Clinical implementation of a commercial synthetic computed tomography solution for radiotherapy treatment of glioblastoma.

Background and Purpose: Magnetic resonance (MR)-only radiotherapy (RT) workflow eliminates uncertainties due to computed tomography (CT)-MR image registration, by using synthetic CT (sCT) images generated from MR. This study describes the clinical implementation process, from retrospective commissioning to prospective validation stage of a commercial artificial intelligence (AI)-based sCT product. Evaluation of the dosimetric performance of the sCT is presented, with emphasis on the impact of voxel size differences between image modalities. Materials and methods: sCT performance was assessed in glioblastoma RT planning. Dose differences for 30 patients in both commissioning and validation cohorts were calculated at various dose-volume-histogram (DVH) points for target and organs-at-risk (OAR). A gamma analysis was conducted on regridded image plans. Quality assurance (QA) guidelines were established based on commissioning phase results. Results: Mean dose difference to target structures was found to be within ± 0.7 % regardless of image resolution and cohort. OARs' mean dose differences were within ± 1.3 % for plans calculated on regridded images for both cohorts, while differences were higher for plans with original voxel size, reaching up to -4.2 % for chiasma D2% in the commissioning cohort. Gamma passing rates for the brain structure using the criteria 1 %/1mm, 2 %/2mm and 3 %/3mm were 93.6 %/99.8 %/100 % and 96.6 %/99.9 %/100 % for commissioning and validation cohorts, respectively. Conclusions: Dosimetric outcomes in both commissioning and validation stages confirmed sCT's equivalence to CT. The large patient cohort in this study aided in establishing a robust QA program for the MR-only workflow, now applied in glioblastoma RT at our center.

Artificial Intelligence and the future of radiotherapy planning: The Australian radiation therapists prepare to be ready.

The use of artificial intelligence (AI) solutions is rapidly changing the way radiation therapy tasks, traditionally relying on human skills, are approached by enabling fast automation. This evolution represents a paradigm shift in all aspects of the profession, particularly for treatment planning applications, opening up opportunities but also causing concerns for the future of the multidisciplinary team. In Australia, radiation therapists (RTs), largely responsible for both treatment planning and delivery, are discussing the impact of the introduction of AI and the potential developments in the future of their role. As medical physicists, who are part of the multidisciplinary team, in this editorial we reflect on the considerations of RTs, and on the implications of this transition to AI.

Contouring practices and artefact management within a synthetic CT-based radiotherapy workflow for the central nervous system.

BACKGROUND: The incorporation of magnetic resonance (MR) imaging in radiotherapy (RT) workflows improves contouring precision, yet it introduces geometrical uncertainties when registered with computed tomography (CT) scans. Synthetic CT (sCT) images could minimize these uncertainties and streamline the RT workflow. This study aims to compare the contouring capabilities of sCT images with conventional CT-based/MR-assisted RT workflows, with an emphasis on managing artefacts caused by surgical fixation devices (SFDs). METHODS: The study comprised a commissioning cohort of 100 patients with cranial tumors treated using a conventional CT-based/MR-assisted RT workflow and a validation cohort of 30 patients with grade IV glioblastomas treated using an MR-only workflow. A CE-marked artificial-intelligence-based sCT product was utilized. The delineation accuracy comparison was performed using dice similarity coefficient (DSC) and average Hausdorff distance (AHD). Artefacts within the commissioning cohort were visually inspected, classified and an estimation of thickness was derived using Hausdorff distance (HD). For the validation cohort, boolean operators were used to extract artefact volumes adjacent to the target and contrasted to the planning treatment volume. RESULTS: The combination of high DSC (0.94) and low AHD (0.04 mm) indicates equal target delineation capacity between sCT images and conventional CT scans. However, the results for organs at risk delineation were less consistent, likely because of voxel size differences between sCT images and CT scans and absence of standardized delineation routines. Artefacts observed in sCT images appeared as enhancements of cranial bone. When close to the target, they could affect its definition. Therefore, in the validation cohort the clinical target volume (CTV) was expanded towards the bone by 3.5 mm, as estimated by HD analysis. Subsequent analysis on cone-beam CT scans showed that the CTV adjustment was enough to provide acceptable target coverage. CONCLUSION: The tested sCT product performed on par with conventional CT in terms of contouring capability. Additionally, this study provides both the first comprehensive classification of metal artefacts on a sCT product and a novel method to assess the clinical impact of artefacts caused by SFDs on target delineation. This methodology encourages similar analysis for other sCT products.

