Radiotherapy & Oncology - Articles in Press

Clinical performance of a transmission detector array for the permanent supervision of IMRT deliveries - Corrected Proof

2010-02-08

Abstract: Background and purpose: Clinical evaluation of a novel dosimetric accessory serving the permanent supervision of MLC function.Materials and methods: The DAVID system (PTW-Freiburg, Germany) is a transparent, multi-wire transmission ionization chamber, placed in the accessory holder of the treatment head. Since each of the 37 individual wires is positioned exactly below the associated leaf pair of the MLC, its signal records the opening of this leaf pair during patient treatment.Results: The DAVID system closes a gap in the quality assurance program, permitting the permanent in-vivo verification of IMRT plans. During dosimetric plan verification with the 2D-ARRAY (PTW-Freiburg, Germany), reference values of the 37 DAVID signals are collected, with which the DAVID readings recorded during daily patient treatment are compared. This comparison is visually displayed in the control room, and warning and alarm levels of any discrepancies can be defined. The properties of the DAVID system as a transmission device, its sensitivity to beam delivery and leaflet errors as well as its stability have been analyzed for clinically relevant examples. In a recent version, the DAVID system has been equipped with 160 wires.Conclusions: The DAVID system permits the on-line detection of clinically relevant MLC discrepancies in IMRT deliveries.

Stereotactic radiation therapy for large vestibular schwannomas - Corrected Proof

2010-02-08

Abstract: Background and purpose: To evaluate the morbidity and tumor-control rate in the treatment of large vestibular schwannomas (VS) after stereotactic radiation therapy in our institution.Material and methods: Twenty-five consecutive patients (17 men, 8 women) with large VS (diameter 3.0cm or larger), treated with stereotactic radiotherapy (SRT) or stereotactic radiosurgery (SRS) between 1992 and 2007, were retrospectively studied after a mean follow-up period of three years with respect to tumor-control rate and complications.Results: Actuarial 5-year maintenance of pre-treatment hearing level probability of 30% was achieved. Five of 17 patients suffered permanent new facial nerve dysfunction. The actuarial 5-year facial nerve preservation probability was 80%. Permanent new trigeminal nerve neuropathy occurred in two of 15 patients, resulting in an actuarial 5-year trigeminal nerve preservation probability of 85%. Tumor progression occurred in four of 25 (16%) patients. The overall 5-year tumor control probability was 82%.Conclusion: Increased morbidity rates were found in patients with large VS treated with SRT or SRS compared to the published series on regular sized VS and other smaller retrospective studies on large VS.

From point A to the sculpted pear: MR image guidance significantly improves tumour dose and sparing of organs at risk in brachytherapy of cervical cancer - Corrected Proof

2010-02-08

Abstract: Background and purpose: Brachytherapy in locally advanced cervical cancer is still widely based on 2D standard dose planning, although 3D image guidance is available. The purpose of this study was to compare point doses to 3D dose volume parameters for tumour and organs at risk (OARs), and to evaluate the improvement of dose parameters with MR image guided adaptive brachytherapy (IGABT).Material and methods: MRI-based IGABT was performed in 72 consecutive patients. HR-CTV, IR-CTV, bladder, rectum and sigmoid were contoured according to GEC-ESTRO recommendations. BT standard dose planning was compared to MRI-based dose optimisation.Results: HR-CTV dose (D90) was highly variable in standard plans with point A dose prescription. In small tumours (<31cc) HR-CTV was well covered by standard plans in 94% of patients, while OAR constraints were exceeded in 72% of patients. Optimisation decreased violation of OAR constraints to only 6% of patients while maintaining excellent target coverage. In large tumours (>31cc) the dose optimisation improved the HR-CTV D90 by a mean of 7Gy resulting in full coverage in 72% of patients as compared to 25% for standard plans, even while reducing violation of OAR constraints.Conclusion: Point A dose is a poor surrogate of HR-CTV dose, and the use of 3D image-based dose planning is encouraged. MRI-based IGABT significantly improves target coverage and OAR dose.

A two-variable linear model of parotid shrinkage during IMRT for head and neck cancer - Corrected Proof

2010-02-01

Abstract: Purpose: To assess anatomical, clinical and dosimetric pre-treatment parameters, possibly predictors of parotid shrinkage during radiotherapy of head and neck cancer (HNC).Materials: Data of 174 parotids from four institutions were analysed; patients were treated with IMRT, with radical and adjuvant intent. Parotid shrinkage was evaluated by the volumetric difference (ΔV) between parotid volumes at the end and those at the start of the therapy, as assessed by CT images (MVCT for 40 patients, KVCT for 47 patients). Correlation between ΔVcc/% and a number of dosimetric, clinical and geometrical parameters was assessed. Univariate as well as stepwise logistic multivariate (MVA) analyses were performed by considering as an end-point a ΔVcc/% larger than the median value. Linear models of ΔV (continuous variable) based on the most predictive variables found at the MVA were developed.Results: Median ΔVcc/% were 6.95cc and 26%, respectively. The most predictive independent variables of ΔVcc at MVA were the initial parotid volume (IPV, OR: 1.100; p=0.0002) and Dmean (OR: 1.059; p=0.038). The main independent predictors of ΔV% at MVA were age (OR: 0.968; p=0.041) and V40 (OR: 1.0338; p=0.013). ΔVcc and ΔV% may be well described by the equations: ΔVcc=−2.44+0.076 Dmean (Gy)+0.279 IPV (cc) and ΔV%=34.23+0.192 V40 (%)−0.2203 age (year). The predictive power of the ΔVcc model is higher than that of the ΔV% model.Conclusions: IPV/age and Dmean/V40 are the major dosimetric and clinical/anatomic predictors of ΔVcc and ΔV%. ΔVcc and ΔV% may be well described by bi-linear models including the above-mentioned variables.

Interstitial fluid pressure of tumors as a function of parameters derived by dynamic contrast-enhanced magnetic resonance imaging: Response to letter by Farace and Boschi - Corrected Proof

Kristine Gulliksrud, Tormod A.M. Egeland, Jon-Vidar Gaustad, Einar K. Rofstad — 2010-02-01

We read with interest the letter by Farace and Boschi sharing their thoughts on strategies for assessing the interstitial fluid pressure (IFP) of tumors by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Interstitial fluid pressure as a function of DCE-MRI derived parameters - Corrected Proof

Paolo Farace, Federico Boschi — 2010-02-01

To the Editor, We read with interest the study of Gulliksrud et al. on interstitial fluid pressure (IFP) – a parameter associated with radiocurability . They investigated high-resolution dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), by Gd-DTPA bolus injection, to provide interstitial fluid pressure (IFP) mapping, alternatively to the slow infusion method proposed by other Authors. They concluded that the bolus injection method is feasible for assessing IFP in tumours without necrosis, but to be clinically useful, a relationship between IFP and the pharmacokinetic parameters should be provided. The slow infusion method, proposed by Hassid et al. , proved that the interstitial (i.e. in the extracellular extravascular space – EES) concentration of Gd-DTPA at steady state of infusion () reflected the spatial distribution of IFP, assuming a negative linear relation between and IFP.

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data - Corrected Proof

Ingrid T. Kuijper, Max Dahele, Suresh Senan, Wilko F.A.R. Verbakel — 2010-02-01

Abstract: Background and purpose: Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).Materials and methods: RA and IMRT plans to deliver a fraction of 16Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n=3), while group 2 had PTVs encompassing the entire vertebra (n=4). Finally, RA delivery parameters in four patients were assessed.Results: Both techniques delivered 16Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V10-partial cord for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2–3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4min.Conclusions: Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.

Inter-observer and intra-observer reliability for lung cancer target volume delineation in the 4D-CT era - Corrected Proof

2010-02-01

Abstract: Background and purpose: To investigate inter-observer and intra-observer target volume delineation (TVD) error in 4D-CT imaging of thoracic tumours.Materials and methods: Primary and nodal gross tumour volumes (GTV) of 10 lung tumours on the 10 respiratory phases of a 4D-CT scan were contoured by six radiation oncologist observers. Inter-observer and intra-observer variability were assessed by the coefficient of variation (COV) and the volume overlap index (VOI). ANOVA was performed to assess differences in inter-observer and intra-observer variability based on patient case difficulty, respiratory phase, physician seniority, and physician observer.Results: VOI analysis determined that inter-observer was a more significant source of error than intra-observer variability. VOI improved with the use of 4D-CT as compared to conventional CT. ANOVA analysis for COVs found case difficulty (easy versus difficult) to be significant for inter-observer primary tumour and intra-observer nodal disease delineation. Physician seniority, respiratory phase, and individual physician were not found to be significant for TVD error.Conclusion: Variability in TVD is a major source of error in 4D-CT treatment planning. Development of measures to reduce inter-observer and intra-observer TVD variability are necessary in order to deliver high quality radiotherapy.

