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An increase of skin dose during head and neck cancer (HNC) radiotherapy is potentially dangerous. Aim of this study was to quantify skin dose variation and to assess the need of planning adaptation (ART) to counteract it.Planning CTs of 32 patients treated with helical tomotherapy (HT) according to a Simultaneous Integrated Boost (SIB) technique delivering 54/66 Gy in 30 fractions were deformably co-registered to MVCTs taken at fractions 15 and 30; in addition, the first fraction was also considered. The delivered dose-of-the-day was calculated on the corresponding deformed images. Superficial body layers (SL) were considered as a surrogate for skin, considering a layer thickness of 2 mm. Variations of SL DVH (∆SL) during therapy were quantified, focusing on ∆SL95% (i.e., 62.7 Gy).Small changes (within ± 1 cc for ∆SL95%) were seen in 15/32 patients. Only 2 patients experienced ∆SL95% 1 cc in at least one of the two monitored fractions. Negative ∆SL95% 1 cc (up to 17 cc) were much more common (15/32 patients). The trend of skin dose changes was mostly detected at the first fraction. Negative changes were correlated with the presence of any overlap between PTV and SL at planning and were explained in terms of how the planning system optimizes the PTV dose coverage near the skin. Acute toxicity was associated with planning DVH and this association was not improved if considering DVHs referring to fractions 15/30.About half of the patients treated with SIB with HT for HNC experienced a skin-sparing effect during therapy; only 6% experienced an increase. Our findings do not support skin-sparing ART, while suggesting the introduction of improved skin-sparing planning techniques.ZWECK: Eine Erhöhung der Hautdosis während der Strahlentherapie von Kopf-Hals-Tumoren (HNC) ist potenziell gefährlich. Das Ziel dieser Studie war es, die Änderung der Hautdosis zu quantifizieren und den Bedarf einer Plananpassung (ART) zu bewerten, um dieser entgegenzuwirken.Planungs-CTs von 32 Patienten, die mittels helikaler Tomotherapie (HT) in einer „Simultaneous Integrated Boost“(SIB)-Technik mit 54/66 Gy bei 30 Fraktionen behandelt wurden, wurden nichtrigide registriert mit MVCTs, die bei Fraktion 15, 30 gefahren wurden; zusätzlich wurde auch die erste Fraktion berücksichtigt. Die verabreichte Tagesdosis wurde auf den entsprechenden deformierten Bildern berechnet. Die äußersten Schichten (SL) wurden als Ersatz für die Haut angesehen, mit einer Schichtdicke von 2 mm. Änderungen der SL-DVH (∆SL) während der Therapie wurden quantifiziert, mit einem Fokus auf ∆SL95 % (d. h. 62,7 Gy).Kleine Änderungen (innerhalb ± 1 cc für ∆SL95 %) ergaben sich bei 15 von 32 Patienten. Bei nur 2 Patienten wurde ein ∆SL95 % 1 cc in mindestens einer der beiden überwachten Fraktionen beobachtet. Negative ∆SL95 % 1 cc (bis zu 17 cc) waren weit häufiger (15 von 32). Der Trend von Hautdosisänderungen wurde zumeist bei der ersten Fraktion festgestellt. Negative Änderungen korrelierten mit der Anwesenheit einer Überlappung von PTV und SL bei der Planung und wurden dahingehend erklärt, wie das Planungssystem die PTV-Dosisabdeckung in der Nähe der Haut optimiert. Eine akute Toxizität war auf das Planungs-DVH zurückzuführen; dies wurde unter Berücksichtigung von DVH bei Fraktion 15 bzw. 30 nicht verbessert.Bei etwa der Hälfte der Patienten, die in SIB-Technik mittels HT für HNC behandelt wurden, ergab sich eine Hautschonung während der Therapie; nur 6 % erfuhren einen Anstieg. Unsere Erkenntnisse unterstützen keine hautschonende Plananpassung (ART), schlagen jedoch die Einführung verbesserter hautschonender Planungstechniken vor.