Cardiac Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase the risk of late cardiac disease. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on late cardiac disease in survivors of childhood cancer treated with RT. METHODS AND MATERIALS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We identified 1496 articles; 4 were included for dose-response modeling between mean cardiac radiation dose and risk of late coronary artery disease, heart failure (HF), valvular disease, and any cardiac disease. RESULTS: For each 10-Gy increase in corrected mean cardiac radiation dose in 1.8- to 2.0-Gy fractions, we estimated a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25) for coronary artery disease, of 1.87 (95% CI, 1.70-2.06) for HF, of 1.87 (95% CI, 1.78-1.96) for valvular disease, and of 1.88 (95% CI, 1.75-2.03) for any cardiac disease. From the same model, for each 100-mg/m2 increase in cumulative anthracycline dose, the hazard ratio for the development of HF was 1.93 (95% CI, 1.58-2.36), equivalent to an increase in mean heart dose of approximately 10.5 Gy. Other nontreatment factors were inconsistently reported in the analyzed articles. CONCLUSIONS: Radiation dose to the heart increases the risk of late cardiac disease, but survivors of childhood cancer who receive a mean dose <10 Gy at standard fractionation are at low absolute risk (<∼2% approximately 30 years after exposure) of late cardiac disease in the absence of anthracycline exposure. Minimizing cardiac radiation dose is especially relevant in children receiving anthracyclines. When cardiac sparing is not possible, we recommend prioritizing target coverage. It is likely that individual cardiac substructure doses will be a better predictor of specific cardiac diseases than mean dose, and we urge the pediatric oncology community to further study these relationships.

Postoperative complications after esophagectomy for cancer, neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy: A single institutional cohort study.

Background: Complications after esophagectomy are common and the possible increase in postoperative complications associated with neoadjuvant chemoradiotherapy is of concern. The aim of our study was to analyze if the addition of radiotherapy to neoadjuvant chemotherapy increases the incidence and severity of postoperative complications, including evaluation of the relation between radiation doses to the heart and lungs and postoperative complications. Methods: The study was based on an institutional surgical database for esophageal cancer. The study period was October 2008 to March 2020. Patients treated with neoadjuvant chemoradiotherapy were compared to patients treated with neoadjuvant chemotherapy and dose/volume parameters for the lungs and heart considered. The primary outcome was 30-day postoperative complications. Results: During the study period, 274 patients underwent surgery for esophageal cancer, 93 patients after neoadjuvant chemotherapy and 181 patients after neoadjuvant chemoradiotherapy. The median prescribed radiation dose to the planning target volume was 41.4 Gy, the median of the mean lung dose was 6.2 Gy, and the median of the mean heart dose was 20.3 Gy. The addition of radiotherapy to neoadjuvant chemotherapy did not increase the incidence of postoperative complications. Neither were radiation doses to the lungs and heart associated with postoperative complications. Taxane-based chemotherapy regimens were however associated with an increased incidence of postoperative complications. Conclusions: In our cohort, the addition of neoadjuvant radiotherapy to chemotherapy was not associated with postoperative complications. However, taxane-based chemotherapy regimens, with or without concomitant radiotherapy, were associated with postoperative complications.

Surface-guided radiotherapy improves rotational accuracy in gynecological cancer patients.

Background: The aim of this study was to determine if rotational uncertainties in gynecological cancer patients can be reduced using surface imaging (SI) compared to aligning three markers on the patient's skin with in-room lasers (marker-laser). Materials and methods: Fifty gynecological cancer patients treated with external-beam radiotherapy were retrospectively analyzed; 25 patients were positioned with marker-laser and 25 patients were positioned with SI. The values of rotational (pitch and roll) deviations of the patient positions between the treatment-planning computed tomography (CT) and online cone-beam computed tomography (CBCT) were collected for both subcohorts and all treatment fractions after performing automatic registration between the two image sets. Statistical analysis of the difference between the two set-up methods was performed using the Mann-Whitney U-test. Results: The median pitch deviation were 1.5° [interquartile range (IQR): 0.6°-2.6°] and 1.1° (IQR: 0.5°-1.9°) for the marker-laser and SI methods, respectively (p < 0.01). The median roll deviation was 0.5° (IQR: 0.2°-0.9°), and 0.7° (IQR: 0.3°-1.2°) for the marker-laser and SI methods, respectively (p < 0.01). Given the shape of the target, pitch deviations had a greater impact on the uncertainty at the periphery of the target and were considered more relevant. Conclusion: By introducing SI as a set-up method in gynecological cancer patients, higher positioning accuracy could be achieved compared with the marker-laser set-up method. This was demonstrated based on residual deviations rather than deviations corrected for by image-guided radiotherapy (IGRT).

Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial.

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04460352.

Breast Hypoplasia and Decreased Lactation From Radiation Therapy in Survivors of Pediatric Malignancy: A PENTEC Comprehensive Review.

PURPOSE: Breast hypoplasia and impaired lactation are poorly studied sequelae of chest radiation therapy (RT) in children. The Pediatric Normal Tissue Effects in the Clinic female breast task force aimed to quantitate the radiation dose-volume effects on these endpoints. METHODS AND MATERIALS: A literature search was conducted of peer-reviewed manuscripts evaluating breast hypoplasia and lactation after chest RT in children, yielding 789 abstracts. Only 2 studies on children irradiated at <4 years of age for angioma of the breast provided dosimetric data correlated with breast hypoplasia. For patients who received brachytherapy, the dose was converted to external beam RT in equivalent 2 Gy fractions (DEBRT), although the limitations of this type of mathematical conversion need to be recognized. We calculated relative risks (RR) and 95% confidence intervals (95% CIs) based on these data. Only 1 study was relevant to the lactation endpoint, in which patients were given RT for Hodgkin lymphoma at age 14 to 40 years. RESULTS: The 3 studies involved 206 patients in total. In patients <4 years old at the time of RT, the prevalence of patient-perceived breast hypoplasia was 38% (RR 2.5; 95% CI, 1.3-4.6) after DEBRT of <0.34 Gy, 61% (RR 4.0; 95% CI, 2.1-7.4) after DEBRT 0.34-0.97 Gy, and 97% (RR 6.3; 95% CI, 3.6-10.8) after DEBRT ≥0.97 Gy to the breast anlage. A simple linear regression model (r = 0.72; P < .001) showed that the treated breast was smaller than the untreated breast by 13% at DEBRT = 0.5 Gy, 20% at DEBRT = 1 Gy, 32% at DEBRT = 2 Gy, 51% at DEBRT = 4 Gy, 66% at DEBRT = 6 Gy, 79% at DEBRT = 8 Gy, and 90% at DEBRT = 10 Gy. The risk of unsuccessful breastfeeding was 39% after a median mediastinal dose of 41 Gy, compared with 21% in a sibling control group (P = .04). RT dose of ≥42 Gy was not associated with less breastfeeding success compared with <42 Gy, and data on lower doses were unavailable. CONCLUSIONS: Based on extremely limited data, young adults exposed to thoracic RT as children seem to be at significant risk of breast hypoplasia and impaired lactation. Doses as low as 0.3 Gy to immature breasts can cause breast hypoplasia. Additional studies are needed to quantify dose and technique effects with modern RT indications. Prospective collection of clinical outcomes and dosimetric factors would enhance our understanding of RT-induced breast hypoplasia and impaired lactation.

Modeling of Xerostomia After Radiotherapy for Head and Neck Cancer: A Registry Study.

AIM: Data from a local quality registry are used to model the risk of late xerostomia after radiotherapy for head and neck cancer (HNC), based on dosimetric- and clinical variables. Strengths and weaknesses of using quality registry data are explored. METHODS: HNC patients treated with radiotherapy at the Karolinska University hospital are entered into a quality registry at routine follow up, recording morbidity according to a modified RTOG/LENT-SOMA scale. Other recorded parameters are performance status, age, gender, tumor location, tumor stage, smoking status, chemotherapy and radiotherapy data, including prescribed dose and organ-at-risk (OAR) dose. Most patients are entered at several time points, but at variable times after treatment. Xerostomia was modeled based on follow-up data from January 2014 to October 2018, resulting in 753 patients. Two endpoints were considered: maximum grade ≥2 (XERG≥2) or grade ≥3 (XERG≥3) late xerostomia. Univariate Cox regression was used to select variables for two multivariate models for each endpoint, one based on the mean dose to the total parotid volume (Dtot) and one based on the mean dose to the contralateral parotid (Dcontra). Cox regression allows the estimation of the risk of xerostomia at different time points; models were presented visually as nomograms estimating the risk at 9, 12, and 24 months respectively. RESULTS: The toxicity rates were 366/753 (49%) for XERG≥2 and 40/753 (5.3%) for XERG≥3. The multivariate models included several variables for XERG≥2, and dose, concomitant chemotherapy and age were included for XERG≥3. Induction chemotherapy and an increased number of fractions per week were associated with a lower risk of XERG≥2. However, since the causality of these relationships have limited support from previous studies, alternative models without these variables were also presented. The models based on the mean dose to the total parotid volume and the contralateral parotid alone were very similar. CONCLUSION: Late xerostomia after radiotherapy can be modeled with reasonable predictive power based on registry data; models are presented for different endpoints highly relevant in clinical practice. However, the risk of modeling indirect relationships, given the unavoidably heterogeneous registry data, needs to be carefully considered in the interpretation of the results.

