Development of a comprehensive cardiac atlas on a 1.5 Tesla Magnetic Resonance Linear Accelerator.

Background and purpose: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines. Materials and methods: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac anatomy was contoured by (AS) and confirmed by a board certified cardiologist (JR) with expertise in cardiac MR imaging. Results: A total of five volunteers had images acquired with the HASTE sequence, with 21 contours created on each image. One of these volunteers had additional images obtained with 3D bSSFP sequences in the axial plane and additional images obtained with HASTE sequences in the key cardiac planes. Contouring guidelines were created and outlined. 15-16 contours were made for the short axis and vertical long axis. The cardiac conduction system was demonstrated with eleven representative contours. There was reasonable variation of contour volume across volunteers, with structures more clearly delineated on the 3D bSSFP sequence. Conclusions: We present a comprehensive cardiac atlas using novel images acquired prospectively on a 1.5 T MRL. This cardiac atlas provides a novel resource for radiation oncologists in delineating cardiac structures for treatment with radiotherapy, with special focus on the cardiac conduction system.

Target volume coverage in clinically designed radiotherapy plan of post-mastectomy adjuvant radiotherapy of breast cancer patients in comparison with radiation therapy oncology group-based contoured plan: A dosimetric study.

Objective: Conventional field radiotherapy based on anatomical landmarks has been the traditional treatment for breast cancer. Having proven efficacy, it is still the current standard of treatment. The Radiation Therapy Oncology Group (RTOG) has published guidelines for contouring target volumes in postmastectomy patients. The impact of this guideline in the current clinical practice is less known; hence, we have analyzed dose-volume histograms (DVHs) for these plans and compared them with the proposed treatment plans to treat RTOG-defined targets. Subjects and Methods: RTOG consensus definitions were used to contour the target volumes in 20 previously treated postmastectomy patients. The prescription was 42.4 Gy in 16 fractions. DVHs were generated from clinically designed plans that had actually been delivered to each patient. For comparing dose to target volumes, new plans were generated with the goal of covering 95% of volume to 90% of prescribed dose. Results: In RTOG contoured Group, coverage improved for the supraclavicular (V90 = 83 vs. 94.9%, P < 0.05) and chest wall (V90 = 89.8 vs. 95.2%, P < 0.05). Axillary nodal coverage improved for Level-1(V90 = 80.35 vs. 96.40%, P < 0.05), Level-II (V90 = 85.93 vs. 97.09%, P < 0.05) and Level III (V90 = 86.67 vs. 98.6%, P < 0.05). The dose to the ipsilateral lung is increased (V20 = 23.87 vs. 28.73%, P < 0.05). Low dose to heart is increased in left-sided cases (V5 = 14.52 vs. 16.72%, P < 0.05) while same in right-sided cases. Conclusions: The study shows that radiotherapy using the RTOG consensus guidelines improves coverage to target volumes with a nonsignificant increase in normal organ dose compared to that based on anatomical landmarks.

Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation.

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.

Deviation from consensus contouring guidelines predicts inferior local control after spine stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To analyze the impact of target delineation on local control (LC) after stereotactic body radiotherapy (SBRT) for spine metastasis. MATERIALS AND METHODS: Patients with de novo metastasis of the spine treated with SBRT, excluding those with prostate or hematologic malignancies, were retrospectively reviewed. Deviations from consensus contouring guidelines included incomplete coverage of involved vertebral compartments, omission of adjacent compartments, or unnecessary circumferential coverage. Univariable and multivariable Cox proportional hazard analyses were performed using death as a competing risk. RESULTS: 283 patients with 360 discrete lesions were included with a median follow up of 14.6 months (range 1.2-131.3). The prescription dose was 24-27 Gy in 2-3 fractions for the majority of lesions. Median survival after SBRT was 18.3 months (95 % confidence interval [CI]: 14.8-22.8). The 1 and 2-year local control (LC) rates were 81.1 % (95 % CI: 75.5-85.6 %) and 70.6 % (95 % CI: 63.2-76.8 %), respectively. In total, 60 deviations (16.7 %) from consensus contouring guidelines were identified. Deviation from guidelines was associated with inferior LC (1-year LC 63.0 % vs 85.5 %, p < 0.001). Gastrointestinal primary, epidural extension, and paraspinal extension were all associated with inferior LC on univariable analyses. After adjusting for confounding factors, deviation from guidelines was the strongest predictor of inferior LC (HR 3.52, 95 % CI: 2.11-5.86, p < 0.001). Among guideline-compliant treatments, progressions were mainly in field (61 %) and/or epidural (49 %), while marginal (42 %) and/or epidural progressions (58 %) were most common for those with deviations. CONCLUSIONS: Adherence to consensus contouring guidelines for spine SBRT is associated with superior LC and fewer marginal misses.

