A Visual Aid Tool for Detection of Pancreatic Tumour-Vessel Contact on Staging CT: A Retrospective Cohort Study.

Purpose: In pancreatic adenocarcinoma, the difficult distinction between normal and affected pancreas on CT studies may lead to discordance between the pre-surgical assessment of vessel involvement and intraoperative findings. We hypothesize that a visual aid tool could improve the performance of radiology residents when detecting vascular invasion in pancreatic adenocarcinoma patients. Methods: This study consisted of 94 pancreatic adenocarcinoma patient CTs. The visual aid compared the estimated body fat density of each patient with the densities surrounding the superior mesenteric artery and mapped them onto the CT scan. Four radiology residents annotated the locations of perceived vascular invasion on each scan with the visual aid overlaid on alternating scans. Using 3 expert radiologists as the reference standard, we quantified the area under the receiver operating characteristic curve to determine the performance of the tool. We then used sensitivity, specificity, balanced accuracy ((sensitivity + specificity)/2), and spatial metrics to determine the performance of the residents with and without the tool. Results: The mean area under the curve was 0.80. Radiology residents' sensitivity/specificity/balanced accuracy for predicting vascular invasion were 50%/85%/68% without the tool and 81%/79%/80% with it compared to expert radiologists, and 58%/85%/72% without the tool and 78%/77%/77% with it compared to the surgical pathology. The tool was not found to impact the spatial metrics calculated on the resident annotations of vascular invasion. Conclusion: The improvements provided by the visual aid were predominantly reflected by increased sensitivity and accuracy, indicating the potential of this tool as a learning aid for trainees.

Predicting stereotactic radiosurgery outcomes with multi-observer qualitative appearance labelling versus MRI radiomics.

Qualitative observer-based and quantitative radiomics-based analyses of T1w contrast-enhanced magnetic resonance imaging (T1w-CE MRI) have both been shown to predict the outcomes of brain metastasis (BM) stereotactic radiosurgery (SRS). Comparison of these methods and interpretation of radiomics-based machine learning (ML) models remains limited. To address this need, we collected a dataset of n = 123 BMs from 99 patients including 12 clinical features, 107 pre-treatment T1w-CE MRI radiomic features, and BM post-SRS progression scores. A previously published outcome model using SRS dose prescription and five-way BM qualitative appearance scoring was evaluated. We found high qualitative scoring interobserver variability across five observers that negatively impacted the model's risk stratification. Radiomics-based ML models trained to replicate the qualitative scoring did so with high accuracy (bootstrap-corrected AUC = 0.84-0.94), but risk stratification using these replicated qualitative scores remained poor. Radiomics-based ML models trained to directly predict post-SRS progression offered enhanced risk stratification (Kaplan-Meier rank-sum p = 0.0003) compared to using qualitative appearance. The qualitative appearance scoring enabled interpretation of the progression radiomics-based ML model, with necrotic BMs and a subset of heterogeneous BMs predicted as being at high-risk of post-SRS progression, in agreement with current radiobiological understanding. Our study's results show that while radiomics-based SRS outcome models out-perform qualitative appearance analysis, qualitative appearance still provides critical insight into ML model operation.

Understanding cancer stem cells and plasticity: Towards better therapeutics.

The ability of cancer cells to finally overcome various lines of treatment in due course has always baffled the scientific community. Even with the most promising therapies, relapse is ultimately seen, and this resilience has proved to be a major hurdle in the management of cancer. Accumulating evidence now attributes this resilience to plasticity. Plasticity is the ability of cells to change their properties and is substantial as it helps in normal tissue regeneration or post-injury repair processes. It also helps in the overall maintenance of homeostasis. Unfortunately, this critical ability of cells, when activated incorrectly, can lead to numerous diseases, including cancer. Therefore, in this review, we focus on the plasticity aspect with an emphasis on cancer stem cells (CSCs). We discuss the various forms of plasticity that provide survival advantages to CSCs. Moreover, we explore various factors that affect plasticity. Furthermore, we provide the therapeutic implications of plasticity. Finally, we provide an insight into the future targeted therapies involving plasticity for better clinical outcomes.

