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).

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.

Risk of ischemic heart disease in women after radiotherapy for breast cancer.

BACKGROUND: Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. METHODS: We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. RESULTS: The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. CONCLUSIONS: Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

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.

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.

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.

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.

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.

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.

NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction.

BACKGROUND: In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. MATERIAL AND METHODS: Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction α/ß = 3 Gy was used and the USC parameters used were: α/ß = 3 Gy, D(0) = 1.0 Gy, [Formula: see text] = 10, α = 0.206 Gy(-1) and d(T) = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether "high doses to small volumes" or "low doses to large volumes" are most important for lung toxicity. RESULTS AND DISCUSSION: NTCP analysis with the LKB-model using parameters m = 0.4, D(50) = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D(50) = 20 Gy n = 0.93 with LQ correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling.

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.

Cardiac doses from Swedish breast cancer radiotherapy since the 1950s.

PURPOSE: To estimate cardiac doses from breast cancer radiotherapy in Sweden from the 1950s to the 1990s. These doses will contribute to deriving dose-response relationships for the risk of radiation-induced heart disease. MATERIALS AND METHODS: The Swedish nationwide cancer register was used to identify women irradiated for breast cancer in the Stockholm area. Virtual simulation, computed tomography planning, and manual planning were used to reconstruct radiotherapy regimens. Estimates of heart and coronary artery dose were derived for each woman. RESULTS: Cardiac doses were assessed in 358 women. Mean heart dose varied from <0.1 to 23.6 Gy and mean left anterior descending coronary artery dose varied from 0.1 to 46.3 Gy. Mean heart doses averaged across women irradiated in each decade for left-sided and right-sided breast cancers, respectively, were 5.1 and 1.8 Gy in the 1950s, 10.5 and 4.7 Gy in the 1970s and 3.0 and 1.9 Gy in the 1990s. CONCLUSIONS: Cardiac doses from Swedish breast cancer radiotherapy increased from the 1950s to the 1970s, and then reduced substantially in the 1980s and 1990s. The wide range of doses observed should provide substantial statistical power for the estimation of dose-response relationships for radiation-induced heart disease.

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.

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.

Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study.

BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.

Early clinical and radiological pulmonary complications following breast cancer radiation therapy: NTCP fit with four different models.

OBJECTIVE: To fit four different NTCP (Normal Tissue Complication Probability) models to prospectively collected data on short-term pulmonary complications following breast cancer radiotherapy (RT). MATERIALS/METHODS: Four hundred and seventy-five breast cancer patients, referred to the Radiotherapy Department at Stockholm Söder Hospital (1994-1998) for adjuvant post-operative RT were prospectively followed for pulmonary complications 1, 4 and 7 months after the completion of RT. Eighty-seven patients with complete dose-volume histogram (DVH) of the ipsilateral lung were selected for the present analysis. Mean dose to the ipsilateral lateral lung ranged from 2.5 to 18Gy (median 12Gy). Three different endpoints were considered: (1) clinical pneumonitis scored according to CTC-NCIC criteria: asymptomatic (grade 0) vs grade 1 and grade 2; (2) radiological changes assessed with diagnostic chest X-ray: no/slight radiological changes vs moderate/severe; (3) radiological changes assessed with CT: no/slight vs moderate/severe. Four NTCP models were used: the Lyman model with DVH reduced to the equivalent uniform dose (LEUD), the Logit model with DVH reduced to EUD, the Mean Lung Dose (MLD) model and the Relative Seriality (RS) model. The data fitting procedure was done using the maximum likelihood analysis. The analysis was done on the entire population (n=87) and on a subgroup of patients treated with loco-regional RT (n=44). RESULTS: 24/87 patients (28%) developed clinical pneumonitis; 28/81 patients (35%) had radiological side effects on chest X-rays and 11/75 patients (15%) showed radiological density changes on Computed Tomography (CT). The analysis showed that the risk of clinical pneumonitis was a smooth function of EUD (calculated from DVH using n=0.86+/-0.10, best fit result). With LEUD, the relationship between EUD and NTCP could be described with a D(50) of 16.4Gy+/-1.1Gy and a steepness parameter m of 0.36+/-0.7. The results found in the overall population were substantially confirmed in the subgroup of patients treated with loco-regional RT. CONCLUSIONS: A large group of prospective patient data (87 pts), including grade 1 pneumonitis, were analysed. The four NTCP models fit quite accurately the considered endpoints. EUD or the mean lung dose are robust and simple parameters correlated with the risk of pneumonitis. For all endpoints the D(50) values ranged in an interval between 10 and 20Gy.

SBRT of lung tumours: Monte Carlo simulation with PENELOPE of dose distributions including respiratory motion and comparison with different treatment planning systems.

The purpose of this work was to simulate with the Monte Carlo (MC) code PENELOPE the dose distribution in lung tumours including breathing motion in stereotactic body radiation therapy (SBRT). Two phantoms were modelled to simulate a pentagonal cross section with chestwall (unit density), lung (density 0.3 g cm(-3)) and two spherical tumours (unit density) of diameters respectively of 2 cm and 5 cm. The phase-space files (PSF) of four different SBRT field sizes of 6 MV from a Varian accelerator were calculated and used as beam sources to obtain both dose profiles and dose-volume histograms (DVHs) in different volumes of interest. Dose distributions were simulated for five beams impinging on the phantom. The simulations were conducted both for the static case and including the influence of respiratory motion. To reproduce the effect of breathing motion different simulations were performed keeping the beam fixed and displacing the phantom geometry in chosen positions in the cranial and caudal and left-right directions. The final result was obtained by combining the different position with two motion patterns. The MC results were compared with those obtained with three commercial treatment planning systems (TPSs), two based on the pencil beam (PB) algorithm, the TMS-HELAX (Nucletron, Sweden) and Eclipse (Varian Medical System, Palo Alto, CA), and one based on the collapsed cone algorithm (CC), Pinnacle(3) (Philips). Some calculations were also carried out with the analytical anisotropic algorithm (AAA) in the Eclipse system. All calculations with the TPSs were performed without simulated breathing motion, according to clinical practice. In order to compare all the TPSs and MC an absolute dose calibration in Gy/MU was performed. The analysis shows that the dose (Gy/MU) in the central part of the gross tumour volume (GTV) is calculated for both tumour sizes with an accuracy of 2-3% with PB and CC algorithms, compared to MC. At the periphery of the GTV the TPSs overestimate the dose up to 10%, while in the lung tissue close to the GTV PB algorithms overestimate the dose and the CC underestimates it. When clinically relevant breathing motions are included in the MC simulations, the static calculations with the TPSs still give a relatively accurate estimate of the dose in the GTV. On the other hand, the dose at the periphery of the GTV is overestimated, compared to the static case.