Publications by authors named "Daniele Regge"

114 Publications

An external validation of the Candiolo nomogram in a cohort of prostate cancer patients treated by external-beam radiotherapy.

Radiat Oncol 2021 May 5;16(1):85. Epub 2021 May 5.

Department of Radiation Oncology, University of Torino, Città della Salute e della Scienza Hospital, Turin, Italy.

Background: the aim of this study is to perform an external validation for the Candiolo nomogram, a predictive algorithm of biochemical and clinical recurrences in prostate cancer patients treated by radical Radiotherapy, published in 2016 on the journal "Radiation Oncology".

Methods: 561 patients, treated by Radiotherapy with curative intent between 2003 and 2012, were classified according to the five risk-classes of the Candiolo nomogram and the three risk-classes of the D'Amico classification for comparison. Patients were treated with a mean prostatic dose of 77.7 Gy and a combined treatment with Androgen-Deprivation-Therapy in 76% of cases. The end-points of the study were biochemical-progression-free-survival (bPFS) and clinical-Progression-Free-Survival (cPFS). With a median follow-up of 50 months, 56 patients (10%) had a biochemical relapse, and 30 patients (5.4%) a clinical progression. The cases were divided according to D'Amico in low-risk 21%, intermediate 40%, high-risk 39%; according to Candiolo very-low-risk 24%, low 37%, intermediate 24%, high 10%, very-high-risk 5%. Statistically, the Kaplan-Meier survival curves were processed and compared using Log-Rank tests and Harrell-C concordance index.

Results: The 5-year bPFS for the Candiolo risk-classes range between 98 and 38%, and the 5-year cPFS between 98 and 50% for very-low and very-high-risk, respectively. The Candiolo nomogram is highly significant for the stratification of both bPFS and cPFS (P < 0.0001), as well as the D'Amico classification (P = 0.004 and P = 0.001, respectively). For the Candiolo nomogram, the C indexes for bPFS and cPFS are 75 and 80%, respectively, while for D'Amico classification they are 64 and 69%, respectively. The Candiolo nomogram can identify a greater number of patients with low and very-low-risk prostate cancer (61% versus 21% according to D'Amico) and it better picks out patients with high and very-high-risk of recurrence, equal to only 15% of the total cases but subject to 48% (27/56) of biochemical relapses and 63% (19/30) of clinical progressions.

Conclusions: the external validation of the Candiolo nomogram was overall successful with C indexes approximately 10% higher than the D'Amico control classification for bPFS and cPFS. Therefore, its clinical use is justified in prostate cancer patients before radical Radiotherapy. Trial registration Retrospectively registered.
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http://dx.doi.org/10.1186/s13014-021-01814-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097839PMC
May 2021

Structured Reporting of Rectal Cancer Staging and Restaging: A Consensus Proposal.

Cancers (Basel) 2021 Apr 28;13(9). Epub 2021 Apr 28.

Division of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Background: Structured reporting (SR) in oncologic imaging is becoming necessary and has recently been recognized by major scientific societies. The aim of this study was to build MRI-based structured reports for rectal cancer (RC) staging and restaging in order to provide clinicians all critical tumor information.

Materials And Methods: A panel of radiologist experts in abdominal imaging, called the members of the Italian Society of Medical and Interventional Radiology, was established. The modified Delphi process was used to build the SR and to assess the level of agreement in all sections. The Cronbach's alpha (Cα) correlation coefficient was used to assess the internal consistency of each section and to measure the quality analysis according to the average inter-item correlation. The intraclass correlation coefficient (ICC) was also evaluated.

Results: After the second Delphi round of the SR RC staging, the panelists' single scores and sum of scores were 3.8 (range 2-4) and 169, and the SR RC restaging panelists' single scores and sum of scores were 3.7 (range 2-4) and 148, respectively. The Cα correlation coefficient was 0.79 for SR staging and 0.81 for SR restaging. The ICCs for the SR RC staging and restaging were 0.78 ( < 0.01) and 0.82 ( < 0.01), respectively. The final SR version was built and included 53 items for RC staging and 50 items for RC restaging.