Dosimetric comparison of high-dose rate cervix brachytherapy with and without interstitial needles and the impact on target volume coverage, and organ at risk constraints.

INTRODUCTION: The aim of this audit was to compare the data from the Wellington Blood and Cancer Centre (WBCC) with international reported experience by quantifying the dosimetric impact of interstitial needles on target coverage and organ at risk (OAR) doses. METHODS: All patients identified as having had interstitial needles as part of their treatment out of a cohort of 120 radically treated cervical cancer patients between 2013 and 2019 were included. Each patient acted as their own control with two treatment plans optimised for each fraction; the clinically treated plan and a re-optimisation without the use of interstitial needles. Plan optimisation was completed according to the departmental protocol and cumulative equivalent doses for 2 Gy fractions (EQD2) were calculated. RESULTS: Eighteen patients were suitable for evaluation. A total of 52 insertions with interstitial needles were performed, of the 148 needles inserted, 119 (80.4%) were loaded. HRCTV D90% coverage mean was EQD2 5.4 Gy (0.5-10.6 Gy) higher for the course containing loaded interstitial needles, while no significant change was observed with regards to OAR doses. This improved coverage is in line with international standards which report 4.4-9.0 Gy. CONCLUSION: WBCC's early experience of interstitial cervix brachytherapy has shown our target coverage improvements meet previously published international standards and confirms the value of this technique. This audit supports ongoing use of interstitial needles at the WBCC.

Adjuvant radiotherapy for endometrial cancer with cervical stromal involvement: A patterns of practice survey in Australia and New Zealand.

INTRODUCTION: The purpose of this study is to describe the patterns of practice in Australia and New Zealand for post-operative radiotherapy in endometrial cancer with cervical stromal involvement. METHODS: A ten-item survey including five clinical case scenarios in endometrial cancer with cervical stromal invasion was emailed to Royal Australian and New Zealand College of Radiologists (RANZCR) radiation oncologists in 2018. Responses were analysed to determine relative frequency distributions and preferred adjuvant treatment modalities for the clinical case scenarios. RESULTS: A total of 65 respondents initiated the survey with 27 respondents treating more than 11 endometrial cancer cases annually. Only 31 respondents answered all five clinical case scenarios. Preferred adjuvant radiotherapy modalities varied for the Stage II cases between vault brachytherapy (VB), pelvic external beam radiotherapy (EBRT) or a combination. For the stage IIIA and IIIC1 cases, the majority recommended pelvic EBRT with or without VB boost (79% and 77%), and of these, most combined with chemotherapy (61% and 88%). For 4 of the 5 case scenarios, when pelvic EBRT was offered, most recommended a VB boost. CONCLUSION: This patterns of practice survey suggests variability in adjuvant radiotherapy recommendations in endometrial cancer with cervical involvement, particularly in cases where there is lack of randomised data and discrepancies in consensus guidelines.

Automatic cancer detection on digital histopathology images of mid-gland radical prostatectomy specimens.

