Savino Cilla

In vivo dosimetry by an aSi‐based EPID

A method for the in vivo determination of the isocenter dose, Diso, and mid-plane dose, Dm, using the transmitted signal St measured by 25 central pixels of an aSi-based EPID is here reported. The method has been applied to check the conformal radiotherapy of pelvic tumors and supplies accurate in vivo dosimetry avoiding many of the disadvantages associated with the use of two diode detectors (at the entrance and exit of the patient) as their periodic recalibration and their positioning. Irradiating water-equivalent phantoms of different thicknesses, a set of correlation functions F(w, l) were obtained by the ratio between St and Dm as a function of the phantom thickness, w, for a different field width, l. For the in vivo determination of Diso and Dm values, the water-equivalent thickness of the patients (along the beam central axis) was evaluated by means of the treatment planning system that uses CT scans calibrated in terms of the electron densities. The Diso and Dm values experimentally determined were compared with the stated doses D(iso,TPS) and D(m,TPS), determined by the treatment planning system for ten pelvic treatments. In particular, for each treatment four fields were checked in six fractions. In these conditions the agreement between the in vivo dosimetry and stated doses at the isocenter point were within 3%. Comparing the 480 dose values obtained in this work with those obtained for 30 patients tested with a similar method, which made use of a small ion-chamber positioned on the EPIDs to obtain the transmitted signal, a similar agreement was observed. The method here proposed is very practical and can be applied in every treatment fraction, supplying useful information about eventual patient dose variations due to the incorrect application of the quality assurance program based on the check of patient setup, machine setting, and calculations.

Complexity index (COMIX) and not type of treatment predicts undetected errors in radiotherapy planning and delivery

BACKGROUND AND PURPOSE Quality assurance procedures (QA) may reduce the risk of errors in radiotherapy. The aim of this study was to assess a QA program based on independent check (IC) procedures in patients undergoing 3D, intensity modulated (IMRT) and extracranial stereotactic (ESRT) radiotherapy. MATERIALS AND METHODS IC for set-up (IC1) and for radiotherapy treatments (IC2) was tested on 622 patients over a year. Fifteen events/parameters and 17 parameters were verified by IC1 and IC2, respectively. A third evaluation check (IC3) was performed before treatment. Potential errors were classified based on their magnitude. Incidents involving only incorrect or incomplete documentation were segregated. Treatments were classified based on a complexity index (COMIX). RESULTS With IC1, 75 documentation incidents and 31 potential errors were checked, and with IC2 111 documentation incidents and 6 potential errors were checked. During the study period 10 errors undetected by standard procedures (IC1, IC2) were detected by chance or by IC3. The incidence of errors and serious errors undetected by standard procedures was 1.6% and 0.6%, respectively. There was no higher incidence of errors undetected in patients undergoing IMRT or ESRT, while there was a higher incidence of errors undetected in more complex treatments (p < 0.001). CONCLUSIONS Systematic QA procedures can reduce the risk of errors. The risk of errors undetected by standard procedures is not correlated with the treatment technological level (3D versus IMRT/ESRT).

Application of a practical method for the isocenter point in vivo dosimetry by a transit signal

