Oligometastatic Prostate Cancer Treated with Stereotactic Body Radiation Therapy: The Role of Three-Dimensional Tumour Volume in Patient Survival.

AIMS: The definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. MATERIALS AND METHODS: This monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan-Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. RESULTS: Between 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4-93.4), 74.9% (95% confidence interval 66.1-81.7) and 57.2% (95% confidence interval 45.8-67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06-3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01-3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34-4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4-70.9), 31.5% (95% confidence interval 22.8-40.6) and 24.7% (95% confidence interval 16.0-34.3). CONCLUSIONS: This study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome.

Risk-group Classification by Recursive Partitioning Analysis of Patients Affected by Oligometastatic Renal Cancer Treated with Stereotactic Radiotherapy.

AIMS: Due to the absence of consensus on metastases-directed treatment in kidney cancer, we conducted an analysis of patients treated with stereotactic radiotherapy (SRT) on cranial or extracranial metastases to classify them in survival class risk according to pre-treatment characteristics. MATERIALS AND METHODS: We included oligometastatic kidney cancer patients treated with SRT on up to five metastases. Concomitant systemic treatment was allowed. End points included overall survival and the binary classification tree approach with recursive partitioning analysis was applied to stratify patients into overall survival risk groups. RESULTS: In total, 129 patients were treated on 242 metastases. The brain was the most common site (34.71%), followed by lung (25.62%). With a median follow-up of 19.4 months, 1- and 3-year overall survival were 82.62 and 55.11%. The recursive partitioning analysis identified four prognostic classes. Class 1 included patients aged ≤ 65 years treated on extracranial metastases, with 3-year overall survival of 82.66%. Class 2 included patients aged > 65 years, without history of metastatic bone disease, treated on extracranial metastases, with a 3-year overall survival of 67.91%. Patients aged > 65 years and a history of bone disease, treated on extracranial metastases, were classified as class 3, with a 3-year overall survival of 37.50%. Class 4 included patients treated on brain metastases, with a 3-year overall survival of 9.70%. CONCLUSION: We produced a stratification model that can predict survival of oligometastatic kidney cancer patients treated with metastases-directed SRT. Site of disease, patient's age and presence of bone disease can help clinicians in the decision-making process.

Long term results of a phase II trial of hypofractionated adjuvant radiotherapy for early-stage breast cancer with volumetric modulated arc therapy and simultaneous integrated boost.

PURPOSE: to report toxicity and cosmetic outcome with a median follow-up of 6 years of a phase II trial of hypofractionated radiotherapy with volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) for early-stage breast cancer after conservative surgery. MATERIALS AND METHODS: From August 2010 to September 2014, patients requiring adjuvant radiotherapy for early-stage breast cancer were treated according to a phase I-II protocol with SIB to 40.5 and 48 Gy to the breast and the boost region, respectively, with VMAT technique. The primary endpoint evaluated the treatment feasibility regarding adherence to required dose constraints for target, heart and lungs. Acute and late toxicity, local and distant control were secondary endpoints. RESULTS: 450 patients were included in the trial and analysed after a median follow-up of 6 years. Acute toxicity was already presented in a previous paper. Regarding late toxicity, 93% of patients had no skin alteration at five years, while 5.3% and 1.3% did record G1 and G2 residual toxicity, respectively. Cosmetic outcome was scored good or excellent in almost all cases (97.2%), fair only in 2.3% of patients. Residual tenderness in the irradiated breast was reported by 10% of patients. Cosmesis and breast pain improved during follow-up. Two cases of G2 pneumonitis and two cases of ischemic cardiopathy were registered during follow-up. Five cases presented local recurrence in the homolateral breast, four patients had a new primary cancer in the contralateral breast, while distant metastasis developed in 7 patients. CONCLUSION: After more than six years, hypofractionated VMAT with SIB for adjuvant radiotherapy in early-stage breast cancer patients remains a safe and effective approach. Mature data on skin toxicity and cosmetic outcome are encouraging. However, longer follow-up is required to evaluate local control, cardiac toxicity and secondary carcinogenesis.

The impact of scanning data measurements on the Acuros dose calculation algorithm configuration.