Purpose: Automatic cancer detection on radical prostatectomy (RP) sections facilitates graphical and quantitative surgical pathology reporting, which can potentially benefit postsurgery follow-up care and treatment planning. It can also support imaging validation studies using a histologic reference standard and pathology research studies. This problem is challenging due to the large sizes of digital histopathology whole-mount whole-slide images (WSIs) of RP sections and staining variability across different WSIs. Approach: We proposed a calibration-free adaptive thresholding algorithm, which compensates for staining variability and yields consistent tissue component maps (TCMs) of the nuclei, lumina, and other tissues. We used and compared three machine learning methods for classifying each cancer versus noncancer region of interest (ROI) throughout each WSI: (1) conventional machine learning methods and 14 texture features extracted from TCMs, (2) transfer learning with pretrained AlexNet fine-tuned by TCM ROIs, and (3) transfer learning with pretrained AlexNet fine-tuned with raw image ROIs. Results: The three methods yielded areas under the receiver operating characteristic curve of 0.96, 0.98, and 0.98, respectively, in leave-one-patient-out cross validation using 1.3 million ROIs from 286 mid-gland whole-mount WSIs from 68 patients. Conclusion: Transfer learning with the use of TCMs demonstrated state-of-the-art overall performance and is more stable with respect to sample size across different tissue types. For the tissue types involving Gleason 5 (most aggressive) cancer, it achieved the best performance compared to the other tested methods. This tool can be translated to clinical workflow to assist graphical and quantitative pathology reporting for surgical specimens upon further multicenter validation.

Histologic tissue components provide major cues for machine learning-based prostate cancer detection and grading on prostatectomy specimens.

Automatically detecting and grading cancerous regions on radical prostatectomy (RP) sections facilitates graphical and quantitative pathology reporting, potentially benefitting post-surgery prognosis, recurrence prediction, and treatment planning after RP. Promising results for detecting and grading prostate cancer on digital histopathology images have been reported using machine learning techniques. However, the importance and applicability of those methods have not been fully investigated. We computed three-class tissue component maps (TCMs) from the images, where each pixel was labeled as nuclei, lumina, or other. We applied seven different machine learning approaches: three non-deep learning classifiers with features extracted from TCMs, and four deep learning, using transfer learning with the 1) TCMs, 2) nuclei maps, 3) lumina maps, and 4) raw images for cancer detection and grading on whole-mount RP tissue sections. We performed leave-one-patient-out cross-validation against expert annotations using 286 whole-slide images from 68 patients. For both cancer detection and grading, transfer learning using TCMs performed best. Transfer learning using nuclei maps yielded slightly inferior overall performance, but the best performance for classifying higher-grade cancer. This suggests that 3-class TCMs provide the major cues for cancer detection and grading primarily using nucleus features, which are the most important information for identifying higher-grade cancer.

Implementation of radiation therapist cylinder insertion for vaginal vault brachytherapy.

Vaginal vault brachytherapy is a common treatment for endometrial cancer. Historically, applicator insertion has been the domain of a radiation oncologist (RO). This commentary outlines a project to improve efficiency and workforce utilisation by introducing a competency framework and training module allowing entitled radiation therapists to perform single-channel cylinder applicator insertions and treatment delivery under RO supervision for fraction one and without supervision for subsequent fractions. The rationale, relevant regulations, implementation process and barriers are explored.

Dosimetric comparison of surface mould HDR brachytherapy with VMAT.

INTRODUCTION: The aim of this study was to investigate the dosimetric differences between surface mould high-dose-rate (HDR) brachytherapy and external beam volumetric-modulated arc therapy (VMAT) for two treatment sites. METHODS: Previously treated HDR brachytherapy surface mould scalp (n = 4) and lower leg (n = 3) treatments were retrospectively analysed. The VMAT plans were optimised using an additional 3-mm setup margin on the clinical target volume (CTV) of the previously treated HDR plans. The HDR plans were calculated and normalised using the TG-43 formalism and recalculated with Acuros BV (AC). RESULTS: On average, the mean brain and normal tissue doses were reduced by 44.8% and 27.4% for scalp and lower leg VMAT cases, respectively, when compared to AC calculated HDR plans. For VMAT plans, the average dose to a 1-mm thick skin structure deep to the target volume was not any lower than that in AC HDR plans. On average, the CTV coverage was 13.8% and 9.6% lower for scalp cases with AC dose calculation than with TG-43 and 8.3% and 5.3% lower for lower leg cases if 0- or 1-cm backscatter material was applied above the catheters, respectively. CONCLUSIONS: VMAT is a feasible treatment option in the case of extensive skin malignancies of the scalp and lower leg. Uncertainties related to delivered dose with HDR brachytherapy when using the TG-43 dose calculation model or possible air gaps between the mould and skin favour the use of VMAT. The potential soft tissue deformation needs to be considered if VMAT is used.

