Sara Broggi

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.

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.

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.

Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients.

PURPOSE To investigate the clinical factors independently predictive of long-term severe urinary sequelae after postprostatectomy radiotherapy. PATIENTS AND METHODS Between 1993 and 2005, 742 consecutive patients underwent postoperative radiotherapy with either adjuvant (n = 556; median radiation dose, 70.2 Gy) or salvage (n = 186; median radiation dose, 72 Gy) intent. RESULTS After a median follow-up of 99 months, the 8-year risk of Grade 2 or greater and Grade 3 late urinary toxicity was almost identical (23.9% vs. 23.7% and 12% vs. 10%) in the adjuvant and salvage cohorts, respectively. On univariate analysis, acute toxicity was significantly predictive of late Grade 2 or greater sequelae in both subgroups (p <.0001 in both cases), and hypertension (p = .02) and whole-pelvis radiotherapy (p = .02) correlated significantly in the adjuvant cohort only. The variables predictive of late Grade 3 sequelae were acute Grade 2 or greater toxicity in both groups and whole-pelvis radiotherapy (8-year risk of Grade 3 events, 21% vs. 11%, p = .007), hypertension (8-year risk, 18% vs. 10%, p = .005), age ≤ 62 years at RT (8-year risk, 16% vs. 11%, p = .04) in the adjuvant subset, and radiation dose >72 Gy (8-year risk, 19% vs. 6%, p = .007) and age >71 years (8-year risk, 16% vs. 6%, p = .006) in the salvage subgroup. Multivariate analysis confirmed the independent predictive role of all the covariates indicated as statistically significant on univariate analysis. CONCLUSIONS The risk of late Grade 2 or greater and Grade 3 urinary toxicity was almost identical, regardless of the RT intent. In the salvage cohort, older age and greater radiation doses resulted in a worse toxicity profile, and younger, hypertensive patients experienced a greater rate of severe late sequelae in the adjuvant setting. The causes of this latter correlation and apparently different etiopathogenesis of chronic damage in the two subgroups were unclear and deserve additional investigation.

PHASE I-II STUDY OF HYPOFRACTIONATED SIMULTANEOUS INTEGRATED BOOST WITH TOMOTHERAPY FOR PROSTATE CANCER

PURPOSE To report planning and acute toxicity data of the first 60 patients treated within a Phase I-II study with moderate hypofractionation by image-guided helical tomotherapy. METHODS AND MATERIALS Various clinical target volumes (CTVs) were defined: CTV1-pelvic nodes; CTV2-upper portion of seminal vesicles; CTV3-lower portion of SV; CTV4-prostate; overlap between planning target volume (PTV) 4 and rectum. Different doses to each PTV were simultaneously delivered in 28 fractions. For 31 low-risk patients: 56.0, 61.6, and 71.4 Gy for PTV2-4, respectively; for 20 intermediate-risk patients: 51.8, 61.6, 65.5, and 74.2 Gy for PTV1-4, respectively; for 9 high-risk patients: 51.8 and 65.5 Gy for PTV1-2 and 74.2 Gy for PTV3-4. For all patients, the dose to overlap was 65.5 Gy. RESULTS The mean fraction of rectum receiving more than 65 Gy (V65) and rectal Dmax were 10% and 70.8 Gy respectively. In cases of pelvic node irradiation, the intestinal cavity (outside PTV) receiving > 45 and 50 Gy was 86 and 12 cc, respectively. A homogeneous dose distribution within each PTV was guaranteed. Acute genitourinary toxicity according to RTOG scoring system was as follows: 21/60 (35%) Grade 1, 12/60 (20%) Grade 2, 2/60 (3%) Grade 3. Acute rectal toxicities were: 18/60 (30%) Grade 1. Twelve (20%) patients showed Grade 1 upper intestinal toxicity (uGI). No patients experienced > or = Grade 2 acute rectal or uGI side effects. CONCLUSIONS This study shows excellent results with regard to acute toxicity. Further research is necessary to assess definitive late toxicity and tumor control outcome.

