Optimal Target Volume Delineation for Pancreatic Cancer: Triangulating What Should be Targeted.

Optimal SUV Threshold of Gross Tumor Volume Delineation Validated by Pathological Examination in Patients With Esophageal Cancer

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During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required. Material and methods. A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node (LN) dissection was used for delineation. During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT. Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus. The Dice similarity coefficient (DSC) was used to evaluate the delineation agreement before and after the consensus. Results. The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes. The consensus provides recommendations for target delineation in a standard patient both in case of breast conservation or mastectomy. Before the consensus, the average value of the DSC was modest for most volumes, but high for the breast CTV and the heart. After the consensus, the DSC increased for all volumes. Conclusion. The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer. The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement. This consensus will be used by the DBCG in our prospective trials.

Patterns of Recurrence After Primary Local Therapy for Pancreatic Ductal Adenocarcinoma – A Critical Review of Rationale and Target Delineation for (Neo)Adjuvant Radiation Therapy

Objective To retrospectively investigate the effect of the distribution of supraclavicular lymph node metastasis ( LNM) on clinical target volume ( CTV) delineation in radiotherapy for breast cancer. Methods Fifty-five patients with breast cancer who underwent helical computed tomography ( CT) scan and were diagnosed with supraclavicular LNM were enrolled as subjects and their CT images were collected. The metastatic lymph nodes in 55 patients were recreated proportionally on the CT images of a standard patient with breast cancer with reference to normal anatomy in the supraclavicular area. The relationship between the distribution of supraclavicular LNM and the CTV recommended by the Radiation Therapy Oncology Group (RTOG) and other literature was analyzed. Results Sixty percent of LNM were pathologically confirmed and distant metastasis occurred in 64% of supraclavicular LNM. Ninety-one percent and eighty-two percent of patients had centers of LNM in the internal and external regions of the supraclavicular area, respectively. Sixty-six percent of patients had LNM located in the subclavian venous confluence. The CTV recommended by literature covered the centers of all LNM in only 20%-42% of patients, while the CTV recommended by the RTOG guide covered the centers of all LNM in only 26% of patients. Seventy-one percent and sixty-six percent of patients had the centers surpassing the lateral and posterior edges of the CTV, respectively. According to the distribution of LNM mentioned above, we expanded the CTV in the supraclavicular area by extending the lateral and posterior edges to the natural anatomical barriers and the new CTV covered the centers of all LNM in up to 82% of patients. Conclusions The locations of supraclavicular LNM surpass the range, particularly the lateral and posterior edges, of the CTV defined by the RTOG guide. Therefore, the CTV in the supraclavicular area needs to be extended to cover those regions mentioned above. Key words: Breast neoplasm; Supraclavicular nodal metastases; Prophylactic radiotherapy; Target volume delineation

Recommendations on how to establish evidence from auto-segmentation software in radiotherapy