Patient-specific calibration of cone-beam computed tomography data sets for radiotherapy dose calculations and treatment plan assessment.

PURPOSE: In this work, we propose a new method of calibrating cone beam computed tomography (CBCT) data sets for radiotherapy dose calculation and plan assessment. The motivation for this patient-specific calibration (PSC) method is to develop an efficient, robust, and accurate CBCT calibration process that is less susceptible to deformable image registration (DIR) errors. METHODS: Instead of mapping the CT numbers voxel-by-voxel with traditional DIR calibration methods, the PSC methods generates correlation plots between deformably registered planning CT and CBCT voxel values, for each image slice. A linear calibration curve specific to each slice is then obtained by least-squares fitting, and applied to the CBCT slice's voxel values. This allows each CBCT slice to be corrected using DIR without altering the patient geometry through regional DIR errors. A retrospective study was performed on 15 head-and-neck cancer patients, each having routine CBCTs and a middle-of-treatment re-planning CT (reCT). The original treatment plan was re-calculated on the patient's reCT image set (serving as the gold standard) as well as the image sets produced by voxel-to-voxel DIR, density-overriding, and the new PSC calibration methods. Dose accuracy of each calibration method was compared to the reference reCT data set using common dose-volume metrics and 3D gamma analysis. A phantom study was also performed to assess the accuracy of the DIR and PSC CBCT calibration methods compared with planning CT. RESULTS: Compared with the gold standard using reCT, the average dose metric differences were ≤ 1.1% for all three methods (PSC: -0.3%; DIR: -0.7%; density-override: -1.1%). The average gamma pass rates with thresholds 3%, 3 mm were also similar among the three techniques (PSC: 95.0%; DIR: 96.1%; density-override: 94.4%). CONCLUSIONS: An automated patient-specific calibration method was developed which yielded strong dosimetric agreement with the results obtained using a re-planning CT for head-and-neck patients.

Treatment plan dosimetric impact after catheter stretch during multi-catheter interstitial breast brachytherapy.

PURPOSE: Nylon 6/6 interstitial brachytherapy catheters may stretch when exposed to moisture, mechanical tension, and body temperature. The purpose of this study is to evaluate the magnitude of catheter stretch during a course of multi-catheter interstitial breast brachytherapy for nylon 6/6 treatment catheters, and to assess the impact this has on treatment plan dosimetry. MATERIAL AND METHODS: Catheters were exposed to water at 37°C for six days and the internal catheter length change (ΔL_W) was measured daily. Additionally, the measured internal catheter length change (ΔL_P), performed prior to each treatment fraction, for seven interstitial breast brachytherapy patients (total of 76 catheters) were retrospectively analyzed. The maximum length change seen in ΔL_P and ΔL_W were introduced as a source positional error to retrospective treatment plans, and treatment plan dosimetry was analyzed. RESULTS: ΔL_W and ΔL_P were on average +4.0% and +1.6% of the catheter lengths in water or tissue after 48 hours. Weak correlation was seen between the average ΔL_P per catheter and both the catheter length within tissue (ρ = 0.36, p = 0.0007), and the mid-catheter depth in tissue (ρ = 0.42, p < 0.0001). The D90CTV decreased 1.5% (p < 0.05) and 8.2% (p < 0.05) when the ΔL_P and ΔL_W were introduced to the initial plans. CONCLUSIONS: Nylon 6/6 catheters stretch during a course of multi-catheter interstitial breast brachytherapy treatment. The observed stretch may affect treatment plan dosimetry, if the catheter internal length is only measured immediately after the insertion. Additional catheter length checks are recommended to verify the actual catheter internal length during the treatment.