Validation and applicability of para-aortic lymph nodal contouring atlas in cervical cancer.

BACKGROUND AND PURPOSE: CTV delineation guidelines for the para-aortic nodal region for patients with cervical cancer have been proposed (Keenan et al., 2018). The purpose of this study was to validate these guidelines with the use of CT datasets of cervical cancer patients with macroscopic PALN treated with definitive (chemo)radiation (CTRT) at our center. MATERIALS AND METHODS: Planning CT datasets of 71 cervical cancer patients with gross PA nodal disease treated with EFRT were used. Two hundred and two PALN were identified based on size and morphology on diagnostic CECT, PET CT, or histologically proven PALN. LN regions were divided into upper, middle, and lower and based on their relation to the aorta and IVC. Macroscopic PALN were contoured, and the CTV for PALN irradiation was generated based on the proposed guidelines on ECLIPSE (Version 13.5). The centre of mass (COMN) was calculated for each gross PALN. The evaluation was done to review the presence of COMN in relation to the CTV PALN. RESULTS: The most common location of PALN was Left para-aortic (105 LN-52%), Aortocaval (55 LN-27.2%), and Precaval (14 LN-6.9%). Lower PALN were the commonest (104 LN-51.5%). Ninety-three were middle PALN (46%), and 5 were upper PALN (2.5%). After excluding upper PALN, COMN for 11 PALN (5.5%) were outside the CTV while 20 were junctional. CONCLUSION: Our study shows that more than 95% of PALN in this patient cohort were covered using these guidelines with the addition of an extra 5 mm margin laterally on the left.

Patterns of pathologic lymph nodes in anal cancer: a PET-CT-based analysis with implications for radiotherapy treatment volumes.

BACKGROUND: This study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines. METHODS: The baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed. RESULTS: PET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region. CONCLUSIONS: The results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.

Patterns of inguinal lymph node metastases in anal canal cancer and recommendations for elective clinical target volume (CTV) delineation.

PURPOSE: Optimal clinical target volume (CTV) for inguinal lymph node irradiation in anal cancer remains uncertain. This study documents the location of radiographically involved inguinal lymph nodes and proposes guidelines for CTV delineation. MATERIALS AND METHODS: Patients with anal canal squamous cell carcinoma with inguinal lymph node metastases were identified. Criteria for lymph node involvement included: >15 mm short axis or suspicious morphology on CT or MRI, increased avidity on 18-FDG-PET, or positive biopsy. Distances from center of involved nodes to femoral vessels and inferior pubic symphysis were measured. RESULTS: Forty patients with 79 inguinal lymph nodes were included. Relative to right femoral vessels, nodes were located: 12:00 (n = 6); 1:00 (n = 28); 2:00 (n = 35), 3:00 (n = 5); 4:00 (n = 1); 10:00 (n = 1); 11:00 (n = 3). No nodes were identified lateral or posterior to vessels. Published AGITG guidelines covered 68% of nodes anteriorly and 85% medially. Margins from nearest femoral vessel to cover 95% of nodes were 30 mm anteriorly and 26 mm medially. Inferior margin to cover 95% of nodes was 14 mm below inferior pubic symphysis. Proposed borders include cranial, where external iliac vessels leave bony pelvis; caudal, 14 mm below inferior pubic symphysis; posterior, posterior border of femoral vessels; lateral, lateral border of femoral vessels; anterior, 30 mm margin on femoral vessels and medial, 26 mm margin on femoral vessels, including radiographically suspicious nodes. CONCLUSIONS: Published guidelines for inguinal CTV in anal cancer may result in inadequate coverage of high risk areas. Updated guidelines based on this study ensure coverage of at-risk areas.

Dosimetric comparison of organs at risk using different contouring guidelines for definition of the clinical target volume in anal cancer.

BACKGROUND: There are different contouring guidelines for definition of the clinical target volume (CTV) for intensity-modulated radiation therapy (IMRT) of anal cancer (AC). We conducted a planning comparison study to evaluate and compare the dose to relevant organs at risk (OARs) while using different CTV definitions. METHODS: Twelve patients with a primary diagnosis of anal cancer, who were treated with primary chemoradiation (CRT), were selected. We generated four guideline-specific CTVs and subsequently planned target volumes (PTVs) on the planning CT scan of each patient. An IMRT plan for volumetric arc therapy (VMAT) was set up for each PTV. Dose parameters of the planned target volume (PTV) and OARs were evaluated and compared, too. RESULTS: The mean volume of the four PTVs ranged from 2138 cc to 2433 cc. The target volumes contoured by the authors based on the recommendations of each group were similar in the pelvis, while they differed significantly in the inguinal region. There were no significant differences between the four target volumes with regard to the dose parameters of the cranially located OARs. Conversely, some dose parameters concerning the genitals and the skin varied significantly among the different guidelines. CONCLUSION: The four contouring guidelines differ significantly concerning the inguinal region. In order to avoid inguinal recurrence and to protect relevant OARs, further investigations are needed to generate uniform standards for definition of the elective clinical target volume in the inguinal region.