Conclusions: The final version of the structured reports of MRI-based RC staging and restaging should be a helpful and promising tool for clinicians in managing cancer patients properly. Structured reports collect all Patient Clinical Data, Clinical Evaluations and relevant key findings of Rectal Cancer, both in staging and restaging, and can facilitate clinical decision-making.
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http://dx.doi.org/10.3390/cancers13092135DOI Listing
April 2021

Radiomics and Magnetic Resonance Imaging of Rectal Cancer: From Engineering to Clinical Practice.

Diagnostics (Basel) 2021 Apr 23;11(5). Epub 2021 Apr 23.

Diagnostic and Interventional Radiology, Department of Translational Research, University of Pisa, 56126 Pisa, Italy.

While cross-sectional imaging has seen continuous progress and plays an undiscussed pivotal role in the diagnostic management and treatment planning of patients with rectal cancer, a largely unmet need remains for improved staging accuracy, assessment of treatment response and prediction of individual patient outcome. Moreover, the increasing availability of target therapies has called for developing reliable diagnostic tools for identifying potential responders and optimizing overall treatment strategy on a personalized basis. Radiomics has emerged as a promising, still fully evolving research topic, which could harness the power of modern computer technology to generate quantitative information from imaging datasets based on advanced data-driven biomathematical models, potentially providing an added value to conventional imaging for improved patient management. The present study aimed to illustrate the contribution that current radiomics methods applied to magnetic resonance imaging can offer to managing patients with rectal cancer.
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http://dx.doi.org/10.3390/diagnostics11050756DOI Listing
April 2021

Diagnostic Accuracy of Single-plane Biparametric and Multiparametric Magnetic Resonance Imaging in Prostate Cancer: A Randomized Noninferiority Trial in Biopsy-naïve Men.

Eur Urol Oncol 2021 Apr 20. Epub 2021 Apr 20.

Department of Urology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

Background: Urological guidelines recommend multiparametric magnetic resonance imaging (mpMRI) in men with a suspicion of prostate cancer (PCa). The resulting increase in MRI demand might place health care systems under substantial stress.

Objective: To determine whether single-plane biparametric MRI (fast MRI) workup could represent an alternative to mpMRI in the detection of clinically significant (cs) PCa.

Design, Setting, And Participants: Between April 2018 and February 2020, 311 biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination were randomly assigned to 1.5-T fast MRI (n = 213) or mpMRI (n = 98).

Intervention: All MRI examinations were classified according to Prostate Imaging-Reporting and Data System (PI-RADS) version 2. Men scored PI-RADS 1-2 underwent 12-core standard biopsy (SBx) and those with PI-RADS 4-5 on fast MRI or PI-RADS 3-5 on mpMRI underwent targeted biopsy in combination with SBx. Equivocal cases on fast MRI (PI-RADS 3) underwent mpMRI and then biopsy according to the findings.

Outcome Measurements And Statistical Analysis: The primary outcome was to compare the detection rate of csPCa in both study arms, setting a 10% difference for noninferiority. The secondary outcome was to assess the role of prostate-specific antigen density (PSAD) in ruling out men who could avoid biopsy among those with equivocal findings on fast MRI.

Results And Limitations: The overall MRI detection rate for csPCa was 23.5% (50/213; 95% confidence interval [CI] 18.0-29.8%) with fast MRI and 32.7% (32/98; 95% CI 23.6-42.9%) with mpMRI (difference 9.2%; p = 0.09). The reproducibility of the study could have been affected by its single-center nature.

Conclusions: Fast MRI followed by mpMRI in equivocal cases is not inferior to mpMRI in the detection of csPCa among biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination. These findings could pave the way to broader use of MRI for PCa diagnosis.

Patient Summary: A faster MRI (magnetic resonance imaging) protocol with no contrast agent and fewer scan sequences for examination of the prostate is not inferior to the typical MRI approach in the detection of clinically significant prostate cancer. If our findings are confirmed in other studies, fast MRI could represent a time-saving and less invasive examination for men with suspicion of prostate cancer. This trial is registered at ClinicalTrials.gov as NCT03693703.
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http://dx.doi.org/10.1016/j.euo.2021.03.007DOI Listing
April 2021

Assessment of morphological CT imaging features for the prediction of risk stratification, mutations, and prognosis of gastrointestinal stromal tumors.

