Association of Skin Microbiome Dynamics With Radiodermatitis in Patients With Breast Cancer.

Importance: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown. Objective: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started. Exposure: Adjuvant radiotherapy for breast cancer for 7 weeks. Main Outcomes and Measures: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration. Results: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load. Conclusions and Relevance: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

Regional nodal irradiation in breast cancer patients: Effects of deep inspiration breath hold on the internal mammary chain location.

The purpose of this study was to investigate the impact of deep inspiration breath hold (DIBH) on the positioning of thoracic structures and provide treatment planning recommendations for internal mammary chain (IMC) irradiation in breast cancer patients. Thirty-two breast cancer patients from our database underwent both DIBH and free breathing (FB) treatment planning. Contouring of the axillary lymph node clinical target volumes (CTVs: level I, II, III, IV, and IMC according to ESTRO), the internal mammary artery (IMA), the heart, and the left anterior descending artery (LAD) was performed. The following were then analyzed: the distance between the IMA and the heart, the craniocaudal distance in which IMC-CTV and heart coexist, the craniocaudal distance between the lower end of the of level III and IV and the upper end of the heart. Several significant geometric differences were observed between DIBH and FB that explain the efficacy of the DIBH for regional nodal irradiation. In >80% of patients the cranial origin of the LAD lies below the lower edge of the IMC-CTV in DIBH. In addition the slices in which the heart/LAD and IMC-CTV coexist decrease during DIBH. The IMA-heart distance is significantly larger in DIBH. Also the craniocaudal distance between the lower border of the CTV level III and IV and the upper border of the heart is larger in DIBH. The observed mechanisms during DIBH contribute significantly to the dose reduction in regional nodal irradiation. To further enhance the benefits of DIBH for the irradiation of the IMC-CTV, it is recommended to implement steep dose gradients in the caudal plane.

Incidental nodal irradiation in patients with esophageal cancer undergoing (chemo)radiation with 3D-CRT or VMAT.

The extent of elective nodal irradiation (ENI) in patients undergoing definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this dosimetric study was to evaluate the extent of incidental nodal irradiation using modern radiation techniques. A planning target volume (PTV) was generated for 30 patients with node-negative esophageal carcinoma (13 cervical/upper third, 7 middle third, 10 lower third/abdomen). Thereby, no elective nodal irradiation (ENI) was intended. Both three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT) treatment plans (50 Gy in 25 fractions) were calculated for all patients. Fifteen nodal stations were contoured according to the definitions of the AJCC and investigated in regard to dosimetric parameters. Compared to 3D-CRT, VMAT was associated with lower dose distribution to the organs at risk (lower Dmean, V20 and V30 for the lungs and lower Dmean and V30 for the heart). For both techniques, the median Dmean surpassed 40 Gy in 12 of 15 (80%) nodal stations. However, VMAT resulted in significantly lower Dmeans and equivalent uniform doses (EUD) compared to 3D-CRT for eight nodal stations (1L, 2L, 2R, 4L, 7, 8L, 10L, 15), while differences did not reach significance for seven nodal station (1R, 4R, 8U, 8M, 10R, 16). For dCRT of ESCC, the use of VMAT was associated with significantly lower median (incidental) doses to eight of 15 regional lymph node areas compared to 3D-CRT. However, given the small absolute differences, these differences probably do not impair (regional) tumor control rates.

As Easy as 1, 2, 3? How to Determine CBCT Frequency in Adjuvant Breast Radiotherapy.

The current study aims to assess the suitability of setup errors during the first three treatment fractions to determine cone-beam computed tomography (CBCT) frequency in adjuvant breast radiotherapy. For this, 45 breast cancer patients receiving non-hypofractionated radiotherapy after lumpectomy, including a simultaneous integrated boost (SIB) to the tumor bed and daily CBCT imaging, were retrospectively selected. In a first step, mean and maximum setup errors on treatment days 1-3 were correlated with the mean setup errors during subsequent treatment days. In a second step, dose distribution was estimated using a dose accumulation workflow based on deformable image registration, and setup errors on treatment days 1-3 were correlated with dose deviations in the clinical target volumes (CTV) and organs at risk (OAR). No significant correlation was found between mean and maximum setup errors on treatment days 1-3 and mean setup errors during subsequent treatment days. In addition, mean and maximum setup errors on treatment days 1-3 correlated poorly with dose coverage of the CTVs and dose to the OARs. Thus, CBCT frequency in adjuvant breast radiotherapy should not be determined solely based on the magnitude of setup errors during the first three treatment fractions.

