Practical and technical key challenges in head and neck adaptive radiotherapy: The GORTEC point of view.

Anatomical variations occur during head and neck (H&N) radiotherapy (RT) treatment. These variations may result in underdosage to the target volume or overdosage to the organ at risk. Replanning during the treatment course can be triggered to overcome this issue. Due to technological, methodological and clinical evolutions, tools for adaptive RT (ART) are becoming increasingly sophisticated. The aim of this paper is to give an overview of the key steps of an H&N ART workflow and tools from the point of view of a group of French-speaking medical physicists and physicians (from GORTEC). Focuses are made on image registration, segmentation, estimation of the delivered dose of the day, workflow and quality assurance for an implementation of H&N offline and online ART. Practical recommendations are given to assist physicians and medical physicists in a clinical workflow.

IAEA methodology for on-site end-to-end IMRT/VMAT audits: an international pilot study.

Background: The IAEA has developed and tested an on-site, end-to-end IMRT/VMAT dosimetry audit methodology for head and neck cases using an anthropomorphic phantom. The audit methodology is described, and the results of the international pilot testing are presented.Material and methods: The audit utilizes a specially designed, commercially available anthropomorphic phantom capable of accommodating a small volume ion chamber (IC) in four locations (three in planning target volumes (PTVs) and one in an organ at risk (OAR)) and a Gafchromic film in a coronal plane for the absorbed dose to water and two-dimensional dose distribution measurements, respectively. The audit consists of a pre-visit and on-site phases. The pre-visit phase is carried out remotely and includes a treatment planning task and a set of computational exercises. The on-site phase aims at comparing the treatment planning system (TPS) calculations with measurements in the anthropomorphic phantom following an end-to-end approach. Two main aspects were tested in the pilot study: feasibility of the planning constraints and the accuracy of IC and film results in comparison with TPS calculations. Treatment plan quality was scored from 0 to 100.Results: Forty-two treatment plans were submitted by 14 institutions from 10 countries, with 79% of them having a plan quality score over 90. Seventeen sets of IC measurement results were collected, and the average measured to calculated dose ratio was 0.988 ± 0.016 for PTVs and 1.020 ± 0.029 for OAR. For 13 film measurement results, the average gamma passing rate was 94.1% using criteria of 3%/3 mm, 20% threshold and global gamma.Conclusions: The audit methodology was proved to be feasible and ready to be adopted by national dosimetry audit networks for local implementation.

A multinational audit of small field output factors calculated by treatment planning systems used in radiotherapy.

BACKGROUND AND PURPOSE: An audit methodology for verifying the implementation of output factors (OFs) of small fields in treatment planning systems (TPSs) used in radiotherapy was developed and tested through a multinational research group and performed on a national level in five different countries. MATERIALS AND METHODS: Centres participating in this study were asked to provide OFs calculated by their TPSs for 10 × 10 cm2, 6 × 6 cm2, 4 × 4 cm2, 3 × 3 cm2 and 2 × 2 cm2 field sizes using an SSD of 100 cm. The ratio of these calculated OFs to reference OFs was analysed. The action limit was ±3% for the 2 × 2 cm2 field and ±2% for all other fields. RESULTS: OFs for more than 200 different beams were collected in total. On average, the OFs for small fields calculated by TPSs were generally larger than measured reference data. These deviations increased with decreasing field size. On a national level, 30% and 31% of the calculated OFs of the 2 × 2 cm2 field exceeded the action limit of 3% for nominal beam energies of 6 MV and for nominal beam energies higher than 6 MV, respectively. CONCLUSION: Modern TPS beam models generally overestimate the OFs for small fields. The verification of calculated small field OFs is a vital step and should be included when commissioning a TPS. The methodology outlined in this study can be used to identify potential discrepancies in clinical beam models.

Quality assurance of radiotherapy in the ongoing EORTC 1219-DAHANCA-29 trial for HPV/p16 negative squamous cell carcinoma of the head and neck: Results of the benchmark case procedure.

BACKGROUND AND PURPOSE: The phase III EORTC 1219-DAHANCA 29 intergroup trial evaluates the influence of nimorazole in patients with locally advanced head and neck cancer when treated with accelerated radiotherapy (RT) in combination with chemotherapy. This article describes the results of the RT Benchmark Case (BC) performed before patient inclusion. MATERIALS AND METHODS: The participating centers were asked to perform a 2-step BC, consisting of (1) a delineation and (2) a planning exercise according to the protocol guidelines. Submissions were prospectively centrally reviewed and feedback was given to the submitting centers. Sørensen-Dice similarity index (DSI) and the 95th percentile Hausdorff distance (HD) were retrospectively used to evaluate the agreement between the centers and the expert contours. RESULTS: Fifty-four submissions (34 delineation and 20 planning exercises) from 19 centers were reviewed. Nine (47%) centers needed to perform the delineation step twice and three (16%) centers 3 times before receiving an approval. An increase in DSI-value and a decrease in HD, in particular for the prophylactic Clinical Target Volume (pCTV), could be found for the resubmitted cases. No unacceptable variations could be found for the planning exercise. CONCLUSIONS: These BC-results highlight the need for effective and prospective RTQA in clinical trials. Even with clearly defined protocol guidelines, delineation and not planning remain the main reason for unacceptable protocol variations. The introduction of more objective quantitative analysis methods, such as the HD and DSI, in future trials might strengthen the evaluation by experts.