Eur Radiol 2021 Apr 21. Epub 2021 Apr 21.

Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, 90127, Palermo, Italy.

Objectives: To investigate the correlation between CT imaging features and risk stratification of gastrointestinal stromal tumors (GISTs), prediction of mutation status, and prognosis.

Methods: This retrospective dual-institution study included patients with pathologically proven GISTs meeting the following criteria: (i) preoperative contrast-enhanced CT performed between 2008 and 2019; (ii) no treatments before imaging; (iii) available pathological analysis. Tumor risk stratification was determined according to the National Institutes of Health (NIH) 2008 criteria. Two readers evaluated the CT features, including enhancement patterns and tumor characteristics in a blinded fashion. The differences in distribution of CT features were assessed using univariate and multivariate analyses. Survival analyses were performed by using the Cox proportional hazard model, Kaplan-Meier method, and log-rank test.

Results: The final population included 88 patients (59 men and 29 women, mean age 60.5 ± 11.1 years) with 45 high-risk and 43 low-to-intermediate-risk GISTs (median size 6.3 cm). At multivariate analysis, lesion size ≥ 5 cm (OR: 10.52, p = 0.009) and enlarged feeding vessels (OR: 12.08, p = 0.040) were independently associated with the high-risk GISTs. Hyperenhancement was significantly more frequent in PDGFRα-mutated/wild-type GISTs compared to GISTs with KIT mutations (59.3% vs 23.0%, p = 0.004). Ill-defined margins were associated with shorter progression-free survival (HR 9.66) at multivariate analysis, while ill-defined margins and hemorrhage remained independently associated with shorter overall survival (HR 44.41 and HR 30.22). Inter-reader agreement ranged from fair to almost perfect (k: 0.32-0.93).

Conclusions: Morphologic contrast-enhanced CT features are significantly different depending on the risk status or mutations and may help to predict prognosis.

Key Points: • Lesions size ≥ 5 cm (OR: 10.52, p = 0.009) and enlarged feeding vessels (OR: 12.08, p = 0.040) are independent predictors of high-risk GISTs. • PDGFRα-mutated/wild-type GISTs demonstrate more frequently hyperenhancement compared to GISTs with KIT mutations (59.3% vs 23.0%, p = 0.004). • Ill-defined margins (hazard ratio 9.66) were associated with shorter progression-free survival at multivariate analysis, while ill-defined margins (hazard ratio 44.41) and intralesional hemorrhage (hazard ratio 30.22) were independently associated with shorter overall survival.
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http://dx.doi.org/10.1007/s00330-021-07961-3DOI Listing
April 2021

Impact of inter-reader contouring variability on textural radiomics of colorectal liver metastases.

Eur Radiol Exp 2020 11 10;4(1):62. Epub 2020 Nov 10.

Department of Radiology, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy.

Background: Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic features (RFs).

Methods: After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI.

Results: The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78-0.89) and Hausdorff distance (0.21 mm, 0.14-0.31 mm). Comparing RF values, MRC ranged 0-752% for 2D and 0-1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability.

Conclusions: A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.
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http://dx.doi.org/10.1186/s41747-020-00189-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652946PMC
November 2020

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

Endoscopy 2020 12 26;52(12):1127-1141. Epub 2020 Oct 26.

Radiology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.

