R. Calandrino

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.

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.

First human Cerenkography.

Abstract. Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.

LETHAL PULMONARY COMPLICATIONS SIGNIFICANTLY CORRELATE WITH INDIVIDUALLY ASSESSED MEAN LUNG DOSE IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES TREATED WITH TOTAL BODY IRRADIATION

PURPOSE To assess the impact of lung dose on lethal pulmonary complications (LPCs) in a single-center group of patients with hematologic malignancies treated with total body irradiation (TBI) in the conditioning regimen for bone marrow transplantation (BMT). METHODS The mean lung dose of 101 TBI-conditioned patients was assessed by a thorough (1 SD around 2%) in vivo transit dosimetry technique. Fractionated TBI (10 Gy, 3.33 Gy/fraction, 1 fraction/d, 0.055 Gy/min) was delivered using a lateral-opposed beam technique with shielding of the lung by the arms. The median lung dose was 9.4 Gy (1 SD 0.8 Gy, range 7.8--11.4). The LPCs included idiopathic interstitial pneumonia (IIP) and non-idiopathic IP (non-IIP). RESULTS Nine LPCs were observed. LPCs were observed in 2 (3.8%) of 52 patients in the group with a lung dose < or = 9.4 Gy and in 7 (14.3%) of 49 patients in the >9.4 Gy group. The 6-month LPC risk was 3.8% and 19.2% (p = 0.05), respectively. A multivariate analysis adjusted by the following variables: type of malignancy (acute leukemia, chronic leukemia, lymphoma, myeloma), type of BMT (allogeneic, autologous), cytomegalovirus infection, graft vs. host disease, and previously administered drugs (bleomycin, cytarabine, cyclophosphamide, nitrosoureas), revealed a significant and independent association between lung dose and LPC risk (p = 0.02; relative risk = 6.7). Of the variables analyzed, BMT type (p = 0.04; relative risk = 6.6) had a risk predictive role. CONCLUSION The mean lung dose is an independent predictor of LPC risk in patients treated with the 3 x 3.33-Gy low-dose-rate TBI technique. Allogeneic BMT is associated with a higher risk of LPCs.

Multispectral Cerenkov luminescence tomography for small animal optical imaging

Quite recently Cerenkov luminescence imaging (CLI) has been introduced as a novel pre-clinical imaging for the in vivo imaging of small animals such as mice. The CLI method is based on the detection of Cerenkov radiation (CR) generated by beta particles as they travel into the animal tissues with an energy such that Cerenkov emission condition is satisfied. This paper describes an image reconstruction method called multi spectral diffuse Cerenkov luminescence tomography (msCLT) in order to obtain 3D images from the detection of CR. The multispectral approach is based on a set of 2D planar images acquired using a number of narrow bandpass filters, and the distinctive information content at each wavelength is used in the 3D image reconstruction process. The proposed msCLT method was tested both in vitro and in vivo using 32P-ATP and all the images were acquired by using the IVIS 200 small animal optical imager (Caliper Life Sciences, Alameda USA). Source depth estimation and spatial resolution measurements were performed using a small capillary source placed between several slices of chicken breast. The theoretical Cerenkov emission spectrum and optical properties of chicken breast were used in the modelling of photon propagation. In vivo imaging was performed by injecting control nude mice with 10 MBq of 32P-ATP and the 3D tracer bio-distribution was reconstructed. Whole body MRI was acquired to provide an anatomical localization of the Cerenkov emission. The spatial resolution obtained from the msCLT reconstructed images of the capillary source showed that the FWHM is about 1.5 mm for a 6 mm depth. Co-registered MRI images showed that the Cerenkov emission regions matches fairly well with anatomical regions, such as the brain, heart and abdomen. Ex vivo imaging of the different organs such as intestine, brain, heart and ribs further confirms these findings. We conclude that in vivo 3D bio-distribution of a pure beta-minus emitting radiopharmaceutical such as 32P-ATP can be obtained using the msCLT reconstruction approach.

Evidence of Limited Motion of the Prostate by Carefully Emptying the Rectum as Assessed by Daily MVCT Image Guidance with Helical Tomotherapy

PURPOSE To assess setup and organ motion error by means of analysis of daily megavoltage computed tomography (MVCT) of patients treated with hypofractionated helical tomotherapy (71.4-74.2 Gy in 28 fractions). METHODS AND MATERIALS Data from 21 patients were analyzed. Patients were instructed to empty the rectum carefully before planning CT and every morning before therapy by means of a self-applied rectal enema. The position of the prostate was assessed by means of automatic bone matching (BM) with the planning kilovoltage CT (BM, setup error) followed by a direct visualization (DV) match on the prostate. Deviations between planning and therapy positions referred to BM and BM + DV were registered for the three main axes. In case of a full rectum at MVCT with evident shift of the prostate, treatment was postponed until after additional rectal emptying procedures; in this case, additional MVCT was performed before delivering the treatment. Data for 522 fractions were available; the impact of post-MVCT procedure was investigated for 17 of 21 patients (410 fractions). RESULTS Prostate motion relative to bony anatomy was limited. Concerning posterior-anterior shifts, only 4.9% and 2.7% of fractions showed deviation of 3 mm or greater of the prostate relative to BM without and with consideration of post-MVCT procedures, respectively. Interobserver variability for BM + DV match was within 0.8 mm (1 SD). CONCLUSIONS Daily MVCT-based correction is feasible. The BM + DV matching was found to be consistent between operators. Rectal emptying using a daily enema is an efficient tool to minimize prostate motion, even for centers that have not yet implemented image-guided radiotherapy.

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.