BACKGROUND: Many dose calculation algorithms for radiotherapy planning need to be configured for each clinical beam using pre-defined measurements. An optimization process adjusts the physical parameters able to estimate the energy released in the medium in any geometrical condition. This work investigates the impact of measured input data quality on the configuration of the type "c" Acuros-XB dose calculation algorithm in the Eclipse (Varian Medical Systems) treatment planning system. METHODS: Different datasets were acquired with the BeamScan water phantom (PTW) to configure 6 MV beams, for both flattened (6X) and flattening filter free mode (6FFF) for a Varian TrueBeam: (i) a correct dataset measured using a Semiflex-3D ion chamber, (ii) a set in missing lateral scatter conditions (MLS), (iii) a set with incorrect effective point of measurement (EPoM), (iv) sets acquired with PinPoint-3D chamber, DiodeP, microDiamond detectors. The Acuros-XB dose calculation algorithm (version 15.6) was configured using the reference dataset, the sets measured with the different detectors, with intentional errors, and using the representative beam data (RBD) made available by the vendor. The physical parameters obtained from each optimization process (spectrum, mean radial energy, electron contamination), were analyzed and compared. Calculated data were finally compared against the input and reference measurements. RESULTS: Concerning the physical parameters, the configurations presenting the largest differences were the MLS conditions (mean radial energy) and the incorrect EPoM (electron contamination). The calculation doses relative to the input data present low accuracy, with mean differences > 2% in some conditions. The PinPoint-3D ion chamber presented lower accuracy for the 6FFF beam. Regarding the RBD, calculations compared well with the input data used for the configuration, but not with the reference data. CONCLUSION: The MLS conditions and the incorrect setting of the EPoM lead to erroneous configurations and should be avoided. The choice of an appropriate detector is important. Whenever the representative beam data is used, a careful check under more clinical geometrical conditions is advised.

Technical Note: Flattening filter free beam from Halcyon linac: Evaluation of the profile parameters for quality assurance.

INTRODUCTION: The use of flattening filter free (FFF) beams generated by standard linear accelerators is increasing in the clinical practice. The radiation intensity peaked toward the beam central axis is properly managed in the optimization process of treatment planning through intensity modulation. Specific FFF parameters for profile analysis, as unflatness and slope for FFF beams, based on the renormalization factor concept has been introduced for quality assurance purposes. Recently, Halcyon, an O-ring based linear accelerator equipped with a 6 MV FFF beam only has been introduced by Varian. METHODS: Renormalization factors and related fit parameters according to Fogliata et al. ["Definition of parameters for quality assurance of FFF photon beams in radiation therapy," Med. Phys. 39, 6455-6464 (2012)] have been evaluated for the 6 MV FFF beam generated by Halcyon units. The Halcyon representative beam data provided by Varian were used. Dose fall-off at the field edges was matched with an unflattened beam generated by a 6 MV from a TrueBeam linac. Consistency of the results was evaluated against measurements on a clinical Halcyon unit, as well as a TrueBeam 6 MV FFF for comparison. RESULTS: The five parameters in the analytical equation for estimating the renormalization factor were determined with an R2 of 0.997. The comparison of the unflatness parameters between the Halcyon representative and hospital beam data was consistent within a range of 0.6%. Consistently with the computed parameters, the Halcyon profiles resulted in a less pronounced peak than TrueBeam. CONCLUSION: Renormalization factors and related fit parameters from the 6 MV FFF beam generated by the Varian Halcyon unit are provided.

RapidPlan knowledge based planning: iterative learning process and model ability to steer planning strategies.