Dose-volume relationships for acute bowel toxicity in patients treated with pelvic nodal irradiation for prostate cancer.

PURPOSE To find correlation between dose-volume histograms (DVHs) of the intestinal cavity (IC) and moderate-severe acute bowel toxicity in men with prostate cancer treated with pelvic nodal irradiation. METHODS AND MATERIALS The study group consisted of 191 patients with localized prostate cancer who underwent whole-pelvis radiotherapy with radical or adjuvant/salvage intent during January 2004 to November 2007. Complete planning/clinical data were available in 175 of these men, 91 of whom were treated with a conventional four-field technique (50.4 Gy, 1.8 Gy/fraction) and 84 of whom were treated with IMRT using conventional Linac (n = 26, 50.4 Gy, 1.8 Gy/fraction) or Helical TomoTherapy (n = 58, 50-54 Gy, 1.8-2 Gy/fraction). The IC outside the planning target volume (PTV) was contoured and the DVH for the first 6 weeks of treatment was recovered in all patients. The correlation between a number of clinical and DVH (V10-V55) variables and toxicity was investigated in univariate and multivariate analyses. The correlation between DVHs for the IC outside the PTV and DVHs for the whole IC was also assessed. RESULTS Twenty-two patients experienced toxicity (3/22 in the IMRT/tomotherapy group). Univariate analyses showed a significant correlation between V20-V50 and toxicity (p = 0.0002-0.001), with a higher predictive value observed for V40-V50. Previous prostatectomy (p = 0.066) and abdominal/pelvic surgery (p = 0.12) also correlated with toxicity. Multivariate analysis that included V45, abdominal/pelvic surgery, and prostatectomy showed that the most predictive parameters were V45 (p = 0.002) and abdominal/pelvic surgery (p = 0.05, HR = 2.4) CONCLUSIONS Our avoidance IMRT approach drastically reduces the incidence of acute bowel toxicity. V40-V50 of IC and, secondarily, previous abdominal/pelvic surgery were the main predictors of acute bowel toxicity.

Sparing the penile bulb in the radical irradiation of clinically localised prostate carcinoma: A comparison between MRI and CT prostatic apex definition in 3DCRT, Linac-IMRT and Helical Tomotherapy

BACKGROUND AND PURPOSE To assess the impact of using MRI and Helical Tomotherapy (HT) compared to 3DCRT and dynamic IMRT on the dose to the penile bulb (PB). MATERIALS AND METHODS Eight patients diagnosed with prostate cancer entered a treatment protocol including CT and MRI simulation. The prostate apex was defined on both MRI and CT. Treatment plans (HT, Linac-IMRT, 3DCRT and conventional technique), were elaborated on both MRI and CT images. A dose of 71.4Gy (2.55Gy/fraction) was prescribed; it was requested that PTVs be covered by 95% isodose line. The mean dose and V50 of PB were evaluated. RESULTS PTV-MRI plans reduced PB mean dose and V50 compared to PTV-CT plans. This improvement, deriving also from the treatment modality, was 89% for 3DCRT, 99% for Linac-IMRT and 97% for HT (p<0.01), considering V50. Conventional plans resulted in a significantly higher mean PB dose/V50 compared to 3DCRT-PTV-CT (+27%/+38%), Linac-IMRT-PTV-CT (+42%/+57%) and HT-PTV-CT (+32%/+48%) (p<0.01). The comparison between conventional and PTV-MRI techniques showed a still larger increase: +73%/+93% 3DCRT; +86%/+99% Linac-IMRT; +56%/+99% HT (p<0.01). The PB mean dose reduction with Linac-IMRT compared to 3DCRT was 24% (p=0.034) and 40% (p=0.027) for PTV-CT and PTV-MRI, respectively. This gain remained significant even when comparing Linac-IMRT to HT: 21% (p=0.07) PTV-CT and 68% (p=0.00002) PTV-MRI. HT was superior to 3DCRT with respect to PTV-CT (average gain 4%, p=0.044), whereas it resulted to be detrimental considering PTV-MRI (26Gy vs 16.5Gy), possibly due to the helical delivery of HT; however, in a patient where the distance bulb-PTV <1cm, HT provided better PB sparing than 3DCRT (29.5Gy vs 45.2Gy). CONCLUSIONS MRI allowed efficient sparing of PB irrespective of the treatment modality. Linac-IMRT was shown to further reduce the dose to the bulb compared to 3DCRT and HT.