PurposeTo implement Knowledge Based (KB) automatic planning for right and left-sided whole breast treatment through a new volumetric technique (ViTAT, Virtual Tangential-fields Arc Therapy) mimicking conventional tangential fields (TF) irradiation.Materials and MethodA total of 193 clinical plans delivering TF with wedged or field-in-field beams were selected to train two KB-models for right(R) and left(L) sided breast cancer patients using the RapidPlan (RP) tool implemented in the Varian Eclipse system. Then, a template for ViTAT optimization, incorporating individual KB-optimized constraints, was interactively fine-tuned. ViTAT plans consisted of four arcs (6 MV) with start/stop angles consistent with the TF geometry variability within our population; the delivery was completely blocked along the arcs, apart from the first and last 20° of rotation for each arc. Optimized fine-tuned KB templates for automatic plan optimization were generated. Validation tests were performed on 60 new patients equally divided in R and L breast treatment: KB automatic ViTAT-plans (KB-ViTAT) were compared against the original TF plans in terms of OARs/PTVs dose-volume parameters. Wilcoxon-tests were used to assess the statistically significant differences.ResultsKB models were successfully generated for both L and R sides. Overall, 1(3%) and 7(23%) out of 30 automatic KB-ViTAT plans were unacceptable compared to TF for R and L side, respectively. After the manual refinement of the start/stop angles, KB-ViTAT plans well fitted TF-performances for these patients as well. PTV coverage was comparable, while PTV D1% was improved with KB-ViTAT by R:0.4/L:0.2 Gy (p < 0.05); ipsilateral OARs Dmean were similar with a slight (i.e., few % volume) improvement/worsening in the 15–35 Gy/2–15 Gy range, respectively. KB-ViTAT better spared contralateral OARs: Dmean of contralateral OARs was 0.1 Gy lower (p < 0.05); integral dose was R:5%/L:8% lower (p < 0.05) than TF. The overall time for the automatic plan optimization and final dose calculation was 12 ± 2 minutes.ConclusionsFully automatic KB-optimization of ViTAT can efficiently replace manually optimized TF planning for whole breast irradiation. This approach was clinically implemented in our institute and may be suggested as a large-scale strategy for efficiently replacing manual planning with large sparing of time, elimination of inter-planner variability and of, seldomly occurring, sub-optimal manual plans.

Aim We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. Methods and materials From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14–70.53) years. Histology: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (−), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. Results Median follow up was 72.43 (IQR: 44.63–104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. Conclusion While the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription., Highlights • Hypofractionated three-weeks radiotherapy ensures good local control whitout boost. • In 1325 early stage breast cancers 5-year local relapse without boost was 2.2%. • Molecular subtypes have a strong impact on estimated probability of local relapse. • 5-year local control (LC) was 99.8% for Luminal A vs 87.9% for HR- Her2+. • 5-year LC was 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 95.1% for TNBC.

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

AimsThe aim of the present work is to assess the main predictors of the most clinically relevant radio-induced effects after Gamma Knife stereotactic radiosurgery (GKRS) for uveal melanoma (UM).Materials and methodsMedical records and three-dimensional dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for GKRS-related complications.ResultsThe fraction of the posterior segment receiving more than 20Gy (V20), Bruch’s membrane rupture and tumour thickness were significant prognostic factors for neovascular glaucoma. A clear relationship with the dose received by 1% of the optic nerve (D1%) was found for radiation retinopathy and papillopathy. Multivariables models resulted for visual acuity (VA) reduction >20% of the basal value and for complete VA loss, both including largest tumour diameter and D1% to the optic nerve. The predictive model for complete VA loss includes also Bruch’s membrane rupture. An alternative model for complete visual acuity loss, including the optic nerve-prescription isodose minimum distance, was also suggested.ConclusionsWe found clinical and dosimetric variables to clearly predict the risk of the main side effects after GKRS for UM. These results may provide dose constraints to critical structures, potentially able to reduce side effects. Constraining D1% to the optic nerve below 12-13Gy may result in a dramatic reduction of blindness risk, while reducing V20 of the posterior segment of the bulb could limit the neovascular glaucoma onset.

