Clinical experiences with online adaptive radiotherapy of vulvar carcinoma.

BACKGROUND AND PURPOSE: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. MATERIALS AND METHODS: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). RESULTS: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. CONCLUSION: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Treatment plan comparison of proton vs photon radiotherapy for lower-grade gliomas.

BACKGROUND AND PURPOSE: Patients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients. MATERIALS AND METHODS: Twenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction. RESULTS: CTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (Dmean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. Dmean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons. CONCLUSION: A significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy.

A step and shoot intensity modulated technique for total body irradiation.

INTRODUCTION: Total body irradiation (TBI) is a part of the conditioning regimen for bone marrow transplant.At the Royal Marsden (Sutton, UK) and Rigshospitalet (Copenhagen, Denmark), we introduced a step and shoot IMRT (SS IMRT) technique for TBI. This technique requires no equipment other than that used to deliver other external beam radiation. In this paper, we describe this technique and report on data from the two clinics. MATERIALS AND METHODS: The patients were positioned supine, supported by vacuum bag(s). The entire body of the patients were CT scanned with 5 mm slices. Multiple multi-leaf collimator (MLC) defined fields were used.In-vivo dosimetry was performed at the Royal Marsden for 113 patients.Calculated doses for 18 adult and 4 paediatric patients from Rigshospitalet were extracted. RESULTS: The in-vivo data from the Royal Marsden showed that the mean TLD measured dose difference was -1.9% with a standard deviation of 4.5%.SS IMRT plans for 22 patients from Rigshospitalet resulted in mean doses to the brain, lungs and kidneys all within the range of 11.1-11.8 Gy, while the V(12 Gy) was below 5% for the brain, 2% for the lungs and 0% for the kidneys. DISCUSSION: SS IMRT is feasible for TBI and can deliver targeted doses to the organs at risk.

A closer look at RapidArc® radiosurgery plans using very small fields.

RapidArc® has become the treatment of choice for an increasing number of treatment sites in many clinics. The extensive use of multiple subfields in RapidArc® treatments presents unique challenges, especially for small targets treated in few fractions. In this work, very small static fields and subsequently RapidArc® and conventional plans for two targets (0.4 and 9.9 cm(3)) were investigated. Doses from static fields 1-4 MLC leaves (0.25-1.00 cm) wide, and larger fields with 1-4 MLC leaves closed in their centres, were measured using the portal dosimeter-based QA system EPIQA (v 1.3) and gafchromic film. RapidArc and conventional plans for two tumours were then measured using EPIQA, gafchromic EBT2 film and the phantom-based QA system Delta4. Eclipse 8.6 and 8.9, grid spacings of 1.25 and 2.50 mm and a Varian HD linac were used. For static fields one MLC leaf wide, the dose was underestimated by Eclipse by as much as 53% (v 8.6, 2.5 mm grid). Eclipse underestimated the dose downstream from a few MLC leaves closed in the centre of a large MLC field by as much as 30%. Eclipse consistently overestimated the width of the penumbra by about 100%. For the conventional plans, there was good agreement between the calculated and measured dose for the 9.9 cm(3) PTV, but a 10% underdose was observed for the 0.4 cm(3) PTV. For the RapidArc® plans, the measured dose for the 9.9 cm(3) PTV was in good agreement with the calculated one. However, for the 0.4 cm(3) PTV about 10% overdosing was detected (Eclipse v 8.6, 2.5 mm grid spacing). EPIQA data indicated that the measured dose profiles were overmodulated compared to the calculated one. The use of small subfields, typically a few MLC leaves wide, or larger fields with one or a few MLC leaves closed in its centre can result in significant errors in the dose calculation. The detector systems used vary in their ability to detect the discrepancies. Using a smaller grid size and newer version of Eclipse reduces the discrepancies observed in this work but does not eliminate them.

Rotational radiotherapy for prostate cancer in clinical practice.