A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery system for intracranial lesions - Corrected Proof

2010-02-01

Abstract: Background and purpose: A comparison of patient positioning and intra-fraction motion using invasive frame-based radiosurgery with a frameless X-ray image-guided system utilizing a thermoplastic mask for immobilization.Materials and methods: Overall system accuracy was determined using 57 hidden-target tests. Positioning agreement between invasive frame-based setup and image-guided (IG) setup, and intra-fraction displacement, was evaluated for 102 frame-based SRS treatments. Pre and post-treatment imaging was also acquired for 7 patients (110 treatments) immobilized with an aquaplast mask receiving fractionated IG treatment.Results: The hidden-target tests demonstrated a mean error magnitude of 0.7mm (SD=0.3mm). For SRS treatments, mean deviation between frame-based and image-guided initial positioning was 1.0mm (SD=0.5mm). Fusion failures were observed among 3 patients resulting in aberrant predicted shifts. The image-guidance system detected frame slippage in one case. The mean intra-fraction shift magnitude observed for the BRW frame was 0.4mm (SD=0.3mm) compared to 0.7mm (SD=0.5mm) for the fractionated patients with the mask system.Conclusions: The overall system accuracy is similar to that reported for invasive frame-based SRS. The intra-fraction motion was larger with mask-immobilization, but remains within a range appropriate for stereotactic treatment. These results support clinical implementation of frameless radiosurgery using the Novalis Body Exac-Trac system.

Is the Roach formula predictive for biochemical outcome in prostate cancer patients with minimal residual disease undergoing local radiotherapy after radical prostatectomy? - Corrected Proof

Gregor Goldner, Johannes Dimopoulos, Richard Pötter — 2010-02-01

Abstract: Purpose: To find out if the risk of biochemical failure can be predicted applying the risk assessment for lymph-node metastases as suggested by the Roach formula for patients with minimal residual disease after radical prostatectomy undergoing adjuvant radiotherapy.Materials and methods: Patients after radical prostatectomy presenting with pT3-tumours or positive surgical margins, negative nodes and with a post-operative and pre-radiotherapy PSA level ⩽0.1ng/ml and without hormonal therapy were selected. Patients had received local 3D-conformal radiotherapy in the prostatic region with 66–72Gy. According to the risk stratification of the Roach formula patients were divided into two groups: Group 1 with probability of positive lymph-nodes <15% and Group 2 with ⩾15%. Biochemical recurrence was defined by reaching a PSA level ⩾0.2ng/ml.Results: A total of 55/288 patients could be identified, 26 patients in Group 1 and 29 patients in Group 2. Mean follow-up was 45months. Biochemical recurrence free survival after 5years was 78% for all patients and showed a significant difference between Group 1 (100%) and Group 2 with (58%; p=0.004).Conclusion: The risk for biochemical failure after adjuvant radiotherapy in post-operative patients presenting with minimal residual disease is significantly influenced by the Roach formula. These findings are considered to provide a rationale for the decision on the volume of post-operative radiotherapy.

Current technological clinical practise in breast radiotherapy; results of a survey in EORTC-Radiation Oncology Group affiliated institutions - Corrected Proof

2010-02-01

Abstract: Purpose: To evaluate the current technological clinical practise of radiation therapy of the breast in institutions participating in the EORTC-Radiation Oncology Group (EORTC-ROG).Materials and methods: A survey was conducted between August 2008 and January 2009 on behalf of the Breast Working Party within the EORTC-ROG. The questionnaire comprised 32 questions on 4 main topics: fractionation schedules, treatment planning methods, volume definitions and position verification procedures.Results: Sixty-eight institutions out of 16 countries responded (a response rate of 47%). The standard fraction dose was generally 2Gy for both breast and boost treatment, although a 2.67Gy boost fraction dose is routinely given in British institutions. The main boost modality was electrons in 55%, photons in 47% and brachytherapy in 3% of the institutions (equal use of photon and electron irradiation in 5% of the institutions). All institutions used CT-based treatment planning. Wide variations are seen in the definition of the breast and boost target volumes, with margins around the resection cavity, ranging from 0 to 30mm. Inverse planned IMRT is available in 27% and breath-hold techniques in 19% of the institutions. The number of patients treated with IMRT and breath-hold varied per institution. Electronic portal imaging for patient set-up is used by 92% of the institutions.Conclusions: This survey provides insight in the current practise of radiation technology used in the treatment of breast cancer among institutions participating in EORTC-ROG clinical trials.

Evaluation of early metabolic responses in rectal cancer during combined radiochemotherapy or radiotherapy alone: Sequential FDG-PET-CT findings - Corrected Proof

2010-02-01

Abstract: Background and purpose: The purpose of this study was to prospectively investigate metabolic changes of rectal tumors after 1week of treatment of either radiochemotherapy (28×1.8Gy+Capecitabine) (RCT) or hypofractionated radiotherapy (5×5Gy) alone (RT).Materials and methods: Fourty-six rectal cancer patients, 25 RCT- and 21 RT-patients, were included in this study. Sequential FDG-PET-CT scans were performed for each of the included patients both prior to treatment and after the first week of treatment. Consecutively, the metabolic treatment response of the tumor was evaluated.Results: For the patients referred for pre-operative RCT, significant reductions of SUVmean (p<0.001) and SUVmax (p<0.001) within the tumor were found already after the first week of treatment (8Gy biological equivalent dose (BED). In contrast, 1week of treatment with RT alone did not result in significant changes in the metabolic activity of the tumor (p=0.767, p=0.434), despite the higher applied RT dose of 38.7Gy BED.Conclusions: Radiochemotherapy of rectal cancer leads to significant early changes in the metabolic activity of the tumor, which was not the case early after hypofractionated radiotherapy alone, despite the higher radiotherapy dose given. Thus, the chemotherapeutic agent Capecitabine might be responsible for the early metabolic treatment responses during radiochemotherapy in rectal cancer.

Validation of functional imaging with pathology for tumor delineation in the prostate - Corrected Proof

2010-02-01

Abstract: Introduction: A study was performed to validate magnetic resonance (MR) based prostate tumor delineations with pathology.Material and methods: Five patients with biopsy proven prostate cancer underwent a T2 weighted (T2w), diffusion weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) scan before prostatectomy. Suspicious regions were delineated based on all available MR information. After prostatectomy whole-mount hematoxylin–eosin stained (H&E) sections were made. Tumor tissue was delineated on the H&E stained sections and compared with the MR based delineations. The registration accuracy between the MR images and H&E stained sections was estimated.Results: A tumor coverage of 44–89% was reached by the MR based tumor delineations. The application of a margin of ∼5mm to the MR based tumor delineations yielded a tumor coverage of 85–100% in all patients. Errors created during the registration procedure were 2–3mm, which cannot completely explain the limited tumor coverage.Conclusions: An accurate tissue processing and registration method was presented (registration error 2–3mm), which enables the validation of MR based tumor delineations with pathology. Reasonable tumor coverage of about 85% and larger was found when applying a margin of ∼5 mm to the MR based tumor delineations.

A reply to evidence-based radiation oncology: oesophagus - Corrected Proof

Richard S. Gillies, Mark R. Middleton, Claire Blesing — 2010-02-01

We read with interest this comprehensive review of the different therapeutic approaches to oesophageal cancer . We must, however, point out an important error in the section “neoadjuvant chemotherapy followed by surgery vs. surgery alone” (page 281), relating to the most recent meta-analysis in this area . We agree that this showed a significant benefit for neoadjuvant chemotherapy for oesophageal adenocarcinoma (hazard ratio for death 0.78; 95% CI, 0.64–0.95; p=0.014), based entirely on the data from the MRC OE02 trial – the only trial to have reported results by histology . The reviewers are incorrect, however, in stating “this benefit is lost in a pooled analysis for mixed tumour types (HR 1.07; 95% CI, 0.87–1.32; p=0.14).” In fact, the pooled analysis for both adenocarcinoma and squamous cell carcinoma showed a significant benefit for neoadjuvant chemotherapy (HR 0.90; 95% CI, 0.81–1.00; p=0.05), equivalent to a 2-year absolute survival benefit of 7%. The data quoted incorrectly relates to the only other trial to have included both tumour types but which, unfortunately, did not report results by histology ; as a result, in figure 3 of the meta-analysis (from which the incorrectly quoted data was extracted) it was described separately and labelled as “mixed tumours.”