1: ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia.Strong recommendation, high quality evidence.ESGE/ESGAR do not recommend barium enema in this setting.Strong recommendation, high quality evidence. 2: ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors.Strong recommendation, low quality evidence.ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete.Weak recommendation, low quality evidence. 3: When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms.Strong recommendation, high quality evidence.Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation.Very low quality evidence.ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms.Strong recommendation, high quality evidence.In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms.Weak recommendation, low quality evidence. 4: Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors.Strong recommendation, high quality evidence.ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer.Weak recommendation, low quality evidence. 5: ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs.Strong recommendation, moderate quality evidence.ESGE/ESGAR also suggest the use of CCE in this setting based on availability.Weak recommendation, moderate quality evidence. 6: ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasibleWeak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in this setting.Very low quality evidence. 7: ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible.Weak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in post-polypectomy surveillance.Very low quality evidence. 8: ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation.Strong recommendation, low quality evidence. 9: ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥ 6 mm detected at CTC or CCE.Follow-up CTC may be clinically considered for 6 - 9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia.Strong recommendation, moderate quality evidence.
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http://dx.doi.org/10.1055/a-1258-4819DOI Listing
December 2020

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

Eur Radiol 2021 May;31(5):2967-2982

Radiology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.

Main Recommendations: 1. ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. Strong recommendation, high quality evidence. ESGE/ESGAR do not recommend barium enema in this setting. Strong recommendation, high quality evidence.2. ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors. Strong recommendation, low quality evidence. ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete. Weak recommendation, low quality evidence.3. When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms. Strong recommendation, high quality evidence. Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation. Very low quality evidence. ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms. Strong recommendation, high quality evidence. In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms. Weak recommendation, low quality evidence.4. Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors. Strong recommendation, high quality evidence. ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer. Weak recommendation, low quality evidence.5. ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs. Strong recommendation, moderate quality evidence. ESGE/ESGAR also suggest the use of CCE in this setting based on availability. Weak recommendation, moderate quality evidence.6. ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in this setting. Very low quality evidence.7. ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in post-polypectomy surveillance. Very low quality evidence.8. ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation. Strong recommendation, low quality evidence.9. ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥6 mm detected at CTC or CCE. Follow-up CTC may be clinically considered for 6-9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia. Strong recommendation, moderate quality evidence. Source and scope This is an update of the 2014-15 Guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of imaging alternatives to standard colonoscopy. A targeted literature search was performed to evaluate the evidence supporting the use of computed tomographic colonography (CTC) or colon capsule endoscopy (CCE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.
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http://dx.doi.org/10.1007/s00330-020-07413-4DOI Listing
May 2021

A Convolutional Neural Network based system for Colorectal cancer segmentation on MRI images.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1675-1678

The aim of the study is to present a new Convolutional Neural Network (CNN) based system for the automatic segmentation of the colorectal cancer. The algorithm implemented consists of several steps: a pre-processing to normalize and highlights the tumoral area, the classification based on CNNs, and a post-processing aimed at reducing false positive elements. The classification is performed using three CNNs: each of them classifies the same regions of interest acquired from three different MR sequences. The final segmentation mask is obtained by a majority voting. Performances were evaluated using a semi-automatic segmentation revised by an experienced radiologist as reference standard. The system obtained Dice Similarity Coefficient (DSC) of 0.60, Precision (Pr) of 0.76 and Recall (Re) of 0.55 on the testing set. After applying the leave-one-out validation, we obtained a median DSC=0.58, Pr=0.74, Re=0.54. The promising results obtained by this system, if validated on a larger dataset, could strongly improve personalized medicine.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175804DOI Listing
July 2020

An innovative radiomics approach to predict response to chemotherapy of liver metastases based on CT images.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1339-1342

Liver metastases (mts) from colorectal cancer (CRC) can have different responses to chemotherapy in the same patient. The aim of this study is to develop and validate a machine learning algorithm to predict response of individual liver mts. 22 radiomic features (RF) were computed on pretreatment portal CT scans following a manual segmentation of mts. RFs were extracted from 7x7 Region of Interests (ROIs) that moved across the image by step of 2 pixels. Liver mts were classified as non-responder (R-) if their largest diameter increased more than 3 mm after 3 months of treatment and responder (R+), otherwise. Features selection (FS) was performed by a genetic algorithm and classification by a Support Vector Machine (SVM) classifier. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values were evaluated for all lesions in the training and validation sets, separately. On the training set, we obtained sensitivity of 86%, specificity of 67%, PPV of 89% and NPV of 61%, while, on the validation set, we reached a sensitivity of 73%, specificity of 47%, PPV of 64% and NPV of 57%. Specificity was biased by the low number of R- lesions on the validation set. The promising results obtained in the validation dataset should be extended to a larger cohort of patient to further validate our method.Clinical Relevance- to personalize treatment of patients with metastastic colorectal cancer, based on the likelihood of response to chemotherapy of each liver metastasis.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176627DOI Listing
July 2020

Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial.