PURPOSE: To determine if the performance of a knowledge based RapidPlan (RP) planning model could be improved with an iterative learning process, i.e. if plans generated by an RP model could be used as new input to re-train the model and achieve better performance. METHODS: Clinical VMAT plans from 83 patients presenting with head and neck cancer were selected to train an RP model, CL-1. With this model, new plans on the same patients were generated, and subsequently used as input to train a novel model, CL-2. Both models were validated on a cohort of 20 patients and dosimetric results compared. Another set of 83 plans was realised on the same patients with different planning criteria, by using a simple template with no attempt to manually improve the plan quality. Those plans were employed to train another model, TP-1. The differences between the plans generated by CL-1 and TP-1 for the validation cohort of patients were compared with respect to the differences between the original plans used to build the two models. RESULTS: The CL-2 model presented an improvement relative to CL-1, with higher R2 values and better regression plots. The mean doses to parallel organs decreased with CL-2, while D1% to serial organs increased (but not significantly). The different models CL-1 and TP-1 were able to yield plans according to each original strategy. CONCLUSION: A refined RP model allowed the generation of plans with improved quality, mostly for parallel organs at risk and, possibly, also the intrinsic model quality.

Collimator scatter factor: Monte Carlo and in-air measurements approaches.

BACKGROUND: Linac output as a function of field sizes has a phantom and a head scatter component. This last term can be measured in-air with appropriate build-up ensuring a complete electron equilibrium and the absence of the contaminant electrons. Equilibrium conditions could be achieved using a build-up cap or a mini-phantom. Monte Carlo simulations in a virtual phantom mimicking a mini-phantom were analysed with the aim of better understanding the setup conditions for measuring the collimator scatter factor that is the head scatter component of the linac output factors. METHODS: Beams of 6 and 15 MV from a TrueBeam, with size from 4 × 4 to 40 × 40 cm2 were simulated in cylindrical acrylic phantoms 20 cm long, of different diameters, from 0.5 to 4 cm, with the cylinder axis coincident with the beam central axis. The PRIMO package, based on PENELOPE Monte Carlo code, was used. The phase-space files for a Varian TrueBeam linac, provided by the linac vendor, were used for the linac head simulation. Depth dose curves were analysed, and collimator scatter factors estimated at different depth in the different phantom conditions. Additionally, in-air measurements using acyrilic and brass build-up caps, as well as acrylic mini-phantom were acquired for 6 and 18 MV beams from a Varian Clinac DHX. RESULTS: The depth dose curves along the cylinders were compared, showing, in each phantom, very similar curves for all analysed field sizes, proving the correctness in estimating the collimator scatter factor in the mini-phantom, provided to position the detector to a sufficient depth to exclude electron contamination. The results were confirmed by the measurements, where the acrylic build-up cap showed to be inadequate to properly estimate the collimator scatter factors, while the mini-phantom and the brass caps gave reasonable measurements. CONCLUSION: A better understanding of the beam characteristics inside a virtual mini-phantom through the analysis of depth dose curves, showed the critical points of using the acrylic build-up cap, and suggested the use of the mini-phantom for the collimator scatter factor measurements in the medium-large field size range.

Evaluation of target dose inhomogeneity in breast cancer treatment due to tissue elemental differences.

BACKGROUND: Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues. METHODS: CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV_lob and CTV_fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system. CT, structures and plans were imported in PRIMO, based on Monte Carlo code Penelope, to run three simulations: AdiMus, where the adipose and muscle tissues were automatically assigned to fat and lobular fractions of the breast; Adi and Mus, where adipose and muscle, respectively were assigned to the whole mammary gland. The specific tissue density was kept identical from the CT dataset. Differences in mean doses in the CTV_lob and CTV_fat structures were evaluated for the different tissue assignments. Differences generated by the tissue composition and estimated by Acuros dose calculations in Eclipse were also analysed. RESULTS: From Monte Carlo simulations, the dose in the lobular fraction of the breast, when adipose tissue is assigned in place of muscle, is overestimated by 1.25 ± 0.45%; the dose in the fat fraction of the breast with muscle tissue assignment is underestimated by 1.14 ± 0.51%. Acuros showed an overestimation of 0.98 ± 0.06% and an underestimation of 0.21 ± 0.14% in the lobular and fat portions, respectively. Reason of this dissimilarity resides in the fact that the two calculations, Monte Carlo and Acuros, differently manage the range of CT numbers and the material assignments, having Acuros an overlapping range, where two tissues are both present in defined proportions. CONCLUSION: Although not clinically significant, the dose deposition difference in the lobular and connective fat fraction of the breast tissue lead to an improved knowledge of the possible dose distribution and homogeneity in the breast radiation treatment.

