A prospective randomized study comparing two frameless immobilization systems for cranial stereotactic radiotherapy.

Introduction: The Dual Shell Encompass Fibreplast™ System (DS-Encompass) by CQ Medical™ is validated for frameless immobilization in stereotactic brain radiotherapy. An alternative mask model has been proposed with the rear shell replaced by a Moldcare® cushion (M-Encompass). To validate the use of this model in our cranial stereotactic workflow method including HyperArc™, we performed a prospective randomized study comparing inter-and intrafractional motion and patients comfort between both masks. Materials & Methods: A prospective randomized study between DS-Encompass and M-Encompass was conducted involving 60 participants. Stratification between DS-Encompass and M-Encompass was carried out based on the fractionation scheme. Treatment plans were created with HyperArc™. During treatment, surface guidance was used for patient positioning and monitoring. A pre-treatment cone-beam CT (CBCT) was acquired to correct interfractional motion and a post-treatment CBCT was acquired to quantify the intrafractional motion. Patients reported comfort was analyzed with a Likert-scale at the end of the treatment. Unpaired t-tests were conducted to determine the level of significance. Results: No significant difference in interfractional translations is present. A significant difference is revealed in roll-axis rotation, where DS-Encompass allows for smaller deviations. Since interfractional motion can be corrected through daily CBCT-scans and 6D-couch corrections, they are clinically irrelevant. Intrafractional motion does not differ significantly and remains below 0.5 mm and 0.5° for both systems. There is no statistical difference in patient-reported comfort. Conclusion: We conclude that Encompass with Moldcare offers a safe alternative to Duall Shell Encompass for non-coplanar stereotactic brain radiotherapy. There is no significant difference in intrafractional motion nor difference in comfort levels.

Validation and IMRT/VMAT delivery quality of a preconfigured fast-rotating O-ring linac system.

PURPOSE: A fast-rotating O-ring dedicated intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) delivery system, the Halcyon, is delivered by default with a fully preconfigured photon beam model in the treatment planning system (TPS). This work reports on the validation and achieved IMRT/VMAT delivery quality on the system. METHODS: Acceptance testing followed the vendor's installation product acceptance and was supplemented with mechanical QA. The dosimetric calibration was performed according to the IAEA TRS-398 code-of-practice, delivering 600 cGy/min at 10 cm depth, a 90 cm source-surface distance, and a 10 × 10 cm² field size. The output factors, multileaf collimator (MLC) transmission and dosimetric leaf gap (DLG) were validated by comparing measurements with the modeled values in the TPS. Validation of IMRT/VMAT was conducted following AAPM reports (MPPG 5.a, TG-119). Next, dose measurements were performed for end-to-end (E2E) checks in heterogeneous anthropomorphic phantoms using radiochromic film in multiple planes and using ionization chambers (IC) point measurements. E2E checks were performed for VMAT (cranial, rectum, spine, and head and neck) and IMRT (lung). Additionally, IROC Houston mailed dosimetry audits were performed for the beam calibration and E2E measurements using a thorax phantom (IMRT) and a head and neck phantom (VMAT). Lastly, extensive patient-specific QA was performed for the first patients of each new indication, 26 in total (nrectum = 2, nspine = 5, nlung = 5, nesophagus = 2, nhead and neck = 7, ncranial = 5), treated on the fast-rotating O-ring linac. The patient-specific QA followed the AAPM TG-218 guidelines and comprised of portal dosimetry, ArcCHECK diode array, radiochromic film dosimetry in a MultiCube phantom, and IC point measurements. RESULTS: The measured output factors showed an agreement <1% for fields ≥3 × 3 cm². Field sizes ≤2 × 2 cm² had a difference of <2%. The measured single-layer MLC transmission was 0.42 ± 0.01% and the measured DLG was 0.27 ± 0.22 mm. The AAPM MPPG 5.a measurements were fully compliant with the guideline criteria. Dose differences larger than 2% were found for the PDD at large depths (>25 cm). TG-119's confidence limits were achieved for the VMAT point dose measurements and for both the IMRT and VMAT radiochromic film measurements. The TG-119 confidence limits were not achieved for IMRT point dose measurements in both the target (5.9%) and the avoidance structure (6.4%). All E2E tests had point differences below 2.3% and gamma agreement scores above 90.6%. The IROC beam calibration audit showed agreement of <1%. The IROC lung IMRT audit and head and neck VMAT audit had results compliant with the IROC Houston's credentialing criteria. All IMRT and VMAT plans selected for patient-specific QA were within the action limits suggested by TG-218. CONCLUSIONS: The fast-rotating O-ring linac and its preconfigured TPS are compliant with the international commissioning criteria of AAPM MPPG 5.a and AAPM TG-119. E2E measurements on heterogeneous anthropomorphic phantoms were within clinically acceptable tolerances. IROC Houston's audits satisfied the credentialing criteria. This work comprises the first extensive dataset reporting on the preconfigured fast-rotating O-ring linac.

