A. Dubouloz

Impact of hydrogel spacer injections on interfraction prostate motion during prostate cancer radiotherapy

Abstract Background The dosimetric advantage of prostate-rectum spacers to displace the anterior rectal wall outside of the high-dose radiation regions has been clearly established in prostate cancer radiotherapy (RT). The aim of this study was to assess the impact of hydrogel spacer (HS) in the interfraction prostate motion in patients undergoing RT for prostate cancer. Material and methods Twenty prostate cancer patients implanted with three fiducial markers (FM) with (n = 10) or without (n = 10) HS were analyzed. Displacements between the prostate isocenter based on the FM’s position and the bony anatomy were quantified in the left-right (LR), anterior-posterior (AP), superior-inferior (SI) axes by offline analyses of 122 cone beam computed tomography scans. Group systematic (M), systematic (Σ) and random (σ) setup errors were determined. Results In patients with or without HS, the overall mean interfraction prostate displacements were 0.4 versus −0.4 mm (p = 0.0001), 0.6 versus 0.6 mm (p = 0.85), and −0.6 mm versus −0.3 mm (p = 0.48) for the LR, AP, and SI axes, respectively. Prostate displacements >5 mm in the AP and SI directions were similar for both groups. No differences in M, Σ and σ setup errors were observed in the three axes between HS + or HS- patients. Conclusions HS implantation does not significantly influence the interfraction prostate motion in patients treated with RT for prostate cancer. The major expected benefit of HS is a reduction of the high-dose levels to the rectal wall without influence in prostate immobilization.

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility, Tolerance and Outcome

AIMS To evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique. MATERIALS AND METHODS Between 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0-50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system. RESULTS All patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049). CONCLUSIONS The use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

PURPOSE This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. METHODS AND MATERIALS 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. RESULTS There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). CONCLUSIONS A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.

In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance

OBJECTIVE To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). METHODS Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. RESULTS A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25-2.02 Gy) and 1.82 Gy (range, 0.19-2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, -0.11/+0.19 Gy, p=0.102) (median difference of 1.1%, range -6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., -8.9%). CONCLUSIONS Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors.

Urethra-sparing stereotactic body radiotherapy for prostate cancer: how much can the rectal wall dose be reduced with or without an endorectal balloon?

BackgroundThis is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate Rwall dose and the potential benefit of an endorectal balloon (ERB) are investigated.MethodsTen prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the Rwall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm1 to Vm5). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for Rwall including the median dose and the dose received by 10 to 60% of the Rwall, bladder wall (Bwall) and femoral heads (FHeads) were compared. The monitor units (MU) per plan were recorded.ResultsVm4 reduced by half D30%, D40%, D50%, and Dmed for Rwall and decreased by a third D60% while HIPTV, HIuPRV and DSC remained stable with and without ERB compared to Vmref. HIPTV worsened at Vm5 both with and without ERB. No statistical differences were observed between paired plans on Rwall, Bwall except a higher D2% for Fheads with and without an ERB.ConclusionsFurther optimization to the Rwall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the Rwall can be significantly reduced using a four-step sequential optimization approach.

EP-1453: Urethra-sparing prostatic SBRT: extreme dosimetric optimization on rectal wall using an endorectal balloon

Materials and Methods: Using the CBCT of the XRAD225Cx preclinical irradiator, 8 tissue equivalent cylinders of known composition and density (Gammex RMI, Middelton, WI) were imaged at 40kVp. The HU variation was plotted versus the product ρ times Zeff that yielded to a monotonically increasing curve. Based on this relationship and the tissues defined in the ICRU-44 report, interpolated tissues were created for ρZeff varying from 2 up to 27 with a 0.2 step. Tissue equivalent cylinders were irradiated with the XRAD225Cx (225kVp). Exit dose was measured with EBT3 films and compared to Monte Carlo (MC) calculations from our GATE model of the irradiator. On the CT images, tissue segmentation was performed either by manual assignation of the elemental composition provided by the manufacturer or by using the (HU, ρ, EC) method. Dosimetric impact of the (HU, ρ, EC) method was evaluated on mice CT comparing with manual segmentation for brain and femoral head irradiations. Results: Tissue equivalent exit dose measurements relative to solid water varied from 1.13 (AP6 adipose) down to 0.36 (SB3 cortical bone). Max 2% deviation was found with MC dose calculation performed with manufacturer data and 4.3% with calculation performed with the (HU, ρ, EC) method. Mean deviations were respectively 1.1% and 1.8%. It must be noticed that the segmentation method was based on real human tissues defined in ICRU-44 whereas measurements were performed with substitutes with elemental composition slightly different from human tissue elemental composition. The (HU, ρ, EC) method applied on mice CT allowed the automatic definition of 125 tissues. Dosimetric impact of the (HU, ρ, EC) was significant for bony tissues (>25%). Conclusions: A robust tissue segmentation method was developed for dose calculation in preclinical radiation therapy based on the (HU, ρZeff) relationship. Our method was successfully tested by comparing exit dose measurements from materials of known composition with MC dose calculation. The method was applied on mice CT for brain and femoral head irradiation with significant dosimetric impact.