BACKGROUND AND PURPOSE: Radiotherapy is the standard treatment in locally advanced prostate cancer. The latest technological improvement is modulated rotational radiotherapy, where one single rotation of the treatment machine is used to conform the dose delivery to the target and spare organs at risk, requiring less than 2 min of beam-on time per treatment fraction. MATERIALS AND METHODS: We report herein our experience from the first 46 patients treated for prostate cancer, clinical stage T1-3 with rotational therapy ("RapidArc®", Varian Medical systems) (RA). This patient group is compared to a group of 50 patients treated with a 5-field Intensity Modulated Radiation Therapy (IMRT) technique over the same period. The comparison parameters include target coverage, dose to OAR, treatment time and number of monitor units. Daily-IGRT using implanted gold markers is used before and after treatment to investigate intra-fractional prostate displacement. RESULTS: RA results in improved sparing of the rectum and achieves desired dose distributions with fewer monitor units and a shorter treatment time (<1.5 min versus up to 8.9 min with IMRT). This shorter treatment time also translates in a decreased risk of patient motion during treatment: daily-IGRT demonstrates reduced prostate motion (<3mm 3D vector) from 16.7% to 4.7% in RA patients. Only slight side-effects were seen in the two groups of patients. CONCLUSIONS: RA results in improved sparing of the rectum, however, at the expense of an increase in dose to the femoral heads in prostate patients. The treatment time is significantly reduced from 4.9 min on average with 5-field IMRT to 1.1 min with RA, which allows for a reduction of infractional prostate motion.

RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo simulation.

The aim of this study was to verify the advanced inhomogeneous dose distribution produced by a volumetric arc therapy technique (RapidArc) using 3D gel measurements and Monte Carlo (MC) simulations. The TPS (treatment planning system)-calculated dose distribution was compared with gel measurements and MC simulations, thus investigating any discrepancy between the planned dose delivery and the actual delivery. Additionally, the reproducibility of the delivery was investigated using repeated gel measurements. A prostate treatment plan was delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC-Arc code. The relative absorbed dose differences were calculated voxel-by-voxel, within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS versus gel and TPS versus MC. The differences between the verification methods, MC versus gel, and between two repeated gel measurements were investigated in the same way. For all volume comparisons, the mean value was within 1% and the standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5 mm (% dose difference and mm distance to agreement) within the volume enclosed by the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)), respectively. All comparisons resulted in very high pass rates. More than 95% of the TPS points were within 3%/3 mm of both the gel measurement and MC simulation, both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements showed excellent consistency, indicating reproducible delivery. Using MC simulations and gel measurements, this verification study successfully demonstrated that the RapidArc plan was both accurately calculated and delivered as planned.

IMRT in a pregnant patient: how to reduce the fetal dose?

The purpose of our study was to find a solution for fetal dose reduction during head-and-neck intensity modulated radiation therapy (IMRT) of a pregnant patient. The first step was optimization of the IMRT treatment plan with as few monitor units (MUs) as possible, while maintaining an acceptable dose distribution. The peripheral dose originating from the final IMRT plan was measured at distances reaching from the most proximal to the most distal fetal position, along the accelerator's longitudinal axis, using an anthropomorphic phantom extended with water-equivalent plastic. The measured peripheral dose was divided into leakage, and internal and collimator scatter, to find the degree to which each component influences the peripheral dose to build an appropriate shield. Collimator scatter was the greatest contributor to the peripheral dose throughout the range of the growing fetus. A shield was built and placed beneath the accelerator head, extending caudally from the field edge, to function as an extra collimator jaw. This shield reduced the fetal dose by a factor of 3.5. The peripheral dose components were also measured for simple rectangular fields and also here the collimator scatter was the greatest contributor to the peripheral dose. Therefore, the shielding used for the IMRT treatment of our patient could also be used when shielding in conventional radiotherapy. It is important for a radiation therapy department to be prepared for treatment of a pregnant patient to shield the fetus efficiently.

Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND AND PURPOSE: The combination of chemotherapy, surgery, and radiotherapy has improved the prognosis for patients with malignant pleural mesothelioma (MPM). Intensity-modulated radiotherapy (IMRT) has allowed for an increase in dose to the pleural cavity and a reduction in radiation doses to organs at risk. The present study reports and analyses the incidence of fatal pulmonary toxicity in patients treated at Rigshospitalet, Copenhagen. MATERIALS AND METHODS: Twenty-six patients were treated with induction chemotherapy followed by extrapleural pneumonectomy and IMRT between April 2003 and April 2006. The entire preoperative pleural surface area was treated to 50 Gy and areas with residual disease or close surgical margins were treated to 60 Gy in 30 fractions. RESULTS: The main toxicities were nausea, vomiting, esophagitis, dyspnea, and thrombocytopenia. One patient died from an intracranial hemorrhage during severe thrombocytopenia. Four patients (15%) experienced grade 5 lung toxicity, i.e. pneumonitis 19-40 days after the completion of radiotherapy. Patients with pneumonitis had a significantly larger lung volume fraction receiving 10 Gy or more (V10) (median: 60.3%, range 56.4-83.2%) compared to patients without pneumonitis (median: 52.6%, range: 25.6-80.3%) (p=0.02). Mean lung dose (MLD) was also significantly higher in patients who developed pneumonitis (median 13.9 Gy, range: 13.6-14.2 Gy) than in patients who did not (median=12.4 Gy, range: 8.4-15.4 Gy) (p=0.04). CONCLUSIONS: Significant differences in MLD and V10 for patients with fatal pulmonary toxicity compared to patients without fatal lung toxicity have been demonstrated. Based on the presented data local lung dose constraints have been modified in order to avoid unacceptable toxicity.

Dosimetric verification of RapidArc treatment delivery.

PURPOSE: Recently, Varian Medical Systems have announced the introduction of a new treatment technique, in which dose is delivered over a single gantry rotation with variable MLC positions, dose rate and gantry speed. In February 2008, a preclinical installation of the RapidArc beam delivery approach was carried out on a Varian Clinac at Rigshospitalet in Copenhagen. The purpose of the installation was to perform measurements to verify the correctness of doses delivered with the RapidArc technique. In May 2008, the clinical release of the RapidArc application was installed at Rigshospitalet. METHODS AND MATERIALS: Nine treatment plans were generated in the Eclipse version 8.5 including the RapidArc optimizer for H&N and prostate cases. The plans were delivered to the Scandidos Delta4 cylindrical diode array phantom. First, the measured dose distributions were compared with the calculated doses. All plans were then delivered several times to verify consistency of the delivery. Gamma analysis was used to verify the correspondence between dose distributions. The temporal resolution of the delivery was analysed by investigating the arc segments between control points separately. RESULTS: Overall, good agreement was observed between measured and calculated doses in most cases with gamma values above 1 in >95% of measured points. The reproducibility of delivery was also very high. Gamma analysis between two consecutive runs of the same delivery plan generally showed gamma values above 1 in none of the measured points, and dose deviation less than 1%. Temporal analysis showed small discrepancies between doses delivered between control points (approximately 2 degrees of the rotation) in consecutive runs of a plan, however these were cancelled out in the accumulated dose. CONCLUSION: The delivery of RapidArc beam delivery has been verified to correspond well with calculated dose distributions for a number of different cases. The delivery was very reproducible, and was carried out with high stability of the accelerator performance.

RapidArc volumetric modulated therapy planning for prostate cancer patients.

