Benefit of Deep Inspiratory Breath Hold for Right Breast Cancer When Regional Lymph Nodes Are Irradiated

BackgroundAlthough deep inspiratory breath-hold (DIBH) is routinely used for left-sided breast cancers, its benefits for right-sided breast cancer (rBC) have yet to be established. We compared free-breathing (FB) and DIBH treatment plans for a cohort of rBC undergoing regional nodal irradiation (RNI) to determine its potential benefits.Methods and MaterialsrBC patients considered for RNI (internal mammary nodal chains, supraclavicular field, with or without axilla) from October 2017 to May 2020 were included in this analysis. For each patient, FB versus DIBH plans were generated and dose volume histograms evaluated the following parameters: mean lung dose, ipsilateral lung V₂₀/V₅ (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V₅ (volumes of heart receiving 5 Gy); liver V_{20 absolute} /V_{30 absolute} (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver D_max, and total liver volume irradiated (TVI_liver). The dosimetric parameters were compared using Wilcoxon signed-rank testing.ResultsFifty-four patients were eligible for analysis, comparing 108 FB and DIBH plans. DIBH significantly decreased all lung and liver parameters: mean lung dose (19.7 Gy-16.2 Gy, P < .001), lung V₂₀ (40.7%-31.7%, P < .001), lung V₅ (61.2%-54.5%, P < .001), TVI_liver (1446 cc vs 1264 cc; P = .006) liver D_max (50.2 Gy vs 48.9 Gy; P = .023), liver V₂₀ (78.8-23.9 cc, P < .001), and liver V₃₀ (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V_5Heart trended on significance (1.25-0.6, P = .067).ConclusionsThis is the largest cohort to date analyzing DIBH for RNI-rBC. Our findings demonstrate significant improvement in all lung and liver parameters with DIBH, supporting its routine consideration for rBC patients undergoing comprehensive RNI.     

Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation

Purpose

To investigate the effects of using volumetric modulated arc therapy (VMAT) and/or voluntary moderate deep inspiration breath-hold (vmDIBH) in the radiation therapy (RT) of left-sided breast cancer including the regional lymph nodes.

Materials and methods

For 13 patients, four treatment combinations were compared; 3D-conformal RT (i.e., forward IMRT) in free-breathing 3D-CRT(FB), 3D-CRT(vmDIBH), 2 partial arcs VMAT(FB), and VMAT(vmDIBH). Prescribed dose was 42.56 Gy in 16 fractions. For 10 additional patients, 3D-CRT and VMAT in vmDIBH only were also compared.

Results

Dose conformity, PTV coverage, ipsilateral and total lung doses were significantly better for VMAT plans compared to 3D-CRT. Mean heart dose (D_mean,heart) reduction in 3D-CRT(vmDIBH) was between 0.9 and 8.6 Gy, depending on initial D_mean,heart (in 3D-CRT(FB) plans). VMAT(vmDIBH) reduced the D_mean,heart further when D_mean,heart was still >3.2 Gy in 3D-CRT(vmDIBH). Mean contralateral breast dose was higher for VMAT plans (2.7 Gy) compared to 3DCRT plans (0.7 Gy).

Conclusions

VMAT and 3D-CRT(vmDIBH) significantly reduced heart dose for patients treated with locoregional RT of left-sided breast cancer. When D_mean,heart exceeded 3.2 Gy in 3D-CRT(vmDIBH) plans, VMAT(vmDIBH) resulted in a cumulative heart dose reduction. VMAT also provided better target coverage and reduced ipsilateral lung dose, at the expense of a small increase in the dose to the contralateral breast.     

Comparison of passive-beam proton therapy,helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy

PurposeSecond cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy.Patients and methodsFourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30 Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20 Gy/10 Gy.ResultsMean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15 Gy with the V_20 Gy equal to 16.4%, compared to 19.7% for proton therapy (P = 0.01) or 22.4% with 3D conformal radiation therapy (P < 0.01). Volumes of lung receiving doses below 15 Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V_10 Gy = 37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10 Gy or more than 4 Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V_4 Gy representing more than a third of one breast volume with helical tomotherapy.ConclusionsHelical tomotherapy achieved a better protection to the lungs for doses above 15 Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.     