Pneumonitis after Stereotactic Thoracic Radioimmunotherapy with Checkpoint Inhibitors: Exploration of the Dose-Volume-Effect Correlation.

Thoracic stereotactic body radiation therapy (SBRT) is extensively used in combination with immune checkpoint blockade (ICB). While current evidence suggests that the occurrence of pneumonitis as a side effect of both treatments is not enhanced for the combination, the dose-volume correlation remains unclear. We investigate dose-volume-effect correlations for pneumonitis after combined SBRT + ICB. We analyzed patient clinical characteristics and dosimetric data for 42 data sets for thoracic SBRT with ICB treatment (13) and without (29). Dose volumes were converted into 2 Gy equivalent doses (EQD2), allowing for dosimetric comparison of different fractionation regimes. Pneumonitis volumes were delineated and corresponding DVHs were analyzed. We noticed a shift towards lower doses for combined SBRT + ICB treatment, supported by a trend of smaller areas under the curve (AUC) for SBRT+ ICB (median AUC 1337.37 vs. 5799.10, p = 0.317). We present a DVH-based dose-volume-effect correlation method and observed large pneumonitis volumes, even with bilateral extent in the SBRT + ICB group. We conclude that further studies using this method with enhanced statistical power are needed to clarify whether adjustments of the radiation dose constraints are required to better estimate risks of pneumonitis after the combination of SBRT and ICB.

Potential Morbidity Reduction for Lung Stereotactic Body Radiation Therapy Using Respiratory Gating.

We investigated the potential of respiratory gating to mitigate the motion-caused misdosage in lung stereotactic body radiotherapy (SBRT). For fourteen patients with lung tumors, we investigated treatment plans for a gating window (GW) including three breathing phases around the maximum exhalation phase, GW40-60. For a subset of six patients, we also assessed a preceding three-phase GW20-40 and six-phase GW20-70. We analyzed the target volume, lung, esophagus, and heart doses. Using normal tissue complication probability (NTCP) models, we estimated radiation pneumonitis and esophagitis risks. Compared to plans without gating, GW40-60 significantly reduced doses to organs at risk without impairing the tumor doses. On average, the mean lung dose decreased by 0.6 Gy (p < 0.001), treated lung V20Gy by 2.4% (p = 0.003), esophageal dose to 5cc by 2.0 Gy (p = 0.003), and maximum heart dose by 3.2 Gy (p = 0.009). The model-estimated mean risks of 11% for pneumonitis and 12% for esophagitis without gating decreased upon GW40-60 to 7% and 9%, respectively. For the highest-risk patient, gating reduced the pneumonitis risk from 43% to 32%. Gating is most beneficial for patients with high-toxicity risks. Pre-treatment toxicity risk assessment may help optimize patient selection for gating, as well as GW selection for individual patients.

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

BACKGROUND: The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. MATERIAL AND METHODS: Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. RESULTS: IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). CONCLUSION: According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

Craniospinal irradiation(CSI) in patients with leptomeningeal metastases: risk-benefit-profile and development of a prognostic score for decision making in the palliative setting.

BACKGROUND: The aim of our study was to assess the feasibility and oncologic outcomes in patients treated with spinal (SI) or craniospinal irradiation (CSI) in patients with leptomeningeal metastases (LM) and to suggest a prognostic score as to which patients are most likely to benefit from this treatment. METHODS: Nineteen patients treated with CSI at our institution were eligible for the study. Demographic data, primary tumor characteristics, outcome and toxicity were assessed retrospectively. The extent of extra-CNS disease was defined by staging CT-scans before the initiation of CSI. Based on outcome parameters a prognostic score was developed for stratification based on patient performance status and tumor staging. RESULTS: Median follow-up and overall survival (OS) for the whole group was 3.4 months (range 0.5-61.5 months). The median overall survival (OS) for patients with LM from breast cancer was 4.7 months and from NSCLC 3.3 months. The median OS was 7.3 months, 3.3 months and 1.5 months for patients with 0, 1 and 2 risk factors according to the proposed prognostic score (KPS < 70 and the presence of extra-CNS disease) respectively. Nonhematologic toxicities were mild. CONCLUSION: CSI demonstrated clinically meaningful survival that is comparable to the reported outcome of intrathecal chemotherapy. A simple scoring system could be used to better select patients for treatment with CSI in this palliative setting. In our opinion, the feasibility of performing CSI with modern radiotherapy techniques with better sparing of healthy tissue gives a further rationale for its use also in the palliative setting.