PURPOSE: Recently, Varian Medical Systems have announced the introduction of a new treatment technique, RapidArc, in which dose is delivered over a single gantry rotation with dynamically variable MLC positions, dose rate and gantry speed. At Rigshospitalet, the RapidArc technique was brought into clinical practice in May 2008 for treatment of prostate cancer patients. We report here our experiences with performing treatment planning using the Eclipse RapidArc optimization software for this patient group. MATERIAL AND METHODS: A stand-alone installation of Eclipse 8.5 with RapidArc optimization capability was performed at Rigshospitalet. Patient data for 8 prostate cancer patients were imported, most of whom were previously treated at Rigshospitalet using IMRT. Three of the patients were treated at Rigshospitalet using the RapidArc technique. Treatment plans were optimized using objectives as given by standard guidelines for clinical treatment planning. RapidArc plans were compared to the IMRT plans by which the patients were actually treated or in the three cases treated with the RapidArc technique to IMRT plans achieved using standard guidelines. Comparison was done with respect to target coverage, doses to rectum and bladder, over-all maximum dose and number of monitor units. RESULTS: Overall, the RapidArc treatment plans gave better or equal sparing of the organs at risk than the IMRT treatment plans. The number of monitor units was lower in most cases, by up to approximately 75%. However, the target dose homogeneity was not as high as for IMRT. The low-dose bath was larger than for IMRT. CONCLUSION: RapidArc optimization is very promising, especially regarding the potential of reducing the number of monitor units, while providing good sparing of organs at risk. Some improvement is still warranted with respect to achieving high target dose homogeneity.

Local control and survival in patients with soft tissue sarcomas treated with limb sparing surgery in combination with interstitial brachytherapy and external radiation.

PURPOSE: The purpose of this study was to evaluate local control, survival and complication rate after treatment of soft tissue sarcoma (STS) with limb-sparing surgery combined with pulsed-dose rate (PDR) interstitial brachytherapy (BRT) and external beam radiotherapy (EBRT). PATIENTS AND METHODS: A retrospective review of 39 adult patients (female/male=25/14, mean age 51(range 21-78) years) with STS who underwent primary limb-sparing surgery combined with PDR BRT (20Gy) and additional post-operative EBRT (50Gy) during the years 1995-2004. RESULTS: Five patients developed local recurrence after a mean follow-up of 3.4 (1.5-5.9) years. The probability of local recurrence free 5 years survival was 83%. At the time of follow-up 10 patients had died (mean follow-up 2.3 (0.8-7.1) years) and 29 patients were still alive (mean follow-up 5.9 (2.1-11.2) years). The overall 5-year survival rate was 76%. Nineteen (49%) patients suffered from some degree of decreased force or function of the affected extremity, 16 (41%) suffered from oedema, 12 (31%) had persistent pain, 8 (21%) suffered from wound complications, and in 4 (10%) of these patients plastic surgery were required. CONCLUSION: Limb sparing surgery, combined with PDR BRT and EBRT can result in good local control in patients with soft tissue sarcomas. BRT is an effective modality with good cosmetic results and acceptable toxicity.

Post-mastectomy radiotherapy in Denmark: from 2D to 3D treatment planning guidelines of The Danish Breast Cancer Cooperative Group.

This paper describes the procedure of changing from 2D to 3D treatment planning guidelines for post-mastectomy radiotherapy in Denmark. The aim of introducing 3D planning for post-mastectomy radiotherapy was to optimize the target coverage and minimize the dose to the normal tissues. Initially, it was investigated whether it was possible to find a treatment technique alternative to the one recommended by the Danish Breast Cancer Cooperative Group (DBCG). A dosimetric comparison of a combined photon/electron 3-field technique (3F) and a partial wide tangent technique (PWT) was carried out on individual planning CT-scans from seven patients selected to represent a wide range of sizes and shapes of chest walls. The heart dose was lower for PWT than for 3F, however, for both techniques the dose was within the accepted constraints. The lung dose was higher but acceptable for six of the seven patients with PWT. The dose to the internal mammary nodes (IMN) was not satisfactory for five of the seven patients for 3F, whereas only two of the seven patients had a minimum dose lower than 95% of the prescribed dose with PWT. Finally, the dose to the contralateral breast was increased when using PWT compared to 3F. It was concluded that PWT was an appropriate choice of technique for future radiation treatment of post-mastectomy patients. A working group was formed and guidelines for 3D planning were developed during a series of workshops where radiation oncologists and physicists from all radiotherapy centres participated. This work also included a definition of the tissue structures needed to be outlined on the planning CT-scan. The work was initiated in 2003 and the guidelines were approved by the DBCG Radiotherapy Committee in 2006. The first of January 2007 the 3D guidelines had been fully implemented in five of the seven radiotherapy centres.