Hypofractionated adjuvant radiotherapy with helical Tomotherapy after radical prostatectomy: Planning data and toxicity results of a Phase I-II study

PURPOSE To report on planning and toxicity findings of hypofractionated adjuvant radiotherapy with helical Tomotherapy (HTT) after radical prostatectomy (RP) for prostate carcinoma (pCa). METHODS AND MATERIALS Fifty consecutive patients submitted to RP for pT2R1/pT3a/pT3b-pN0 pCa were enrolled in a Phase I-II trial to receive 58Gy/20 fractions (5/week) on tumoral bed. Endpoint was to verify a risk of toxicity and biochemical failure not exceeding that observed in our Institutional 3DCRT, conventionally fractionated series (153 patients). Toxicities were graded according the RTOG scoring system. RESULTS Excellent coverage of PTV and high homogeneity of dose distribution were always achieved. Median follow-up was 25 months. Acute G2-3 RTOG genitourinary (GU) and acute G2 intestinal toxicities were similar (12% vs 15.6% and 4% vs 7%, respectively), while acute G2 proctitis was 0% vs 9% in HTT and 3DCRT group, respectively. Similarly, late Grade 2 gastrointestinal sequelae were 0% vs 8.5%. The incidence of late urethral stricture, 8% and 9% in HTT and 3DCRT group, respectively, is comparable to that of RP-only series. CONCLUSIONS Acute toxicity and early late toxicity outcomes of a moderately hypofractionated regimen with HTT post-RP are excellent. A longer follow-up is needed to fully assess the validity of this approach.

Physics aspects of prostate tomotherapy : Planning optimization and image-guidance issues

Purpose. To review planning and image-guidance aspects of more than 3 years experience in the treatment of prostate cancer with Helical Tomotherapy (HT). Methods and materials. Planning issues concerning two Phase I-II clinical studies were addressed: in the first one, 58 Gy in 20 fractions were delivered to the prostatic bed for post-prostatectomy patients: in the second one, a simultaneous integrated boost (SIB) approach was applied for radical treatment, delivering 71.4–74.2 Gy to the prostate in 28 fractions. On-line daily MVCT image guidance was applied: bone match was used for post-operative patients while prostate match was applied for radically treated patients. MVCT data of a large sample of both categories of patients were reviewed. Results. At now, more than 250 patients were treated. Planning data show the ability of HT in creating highly homogeneous dose distributions within PTVs. Organs at risk (OAR) sparing also showed to be excellent. HT was also found to favorably compare to inversely-optimized IMAT in terms of PTVs coverage and dose distribution homogeneity. In the case of pelvic nodes irradiation, a large sparing of bowel was evident compared to 3DCRT and conventional 5-fields IMRT. The analysis of MVCT data showed a limited motion of the prostate (about 5% of the fractions show a deviation ≥3 mm in posterior-anterior direction), due to the careful application of rectal emptying procedures. Based on phantom measurements and on the comparison with intra-prostatic calcification-based match, direct visualization prostate match seems to be sufficiently reliable in assessing shifts ≥3 mm. Conclusions. HT offers excellent planning solutions for prostate cancer, showing to be highly efficient in a SIB scenario. Daily MVCT information showed evidence of a limited motion of the prostate in the context of rectal filling control obtained by instructing patients in self-administrating a rectal enema.