The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland in patients with breast cancer

PurposeThe thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiation therapy (RT) for breast cancer. We compared the dosimetric impact of the following 2 RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined clinically; and (2) 3-dimensional conformal radiation therapy (3DCRT) planning to encompass the computed tomography (CT)-contoured SC nodal volume.Methods and MaterialsThe thyroid, SC nodal volumes, and organs at risk were contoured on the planning CT of 20 patients who received 50 Gy in 2-Gy daily fractions to the breast or chest wall, and SC nodes. Comparisons of dosimetric parameters between the techniques were performed: thyroid, mean and maximum dose, V5, V30, and V50 (percentage of thyroid receiving ≥ 5 Gy, ≥ 30 Gy, and ≥ 50 Gy, respectively); SC nodal volume, homogeneity index (HI, percentage volume receiving 95%-107% of prescribed dose); and maximum doses of spinal cord and brachial plexus. Anatomic characteristics that influenced the dose distributions were investigated.ResultsThe 3DCRT planning technique significantly increased all thyroid dosimetric measures (mean dose 17.2 Gy vs 26.7 Gy; maximum dose 48.5 Gy vs 51.9 Gy; V5 45.7% vs 64.9%; V30 33.7% vs 48%; and V50 0.6% vs 26.7%; P < .001). It improved HI for the SC nodal volumes (P < .001) but resulted in higher maximum doses to the spinal cord (6.1 Gy vs 30 Gy) and brachial plexus (43.2 Gy vs 51.4 Gy). The thyroid volume and depth of SC nodes did not influence the thyroid dose distribution. The depth of SC nodes impacted on the HI of SC nodal volumes in the conventional technique (P = .004).ConclusionsThe 3DCRT planning improved dosimetric coverage of the SC nodal volume but increased thyroid radiation doses. The potential adverse effects of incidental thyroid irradiation should be considered while improving dosimetric coverage in SC nodal irradiation for breast cancer.     

Impact of adjuvant radiotherapy on biological and clinical parameters in right-sided breast cancer

PurposeIn patients with right-sided breast cancer (BC) the liver might be partially irradiated during adjuvant radiotherapy (RT). Thus, we performed a prospective observational study to evaluate the dose delivered to the liver, and its potential biological impact.Patients and methodsWe enrolled 34 patients with right-sided BC treated with adjuvant RT. The RT schedules were either the Canadian (42.5 Gy in 16 fx) or standard fractionated (50 Gy in 25 fx) regimen respectively with 9 (26.5%) and 25 (73.5%) patients each, ± a boost of 10–16 Gy. Each patient had a complete blood count and liver enzymes analysis, before starting and during the last week of treatment.ResultsA significant decrease in white blood cells and thrombocytes counts was observed during RT. We observed a significant correlation between certain hepatic parameters and the volume of the irradiated liver and/or the mean liver dose. A significant correlation between the volume of the right lung and the liver mean dose was found (P = 0.008). In the bivariate analysis, a significant correlation between fatigue and the white blood cell count's evolution was observed (P < 0.025).ConclusionWith the standard RT technique, incidental irradiation of the liver was documented in a large number of patients, and some significant hepatic parameters alterations were observed, without an apparent clinical impact, but this study cannot exclude them. The liver mean dose was correlated with the right lung volume suggesting that deep inspiration breath hold (DIBH) techniques may represent a way to decrease the liver dose. These findings need to be evaluated in further larger studies.     

Comparison of Techniques for Involved-Site Radiation Therapy in Patients With Lower Mediastinal Lymphoma