First year experience with IORT for breast cancer at the Geneva University Hospitals

Purpose: The Breast Centre at the Geneva University Hospitals implemented guidelines for breast cancer intraoperative radiotherapy (IORT) in 2012. The present study evaluates early breast and skin toxicities observed during the first year of the implementation. Material and methods: From February 2012 to January 2013, 52 women received IORT for primary breast cancer treated with conservative surgery. IORT was delivered with the Intrabeam ® system. The prescribed dose was 20 Gy at the applicator’s surface. No further radiation was to be given according to the following criteria: age ≥50 years old, histopathology of invasive ductal, mucinous, tubular, medullar or colloid carcinoma, unifocal tumor, absence of lymphovascular invasion (LVI), absence of extensive in situ component, tumor size ≤30 mm, pathological nodal status pN0 by sentinel node biopsy or pN1mi by axillary dissection, and clear resection margins ≥2 mm. If the criteria were not met, additional whole breast radiotherapy (WBRT) to an equivalent dose of 50 Gy in 2-Gy fractions was to be given post-operatively. Toxicity grades were based on LENT-SOMA scoring tables. Results: IORT was given as exclusive radiation therapy in 34 (65%) patients, whereas 18 (35%) patients received an additional hypofractionated WBRT of 40-47.25 Gy in 15-21 fractions, one of whom further received after IORT-WBRT an additional electron boost of 13.5 Gy to the tumor bed in 6 fractions. At 1-month post-IORT, no heart toxicity was recorded. Six (11.5%) patients presented grade 2 lung symptoms. Breast/skin most frequent toxicities were seroma, grade 3 in 13 of 52 (25%) patients. One patient had a wound dehiscence requiring suture, and one patient had hematoma after immediate bilateral breast reconstruction with implants. Regarding the 18 patients who received additional WBRT, subsequent reevaluation after the WBRT found no heart toxicity, grade 1 lung symptoms in 1 (5%) patient, and grade 3 breast and skin toxicity in 2 (11%) patients (1 persistent seroma and 1 skin dryness). The breast and skin toxicity observed in patients after additional WBRT was not significantly increased as compared with the toxicity earlier observed after IORT, P=0.631. Conclusions: Early evaluation of IORT found mild to moderate breast and skin toxicity. Toxicity was not significantly increased in patients receiving additional WBRT.

EP-1531: Stereotactic radiosurgery dose quality assurance: a commercial plastic scintillation versus a diamond detector

A total of 15 patients plans and 79 DCA generated in iPlan RT Dose 4.1.2 (BrainLAB, AG, Germany), with a Pencil Beam algorithm using a kernel resolution of 2.5mm were tested. Mean equivalent MLC field size was of 16.6 mm (range 7.5-32.7mm). Plans were delivered on a Novalis TX, using the 6XSRS energy mode with a D/R of 1000 MU/min and a HDMLC multileaf collimator (2.5 mm leaf size at isocenter). Using a Lucy® 3D QA Phantom (Standard Imaging, Inc., USA), dose distributions were recalculated for each plan and Figure 2. In blue the Lucy phantom with the DD and in grey, bottom, with the PSD, position “tip down”. The water equivalence and absence of metal in the PSD resulted in no change in data for this detector. Both DD and PSD results were within the overall measurements accuracy. Analysis of the measurements performed with the detectors tip up and down, Fig.3, are shown below in Table 3.