A. Pierelli

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.

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.

Helical tomotherapy vs. intensity-modulated proton therapy for whole pelvis irradiation in high-risk prostate cancer patients: dosimetric, normal tissue complication probability, and generalized equivalent uniform dose analysis.

PURPOSE To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. METHODS AND MATERIALS The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100°; 100°) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normal tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. RESULTS A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving ≥ 95% of the prescribed dose (V(95%)) was on average > 97% in HT and > 99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. CONCLUSIONS Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.

Relationships between bladder dose–volume/surface histograms and acute urinary toxicity after radiotherapy for prostate cancer

BACKGROUND AND PURPOSE DUE01 is an observational study aimed at developing predictive models of genito-urinary toxicity of patients treated for prostate cancer with conventional (1.8-2Gy/fr, CONV) or moderate hypo-fractionation (2.35-2.7Gy/fr, HYPO). The current analysis focused on the relationship between bladder DVH/DSH and the risk of International Prostate Symptoms Score (IPSS)⩾15/20 at the end of radiotherapy. MATERIALS AND METHODS Planning and relevant clinical parameters were prospectively collected, including DVH/DSH, LQ-corrected (DVHc/DSHc) and weekly (DVHw/DSHw) histograms. Best parameters were selected by the differences between patients with/without IPSS⩾15/20 at the end of radiotherapy. Logistic uni- and backward multi-variable (MVA) analyses were performed. RESULTS Data of 247 patients were available (CONV: 116, HYPO: 131). Absolute DVHw/DSHw and DVHc/DSHc predicted the risk of IPSS⩾15 at the end of radiotherapy (n=77/247); an MVA model including baseline IPSS, anti-hypertensive, T stage, the absolute surface receiving ⩾8.5Gy/week and ⩾12.5Gy/week was developed (AUC=0.78, 95% CI: 0.72-0.83). Similar AUC values were found if replacing DSHw with DVHw/DVHc/DSHc parameters. The impact of dose-volume/surface parameters remained when excluding patients with baseline IPSS⩾15 and in HYPO. IPSS⩾20 at the end of radiotherapy (n=27/247) was mainly correlated to baseline IPSS and T stage. CONCLUSIONS Although the baseline IPSS was the main predictor, constraining v8.5w<56cc and v12.5w<5cc may significantly reduce acute GU toxicity.

Helical tomotherapy and intensity modulated proton therapy in the treatment of early stage prostate cancer: A treatment planning comparison

PURPOSE To compare helical tomotherapy (HT) and intensity modulated proton therapy (IMPT) on early stage prostate cancer treatments delivered with simultaneous integrated boost (SIB) in moderate hypofractionation. MATERIAL/METHODS Eight patients treated with HT were replanned with two-field IMPT (2fIMPT) and five-field IMPT (5fIMPT), using a small pencil beam size (3 mm sigma). The prescribed dose was 74.3 Gy in 28 fractions on PTV1 (prostate) and PTV2 (proximal seminal vesicles), 65.5 Gy on PTV3 (distal seminal vesicles) and on the overlap between rectum and PTVs. RESULTS IMPT and HT achieved similar target coverage and dose homogeneity, with 5fIMPT providing the best results. The conformity indexes of IMPT were significantly lower for PTV1+2 and PTV3. Above 65 Gy, HT and IMPT were equivalent in the rectum, while IMPT spared the bladder and the penile bulb from 0 to 70 Gy. From 0 up to 60 Gy, IMPT dosimetric values were (much) lower for all OARs except the femur heads, where HT was better than 2fIMPT in the 25-35 Gy dose range. OARs mean doses were typically reduced by 30-50% by IMPT. NTCPs for the rectum were within 1% between the two techniques, except when the endpoint was stool frequency, where IMPT showed a small (though statistically significant) benefit. CONCLUSIONS HT and IMPT produce similar dose distributions in the target volume. The current knowledge on dose-effect relations does not allow to quantify the clinical impact of the large sparing of IMPT at medium-to-low doses.

Multi-variable models of large International Prostate Symptom Score worsening at the end of therapy in prostate cancer radiotherapy

PURPOSE/OBJECTIVE Prospectively assessing clinical/dosimetry factors affecting the acute worsening of urinary functionality after radiotherapy for prostate cancer. MATERIAL/METHODS DUE01 population was considered, including patients treated with conventional or moderate hypo-fractionation (2.2-2.7 Gy/fr). Relevant clinical factors were collected, urinary symptoms were self-reported through the International Prostate Symptom Score (IPSS) before and at the end of radiotherapy; while absolute weekly dose-surface histograms (DSHw) were chosen as dosimetry descriptors. An IPSS increase of at least 10 and 15 points (ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15) were chosen as endpoints. Patients with baseline IPSS>20 were excluded. Relevant factors were chosen through a bootstrap-based in silico methodology. RESULTS Complete information was available for 380 patients: 77/380 (20%) and 28/380 (7%) with ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15, respectively. Neoadjuvant hormone was protective (OR=0.49 and 0.69). DSHw at 8.5 Gy/week and 12 Gy/week were risk factors, with additional risk for patients who use cardiovascular drugs and anti-hypercholesterolemia drugs. In the hypo-fractionated subgroup (n=209) the role of cardiovascular drugs (OR=2.16) for ΔIPSS ⩾ 10 and anti-hypercholesterolemia drugs (OR=2.80) for ΔIPSS⩾15, together with DSHw (10 Gy/week and 12.5 Gy/week, respectively), was confirmed. CONCLUSION Current study shows a dose-surface/volume effect for acute large worsening of urinary functionality; several clinical variables largely impact the risk and especially all the factors related with vascular diseases.

PO-0875: Multivariable models for urinary symptoms at 6-24 months after radical RT of prostate cancer

Conclusion: The delivery of a voxel by voxel iso-effective plan, if different RBE models are employed, is not feasible; it is however possible to minimize differences in dose deposited in the target. Dose prescription is a clinical task which ultimately depends only on the radiation oncologist clinical decision; in this study we made an attempt to avoid systematic errors which could potentially compromise tumor control. Initial clinical data on local control of adenoid cystic carcinoma treated in our facility confirms the validity of this approach.

Modeling acute urinary toxicity after radiotherapy for prostate cancer.

156 Background: DUE-01 is a multi-centric observational study aimed at developing predictive models of genito-urinary toxicity and erectile dysfunction for prostate cancer patients treated with conventional (1.8-2Gy/fr, CONV) or moderate hypofractionation (2.5-2.7Gy/fr, HYPO). Current analysis focused on modelling the relationship between the risk of IPSS≥15 (IPSS15end) at the end of radiotherapy and clinincal/dosimetric risk factors. Methods: Planning data and relevant clinical factors were prospectively collected, including DVH/DSH referred to the whole treatment and to the weekly delivered dose (DVHw/DSHw). Best discriminating DVH/DSH parameters were selected by the differences between patients with/without IPSS15end=1 (t-test). Bootstrap variable selection techniques (300 resamples) in the framework of logistic backward feature selection was used to improve model building (El Naqa, IJROBP 2006). Graphical and quantitative analyses of the variable selection process applied to bootstrap data replicates ...