Small field characterization of a Nanochamber prototype under flattening filter free photon beams.

INTRODUCTION: Nanochambers present some advantages in terms of energy independence and absolute dose measurement for small field dosimetry in the SBRT scenario. Characterization of a micro-chamber prototype was carried out both under flattened and flattening-filter-free (FFF) beams with particular focus on stem effect. METHODS: The study included characterization of leakage and stem effects, dose rate and dose per pulse dependence, measurement of profiles, and percentage depth doses (PDDs). Ion collection efficiency and polarity effects were measured and evaluated against field size and dose per pulse. The 6_MV, 6_MV_FFF and 10_MV FFF beams of a Varian EDGE were used. Output factors were measured for field sizes ranging from 0.8×0.8cm2 to 20×20cm2 and were compared with other detectors. RESULTS: The 2mm diameter of this chamber guarantees a high spatial resolution with low penumbra values. In orthogonal configuration a strong stem (and cable) effect was observed for small fields. Dose rate and dose per pulse dependence were <0.3% and 0.6% respectively for the whole range of considered values. The Nanochamber exhibits a field size (FS) dependence of the polarity correction >2%. The OF values were compared with other small field detectors showing a good agreement for field sizes >2×2cm2. The large field over-response was corrected applying kpol(FS). CONCLUSIONS: Nanochamber is an interesting option for small field measurements. The spherical shape of the active volume is an advantage in terms of reduced angular dependence. An interesting feature of the Nanochamber is its beam quality independence and, as a future development, the possibility to use it for small field absolute dosimetry.

RapidPlan head and neck model: the objectives and possible clinical benefit.

BACKGROUND: To evaluate a knowledge based planning model for RapidPlan (RP) generated for advanced head and neck cancer (HNC) patient treatments, as well its ability to possibly improve the clinical plan quality. The stability of the model was assessed also for a different beam geometry, different dose fractionation and different management of bilateral structures (parotids). METHODS: Dosimetric and geometric data from plans of 83 patients presenting HNC were selected for the model training. All the plans used volumetric modulated arc therapy (VMAT, RapidArc) to treat two targets at dose levels of 69.96 and 54.45 Gy in 33 fractions with simultaneous integrated boost. Two models were generated, the first separating the ipsi- and contra-lateral parotids, while the second associating the two parotids to a single structure for training. The optimization objectives were adjusted to the final model to better translate the institutional planning and dosimetric strategies and trade-offs. The models were validated on 20 HNC patients, comparing the RP generated plans and the clinical plans. RP generated plans were also compared between the clinical beam arrangement and a simpler geometry, as well as for a different fractionation scheme. RESULTS: RP improved significantly the clinical plan quality, with a reduction of 2 Gy, 5 Gy, and 10 Gy of the mean parotid, oral cavity and laryngeal doses, respectively. A simpler beam geometry was deteriorating the plan quality, but in a small amount, keeping a significant improvement relative to the clinical plan. The two models, with one or two parotid structures, showed very similar results. NTCP evaluations indicated the possibility of improving (NTCP decreasing of about 7%) the toxicity profile when using the RP solution. CONCLUSIONS: The HNC RP model showed improved plan quality and planning stability for beam geometry and fractionation. An adequate choice of the objectives in the model is necessary for the trade-offs strategies.

Organs at risk in lung SBRT.

Lung stereotactic body radiotherapy (SBRT) is an accurate and precise technique to treat lung tumors with high 'ablative' doses. Given the encouraging data in terms of local control and toxicity profile, SBRT has currently become a treatment option for both early stage lung cancer and lung oligometastatic disease in patients who are medically inoperable or refuse surgical resection. Dose-adapted fractionation schedules and ongoing prospective trials should provide further evidence of SBRT safety trying to reduce toxicities and complications. In this heterogeneous scenario, a non-systematic review of dose constraints for lung SBRT was performed, including the main organs at risk in the thorax.

High-quality Linac-based Stereotactic Body Radiation Therapy with Flattening Filter Free Beams and Volumetric Modulated Arc Therapy for Low-Intermediate Risk Prostate Cancer. A Mono-institutional Experience with 90 Patients.