Purpose An increase of skin dose during RT for head-neck (HN) cancer due to anatomy deformation may potentially translate into an increased risk of skin toxicity, suggesting a potential benefit from planning adaptation (ART) to counteract this effect. Current study applied an original method for dose-of-the-day calculation in quantifying changes of skin dose during Tomotherapy for head and neck (HN) cancer in order to identify those patients that could benefit of ART. Methods Planning CTs of 32 patients (SIB: 54/66 Gy, 30 fractions) were deformable registered to MVCT images taken at fraction 15 and 30 using a constrained-intensity-based algorithm. Dose-of-the-day were calculated on the deformed images; this approach was previously validated by comparing dose distributions of deformed CT and diagnostic kVCT of the same day. Superficial body layers (SL) were considered as a surrogate of skin, considering a 2 mm thickness. Skin dose variation during therapy ( Δ SL) in terms of fraction of SL receiving at least 95%–105% of the prescribed PTV dose (66 Gy) were considered. Based on the previous validation, a change ≥ + 1 cc was assessed to define patients that may benefit of ART. Results Δ SL occurred during treatment with individually variable patterns, depending on several factors like the PTV location/dimension/shape/shrinkage. Only 3 patients experienced >1 cc change of SL95%-105% during treatment (maximum variation: 6 cc) while negative Δ SL95%-105% > 1 cc, up to 17 cc, were seen in 15/33 patients. A negative change was correlated with the presence of some overlap between PTV and SL at planning (p = 0.03). Δ SL 95% are shown for all patients in Fig. 1. Download : Download high-res image (301KB) Download : Download full-size image Conclusions Most patients treated with a SIB approach with Tomotherapy for HN cancer showed negative or irrelevant changes to the dose delivered to the skin. Less than 10% of patients seem to be candidate to ART to counteract any significant skin dose increase during therapy.

Purpose To compare 3D-CRT, Field-in-Field (FIF) and VMAT for adjuvant radiotherapy of breast cancer. Methods 26 patients (13 with left-sided breast cancer, 13 with right-sided) treated to a prescribed dose of 40 Gy (2.667 Gy/fraction; normalized to the target mean) were considered. For all patients a 3D-CRT and a VMAT plan were simulated. 3D-CRTs were planned with 2 primary tangential fields with physical wedges and 2 additional low weighted segments. VMAT plans were performed with a Rapid Arc (RA) technique using 2 partial arc. In a subgroup of 15 patients FIF technique was implemented, combining two open fields with 2–3 segments in two tangential beam directions, without using wedges. Comparisons were performed in terms of PTV coverage and OARs dose-volume histogram (DVH) parameters, considering optimal/acceptable constraints of RTOG-1005 protocol. The dosimetric value of omolateral (lung/heart) OARs were related to the OARs volume included in the chest concavity and to OAR’s inclusion maximum depth. Results Concerning PTV, coverage was similar for the three techniques. The mean dose to OARs are summarized in the table. RA was sub-optimal for all contralateral OARs because mean doses were significantly (p Conclusions The FIF (3D-CRT) technique is similar to RA for PTV data and presents the best results all contralateral OARs. Only when (omolateral) lung and heart have an inclusion in chest concavity >1.5 cm, RA significantly reduces dose in the high DVH region.

Purpose The aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT). Methods For each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences

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 51.8 Gy (range 50.4–54.4, 1.7–2 Gy/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 > 470 cc, V30 > 245 cc, V42 > 110 cc; 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, R 2 = 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.