Long term experience with 3D image guided brachytherapy and clinical outcome in cervical cancer patients.

BACKGROUND AND PURPOSE: To report our 10years' experience and learning curve of the treatment of cervical cancer patients with chemo radiotherapy and MRI (or CT in 9 selected patients) guided brachytherapy using pulsed dose rate (PDR) brachytherapy (BT). METHODS AND MATERIALS: Hundred and seventy consecutive patients with cervical cancer FIGO stage IB-IVB (without metastases beyond the para-aortic nodal region) were treated in our institute between 2002 and 2012. Patients received external beam radiotherapy (nodal boost to the lymph nodes positive at diagnosis)±chemotherapy followed by a pulsed or low dose rate brachytherapy boost. MRI (or CT) images were taken with the applicator in situ. The first 16 patients were treated according to X-ray-based plans, optimized on MRI. High-risk CTV, intermediate-risk CTV, bladder, rectum and sigmoid were retrospectively contoured according to the GEC-ESTRO recommendations. In all other patients, treatment plans were optimized after delineation of the target volumes and organs at risk at MRI (or CT). Doses were converted to the equivalent dose in 2Gy (EQD2) by applying the linear quadratic model. The median age of the patients was 55years (range 16-88). 41% had stage III or IV disease. Of the 170 patients, 91 patients had on imaging metastatic lymph nodes at diagnosis (62 patients pelvic lymph node involvement and 29 para-aortic). In 27 (16%) patients the intracavitary technique was combined with interstitial brachytherapy. RESULTS: The mean D90 and D100 for the high-risk CTV were 84.8±8.36Gy and 67.5±6.29Gy for the entire patient group. Mean D90 and D100 values for the IR CTV were 68.7±5.5Gy and 56.5±6.25Gy. There was an important learning curve between both patient groups, with an increase in mean D90 of 75.8Gy for the first 16 patients compared to 85.8Gy for the second group. At the same time, the mean dose to 2cm3 of bladder and sigmoid decreased from 86.1Gy to 82.7Gy and from 70Gy to 61.7Gy, respectively. At a median follow-up of 37months (range 2-136months), local control rate for all patients was 96%, the regional control (pelvic and para-aortic) rate 81% and crude disease free survival rate 55%. The overall survival at 5years is 65%. The higher dose to the target volume resulted in an increase in local control from 88% in the first 16 patients compared to 97% in the second patient group. Regarding late toxicity, 21 patients (12%) presented grade 3-4 late morbidity. Rectal, urinary, sigmoid and vaginal morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006). CONCLUSION: Although the majority of the patients presented with locally advanced carcinoma, excellent local and regional control rates were achieved. Rectal, urinary, sigmoid and vaginal grade 3-4 morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006).

Multicentre treatment planning study of MRI-guided brachytherapy for cervical cancer: comparison between tandem-ovoid applicator users.

