Mirjana Josipovic

Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: National guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group

Abstract During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required. Material and methods. A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node (LN) dissection was used for delineation. During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT. Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus. The Dice similarity coefficient (DSC) was used to evaluate the delineation agreement before and after the consensus. Results. The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes. The consensus provides recommendations for target delineation in a standard patient both in case of breast conservation or mastectomy. Before the consensus, the average value of the DSC was modest for most volumes, but high for the breast CTV and the heart. After the consensus, the DSC increased for all volumes. Conclusion. The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer. The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement. This consensus will be used by the DBCG in our prospective trials.

The updated ESTRO core curricula 2011 for clinicians, medical physicists and RTTs in radiotherapy/radiation oncology

INTRODUCTIONnIn 2007 ESTRO proposed a revision and harmonisation of the core curricula for radiation oncologists, medical physicists and RTTs to encourage harmonised education programmes for the professional disciplines, to facilitate mobility between EU member states, to reflect the rapid development of the professions and to secure the best evidence-based education across Europe.nnnMATERIAL AND METHODSnWorking parties for each core curriculum were established and included a broad representation with geographic spread and different experience with education from the ESTRO Educational Committee, local representatives appointed by the National Societies and support from ESTRO staff.nnnRESULTSnThe revised curricula have been presented for the ESTRO community and endorsement is ongoing. All three curricula have been changed to competency based education and training, teaching methodology and assessment and include the recent introduction of the new dose planning and delivery techniques and the integration of drugs and radiation. The curricula can be downloaded at http://www.estro-education.org/europeantraining/Pages/EuropeanCurricula.aspx.nnnCONCLUSIONnThe main objective of the ESTRO core curricula is to update and harmonise training of the radiation oncologists, medical physicists and RTTs in Europe. It is recommended that the authorities in charge of the respective training programmes throughout Europe harmonise their own curricula according to the common framework.

Evaluation of dose to cardiac structures during breast irradiation

OBJECTIVEnAdjuvant radiotherapy for breast cancer can lead to late cardiac complications. The highest radiation doses are likely to be to the anterior portion of the heart, including the left anterior descending coronary artery (LAD). The purpose of this work was to assess the radiation doses delivered to the heart and the LAD in respiration-adapted radiotherapy of patients with left-sided breast cancer.nnnMETHODSn24 patients referred for adjuvant radiotherapy after breast-conserving surgery for left-sided lymph node positive breast cancer were evaluated. The whole heart, the arch of the LAD and the whole LAD were contoured. The radiation doses to all three cardiac structures were evaluated.nnnRESULTSnFor 13 patients, the plans were acceptable based on the criteria set for all 3 contours. For seven patients, the volume of heart irradiated was well below the set clinical threshold whereas a high dose was still being delivered to the LAD. In 1 case, the dose to the LAD was low while 19% of the contoured heart volume received over 20 Gy. In five patients, the dose to the arch LAD was relatively low while the dose to the whole LAD was considerably higher.nnnCONCLUSIONnThis study indicates that it is necessary to assess the dose delivered to the whole heart as well as to the whole LAD when investigating the acceptability of a breast irradiation treatment. Assessing the dose to only one of these structures could lead to excessive heart irradiation and thereby increased risk of cardiac complications for breast cancer radiotherapy patients.

CT-planned internal mammary node radiotherapy in the DBCG-IMN study: Benefit versus potentially harmful effects

Abstract Background. The DBCG-IMN is a nationwide population-based cohort study on the effect of internal mammary node radiotherapy (IMN-RT) in patients with node positive early breast cancer. Due to the risk of RT-induced heart disease, only patients with right-sided breast cancer received IMN-RT, whereas patients with left-sided breast cancer did not. At seven-year median follow-up, a 3% gain in overall survival with IMN-RT has been reported. This study estimates IMN doses and doses to organs at risk (OAR) in patients from the DBCG-IMN. Numbers needed to harm (NNH) if patients with left-sided breast cancer had received IMN-RT are compared to the number needed to treat (NNT). Material and methods. Ten percent of CT-guided treatment plans from the DBCG-IMN patients were selected randomly. IMNs and OAR were contoured in 68 planning CT scans. Dose distributions were re-calculated. IMNs and OAR dose estimates were compared in right-sided versus left-sided breast cancer patients. In six left-sided patients, IMN-RT was simulated, and OAR doses were compared to those in the original plan. The NNH resulting from the change in mean heart dose (MHD) was calculated using a published model for risk of RT-related ischemic heart death. Results. In original plans, the absolute difference between right- and left-sided V90% to the IMNs was 38.0% [95% confidence interval (5.5%; 70.5%), p < 0.05]. Heart doses were higher in left-sided plans. With IMN-RT simulation without regard to OAR constraints, MHD increased 4.8 Gy (0.9 Gy; 8.7 Gy), p < 0.05. Resulting NNHs from ischemic heart death were consistently larger than the NNT with IMN-RT. Conclusion. Refraining from IMN-RT on the left side may have spared some ischemic heart deaths. Assuming left-sided patients benefit as much from IMN-RT as right-sided patients, the benefits from IMN-RT outweigh the costs in terms of ischemic heart death.

