Applications of Artificial Intelligence and Radiomics in Molecular Hybrid Imaging and Theragnostics for Neuro-Endocrine Neoplasms (NENs).

Nuclear medicine has acquired a crucial role in the management of patients with neuroendocrine neoplasms (NENs) by improving the accuracy of diagnosis and staging as well as their risk stratification and personalized therapies, including radioligand therapies (RLT). Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both diagnostic and therapeutic settings by improving the prediction of the tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art AI and radiomics applications in the molecular imaging of NENs.

Helical tomotherapy and two types of volumetric modulated arc therapy: dosimetric and clinical comparison for several cancer sites.

Radiotherapy accelerators have undergone continuous technological developments. We investigated the differences between Radixact™ and VMAT treatment plans. Sixty patients were included in this study. Dosimetric comparison between the Radixact™ and VMAT plans was performed for six cancer sites: whole-brain, head and neck, lymphoma, lung, prostate, and rectum. The VMAT plans were generated with two Elekta linear accelerators (Synergy® and Versa HD™). The planning target volume (PTV) coverage, organs-at-risk dose constraints, and four dosimetric indexes were considered. The deliverability of the plans was assessed using quality assurance (gamma index evaluation) measurements; clinical judgment was included in the assessment. The mean AAPM TG218 (3%-2 mm, global normalization) gamma index values were 99.4%, 97.8%, and 96.6% for Radixact™, Versa HD™, and Synergy®, respectively. Radixact™ performed better than Versa HD™ in terms of dosimetric indexes, hippocampi D100%, spinal cord Dmax, rectum V38.4  Gy, bladder V30 Gy, and V40 Gy. Versa HD™ saved more of the (lungs-PTV) V5 Gy and (lungs-PTV) Dmean, heart Dmean, breasts V4 Gy, and bowel V45 Gy. Regarding Synergy®, the head and neck Radixact™ plan saved more of the parotid gland, oral cavity, and supraglottic larynx. From a clinical point of view, for the head and neck, prostate, and rectal sites, the Radixact™ and Versa HD™ plans were similar; Radixact™ plans were preferable for the head and neck and rectum to Synergy® plans. The quality of linac plans has improved, and differences with tomotherapy have decreased. However, tomotherapy continues to be an essential add-on in multi-machine departments.

A case report of long-term successful stereotactic arrhythmia radioablation in a cardiac contractility modulation device carrier with giant left atrium, including a detailed dosimetric analysis.

Introduction: Catheter ablation (CA) is the current standard of care for patients suffering drug-refractory monomorphic ventricular tachycardias (MMVTs). Yet, despite significant technological improvements, recurrences remain common, leading to increased morbidity and mortality. Stereotactic arrhythmia radioablation (STAR) is increasingly being adopted to overcome the limitations of conventional CA, but its safety and efficacy are still under evaluation. Case presentation: We hereby present the case of a 73-year-old patient implanted with a mitral valve prosthesis, a cardiac resynchronization therapy-defibrillator, and a cardiac contractility modulation device, who was successfully treated with STAR for recurrent drug and CA-resistant MMVT in the setting of advanced heart failure and a giant left atrium. We report a 2-year follow-up and a detailed dosimetric analysis. Conclusion: Our case report supports the early as well as the long-term efficacy of 25 Gy single-session STAR. Despite the concomitant severe heart failure, with an overall heart minus planned target volume mean dosage below 5 Gy, no major detrimental cardiac side effects were detected. To the best of our knowledge, our dosimetric analysis is the most accurate reported so far in the setting of STAR, particularly for what concerns cardiac substructures and coronary arteries. A shared dosimetric planning among centers performing STAR will be crucial in the next future to fully disclose its safety profile.

Prognostic Value of Whole-Body PET Volumetric Parameters Extracted from 68Ga-DOTATOC PET/CT in Well-Differentiated Neuroendocrine Tumors.