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT.

Purpose: The aim of this work was to determine how the spatial pattern of dose in the ano-rectal wall is related to late gastro-intestinal toxicity for prostate cancer patients treated with mainly IMRT.Patients and methods: Patients from the DUE-01 multicentre study with patient-reported (prospective) follow-up and available dosimetric data were included. Conventionally fractionated patients received 74-80 Gy and hypofractionated patients received 65-75.2 Gy. A large majority of the patients were treated with intensity-modulated radiotherapy (IMRT). Dose-surface maps (DSMs) for the anal canal and rectum as a single structure, and for the anal canal and the rectum separately, were co-registered rigidly in two dimensions and, for the patients with and without toxicity, respectively, the mean value of the dose in each pixel was calculated. A pixel-wise t-test was used to highlight the anatomical areas where there was a significant difference between the 'mean dose maps' of each group. Univariate models were also fitted to a range of spatial parameters. The endpoints considered were a mean grade ≥1 late fecal incontinence and a maximum grade ≥2 late rectal bleeding.Results: Twenty-six out of 213 patients had fecal incontinence, while 21/225 patients had rectal bleeding. Incontinence was associated with a higher dose in the caudal region of the anal canal; the most relevant spatial parameter was the lateral extent of the low and medium isodoses (5-49 Gy in EQD2). Bleeding was associated with high isodoses reaching the posterior rectal wall. The spatial dose parameters with the highest AUC value (.69) were the lateral extent of the 60-70 Gy isodoses.Conclusions: To avoid fecal incontinence it is important to limit the portion of the anal canal irradiated. Our analysis confirms that rectal bleeding is a function of similar spatial dose parameters for patients treated with IMRT, compared to previous studies on patients treated with three-dimensional conformal radiotherapy.

The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors.

BACKGROUND: To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC). METHODS: The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient's original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location. RESULTS: The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p = 0.005). Women receiving mean doses of 1-5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47-1.74) for a later coronary intervention compared to women receiving mean doses of 0-1 Gy to the mid LAD. In women receiving mean doses of 5-20 Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52-2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01-13.6) for mean doses over 20 Gy, when compared to women receiving mean doses of 0-1 Gy to the mid LAD. CONCLUSIONS: In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

Post-mastectomy radiation therapy with or without implant-based reconstruction is safe in terms of clinical target volume coverage and survival - A matched cohort study.

BACKGROUND AND PURPOSE: Patients with breast cancer receiving mastectomy in our institution are offered immediate breast reconstruction (IBR). IBR may have an impact on the optimisation of radiation therapy (RT). Therefore, we aimed to evaluate the clinical target volume (CTV) dose coverage when disregarding the dose received by the breast implant in women treated for breast cancer. Furthermore, to investigate the safety of immediate breast reconstruction (IBR) with an implant (IBR+) in terms of recurrence and survival compared to patients without an implant (IBR-). PATIENTS AND METHODS: This matched-cohort included 128 patients with IBR+ and 252 IBR- patients (controls). The potential confounding effects of tumour stage and treatment were controlled for. For IBR+ patients, the implant volume was excluded from the CTV in the RT planning images, and the RT target coverage (V95%: CTV covered by ≥the 95% isodose) was compared between the IBR+ and IBR- groups. RESULTS: A limited under dosage was observed in patients without lymph-node irradiation; the V95% mean values for the CTV subtracting the implant were 84% and 92%, for IBR+ and IBR- groups, respectively. Median follow-up duration was 5.8 years (0.1-7.5 years). In comparing IBR+ and IBR- groups, no statistically significant differences were found in the incidence of recurrence rate ratios or recurrence free survival (log-rank p = 0.142), overall survival (log-rank p = 0.096), or breast cancer specific survival (log-rank p = 0.147). CONCLUSIONS: Post-mastectomy radiation therapy and implant-based reconstruction lead to minor under dosage of the target, due to the projection of the subcutaneous tissue in the presence of the implant. However, recurrence and survival rates were equally distributed among IBR+ and IBR- patients indicating that the overall treatment protocol used in our institution is safe.