Prospective phase II trial of image-guided radiotherapy in Hodgkin lymphoma: benefit of deep inspiration breath-hold.

Abstract Background. Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. In this prospective study we investigate whether radiotherapy with deep inspiration breath-hold (DIBH) can reduce radiation doses to the lungs, heart, and cardiac structures without compromising the target dose. Patients and methods. Twenty-two patients (14 female, 8 male), median age 30 years (18–65 years), with supra-diaphragmatic HL were enrolled and had a thoracic PET/CT with DIBH in addition to staging FDG-PET/CT in free breathing (FB) and a planning CT in both FB and DIBH. For each patient an involved-node radiotherapy plan was done for both DIBH and FB, and the doses to the lungs, heart, and female breasts were recorded prospectively. Mean doses to the heart valves and coronary arteries were recorded retrospectively. Patients were treated with the technique yielding the lowest doses to normal structures. Results. Nineteen patients were treated with DIBH and three with FB. DIBH reduced the mean estimated lung dose by 2.0 Gy (median: 8.5 Gy vs. 7.2 Gy) (p < 0.01) and the mean heart dose by 1.4 Gy (6.0 Gy vs. 3.9 Gy) (p < 0.01) compared to FB. The lung and heart V20Gy were reduced with a median of 5.3% and 6.3%. Mean doses to the female breasts were equal with FB and DIBH. Conclusion. DIBH can significantly decrease the estimated mean doses to the heart and lungs without lowering the dose to the target in radiotherapy for patients with mediastinal HL.

Translational and rotational intra- and inter-fractional errors in patient and target position during a short course of frameless stereotactic body radiotherapy

Abstract Background. Implementation of cone beam computed tomography (CBCT) in frameless stereotactic body radiotherapy (SBRT) of lung tumours enables setup correction based on tumour position. The aim of this study was to compare setup accuracy with daily soft tissue matching to bony anatomy matching and evaluate intra- and inter-fractional translational and rotational errors in patient and target positions. Material and methods. Fifteen consecutive SBRT patients were included in the study. Vacuum cushions were used for immobilisation. SBRT plans were based on midventilation phase of four-dimensional (4D)-CT or three-dimensional (3D)-CT from PET/CT. Margins of 5 mm in the transversal plane and 10 mm in the cranio-caudal (CC) direction were applied. SBRT was delivered in three fractions within a week. At each fraction, CBCT was performed before and after the treatment. Setup accuracy comparison between soft tissue matching and bony anatomy matching was evaluated on pretreatment CBCTs. From differences in pre- and post-treatment CBCTs, we evaluated the extent of translational and rotational intra-fractional changes in patient position, tumour position and tumour baseline shift. All image registration was rigid with six degrees of freedom. Results. The median 3D difference between patient position based on bony anatomy matching and soft tissue matching was 3.0 mm (0–8.3 mm). The median 3D intra-fractional change in patient position was 1.4 mm (0–12.2 mm) and 2.2 mm (0–13.2 mm) in tumour position. The median 3D intra-fractional baseline shift was 2.2 mm (0–4.7 mm). With correction of translational errors, the remaining systematic and random errors were approximately 1°. Conclusion. Soft tissue tumour matching improved precision of treatment delivery in frameless SBRT of lung tumours compared to image guidance using bone matching. The intra-fractional displacement of the target position was affected by both translational and rotational changes in tumour baseline position relative to the bony anatomy and by changes in patient position.