BACKGROUND AND PURPOSE: To compare MRI-guided treatment planning approaches between four centres that use tandem-ovoid applicators. MATERIAL AND METHODS: Four centres generated three treatment plans for four patients: standard, optimised intracavitary, and optimised intracavitary/interstitial. Prescribed D90 High-Risk CTV (HR-CTV) was 85 Gy EQD2 (external-beam radiotherapy and brachytherapy), while the D(2cc) OAR limit was 90 Gy EQD2 for bladder and 75 Gy EQD2 for rectum, sigmoid, and bowel, respectively. DVH-parameters, source loading patterns and spatial dose distributions of the three treatment plans were compared. RESULTS: The standard plans of the different centres were comparable with respect to the D90 HR-CTV, but differed in OAR doses. MRI-guided intracavitary optimisation resulted in organ sparing and smaller variation in DVH parameters between the centres. Adding interstitial needles led to target dose escalation while respecting the OAR constraints. However, substantial differences in relative weights of the applicator parts resulted in an increased variation in DVH parameters and locations of high dose regions. CONCLUSIONS: MRI-guided brachytherapy treatment planning optimisation provides the possibility to increase the dose to the HR-CTV and spare the OARs. Depending on the degree of conformity the centres make different choices in relative weighting of applicator parts, leading to different dose distributions.

Intensity-modulated radiotherapy for locally advanced non-small-cell lung cancer: a dose-escalation planning study.

PURPOSE: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). METHODS AND MATERIALS: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). RESULTS: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. CONCLUSION: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

Potential of dose optimisation in MRI-based PDR brachytherapy of cervix carcinoma.

BACKGROUND AND PURPOSE: In this study on PDR treatment planning of utero-vaginal carcinoma, we analysed the dosimetry of traditional X-ray based plans as it presents on MR images. The potential gain of MRI-based dose optimisation was assessed. PATIENTS AND METHODS: Sixteen patients boosted with PDR brachytherapy after external beam therapy were included. The clinical X-ray based plans were projected on MR images. The GTV, HR-CTV and IR-CTV were retrospectively contoured, as well as the bladder, rectum and sigmoid colon. The dose in the critical organs and target coverage was investigated. In a second phase, the plans were manually optimised using the MR information. The objectives were to lower the dose in the critical organs (or= 85 Gy(alphabeta10). RESULTS: In the X-ray based plans, D(2cc) in bladder and sigmoid colon exceeded the tolerance doses in 10/16 and 7/16 patients, respectively. Coverage of the IR-CTV with the 60 Gy(alphabeta10) was acceptable. D90 of the HR-CTV was below 85 Gy(alphabeta10) in 13 out of 16 patients. After optimisation, the dose constraints in the OAR were not exceeded anymore in any patient. The average D(2cc) dose reduction was 7+/-6 Gy(alphabeta3) in the bladder and 7+/-4 Gy(alphabeta3) in the sigmoid colon for those patients in which the dose constraint was initially exceeded. In addition, an average dose increase of 3 Gy(alphabeta10) was accomplished in the HR-CTV. CONCLUSIONS: MRI-based dose optimisation can play an important role to reduce the dose delivered to the critical organs and to improve target coverage.

Post-operative intensity-modulated radiotherapy for malignancies of the nasal cavity and paranasal sinuses.

PURPOSE: To evaluate the clinical outcome and toxicity of post-operative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. METHODS AND MATERIALS: Twenty-five patients with histological proven cancer of the paranasal sinuses (n=21) or nasal cavity (n=4) were post-operatively treated with IMRT at the Leuven department to a total dose of 60 Gy (n=15) or 66 Gy (n=10). Both acute and chronic toxicity were prospectively scored in all patients. RESULTS: Median follow-up was 27 months (range: 12-47 months) among surviving patients. The actuarial 2-year local control (LC), overall survival (OS) and disease-free survival (DFS) rates were 81%, 88% and 77%, respectively. One patient developed isolated distant metastasis, while none of the patients developed regional failure. No grade 3 or 4 toxicity was reported, either acute or chronic. No radiation-induced blindness or brain necrosis was reported to date, although longer follow-up has to be awaited for definitive results. CONCLUSION: Post-operative IMRT for sinonasal cancer resulted in similar local control and survival rates as conventional or 3D-conformal radiotherapy techniques, and was associated with little acute toxicity. Longer follow-up is necessary to confirm the lack of late complications.

Quantitative evaluation of a beam-matching procedure using one-dimensional gamma analysis.