Tuberculosis: Still an emerging threat.

Primary care providers must be aggressive in their assessment and screening of tuberculosis (TB) infection, which is still a major cause of mortality and morbidity worldwide. This article highlights the overall management of TB infection including the appropriate screening, diagnosis, and treatment of both latent and active infection.

Inflammation and Nitrosative Stress Effects in Ovarian and Prostate Pathology and Carcinogenesis.

SIGNIFICANCE: Prostate and ovarian cancers are major contributors to cancer-related deaths worldwide. Recently, inflammation and nitrosative stress have been implicated in carcinogenesis, with the overexpression of NOS2 and concomitant release of nitric oxide (NO) associated with cancer initiation and progression. Recent Advances: An increasing body of evidence indicates an association between NOS2 expression and aggressive ovarian cancer. Research also indicates a role for NO in prostate disease pathology and prostate cancer. A therapeutic role for NOS2 inhibition and/or NO drugs exists for the treatment of both ovarian and prostate tumors. CRITICAL ISSUES: Herein, we review the key molecular effects associated with NOS2 in ovarian and prostate cancer. NOS2 increases angiogenesis and tumor proliferation and correlates with aggressive type II ovarian tumors. NOS2 expressing tumors are sensitive to cisplatin chemotherapy, and NO may be used to sensitize cisplatin-resistant tumors to chemotherapy. NOS2 is highly expressed in prostate tumors compared to non-neoplastic prostate pathologies. NO may play a role in the development of androgen-independent prostate cancer via s-nitrosylation of the androgen receptor. Moreover, NOS2 inhibitors and NO donor drugs show therapeutic potential in ovarian and prostate cancer as single agents or dual drugs, by either inhibiting the effects of NOS2 or increasing NO levels to induce cytotoxic effects. FUTURE DIRECTIONS: NOS2 and NO present new targets for the treatment of ovarian and prostate tumors. Furthermore, understanding NO-related tumor biology in these cancers presents a new means for improved patient stratification to the appropriate treatment regimen. Antioxid. Redox Signal. 26, 1078-1090.

Distribution of RANK and RANK Ligand in Normal Human Tissues as Determined by an Optimized Immunohistochemical Method.

The expression and tissue distribution of RANK (Receptor Activator of Nuclear Factor κ B) and RANK Ligand (RANKL) are of critical interest in relation to efficacy and safety of antibodies against RANK or RANKL that are approved or under consideration as potential therapeutic agents. Data from the literature using protein or mRNA analyses of rodent and human tissues or immunohistochemical (IHC) studies with a variety of antibodies and methods have provided some background of the distribution of RANK and RANKL but have yielded inconsistent findings. The present study reports the generation of carefully validated antibodies to RANK and RANKL and the development of an optimized IHC method, with confirmatory data from 2 well-validated alternative protocols that were developed and performed in separate laboratories at USC and at Amgen. Tissue expression of RANK and RANKL is reported for the optimized IHC assay.

Metastatic endometrial endometrioid carcinoma mimicking pilomatrixoma of the distal vagina.

Endometrioid carcinoma with a prominent squamous component has the ability to mimic pilomatrixoma. One previous case is documented of cutaneous metastasis in the upper limb derived from ovarian endometrioid carcinoma mimicking pilomatrixoma. Here, we describe a case of metastasis of endometrial endometrioid carcinoma in the distal vagina, treated with radiotherapy and later resected. The histology of the lesion was thought initially to represent pilomatrixoma; this has not previously been described in the vagina, where no hair matrix cells are normally present. We hypothesise that radiotherapy may have effectively 'sterilised' the glandular component, blinding the malignant features. Further management was significantly altered by the reinterpretation of this result as metastatic disease. We emphasise that in the context of known endometrioid carcinoma, the diagnosis of pilomatrixoma should be made with caution, particularly where radiotherapy has been used.