Over the past decade PET/CT scanning has become an invaluable tool in the evaluation of many oncologic processes. A lesion seen on a PET scan will become blurred if affected by respiratory motion, an effect similar to that created when a person moves while a photograph is taken with a slow shutter speed in low-light conditions. The compounding effects of blurring and mis-registration in whole body PET/CT imaging make accurate characterization of disease in areas of high respiratory motion challenging. A scanning technique known as respiratory gated or 4D-PET/CT scanning is a tool that can control for the effects for respiratory motion. This thesis comprises of a series of studies investigating the clinical application of 4D-PET/CT in lung cancer diagnosis and therapy. This thesis begins by presenting a review of the literature in chapter two. This chapter is a published review of the literature, performed by the candidate, which encompasses the literature up until the commencement of this thesis. The review is then updated in the second part of chapter two which reports on the progress of 4D-PET/CT in the literature during the preparation of this thesis. The first stage in the management of lung cancer is a correct diagnosis. The study presented in chapter three investigates the added value of 4D-PET/CT in correctly classifying a lung nodule as either benign of malignant. In a series of 20 patients it was found that an additional 4D-PET/CT scan only influenced the final diagnosis when the standard whole body scan was of indeterminate aetiology. These results show that use of 4D-PET/CT scanning isn’t necessary in every case but that it can be a valuable tool to aid in the timely diagnosis of lung cancer for indeterminate nodules. The use of 4D-PET/CT scanning in the treatment of known lung cancer is covered in chapters four and five. A malignant lung lesion that is unable to be resected is most likely to be treated with a course of radical radiation therapy. This involves the delivery of a prescribed dose of radiation to a target volume defined on imaging. The delineation of internal target volumes (ITV) in radiotherapy of lung tumours is currently performed using either a free-breathing (FB) FDG-PET/CT or a 4D-CT maximum intensity projection (MIP). In chapter four of this thesis I present our validation of a 4D-PET-MIP, equivalent to a 4D-CT-MIP, for the delineation of target volumes in both a phantom and in patients. In the study comparing 4D-PET and CT MIPs we were able to confirm that a 4D-PET-MIP produces volumes with high concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. This can be achieved without the additional radiation exposure for a separate planning 4D-CT scan. Chapter five presents our study analysing the consequences of only using 3D-PET/CT for target volume delineation. The purpose was to investigate geographic miss of lung tumours due to respiratory motion for target volumes defined on a standard 3D-PET/CT scan when compared to target volumes defined on a 4D-PET/CT scan. In this study it was found that without any form of motion suppression the current standard of a 3D- PET/CT and 15mm PTV margin employed for lung lesions has an increasing risk of significant geographic miss in particular when tumour motion increases. Chapter six presents our study investigating the effects of respiratory motion on VQ-PET/CT scanning and determine if 4D imaging will improve co-registration between PET and CT modalities enabling more accurate ability to quantify regional lung function to allow monitoring of the effect of radiation therapy on the normal lung. In this study we were able to show for the first time that ⁶⁸Ga-VQ 4D PET/CT is feasible and the blurring caused by respiratory motion is well corrected with 4D acquisition. The results presented in this thesis show that 4D-PET/CT can have a clinical impact on the management of patients with lung cancer from the point of diagnosis to their treatment and the monitoring of the effects of radiation therapy. The use of 4D-PET/CT is now establishing itself as routine clinical tool that will likely improve outcomes for patient with highly mobile lung tumours.

BACKGROUNDAccurate target volume delineation is the premise for the implementation of precise radiotherapy. Inadequate target volume delineation may diminish tumor control or increase toxicity. Although several clinical target volume (CTV) delineation guidelines for rectal cancer have been published in recent years, significant interobserver variation (IOV) in CTV delineation still exists among radiation oncologists. However, proper education may serve as a bridge that connects complex guidelines with clinical practice.AIMTo examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer.METHODSThe study consisted of a baseline target volume delineation, a 150-min education intervention, and a follow-up evaluation. A 42-year-old man diagnosed with stage IIIC (T3N2bM0) rectal adenocarcinoma was selected for target volume delineation. CTVs obtained before and after the program were compared. Dice similarity coefficient (DSC), inclusiveness index (IncI), conformal index (CI), and relative volume difference [ΔV (%)] were analyzed to quantitatively evaluate the disparities between the participants’ delineation and the standard CTV. Maximum volume ratio (MVR) and coefficient of variation (CV) were calculated to assess the IOV. Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume, external iliac area, groin area, and ischiorectal fossa.RESULTSOf the 18 radiation oncologists from 10 provinces in China, 13 completed two sets of CTVs. In quantitative analysis, the average CTV volume decreased from 809.82 cm3 to 705.21 cm3 (P = 0.001) after the education program. Regarding the indices for geometric comparison, the mean DSC, IncI, and CI increased significantly, while ΔV (%) decreased remarkably, indicating improved agreement between participants’ delineation and the standard CTV. Moreover, an 11.80% reduction in MVR and 18.19% reduction in CV were noted, demonstrating a smaller IOV in delineation after the education program. Regarding qualitative analysis, the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa; 61.54% (8/13) and 53.85% (7/13) of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa, respectively. However, the education program reduced these variations.CONCLUSIONWide variations in CTV delineation for rectal cancer are present among radiation oncologists in mainland China. A well-structured education program could improve delineation accuracy and reduce IOVs.