6D image guidance for spinal non-invasive stereotactic body radiation therapy: Comparison between ExacTrac X-ray 6D with kilo-voltage cone-beam CT - Corrected Proof

2010-02-01

Abstract: Purpose: To investigate setup discrepancies measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for patients under treatments of stereotactic body radiation therapy (SBRT).Materials and methods: In this work, phantom and patient studies were performed. In the phantom studies, an anthropomorphic phantom was placed with pre-defined positions, and imaged with ExacTrac X-ray 6D and CBCT to test the accuracy of the imaging systems. In the patient studies, 16 spinal SBRT patient cases were retrospectively analyzed. The patients were initially positioned in customized immobilization cradles and then aligned with ExacTrac X-ray 6D and CBCT. The setup discrepancies were computed and quantitatively analyzed.Results: This study indicates modest discrepancies between ExacTrac X-ray 6D and CBCT with spinal SBRT. The phantom experiments showed that translational and rotational discrepancies in root-mean-square (RMS) between ExacTrac X-ray 6D and CBCT were, respectively, <1.0mm and <1°. In the retrospective patient studies, translational and rotational discrepancies in RMS between ExacTrac X-ray 6D and CBCT were <2.0mm and <1.5°.Conclusions: ExacTrac X-ray 6D represents a potential alternative to CBCT; however, pre-caution should be taken when only ExacTrac X-ray 6D is used to guide SBRT with small setup margins.

Comparison of electron IMRT to helical photon IMRT and conventional photon irradiation for treatment of breast and chest wall tumours - Corrected Proof

Tobias Gauer, Konrad Engel, Antje Kiesel, Dirk Albers, Dirk Rades — 2010-02-01

Abstract: Background and purpose: Conventional irradiation of breast and chest wall tumours may cause high doses in underlying organs. Intensity-modulated radiation therapy (IMRT) with photons achieves high conformity between treated and tumour volume but is associated with considerable low-dose effects which may induce secondary malignancies. We compare treatment plans of electron IMRT to helical photon IMRT and conventional irradiation.Material and methods: Treatment planning for three patients (breast, chest wall plus lymph nodes, sarcoma of medial chest wall/sternum) was performed using XiO 4.3.3 (CMS) for conventional photon irradiation, Hi-Art 2.2.2.05 (TomoTherapy) for helical photon IMRT, and a self-designed programme for electron IMRT.Results: The techniques resulted in similar mean and maximum target doses. Target coverage by the 95%-isodose was best with tomotherapy. Mean ipsilateral lung doses were similar with all techniques. Electron IMRT achieved best sparing of heart, and contralateral breast. Compared with photon IMRT, electron IMRT allowed better sparing of contralateral lung and total healthy tissue.Conclusions: Electron IMRT is superior to conventional irradiation, as it allows satisfying target coverage and avoids high doses in underlying organs. Its advantage over photon IMRT is better sparing of most organs at risk (low-dose effects) which reduces the risk of radiation-induced malignancies.

Information needs of early-stage prostate cancer patients: A comparison of nine countries - Corrected Proof

2010-02-01

Abstract: Background and purpose: Providing information to patients can improve their medical and psychological outcomes. We sought to identify core information needs common to most early-stage prostate cancer patients in participating countries.Material and methods: Convenience samples of patients treated 3–24months earlier were surveyed in Canada, England, Italy, Germany, Poland, Portugal, Netherlands, Spain, and Turkey. Each participant rated the importance of addressing each of 92 questions in the diagnosis-to-treatment decision interval (essential/desired/no opinion/avoid). Multivariate modelling determined the extent of variance accounted by covariates, and produced an unbiased prediction of the proportion of essential responses for each question.Results: Six hundred and fifty-nine patients responded (response rates 45–77%). On average, 35–53 questions were essential within each country; similar questions were essential to most patients in most countries. Beyond cross-country similarities, each country showed wide variability in the number and which questions were essential. Multivariate modelling showed an adjusted R-squared with predictors country, age, education, and treatment group of only 6% of the variance. A core of 20 questions were predicted to be essential to >2/3 of patients.Conclusions: Core information can be identified across countries. However, providing the core should only be a first step; each country should then provide information tailored to the needs of the individual patient.

Volumetric modulated arc therapy for delivery of hypofractionated stereotactic lung radiotherapy: A dosimetric and treatment efficiency analysis - Corrected Proof

2010-02-01

Abstract: Purpose/objective(s): Volumetric modulated arc therapy (VMAT) allows for intensity-modulated radiation delivery during gantry rotation with dynamic MLC motion, variable dose rates and gantry speed modulation. We compared VMAT plans with 3D-CRT for hypofractionated lung radiotherapy.Materials/methods: Twenty-one 3D-CRT plans for Stage IA lung cancer previously treated stereotactically were selected. VMAT plans were generated by optimizing machine aperture shape and radiation intensity at 10° intervals. A partial arc range of 180° was manually selected to coincide with tumor location. The arc was resampled down to 5° intervals to ensure dose calculation accuracy. Identical planning objectives were used for VMAT/3D-CRT. Parameters assessed included dose to PTV and organs-at-risk (OAR), monitor units, and multiple conformity and homogeneity indices. Plans were delivered to a phantom for time comparison.Results: Lung V20/12.5/10/5 were less with VMAT (relative reduction 4.5%, p=.02; 3.2%, p=.01; 2.6%, p=.01; 4.2%, p=.03, respectively). Mean/maximum-doses to PTV, dose to additional OARs, 95% isodose line conformity, and target volume homogeneity were equivalent. VMAT improved conformity at both the 80% (1.87 vs. 1.93, p=.08) and 50% isodose lines (5.19 vs. 5.65, p=.01). Treatment times were reduced significantly with VMAT (mean 6.1 vs. 11.9min, p<.01).Conclusions: Single arc VMAT planning achieves highly conformal dose distributions while controlling dose to critical structures, including significant reduction in lung dose volume parameters. Employing a VMAT technique decreases treatment times by 37–63%, reducing the chance of error introduced by intrafraction variation. The quality and efficiency of VMAT is ideally suited for stereotactic lung radiotherapy delivery.

Applying failure mode effects and criticality analysis in radiotherapy: Lessons learned and perspectives of enhancement - Corrected Proof

2010-02-01

Abstract: Introduction: The radiation oncology process along with its unique therapeutic properties is also potentially dangerous for the patient, and thus it should be delivered under a systematic risk control. To this aim incident reporting and analysis are not sufficient for assuring patient safety and proactive risk assessment should also be implemented. The paper accounts for some methodological solutions, lessons learned and opportunities for improvement, starting from the systematic application of the failure mode effects and criticality analysis (FMECA) technique to the radiotherapy process of an Italian hospital.Materials and methods: The analysis, performed by a working group made of experts of the radiotherapy unit, was organised into the following steps: (1) complete and detailed analysis of the process (integration definition for function modelling); (2) identification of possible failure modes (FM) of the process, representing sources of adverse events for the patient; (3) qualitative risk assessment of FMs, aimed at identifying priorities of intervention; (4) identification and planning of corrective actions.Results: Organisational and procedural corrective measures were implemented; a set of safety indexes for the process was integrated within the traditional quality assurance indicators measured by the unit. A strong commitment of all the professionals involved was observed and the study revealed to be a powerful “tool” for dissemination of patient safety culture.Conclusion: The feasibility of FMECA in fostering radiotherapy safety was proven; nevertheless, some lessons learned as well as weaknesses of current practices in risk management open to future research for the integration of retrospective methods (e.g. incident reporting or root cause analysis) and risk assessment.

Automated analysis of images acquired with electronic portal imaging device during delivery of quality assurance plans for inversely optimized arc therapy - Corrected Proof

Anna Fredh, Stine Korreman, Per Munck af Rosenschöld — 2010-02-01

Abstract: This work presents an automated method for comprehensively analyzing EPID images acquired for quality assurance of RapidArc® treatment delivery. In-house-developed software has been used for the analysis and long-term results from measurements on three linacs are presented.

