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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 patient's 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. Thelung 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. © 2009 American Association of Physicists in Medicine.

Aims and background The aim of the study was to analyze the dose to be administered with two-dimensional involved-field palliative radiotherapy in advanced pancreatic carcinoma with respect to current dose-volume constraints (QUANTEC). Methods and study design The following standard regimens were evaluated: 30 Gy at 3 Gy/fraction (regimen A), 36 Gy at 2.4 Gy/fraction (regimen B), 45 Gy at 1.8 Gy/fraction (regimen C), and 50 Gy at 2 Gy/fraction (regimen D). The following constraints were considered: spinal cord Dmax max mean mean 10/15 patients of constraints for kidneys and liver. Therefore, minor violations (Results In regimen A (30 Gy, 3 Gy/fraction), evaluated constraints were respected in all patients, regardless of the type of energy. In regimen B (36 Gy, 2.4 Gy/fraction), constraints were met in all patients undergoing irradiation with 6 and 15 MV photons. However, using the cobalt unit, kidney constraint was respected only in 5 of 15 patients. In regimens C and D (45 Gy, 1.8 Gy/fraction and 50 Gy, 2 Gy/fraction, respectively), the constraint for the kidney was respected only in 2–5 patients, depending on the energy used. Furthermore, using 50 Gy, the spinal cord constraint was not respected in 2–3 patients, depending on the beam used. Therefore, only the following treatments were considered acceptable: 1) 30 Gy, 3 Gy/fraction, regardless of the energy used; 2) 36 Gy, 2.4 Gy/fraction, only for treatments performed with linear accelerator (6–15 MV). Conclusions The clinical benefits of radiotherapy in pancreatic tumors should not be withheld from patients treated in centers only with two-dimensional technology. Prospective trials, particularly in developing countries, would be useful to evaluate the efficacy in this setting of involved-field two-dimensional treatments using the dose and fractionation defined in this analysis.

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). © 2008 Elsevier Ireland Ltd. All rights reserved.

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36. min/Gy. The mean number of monitor units was 3162, i.e., 121.6. MU/Gy. Pretreatment verification (3%-3. mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.

OBJECTIVE: To explore the potential of volumetric-modulated arc therapy (VMAT) to reduce the risk of swallowing problems after curative chemoradiotherapy. METHODS: 20 patients with head and neck cancer who previously underwent radiotherapy were selected. Radiotherapy was prescribed according to simultaneous integrated boost technique with all targets irradiated simultaneously over 30 daily fractions. Doses of 70.5 (67.5), 60.0 and 55.5 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Pharyngeal constrictor muscles (PCM) and glottic and supraglottic larynx (SGL) were considered organs at risk related to swallowing dysfunction (SW-OARs). Upper pharyngeal constrictor muscles (uPCM), middle pharyngeal constrictor muscles (mPCM) and lower pharyngeal constrictor muscles (lPCM) part of PCM were also outlined separately. Clinical standard plans (standard-VMAT) and plans aiming to spare SW-OARs (swallowing dysfunction-VMAT) were also created. Normal tissue complication probabilities (NTCP) for physician-rated swallowing dysfunction were calculated using a recently predictive model developed by Christianen et al. RESULTS: Planning with two strategies demonstrated comparable planning target volume coverage and no differences in sparing of parotid glands and other non-swallowing organs at risk. SW-VMAT plans provided mean dose reduction for uPCM and SGL by 3.9 and 4.5 Gy, respectively. NTCP values for Radiation Therapy Oncology Group grade 2-4 swallowing dysfunction was decreased by 9.2%. Dose reductions with SW-VMAT depended on tumour location and overlap with SW-OARs. CONCLUSION: VMAT plans aiming at sparing swallowing structures are feasible, providing a significant reduction in NTCP swallowing dysfunction with respect to conventional VMAT. ADVANCES IN KNOWLEDGE: Dysphagia is today considered one of the dose-limiting toxicities of chemoradiotherapy. The dose sparing of swallowing structures represents a major challenge in radiotherapy. VMAT is a complex new technology having the potential to significantly reduce the risk of dysphagia after curative chemoradiotherapy.

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.

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.

Purpose: To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence. Patients and Methods: A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated by a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity. Results: Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable. Conclusions: The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy. © 2010 Elsevier Inc. All rights reserved.

Scarce data are available on the use of extracranial stereotactic radiotherapy in recurrent gynecological tumors. The aim of this report was to analyze the results of our preliminary experience with extracranial stereotactic radiotherapy in locally or distantly recurrent gynecological tumors. Extracranial stereotactic radiotherapy was planned by the Precise-Plan treatment planning system. Patients were immobilized using the Stereotactic Body-Frame. Five consecutive daily fractions were delivered; dose/fraction and total dose were defined based on an institutional dose-escalation protocol. A class solution with 4 non-coplanar fixed beams based on the tetrad configuration was used in all patients. Eleven patients (12 lesions), were included in the analysis. Stereotactic radiotherapy was delivered as first radiotherapy treatment (5 patients), or as retreatment (6 patients). Complete clinical response was achieved in 8/12 lesions (66.6%), while partial response was documented in 2/12 lesions (16.6%). With a median follow-up of 19 months (range, 2-37 months), 7 patients (63%) experienced local and/or distant progression of disease. The 2-year local progression-free survival was 81.8%, while the 2-year metastases-free survival was 54.4%. The 2-year overall survival was 63.6%. Acute and late toxicities were grade 2 or less. There was no difference in quality of life scores between the data collected before extracranial stereotactic radiotherapy and at first follow-up evaluation. Fractionated extracranial stereotactic radiotherapy administered up to a dose of 30 Gy in five fractions is well tolerated. Further studies of extracranial stereotactic radiotherapy and novel radiotherapy techniques are warranted in the challenging setting of recurrent gynecological tumors.