Reduced lung dose and improved inspiration level reproducibility in visually guided DIBH compared to audio coached EIG radiotherapy for breast cancer patients

Abstract Introduction. Patients with left-sided breast cancer with lymph node involvement have routinely been treated with enhanced inspiration gating (EIG) for a decade at our institution. In a transition from EIG to deep inspiration breath hold (DIBH) we compared the two techniques with focus on target coverage, dose to organs at risk and reproducibility of the inspiration level (IL). Material and methods. Twenty-four patients were computed tomography (CT) scanned with EIG and DIBH. For DIBH we used visual feedback and for EIG audio coaching, both during scan and treatment. Treatment plans for 50 Gy over 25 fractions were calculated. Seventeen of the patients were included in the analysis of reproducibility. They were audio coached for one minute before beam-on in DIBH at nine treatment sessions. These respiration curves were analysed with average maximum IL and standard deviation (SD) for the EIG part of the respiratory signal, and mean IL and SD for the DIBH. Comparison of dosimetric and respiration parameters were performed with the Wilcoxon signed rank-sum test. Results. In DIBH, the ipsilateral lung volume increased further compared to EIG (p < 0.0004, mean increase 11%). This lead to a 9% mean reduction (p = 0.002) of the ipsilateral lung volume receiving 20 Gy (V20 Gy). We found no other significant dosimetric differences between the two methods. The reproducibility of the IL was better with the DIBH method, observed as a significantly smaller SD in most patients (p < 0.04 for 16 of 17 patients). Conclusion. The DIBH method resulted in a significantly larger lung volume and lower ipsilateral lung V20 Gy compared to EIG. The IL for visually guided DIBH was more reproducible than audio-coached EIG. Based on these findings, the DIBH technique is our new breathing adaptation standard for radiotherapy of patients with left-sided breast cancer with lymph node involvement.

Deep inspiration breath hold radiotherapy for locally advanced lung cancer: Comparison of different treatment techniques on target coverage, lung dose and treatment delivery time

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Liquid fiducial marker performance during radiotherapy of locally advanced non small cell lung cancer

BACKGROUND AND PURPOSEnWe analysed the positional and structural stability of a long-term biodegradable liquid fiducial marker (BioXmark) for radiotherapy in patients with locally advanced lung cancer.nnnMATERIAL AND METHODSnMarkers were injected via endoscopic- or endobronchial ultrasound in lymph nodes and reachable primary tumours. Marker volume and Hounsfield Units (HU) changing rates were estimated using breath-hold CBCT. Inter-fraction variation in marker position relative to gross tumour volume (GTV) position was established, as well as the inter-fraction variation in mediastinal marker registration relative to a carina registration through the treatment.nnnRESULTSnFifteen patients were included and 29 markers analysed. All markers that were in situ at planning were visible through the treatment. Mean HU was 902±165HU for lymph node and 991±219HU for tumour markers. Volume degradation rates were -5% in lymph nodes and -23% in primary tumours. Three-dimensional inter-fraction variation for marker position relative to the GTV position was -0.1±0.7mm in lymph nodes and -1.5±2.3mm in primary tumours. Inter-fraction variations in marker registration relative to carina registration were -0.4±1.2mm in left-right, 0.2±2.0mm in anterior-posterior and -0.5±2.0mm in cranio-caudal directions.nnnCONCLUSIONSnThe liquid fiducial markers were visible and stable in size and position throughout the treatment course.

Geometric uncertainties in voluntary deep inspiration breath hold radiotherapy for locally advanced lung cancer

BACKGROUND AND PURPOSEnDeep inspiration breath hold (DIBH) increases lung volume and can potentially reduce treatment-related toxicity in locally advanced lung cancer. We estimated geometric uncertainties in visually guided voluntary DIBH and derived the appropriate treatment margins for different image-guidance strategies.nnnMATERIAL AND METHODSnSeventeen patients were included prospectively. An optical marker-based respiratory monitoring with visual guidance enabled comfortable DIBHs, adjusted to each patients performance. All patients had three consecutive DIBH CTs at each of the treatment fractions 2, 16 and 31. DIBH reproducibility was evaluated as inter- and intra-fractional variations in lung volume, tumour position and differential motion between primary tumour and mediastinal lymph nodes.nnnRESULTSnLung volume increased by median 60% in DIBH. Inter- and intra-fractional lung volume variations were median 2.1% and 1.1%, respectively. Inter- and intra-fractional uncertainties in 3D tumour position were 4.8 ± 2.8 mm and 1.7 ± 1.4 mm (mean ± SD). Inter- and intra-fractional differential motion was 4.8 ± 3.3 mm and 0.0 ± 1.1 mm.nnnCONCLUSIONSnFor single targets, visually guided voluntary DIBH radiotherapy is highly reproducible provided an image-guidance strategy with tumour registration is performed. If the primary tumour is separated from the mediastinal lymph nodes, inter-fractional differential motion remains a challenge and margins must be adapted to reflect the image registration strategy.