AIMS: The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer. MATERIALS AND METHODS: Biopsy-confirmed prostate cancer patients were enrolled, provided that they had the following characteristics: initial prostate-specific antigen (PSA) ≤ 20 ng/ml, Gleason Score < 7, International Prostate Symptom Score < 7. The treatment schedule was 35 Gy in five fractions, delivered with volumetric modulated arcs with flattening filter free beams. Toxicity was recorded according to CTCAE criteria v4.0. Biochemical failure was calculated according to the Phoenix definition. The Expanded Prostate Cancer Index Composite questionnaire was used to record health-related quality of life. RESULTS: Between December 2011 and March 2015, 90 patients were enrolled (53 low risk, 37 intermediate risk). The median age was 71 years (range 48-82). In total, 58 (64.5%) of the patients had Gleason Score=6, the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml (range 2.7-17.0). Acute toxicity was mild, with 32.2 patients presenting grade 1 urinary toxicity and 32.2% of patients presenting grade 2 urinary toxicity, mainly represented by urgency, dysuria and stranguria. Rectal grade 1 toxicity was found in 15.5% of patients, whereas grade 2 toxicity was recorded in 6.6% of patients. Regarding late toxicity, grade 1 proctitis was recorded in 11.1% of patients and grade 1 urinary in 38.8%; only two events of grade 2 urinary toxicity were observed (transient urethral stenosis, resolved by a 24 h catheterisation). At a median follow-up of 27 months (6-62 months) only two intermediate risk patients experienced a biochemical failure. Health-related quality of life revealed a slight worsening in all the domains during treatment, with a return to baseline 3 months after treatment. CONCLUSIONS: Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life.

Total monitor units influence on plan quality parameters in volumetric modulated arc therapy for breast case.

PURPOSE: To investigate the correlation between total monitor units (MU), dosimetric findings, and pre-treatment quality assurance for volumetric modulated arc therapy (VMAT) by RapidArc (RA). METHODS AND MATERIALS: Ten patients with breast cancer were considered. Dose prescriptions were: 48 Gy and 40.5 Gy in 15 fractions to, respectively, PTV(Boost) and PTVWholeBreast. A reference plan was optimized and four more plans using the "MU Objective", a tool for total MU controlling, were prepared imposing ± 20 and ± 50% total MU for inducing different complexities. Plan objectives were: D95% > 95% for both PTVs, and D2% < 107% for PTV(Boost); mean dose < 9.5 Gy and V20 Gy < 10% for ipsilateral lung; V18 Gy < 5% for heart; mean dose <3 Gy for controlateral breast; furthermore V5 Gy, V10 Gy, V20 Gy, and V30 Gy to body were minimized. Plans were evaluated in terms of technical parameters, dosimetric plan objectives findings and pre-treatment quality assurance (QA). RESULTS: Concerning PTVs, there were no significant differences for target coverage (D95%); mean doses for ipsilateral lung and controlateral breast, and V18 Gy for heart decreased with MUs increasing, reaching a plateau with reference plan. Body volume receiving low dose (V5-10 Gy) was minimized for reference plans. All plans had GAI (3 mm, 3%) > 95%. CONCLUSIONS: The data suggest that the best plan is the reference one, where the "MU Objective" tool was not used during optimisation. Nevertheless, it is advisable to use the "MU Objective" tool for re-planning when low GAI is found to increase its value. In this case, attention should be paid to OARs dose limits, since their values may be increased.

Moderate hypofractionation and simultaneous integrated boost with volumetric modulated arc therapy (RapidArc) for prostate cancer. Report of feasibility and acute toxicity.