This work reports the results of the application of a practical method to determine the in vivo dose at the isocenter point, D(iso), of brain thorax and pelvic treatments using a transit signal S(t). The use of a stable detector for the measurement of the signal S(t) (obtained by the x-ray beam transmitted through the patient) reduces many of the disadvantages associated with the use of solid-state detectors positioned on the patient as their periodic recalibration, and their positioning is time consuming. The method makes use of a set of correlation functions, obtained by the ratio between S(t) and the mid-plane dose value, D(m), in standard water-equivalent phantoms, both determined along the beam central axis. The in vivo measurement of D(iso) required the determination of the water-equivalent thickness of the patient along the beam central axis by the treatment planning system that uses the electron densities supplied by calibrated Hounsfield numbers of the computed tomography scanner. This way it is, therefore, possible to compare D(iso) with the stated doses, D(iso,TPS), generally used by the treatment planning system for the determination of the monitor units. The method was applied in five Italian centers that used beams of 6 MV, 10 MV, 15 MV x-rays and (60)Co gamma-rays. In particular, in four centers small ion-chambers were positioned below the patient and used for the S(t) measurement. In only one center, the S(t) signals were obtained directly by the central pixels of an EPID (electronic portal imaging device) equipped with commercial software that enabled its use as a stable detector. In the four centers where an ion-chamber was positioned on the EPID, 60 pelvic treatments were followed for two fields, an anterior-posterior or a posterior-anterior irradiation and a lateral-lateral irradiation. Moreover, ten brain tumors were checked for a lateral-lateral irradiation, and five lung tumors carried out with three irradiations with different gantry angles were followed. One center used the EPID as a detector for the S(t) measurement and five pelvic treatments with six fields (many with oblique incidence) were followed. These last results are reported together with those obtained in the same center during a pilot study on ten pelvic treatments carried out by four orthogonal fields. The tolerance/action levels for every radiotherapy fraction were 4% and 5% for the brain (symmetric inhomogeneities) and thorax/pelvic (asymmetric inhomogeneities) irradiations, respectively. This way the variations between the total measured and prescribed doses at the isocenter point in five fractions were well within 2% for the brain treatment, and 4% for thorax/pelvic treatments. Only 4 out of 90 patients needed new replanning, 2 patients of which needed a new CT scan.

A PHASE I DOSE-ESCALATION STUDY (ISIDE-BT-1) OF ACCELERATED IMRT WITH TEMOZOLOMIDE IN PATIENTS WITH GLIOBLASTOMA

PURPOSE To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. METHODS AND MATERIALS A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +/- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >or=3 or any hematological toxicity rated as >or=4 by Radiation Therapy Oncology Group (RTOG) criteria. RESULTS Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. CONCLUSION Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

Intensity-modulated radiotherapy with simultaneous integrated boost to dominant intraprostatic lesion: preliminary report on toxicity.

ObjectivesTo evaluate the feasibility of intensity-modulated radiotherapy with simultaneous integrated boost to the dominant intraprostatic lesion for definitive treatment of prostate cancer. Materials and MethodsPatients were deemed eligible for the study if they had histologically proven stage cT2-T3 N0M0 prostate adenocarcinoma. In addition <20% risk of lymph nodal involvement according to Roach formula, was required for enrollment. Patients were treated with intensity-modulated radiotherapy with simultaneous integrated boost technique to the dominant intraprostatic lesion defined by magnetic resonance imaging. The prescribed dose to the prostate and seminal vesicles was 72 Gy (1.8 Gy per fraction). The dose delivered to the intraprostatic lesion received was 80 Gy (2 Gy per fraction). Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated weekly during treatment, and at 1 and 3 months thereafter. Late GI and GU toxicity was evaluated by Kaplan Meier method. ResultsForty patients were deemed evaluable. Acute and late GI and GU toxicity were evaluated in all patients. Two patients (5%) developed acute grade 3 GI toxicity and 1 patient (2.5%) developed acute grade 3 GU toxicity. No grade 4 acute GI or GU toxicity occurred. With a median follow-up of 19 months (interquartile range, 15 to 26 mo), the 2-year actuarial cumulative incidence of grade ≥2 rectal toxicity was 9.5%. The 2-year actuarial cumulative incidence of grade ≥2 urinary toxicity was 13.3%. ConclusionsTreatment related acute toxicity was low in our cohort. Prolonged observation with a larger series of patients is necessary to evaluate late toxicity and local control.