ESMO Open 2020 09;5(5):e000911

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano (La Statale), Milano, Italy. Electronic address:

Background: HER2 is a therapeutic target for metastatic colorectal cancer (mCRC), as demonstrated in the pivotal HERACLES-A (HER2 Amplification for Colo-rectaL cancer Enhanced Stratification) trial with trastuzumab and lapatinib. The aim of HERACLES-B trial is to assess the efficacy of the combination of pertuzumab and trastuzumab-emtansine (T-DM1) in this setting.

Methods: HERACLES-B was a single-arm, phase II trial, in patients with histologically confirmed wild-type and HER2+ mCRC refractory to standard treatments. HER2 positivity was assessed by immunohistochemistry and in situ hybridisation according to HERACLES criteria. Patients were treated with pertuzumab (840 mg intravenous load followed by 420 mg intravenous every 3 weeks) and T-DM1 (3.6 mg/kg every 3 weeks) until disease progression or toxicity. Primary and secondary end points were objective response rate (ORR) and progression-free survival (PFS). With a Fleming/Hern design (H0=ORR 10%; α=0.05; power=0.85), 7/30 responses were required to demonstrate an ORR ≥30% (H1).

Results: Thirty-one patients, 48% with ≥4 lines of previous therapies, were treated and evaluable. ORR was 9.7% (95% CI: 0 to 28) and stable disease (SD) 67.7% (95% CI: 50 to 85). OR/SD ≥4 months was associated with higher HER2 immunohistochemistry score (3+ vs 2+) (p = 0.03). Median PFS was 4.1 months (95% CI: 3.6 to 5.9). Drug-related grade (G) 3 adverse events were observed in two patients (thrombocytopaenia); G≤2 AE in 84% of cycles (n = 296), mainly nausea and fatigue.

Conclusions: HERACLES-B trial did not reach its primary end point of ORR; however, based on high disease control, PFS similar to other anti-HER2 regimens, and low toxicity, pertuzumab in combination with T-DM1 can be considered for HER2+mCRC as a potential therapeutic resource.

Trial Registration Number: 2012-002128-33 and NCT03225937.
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http://dx.doi.org/10.1136/esmoopen-2020-000911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523198PMC
September 2020

Long-term Clinical Outcome of Trastuzumab and Lapatinib for HER2-positive Metastatic Colorectal Cancer.

Clin Colorectal Cancer 2020 12 27;19(4):256-262.e2. Epub 2020 Jun 27.

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milan, Italy. Electronic address:

Background: ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences.

Patients And Methods: Patients had histologically confirmed KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive mCRC. HER2 positivity was assessed by immunohistochemistry and in situ hybridization HERACLES diagnostic criteria. Patients were treated with intravenous trastuzumab 4 mg/kg loading dose, then 2 mg/kg once per week, and oral lapatinib 1000 mg per day until disease progression or toxicity. Patients who presented with symptoms or signs of CNS disease received brain computed tomography scan or magnetic resonance imaging.

Results: A total of 35 patients received trastuzumab and lapatinib and 32 were evaluable for response. One patient (3%) achieved complete response (CR), 8 (25%) partial response, and 13 (41%) stable disease. Therefore, response rate was 28%. Median progression-free survival was 4.7 months (95% confidence interval [CI] 3.7-6.1). Median overall survival was 10.0 months (95% CI 7.9-15.8). One patient achieved sustained CR still maintained at 7 years of follow-up. Progression in the central nervous system (CNS) occurred in 6 (19%) of 32 patients.