Purpose To assess inter-fraction bowel loops (BL) motion and quantify its impact on BL DVHs in prostate radiotherapy including pelvic nodes irradiation. Methods Ten patients treated by Helical Tomotherapy, with adjuvant (5) or radical (5) intent, delivering 52.5/51.8 Gy to pelvic-nodes in 30/28 fractions respectively, were enrolled. For each patient, BL contours were drawn on fifteen daily MVCTs, using a validated method for segmentation: BL were propagated from the planning CT to in-room MVCTs by elastic registration and then manually corrected. Based on BL daily contours overlayed on the planning CT, 50% and 80% coverage probability maps (CPM) of BL position were generated using an ad hoc module of the VODCA software (BMSInc.). Average BL DVH during radiotherapy (DVHm) and DVH of BL50%/BL80% were compared against planning DVH (DVHpl). Results The figure and Table 1 summarize the results: the differences between planning and BL50% values of V45-V50 were Conclusions Daily MVCTs permitted to quantify bowel CPM assessing the most likely location of stable BL during pelvic radiotherapy. BL next to external iliac lymphnodes were quite stable while small bowel was associated to large random motion. Bowel planning strategies should be implemented to take into account the anatomical segments more likely to remain stable during radiotherapy. Download : Download high-res image (111KB) Download : Download full-size image

Purpose We proposed a new technique for breast cancer rotational radiotherapy using kilovoltage synchrotron radiation (SR) [1] . Here, we compared 2D dose distributions in a breast phantom at 6 MV in circular orbit Volumetric Arc Therapy (VMAT) with respect to 100 keV irradiation in rotational radiotherapy with SR. Methods The dose distribution was evaluated with calibrated EBT3 radiochromic films inserted at midplane in a 14-cm diameter PMMA cylindrical phantom, simulating the pendant breast. We irradiated a cylindrical target (15 × 20 mm2 (W × H)) at the centre of phantom. Measurements were performed at the Imaging and Medical Beamline (Australian Synchrotron, Clayton, Australia) at 100 keV, with a SR beam of size 15 × 20 mm2 (W × H) continuously irradiating the phantom during a 360 deg rotation around the cylinder axis with a central dose to the target of 7 Gy. Megavoltage measurements were performed at 6 MV using a Varian Clinac iX System Linac, with a target dose of 6 Gy. Results The principle of dose summation along the axis of rotation produced a dose distribution peaked at the centre of rotation for small fields. The target-to-surface dose ratio was 20:1 at 6 MV and 9:1 at 100 keV, for a target at the center of the phantom. Conclusions We performed a feasibility test of kilovoltage rotational radiotherapy dedicated to the breast showing a target-to-surface dose ratio higher than with MV radiotherapy but still acceptable for skin tissue sparing.

Purpose/objective Whole pelvis irradiation with IMRT (WPRT–IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity. Materials and methods Ninety-six patients treated with WPRT–IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves. Results 15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose–volume predictors were the fraction of loops receiving more than 45, 50 and 55Gy (respectively, V45TL⩾50cc, V50TL⩾13cc, V55TL⩾3cc; p -values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02–1.25; p =0.021) and V50TL (⩾13cc, OR: 8.2; 95%CI: 1.7–40; p =0.009). Conclusions The risk of moderate acute uGI toxicity during WPRT–IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.

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 ⩾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.

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

The aim of this study was to evaluate the risk of second tumor induction for prostate patients treated with volumetric modulated arc therapy in age classes 50-70. Based on both age-dependent models and doses to critical organs, the risk of second tumor induction was evaluated simulating the small field (prostate and seminal vesicles) and large field (whole pelvis) for Helical Tomotherapy and Rapid Arc. The doses to the organs closest to the treatment volume were derived from treatment planning system data. Whereas, due to the lack of calculation algorithms where leakage and internal radiation scattering are unreliable at a large distance from target, the doses to the organs outside the treatment volume were measured in an anthropomorphic phantom. Doses from Image Guided Radiotherapy (IGRT) were also assessed on phantom measurements. The Lifetime Attributable Risk (LAR) for second tumor induction increases from 2.2 to 13.7% as irradiated volume increases and age decreases. IGRT could add a non-negligible factor to the risk when daily set-up verification with high-resolution modality is included. As prostate cancer is detected earlier, the probability of an increase in early stage patients rises, and life expectancy thus increases. Radiotherapy has improved its capability in the tailoring of the dose around the target at the cost of a greater dose to surrounding organs, thus increasing the risk of second tumor induction, especially for those patients expected to survive 15 y or more.