High-risk CTV delineation for cervix brachytherapy: Application of GEC-ESTRO guidelines in Australia and New Zealand.

INTRODUCTION: Image-based brachytherapy for cervical cancer using MRI has been implemented in Australia and New Zealand. The aims of this study were to measure variability in High-risk CTV (HR-CTV) delineation and evaluate dosimetric consequences of this. METHODS: Nine radiation oncologists, one radiation therapist and two radiologists contoured HR-CTV on 3T MRI datasets from ten consecutive patients undergoing cervical brachytherapy at a single institution. Contour comparisons were performed using the Dice Similarity Coefficient (DSC) and Mean Absolute Surface Distance (MASD). Two reference contours were created for brachytherapy planning: a Simultaneous Truth and Performance Level Estimation (STAPLE) and a consensus contour (CONSENSUS). Optimized plans (8 Gy) for both these contours were applied to individual participant's contours to assess D90 and D100 coverage of HR CTV. To compare variability in dosimetry, relative standard deviation (rSD) was calculated. RESULTS: Good concordance (mean DSC≥0.7, MASD≤5 mm) was achieved in 8/10 cases when compared to the STAPLE reference and 6/10 cases when compared to the CONSENSUS reference. Greatest variation was visually seen in the cranio-caudal direction. The average mean rSD across all patients was 27% and 34% for the STAPLE HR-CTV D90 and D100, respectively, and 28% and 35% for the CONSENSUS HR-CTV D90 and D100. Delineation uncertainty resulted in an average dosimetric uncertainty of ±1.5-1.6 Gy per fraction based on an 8 Gy prescribed fraction. CONCLUSIONS: Delineation of HR-CTV for cervical cancer brachytherapy was consistent amongst observers, suggesting similar interpretation of GEC-ESTRO guidelines. Despite the good concordance, there was dosimetric variation noted, which could be clinically significant.

Patients' and clinicians' preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial.

BACKGROUND: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer. METHODS: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%. RESULTS: Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians' preferences varied less (IQR 0.5-1.5 years vs 0.4-2 years, P=0.0007; 5-10% vs 1-13%, P=0.004). Patients' preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients' or clinicians' preferences. CONCLUSIONS: Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers.

Detection of Local Cancer Recurrence After Stereotactic Ablative Radiation Therapy for Lung Cancer: Physician Performance Versus Radiomic Assessment.

PURPOSE: Stereotactic ablative radiation therapy (SABR) is a guideline-specified treatment option for early-stage lung cancer. However, significant posttreatment fibrosis can occur and obfuscate the detection of local recurrence. The goal of this study was to assess physician ability to detect timely local recurrence and to compare physician performance with a radiomics tool. METHODS AND MATERIALS: Posttreatment computed tomography (CT) scans (n=182) from 45 patients treated with SABR (15 with local recurrence matched to 30 with no local recurrence) were used to measure physician and radiomic performance in assessing response. Scans were individually scored by 3 thoracic radiation oncologists and 3 thoracic radiologists, all of whom were blinded to clinical outcomes. Radiomic features were extracted from the same images. Performances of the physician assessors and the radiomics signature were compared. RESULTS: When taking into account all CT scans during the whole follow-up period, median sensitivity for physician assessment of local recurrence was 83% (range, 67%-100%), and specificity was 75% (range, 67%-87%), with only moderate interobserver agreement (κ = 0.54) and a median time to detection of recurrence of 15.5 months. When determining the early prediction of recurrence within <6 months after SABR, physicians assessed the majority of images as benign injury/no recurrence, with a mean error of 35%, false positive rate (FPR) of 1%, and false negative rate (FNR) of 99%. At the same time point, a radiomic signature consisting of 5 image-appearance features demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.85, classification error of 24%, FPR of 24%, and FNR of 23%. CONCLUSIONS: These results suggest that radiomics can detect early changes associated with local recurrence that are not typically considered by physicians. This decision support system could potentially allow for early salvage therapy of patients with local recurrence after SABR.