Conclusions: Long-term (6.7 years) follow-up analysis of HERACLES-A supports using of trastuzumab and lapatinib as treatment reference for KRAS wild-type, chemorefractory HER2-positive mCRC. In this subset of patients, prolongation of survival is accompanied by CNS recurrences that will require diagnostic and therapeutic attention in future studies. Clinicaltrials. Gov identifier: NCT 03225937.
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http://dx.doi.org/10.1016/j.clcc.2020.06.009DOI Listing
December 2020

Radiomics predicts response of individual HER2-amplified colorectal cancer liver metastases in patients treated with HER2-targeted therapy.

Int J Cancer 2020 12 14;147(11):3215-3223. Epub 2020 Sep 14.

Radiology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.

The aim of our study was to develop and validate a machine learning algorithm to predict response of individual HER2-amplified colorectal cancer liver metastases (lmCRC) undergoing dual HER2-targeted therapy. Twenty-four radiomics features were extracted after 3D manual segmentation of 141 lmCRC on pretreatment portal CT scans of a cohort including 38 HER2-amplified patients; feature selection was then performed using genetic algorithms. lmCRC were classified as nonresponders (R-), if their largest diameter increased more than 10% at a CT scan performed after 3 months of treatment, responders (R+) otherwise. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values in correctly classifying individual lesion and overall patient response were assessed on a training dataset and then validated on a second dataset using a Gaussian naïve Bayesian classifier. Per-lesion sensitivity, specificity, NPV and PPV were 89%, 85%, 93%, 78% and 90%, 42%, 73%, 71% respectively in the testing and validation datasets. Per-patient sensitivity and specificity were 92% and 86%. Heterogeneous response was observed in 9 of 38 patients (24%). Five of nine patients were carriers of nonresponder lesions correctly classified as such by our radiomics signature, including four of seven harboring only one nonresponder lesion. The developed method has been proven effective in predicting behavior of individual metastases to targeted treatment in a cohort of HER2 amplified patients. The model accurately detects responder lesions and identifies nonresponder lesions in patients with heterogeneous response, potentially paving the way to multimodal treatment in selected patients. Further validation will be needed to confirm our findings.
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http://dx.doi.org/10.1002/ijc.33271DOI Listing
December 2020

Reoperation rate after breast conserving surgery as quality indicator in breast cancer treatment: A reappraisal.

Breast 2020 Oct 13;53:181-188. Epub 2020 Aug 13.

Gynecological Oncology Unit, Candiolo Cancer Institute, FPO - IRCCS, Strada Provinciale 142 Km 3.95, 10060, Candiolo, Italy. Electronic address:

Aim: To analyse the role of repeated breast surgery (RBS) after breast conserving surgery (BCS) as a quality indicator in a consecutive series of breast cancer patients.

Methods: Data from 1233 breast cancer patients submitted to BCS from 2015 to 2019 were reviewed. The influence of several variables on RBS rate (182/1232; 14.8%) was examined. Univariate and multivariate analyses were conducted to look for significant associations with the risk of RBS.

Results: Surgical workload, BCS rate and clinicopathological variables were consistent over the study period, while RBS rate decreased after the introduction of shaving of cavity margins (from 17.9% to 9.5%). Tumor persistence at RBS was higher for mastectomy vs. re-excision (87.3% vs. 37.8%; p = 0.05), inconclusive vs. positive diagnostic biopsy (48.2% vs. 69.4%; p = 0.003), ductal carcinoma in situ vs. invasive carcinoma (69.0% vs. 51.3%; p = 0.046) and lower after neoadjuvant therapy (14.3% vs. 57.8%; p = 0.044). Several clinicopathological variables were associated with the risk of RBS, but only multifocality [Odds Ratio (OR): 1.8; p = 0.009], microcalcifications (OR: 2.0, p = 0.000), neoadjuvant therapy (OR: 0.4; p = 0.014), pathological intraoperative assessment (OR: 0.6; p = 0.010) and shaving of cavity margins (OR: 0.3; p = 0.000) retained independent value at multivariate analysis.