Background and purpose: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. Materials and methods: Prescribed dose to the breast was 50.4 Gy in the CG, 40 Gy in MARA-1 (low risk of local recurrence), and 50 Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4 Gy (sequential 10 Gy electron boost), 44 Gy (concomitant 4 Gy boost), and 60 Gy (concomitant 10 Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4 weeks); 16 fractions for MARA-1 study (3.2 weeks) and 25 fractions for MARA-2 study (5 weeks). Results: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed Dmax and V107% reduction (p < 0.001) and Dmin improvement (p < 0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p < 0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. Conclusions: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6 weeks; MARA-1, 3.2 weeks; MARA-2, 5 weeks) with acceptable short-term toxicity. © 2008 Elsevier Ireland Ltd. All rights reserved.

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 ≥3 or any hematological toxicity rated as ≥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. © 2010 Elsevier Inc. All rights reserved.

Introduction. The breath-hold is one of the techniques to obtain the dose escalation for lung tumors. However, the change of the patient's breath pattern can influence the stability of the inhaled air volume, IAV, used in this work as a surrogate parameter to assure the tumor position reproducibility during dose delivery. Materials. and method. In this paper, an Elekta active breathing coordinator has been used for lung tumor irradiation. This device is not an absolute spirometer and the feasibility study here presented developed (i) the possibility to select a specific range ε of IAV values comfortable for the patient and (ii) the ability of a transit signal rate Ṡt, obtained by a small ion-chamber positioned on the portal image device, to supply in real time the in vivo isocenter dose reproducibility. Indeed, while the selection of the IAV range depends on the patient's ability to follow instructions for breath-hold, the Ṡt monitoring can supply to the radiation therapist a surrogate of the tumor irradiation reproducibility. Results. The detection of the Ṡt in real time during breath-hold was used to determine the interfraction isocenter dose variations due to the reproducibility of the patient's breathing pattern. The agreement between the reconstructed and planned isocenter dose in breath-hold at the interfraction level was well within 1.5%, while in free breathing a disagreement up to 8% was observed. The standard deviation of the Ṡt in breath-hold observed at the intrafraction level is a bit higher than the one obtained without the patient and this can be justified by the presence of a small residual tumor motion as heartbeat. Conclusion. The technique is simple and can be implemented for routine use in a busy clinic. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).

This work reports a practical method for the determination of the in vivo breast middle dose value, Dm, on the beam central axis, using a signal St, obtained by a small thimble ion chamber positioned at the center of the electronic portal imaging device, and irradiated by the x-ray beam transmitted through the patient. The use of a stable ion chamber reduces many of the disadvantages associated with the use of diodes as their periodic recalibration and positioning is time consuming. The method makes use of a set of correlation functions obtained by the ratios St Dm, determined by irradiating cylindrical water phantoms with different diameters. The method proposed here is based on the determination of the water-equivalent thickness of the patient, along the beam central axis, by the treatment planning system that makes use of the electron densities obtained by a computed tomography scanner. The method has been applied for the breast in vivo dosimetry of ten patients treated with a manual intensity modulation with four asymmetric beams. In particular, two tangential rectangular fields were first delivered, thereafter a fraction of the dose (typically less than 10%) was delivered with two multi leaf-shaped beams which included only the mammarian tissue. Only the two rectangular fields were tested and for every checked field five measurements were carried out. Applying a continuous quality assurance program based on the tests of patient setup, machine settings and dose planning, the proposed method is able to verify agreements between the computed dose Dm,TPS and the in vivo dose value Dm, within 4%. © American Association of Physicists in Medicine.

The case is reported of a patient with locally recurrent carcinoma of the tongue treated with intensity-modulated radiotherapy (IMRT) (simultaneous integrated boost) plus concurrent chemotherapy, who during the third week of radiotherapy developed grade 3 mucositis. Treatment was interrupted for 10 days until significant resolution of the symptoms. At the time of treatment resumption the patient showed 8% weight loss, and in vivo portal dose verification revealed large discrepancies between the computed and measured doses. A new CT scan showed marked tumor shrinkage and modifications to the critical structures. The comparison between the original plan and the hybrid IMRT showed a minimal dose increase in the new target volumes and a marked dose increase in the organs at risk. This case confirms the need for a robust quality assurance program when using IMRT, the feasibility and efficacy of in vivo dosimetry to detect significant discrepancies between planned and delivered dose, and the need to combine IMRT with 4-dimensional radiotherapy, at least for head and neck cancer.