C. Sini

Dose–response of EBT3 radiochromic films to proton and carbon ion clinical beams

We investigated the dose-response of the external beam therapy 3 (EBT3) films for proton and carbon ion clinical beams, in comparison with conventional radiotherapy beams; we also measured the film response along the energy deposition-curve in water. We performed measurements at three hadrontherapy centres by delivering monoenergetic pencil beams (protons: 63-230 MeV; carbon ions: 115-400 MeV/u), at 0.4-20 Gy dose to water, in the plateau of the depth-dose curve. We also irradiated the films to clinical MV-photon and electron beams. We placed the EBT3 films in water along the whole depth-dose curve for 148.8 MeV protons and 398.9 MeV/u carbon ions, in comparison with measurements provided by a plane-parallel ionization chamber. For protons, the response of EBT3 in the plateau of the depth-dose curve is not different from that of photons, within experimental uncertainties. For carbon ions, we observed an energy dependent under-response of EBT3 film, from 16% to 29% with respect to photon beams. Moreover, we observed an under-response in the Bragg peak region of about 10% for 148.8 MeV protons and of about 42% for 398.9 MeV/u carbon ions. For proton and carbon ion clinical beams, an under-response occurs at the Bragg peak. For carbon ions, we also observed an under-response of the EBT3 in the plateau of the depth-dose curve. This effect is the highest at the lowest initial energy of the clinical beams, a phenomenon related to the corresponding higher LET in the film sensitive layer. This behavior should be properly modeled when using EBT3 films for accurate 3D dosimetry.

Deformable registration-based segmentation of the bowel on Megavoltage CT during pelvic radiotherapy

During pelvic radiotherapy bowel loops (BL) are subject to inter-fraction changes. MVCT images have the potential to provide daily bowel segmentation. We assess the feasibility of deformable registration and contour propagation in replacing manual BL segmentation on MVCT. Four observers delineated BL on the planning kVCT and on one therapy MVCT in eight patients. Inter-observer variations in BLs contouring were quantified using DICE index. BLs were then automatically propagated onto MVCT by a commercial software for image deformation and subsequently manually corrected. The agreement between propagated BL/propagated+manually corrected BL vs manual were quantified using the DICE. Contouring times were also compared. The impact on DVH of using the deformable-registration method was assessed. The same procedures were repeated on high-resolution planning-kVCT and therapy-kVCT. MVCTs are adequate to visualize BL (average DICE: 0.815), although worse than kVCT (average DICE:0.889). When comparing propagated vs manual BL, a poor agreement was found (average DICE: 0.564/0.646 for MVCT/KVCT). After manual correction, average DICE indexes increased to 0.810/0.897. The contouring time was reduced to 15min with the semi-automatic approach from 30min with manual contouring. DVH parameters of propagated BL were significantly different from manual BL (p<0.0001); after manual correction, no significant differences were seen. MVCT are suitable for BL visualization. The use of a software to segment BL on MVCT starting from BL-kVCT contours was feasible if followed by manual correction. The method resulted in a substantial reduction of contouring time without detrimental effect on the quality of bowel segmentation and DVH estimates.

Accuracy of dose calculation algorithms for static and rotational IMRT of lung cancer: A phantom study

PURPOSE To evaluate the dosimetric accuracy of Pencil beam (PB), Anisotropic Analytical Algorithm (AAA) and Collapsed Cone Convolution Superposition (CCCS) in thoracic tumours for various IMRT techniques. METHODS Step-and-shoot Linac IMRT (IMRT), arc volumetric RapidArc (RA) and Helical Tomotherapy (HT) lung treatments for different clinical situations (mediastinum tumour, single metastasis and multiple metastases) were simulated and calculated with PB/AAA, AAA, CCCS, respectively. Delivery quality assurance plans were first verified in homogeneous media (Cheese phantom and ArcCHECK); then several low-density inhomogeneous phantoms were used: the Multiplug ArcCHECK, the commercial ArcCHECK slightly modified with a low density lung-shape insert and a custom-made slab heterogeneous phantom simulating the thorax region. Absolute doses and planar dose maps were checked to assess the agreement between measured and calculated dose distributions. RESULTS In total, data referred to 195 point dose measurements and 189 planar measurements were considered. Average point absolute deviations <3% were found for all the delivery techniques/dose algorithms. In small targets completely embedded in very low density media, deviations up to 7-10% and 4-5% were found for PB and AAA/CCCS respectively. Excellent results were found for planar measurements in ArcCHECK configurations, where ≥ 95% of points satisfy the 3%/3 mm acceptance criteria for all the algorithms. CONCLUSIONS A satisfactory agreement (<2%) between planned and measured doses was generally found for CCCS and AAA, excepting the very critical situation of a small tumour completely embedded in air. A significant dose overestimation (from few to 5-7%) was confirmed for PB in complex inhomogeneous arrangements.

Dose–volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation

PURPOSE To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. MATERIAL AND METHODS Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. RESULTS Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. CONCLUSIONS Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT.