How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons - Corrected Proof

2010-01-27

Abstract: Purpose: Particle therapy has potentially a better therapeutic ratio than photon therapy. However, investment costs are much higher. This study provides an estimation and comparison of the costs of these therapies.Methods: Within an extensive analytical framework capital and operational costs, cost per fraction, and four tumor specific treatment costs are calculated for three facilities: combined carbon-ion/proton, proton-only, and photon.Results: Capital costs for the combined, proton-only and photon facilities are: € 138.6 million, € 94.9 million, € 23.4 million. Total costs per year are: € 36.7 million, € 24.9 million, € 9.6 million. Cost per fraction is: € 1128 (€ 877–1974), € 743 (€ 578–1300), € 233 (€ 190–407). Cost ratio particle/photon therapy is 4.8 for the combined and 3.2 for the proton-only facility. Particle treatment costs vary from € 10,030 (c-ion: lung cancer) to € 39,610 (proton: head & neck tumors). Cost difference between particle and photon therapies is relatively small for lung and prostate cancer, larger for skull-base chordoma and head & neck tumors.Conclusion: Investment costs are highest for the combined carbon-ion/proton facility and lowest for the photon facility. Cost differences become smaller when total costs per year and specific treatment costs are compared. Lower fractionation schedule of particle therapy might further reduce its costs.

Postmastectomy intensity modulated radiation therapy following immediate expander-implant reconstruction - Corrected Proof

2010-01-25

Abstract: Background/purpose: To evaluate radiation plans of patients undergoing mastectomy with immediate expander-implant reconstruction followed by postmastectomy radiation therapy (PMRT).Materials/methods: We identified 41 patients from June 2004 to May 2007 who underwent mastectomy, immediate expander-implant reconstruction, and PMRT with intensity-modulated radiation therapy. We assessed chest wall (CW) coverage and volume of heart and lung irradiated.Results: In 73% of patients, all CW borders were adequately covered, and in 22%, all but 1 border were adequately covered. The total lung V20 was<20% in 39/41 patients. The mean lung V20 was 13% (range, 3–23%), and the mean heart Dmean was 2.81Gy (range, 0.53–9.60Gy). In patients with left-sided lesions without internal mammary nodes (IMNs) treatment (n=22), the mean lung V20 was 12.6% and the mean heart Dmean was 3.90Gy, and in the patient with IMN treatment, the lung V20 was 18% and heart Dmean was 8.04Gy. For right-sided lesions without IMN treatment (n=12), the mean lung V20 was 12.4% and the mean heart Dmean was 0.90Gy, and in patients with IMN treatment (n=6), these numbers were 17.8% and 1.76Gy. At a median follow-up of 29months, the 30-month actuarial local control was 97%.Conclusions: In women undergoing immediate expander-implant reconstruction, PMRT can achieve excellent local control with acceptable heart and lung doses. These results can be achieved even when the IMN are being treated, although doses to the heart and lungs will be higher.

No association between SNPs regulating TGF-β1 secretion and late radiotherapy toxicity to the breast: Results from the RAPPER study - Corrected Proof

2010-01-25

Abstract: Background and purpose: Several small studies have reported associations between TGFB1 single nucleotide polymorphisms (SNPs), considered to increase secretion of TGF-β1, and greater than 3-fold increases in incidence of fibrosis – an indicator of late toxicity after radiotherapy in breast cancer patients.Materials and methods: Two SNPs in TGFB1, C-509T (rs1800469) and L10P (rs1800470), were genotyped in 778 breast cancer patients who had received radiotherapy to the breast. Late radiotherapy toxicity was assessed two years after radiotherapy using a validated photographic technique, clinical assessment and patient questionnaires.Results: On photographic assessment, 210 (27%) patients showed some degree of breast shrinkage, whilst 45 (6%) patients showed marked breast shrinkage. There was no significant association of genotype at either of the TGFB1 SNPs with any measure of late radiation toxicity.Conclusion: This adequately powered trial failed to confirm previously reported increases in fibrosis with TGFB1 genotype – any increase greater than 1.36 can be excluded with 95% confidence. Similar frequent failures to replicate associations with candidate genes have been resolved using genome-wide association scans: this methodology detects common, low risk alleles but requires even larger patient numbers for adequate statistical power.

A comparison of dose–volume constraints derived using peak and longitudinal definitions of late rectal toxicity - Corrected Proof

2010-01-25

Abstract: Background and purpose: Accurate reporting of complications following radiotherapy is an important part of the feedback loop to improve radiotherapy techniques. The definition of toxicity is normally regarded as the maximum or peak (P) grade of toxicity reported over the follow-up period. An alternative definition (integrated longitudinal toxicity (ILT)) is proposed which takes into account both the severity and the duration of the complication.Methods and materials: In this work, both definitions of toxicity were used to derive dose–volume constraints for six specific endpoints of late rectal toxicity from a cohort of patients who received prostate radiotherapy in the MRC RT01 trial. The dose–volume constraints were derived using ROC analysis for 30, 40, 50, 60, 65 and 70Gy.Results: Statistically significant dose–volume constraints were not derived for all dose levels tested for each endpoint and toxicity definition. However, where both definitions produced constraints, there was generally good agreement. Variation in the derived dose–volume constraints was observed to be larger between endpoints than between the two definitions of toxicity. For one endpoint (stool frequency (LENT/SOM)) statistically significant dose–volume constraints were only derived using ILT.Conclusions: The longitudinal definition of toxicity (ILT) produced results consistent with those derived using peak toxicity and in some cases provided additional information which was not seen by analysing peak toxicity alone.

The value of magnetic resonance imaging in target volume delineation of base of tongue tumours – A study using flexible surface coils - Corrected Proof

2010-01-25

Abstract: Introduction: Magnetic resonance imaging (MRI) provides superior diagnostic accuracy over computed tomography (CT) in oropharyngeal tumours. Precise delineation of the gross tumour volume (GTV) is mandatory in radiotherapy planning when a GTV boost is required. CT volume definition in this regard is poor. We studied the feasibility of using flexible surface (flex-L) coils to obtain MR images for MR–CT fusion to assess the benefit of MRI over CT alone in planning base of tongue tumours.Methods: Eight patients underwent CT and MRI radiotherapy planning scans with an immobilisation device. Distortion-corrected T1-weighted post-contrast MR scans were fused to contrast-enhanced planning CT scans. GTV, clinical target and planning target volumes (CTV, PTV) and organs at risk (OAR) were delineated on CT, then on MRI with blinding to the CT images. The volumetric and spatial differences between MRI and CT volumes for GTV, CTV, PTV and OAR were compared. MR image distortions due to field inhomogeneity and non-linear gradients were corrected and the need for such correction was evaluated.Results: The mean primary GTV was larger on MRI (22.2 vs. 9.5cm3, p=0.05) than CT. The mean primary and nodal GTV (i.e. BOT and macroscopic nodes) was significantly larger on MRI (27.2 vs. 14.4cm3, p=0.05). The volume overlap index (VOI) between MRI and CT for the primary was 0.34 suggesting that MRI depicts parts of the primary tumour not detected by CT. There was no significant difference in volume delineation between MR and CT for CTV, PTV, nodal CTV and nodal PTV. MRI volumes for brainstem and spinal cord were significantly smaller due to improved organ definition (p=0.002). Susceptibility and gradient-related distortions were not found to be clinically significant.Conclusion: MRI improves the definition of tongue base tumours and neurological structures. The use of MRI is recommended for GTV dose-escalation techniques to provide precise depiction of GTV and improved sparing of spinal cord and brainstem.

