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.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography-based Lymph Node Atlas for Salvage Radiotherapy in Patients with Recurrent Prostate Cancer: A Validation of the New NRG Oncology 2020 guideline.

BACKGROUND: Approximately 20-40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020). OBJECTIVE: To evaluate and validate the updated NRG 2020 guideline with our established LN atlas. DESIGN, SETTING, AND PARTICIPANTS: We screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10-90%), or outside (<10%). RESULTS AND LIMITATIONS: In comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results. CONCLUSIONS: The updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread. PATIENT SUMMARY: We compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

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.

Comparison of the distribution of lymph node metastases compared to healthy lymph nodes in breast cancer.

BACKGROUND: Current literature lacks a comparison of lymph node metastases and non-pathological lymph nodes distribution in breast cancer patients. The aim of the current retrospective study was to generate a comprehensive atlas of the lymph node system. METHODS: 143 breast cancer patients underwent F-18-FDG-PET/CT (PET/CT) imaging for staging purposes and were diagnosed with regional lymph node metastases. Based on the PET/CT data set a total of 326 lymph node metastases and 1826 non-pathological lymph nodes were detected and contoured manually in the patient collective. Using rigid and deformable registration algorithms all structures were transferred to a template planning CT of a standard patient. Subsequently, a 3D-atlas of the distribution of lymph node metastases and non-pathological lymph nodes were generated and compared to each other. RESULTS: Both, lymph node metastases and non-pathological lymph nodes, accumulated in certain areas ("hot-spots") within the lymphatic drainage system. However large differences regarding the distribution patterns were detected: lymph node metastases hot spots occurred in close proximity to the subclavian vein in level I-III, whereas the non-pathological lymph nodes accumulated mostly (within a wider range) in level I. In level II and III lymph node metastases exceeded clearly the areas in which non-pathological lymph nodes occurred. CONCLUSION: Lymph node metastases and non-pathological lymph node distribution within the lymph node system differ clearly. Based on our results, an individual adjustment of the CTV in order to include visible lymph nodes in level II and III should be discussed.

Impact of CBCT frequency on target coverage and dose to the organs at risk in adjuvant breast cancer radiotherapy.

The current study aims to assess the effect of cone beam computed tomography (CBCT) frequency during adjuvant breast cancer radiotherapy with simultaneous integrated boost (SIB) on target volume coverage and dose to the organs at risk (OAR). 50 breast cancer patients receiving either non-hypofractionated or hypofractionated radiotherapy after lumpectomy including a SIB to the tumor bed were selected for this study. All patients were treated in volumetric modulated arc therapy (VMAT) technique and underwent daily CBCT imaging. In order to estimate the delivered dose during the treatment, the applied fraction doses were recalculated on daily CBCT scans and accumulated using deformable image registration. Based on a total of 2440 dose recalculations, dose coverage in the clinical target volumes (CTV) and OAR was compared depending on the CBCT frequency. The estimated delivered dose (V95%) for breast-CTV and SIB-CTV was significantly lower than the planned dose distribution, irrespective of the CBCT-frequency. Between daily CBCT and CBCT on alternate days, no significant dose differences were found regarding V95% for both, breast-CTV and SIB-CTV. Dose distribution in the OAR was similar for both imaging protocols. Weekly CBCT though led to a significant decrease in dose coverage compared to daily CBCT and a small but significant dose increase in most OAR. Daily CBCT imaging might not be necessary to ensure adequate dose coverage in the target volumes while efficiently sparing the OAR during adjuvant breast cancer radiotherapy with SIB.

Excluding Lung Tissue from the PTV during Internal Mammary Irradiation. A Safe Technique for OAR-Sparing?