Patient-reported urinary incontinence after radiotherapy for prostate cancer: Quantifying the dose–effect

BACKGROUND AND PURPOSE Urinary incontinence following radiotherapy (RT) for prostate cancer (PCa) has a relevant impact on patients quality of life. The aim of the study was to assess the unknown dose-effect relationship for late patient-reported urinary incontinence (LPRUI). METHODS AND MATERIALS Patients were enrolled within the multi-centric study DUE01. Clinical and dosimetry data including the prescribed 2Gy equivalent dose (EQD2) were prospectively collected. LPRUI was evaluated through the ICIQ-SF questionnaire filled in by the patients at RT start/end and therefore every 6months. Patients were treated with conventional (74-80Gy, 1.8-2Gy/fr) or moderately hypo-fractionated RT (65-75.2Gy, 2.2-2.7Gy/fr) in 5 fractions/week with intensity-modulated radiotherapy. Six different end-points of 3-year LPRUI, including or not patients perception (respectively, subjective and objective end-points), were considered. Multivariable logistic models were developed for each end-point. RESULTS Data of 298 patients were analyzed. The incidence of the most severe end-point (ICIQ-SF>12) was 5.1%. EQD2 calculated with alpha-beta=0.8Gy showed the best performance in fitting data: the risk of LPRUI markedly increased for EQD2>80Gy. Previous abdominal/pelvic surgery and previous TURP were the clinical factors more significantly predictive of LPRUI. Models showed excellent performances in terms of goodness-of-fit and calibration, confirmed by bootstrap-based internal validation. When included in the analyses, baseline symptoms were a major predictor for 5 out of six end-points. CONCLUSIONS LPRUI after RT for PCa dramatically depends on EQD2 and few clinical factors. Results are consistent with a larger than expected impact of moderate hypo-fractionation on the risk of LPRUI. As expected, baseline symptoms, as captured by ICIQ-SF, are associated to an increased risk of LPRUI.

Patient-reported intestinal toxicity from whole pelvis intensity-modulated radiotherapy: First quantification of bowel dose–volume effects

BACKGROUND AND PURPOSE Intestinal toxicity is commonly experienced during whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. The aim of the current study was to assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with WPRT for prostate cancer. MATERIALS AND METHODS Complete data of 206 patients were available; the median dose to pelvic nodes was 51.8Gy (range 50.4-54.4, 1.7-2Gy/fr). Intestinal symptoms were assessed as changes in the Inflammatory Bowel Disease Questionnaire scores relative to the Bowel Domain (IBDQ-B) between baseline and radiotherapy mid-point/end. The 25th percentiles of the most severe worsening from baseline (ΔIBDQ-B) were set as end-points. The impact of bowel loops and sigmoid colon dose-volume/surface parameters as well as selected clinical parameters were investigated using multivariate logistic regression. RESULTS Analyses were focused on the four questions showing a median ΔIBDQ-B>0. No dose volume/surface parameters were predictive, other than ΔIBDQ5≥3 (loose stools): when grouping patients according to bowel DVHs (high risk: V20>470cc, V30>245cc, V42>110cc; low risk: all the remaining patients), a two-variable model including high-risk DVH-shape (OR: 9.3) and age (protective, OR: 0.94) was assessed. The model showed good calibration (slope: 1.003, R2=0.92) and was found to be robust after bootstrap-based internal validation. CONCLUSIONS Constraining the bowel loops may reduce the risk of loose stools. The risk is higher for younger patients.

EP-1725: Predictors of diarrhea after whole-pelvis post-prostatectomy radiotherapy

S807 ________________________________________________________________________________ was maintained as long as the effect metric used for Cox regression had a linear correlation with the true effect metric of at least 0.50. The conclusions held if the trial cohort consisted of an expected high benefit population (22% reduced sample size), but the effect was even stronger if the cohort was a population with modest expected benefit (31% reduced sample size).

PO-0749: Factors predicting late severe urinary incontinence after postprostatectomy RT: a longitudinal study

Results: Finally 550 patients with prostate cancer were included, with median age of 70 years old (47-85), Mean follow-up time was 136.8 months, between 5,6 and 245,8 months. D’Amico risk classification distribution was for low risk, mediun and high 20.4%, 36,5% and 43,1% respectively. RCI distribution categories was as follows 61,5%, 21,8 and 16,7%. Survival analysis showed significant differences (p<0.001) between RCI groups at 5 and 10 years. Survival probability was 98,2 and 88,5% ; 95% and 79,6% ; and 52,2% and 8,9% was respectively for each RCI category.

EP-2053: In-vivo imaging of rat leukocytes redistribution after pelvic irradiation

Purpose or Objective: The standard treatment regimen of patients with primary glioblastoma multiforme (PGBM) consists of neurosurgery, radioand chemotherapy. Despite this multimodal treatment the overall survival of patients with PGBM is still approximately 15 months. The stress-inducible heat shock protein 70 (Hsp70) contributes to tumor cell survival and is associated with poor prognosis, metastasis and therapy resistance. Therefore, the aim of this study is to analyze Hsp70 in PGBM tumor samples as a future prognostic biomarker and possible therapy target.