Integration between in vivo dosimetry and image guided radiotherapy for lung tumors

The article reports a feasibility study about the potentiality of an in vivo dosimetry method for the adaptive radiotherapy of the lung tumors treated by 3D conformal radiotherapy techniques (3D CRTs). At the moment image guided radiotherapy (IGRT) has been used for this aim, but it requires taking many periodic radiological images during the treatment that increase workload and patient dose. In vivo dosimetry reported here can reduce the above efforts, alerting the medical staff for the commissioning of new radiological images for an eventual adaptive plan. The in vivo dosimetry method applied on 20 patients makes use of the transit signal St on the beam central axis measured by a small ion chamber positioned on an electronic portal imaging device (EPID) or by the EPID itself. The reconstructed in vivo dosimetry at the isocenter point Diso requires a convolution between the transit signal St and a dose reconstruction factor C that essentially depends on (i) tissue inhomogeneities along the beam central axis and (ii) the in-patient isocenter depth. The C factors, one for every gantry angle, are obtained by processing the patients computed tomography scan. The method has been recently applied in some Italian centers to check the radiotherapy of pelvis, breast, head, and thorax treatments. In this work the dose reconstruction was carried out in five centers to check the Diso in the lung tumor during the 3D CRT, and the results have been used to detect the interfraction tumor anatomy variations that can require new CT imaging and an adaptive plan. In particular, in three centers a small ion chamber was positioned below the patient and used for the St measurement. In two centers, the St signal was obtained directly by 25 central pixels of an a-Si EPID, equipped with commercial software that enabled its use as a stable detector. A tolerance action level of +/- 6% for every checked beam was assumed. This means that when a difference greater than 6% between the predicted dose by the treatment planning system, Diso,TPS, and the Diso was observed, the clinical action started to detect possible errors. 60% of the patients examined presented morphological changes during the treatment that were checked by the in vivo dosimetry and successively confirmed by the new CT scans. In this work, a patient that showed for all beams Diso values outside the tolerance level, new CT scans were commissioned for an adaptive plan. The lung dose volume histograms (DVHs) for a Diso,TPs=2 Gy for fraction suggested the adaptive plan to reduce the dose in lung tissue. The results of this research show that the dose guided radiotherapy (DGRT) by the Diso reconstruction was feasible for daily or periodic investigation on morphological lung tumor changes. In other words, since during 3D CRT treatments the anatomical lung tumor changes occur frequently, the DGRT can be well integrated with the IGRT.

Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost for Locally Advanced Rectal Cancer

AIMS To report the feasibility of volumetric modulated arc therapy (VMAT) for neoadjuvant radiotherapy in locally advanced rectal cancer in a dose-escalation protocol and simultaneous integrated boost (SIB) approach. Moreover, the VMAT technique was compared with three-dimensional conformal radiotherapy (3D-CRT) and fixed-field intensity modulated radiotherapy (IMRT), in terms of target coverage and irradiation of organs at risk. MATERIALS AND METHODS Eight patients with locally advanced rectal cancer were treated with the SIB-VMAT technique. The VMAT plans were compared with 3D-CRT and IMRT techniques in terms of several clinically dosimetric parameters. The number of monitor units and the delivery time were analysed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a two-dimensional array of ionisation chambers. RESULTS All techniques meet the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformality. VMAT is associated with 40, 53 and 58% reduction in the percentage of volume of small bowel irradiated to 30, 40 and 50Gy, compared with 3D-CRT. No significant differences were found with respect to SIB-IMRT. VMAT plans showed a significant reduction of monitor units by nearly 20% with respect to IMRT and reduced treatment time from 14 to 5min for a single fraction. CONCLUSIONS SIB-VMAT plans can be planned and carried out with high quality and efficiency for rectal cancer, providing similar sparing of organs at risk to SIB-IMRT and resulting in the most efficient treatment option. SIB-VMAT is currently our standard approach for radiotherapy of locally advanced rectal cancer.