Clinical evaluation of monitor unit software and the application of action levels.

PURPOSE: The aim of this study was the clinical evaluation of an independent dose and monitor unit verification (MUV) software which is based on sophisticated semi-analytical modelling. The software was developed within the framework of an ESTRO project. Finally, consistent handling of dose calculation deviations applying individual action levels is discussed. MATERIALS AND METHODS: A Matlab-based software ("MUV") was distributed to five well-established treatment centres in Europe (Vienna, Graz, Basel, Copenhagen, and Umeå) and evaluated as a quality assurance (QA) tool in clinical routine. Results were acquired for 226 individual treatment plans including a total of 815 radiation fields. About 150 beam verification measurements were performed for a portion of the individual treatment plans, mainly with time variable fluence patterns. The deviations between dose calculations performed with a treatment planning system (TPS) and the MUV software were scored with respect to treatment area, treatment technique, geometrical depth, radiological depth, etc. RESULTS: In general good agreement was found between calculations performed with the different TPSs and MUV, with a mean deviation per field of 0.2+/-3.5% (1 SD) and mean deviations of 0.2+/-2.2% for composite treatment plans. For pelvic treatments less than 10% of all fields showed deviations larger than 3%. In general, when using the radiological depth for verification calculations the results and the spread in the results improved significantly, especially for head-and-neck and for thorax treatments. For IMRT head-and-neck beams, mean deviations between MUV and the local TPS were -1.0+/-7.3% for dynamic, and -1.3+/-3.2% for step-and-shoot IMRT delivery. For dynamic IMRT beams in the pelvis good agreement was obtained between MUV and the local TPS (mean: -1.6+/-1.5%). Treatment site and treatment technique dependent action levels between +/-3% and +/-5% seem to be clinically realistic if a radiological depth correction is performed, even for dynamic wedges and IMRT. CONCLUSION: The software MUV is well suited for patient specific treatment plan QA applications and can handle all currently available treatment techniques that can be applied with standard linear accelerators. The highly sophisticated dose calculation model implemented in MUV allows investigation of systematic TPS deviations by performing calculations in homogeneous conditions.

Nasopharyngeal carcinoma. Treatment planning with IMRT and 3D conformal radiotherapy.

The study was undertaken in order to compare dose plans for intensity-modulated radiotherapy (IMRT) with 3D conformal radiotherapy (3D-CRT) dose plans in patients with nasopharyngeal carcinoma (NPC). Clinical data from 20 consecutive patients treated with IMRT are presented. For 11 patients 3D-CRT plans were made and compared to the IMRT plans with respect to doses to the planning target volumes (PTVs) and to organs at risk (OARs). For comparison of the conformation of dose to defined target volumes the conformity index (CI) was used. Target volume coverage and critical organ protection were significantly improved with IMRT compared to 3D-CRT. One-year loco-regional control, distant metastasis-free survival, and overall survival were 79%, 72%, and 80%. Two patients have had recurrence in the clinical target volume (CTV) only and seven patients have relapsed in distant organs and/or in head-and-neck areas outside the target areas. The study confirms that IMRT is superior to 3D-CRT in the treatment of NPC. As locoregional control of NPC improves we are facing an increasing number of recurrences outside the irradiated area.

Real-time optical-fibre luminescence dosimetry for radiotherapy: physical characteristics and applications in photon beams.

A new optical-fibre radiation dosimeter system, based on radioluminescence and optically stimulated luminescence from carbon-doped aluminium oxide, was developed and tested in clinical photon beams. This prototype offers several features, such as a small detector (1 x 1 x 2 mm3), high sensitivity, real-time read-out and the ability to measure both dose rate and absorbed dose. The measurements describing reproducibility and output dependence on dose rate, field size and energy all had standard deviations smaller than 1%. The signal variation with the angle of incidence was smaller than 2% (1 SD). Measurements performed in clinical situations suggest the potential of using this real-time system for in vivo dosimetry in radiotherapy.