Irradiation of regional lymph node areas in breast cancer - Dose evaluation according to the Z0011, AMAROS, EORTC 10981-22023 and MA-20 field design.

OBJECTIVE: The purpose of this study was to estimate the dose distribution from randomized trials (MA.20, EORTC 22922-10925 (EORTC), AMAROS and the Z0011 trial) on lymph node (LN) irradiation on a large LN atlas. METHODS: 580 F18-FDG-PET/CT positive LN metastases of 235 patients were transferred rigidly and non-rigidly to three "template CTs" (standard, obese and slender patient). Further, the LN clinical target volumes (CTVs) were contoured according to the ESTRO-guidelines. Treatment plans were designed (each for the left and right side) for all patients based on the study protocols of the MA.20, EORTC, AMAROS and Z0011 trial. Subsequently, the dose distribution in the ESTRO-CTVs and in the 580 LNs were assessed. RESULTS: Our results reveal variable dose coverage (26.8 ±â€¯17.3 Gy-53.0 ±â€¯1.8 Gy) in the targeted LN areas (ESTRO-CTV and LN) in dependence of the treatment planning design and the patients' body shape. None of the treatment plan designs provided full dose coverage to the lymphatic drainage system. High tangent irradiation resulted in a similar dose distribution in L I and II compared to the AMAROS field design. CONCLUSION: Inclusion of the entire lymphatic system may not be necessary for all patients to reproduce the oncologic benefit shown in the randomized LN-irradiation trials. Inclusion of axillary level II and extension of the supraclavicular CTV can be considered in selected high-risk patients, based on dose recalculation of the MA.20 trial. Further, our results amplify earlier assumptions that irradiation may have accounted for the good results after SLND alone in the Z0011 trial.

MRI based neuroanatomical segmentation in breast cancer patients: leptomeningeal carcinomatosis vs. oligometastatic brain disease vs. multimetastastic brain disease.

PURPOSE: Pathogenesis of brain metastases/meningeal cancer and the emotional and neurological outcomes are not yet well understood. The hypothesis of our study is that patients with leptomeningeal cancer show volumetric differences in brain substructures compared to patients with cerebral metastases. METHODS: Three groups consisting of female breast cancer patients prior to brain radiotherapy were compared. Leptomeningeal cancer patients (LMC Group), oligometastatic patients (1-3 brain metastases) prior to radiosurgery (OMRS Group) and patients prior to whole brain radiation (WB Group) were included. All patients had MRI imaging before treatment. T1 MRI sequences were segmented using automatic segmentation. For each patient, 14 bilateral and 11 central/median subcortical structures were tested. Overall 1127 structures were analyzed and compared between groups using age matched two-sided t-tests. RESULTS: The average age of patients in the OMRS group was 60.8 years (± 14.7), 65.3 (± 10.3) in the LMC group and 62.6 (± 10.2) in the WB group. LMC patients showed a significantly larger fourth ventricle compared to OMRS (p = 0.001) and WB (p = 0.003). The central corpus callosum appeared smaller in the LMC group (LMC vs OMRS p = 0.01; LMC vs WB p = 0.026). The right amygdala in the WB group appeared larger compared with the OMRS (p = 0.035). CONCLUSIONS: Differences in the size of brain substructures of the three groups were found. The results appear promising and should be taken into account for further prospective studies also involving healthy controls. The volumetrically determined size of the fourth ventricle might be a helpful diagnostic marker in the future.

Outcomes of immediate oncoplastic surgery and adjuvant radiotherapy in breast cancer patients.