Purpose To test the hypothesis that patients with pancreatic adenocarcinoma who otherwise are viewed to have resectable disease but have preoperative findings of extrapancreatic perineural invasion (EPNI) and/or duodenal invasion at multidetector computed tomography (CT) have reduced postoperative survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). Materials and Methods This study was approved by the institutional review board and complied with HIPAA. The authors retrospectively evaluated 76 consecutive patients with PDAC who underwent preoperative multidetector CT and subsequent pancreaticoduodenectomy. Two radiologists blinded to surgical pathology results and clinical outcome evaluated multidetector CT images for evidence of EPNI and duodenal invasion; discrepancies were resolved by consensus. Also determined for each patient were resected lymph node status, tumor size, surgical margin status, time to progression, and time to death. Data were assessed with the Goodman-Kruskal gamma for correlations among indicators and the log-rank test, Kaplan-Meier estimates, and multivariate Cox proportional hazards regression for survival analysis. Results In univariate analysis, duodenal invasion and/or EPNI on preoperativemultidetector CT images was associated with significantly decreased progression-free survival (P < .0001) and overall survival (P = .0013), and the clinical indicators (lymph node status, tumor size, and surgical margin status) as well as duodenal invasion and/or EPNI showed correlation with each other. In multivariate regression that included multidetector CT findings as well as the three traditional clinical indicators, only duodenal invasion and/or EPNI showed significant independent association with reduction in both modes of survival (P < .0001 and P = .014, respectively). Interobserver agreement was substantial with respect to EPNI and duodenal invasion (κ = 0.691 and 0.682, respectively). Conclusion Patients with evidence of EPNI and/or duodenal invasion on preoperative multidetector CT images have significantly reduced survival after pancreaticoduodenectomy for PDAC. © RSNA, 2016.

e18060 Background: Target volume delineation in nasopharyngeal carcinoma (NPC) remains a challenge because of the narrow therapeutic margin. There are no-well established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony structure and experience from conventional two and three- dimensional radiation. The aim of our study, is to clarify different anatomic distribution of local recurrence of NPC based on various T stages and spread patterns, provide a high-risk map of local recurrence of NPC, and thus provide suggestion for modification of CTV delineation based on T stages and spread patterns. Methods: We retrospectively enrolled 869 patients with newly diagnosed nonmetastatic NPC treated with definitive IMRT in our institution. With a median follow-up of 54.4 months, 72 patients developed local failure. All the cases of local failure were reviewed and those of local residual disease were excluded. After that, 52 cases with tracaeble primary radiotherapy plans and MR imaging of local recurrence were included in this study. Gross tumor volume of local recurrence (GTVr) and normal structures were delineated in each recurrent patient on primary CT of radiotherapy. The overlap of normal structures with GTVr were analyzed, as well as the stepwise patterns of tumor spread in NPC, based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%, etc). Results: The anatomic distributions of local recurrence of various primary T stages were compared between early and late stages of NPC. Of note, these structures were significantly highly involved in T3/4 cases, compared with T1/2 cases, including lateral pterygoid muscle, inferior orbital fissure，posterior ethmoid sinus，cavernous sinus as well as hypoglossal canal. As for tumor spread patterns of local relapse, most cases relapsed in the nasopharynx and retropharyngeal lymph node (38.5%), followed by anterior-lateral tumor extension (via nasal cavity-pterygoid process-pterygopalatine fossa, 17.31%), posterior tumor extension (via prevertebral muscle-clivus, 13.46%), anterior-superior extension (via nasal cavity-ethmoid sinus-sphenoidal sinus,13.46%), superior extension(via foramen lacerum-cavernous sinus, 11.54%), etc. Finally, we depicted a map of high-risk area based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%). Conclusions: Comprehensive analysis of local recurrence distributions and tumor spread patterns in real-world IMRT provides important reference for modification of CTV delineation for primary NPC. Certain structures such as cavernous sinus and lateral pterygoid muscle are not routinely recommended in the delineation of high-risk CTV for T1-2 disease. Future individualized delineations should be based on relapsed risk and tumor spread patterns.