PurposePatients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity modulated radiation therapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML.Methods and MaterialsTwenty-one patients with LML underwent 4-dimensional computed tomography and 3 sequential DIBH scans at simulation. Involved-site radiation therapy target volumes and organ-at-risk contours were developed for both DIBH and FB scans. FB-IMRT, DIBH-IMRT, FB-PT, and DIBH-PT plans were generated for each patient for comparison.ResultsThe median difference in lung volume between the DIBH and FB scans was 1275 mL; the average difference in clinical target volume was 5.7 mL. DIBH-IMRT produced a lower mean lung dose (10.8 vs 11.9 Gy; P < .001) than FB-IMRT, with no difference in mean heart dose (MHD; 16.1 vs 15.0 Gy; P = .992). Both PT plans produced a significantly lower mean dose to the lung, heart, left ventricle, esophagus, and nontarget body than DIBH-IMRT. DIBH-PT reduced the median MHD by 4.2 Gy (P < .0001); left ventricle dose by 5.1 Gy (P < .0001); and lung V5 by 26% (P < .0001) versus DIBH-IMRT. The 2 PT plans were comparable, with DIBH-PT reducing mean lung dose (7.0 vs 7.7 Gy; P = .063) and with no difference in MHD (10.3 vs 9.5 Gy; P = .992).ConclusionsAmong patients with LML, DIBH (IMRT or PT) improved lung dosimetry over FB but had little influence on MHD. PT (DIBH and FB) significantly reduced lung, heart, esophagus, and nontarget body dose compared with DIBH IMRT, potentially reducing the risk of late complications.     

A treatment planning study using non-coplanar static fields and coplanar arcs for whole breast radiotherapy of patients with concave geometry

PurposeA treatment planning study was performed to evaluate the performance of new radiotherapy techniques based on non-coplanar multiple fields or on dynamic conformal arcs for early stage breast treatments.Methods and materialsCT datasets of 7 different patients that were deemed unsuitable for tangential beam treatment due to a large volume of lung in the treatment fields were used as input for the study. Standard tangential field plans and inversely modulated IMRT plans were used as benchmark to evaluate performances of conformal plans with 3 non-coplanar fields (3F-NC), with 2 short dynamic conformal arcs (2-Arc) or hybrid plans with one static conformal field and one dynamic conformal arc (P-Arc). All plans were designed to achieve the higher target coverage and minimum ipsilateral lung involvement depending on the planning technique with a key objective to avoid involvement of the contralateral breast. The following planning objectives were selected. For PTV: D_1% (maximum significant dose) lower than 110% and D_99% (minimum significant dose) higher than 90%. For the ipsilateral lung a mean dose lower than 15 Gy and/or a volume receiving more than 20 Gy lower than 22%. For contralateral breast, all techniques but IMRT were set to have no beam impinging this organ at risk, while for IMRT plans were further designed to keep the mean dose lower than 5 Gy and to minimise the volume receiving a dose higher than 70% of the prescribed dose.ResultsP-Arc resulted to be on average a better technique, as it provides a PTV dose distribution highly conformal (Conformity index 1.45), homogeneous (D_5% − D_95% = 15.6%), with adequate coverage (V_90% = 96.4%) and a limited involvement of the ipsilateral lung (MLD ∼ 9 Gy, V_5Gy ∼ 36%, NTCP < 2%) when compared to four other treatment techniques. 3F-NC presented similar but slightly worse performances on target: Conformity index 1.57, D_5% − D_95% = 18.1%, V_90% = 95.7%). 3F-NC on ipsilateral lung resulted as the P-Arc. The tangential approach, the 2-Arc or the IMRT techniques, resulted to be inferior to the previous in either conformality (tangentials), ipsilateral lung sparing (tangentials, 2-Arc and IMRT) and in contralateral or healthy tissue involvement (IMRT).ConclusionFor early stage breast cancer when high sparing of lung tissues is required and no involvement of contralateral breast is allowed, the P-Arc or the 3F-NC techniques might be recommended in terms of dosimetric expectations.     

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PurposeDeep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI).Materials and methodsThis retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient.ResultsMean heart dose was 7.9 Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint < 8 Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (r_s = –0.25, P = 0.050) and between mean heart dose and CCDps (r_s = 0.25, P = 0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant.ConclusionOur dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.     