Our objective was to evaluate the prognostic value of somatostatin receptor tumor burden on 68Ga-DOTATOC PET/CT in patients with well-differentiated (WD) neuroendocrine tumors (NETs). Methods: We retrospectively analyzed the 68Ga-DOTATOC PET/CT scans of 84 patients with histologically confirmed WD NETs (51 grade 1, 30 grade 2, and 3 grade 3). For each PET/CT scan, all 68Ga-DOTATOC-avid lesions were independently segmented by 2 operators using a customized threshold based on the healthy liver SUVmax (LIFEx, version 5.1). Somatostatin receptor-expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE = SRETV × SUVmean) were extracted for each lesion, and then whole-body SRETV and TLSRE (SRETVwb and TLSREwb, respectively) were defined as the sum of SRETV and TLSRE, respectively, for all segmented lesions in each patient. Time to progression (TTP) was defined as the combination of disease-free survival in patients undergoing curative surgery (n = 10) and progression-free survival for patients with unresectable or metastatic disease (n = 74). TTP and overall survival were calculated by Kaplan-Meier analysis, log-rank testing, and the Cox proportional-hazards regression model. Results: After a median follow-up of 15.5 mo, disease progression was confirmed in 35 patients (41.7%) and 14 patients died. A higher SRETVwb (>39.1 cm3) and TLSREwb (>306.8 g) correlated significantly with a shorter median TTP (12 mo vs. not reached; P < 0.001). In multivariate analysis, SRETVwb (P = 0.005) was the only independent predictor of TTP regardless of histopathologic grade and TNM staging. Conclusion: According to our results, SRETVwb and TLSREwb extracted from 68Ga-DOTATOC PET/CT could predict TTP or overall survival and might have important clinical utility in the management of patients with WD NETs.

The influence of basic plan parameters on calculated small field output factors - A multicenter study.

PURPOSE: The influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study. METHODS AND MATERIALS: Three computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm2 field sizes (FSs) (normalized to 10x10 cm2 FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs. RESULTS: A total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible. CONCLUSIONS: Modern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs.

Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial.

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon's design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; ß = 0.20). A minimum of 21/39 (54%) with G0-G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as 'promising'. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0-G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy.

PURPOSE: To perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results. MATERIALS AND METHODS: A Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015-2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging. RESULTS: The Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019. CONCLUSIONS: We are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.

Diagnostic Value of Conventional PET Parameters and Radiomic Features Extracted from 18F-FDG-PET/CT for Histologic Subtype Classification and Characterization of Lung Neuroendocrine Neoplasms.

AIM: To evaluate if conventional Positron emission tomography (PET) parameters and radiomic features (RFs) extracted by 18F-FDG-PET/CT can differentiate among different histological subtypes of lung neuroendocrine neoplasms (Lu-NENs). METHODS: Forty-four naïve-treatment patients on whom 18F-FDG-PET/CT was performed for histologically confirmed Lu-NEN (n = 46) were retrospectively included. Manual segmentation was performed by two operators allowing for extraction of four conventional PET parameters (SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) and 41 RFs. Lu-NENs were classified into two groups: lung neuroendocrine tumors (Lu-NETs) vs. lung neuroendocrine carcinomas (Lu-NECs). Lu-NETs were classified according to histological subtypes (typical (TC)/atypical carcinoid (AC)), Ki67-level, and TNM staging. The least absolute shrink age and selection operator (LASSO) method was used to select the most predictive RFs for classification and Pearson correlation analysis was performed between conventional PET parameters and selected RFs. RESULTS: PET parameters, in particular, SUVmax (area under the curve (AUC) = 0.91; cut-off = 5.16) were higher in Lu-NECs vs. Lu-NETs (p < 0.001). Among RFs, HISTO_Entropy_log10 was the most predictive (AUC = 0.90), but correlated with SUVmax/SUVmean (r = 0.95/r = 0.94, respectively). No statistical differences were found between conventional PET parameters and RFs (p > 0.05) and TC vs. AC classification. Conventional PET parameters were correlated with N+ status in Lu-NETs. CONCLUSION: In our study, conventional PET parameters were able to distinguish Lu-NECs from Lu-NETs, but not TC from AC. RFs did not provide additional information.

Impact of segmentation and discretization on radiomic features in 68Ga-DOTA-TOC PET/CT images of neuroendocrine tumor.