Quality assurance for the EORTC 22071-26071 study: dummy run prospective analysis.

PURPOSE: The phase III 22071-26071 trial was designed to evaluate the addition of panitumumab to adjuvant chemotherapy plus intensity modulated radiotherapy (IMRT) in locally advanced resected squamous cell head and neck cancer. We report the results of the dummy run (DR) performed to detect deviations from protocol guidelines. METHODS AND MATERIALS: DR datasets consisting of target volumes, organs at risk (OAR) and treatment plans were digitally uploaded, then compared with reference contours and protocol guidelines by six central reviewers. Summary statistics and analyses of potential correlations between delineations and plan characteristics were performed. RESULTS: Of 23 datasets, 20 (87.0%) GTVs were evaluated as acceptable/borderline, along with 13 (56.5%) CTVs and 10 (43.5%) PTVs. All PTV dose requirements were met by 73.9% of cases. Dose constraints were met for 65.2-100% of mandatory OARs. Statistically significant correlations were observed between the subjective acceptability of contours and the ability to meet dose constraints for all OARs (p ≤ 0.01) except for the parotids and spinal cord. Ipsilateral parotid doses correlated significantly with CTV and PTV volumes (p ≤ 0.05). CONCLUSIONS: The observed wide variations in treatment planning, despite strict guidelines, confirms the complexity of development and quality assurance of IMRT-based multicentre studies for head and neck cancer.

[Quality criteria in radiotherapy for head and neck cancers under the aegis of Head and Neck Intergroup]. / Critères de qualité en radiothérapie des cancers de la tête et du cou sous l'égide de l'Intergroupe ORL.

The aim of radiotherapy is to deliver enough radiation to the tumor in order to achieve maximum tumour control in the irradiated volume with as few serious complications as possible with an irradiation dose as low as possible to normal tissue. The quality of radiotherapy is essential for optimal treatment and quality control is to reduce the bias in clinical trials avoiding possible major deviations. The assurance and quality control programs have been developed in large european (EORTC, GORTEC) and american cooperative groups (RTOG) of radiation oncology since the 1980s. We insist here on the importance of quality assurance in radiotherapy and the current status in this domain and the criteria for quality control especially for current clinical trials within GORTEC are discussed here.

QA makes a clinical trial stronger: evidence-based medicine in radiation therapy.

Quality assurance (QA) for radiation therapy (RT) in clinical trials is necessary to ensure treatment is safely and effectively administered. QA assurance requires however substantial human and financial resources, as it has become more comprehensive and labor intensive in recent RT trials. It is presumed that RT deviations decrease therapeutic effectiveness of the studied regimen. This study assesses the impact of RT protocol-deviations on patient's outcome in prospective phase II-III RT trials. PubMed, Medline and Embase identified nine prospective RT trials detailing QA RT violation and patient's outcome. Planned QA analysis was preformed retrospectively and prospectively in eight and one studies, respectively. Non-adherence to protocol-specified RT requirements in prospective trials is frequent: the observed major deviation rates range from 11.8% to 48.0% (mean, 28.1 ± 17.9%). QA RT deviations had a significant impact on the primary study end-point in a majority (62.5%) of studies. The number of patients accrued per center was a significant predictive factor for RT deviations in the largest series. These QA data stemming from prospective clinical trials show undisputedly that non adherence to protocol-specified RT requirements is associated with reduced survival, local control and potentially increased toxicity.

Adaptive biological image-guided IMRT with anatomic and functional imaging in pharyngo-laryngeal tumors: impact on target volume delineation and dose distribution using helical tomotherapy.

BACKGROUND AND PURPOSE: Adaptive image-guided IMRT appears to be a promising approach for dose escalation in pharyngo-laryngeal tumors. In this framework, we assessed in a proof of concept study the impact of anatomic and functional imaging modalities acquired prior and during radiotherapy on the target volume delineation and the dose distribution using helical tomotherapy. MATERIALS AND METHODS: Ten patients with pharyngo-laryngeal squamous cell carcinoma were treated by concomitant chemo-radiation delivered in 7 weeks. CT, T2-MRI, fat suppressed T2-MRI, and static and dynamic FDG-PET were acquired for each patient before the start of treatment and during radiotherapy, after mean prescribed doses of 14, 25, 35 and 45 Gy. GTVs were manually delineated on CT and MRI images while PET images were automatically segmented by means of a gradient-based method. From these volumes, CTVs and PTVs were derived using consistent guidelines. Simultaneous integrated boost IMRT planning was performed using helical tomotherapy. RESULTS: GTVs significantly decreased throughout the course of RT for all imaging modalities (p<0.001). Clinically non-significant differences and high correlations were found between GTVs delineated on CT and MRI, irrespective of the sequence used. By contrast, FDG-PET-based GTVs segmented from pre- and per-treatment images were significantly smaller compared to anatomical imaging modalities, without any difference existing between static and dynamic acquisition. These differences in GTVs translated into parallel reductions of both prophylactic and therapeutic CTVs and PTVs. Resulting FDG-PET-based and adaptive IMRT planning reduced the irradiated volumes by 15-40% compared to pre-treatment CT planning (V(90), V(95) and V(100)), but did marginally impact on doses to the OAR such as the spinal cord and the parotid glands. CONCLUSIONS: Adaptive IMRT with FDG-PET images has a significant impact on the delineation of TVs and on the dose distribution in pharyngo-laryngeal tumors. Such an approach might thus be considered for dose escalation strategies.