Techniques classique bidimensionnelle et mono-isocentrique tridimensionnelle dans l’irradiation du sein et des aires ganglionnaires : comparaison dosimétrique

PurposeThe activity of our radiation oncology department mainly relies on breast pathology. Since July 2009, all the irradiations delivered simultaneously to the breast (CTV1), the surgical bed (CTV2), the internal mammary chain and the supra- and infraclavicular areas have been carried out using a mono-isocentric technique. This study aimed to compare dosimetric results between conventional 2D and mono-isocentric 3D techniques with or without optimization.Patients and methodsFrom January to August 2009, 20 patients with breast cancer in whom irradiation of the CTV1, CTV2, internal mammary chain and supra- and infraclavicular areas was retained, were included in a specific cohort. In each case, we have compared dosimetric results obtained with the conventional technique and with a mono-isocentric 3D technique, either with manual field in the field segmentation or with automatic segmentation (Oncentra Masterplan^® from Nucletron^®, Optimizer^® solution). Selected criteria were as follows: V95, V107 and mean dose (Dmean) to the target volumes, V20 and V30 to the ipsilateral lung, V35 and mean dose to the heart and maximal dose (Dmax) to the spinal cord.ResultsSupra- and infraclavicular areas irradiation was significantly better using the mono-isocentric 3D technique (V95 %: 89.7 % vs. 77.1 %; P = 0.001) as well as dose homogeneity (Dmean: 46.3 Gy vs. 45.1 Gy; P = 0.008). No statistical difference was observed for the other target volumes. Heart and spinal cord protection were better with the mono-isocentric 3D technique (respectively Dmean: 8.4 Gy vs. 11.1 Gy; P < 0.0001 and Dmax: 29.2 Gy vs. 35.8 Gy; P = 0.0003).ConclusionMono-isocentric irradiation of the breast and lymphatic areas is a modern technique that benefits from imaging and computer progresses while being simple to carry out using standard planning system and linear accelerators. Mono-isocentric 3D irradiation with manual segmentation of the breast and the nodal areas provides a target volume irradiation comparing with conventional technique 2D and a better protection of the heart and of the spinal cord.     

Deep inspiration breath hold technique reduces heart dose from radiotherapy for left-sided breast cancer

Introduction: Adjuvant left breast radiotherapy (ALBR) for breast cancer can result in significant radiation dose to the heart. Current evidence suggests a dose–response relationship between the risk of cardiac morbidity and radiation dose to cardiac volumes. This study explores the potential benefit of utilising a deep inspiration breath hold (DIBH) technique to reduce cardiac doses. Methods: Thirty patients with left‐sided breast cancer underwent CT‐simulation scans in free breathing (FB) and DIBH. Treatment plans were generated using a hybrid intensity‐modulated radiation therapy technique with simultaneous integrated boost. A dosimetric comparison was made between the two techniques for the heart, left anterior descending coronary artery (LAD), left lung and contralateral breast. Results: Compared with FB, DIBH resulted in a significant reduction in heart V30 (7.1 vs. 2.4%, P < 0.0001), mean heart dose (6.9 vs. 3.9 Gy, P < 0.001), maximum LAD planning risk volume (PRV) dose, (51.6 vs. 45.6 Gy, P = 0.0032) and the mean LAD PRV dose (31.7 vs. 21.9 Gy, P < 0.001). No significant difference was noted for lung V20, mean lung dose or mean dose to the contralateral breast. The DIBH plans demonstrated significantly larger total lung volumes (1126 vs. 2051 cc, P < 0.0001), smaller maximum heart depth (2.08 vs. 1.17 cm, P < 0.0001) and irradiated heart volume (36.9 vs. 12.1 cc, P < 0.0001). Conclusions: DIBH resulted in a significant reduction in radiation dose to the heart and LAD compared with an FB technique for ALBR. Ongoing research is required to determine optimal cardiac dose constraints and methods of predicting which patients will derive the most benefit from a DIBH technique.     

Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers

BackgroundRAD51D is involved in DNA double-strand break repair by homologous recombination and plays an important role in the maintenance of genomic stability. The associations between RAD51D germline mutations and breast cancer risk and survival are not fully elucidated.Patients and methodsRAD51D germline mutations were determined using a multigene panel in 7657 unselected breast cancer patients who were negative for BRCA1/2 germline mutations. The RAD51D recurrent mutation p.K91fs was screened in 7947 healthy controls by Sanger sequencing.ResultsA total of 29 cases (0.38%) carried deleterious RAD51D germline mutations among this cohort of 7657 unselected breast cancer patients. The RAD51D recurrent mutation p.K91fs was identified in 18 cases (0.24%) of these 7657 patients. In contrast, the p.K91fs mutation was found in 8 of 7947 healthy controls with a frequency of 0.10%. The RAD51D p.K91fs mutation was significantly associated with increased breast cancer risk in unselected breast cancer [odds ratio = 2.34, 95% confidence interval (CI) 1.02–5.38; P = 0.040]. RAD51D mutation carriers were diagnosed at a younger age (P = 0.006) and were more likely to be triple-negative breast cancer (P = 0.003), estrogen receptor negative (P = 0.005) and high-grade cancers (P = 0.023) than noncarriers. Furthermore, RAD51D mutation carriers had a significantly worse recurrence-free survival [unadjusted hazard ratio (HR) = 3.00, 95% CI 1.56–5.80; P = 0.001] and distant recurrence-free survival (unadjusted HR = 2.54, 95% CI 1.14–5.67; P = 0.023) than noncarriers.ConclusionThe RAD51D recurrent mutation, p.K91fs, confers a moderately increased breast cancer risk, and RAD51D mutation carriers have an unfavorable survival compared with noncarriers.     

Different radiation techniques to deliver therapeutic dose to the axilla in patients with sentinel lymph node-positive breast cancer: Doses,techniques challenges and clinical considerations

Purpose

To evaluate the coverage of different levels of axillary lymph nodes and organs at risk according to the field design of AMAROS study (levels I–II–III–IV), breast tangents with supraclavicular and infraclavicular fields (levels II–III–IV) and high tangent fields to the breast after breast-conserving surgery.

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Anthropomorphic lung phantom based validation of in-room proton therapy 4D-CBCT image correction for dose calculation

PurposeVentilation-induced tumour motion remains a challenge for the accuracy of proton therapy treatments in lung patients. We investigated the feasibility of using a 4D virtual CT (4D-vCT) approach based on deformable image registration (DIR) and motion-aware 4D CBCT reconstruction (MA-ROOSTER) to enable accurate daily proton dose calculation using a gantry-mounted CBCT scanner tailored to proton therapy.MethodsVentilation correlated data of 10 breathing phases were acquired from a porcine ex-vivo functional lung phantom using CT and CBCT. 4D-vCTs were generated by (1) DIR of the mid-position 4D-CT to the mid-position 4D-CBCT (reconstructed with the MA-ROOSTER) using a diffeomorphic Morphons algorithm and (2) subsequent propagation of the obtained mid-position vCT to the individual 4D-CBCT phases. Proton therapy treatment planning was performed to evaluate dose calculation accuracy of the 4D-vCTs. A robust treatment plan delivering a nominal dose of 60 Gy was generated on the average intensity image of the 4D-CT for an approximated internal target volume (ITV). Dose distributions were then recalculated on individual phases of the 4D-CT and the 4D-vCT based on the optimized plan.Dose accumulation was performed for 4D-vCT and 4D-CT using DIR of each phase to the mid position, which was chosen as reference. Dose based on the 4D-vCT was then evaluated against the dose calculated on 4D-CT both, phase-by-phase as well as accumulated, by comparing dose volume histogram (DVH) values (D_mean, D_2%, D_98%, D_95%) for the ITV, and by a 3D-gamma index analysis (global, 3%/3 mm, 5 Gy, 20 Gy and 30 Gy dose thresholds).ResultsGood agreement was found between the 4D-CT and 4D-vCT-based ITV-DVH curves. The relative differences ((CT-vCT)/CT) between accumulated values of ITV D_mean, D_2%, D_95% and D_98% for the 4D-CT and 4D-vCT-based dose distributions were ?0.2%, 0.0%, ?0.1% and ?0.1%, respectively. Phase specific values varied between ?0.5% and 0.2%, ?0.2% and 0.5%, ?3.5% and 1.5%, and ?5.7% and 2.3%. The relative difference of accumulated D_mean over the lungs was 2.3% and D_mean for the phases varied between ?5.4% and 5.8%. The gamma pass-rates with 5 Gy, 20 Gy and 30 Gy thresholds for the accumulated doses were 96.7%, 99.6% and 99.9%, respectively. Phase-by-phase comparison yielded pass-rates between 86% and 97%, 88% and 98%, and 94% and 100%.ConclusionsFeasibility of the suggested 4D-vCT workflow using proton therapy specific imaging equipment was shown. Results indicate the potential of the method to be applied for daily 4D proton dose estimation.     