OBJECTIVE: To identify the impact of segmentation methods and intensity discretization on radiomic features (RFs) extraction from 68Ga-DOTA-TOC PET images in patients with neuroendocrine tumors. METHODS: Forty-nine patients were retrospectively analyzed. Tumor contouring was performed manually by four different operators and with a semi-automatic edge-based segmentation (SAEB) algorithm. Three SUVmax fixed thresholds (20, 30, 40%) were applied. Fifty-one RFs were extracted applying two different intensity rescale factors for gray-level discretization: one absolute (AR60 = SUV from 0 to 60) and one relative (RR = min-max of the VOI SUV). Dice similarity coefficient (DSC) was calculated to quantify segmentation agreement between different segmentation methods. The impact of segmentation and discretization on RFs was assessed by intra-class correlation coefficients (ICC) and the coefficient of variance (COVL). The RFs' correlation with volume and SUVmax was analyzed by calculating Pearson's correlation coefficients. RESULTS: DSC mean value was 0.75 ± 0.11 (0.45-0.92) between SAEB and operators and 0.78 ± 0.09 (0.36-0.97), among the four manual segmentations. The study showed high robustness (ICC > 0.9): (a) in 64.7% of RFs for segmentation methods using AR60, improved by applying SUVmax threshold of 40% (86.5%); (b) in 50.9% of RFs for different SUVmax thresholds using AR60; and (c) in 37% of RFs for discretization settings using different segmentation methods. Several RFs were not correlated with volume and SUVmax. CONCLUSIONS: RFs robustness to manual segmentation resulted higher in NET 68Ga-DOTA-TOC images compared to 18F-FDG PET/CT images. Forty percent SUVmax thresholds yield superior RFs stability among operators, however leading to a possible loss of biological information. SAEB segmentation appears to be an optimal alternative to manual segmentation, but further validations are needed. Finally, discretization settings highly impacted on RFs robustness and should always be stated.

Role of Radiotherapy in Post-transplant Lymphoproliferative Disorders: Three Case Reports and Review of the Literature.

Post-transplant lymphoproliferative disorder (PTLD) is an aggressive malignancy that occurs in patients who have undergone solid organ transplantation or hematopoietic stem cell transplantation. It develops as the result of uncontrolled cell proliferations owing to reduced immunological surveillance. PTLD may occur with a various spectrum of clinical presentations, including both localized and extensive disease. Management can be significantly variable according both to the clinical presentation and to the histologic features. The most important systemic treatment strategies are reduction of immunosuppressive therapy, chemotherapy, anti B-cell antibodies, especially rituximab and cytokine-based therapies. The localized form of PTLD could be efficiently treated, and potentially cured, with surgery or radiotherapy (RT). Involved site RT may be a feasible effective option for the treatment of patients with PTLD, given the excellent radio-sensitivity of lymphoid disorders. In this report, we describe 3 adult patients with PTLD treated with moderate-dose RT (24-36 Gy) having a good local control with negligible toxicity. We also review the literature data on the role of radiation therapy in this particular setting.

Adoption of Expansion Margins to Reduce the Dose Received by the Coronary Arteries and the Risk of Cardiovascular Events in Lymphoma Patients.

PURPOSE: Mediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit. METHODS AND MATERIALS: Forty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (Dmax), median (Dmed), and mean (Dmean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications. RESULTS: Plan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in Dmax, Dmed, and Dmean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV. CONCLUSIONS: Integration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

PURPOSE: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. METHODS: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the ß = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. RESULTS: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design. CONCLUSION: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival.

OBJECTIVES: (1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the application of radiomics analysis of the primary lesion to identify features predictive of response to immunotherapy; (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT (N and M factors) is associated with PFS and OS. MATERIALS AND METHODS: we retrospectively analyzed clinical records of advanced NCSLC patients (stage IIIb/c or stage IV) candidate to immunotherapy who performed 18F-FDG PET/CT before treatment to stage the disease. Fifty-seven (57) patients were included in the analysis (F:M 17:40; median age = 69 years old). Notably, 38/57 of patients had adenocarcinoma (AC), 10/57 squamous cell carcinoma (SCC) and 9/57 were not otherwise specified (NOS). Overall, 47.4% patients were stage IVA, 42.1% IVB and 8.8% IIIB. Immunotherapy was performed as front-line therapy in 42/57 patients and as second line therapy after chemotherapy platinum-based in 15/57. The median follow up after starting immunotherapy was 10 months (range: 1.5-68.6). Therapy response was assessed by RECIST 1.1 criteria (CT evaluation every 4 cycles of therapy) in 48/57 patients or when not feasible by clinical and laboratory data (fast disease progression or worsening of patient clinical condition in nine patients). Radiomics analysis was performed by applying regions of interest (ROIs) of the primary tumor delineated manually by two operators and semi-automatically applying a threshold at 40% of SUVmax. RESULTS: (1.1) metabolic tumor volume (MTV) (p = 0.028) and total lesion glycolysis (TLG) (p = 0.035) were significantly associated with progressive vs. non-progressive disease status. Patients with higher values of MTV and TLG had higher probability of disease progression, compared to those patients presenting with lower values. SUVmax did not show correlation with PD status, PFS and OS. MTV (p = 0.027) and TLG (p = 0.022) also resulted in being significantly different among PR, SD and PD groups, while SUVmax was confirmed to not be associated with response to therapy (p = 0.427). (1.2) We observed the association of several radiomics features with PD status. Namely, patients with high tumor volume, TLG and heterogeneity expressed by "skewness" and "kurtosis" had a higher probability of failing immunotherapy. (1.3) M status at 18F-FDG PET/CT was significantly associated with PFS (p = 0.002) and OS (p = 0.049). No significant associations were observed for N status. CONCLUSIONS: 18F-FDG PET/CT performed before the start of immunotherapy might be an important prognostic tool able to predict the disease progression and response to immunotherapy in patients with advanced NSCLC, since MTV, TLG and radiomics features (volume and heterogeneity) are associated with disease progression.