This article provides a quantitative evaluation of Varian Medical Systems' beam matching procedure. A one-dimensional y analysis is employed to investigate the level of agreement of matched beams. A customized concept of one-dimensional gamma evaluation was designed. Our algorithm first performs a "local" fit of the reference and the evaluated datasets. For a particular point on the fitted evaluated curve, the y is derived as the shortest distance between the point and the fitted reference curve. This approach removes variations of the obtained y value related to the discrete character and noise in the original datasets. Criteria of 1 mm distance-to-agreement and 1% dose difference were used to evaluate the level of agreement of according profiles. Relative point and profile measurements were performed for all photon and electron beams of two Varian Clinacs 2100C/D. Matched beams show a good level of agreement. 70% of profiles completely pass the chosen criteria. The analysis of remaining 30% of the profiles demonstrates that measurement error becomes a limiting factor in achieving a better score. The highest obtained y value was 1.70. The quality of beam matching allowed us to treat according beams of both treatment units as "identical" and to use the reference beam data for the new unit. Nevertheless, the vendor's acceptance criteria of beam matching are much more benevolent. It might happen that the acceptance criteria are met, however, resulting quality of beam matching does not allow full interchangeability of beams.

Intercomparison of treatment concepts for MR image assisted brachytherapy of cervical carcinoma based on GYN GEC-ESTRO recommendations.

PURPOSE: To perform a multicentre intercomparison study of treatment concepts for MRI assisted brachytherapy of cervix cancer based on recommendations of the Gynaecological GEC-ESTRO Working Group. METHODS: Each participating centre (IGR Paris, University Hospital Leuven, Medical University of Vienna) contributed data of one patient with comparable clinical features. GTV, High Risk CTV (HR CTV), Intermediate Risk CTV (IR CTV) and organ walls of bladder, rectum and sigmoid colon were delineated at the time of each brachytherapy fraction on axial MR images with the applicator in place. Dose-volume histograms were calculated to evaluate doses to tumour, target volumes and organs at risk. Dose values were biologically normalised to equivalent doses in 2 Gy fractions (EQD(2), equivalent to 50 cGy/h low dose rate) applying the linear-quadratic model. RESULTS: Total doses to point A from external beam therapy plus brachytherapy ranged from 85 to 91 Gy and were close to the dose covering 90% of HR CTV (D90=85-87 Gy). D90 of IR CTV was within 69-73 Gy. Doses to organs at risk were comparable. CONCLUSIONS: This study indicates the feasibility of the GEC-ESTRO recommendations. Despite different treatment concepts, biologically normalised total doses to tumour, target volumes and organs at risk were comparable.

Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.

The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, Pötter R, Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (I): concepts and terms in 3D image-based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV.

BACKGROUND AND PURPOSE: Brachytherapy (BT) plays a crucial role in the management of invasive cervix cancer from stage I to IV. Intracavitary techniques are based on afterloading devices, with different types of applicators. CT and/or MRI compatible applicators allow a sectional image based approach with a better assessment of gross tumour volume (GTV) and definition and delineation of target volume (CTV) compared to traditional approaches. Accurate and reproducible delineation of GTV, CTV and PTV, as well as of critical organs has a direct impact on BT treatment planning, especially if it is possible to adapt the pear-shape isodose by optimisation using DVH analysis. When introducing a 3D image based approach for GTV and CTV assessment, there is a need for a common language to describe the concepts and to define the terms which are to be used. METHODS: In 2000, GEC-ESTRO decided to support 3D imaging based 3D treatment planning approach in cervix cancer BT with the creation of a Working Group. The task was to describe basic concepts and terms and to work out a terminology enabling various groups working in this advanced field to use a common language. The recommendations described in this report were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and were stepwise validated against the background of different clinical experience. CONCLUSIONS: As GTV and CTV for BT change significantly during treatment, time frame for assessment of GTV and CTV for BT is specified in this report: at time of diagnosis GTV(D), CTV(D) and at time of BT GTV(B), CTV(B). Furthermore, CTV for BT is defined related to risk for recurrence: high risk CTV and intermediate risk CTV. Beside verbal descriptions detailed examples are given, partly in form of schematic drawings.