Évaluation prospective des dysthyroïdies radio-induites après irradiation mammaire et sus-claviculaire

PurposeThe thyroid is an endocrine gland playing a major role in metabolism and development by the secretion of T4 and T3 thyroid hormones. Due to its anatomical position, it is often included in the target volume for the irradiation of certain tumours and thus receives significant doses (10 to 80 Gy). The treatment of breast cancer requires in most cases a breast irradiation associated or not with a lymph node irradiation. The aim of our study was to investigate prospectively the frequency of thyroid disorders in patients with breast cancer treated by radiation, with or without irradiation of the supra- and subclavicular lymph nodes.Material and methodsThis prospective multicentre study (institut Godinot, institut de cancérologie Strasbourg Europe and institut de cancérologie de Lorraine) concerned adult patients with non-metastatic breast carcinoma treated by adjuvant irradiation. They were included in a non-randomized way between February 2013 and June 2015 and divided into two groups according to treatment: (i) breast radiotherapy associated with irradiation of the supra- and subclavicular lymph nodes (group 1), or (ii) breast irradiation alone (group 2). The dose – volume histogram of the thyroid was systematically edited by the physics department. Each patient had a consultation with an endocrinologist at the beginning of the treatment and was monitored by blood analyses including TSH, T4L, antithyroglobulin and antiperoxidase antibodies every 6 months until the 60th month after the end of radiotherapy. Data were described by numbers and percentages for qualitative variables; by means, medians, standard deviation and ranges for quantitative variables. Statistical associations were tested by Chi², Fisher's, Student's, or analysis of variance tests depending on the conditions of application. Survival analyses were performed by log rank tests and Cox models.ResultsThis study initially included 500 patients, 245 in group 1 and 252 in group 2 (three patients were later excluded for false inclusion). Thyroid abnormalities occurred in 76 patients, representing an incidence of 15.3%. The mean time of the first occurrence of thyroid disorders was 24.3 months. It was more frequent in group 1 with a prevalence of 19.2% against 11.5% in group 2 (P = 0.01745). A maximal radiation dose delivered to the thyroid gland greater than 20 Gy (odds ratio [OR]: 1.82; P = 0.018) or 30 Gy (OR: 1.89; P = 0.013) was significantly associated with a higher incidence of thyroid disorders, as was a mean dose greater than 30 Gy (OR: 5.69; P = 0.049). A percentage of thyroid volume receiving 30 Gy (V30) greater than 50% (P = 0.006) or greater than 62.5% (P = 0.021) was significantly associated with an increased incidence of thyroid disorder and more precisely, hypothyroidism (P = 0.0007). In multivariate analysis, no factor associated with the occurrence of thyroid disorder was identified. However, in the subgroup analysis concerning group 1 (receiving supraclavicular irradiation), a maximal radiation dose greater than 30 Gy appeared to be a risk factor for the occurrence of thyroid disorders (P = 0.040).ConclusionThyroid disorder, and in particular hypothyroidism, may be a late side effect of locoregional breast radiotherapy. Patients receiving this treatment should have a biological monitoring of thyroid function.     

Dose distribution of the brain tissue associated with cognitive functions in high-grade glioma patients

PurposeThe purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT).Patients and methodsThirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60 Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test.ResultsConformity indexes remained similar with both techniques. The mean values were 0.96 (0.19–1.00) for VMAT and 0.98 (range, 0.84–1.00) for HT, respectively (P = 0.73). Significant D_50% reductions were observed with VMAT compared to HT: 14.6 Gy (3.8–28.0) versus 17.4 Gy (12.1–25.0) for the normal brain (P = 0.014); 32.5 Gy (10.3–60.0) versus 35.6 Gy (17.1–58.0) for the corpus callosum (P = 0.038); 8.1 Gy (0.4–34.0) versus 12.8 Gy (0.8–27.0) for the cerebellum (P < 0.001), respectively.ConclusionThe VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.