The current study aims to determine whether exclusion of lung tissue from planning treatment volume (PTV) is a valid organ at risk (OAR)-sparing technique during internal mammary irradiation (IMNI). Twenty patients with left-sided breast cancer undergoing adjuvant radiotherapy including IMNI after mastectomy or lumpectomy with daily ConeBeam CT (CBCT; median n = 28) were enrolled in the current study. The daily dose distribution of the patients was estimated by recalculating treatment plans on CBCT-scans based on a standard PTV (PTV margin: 5mm-STD) and a modified PTV, which excluded overlapping lung tissue (ExLung). Using 3D-deformable dose accumulation, the dose coverage in the target volume was estimated in dependence of the PTV-margins. The estimated delivered dose in the IMN-CTV was significantly lower for the ExLung PTV compared to the STD PTV: ExLung: V95%: 76.6 ± 22.9%; V90%: 89.6 ± 13.2%, STD: V95%: 95.6 ± 7.4%; V90%: 99.1 ± 2.7%. Daily CBCT imaging cannot sufficiently compensate the anatomic changes and intrafraction movement throughout the treatment. Therefore, to ensure adequate delivery of the prescribed dose to the IMN-CTV, exclusion of lung tissue from the PTV to spare the OARs is not recommended.

PSMA-PET/CT-based Lymph Node Atlas for Prostate Cancer Patients Recurring After Primary Treatment: Clinical Implications for Salvage Radiation Therapy.

BACKGROUND: Many patients experience recurrence of prostate cancer after radical prostatectomy. OBJECTIVE: The aim of this study was to visually analyze typical patterns of lymph node (LN) involvement for prostate cancer (PC) patients with biochemical recurrence after radical prostatectomy and lymphadenectomy by creating a color-coded heat map using gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET) imaging. Further, we evaluated which LNs were covered by the Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) contouring guidelines. DESIGN, SETTING, AND PARTICIPANTS: A total of 1653 68Ga-PSMA-PET/computed tomography (CT) datasets were screened retrospectively. After meeting the eligibility criteria, 233 patients with 799 LN metastases were included in our study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We created a comprehensive three-dimensional color-coded LN atlas. Further, the coverage of LN metastases by RTOG CTV was assessed and stratification for risk factors was performed. RESULTS AND LIMITATIONS: In the overall, mainly high risk, collective, complete coverage by the standard RTOG CTV was accomplished in 31.0% of all LN metastases. The vast majority of uncovered LNs are situated in the para-aortal, pararectal, paravesical, preacetabular, presacral, and inguinal regions. Concerning examined stratification factors, prostate-specific antigen (PSA) levels at the time of PET/CT imaging had the highest predictive value for extrapelvic metastatic LN spread. Every increase of 1 ng/mL in PSA raises the risk of metastases outside the CTV by a factor of 1.43. CONCLUSIONS: We developed the first LN atlas for patients with recurrent PC using a heat map technique, in order to illustrate hot spots of LN recurrence. The vast majority of detected LNs are not covered by a standard CTV as recommended by the RTOG. Application of the standard RTOG CTV for pelvic irradiation in the salvage setting for high-risk PC patients seems to be inappropriate. PATIENT SUMMARY: We visualized typical lymph node recurrence sites for patients after prostate cancer surgery.

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.

The dosimetric impact of stabilizing spinal implants in radiotherapy treatment planning with protons and photons: standard titanium alloy vs. radiolucent carbon-fiber-reinforced PEEK systems.