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.

Have we achieved adequate recommendations for target volume definitions in anal cancer? A PET imaging based patterns of failure analysis in the context of established contouring guidelines.

BACKGROUND: There are different contouring guidelines for the clinical target volume (CTV) in anal cancer (AC) which vary concerning recommendations for radiation margins in different anatomical regions, especially on inguinal site. PET imaging has become more important in primary staging of AC as a very sensitive method to detect lymph node (LN) metastases. Using PET imaging, we evaluated patterns of LN spread, and examined the differences of the respective contouring guidelines on the basis of our results. METHODS: We carried out a retrospective study of thirty-seven AC patients treated with chemoradiation (CRT) who underwent FDG-PET imaging for primary staging in our department between 2011 and 2018. Patients showing PET positive LN were included in this analysis. Using a color code, LN metastases of all patients were delineated on a template with "standard anatomy" and were divided indicating whether their location was in- or out-field of the standard CTV as recommended by the Radiation Therapy Oncology Group (RTOG), the Australasian Gastrointestinal Trials Group (AGITG) or the British National Guidance (BNG). Furthermore, a detailed analysis of the location of LN of the inguinal region was performed. RESULTS: Twenty-two out of thirty-seven AC patients with pre-treatment PET imaging had PET positive LN metastases, accumulating to a total of 154 LN. The most commonly affected anatomical region was inguinal (49 LN, 32%). All para-rectal, external/internal iliac, and pre-sacral LN were covered by the recommended CTVs of the three different guidelines. Of forty-nine involved inguinal LN, fourteen (29%), seven (14%) and five (10%) were situated outside of the recommended CTVs by RTOG, AGITG and BNG. Inguinal LN could be located up to 5.7 cm inferiorly to the femoral saphenous junction and 2.8 cm medial or laterally to the big femoral vessels. CONCLUSION: Pelvis-related, various recommendations are largely consistent, and all LN are covered by the recommended CTVs. LN "misses" appear generally cranially (common iliac or para-aortic) or caudally (inguinal) to the recommended CTVs. The established guidelines differ significantly, particular regarding the inguinal region. Based on our results, we presented our suggestions for CTV definition of the inguinal region. LN involvement of a larger number of patients should be investigated to enable final recommendations.

Tumor Cavity Recurrence after Stereotactic Radiosurgery of Surgically Resected Brain Metastases: Implication of Deviations from Contouring Guidelines.

BACKGROUND: Significant heterogeneity exists in target volumes for postoperative stereotactic radiosurgery (SRS) for brain metastases. A set of contouring guidelines was recently published, and we investigated the impact of deviations. METHODS: Patients (n = 41) undergoing single-fraction Gamma Knife SRS following surgical resection of brain metastases from 2011 to 2017 were retrospectively reviewed. SRS included the entire contrast-enhancing cavity with heterogeneity in inclusion of the surgical tract and no routine margin along the dura or clinical target volume margin. Follow-up MR imaging was fused with SRS plans to assess patterns of failure. RESULTS: The median follow-up was 11.1 months with a median prescription of 18 Gy. There were 5 local failures: infield (n = 3, 60%), surgical tract (n = 1, 20%), and marginal > 5 mm from the resection cavity (n = 1, 20%). No marginal failures < 5 mm or dural margin failures were noted. For deep lesions (n = 13), 62% (n = 8) had the entire tract covered. The only tract recurrence was in a deep lesion without coverage of the surgical tract (n = 1/5). CONCLUSION: In this small preliminary experience, despite no routine inclusion of the dural tract or bone flap, no failures were noted in these locations. Omission of the surgical tract in deep lesions may increase failure rates.

Contouring consensus guidelines in breast cancer radiotherapy: Comparison and systematic review of patterns of failure.

