselben Begrenzungen eingehalten. Der Planer versuchte auch, die Strahlungsdosis auf andere Regionen (Mukosa außerhalb von PTV1, Larynx, Ösophagus, Innenohr, Schilddrüse, Hirn, Lunge, Bindegewebe und Knochen unterhalb des Kinns) so stark wie möglich zu reduzieren.Ergebnisse:Der PTV-Anteil, der mehr als 95% der verschriebenen Strahlungsdosis (V95%) erhielt, erhöhte sich für PTV1 und PTV3 von 97,6% bzw. 94,3% (IMRT) auf 99,6% bzw. 97% (HT) (p < 0,05); die mediane Dosis der Parotiden verminderte sich von 30,1 Gy bei IMRT auf 25,0 Gy bei HT (p < 0,05). Signifikante Vorteile (p < 0,05) zeigten sich für die meisten Risikoorgane: Mukosa (V30-Verminderung von 44 cm3 [IMRT] auf 18 cm3 [HT]), Larynx (V30: 25 cm3 vs. 11 cm3), Schilddrüse (mittlere Strahlungsdosis: 48,7 Gy vs. 41,5 Gy), Ösophagus (V45: 4 cm3 vs. 1 cm3), Stammhirn (D1%: 45,1 Gy vs. 37,7 Gy).Schlussfolgerung:Verglichen mit der Linac-5-Felder-IMRT verbessert HT die Homogenität der Dosisverteilung innerhalb des PTV und die PTV-Erfassung bei signifkant besserer Schonung von Risikoorganen.

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.

Simultaneous Integrated Boost (SIB) for Nasopharynx Cancer with Helical Tomotherapy

Purpose:To explore the potential of helical tomotherapy (HT) in the treatment of nasopharynx cancer.Patients and Methods:Six T1–4 N1–3 patients were considered. A simultaneous integrated boost (SIB) technique was planned with inversely optimized conventional intensity-modulated radiotherapy (IMRT; dynamic multileaf collimator using the Eclipse-Helios Varian system) and HT. The prescribed (median) doses were 54 Gy, 61.5 Gy, and 64.5 Gy delivered in 30 fractions to PTV1 (planning target volume), PTV2, and PTV3, respectively. The same constraints for PTV coverage and for parotids, spinal cord, mandible, optic structures, and brain stem were followed in both modalities. The planner also tried to reduce the dose to other structures (mucosae outside PTV1, larynx, esophagus, inner ear, thyroid, brain, lungs, submental connective tissue, bony structures) as much as possible.Results:The fraction of PTV receiving > 95% of the prescribed dose (V95%) increased from 97.6% and 94.3% (IMRT) to 99.6% and 97% (HT) for PTV1 and PTV3, respectively (p < 0.05); median dose to parotids decreased from 30.1 Gy for IMRT to 25.0 Gy for HT (p < 0.05). Significant gains (p < 0.05) were found for most organs at risk (OARs): mucosae (V30 decreased from 44 cm3 [IMRT] to 18 cm3 [HT]); larynx (V30: 25 cm3 vs. 11 cm3); thyroid (mean dose: 48.7 Gy vs. 41.5 Gy); esophagus (V45: 4 cm3 vs. 1 cm3); brain stem (D1%: 45.1 Gy vs. 37.7 Gy).Conclusion:HT improves the homogeneity of dose distribution within PTV and PTV coverage together with a significantly greater sparing of OARs compared to linac five-field IMRT.Ziele:Untersuchung des Potentials der helikalen Tomotherapie (HT) beim Nasopharynxkarzinom.Patienten und Methodik:Sechs T1–4 N1–3-Patienten wurden einbezogen. Eine Technik des simultanen integrierten Boost (SIB) wurde geplant mit invers optimierter konventioneller intensitätsmodulierter Radiotherapie (IMRT; dynamischer Multileaf-Kollimator des Eclipse-Helios Varian-Systems) und mit HT. Die verschriebenen (medianen) Strahlungsdosen waren 54 Gy, 61,5 Gy und 64,5 Gy, die in 30 Fraktionen auf die Planungszielvolumina PTV1, PTV2 bzw. PTV3 gegeben wurden. Bei beiden Modalitäten, HT und IMRT, wurden für die PTV-Erfassung sowie für Parotiden, Rückenmark, Kiefer, optischen Apparat und Stammhirn dieselben Begrenzungen eingehalten. Der Planer versuchte auch, die Strahlungsdosis auf andere Regionen (Mukosa außerhalb von PTV1, Larynx, Ösophagus, Innenohr, Schilddrüse, Hirn, Lunge, Bindegewebe und Knochen unterhalb des Kinns) so stark wie möglich zu reduzieren.Ergebnisse:Der PTV-Anteil, der mehr als 95% der verschriebenen Strahlungsdosis (V95%) erhielt, erhöhte sich für PTV1 und PTV3 von 97,6% bzw. 94,3% (IMRT) auf 99,6% bzw. 97% (HT) (p < 0,05); die mediane Dosis der Parotiden verminderte sich von 30,1 Gy bei IMRT auf 25,0 Gy bei HT (p < 0,05). Signifikante Vorteile (p < 0,05) zeigten sich für die meisten Risikoorgane: Mukosa (V30-Verminderung von 44 cm3 [IMRT] auf 18 cm3 [HT]), Larynx (V30: 25 cm3 vs. 11 cm3), Schilddrüse (mittlere Strahlungsdosis: 48,7 Gy vs. 41,5 Gy), Ösophagus (V45: 4 cm3 vs. 1 cm3), Stammhirn (D1%: 45,1 Gy vs. 37,7 Gy).Schlussfolgerung:Verglichen mit der Linac-5-Felder-IMRT verbessert HT die Homogenität der Dosisverteilung innerhalb des PTV und die PTV-Erfassung bei signifkant besserer Schonung von Risikoorganen.

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.

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).