PURPOSE: In the present study, the acute toxicity profiles for prostate patients treated with simultaneous integrated boost (SIB) with volumetric modulated arcs in a hypofractionated regime are reported. PATIENTS AND METHODS: A total of 70 patients treated with RapidArc between May 2010 and September 2011 were retrospectively evaluated. Patients were stratified into low (36%), intermediate (49%), and high-risk (16%) groups. Target volumes (expanded to define the planning volumes (PTV)) were clinical target volume (CTV) 1: prostate; CTV2: CTV1 + seminal vesicles; CTV3: CTV2 + pelvic nodes. Low-risk patients received 71.4 Gy to PTV1; intermediate-risk 74.2 Gy to PTV1 and 61.6 or 65.5 Gy to PTV2; high-risk 74.2 Gy to PTV1, 61.6 or 65.5 Gy to PTV2, and 51.8 Gy to PTV3. All treatments were in 28 fractions. The median follow-up was 11 months (range 3.5-23 months). The acute rectal, gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to EORTC/RTOG scales. RESULTS: Acute toxicities were recorded for the GU [G0 = 31/70 (44%), G1 = 22/70 (31%); G2 = 16/70 (23%); G3 = 1/70 (1%)], the rectum [G0 = 46/70 (66%); G1 = 12/70 (17%); G2 = 12/70 (17%); no G3], and the GI [G0 = 54/69 (77%); G1 = 11/69 (16%); G2 = 4/69 (6%); no G3]. Median time to rectal, GU, and GI toxicities were 27, 30, and 33 days, respectively. Only the GI toxicity correlated with stage and pelvic irradiation. Univariate analysis presented significant correlations between GI toxicity and intestinal irradiation (V(50 Gy) and V(60 Gy)). In the multivariate analysis, the only significant dosimetric variable was V(50 Gy) for the intestinal cavity. CONCLUSION: Moderate hypofractionation with SIB and RapidArc was shown to be safe, with acceptable acute toxicity. Longer follow-up is needed to assess late toxicity and clinical outcome.

Prospective phase II trial of cetuximab plus VMAT-SIB in locally advanced head and neck squamous cell carcinoma. Feasibility and tolerability in elderly and chemotherapy-ineligible patients.

INTRODUCTION: Cetuximab plus radiotherapy (RT) may be an effective alternative to chemoradiation in locally advanced head and neck squamous cell carcinoma (LASCCHN) patients. We analyzed a group of patients treated at our institute with cetuximab plus volumetric modulation arc therapy (VMAT) with the RapidArc technique in a simultaneous integrated boost (SIB) regime. The primary end point was the assessment of acute toxicity and the feasibility of the combined approach. MATERIALS AND METHODS: Between December 2008 and March 2010, 22 patients were submitted to IMRT-SIB plus cetuximab for radical intent in case of LASCCHN. None of the patients was suitable for chemotherapy because of important comorbidities (the majority suffered of heart chronic diseases). All patients underwent planning CT (additional image modalities were acquired for contouring purposes in the same treatment position: MRI in 12 and FDG-PET in 4 out of 22 patients). VMAT, by means of RapidArc, and SIB with two dose levels of 54.45 Gy and 69.96 Gy in 33 fractions were adopted. All patients included in the analysis were concomitantly treated with cetuximab: administration of the drug was initiated 1 week before RT at a loading dose of 400 mg/m(2) body surface area over a period of 120 min, follow by a weekly 60 min infusion of 250 mg/m(2) for the duration of RT. Patients were assessed for toxicities according to the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: All but 2 patients completed treatment and achieved the minimum follow-up of 12 months after the end of the treatment. Of the 22 patients, 18% (4 patients) showed grade 1, 36% (8 patients) grade 2, and 36% (8 patients) showed grade 3 dermatitis, while 9% (2 patients) had grade 1, 36% (8 patients) grade 2, and 45% (10 patients) had grade 3 mucositis/stomatitis. No grade 4 toxicities were recorded. Considering blood parameters, 3 cases of grade 1 anemia and 1 case of grade 2 thrombocytopenia were observed. Nobody required feeding tube placement during treatment. CONCLUSION: The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.

[Analysis of comments on 26 cases of biliary ileus]. / Analisi e considerazioni su 26 casi di ileo biliare.

The Authors describe a case of gall-stone ileus complicated by a bowel perforation they had the chance to observe. They have treated it surgically with success. Starting from this clinical care, they have analysed the cases of gall-stone ileus in their department in these last ten years, then they have looked over the literature and the draw conclusions concerning diagnosis, time of hospitalisation and a surgical treatment and the levels where occlusions occur more frequently.