BACKGROUND: Oncoplastic surgery techniques lead to a rearrangement of the breast tissue and impede target definition during adjuvant radiotherapy (RT). The aim of this study was to assess local control rates after immediate oncoplastic surgery and adjuvant RT. METHODS: This study comprises 965 patients who underwent breast-conserving therapy and adjuvant RT between 01/2000 and 12/2005. 288 patients received immediate oncoplastic surgery (ONC) and 677 patients breast-conserving surgery only (NONC). All patients were treated with adjuvant external tangential-beam RT (total dose: 50/50.4 Gy; fraction dose 1.8/2.0 Gy). An additional boost dose of 10-16 Gy to the primary tumor bed was given in 900 cases (93.3%). Local control rates (LCR), Progression free survival (PFS) and overall survival (OS) were assessed retrospectively after a median follow-up period of 67 (Q25-Q75: 51-84) months. RESULTS: No significant difference was found between ONC and NONC in regard to LCR (5-yr: ONC 96.8% vs. NONC 95.3%; p = 0.25). This held also true for PFS (5-yr: ONC 92.1% vs. NONC 89.3%; p = 0.09) and OS (5-yr: ONC 96.0% vs. NONC 94.8%; p = 0.53). On univariate analyses G2-3 (p = 0.04), a younger age (p = 0.01), T-stage (p < 0.01) lymph node involvement (p < 0.01) as well as triple negative tumors (p < 0.01) were identified as risk factors for local recurrence. In a propensity score stratified Cox-regression model no significant impact of oncoplastic surgery on local control rate was found (HR: 2.05, 95% CI [0.93; 4.51], p = 0.08). CONCLUSION: Immediate oncoplastic surgery seems not to affect the effectiveness of adjuvant whole breast RT on local control rates in breast cancer patients.

Incidental dose distribution to locoregional lymph nodes of breast cancer patients undergoing adjuvant radiotherapy with tomotherapy - is it time to adjust current contouring guidelines to the radiation technique?

PURPOSE/OBJECTIVE(S): Along with breast-conserving surgery (BCS), adjuvant radiotherapy (RT) of patients with early breast cancer plays a crucial role in the oncologic treatment concept. Conventionally, irradiation is carried out with the aid of tangentially arranged fields. However, more modern and more complex radiation techniques such as IMRT (intensity-modulated radio therapy) are used more frequently, as they improve dose conformity and homogeneity and, in some cases, achieve better protection of adjacent risk factors. The use of this technique has implications for the incidental- and thus unintended- irradiation of adjacent loco regional lymph drainage in axillary lymph node levels I-III and internal mammary lymph nodes (IMLNs). A comparison of a homogeneous "real-life" patient collective, treated with helical tomotherapy (TT), patients treated with 3D conformal RT conventional tangentially arranged fields (3DCRT) and deep inspiration breath hold (3DCRT-DIBH), was conducted. MATERIALS/METHODS: This study included 90 treatment plans after BCS, irradiated in our clinic from January 2012 to August 2016 with TT (n = 30) and 3D-CRT (n = 30), 3DCRT DIBH (n = 30). PTVs were contoured at different time points by different radiation oncologists (> 7). TT was performed with a total dose of 50.4 Gy and a single dose of 1.8 Gy with a simultaneous integrated boost (SIB) to the tumor cavity (TT group). Patients irradiated with 3DCRT/3DCRT DIBH received 50 Gy à 2 Gy and a sequential boost. Contouring of lymph drainage routes was performed retrospectively according to RTOG guidelines. RESULTS: Average doses (DMean) in axillary lymph node Level I/Level II/Level III were 31.6 Gy/8.43 Gy/2.38 Gy for TT, 24.0 Gy/11.2 Gy/3.97 Gy for 3DCRT and 24.7 Gy/13.3 Gy/5.59 Gy for 3DCRT-DIBH patients. Internal mammary lymph nodes (IMLNs) Dmean were 27.8 Gy (TT), 13.5 Gy (3DCRT), and 18.7 Gy (3DCRT-DIBH). Comparing TT to 3DCRT-DIBH dose varied significantly in all axillary lymph node levels and the IMLNs. Comparing TT to 3DCRT significant dose difference in Level I and IMLNs was observed. CONCLUSION: Dose applied to locoregional lymph drainage pathways varies comparing tomotherapy plans to conventional tangentially arranged fields. Studies are warranted whether dose variations influence loco-regional spread and must have implications for target volume definition guidelines.