Breaking the matching in nested case-control data offered several advantages for risk estimation.

OBJECTIVE: To demonstrate the advantage of using weighted Cox regression to analyze nested case-control data in overcoming limitations encountered with traditional conditional logistic regression. STUDY DESIGN AND SETTING: We analyzed data from 1,051 women who were sampled in a case-control study of lung cancer nested within a cohort of breast cancer patients. We investigated how lung cancer risk is associated with radiation therapy and modified by smoking, with both conditional logistic regression and weighted Cox regression models. RESULTS: In contrast to logistic regression, weighted Cox regression exploited the information regarding radiation dose received by each individual lung. The weighted method also mitigated a problem of overmatching apparent in the data and revealed that the risk of radiotherapy-associated lung cancer was modified by smoking (P = 0.026) with a hazard ratio of 4.09 (2.31, 7.24) in unexposed smokers and 8.63 (5.04, 14.79) in smokers receiving doses >13 Gy. The cumulative risk of lung cancer increased steadily with increasing radiotherapy dose in smokers, whereas no such effect was found in nonsmokers. CONCLUSION: The weighted Cox regression makes optimal and versatile use of the information in a nested case-control design, allowing dose-response analysis of exposure to paired organs and enabling the estimation of cumulative risk.

A national approach for automated collection of standardized and population-based radiation therapy data in Sweden.

PURPOSE: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. MATERIALS AND METHODS: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. RESULTS: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA®, Mosaiq®, Eclipse™, and Oncentra® is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. CONCLUSIONS: An infrastructure for structured and automated prospective collection of syntactically interoperable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.

A template for writing radiotherapy protocols.

BACKGROUND: Well-specified and unambiguous treatment protocols are essential both for current practice and for the future development of radiation therapy. In order to provide assistance for writing good protocols, irrespective of treatment intention and complexity, up-to-date guidelines are highly desirable. METHODS: We have analysed the radiotherapy work-flow, including clinical and physical aspects, such as preparatory imaging, treatment planning, delivery and evaluation, with the aim to outline a consistent framework covering the entire radiotherapy process. RESULTS: Based on the analysis, a recipe-style template for specifying the description of the radiotherapy process has been designed. The template is written in a general format, which allows for modified phrasing, and should be customised for the specific clinical situation and diagnosis, as well as facility resources. CONCLUSIONS: The template can be used as a tool to ensure a consistent and comprehensive description of the radiotherapy section of clinical guidelines, care programmes and clinical trial protocols.

No difference in dose distribution in organs at risk in postmastectomy radiotherapy with or without breast implant reconstruction.

The aim of this study was to quantify the variation in doses to organs at risk (ipsilateral lung and heart) and the clinical target volume (CTV) in the presence of breast implants. In this retrospective cohort study, patients were identified through the National Breast Cancer Register. Consecutive breast cancer patients undergoing mastectomy between 2009 and 2011 and completing a full course of postmastectomy radiotherapy (PMRT) were eligible. All included patients (n = 818) were identified in the ARIA© oncology information system and further stratified for immediate breast reconstruction (IBR+, n = 162) and no immediate breast reconstruction (IBR-, n = 656). Dose statistics for ipsilateral lung, heart and CTV were retrieved from the system. Radiation plans for patients with chest wall (CW) only (n = 242) and CW plus lymph nodes (n = 576) irradiation were studied separately.The outcome variables were dichotomized as follows: lung, V(20Gy) ≤ 30% vs. V(20Gy) > 30%; heart, D(mean) ≤ 5 Gy vs. D(mean) > 5 Gy; CTV, V95% ≥ median vs. V95% < median.In the univariate and multivariate regression models no correlation between potential confounders (i.e. breast reconstruction, side of PMRT, CW index) and the outcome variables was found. Multivariate analysis of CW plus lymph nodes radiation plans, for example, showed no association of breast reconstruction with dosimetric outcomes in neither lung nor heart- lung V(20Gy) (odds ratio [OR]: 0.6, 95%CI, 0.4 to 1.0, p = 0.07) or heart D(mean) (OR: 1.2, 95%CI, 0.5 to 3.1, p = 0.72), respectively.CTV was statistically significantly larger in the IBR+ group (i.e. included breast implant), but no correlation between the implant type and dosimetric characteristics of the organs at risk was revealed.In the current study, the presence of breast implants during postmastectomy radiotherapy was not associated with increased doses to ipsilateral lung and heart, but CTV definition and its dosimetric characteristics urge further evaluation.