Monte Carlo-based analytical model for small and variable fields delivered by TomoTherapy - Corrected Proof

2010-01-21

Abstract: Background and purpose: Extend to very small fields the validity of a Monte Carlo (MC) based model of TomoTherapy called TomoPen for future implementation of the dynamic jaws feature for helical TomoTherapy.Materials and methods: First, the modelling of the electron source was revisited using a new method to measure source obscuration for very small fields (<1cm). The method consisted in MC simulations simulations and measurements of the central dose in a water phantom for a 10cm×FW field scanned to deliver a 10×10cm2 fluence. FW, the longitudinal field width, was varied from 0.4 to 5cm. The second part of the work consisted of adapting TomoPen to account for any configuration of the jaws in a fast and efficient way by using routinely only the phase-space file of the largest field (5cm) and interpolated analytical information of phase-space files of smaller field widths.Results: For the electron source fine tuning, it was shown that the best results were obtained for a 1.1mm wide spot. Our single phase-space method showed no significant differences compared to MC simulations of various field widths even though only longitudinal intensity and angular analytical functions were applied to the 5cm phase-space.Conclusion: The designed model is able to simulate all jaw openings from the 5cm field phase-space file by applying a bi-dimensional analytical function accounting for the fluence and the angular distribution in the longitudinal direction.

3D Dosimetric verification of volumetric-modulated arc therapy by portal dosimetry - Corrected Proof

2010-01-20

Abstract: Background and purpose: To demonstrate the feasibility of back-projection portal dosimetry for accurate 3D dosimetric verification of volumetric-modulated arc therapy (VMAT), pre-treatment as well as in vivo.Materials and methods: Several modifications to our existing approach were implemented to make the method applicable to VMAT: (i) gantry angle-resolved data acquisition, (ii) calculation of the patient transmission, (iii) compensation for detector ‘flex’ and (iv) 3D dose reconstruction and evaluation.Results: Planned and EPID-(Electronic Portal Image Detector)-reconstructed dose distributions show good agreement for pre-treatment verification of two prostate, a stereotactic lung and a head-and-neck VMAT plan and for in vivo verification of VMAT treatments of prostate and lung cancer. Averaged over pre-treatment verifications, planned and measured isocentre dose ratios were −1.2% (range [−4.7%,1.8%]). 3D gamma analysis (3% maximum dose, 3mm) revealed mean γ 〈γmean〉=0.37 [0.34,0.39], maximum 1% γ 〈γ1%〉=0.72 [0.66,0.81] and percentage of points with γ⩽1 〈Pγ⩽1〉=99% [97%,100%]. For in vivo verification, the average isocentre dose ratio was −1.2% [−0.8%,−1.7%], 〈γmean〉=0.52 [0.40,0.64], 〈γ1%〉=0.92 [0.76,1.08] and 〈Pγ⩽1〉=96% [93%,100%].Conclusions: Our portal dosimetry method was successfully adapted for verification of VMAT treatments, pre-treatment as well as in vivo.

Real-time dynamic MLC tracking for inversely optimized arc radiotherapy - Corrected Proof

2010-01-20

Abstract: Background and purpose: Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory.Materials and methods: An MLC-tracking algorithm was used to adjust the MLC positions according to the target movements using information from an optical real-time positioning management system. Two plans with collimator angles of 45° and 90°, respectively, were delivered and measured using the Delta4® dosimetric device moving in the superior–inferior direction with peak-to-peak displacements of 5, 10, 15, 20 and 25mm and a cycle time of 6s.Results: Gamma index evaluation for plan delivery with MLC tracking gave a pass rate higher than 98% for criteria 3% and 3mm for both plans and for all sizes of the target displacement. With no motion compensation, the average pass rate was 75% for plan 1 and 70% for plan 2 for 25mm peak-to-peak displacement.Conclusion: MLC tracking improves the accuracy of inversely optimized arc delivery for the cases studied. With MLC tracking, the dosimetric accuracy was independent of the magnitude of the peak-to-peak displacement of the target and not significantly affected by the angle between the leaf trajectory and the target movements.

The use of probability maps to deal with the uncertainties in prostate cancer delineation - Corrected Proof

2010-01-20

Abstract: Background and purpose: The use of dynamic contrast-enhanced (DCE) imaging for delineation of prostate tumors requires that decisions are made on a voxel wise basis about the presence of tumor. While the sensitivity and specificity of this technique is high, we propose a probabilistic approach to deal with the intrinsic imaging uncertainty.Material and methods: Twenty-nine patients with biopsy-proven prostate cancer underwent a DCE-CT exam prior to radiotherapy. From a logistic regression on Ktrans values from healthy and diseased appearing prostate regions we obtained a probability function for the presence of tumor. Ktrans parameter maps were converted into probability maps and a stratification was applied at the 5% and 95% probability level, to identify low-, intermediate-, and high-risk areas for the presence of tumor.Results: In all patients, regions with high-, intermediate-, and low-risk were identified, with median volume percentages of 7.6%, 40.0%, and 52.1%, respectively. The contiguous areas that resulted from the voxel wise stratification can be interpreted as GTV, high-risk CTV, and CTV.Conclusions: Ktrans parameter maps from a DCE-CT exam can be converted into probability maps for the presence of tumor. In this way, the intrinsic uncertainty that a voxel contains tumor can be incorporated into the treatment planning process.

Target volume definition for external beam partial breast radiotherapy: Clinical, pathological and technical studies informing current approaches - Corrected Proof

Anna M. Kirby, Charlotte E. Coles, John R. Yarnold — 2010-01-18

Abstract: Partial breast irradiation (PBI) is currently under investigation in several phase III trials and, following a recent consensus statement, its use off-study may increase despite ongoing uncertainty regarding optimal target volume definition. We review the clinical, pathological and technical evidence for target volume definition in external beam partial breast irradiation (EB-PBI). The optimal method of tumour bed (TB) delineation requires X-ray CT imaging of implanted excision cavity wall markers. The definition of clinical target volume (CTV) as TB plus concentric 15mm margins is based on the anatomical distribution of multifocal and multicentric disease around the primary tumour in mastectomy specimens, and the clinical locations of local tumour relapse (LR) after breast conservation surgery. If the majority of LR originate from foci of residual invasive and/or intraduct disease in the vicinity of the TB after complete microscopic resection, CTV margin logically takes account of the position of primary tumour within the surgical resection specimen. The uncertain significance of independent primary tumours as sources of preventable LR, and of wound healing responses in stimulating LR, increases the difficulties in defining optimal CTV. These uncertainties may resolve after long-term follow-up of current PBI trials. By contrast, a commonly used 10mm clinical to planning target volume (PTV) margin has a stronger evidence base, although departmental set-up errors need to be confirmed locally. A CTV–PTV margin >10mm may be required in women with larger breasts and/or large seromas, whilst the role of image-guided radiotherapy with or without TB markers in reducing CTV–PTV margins needs to be explored.

Determining DVH parameters for combined external beam and brachytherapy treatment: 3D biological dose adding for patients with cervical cancer - Corrected Proof

2010-01-18

Abstract: Purpose: To compare two methods of DVH parameter determination for combined external beam and brachytherapy treatment of cervical cancer.Materials and methods: Clinical treatment plans from five patients were used in this study. We simulated two applications given with PDR (32×60cGy per application, given hourly) or HDR (4×7Gy in two applications; each application of two fractions of 7Gy, given within 17h) standard and optimised treatment plans, all combined with IMRT (25×1.8Gy). Additionally, we simulated an external beam (EBRT) boost to pathological lymph nodes or the parametrium (7×2Gy).We determined D90 of the high-risk CTV (HR-CTV) and D2cc of bladder and rectum in EQD2 in two ways. (1) ‘Parameter adding’: assuming a uniform contribution of the EBRT dose distribution and adding the values of DVH parameters for the two brachytherapy insertions, and (2) ‘distributions adding’: summing 3D biological dose distributions of IMRT and brachytherapy plans and subsequently determining the values of the DVH parameters. We took α/β=10Gy for HR-CTV, α/β=3Gy otherwise and half-time of repair 1.5h.Results: Without EBRT boost, ‘parameter adding’ yielded a good approximation. With an EBRT boost to lymph nodes, the total D90 HR-CTV was underestimated by 2.6 (SD 1.3)% for PDR and 2.8 (SD 1.4)% for HDR. This was even worse with a parametrium boost: 9.1 (SD 6.2)% for PDR and 9.9 (SD 6.2)% for HDR.Conclusion: Without an EBRT boost ‘parameter adding’, as proposed by the GEC-ESTRO, yielded accurate results for the values for DVH parameters. If an EBRT boost is given ‘distributions adding’ should be considered.