Impact of the type of imaging modality on target volumes delineation and dose distribution in pharyngo-laryngeal squamous cell carcinoma: comparison between pre- and per-treatment studies.

BACKGROUND AND PURPOSE: It has been shown that the use of pre-treatment FDG-PET impacted on the GTV delineation of pharyngo-laryngeal tumors. The goals of this study were to evaluate (1) the impact of FDG-PET GTV on dose distribution, and (2) the impact of per-treatment re-imaging on target volume delineation and dose distribution. MATERIALS AND METHODS: Eighteen patients with squamous cell carcinoma of the oropharynx or larynx/hypopharynx were treated with curative intent by forward planning IMRT. Prior to treatment and on average after a dose of 46 Gy, all patients underwent contrast-enhanced CT, MRI and FDG-PET. After coregistration, GTVs were delineated manually on CT and MRI and automatically on FDG-PET. From these volumes, CTVs and PTVs were derived using consistent guidelines. Planning was performed using conformal radiotherapy. RESULTS: GTVs, CTVs and PTVs based on pre-treatment FDG-PET were significantly smaller than those based on pre-treatment CT. Such difference in target volumes (TV) translated into a significant reduction in the irradiated volumes (reduction of 13 and 18% of the V50 and V95, respectively), Dmean to ipsilateral parotids (30.7 and 38.6% for FDG-PET and CT based plans, respectively) and to controlateral parotids (11.2 and 14.4% for FDG-PET and CT based plans, respectively). TVs based on per-treatment CT or MRI were also significantly smaller compared to those delineated from pre-treatment CT. Volumes delineated with MRI were significantly smaller than those delineated with CT. Due to radiotherapy-induced peri-tumoral inflammation, automatic delineation of FDG-PET GTV could not be performed. Such reductions in TVs translated into a reduction of the irradiated volumes compared to pre-treatment CT planning (reduction for V50 of 19 and 32%, and for V95 of 22 and 40%, for CT and MRI, respectively); Dmean to the ipsilateral parotids were also reduced (ipsilateral parotid Dmean of 20.4% for CT and of 20.1% for MRI compared to 24.7% for pre-treatment CT). CONCLUSIONS: The use of pre-treatment FDG-PET and per-treatment CT or MRI significantly impacts on the delineation of TVs in pharyngo-laryngeal SCC, translating into more normal tissue sparing after conformal radiotherapy planning.

A dosimetry study comparing NCS report-5, IAEA TRS-381, AAPM TG-51 and IAEA TRS-398 in three clinical electron beam energies.

New codes of practice for reference dosimetry in clinical high-energy photon and electron beams have been published recently, to replace the air kerma based codes of practice that have determined the dosimetry of these beams for the past twenty years. In the present work, we compared dosimetry based on the two most widespread absorbed dose based recommendations (AAPM TG-51 and IAEA TRS-398) with two air kerma based recommendations (NCS report-5 and IAEA TRS-381). Measurements were performed in three clinical electron beam energies using two NE2571-type cylindrical chambers, two Markus-type plane-parallel chambers and two NACP-02-type plane-parallel chambers. Dosimetry based on direct calibrations of all chambers in 60Co was investigated, as well as dosimetry based on cross-calibrations of plane-parallel chambers against a cylindrical chamber in a high-energy electron beam. Furthermore, 60Co perturbation factors for plane-parallel chambers were derived. It is shown that the use of 60Co calibration factors could result in deviations of more than 2% for plane-parallel chambers between the old and new codes of practice, whereas the use of cross-calibration factors, which is the first recommendation in the new codes, reduces the differences to less than 0.8% for all situations investigated here. The results thus show that neither the chamber-to-chamber variations, nor the obtained absolute dose values are significantly altered by changing from air kerma based dosimetry to absorbed dose based dosimetry when using calibration factors obtained from the Laboratory for Standard Dosimetry, Ghent, Belgium. The values of the 60Co perturbation factor for plane-parallel chambers (k(att) x k(m) for the air kerma based and p(wall) for the absorbed based codes of practice) that are obtained from comparing the results based on 60Co calibrations and cross-calibrations are within the experimental uncertainties in agreement with the results from other investigators.