Variability in volume delineation is a possible error source in brachytherapy. This study assessed the interobserver variations in clinical target volume (CTV) delineation in postoperative adjuvant 125I seed implant brachytherapy after parotid gland cancer surgical resection and evaluated the image fusion technique for target volume delineation. Five radiation oncologists delineated gross tumor volume (GTV) and CTV in 20 patients using conventional delineation and image fusion methods. The consistency in target volume delineation was determined on the basis of differences between the oncologists. Variability was determined using Kendall's W-test, the mean conformity index (CI), the mean distance to conformity (MDC), and the center of gravity distance (CGD). There were significant variations in the delineated target volumes among radiation oncologists, but the CTV consistency was significantly enhanced using the image fusion technique, based on Kendall's W, mean CI, average MDC, and average CGD, which were 0.752, 0.41, 2.75, and 4.997, respectively, using the conventional method, and 0.987, 0.86, 0.55, and 1.27, respectively, using the image fusion method. The interobserver variation in the delineation of the postoperative parotid target volume is large, but it can be considerably decreased using image fusion technology, which resulted in a noticeable improvement in the delineation precision of the target volume for parotid gland cancer. Thus, this technology can enhance the efficacy of 125I seed implant brachytherapy and decrease any adverse effects induced by errors in target delineation.

Variability of clinical target volume delineation for definitive radiotherapy in cervix cancer

Individualization of Clinical Target Volume Delineation Based on Stepwise Spread of Nasopharyngeal Carcinoma: Outcome of More Than a Decade of Clinical Experience

PurposeTo investigate the interobserver variations in delineation of lumpectomy cavity (LC) and clinical target volume (CTV), and its impact on irradiated volume in accelerated partial breast irradiation using intraoperative multicatheter brachytherapy.Material and methodsDelineation of LC and CTV was done by five radiation oncologists on planning computed tomography (CT) scans of 20 patients with intraoperative interstitial breast implant. Cavity visualization index (CVI), four-point index ranging from (0 = poor) to (3 = excellent) was created and assigned by observers for each patient. In total, 200 contours for all observers and 100 treatment plans were evaluated. Spatial concordance (conformity index, CIcommon, and CIgen), average shift in the center of mass (COM), and ratio of maximum and minimum volumes (Vmax/Vmin) of LC and CTV were quantified among all observers and statistically analyzed. Variation in active dwell positions (0.5 cm step) for each catheter, total reference air kerma (TRAK), volume enclosed by prescription isodose (V100%) among observers and its spatial concordance were analyzed.ResultsThe mean ± SD CIcommon of LC and CTV was 0.54 ± 0.09, and 0.58 ± 0.08, respectively. Conformity index tends to increase, shift in COM and Vmax/Vmin decrease significantly (p < 0.05), as CVI increased. Out of total 309 catheters, 29.8% catheters had no change, 29.8% and 17.5% catheters had variations of 1 and 2 dwell positions (0.5 cm and 1 cm), respectively. 9.3% catheters shown variations ≥ 10 dwell positions (5 cm). The mean ± SD CIcommon of V100% was 0.75 ± 0.11. The mean observed Vmax/Vmin of prescription isodose and TRAK was 1.18 (range, 1.03 to 1.56) and 1.11 (range, 1.03 to 1.35), respectively.ConclusionsInterobserver variability in delineation of target volume was found to be significantly related to CVI. Smaller variability was observed with excellent visualization of LC. Interobserver variations showed dosimetric impact on irradiation of breast tissue volume with prescription dose.

To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in acomparative retrospective contouring study. Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a)based on conventional imaging (CT/MRI) and (b)based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared. With the additional information from PSMA ligand PET, 47lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9-565.2] versus 44.9 ml [range 4.9-481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRI × 100) were 45.7% (range 0-96.9) for the GTV and 71.7% (range 9.8-98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003). 68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.