Tumor perfusion increases during hypofractionated short-course radiotherapy in rectal cancer: Sequential perfusion-CT findings - Corrected Proof

2010-01-18

Abstract: Purpose: The purpose of this study was to investigate perfusion of rectal tumors and to determine early responses to short-course hypofractionated radiotherapy (RT).Material and methods: Twenty-three rectal cancer patients were included, which underwent perfusion-CT imaging before (pre-scan) and after treatment (post-scan). Contrast-enhancement was measured in tumor and muscle tissues and in the external iliac artery. Perfusion was quantified with three pharmacokinetic parameters: Ktrans, ve and vp. Perfusion differences between tumor and normal tissue and changes of the pharmacokinetic parameters between both scans were evaluated.Results: The median tumors Ktrans values increased significantly from the pre-scan (0.36±0.11 (min−1)) to the post-scan (0.44±0.13 (min−1)) (p<0.001). Also, histogram analysis showed a shift of tumor voxels from lower Ktrans values towards higher Ktrans values. Furthermore, the median Ktrans values were significantly higher for tumor than for muscle tissue on both the pre-scan (0.10±0.05 (min−1), p<0.001) and the post-scan (0.10±0.04 (min−1), p<0.001). In contrast, no differences between tumor and muscle tissues were found for ve and vp. Also, no significant differences were observed for ve and vp between the two pCT-imaging time-points.Conclusions: Hypofractionated radiotherapy of rectal cancer leads to an increased tumor perfusion as reflected by an elevated Ktrans, possibly improving the bioavailability of cytotoxic agents in rectal tumors, often administered early after radiotherapy treatment.

Minimising contralateral breast dose in post-mastectomy intensity-modulated radiotherapy by incorporating conformal electron irradiation - Corrected Proof

2010-01-18

Abstract: Purpose: To assess the potential benefit of incorporating conformal electron irradiation in intensity-modulated radiotherapy (IMRT) for loco-regional post-mastectomy RT.Patients and methods: Ten consecutive patients that underwent left-sided mastectomy were selected for this comparative planning study. Three-dimensional conformal radiotherapy (3D-CRT) photon–electron dose plans were compared to photon-only IMRT (IMRTp) and photon IMRT with conformal electron irradiation (IMRTp/e). The planning target volume (PTV) was prescribed 50Gy and included the chest wall and the internal mammary and supra-clavicular lymph node regions. It was attempted to minimise dose delivered to heart, lungs and contralateral breast (CB), while maintaining adequate PTV coverage.Results: All plans complied with objectives for PTV coverage. IMRTp/e eliminated volumes receiving ⩾70Gy (V70) that were present in 3D-CRT at the junction of photon and electron beams. Both IMRT strategies reduced heart V30 significantly below 3D-CRT levels. Mean heart dose with IMRTp/e was the lowest and was equal to that with 3D-CRT. Minimising heart dose with IMRTp resulted in irradiated CB volumes much larger than that with 3D-CRT. With IMRTp/e, CB dose was only slightly increased when compared to 3D-CRT. Mean lung dose values were similar for IMRT and 3D-CRT. With IMRT, lung V20 was smaller, whereas V5 values for heart, lung and CB were higher than those with 3D-CRT.Conclusions: Incorporation of conformal electron irradiation in post-mastectomy IMRTp/e enables a heart dose reduction which can only be obtained with IMRTp when allowing large irradiated volumes in the contralateral breast.

Correction strategies to manage deformations in head-and-neck radiotherapy - Corrected Proof

2010-01-18

Abstract: Background and purpose: To optimize couch shifts based on multiple region-of-interest (ROI) registrations and derive criteria for adaptive replanning for management of deformations in head-and-neck (H&N) cancer patients.Materials and methods: Eight ROIs containing bony structures were defined on the planning-CT and individually registered to daily cone-beam CTs for 19 H&N cancer patients. Online couch shifts were retrospectively optimized to correct the mean setup error over all ROIs (mean correction) or to minimize the maximum error (MiniMax correction). Residual error distributions were analyzed for both methods. The number of measurements before adaptive-intervention and corresponding action-level were optimized.Results: Overall residual setup errors were smallest for the mean corrections, while MiniMax corrections reduced the largest errors. The percentage of fractions with residual errors >5mm was 38% versus 19%. Reduction of deformations by single plan adaptation was most effective after eight fractions: systematic deformations reduced from 1.7 to 0.9mm. Fifty percent of this reduction can already be achieved by replanning 1/3 of the patients.Conclusion: Two correction methods based on multiple ROI registration were introduced to manage setup errors from deformations that either minimize overall geometrical uncertainties or maximum errors. Moreover, the registrations could be used to select patient with large deformations for replanning.

First clinical experience with a multiple region of interest registration and correction method in radiotherapy of head-and-neck cancer patients - Corrected Proof

2010-01-18

Abstract: Purpose: To discuss the first clinical experience with a multiple region of interest (mROI) registration and correction method for high-precision radiotherapy of head-and-neck cancer patients.Materials and methods: 12–13 3D rectangular-shaped ROIs were automatically placed around bony structures on the planning CT scans (n=50 patients) which were individually registered to subsequent CBCT scans. mROI registration was used to quantify global and local setup errors. The time required to perform the mROI registration was compared with that of a previously used single-ROI method. The number of scans with residual local setup error exceeding 5mm/5° (warnings) was scored together with the frequency ROIs exceeding these limits for three or more consecutive imaging fractions (systematic errors).Results: In 40% of the CBCT scans, one or more ROI-registrations exceeded the 5mm/5°. Most warnings were seen in ROI “hyoid”, 31% of the rotation warnings and 14% of the translation warnings. Systematic errors lead to 52 consults of the treating physician. The preparation and registration time was similar for both registration methods.Conclusions: The mROI registration method is easy to use with little extra workload, provides additional information on local setup errors, and helps to select patients for re-planning.

3D dose delivery verification using repeated cone-beam imaging and EPID dosimetry for stereotactic body radiotherapy of non-small cell lung cancer - Corrected Proof

Wouter van Elmpt, Steven Petit, Dirk De Ruysscher, Philippe Lambin, André Dekker — 2010-01-18

Abstract: Purpose: To implement a 3D dose verification procedure, based on in-room cone-beam CT imaging and portal dosimetry, for lung cancer patients treated with stereotactic body radiotherapy (SBRT).Materials and methods: MV cone-beam CT scans were made for patient positioning and calibrated for dose calculation purposes. Prior to treatment, the treatment fields were captured using a calibrated electronic portal imaging device (EPID). A Monte Carlo dose reconstruction model was used to estimate the 3D dose delivered to the patient inside the cone-beam CT images. The planned and delivered dose distributions were compared for 4 patients and 10 treatment fractions using dose–volume histograms and gamma analysis.Results: The gamma analysis showed a good agreement between the planned and delivered dose distributions for patients without changes in anatomy. The delivered mean dose per fraction inside the target volume deviated on average 1.1±1.4% from the planned dose. For the critical organs, only minor differences were observed between the reconstructed and planned dose.Conclusions: A method was presented that allows verification of the dose delivered in 3D for lung cancer patients treated with SBRT. The procedure is independent of the treatment planning system and uses in-room MV cone-beam CT imaging and portal dosimetry.

Dose recalculation in megavoltage cone-beam CT for treatment evaluation: Removal of cupping and truncation artefacts in scans of the thorax and abdomen - Corrected Proof

Steven F. Petit, Wouter J.C. van Elmpt, Philippe Lambin, André L.A.J. Dekker — 2010-01-08

Abstract: Purpose: To correct megavoltage cone-beam CT (MVCBCT) images of the thorax and abdomen for cupping and truncation artefacts to reconstruct the 3D-delivered dose distribution for treatment evaluation.Materials and methods: MVCBCT scans of three phantoms, three lung and two rectal cancer patients were acquired. The cone-beam projection images were iteratively corrected for cupping and truncation artefacts and the resulting primary transmission was used for cone-beam reconstruction. The reconstructed scans were merged into the planning CT scan (MVCBCT+). Dose distributions of clinical IMRT, stereotactic and conformal treatment plans were recalculated on the uncorrected and corrected MVCBCT+ scans using the treatment planning system and compared to the planned dose distribution.Results: The dose distributions on the corrected MVCBCT+ of the phantoms were accurate for 99% of the voxels within 2% or 2mm. Using this method the errors in mean GTV dose reduced from about 10% to 1% for the patients.Conclusions: The method corrects cupping and truncation artefacts in cone-beam scans of the thorax and abdomen in addition to head-and-neck (demonstrated previously). The corrected scans can be used to calculate the influence of anatomical changes on the 3D-delivered dose distribution.