BACKGROUND: Throughout the last years, carbon-fibre-reinforced PEEK (CFP) pedicle screw systems were introduced to replace standard titanium alloy (Ti) implants for spinal instrumentation, promising improved radiotherapy (RT) treatment planning accuracy. We compared the dosimetric impact of both implants for intensity modulated proton (IMPT) and volumetric arc photon therapy (VMAT), with the focus on uncertainties in Hounsfield unit assignment of titanium alloy. METHODS: Retrospective planning was performed on CT data of five patients with Ti and five with CFP implants. Carbon-fibre-reinforced PEEK systems comprised radiolucent pedicle screws with thin titanium-coated regions and titanium tulips. For each patient, one IMPT and one VMAT plan were generated with a nominal relative stopping power (SP) (IMPT) and electron density (ρ) (VMAT) and recalculated onto the identical CT with increased and decreased SP or ρ by ±6% for the titanium components. RESULTS: Recalculated VMAT dose distributions hardly deviated from the nominal plans for both screw types. IMPT plans resulted in more heterogeneous target coverage, measured by the standard deviation σ inside the target, which increased on average by 7.6 ± 2.3% (Ti) vs 3.4 ± 1.2% (CFP). Larger SPs lead to lower target minimum doses, lower SPs to higher dose maxima, with a more pronounced effect for Ti screws. CONCLUSIONS: While VMAT plans showed no relevant difference in dosimetric quality between both screw types, IMPT plans demonstrated the benefit of CFP screws through a smaller dosimetric impact of CT-value uncertainties compared to Ti. Reducing metal components in implants will therefore improve dose calculation accuracy and lower the risk for tumor underdosage.

Effect of hypofractionation on the incidental axilla dose during tangential field radiotherapy in breast cancer.

OBJECTIVE: Tangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed. MATERIALS AND METHODS: Biological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 Gy in 16 fractions [Fx]; 40.05 Gy in 15 Fx; 27 Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an α/ß ratio of 4 Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases. RESULTS: The extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 ± 6.4% to 57.5 ± 22.9%, depending on the patient's anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules. CONCLUSION: Our data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.

Real-time 4DMRI-based internal target volume definition for moving lung tumors.

PURPOSE: In photon radiotherapy, respiratory-induced target motion can be accounted for by internal target volumes (ITV) or mid-ventilation target volumes (midV) defined on the basis of four-dimensional computed tomography (4D-CT). Intrinsic limitations of these approaches can result in target volumes that are not representative for the gross tumor volume (GTV) motion over the course of treatment. To address these limitations, we propose a novel patient-specific ITV definition method based on real-time 4D magnetic resonance imaging (rt-4DMRI). METHODS: Three lung cancer patients underwent weekly rt-4DMRI scans. A total of 24 datasets were included in this retrospective study. The GTV was contoured on breath-hold MR images and propagated to all rt-4DMRI images by deformable image registration. Different targets were created for the first (reference) imaging sessions: ITVs encompassing all GTV positions over the complete (ITV 80 s ) or partial acquisition time ( ITV 10 s ), ITVs including only voxels with a GTV probability-of-presence (POP) of at least 5% ( ITV 5 % ) or 10% ( ITV 10 % ), and the mid-ventilation GTV position. Reference planning target volumes ( PTV r ) were created by adding margins around the ITVs and midV target volumes. The geometrical overlap of the PTV r with ITV n 5 % from the six to eight subsequent imaging sessions on days n was quantified in terms of the Dice similarity coefficient (DSC), sensitivity [SE: ( PTV r ∩ ITV n 5 % )/ ITV n 5 % ] and precision [PRE: ( PTV r ∩ ITV n 5 % )/ PTV r ] as surrogates for target coverage and normal tissue sparing. RESULTS: Patient-specific analysis yielded a high variance of the overlap values of PTV r 10 s , when different periods within the reference imaging session were sampled. The mid-ventilation-based PTVs were smaller than the ITV-based PTVs. While the SE was high for patients with small breathing pattern variations, changes of the median breathing amplitudes in different imaging sessions led to inferior SE values for the mid-ventilation PTV for one patient. In contrast, PTV r 5 % and PTV r 10 % showed higher SE values with a higher robustness against interfractional changes, at the cost of larger target volumes. CONCLUSIONS: The results indicate that rt-4DMRI could be valuable for the definition of target volumes based on the GTV POP to achieve a higher robustness against interfractional changes than feasible with today's 4D-CT-based target definition concepts.

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.

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).