Radiation therapy for oligometastatic oropharyngeal cancer.

At presentation, isolated metastasis from oropharyngeal squamous cell carcinoma is rare. Liver is a relatively uncommon first site of failure, especially in the absence of other distant metastases, particularly without diagnosis of lung metastases. We report on a case of HPV-related oropharyngeal squamous cell carcinoma with synchronous liver metastasis treated with radiation therapy. This condition, defined as "oligometastatic state," describes a subset of patients with limited volume metastatic disease in whom favorable outcomes were reported with the use of local ablative therapies on both the primary tumor and metastatic sites. As a definitive treatment, we offered the patient, ineligible for other therapeutic approaches, exclusive radiation treatment on the head and neck region and a stereotactic ablative approach targeted to the liver metastasis.

68Ga-DOTATOC PET/CT-Based Radiomic Analysis and PRRT Outcome: A Preliminary Evaluation Based on an Exploratory Radiomic Analysis on Two Patients.

Aim: This work aims to evaluate whether the radiomic features extracted by 68Ga-DOTATOC-PET/CT of two patients are associated with the response to peptide receptor radionuclide therapy (PRRT) in patients affected by neuroendocrine tumor (NET). Methods: This is a pilot report in two NET patients who experienced a discordant response to PRRT (responder vs. non-responder) according to RECIST1.1. The patients presented with liver metastasis from the rectum and pancreas G3-NET, respectively. Whole-body total-lesion somatostatin receptor-expression (TLSREwb-50) and somatostatin receptor-expressing tumor volume (SRETV wb-50) were obtained in pre- and post-PRRT PET/CT. Radiomic analysis was performed, extracting 38 radiomic features (RFs) from the patients' lesions. The Mann-Whitney test was used to compare RFs in the responder patient vs. the non-responder patient. Pearson correlation and principal component analysis (PCA) were used to evaluate the correlation and independence of the different RFs. Results: TLSREwb-50 and SRETVwb-50 modifications correlate with RECIST1.1 response. A total of 28 RFs extracted on pre-therapy PET/CT showed significant differences between the two patients in the Mann-Whitney test (p < 0.05). A total of seven second-order features, with poor correlation with SUVmax and PET volume, were identified by the Pearson correlation matrix. Finally, the first two PCA principal components explain 83.8% of total variance. Conclusion: TLSREwb-50 and SRETVwb-50 are parameters that might be used to predict and to assess the PET response to PRRT. RFs might have a role in defining inter-patient heterogeneity and in the prediction of therapy response. It is important to implement future studies with larger and more homogeneous patient populations to confirm the efficacy of these biomarkers.

Small field correction factors determination for several active detectors using a Monte Carlo method in the Elekta Axesse linac equipped with circular cones.

A Monte Carlo (MC) method was used to determine small field output correction factors for several active detectors (Exradin A16, Exradin A26, PTW microLion, PTW microDiamond, Exradin W1 and IBA RAZOR) for an Elekta Axesse linac equipped with circular cones. MC model of the linac was built with the GamBet software, using the Penelope code system. The dose-to-water simulation for each cone, ranging from 5 to 30 mm of diameter size, was used to calculate field factors and the results were validated together with Gafchromic EBT3 film. Output factors (OFs) were measured with the active detectors and correction factors were determined using the MC results. The MC simulations agreed with films within 1.2%. OFs measured with Exradin W1 scintillator were in agreement within 0.8% with MC simulations. The Exradin A16 and A26 microchambers under-responded for small fields relative to the MC (-13.1% and -4.6%, respectively). PTW microLion, IBA RAZOR and PTW microDiamond overestimated the output factor for the smallest field (+3.9%, +5.4 and +7.1%, respectively). The present study pointed out that it is crucial to apply the appropriate correction factors in order to provide accurate measurements in small beams geometry. The results showed that the Exradin W1 can be used for very small field dosimetry without correction factors, which shall be contrariwise employed for other detectors.