Unilateral radiotherapy for tonsil cancer: Potential dose distribution optimization with a simple two-field intensity-modulated radiation therapy beam arrangement - Corrected Proof

2009-12-21

Abstract: Background and purpose: To evaluate the feasibility and dosimetric optimization potential of a unilateral two-field intensity-modulated radiotherapy (IMRT) technique in the curative treatment of lateralized tonsil cancer.Materials and methods: Six patients with lateralized tonsillar carcinoma were treated unilaterally with a two-field IMRT technique (oblique-anterior and oblique-posterior fields, with or without collimator and couch rotation). Alternative IMRT plans using seven non-opposed coplanar fields were compared with the two-field plans for each patient.Results: Planning target volume (PTV) coverage was excellent with the two-field technique, using a relatively low number of monitor units (MU) (median, 441; range, 309–550). Dose constraints were respected for all organs at risk (OAR). Mean doses to contralateral parotid and submandibular glands were 3.9 and 17.7Gy, respectively. Seven-field IMRT provided similar PTV coverage, with statistically significant better dose homogeneity and conformality. However, the mean delivered dose to the contralateral parotid (3.9 vs. 9.0Gy, p=0.001) as well as the mean number of MU (437 vs. 814, p=0.002) and consequently machine time were lower with two-field IMRT.Conclusions: Unilateral two-field IMRT is a simple and feasible technique providing excellent tumor coverage and optimal OAR sparing while reducing the number of MU and treatment time.

Prognostic impact of peritonealisation in rectal cancer treated with preoperative chemoradiotherapy: Extraperitoneal versus intraperitoneal rectal cancer - Corrected Proof

2009-12-14

Abstract: Background and purpose: The oncologic outcomes of extraperitoneal (EP) rectal cancer are known to differ from those of intraperitoneal (IP) rectal cancer; however, these differences have not been studied in rectal patients treated by preoperative chemoradiotherapy (CRT). The aim of this study is to evaluate the prognostic impact of peritonealisation in rectal patients treated by preoperative CRT.Materials and methods: This study analyzed the data of 362 patients who received preoperative CRT and underwent curative surgery for locally advanced rectal cancer at 3–9cm above the anal verge. Patients were categorised into EP and IP groups based on whether peritonealisation was present, according to pathology reports. The oncologic outcomes between the two groups were compared.Results: Peritonealisation was absent in 330 patients and present in 32 patients. In univariate analysis, disease-free survival was significantly worse in the EP group than in the IP group (73.0% versus 93.5%, p=0.035). Multivariate analysis revealed the following independent risk factors for recurrence: the absence of peritonealisation (p=0.023), ypT stage (p=0.015) and ypN stage (p<.0001).Conclusions: Peritonealisation of rectal cancer may be a prognostic factor of disease-free survival in patients with rectal cancer treated by preoperative CRT and surgery.

How does knowledge of three-dimensional excision margins following breast conservation surgery impact upon clinical target volume definition for partial-breast radiotherapy? - Corrected Proof

2009-12-07

Abstract: Background and purpose: To compare partial-breast clinical target volumes generated using a standard 15mm margin (CTVstandard) with those generated using three-dimensional surgical excision margins (CTVtailored30) in women who have undergone wide local excision (WLE) for breast cancer.Material and methods: Thirty-five women underwent WLE with placement of clips in the anterior, deep and coronal excision cavity walls. Distances from tumour to each of six margins were measured microscopically. Tumour bed was defined on kV-CT images using clips. CTVstandard was generated by adding a uniform three-dimensional 15mm margin, and CTVtailored30 was generated by adding 30mm minus the excision margin in three-dimensions. Concordance between CTVstandard and CTVtailored30 was quantified using conformity (CoI), geographical-miss (GMI) and normal-tissue (NTI) indices. An external-beam partial-breast irradiation (PBI) plan was generated to cover 95% of CTVstandard with the 95% isodose. Percentage-volume coverage of CTVtailored30 by the 95% isodose was measured.Results: Median (range) coronal, superficial and deep excision margins were 15.0 (0.5–76.0)mm, 4.0 (0.0–60.0)mm and 4.0 (0.5–35.0)mm, respectively. Median CoI, GMI and NTI were 0.62, 0.16 and 0.20, respectively. Median coverage of CTVtailored30 by the PBI-plan was 97.7% (range 84.9–100.0%). CTVtailored30 was inadequately covered by the 95% isodose in 4/29 cases. In three cases, the excision margin in the direction of inadequate coverage was ⩽2mm.Conclusions: CTVs based on 3D excision margin data are discordant with those defined using a standard uniform 15mm TB–CTV margin. In women with narrow excision margins, the standard TB–CTV margin could result in a geographical miss. Therefore, wider TB–CTV margins should be considered where re-excision does not occur.

Variation of treatment planning parameters (D90 HR-CTV, D2cc for OAR) for cervical cancer tandem ring brachytherapy in a multicentre setting: Comparison of standard planning and 3D image guided optimisation based on a joint protocol for dose–volume constraints - Corrected Proof

2009-11-30

Abstract: Purpose: To perform a qualitative and quantitative comparison of different treatment planning methods used in different centres for MRI-based brachytherapy (BT) of cervical cancer.Materials and methods: Two representative patients with advanced cervical cancer (1 “limited volume case”; 1 “extensive volume case”) were planned for brachytherapy (BT) with a tandem-ring applicator by six different centres. During a workshop all centres produced an institutional standard plan and an MRI-based adaptive treatment plan for each case. Optimisation was based on the fractionation schedule (HDR, PDR) and method according to the institutional protocol.Results: The loading pattern, dwell times, shape of the point A isodose varied considerably between institutional standard plans, as did dose–volume parameters for high risk CTV (HR-CTV) and also for the D2cc for OAR, violating the dose–volume constraints in many situations. During optimisation, the centres stayed as close as possible to the standard loading pattern and dwell times. The dose distributions and dose–volume parameters between the plans from the different centres became much more comparable after optimisation. The prescribed dose to the HR-CTV could be achieved in the limited volume case by all centres, in the extensive case only if additional needles were applied.Conclusion: Treatment planning for gynaecologic brachytherapy based on different traditions shows less variation in regard to target coverage and OAR dose, when 3D image-based optimisation is performed with a uniform prescription protocol.

Applicator reconstruction for HDR cervix treatment planning using images from 0.35T open MR scanner - Corrected Proof

2009-11-23

Abstract: Background and purposes: Magnetic resonance (MR) imaging is widely recognised as the modality of choice for imaging soft tissue such as the target volume and critical structures relevant to high dose rate (HDR) brachytherapy of the cervix. This work sets out to assess some of the issues faced when introducing this technique clinically compared to the more widely used computed tomography (CT). MR can be used either as the sole imaging modality, or in conjunction with CT.Materials and methods: Distortion of the images produced by the MR scanner was assessed with a geometrical phantom. Distortion local to the titanium applicators, introduced by the susceptibility of the applicators themselves, was also measured. The technique used to reconstruct applicators is briefly described. An inter-operator study was performed to assess the variability of applicator reconstruction between operators when MR images are used alone to reconstruct the applicators.Results: A 14-cm cube within which distortion was less than 2mm at all points was identified. The inter-operator study showed some variability in applicator reconstruction with both MR and CT (median MR/CT 1.3mm/0.9mm, range 0–3.6mm/0–3.3mm). Inter-operator variation in planning target volume (PTV) V100% and PTV D90% for MR/CT was 6.1%/3.0% and 7.4%/6.3%, respectively, and D2cc OAR doses varied by up to 1.0Gy between operators for both MR and CT.Conclusions: In this study distortion was minimal within a defined volume and inter-observer errors were comparable on MR and CT when used to define applicators and when applied to dose–volume histograms (DVHs). However this does not assure the technique is appropriate with other scanners and applicator sets without further commissioning.

CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell line HCT-116 - Corrected Proof

2009-11-18

Abstract: Background and purpose: CD133 is controversially discussed as putative (surrogate) marker for cancer stem/tumor-initiating cell populations (CSC/TIC) in epithelial tumors including colorectal carcinomas (CRCs). We studied CD133 expression in established CRC cell lines and examined in vitro behavior, radioresponse and in vivo tumor formation of CD133+/− subpopulations of one cell line of interest.Materials and methods: Ten CRC cell lines were analyzed for CD133 expression using flow cytometry and Western blotting. CD133+ and CD133− HCT-116 subpopulations were separated by FACS and studied in 2-D and 3-D culture and colony formation assays after irradiation. Subcutaneous xenograft formation was monitored in NMRI (nu/nu) mice.Results and conclusions: CRC cell lines could be classified into three groups: (i) CD133−, (ii) CD133+ and (iii) those with two distinct CD133+ and CD133− subpopulations. Isolated CD133+/− HCT-116 subpopulations were studied relative to the original fraction. No difference was found in 2-D growth, spheroid formation or radioresponse in vitro. Also, tumor formation and growth rate did not differ for the sorted subpopulations. However, a subset of xenografts originated from CD133− HCT-116 showed a striking enrichment in the CD133+ fraction. Our data show that CD133 expression is not selective for sphere forming, tumor-initiating or radioresistant subpopulations in the HCT-116 CRC cell line. This implies that CD133 cannot be regarded as a CSC/TIC marker in all CRC cell lines and that functional measurements of tumor formation have to generally accompany CSC/TIC-directed mechanistic or therapeutic studies.

Accelerated partial breast irradiation as part of breast conserving therapy of early breast carcinoma: A systematic review - Corrected Proof

Olaf Nairz, Felix Sedlmayer — 2009-10-23

We congratulate Offersen et al. for the excellent overview on partial breast irradiation (pbi) . Common for all radiation techniques is the desire for good dose homogeneity inside the target volume. We would like to draw attention to the aspect of dose homogeneity for a special subgroup of pbi techniques, namely intraoperative radiation therapy (IORT). We recently compared the dosimetric properties of four techniques : IORT with electrons (IOERT), an orthovolt system (Intrabeam), interstitial brachytherapy, and brachytherapy using the MammoSite system.

Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions - Corrected Proof

2009-10-05

Abstract: Background and purpose: To investigate the cytogenetic damage in blood lymphocytes of patients treated for prostate cancer with different radiation qualities and target volumes.Materials and methods: Twenty patients receiving carbon-ion boost irradiation followed by IMRT or IMRT alone for the treatment of prostate cancer entered the study. Cytogenetic damage induced in peripheral blood lymphocytes of these patients was investigated at different times during the radiotherapy course using Giemsa staining and mFISH. A blood sample from each patient was taken before initiation of radiation therapy and irradiated in vitro to test for individual radiosensitivity. In addition, in vitro dose–effect curves for the induction of chromosomal exchanges by X-rays and carbon ions of different energies were measured.Results: The yield of chromosome aberrations increased during the therapy course, and the frequency was lower in patients irradiated with carbon ions as compared to patients treated with IMRT with similar target volumes. A higher frequency of aberrations was measured by increasing the target volume. In vitro, high-LET carbon ions were more effective than X-rays in inducing aberrations and yielded a higher fraction of complex exchanges. The yield of complex aberrations observed in vivo was very low.Conclusion: The investigation showed no higher aberration yield induced by treatment with a carbon-ion boost. In contrast, the reduced integral dose to the normal tissue is reflected in a lower chromosomal aberration yield when a carbon-ion boost is used instead of IMRT alone. No cytogenetic “signature” of exposure to densely ionizing carbon ions could be detected in vivo.

Dose–volume histogram and dose–surface histogram analysis for skin reactions to carbon ion radiotherapy for bone and soft tissue sarcoma - Corrected Proof

2009-09-22

Abstract: Background and purpose: To evaluate the usefulness of the dose–volume histogram (DVH) and dose–surface histogram (DSH) as clinically relevant and available parameters that helped to identify bone and soft tissue sarcoma patients at risk of developing late skin reactions, including ulceration, when treated with carbon ion radiotherapy.Materials and methods: Thirty-five patients with bone and soft tissue sarcoma treated with carbon ion beams were studied. The clinical skin reactions were evaluated. Some pretreatment variables were compared with the grade of late skin reactions.Results: Average DVH and DSH were established in accordance with the grading of the skin reactions. Prescribed dose, the difference in depths between the skin surface and the proximal extent of the tumor, and some DVH/DSH parameters were correlated with late skin reaction (grade 3) according to univariate analysis. Furthermore, the area irradiated with over 60GyE (S60>20cm2) on DSH was the most important factor by multivariate analysis.Conclusions: The area irradiated with over 60GyE (S60>20cm2) on DSH was found to be a parameter for use as a predictor of late skin reactions.

Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: A meta-analysis - Corrected Proof

2009-09-07

Abstract: Purpose: To provide a comparison between radiotherapy with photons, protons and carbon-ions in the treatment of Non-Small-Cell Lung Cancer (NSCLC), performing a meta-analysis of observational studies. Methods: Eligible studies on conventional radiotherapy (CRT), stereotactic radiotherapy (SBRT), concurrent chemoradiation (CCR), proton therapy and carbon-ion therapy were searched through a systematic review. To obtain pooled estimates of 2- and 5-year disease-specific and overall survival and the occurrence of severe adverse events for each treatment modality, a random effects meta-analysis was carried out. Pooled estimates were corrected for effect modifiers. Results: Corrected pooled estimates for 2-year overall survival in stage I inoperable NSCLC ranged from 53% for CRT to 74% for carbon-ion therapy. Five-year overall survival for CRT (20%) was statistically significantly lower than that for SBRT (42%), proton therapy (40%) and carbon-ion therapy (42%). However, caution is warranted due to the limited number of patients and limited length of follow-up of the particle studies. Conclusion: Survival rates for particle therapy were higher than those for CRT, but similar to SBRT in stage I inoperable NSCLC. Particle therapy may be more beneficial in stage III NSCLC, especially in reducing adverse events.

Trials and tribulations in charged particle radiotherapy - Corrected Proof

Michael Goitein — 2009-07-08

Abstract: A number of aspects of radiotherapy using protons and ions such as carbon and neon are discussed, focusing less on the oft-enumerated advantages or potential advantages of these particles as on those aspects which are, or may be, problematic. First, for protons and so-called heavy ions separately, the potential advantages and disadvantages of the particles, on physical and radiobiological grounds, are reviewed and some outstanding problems, both technical and scientific, are enumerated. Then, mention is made of the danger that financial pressures can lead to suboptimal medical care of patients. Finally, the issue of clinical trials, and especially randomized clinical trials, is addressed. On the one hand, very few randomized trials have been reported. On the other hand, there is a widespread desire to see trials of charged particle therapy undertaken. The ethical considerations are briefly reviewed and it is concluded that they pose strong limitations on the types of trials which can be undertaken. Nevertheless, some clinical trials would certainly be appropriate and desirable and a number are suggested, under the categories of retrospective non-randomized clinical trials, prospective non-randomized clinical trials, and prospective-randomized clinical trials.

Spread-out antiproton beams deliver poor physical dose distributions for radiation therapy - Corrected Proof

Harald Paganetti, Michael Goitein, Katia Parodi — 2009-04-27

Abstract: Background and purpose: Antiprotons have been suggested as a possibly superior modality for radiotherapy, due to the energy released when they annihilate, which enhances the Bragg peak and introduces a high-LET component to the dose. Previous studies have focused on small-diameter near-monoenergetic antiproton beams. The goal of this work was to study more clinically relevant beams.Methods: We used Monte Carlo techniques to simulate 120 and 200MeV beams of both antiprotons and protons of 1×1 and 10×10cm2 areas, impinging on water.Results: An annihilating antiproton loses little energy locally; most goes into long-range secondary particles. When clinically typical field sizes are considered, these particles create a substantial dose halo around the primary field and degrade its lateral fall-off. Spreading the dose in depth further intensifies these effects.Conclusions: The physical dose distributions of spread-out antiproton beams of clinically relevant size (e.g. 10×10cm2 area) are substantially inferior to those of proton beams, exhibiting a dose halo and broadened penumbra. Studies on the value of antiproton beams, taking radiobiological effectiveness into account, need to assess such realistic beams and determine whether their inferior dose distributions do not undermine the potential value of antiprotons for all but the smallest fields.

REMOVED: Boron neutron capture therapy (BNCT) for glioblastoma multiforme: A phase 2 study evaluating a prolonged high dose of boronophenylalanine (BPA) - Corrected Proof

2006-05-24

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