During a radiotherapy treatment, a dosimetric verification or a geometric localization can be done, in order to assess the quality of the treatment. The dosimetric verification is generally performed measuring the dose at some points inside (natural cavities) or outside the patient, and comparing it to the dose at the same points calculated and predicted by the treatment planning system. This can be done either with thermoluminescent or diodes dosimeters or with ionization chambers. The geometric localization can be done acquiring a portal image of the patient. Portal imaging can be performed either with films placed between metallic screens, or with an electronic portal imaging device such as fluoroscopic systems, solid state devices or matrix ionization chamber systems. In order to assess possible field placement errors, the portal images have to be compared with images obtained with the simulator in the same geometric conditions and/or with the digitally reconstructed radiograph (DRR) obtained with the treatment planning system. In particular, when using matrix ionization chamber systems, the portal images contain also information regarding the exit dose. This means that this kind of imaging device can be used both for geometric localization and for dosimetric verification. In this case, the exit dose measured by the portal image can be compared with the exit dose calculated and predicted by the treatment planning system. Some “in-vivo” applications of this methodology are presented.

Purpose To compare helical Tomotherapy (HT), two volumetric-modulated arc techniques and conventional fixed-field intensity modulated techniques (S-IMRT) for head-neck (HN) cancers. Methods and materials Eighteen HN patients were considered. Four treatment plans were generated for each patient: HT, S-IMRT optimised with Eclipse treatment planning system and two volumetric techniques using Elekta–Oncentra approach (VMAT) and Varian-RapidArc (RA), using two full arcs. All techniques were optimised to simultaneously deliver 66Gy to PTV1 (GTV and enlarged nodes) and 54Gy to PTV2 (subclinical and electively treated nodes). Comparisons were assessed on several dosimetric parameters and, secondarily, on planned MUs and delivery time. Results Concerning PTV coverage, significantly better results were found for HT and RA. HT significantly improved the target coverage both compared to S-IMRT and VMAT. No significant differences were found between S-IMRT and volumetric techniques in terms of dose homogeneity. For OARs, all the techniques were able to satisfy all hard constraints; significantly better results were found for HT, especially in the intermediate dose range (15–30 Gy). S-IMRT reached a significantly better OARs sparing with respect to VMAT and RA. No significant differences were found for body mean dose, excepting higher values of V5–V10 for HT. A reduction of planned MUs and delivery treatment time was found with volumetric techniques. Conclusions The objectives of satisfying target coverage and sparing of critical structures were reached with all techniques. S-IMRT techniques were found more advantageous compared to RA and VMAT for OARs sparing. HT reached the best overall treatment plan quality.

The aim of this study was to evaluate the correlation between the 'true' absolute and relative dose-volume histograms (DVHs) of the bladder wall, dose-wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose-surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose-volume/surface histogram. Correlation was quantified for selected dose-volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD

The purpose of this study is to evaluate the use of MapCHECK2 in a patient-specific quality assurance (QA) procedure for Rapid Arc (RA) radiotherapy and to obtain reference values of gamma index (γ) for different irradiation geometries. Dose distributions of 386 patients, optimized with Eclipse treatment planning system for RA on Varian Clinac 2300IX were exported and measured with MapCHECK2 detector array inserted in a MapPHAN dedicated phantom. Gamma index analysis was used to evaluate differences between calculated and delivered doses; collected data were analysed on the basis of complexity of plans and type of disease. Angular dependence and dose drift of detectors were estimated. The overall mean passing rate (percentage of points with γ 1) was equal to 97.0% ± 3.1%; plan-specific evaluation of %γ 1 showed significant differences among different treatment protocols (pancreas 98.6% ± 1.5%, prostate 96.6% ± 2.8% and rectum 92.8% ± 5.7%). MapCHECK2 demonstrated a strong angular dependence over a restricted range of angles (90° ± 5° and 270° ± 5°); this condition affected the result of pre-treatment QA only for plans with intense lateral fluence. The drift of diode array response due to the accumulated dose was found to be comparable with the manufacturer's declaration (0.5% per 1000 Gy). MapCHECK2 proved to be a useful and accurate tool in the process of patient-specific QA for RA treatment. Excluding the irradiation geometries with a high contribution of lateral fluence, the mean percentage of cases with γ-index 95% equal to 90.3% was obtained instead of 81.7% including all plans.

Introduction Uveal melanoma (UM) is a life threatening intraocular malignant tumor. Gamma Knife Stereotactic Radiosurgery (GKSRS) is a well-assessed strategy for conservative treatment of UM providing good results for survival, local control and eye preservation. Purpose Our aim is to develop predictive models for radio-induced effects in UM patients treated with exclusive GKSRS. Materials and methods Medical records and 3D dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for most clinically relevant GKSRS-related complications: radiation vasculopathy(RV), radiation papillopathy (RP) and neovascular glaucoma(NVG), visual acuity(VA) reduction >20% (VA20%) and complete loss of basal VA (VA100%). ROC curve analysis allowed predicting cutoff values of significant variables. Results The 2 years incidences were: RV 10%, RP 12%, NVG 14%, VA20% 59% and VA100% 27%. A clear relationship with D1% to optic nerve (ON) was found for RP and RV. Also, for RV, the prescription isodose-ON distance (PIOND) and the anterior to equator position of the tumor resulted as protective variables. The V20 of posterior segment and tumor thickness were predictive for NVG. Multivariate analyses resulted in two variables predictive model both for VA20% and VA100%, including tumor largest diameter and D1% to ON. A second predictive model, including PIOND, was found for VA100%. Conclusion We found clinical and dosimetric variables to predict the risk of main side effects after GKSRS for UM. These results may provide new dose constraints to critical structures potentially able to reduce toxicities. Disclosure Antonella del Vecchio has a contract as starter-up with Elekta Instrument AB. No other conflict of interest to declare for the other authors.

The correlation between bladder dose-wall-histogram (DWH) and dose-volume-histogram (DVH), dose-surface-histogram (DSH), and DVH-5/10 was investigated in a group of 28 patients; bladder walls were drawn on T2-MRI. DVH showed the poorest correlation with DWH; DSH or DVH-5/10 should be preferred in planning; absolute DVH may be used for radical patients, although less robust.

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 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. (C) 2012 Elsevier Inc.

Within a multicenter study (DUE-01) focused on the search of predictors of erectile dysfunction and urinary toxicity after radiotherapy for prostate cancer, a dummy run exercise on penile bulb (PB) contouring on computed tomography (CT) images was carried out. The aim of this study was to quantitatively assess interobserver contouring variability by the application of the generalized DICE index.Fifteen physicians from different Institutes drew the PB on CT images of 10 patients. The spread of DICE values was used to objectively select those observers who significantly disagreed with the others. The analyses were performed with a dedicated module in the VODCA software package.DICE values were found to significantly change among observers and patients. The mean DICE value was 0.67, ranging between 0.43 and 0.80. The statistics of DICE coefficients identified 4 of 15 observers who systematically showed a value below the average (p value range, 0.013 - 0.059): Mean DICE values were 0.62 for the 4 "bad" observers compared to 0.69 of the 11 "good" observers. For all bad observers, the main cause of the disagreement was identified. Average DICE values were significantly worse from the average in 2 of 10 patients (0.60 vs. 0.70, p0.05) because of the limited visibility of the PB. Excluding the bad observers and the "bad" patients," the mean DICE value increased from 0.67 to 0.70; interobserver variability, expressed in terms of standard deviation of DICE spread, was also reduced.The obtained values of DICE around 0.7 shows an acceptable agreement, considered the small dimension of the PB. Additional strategies to improve this agreement are under consideration and include an additional tutorial of the so-called bad observers with a recontouring procedure, or the recontouring by a single observer of the PB for all patients included in the DUE-01 study.

Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FES], 51%). WBRT doses >= 40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose >= 40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity. (C) 2011 Elsevier Inc.

Purpose Assessing predictors of acute bowel toxicity after whole-pelvis irradiation (WPRT) Image-guided Tomotherapy with simultaneous integrated boost on prostate/prostate bed. Methods and materials In the period March 2005–April 2009, 178 patients were treated with radical or adjuvant/salvage intent with WPRT Tomotherapy. Median dose to the pelvic nodes was 51.8Gy/28 fractions while concomitantly delivering 65.5–74.2Gy to prostate/prostatic bed. The impact of many anatomical and clinical parameters on ⩾Grade 2 acute bowel toxicity was investigated by logistic analyses. Results Only 15/178 patients (8.4%) experienced Grade 2 toxicity (none Grade 3). Main predictors at univariate analysis were nodal CTV (CTVN⩾380cc; OR: 3.7, p =0.017), treatment duration ( p =0.006) and Grade 2 acute rectal toxicity (OR: 6.5, p =0.015). A multivariate analysis including only pre-treatment variables revealed an independent role of CTVN and age; if including treatment-related factors the best predictors were age, treatment duration and Grade 2 rectal toxicity. This last was correlated with the overlap between PTVN and loops (OVPN⩾51cc; OR: 14.4, p =0.0003) that is representative of the volume of loops receiving the prescribed dose (51.8Gy, 1.85Gy/fr). Conclusions Acute bowel toxicity after WPRT Tomotherapy is mild, relatively rare and associated to larger CTVN and older age. While efforts to further reduce it do not appear to be relevant, the pre-treatment assessment of "high-risk" patients may help physicians in better managing symptoms. A prospective validation would be very important in confirming these results and in better refining dose-volume bowel effects including symptoms milder that the ones here investigated and retrospectively assessed.

To evaluate clinical and physico-dosimetric variables affecting clinical outcome of patients treated with Gamma Knife radiosurgery (GKRS) for brain metastases from non-small cell lung cancer (NSCLC).Between 2001 and 2006, 373 patients (298 men and 75 women, median age 65 years) with brain metastases from NSCLC underwent GKRS. All of them had KPS ≥ 60%, eight or fewer brain metastases, confirmed histopathological diagnosis and recent work-up (3 months). Thirty-five patients belonged to recursive partitioning analysis (RPA) Class I, 307 patients were in RPA Class II, 7 patients were in RPA Class III. Median tumor volume was 3.6 cm(3). Median marginal dose was 22.5 Gy at 50% isodose.; median 10 Gy and 12 Gy isodose volumes were 30.8 cm(3) and 15.8 cm(3), respectively. Follow-up with MRI was performed every 3 months. Overall survival data were collected from internal database, telephone interviews, and identifying registries.Mean follow-up after GKRS was 51 months (range, 6 to 96 months); mean overall survival was 14.2 months. Of 373 patients, 29 were alive at time of writing, 104 had died of cerebral progression, and 176 had died of systemic progression. In 64 cases it was not possible to ascertain the cause. Univariate and multivariate analysis were adjusted for the following: RPA class, surgery, WBRT, age, gender, number of lesions, median tumor volume, median peripheral dose, and 10 Gy and 12 Gy volumes. Identified RPA class and overall tumor volume5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression.Global volume of brain disease should be the main parameter to consider for performing GKRS, which is a first-line therapy for patient in good general condition and controlled systemic disease.