Deep inspiration breath-hold for left-sided breast irradiation: Analysis of dose-mass histograms and the impact of lung expansion.

BACKGROUND: The aim of this study was to compare dose-volume histogram (DVH) with dose-mass histogram (DMH) parameters for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB). Additionally, lung expansion and anatomical factors were analyzed and correlated to dose differences. METHODS: For 31 patients 3D conformal radiation therapy plans were retrospectively calculated on FB and DIBH CTs in the treatment planning system. The calculated doses, structures and CT data were transferred into MATLAB and DVHs and DMHs were calculated. Mean doses (Dmean), volumes and masses receiving certain doses (Vx, Mx) were determined for the left lung and the heart. Additionally, expansion of the left lung was evaluated using deformable image registration. Differences in DVH and DMH dose parameters between FB and DIBH were statistically analyzed and correlated to lung expansion and anatomical factors. RESULTS: DIBH reduced Dmean (DVH) and relative V20 (V20 [%]) of the left lung in all patients, on average by - 19 ± 9% (mean ± standard deviation) and - 24 ± 10%. Dmean (DMH) and M20 [%] were also significantly reduced (- 12 ± 11%, - 16 ± 13%), however 4 patients had higher DMH values in DIBH than in FB. Linear regression showed good correlations between DVH and DMH parameters, e.g. a dosimetric benefit smaller than 8.4% for Dmean (DVH) in DIBH indicated more irradiated lung mass in DIBH than in FB. The mean expansion of the left lung between FB and DIBH was 1.5 ± 2.4 mm (left), 16.0 ± 4.0 mm (anterior) and 12.2 ± 4.6 mm (caudal). No significant correlations were found between expansions and differences in Dmean for the left lung. The heart dose in DIBH was reduced in all patients by 53% (Dmean) and this dosimetric benefit correlated to lung expansion in anterior. CONCLUSIONS: Treatment of left-sided breast cancer in DIBH reduced dose to the heart and in most cases the lung dose, relative irradiated lung volume and lung mass. A mass related dosimetric benefit in DIBH can be achieved as long as the volume related benefit is about ≥8-9%. The lung expansion (breathing pattern) showed no impact on lung dose, but on heart dose. A stronger chest breathing (anterior expansion) for DIBH seems to be more beneficial than abdominal breathing.

FDG/PET-CT-Based Lymph Node Atlas in Breast Cancer Patients.

PURPOSE: The aim of this study was to localize locoregional lymph node metastases using positron emission tomography with fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) data sets in a large cohort of patients and to evaluate the existing Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) and the European Society for Radiation Therapy & Oncology (ESTRO) CTV contouring guidelines. METHODS AND MATERIALS: A total of 235 patients with 580 FDG/PET-CT positive locoregional lymph node metastases were included in our analysis. The patients were divided into 4 groups according to their course of disease (primary vs recurrent breast cancer) and the presence or absence of distant metastasis at the time of the FDG-PET/CT staging (distant metastasis vs no distant metastasis). All imaging data were imported into the planning system, and each lymph node was manually contoured. A patient with "standard anatomy" was chosen as a template, and all contoured structures were registered rigidly and nonrigidly to this patient. A comprehensive 3-dimensional atlas was created, including all identified lymph node metastases. The incidences of lymph node metastases were analyzed and are presented with color coding in the atlas. Lymph node levels (axillary, internal mammary, supraclavicular) were contoured according to RTOG and ESTRO guidelines and evaluated. RESULTS: The mean volume of the lymph nodes was 1.7 ± 2.6 cm3 with an average diameter of 1.3 ± 0.7 cm. Most lymph nodes were in level I (n = 316; 54.5%) followed by the supraclavicular region (n = 80; 13.8%), level II (n = 57; 9.8%), level III (n = 58; 10.0%), and the internal mammary region (n = 55; 9.5%). The covered lymph node volume was 69.8% ± 35.5% (69.1% ± 36.3%) for primary breast cancer and 57.6% ± 38.9% (51.1% ± 39.1%) for recurrent breast cancer using the RTOG (ESTRO) guidelines. The internal mammary region and supraclavicular region were affected more often in recurrent breast cancer compared with primary breast cancer. The occurrence of lymph node metastases outside the RTOG and ESTRO margins in patients with and without distant metastases was similar. The largest geometric deviations between RTOG/ESTRO CTV contours and lymph node occurrence were measured in the supraclavicular region, the internal mammary region, and level II. CONCLUSIONS: The provided lymph node atlas illustrates where lymph node metastases occur in different clinical situations and presents areas at high risk (ie "hot spots" of lymph node metastases).