Incidental radiation to uninvolved internal mammary lymph nodes in breast cancer.

Routine treatment of clinically uninvolved internal mammary nodes in breast cancer patients requiring post-mastectomy radiation therapy is controversial. The purpose of this study was to measure the incidental radiation dose to the internal mammary lymph nodes not included in the planning target volume (PTV) in women with breast cancer receiving post-mastectomy radiation therapy. This retrospective protocol utilized CT-based 3D conformal treatment plans. Fifty consecutive patients were included in the analysis: 25 left breast and 25 right breast patients. 3D conformal treatment plans chest wall tangent fields and matched supraclavicular were used. All plans were prescribed to a total dose of 50 Gy in 25 fractions to the chest wall and 46 Gy in 23 fractions to the supraclavicular field. The internal mammary node chain was intentionally not included in the target volume. For purposes of this study, internal mammary vessels were contoured following the Radiation Therapy Oncologist Group atlas with a 7-mm PTV expansion, utilizing original CT simulation images. The internal mammary nodes were contoured in between the first 3 and first 5 intercostal spaces for comparison. Percent volume of internal mammary node PTV receiving 95 % of the prescribed dose (47.5 Gy) with 7-mm expansion and first 5 intercostal spaces for all patients was 25.2 % (range 0.04-97.6 %, standard deviation (SD) 23.5). The mean internal mammary node dose for all patients was 24.98 Gy (range 3.54-55.93 Gy, SD 16). Results of this study suggest the incidental dose to the internal mammary nodes does not achieve clinically significant therapeutic levels in post-mastectomy breast cancer patients treated with standard 3D conformal radiation therapy chest wall irradiation. If risk factors for microscopic involvement are present, internal mammary nodes must be specifically included in target volumes in order to be adequately treated.

Impact of target volume segmentation accuracy and variability on treatment planning for 4D-CT-based non-small cell lung cancer radiotherapy.

BACKGROUND: Accurate target volume segmentation is crucial for success in image-guided radiotherapy. However, variability in anatomical segmentation is one of the most significant contributors to uncertainty in radiotherapy treatment planning. This is especially true for lung cancer where target volumes are subject to varying magnitudes of respiratory motion. MATERIAL AND METHODS: This study aims to analyze multiple observer target volume segmentations and subsequent intensity-modulated radiotherapy (IMRT) treatment plans defined by those segmentations against a reference standard for lung cancer patients imaged with four-dimensional computed tomography (4D-CT). Target volume segmentations of 10 patients were performed manually by six physicians, allowing for the calculation of ground truth estimate segmentations via the simultaneous truth and performance level estimation (STAPLE) algorithm. Segmentation variability was assessed in terms of distance- and volume-based metrics. Treatment plans defined by these segmentations were then subject to dosimetric evaluation consisting of both physical and radiobiological analysis of optimized 3D dose distributions. RESULTS: Significant differences were noticed amongst observers in comparison to STAPLE segmentations and this variability directly extended into the treatment planning stages in the context of all dosimetric parameters used in this study. Mean primary tumor control probability (TCP) ranged from (22.6±11.9)% to (33.7±0.6)%, with standard deviation ranging from 0.5% to 11.9%. However, mean normal tissue complication probabilities (NTCP) based on treatment plans for each physician-derived target volume well as the NTCP derived from STAPLE-based treatment plans demonstrated no discernible trends and variability appeared to be patient-specific. This type of variability demonstrated the large-scale impact that target volume segmentation uncertainty can play in IMRT treatment planning. CONCLUSIONS: Significant target volume segmentation and dosimetric variability exists in IMRT treatment planning amongst experts in the presence of a reference standard for 4D-CT-based lung cancer radiotherapy. Future work is needed to mitigate this uncertainty and ensure highly accurate and effective radiotherapy for lung cancer patients.