Generalized EPID calibration for in vivo transit dosimetry

Many researchers are studying new in vivo dosimetry methods based on the use of Elelctronic portal imaging devices (EPIDs) that are simple and efficient in their daily use. However the need of time consuming implementation measurements with solid water phantoms for the in vivo dosimetry implementation can discourage someone in their use. In this paper a procedure has been proposed to calibrate aSi EPIDs for in vivo transit dosimetry. The dosimetric equivalence of three aSi Varian EPIDs has been investigated in terms of signal reproducibility and long term stability, signal linearity with MU and dose per pulse and signal dependence on the field dimensions. The signal reproducibility was within ± 0.5% (2SD), while the long term signal stability has been maintained well within ± 2%. The signal linearity with the monitor units (MU) was within ± 2% and within ± 0.5% for the EPIDs controlled by the IAS 2, and IAS 3 respectively. In particular it was verified that the correction factor for the signal linearity with the monitor units, k(lin), is independent of the beam quality, and the dose per pulse absorbed by the EPID. For 6, 10 and 15 MV photon beams, a generalized set of correlation functions F(TPR,w,L) and empirical factors f(TPR,d,L) as a function of the Tissue Phantom Ratio (TPR), the phantom thickness, w, the square field side, L, and the distance, d, between the phantom mid-plane and the isocentre were determined to reconstruct the isocenter dose. The tolerance levels of the present in vivo dosimetry method ranged between ± 5% and ± 6% depending on the tumor body location. In conclusion, the procedure proposed, that use generalized correlation functions, reduces the effort for the in vivo dosimetry method implementation for those photon beams with TPR within ± 0.3% as respect those here used.

Initial clinical experience with Epid-based in-vivo dosimetry for VMAT treatments of head-and-neck tumors

We evaluated an EPID-based in-vivo dosimetry algorithm (IVD) for complex VMAT treatments in clinical routine. 19 consecutive patients with head-and-neck tumors and treated with Elekta VMAT technique using Simultaneous Integrated Boost strategy were enrolled. In-vivo tests were evaluated by means of (i) ratio R between daily in-vivo isocenter dose and planned dose and (ii) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ%) and mean γ-values (γmean), using a global 3%-3 mm criteria. Alert criteria of ±5% for R ratio, γ% < 90% and γmean > 0.67 were chosen. A total of 350 transit EPID images were acquired during the treatment fractions. The overall mean R ratio was equal to 1.002 ± 0.019 (1 SD), with 95.9% of tests within ±5%. The 2D portal images of γ-analysis showed an overall γmean of 0.42 ± 0.16 with 93.3% of tests within alert criteria, and a mean γ% equal to 92.9 ± 5.1% with 85.9% of tests within alert criteria. Relevant discrepancies were observed in three patients: a set-up error was detected for one patient and two patients showed major anatomical variations (weight loss/tumor shrinkage) in the second half of treatment. The results are supplied in quasi real-time, with IVD tests displayed after only 1 minute from the end of arc delivery. This procedure was able to detect when delivery was inconsistent with the original plans, allowing physics and medical staff to promptly act in case of major deviations between measured and planned dose.

Daily on-line set-up correction in 3D-conformal radiotherapy: is it feasible?

AIMS AND BACKGROUND The aim of this report was to investigate the feasibility in terms of treatment time prolongation of an on-line no-action level correction protocol, based on daily electronic portal image verification. METHODS AND STUDY DESIGN The occupation of a linear accelerator (LINAC) delivering 3-D conformal treatments was monitored for two weeks (from Monday to Friday, 10 working days). An electronic portal image device I-View (Elekta, UK) was used for setup verification. Single-exposure portal images were acquired daily using the initial 8 monitor units delivered for each treatment field. Translational deviations of isocenter position larger than 5 mm or 7 mm, for radical or palliative treatments, respectively, were immediately corrected. In order to estimate the extra workload involved with the on-line protocol, the time required for isocenter check and table correction was specifically monitored. RESULTS Forty-eight patients were treated. In all, 482 fractions had electronic portal images taken. Two hundred and forty-five setup corrections were made (50.8% of all fractions). The occupation of the LINAC lasted 106 h on the whole. Twelve h and 25 min (11.7% of LINAC occupation time) were spent for portal image verification and setup correction. On the average, 4.3 fractions per hour were carried out. CONCLUSIONS When used by trained therapists, ideally, portal imaging may be carried out before each fraction, requiring approximately 10% of LINAC occupation time.