Moving targets in 4D-CTs versus MIP and AIP: comparison of patients data to phantom data.

PURPOSE: Maximum (MIP) and average intensity projection (AIP) CTs allow rapid definition of internal target volumes in a 4D-CT. The purpose of this study was to assess the accuracy of these techniques in a large patient cohort in combination with simulations on a lung phantom. METHODS: 4DCT data from a self-developed 3D lung phantom and from 50 patients with lung tumors were analyzed. ITVs were contoured in maximum (ITVMIP) and average intensity projection (ITVAIP) and subsequently compared to ITVs contoured in 10 phases of a 4D-CT (ITV10). In the phantom study additionally a theoretical target volume was calculated for each motion and compared to the contoured volumes. RESULTS: ITV10 overestimated the actual target volume by 9.5% whereas ITVMIP and ITVAIP lead to an underestimation of - 1.8% and - 11.4% in the phantom study. The ITVMIP (ITVAIP) was in average - 10.0% (- 18.7%) smaller compared to the ITV10. In the patient CTs deviations between ITV10 and MIP/AIP were significantly larger (MIP: - 20.2% AIP: -33.7%) compared to this. Tumors adjacent to the chestwall, the mediastinum or the diaphragm showed lower conformity between ITV10 and ITVMIP (ITVAIP) compared to tumors solely surrounded by lung tissue. Large tumor diameters (> 3.5 cm) and large motion amplitudes (> 1 cm) were associated with lower conformity between intensity projection CTs and ITV10-. CONCLUSION: The application of MIP and AIP in the clinical practice should not be a standard procedure for every patient, since relevant underestimation of tumor volumes may occur. This is especially true if the tumor borders the mediastinum, the chest wall or the diaphragm and if tumors show a large motion amplitude.

Deep-Inspiration Breath-Hold Radiation Therapy in Breast Cancer: A Word of Caution on the Dose to the Axillary Lymph Node Levels.

PURPOSE: To assess the differences in unintended regional nodal irradiation between free breathing (FB) and deep-inspiration breath-hold (DIBH) during tangential field irradiation. METHODS AND MATERIALS: We randomly chose 32 patients from our database who underwent both DIBH and FB treatment planning. Contouring of the axillary lymph node levels (LI, LII, and LIII) was performed retrospectively according to the Radiation Therapy Oncology Group contouring atlas. We assessed the center of mass of each level and the planning target volume, as well as the dose distribution (Dmean, Dmedian, Dmax, Dmin, V30, and V40) in the lymph node levels I-III. Subsequently center of mass movement and dose changes due to deep inspiration treatment planning were calculated. RESULTS: All lymph node levels showed significant (P<.001) movement in anterior and cranial directions due to DIBH. The overall median movement (range) in the x (lateral), y (anterior-posterior), and z (cranio-caudal) directions was 0.1 cm (0.0-1.1 cm), 0.9 cm (0.1-2.0 cm), and 1.2 cm (0.0-2.6 cm), respectively. Movement of the planning target volume showed significant correlation (r=0.72, r=0.63, r=0.63; P<.05) with levels I-III. The average Dmean during FB/DIBH was as follows: LI 33.9 Gy/30.8 Gy (P<.001), LII 23.7 Gy/24.1 Gy (P=.74), and LIII 14.0 Gy/15.6 Gy (P=.14). V30 was as follows: LI 63.8%/56.5% (P<.001), LII 44.6%/45.5% (P=.76), and LIII 24.2%/27.8% (P<.05). V40 was as follows: LI 58.9%/51.0% (P<.001), LII 39.3%/40.1% (P=.79), and LIII 20.4%/23.9% (P<.05). CONCLUSIONS: Deep-inspiration breath-hold results in a significant dose reduction in level I. Only minor changes in dose distribution were recorded for levels II and III. Thus, DIBH seems to have an impact on unintended regional nodal irradiation as compared with FB.