Adequate coverage of sites harbouring potential microscopic disease is paramount, where the clinical decision has been made to include regional lymph node radiotherapy for patients with breast cancer. This must be achieved in balance with minimising dose to normal tissues. Several international consensus guidelines detailing clinical target volumes (CTVs) are available, but there is currently no agreement as to which is most appropriate for a given clinical situation. Contouring guidelines are beneficial for routine practice and essential for clinical trial quality assurance. The aims of this study were as follows: to provide a single point of comparison of four commonly used contouring guidelines, including one used in a current Trans-Tasman Radiation Oncology Group trial; and to undertake a systematic review of existing studies which map sites of breast cancer recurrence against contouring guidelines. Two international consensus guidelines (European Society for Radiotherapy and Oncology, and Radiation Therapy Oncology Group) were compared with two clinical trial guidelines (TROG 12.02 PET LABRADOR and the Proton/Photon trial NCT02603341 RADCOMP). Comprehensive literature search for patterns of failure studies was undertaken using Embase and Pubmed. We detail the small but significant differences between the breast consensus guidelines, particularly the supraclavicular (SCF) and internal mammary chain CTVs. Seven series were found mapping recurrence patterns. These results are discussed in the context of the contouring guidelines. Several studies found the SCF CTV is the area at greatest risk of geographical 'miss'. This review will facilitate further discussion about guideline selection and modification, particularly for future clinical trials in Australia and New Zealand.

The Impact of Positron Emission Tomography/Computed Tomography Addition to Contrast-Enhanced Computed Tomography Findings during Radiation Treatment Planning of Locally Advanced Carcinoma Esophagus.

INTRODUCTION: Does metabolic imaging help in better definition of target during radiation treatment planning by bringing about changes in dimensions of the primary tumor in terms of diameter, length, and picking up new skip lesions or nodal stations which in turn prevents geographic misses by including more 18F-fluorodeoxyglucose avid regions not visible on conventional imaging? MATERIALS AND METHODS: We compared the length and radial dimensions of the primary tumor as well as changes brought about due to addition of new nodal stations, involved structures, and skip lesions in 50 patients of carcinoma esophagus treated between 2011 and 2013, as seen on contrast-enhanced computed tomography (CT) thorax and positron emission tomography (PET)/CT and drew conclusions regarding the technical changes brought about in treatment planning by the additional input of PET/CT. RESULTS AND CONCLUSIONS: PET-CT tremendously changes treatment plans by expanding the gross tumor volume and including regions which might otherwise have been missed on purely CT-based plans. Of the 50 patients, it changed the contouring and treatment planning of 35 patients and did not impact the remaining 15. Whether this translates into better long-term controls requires further validation by randomized controlled trials, which was not our present objective.

Challenges for Quality Assurance of Target Volume Delineation in Clinical Trials.

In recent years, new radiotherapy techniques have emerged that aim to improve treatment outcome and reduce toxicity. The standard method of evaluating such techniques is to conduct large scale multicenter clinical trials, often across continents. A major challenge for such trials is quality assurance to ensure consistency of treatment across all participating centers. Analyses from previous studies have shown that poor compliance and protocol violation have a significant adverse effect on treatment outcomes. The results of the clinical trials may, therefore, be confounded by poor quality radiotherapy. Target volume delineation (TVD) is one of the most critical steps in the radiotherapy process. Many studies have shown large inter-observer variations in contouring, both within and outside of clinical trials. High precision techniques, such as intensity-modulated radiotherapy, image-guided brachytherapy, and stereotactic radiotherapy have steep dose gradients, and errors in contouring may lead to inadequate dose to the tumor and consequently, reduce the chance of cure. Similarly, variation in organ at risk delineation will make it difficult to evaluate dose response for toxicity. This article reviews the literature on TVD variability and its impact on dosimetry and clinical outcomes. The implications for quality assurance in clinical trials are discussed.

[Guidelines for delineation of pelvic lymph nodes in anal cancer treatment]. / Recommandations pour la délinéation des aires ganglionnaires pelviennes dans le cancer du canal anal.

Squamous cell anal cancer is a rare malignancy, its incidence increases due to higher exposure of the young adults to risk factors. The current management is based on chemoradiotherapy, which is highly effective and achieves locoregional control but causes important morbidity. Improvement of radiation technique such as intensity modulated radiation therapy has led to reduce acute toxicities, but also requires an accurate delineation of the target volumes in order not to underestimate potential and pathological sites resulting in an increase of the locoregional failures. PET scanner has an important place in the pretreatment work-up for staging and targeting the delineation of the volumes, allowing to select patients with localized disease, avoid geographic miss and appropriately boost nodal disease. The study of recurrences sites has not yet provided a real mapping of the recurrences depending on the treatment volumes. Different radiation oncologist cooperative groups have published guidelines and tools for delineation, in order to provide homogeneity but also customize the management of anal carcinoma.