Clinical evaluation of a transmission detector system and comparison with a homogeneous 3D phantom dosimeter.

PURPOSE: To evaluate the performances of the Dolphin system for pre-treatment verification (IBA Dosimetry, Schwarzenbruck, Germany) based on transmission measurements, employing a clinical perspective. METHODS AND MATERIALS: Fifty treatment plans were verified by Dolphin and Delta4 detectors (Scandidos, Uppsala, Sweden) during the same session and subsequently by the Delta4 itself. The attenuation factor of the transmission detector (required for on-line dosimetry) was evaluated by comparing Delta4 measurements with and without Dolphin. Gamma evaluation was performed to compare the plan dose with the one delivered in case of Delta4 and Dolphin (gamma analysis within the structures). Dose-volume based parameters for PTV and OARs doses were considered for Compass calculation and Dolphin reconstruction and clinical decisions were made by two expert physicians in order to assess the "pass", "fail" or "evaluate" grade of the treatment plans. A statistical analysis was performed to investigate the eventual correlation between Delta4 gamma analysis and Dolphin clinical evaluation. RESULTS: A value of 10.7% ±â€¯0.7% was found for detector attenuation. No patients were classified as "fail" by the two instruments as well as by physicians. No correlation was found between the Delta4gamma metric and physician classification; conversely, a significant correlation was observed for Dolphin between the numbers of points with gamma ≥1 (gamma failure rate, as evaluated by the Dolphin) in the PTV area and clinical decision. CONCLUSION: The Dolphin system demonstrated to be an accurate detector for pre-treatment purposes and could be used as a clinical decision making tool for plan acceptance.

Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation.

PURPOSE: To investigate whether irradiated volume of pelvic active bone marrow (ACTBM) may predict decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation. METHODS: Forty-four patients were analyzed and pelvic active bone marrow (ACTBM) was characterized employing 18FDG-PET. Dosimetric parameters on dose-volume histograms were correlated to nadirs with generalized linear modeling. RESULTS: ACTBM mean dose was significantly correlated to white blood cell (ß = -1.338; 95%CI: -2.455/-0.221; p = 0.020), absolute neutrophil count (ß = -1.651; 95%CI: -3.284/-0.183; p = 0.048), and platelets (ß = -0.031; 95%CI: -0.057/-0.004; p = 0.024) nadirs. Other dosimetric parameters were found to be correlated (ACTBM-V10,-V20,-V30and-V40). CONCLUSIONS: 18FDG-PET is able to define active bone marrow and may predict for decreased blood cells count nadirs.

Variability of clinical target volume delineation for rectal cancer patients planned for neoadjuvant radiotherapy with the aid of the platform Anatom-e.

OBJECTIVE: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. MATERIALS AND METHODS: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). RESULTS: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58-0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67-0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85-4.78) than without (4.14; SD: ±2.97; range: 2.18-5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08-32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14-48.72). CONCLUSIONS: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols.

Evaluation of a commercial automatic treatment planning system for liver stereotactic body radiation therapy treatments.

PURPOSE: Automated treatment planning is a new frontier in radiotherapy. The Auto-Planning module of the Pinnacle3 treatment planning system (TPS) was evaluated for liver stereotactic body radiation therapy treatments. METHODS: Ten cases were included in the study. Six plans were generated for each case by four medical physics experts. The first two planned with Pinnacle TPS, both with manual module (MP) and Auto-Planning one (AP). The other two physicists generated two plans with Monaco TPS (VM). Treatment plan comparisons were then carried on the various dosimetric parameters of target and organs at risk, monitor units, number of segments, plan complexity metrics and human resource planning time. The user dependency of Auto-Planning was also tested and the plans were evaluated by a trained physician. RESULTS: Statistically significant differences (Anova test) were observed for spinal cord doses, plan average beam irregularity, number of segments, monitor units and human planning time. The Fisher-Hayter test applied to these parameters showed significant statistical differences between AP e MP for spinal cord doses and human planning time; between MP and VM for monitor units, number of segments and plan irregularity; for all those between AP and VM. The two plans created by different planners with AP were similar to each other. CONCLUSIONS: The plans created with Auto-Planning were comparable to the manually generated plans. The time saved in planning enables the planner to commit more resources to more complex cases. The independence of the planner enables to standardize plan quality.