Tangential Field Radiotherapy for Breast Cancer-The Dose to the Heart and Heart Subvolumes: What Structures Must Be Contoured in Future Clinical Trials?

BACKGROUND AND PURPOSE: The aim of the present study was to evaluate if it is feasible for experienced radiation oncologists to visually sort out patients with a large dose to the heart. This would facilitate large retrospective data evaluations. And in case of an insufficient visual assessment, to define which structures should be contoured and which structures can be skipped as their dose can be derived from other easily contoured structures for future clinical trials. MATERIAL AND METHODS: Planning CTs of left-sided breast cancer patients treated with 3D-conformal radiotherapy by tangential fields were visually divided into two groups: with an estimated high dose (HiD) and with an estimated low dose (LoD) to the heart. For 46 patients (22 HiD and 24 LoD), the heart, the left ventricle, the left anterior descending artery (LAD), the right coronary artery, and the ramus circumflexus were contoured. A helper structure (HS) around the LAD was generated in order to consider if contouring uncertainties of the LAD could be acceptable. We analyzed the mean dose (Dmean), the maximum dose, the V10, V20, V30, V40, and the length of the LAD that received 20 and 40 Gy. RESULTS: The two groups had a significant different Dmean of the heart (p < 0.001). The average Dmean to the heart was 4.0 ± 1.3 Gy (HiD) and 2.3 ± 0.8 Gy (LoD). The average Dmean to the LAD was 26.2 ± 7.4 Gy (HiD) and 13.0 ± 7.5Gy (LoD) with a very strong positive correlation between Dmean LAD and Dmean HS in both groups. The Dmean heart is not a good surrogate parameter for the dose to the LAD since it might underestimate clinically significant doses in 1/3 of the patients in LoD group. CONCLUSION: A visual assessment of the dose to the heart could be reliable if performed by experienced radiation oncologists. However, the Dmean heart is not always a good surrogate parameter for the dose to the LAD or for the Dmean to the left ventricle. Thus, if specific late toxicities are evaluated, we strongly recommend contouring of the specific heart substructures as a heart Dmean is not highly specific.

The importance of surrounding tissues and window settings for contouring of moving targets.

AIM: The aim of the study was to assess the importance of surrounding tissues for the delineation of moving targets in tissue-specific phantoms and to find optimal settings for lung, soft tissue, and liver tumors. MATERIALS AND METHODS: Tumor movement was simulated by a water-filled table tennis ball (target volume, TV). Three phantoms were created: corkboards to simulate lung tissue (lung phantom, LunPh), animal fat as fatty soft tissue (fatty tissue phantom, FatPh), and water enhanced with contrast medium as the liver tissue (liver phantom, LivPh). Slow planning three-dimensional compute tomography images (3D-CTs) were acquired with and without phantom movements. One-dimensional tumor movement (1D), three-dimensional tumor movement (3D), as well as a real patient's tumor trajectories were simulated. The TV was contoured using two lung window settings, two soft-tissue window settings, and one liver window setting. The volumes were compared to mathematical calculated values. RESULTS: TVs were underestimated in all phantoms due to movement. The use of soft-tissue windows in the LivPh led to a significant underestimation of the TV (70.8% of calculated TV). When common window settings [LunPh + 200 HU/-1,000 HU (upper window/lower window threshold); FatPh: + 240 HU/-120 HU; LivPh: + 175 HU/+ 50 HU] were used, the contoured TVs were: LivPh, 84.0%; LunPh, 93.2%, and FatPh, 92.8%. The lower window threshold had a significant impact on the size of the delineated TV, whereas changes of the upper threshold led only to small differences. CONCLUSION: The decisive factor for window settings is the lower window threshold (for adequate TV delineation in the lung and fatty-soft tissue it should be lower than density values of surrounding tissue). The use of a liver window should be considered.