Conclusions: RBS rate can be reduced by shaving of cavity margins. Current standards for RBS should not be made more stringent due to the existence of non-actionable risk factors. The value of RBS as a quality indicator should be scrutinzed.
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http://dx.doi.org/10.1016/j.breast.2020.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451417PMC
October 2020

Involvement of radiologists in oncologic multidisciplinary team meetings: an international survey by the European Society of Oncologic Imaging.

Eur Radiol 2021 Feb 24;31(2):983-991. Epub 2020 Aug 24.

Department of Radiological Sciences, Oncological and Pathological Sciences, University of Rome "Sapienza", Sant'Andrea University Hospital, Rome, Italy.

Objectives: Multidisciplinary tumour boards (MTBs) play an increasingly important role in managing cancer patients from diagnosis to treatment. However, many problems arise around the organisation of MTBs, both in terms of organisation-administration and time management. In this context, the European Society of Oncologic Imaging (ESOI) conducted a survey among its members, aimed at assessing the quality and amount of involvement of radiologists in MTBs, their role in it and related issues.

Methods: All members were invited to fill in a questionnaire consisting of 15 questions with both open and multiple-choice answers. Simple descriptive analyses and graphs were performed.

Results: A total of 292 ESOI members in full standing for the year 2018 joined the survey. Most respondents (89%) declared to attend MT-Bs, but only 114 respondents (43.9%) review over 70% of exams prior to MTB meetings, mainly due to lack of time due to a busy schedule for imaging and reporting (46.6%). Perceived benefits (i.e. surgical and histological feedback (86.9%), improved knowledge of cancer treatment (82.7%) and better interaction between radiologists and referring clinicians for discussing rare cases (56.9%)) and issues (i.e. attending MTB meetings during regular working hours (71.9%) and lack of accreditation with continuing medical education (CME) (85%)) are reported.

Conclusions: Despite the value and benefits of radiologists' participation in MTBs, issues like improper preparation due to a busy schedule and no counterpart in CME accreditation require efforts to improve the role of radiologists for a better patient care.

Key Points: • Most radiologists attend multidisciplinary tumour boards, but less than half of them review images in advance, mostly due to time constraints. • Feedback about radiological diagnoses, improved knowledge of cancer treatment and interaction with referring clinicians are perceived as major benefits. • Concerns were expressed about scheduling multidisciplinary tumour boards during regular working hours and lack of accreditation with continuing medical education.
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http://dx.doi.org/10.1007/s00330-020-07178-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813742PMC
February 2021

Standardization of CT radiomics features for multi-center analysis: impact of software settings and parameters.

Phys Med Biol 2020 09 29;65(19):195012. Epub 2020 Sep 29.

Department of Radiology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. Department of Surgical Sciences, University of Turin, Turin, Italy.

The aim of this multicentric study is an inter-center benchmarking, to assess how different set tools applied to the same radiomics workflow affected the radiomics features (RFs) values. This topic is of key importance to start collaboration between different centers and to bring radiomic studies from benchmark to bedside. A per-lesion analysis was performed on 56 metastases (mts) selected from 14 patients. A single radiologist performed the segmentation of all mts, and RFs were extracted from the same segmentation of each mts, using two different software and file formats. Potential sources of discrepancies were evaluated. The intraclass correlation coefficient was used to describe how strongly the same radiomic measurements calculated in the two different centers resemble each other. Moreover, means of the relative changes of each RF were calculated, compared and gradually reduced. We showed that, after matching all formulas, discrepancies in RFs calculation between two centers ranged from 1% to 277%. Therefore, we evaluated other sources of variability using a stepwise approach, which led us to reduce the inter-center discrepancies to 0% for 22/25 RFs and below 2% for 3 RFs out of 25. In this study we demonstrated that different radiomic applications and masks formats might strongly impact the computation of some RFs. Therefore, when dealing with multi-center studies it is mandatory to adopt all strategies that can help in limiting the differences, thus keeping in mind the feasibility of these strategies in large cohort studies.
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http://dx.doi.org/10.1088/1361-6560/ab9f61DOI Listing
September 2020

Artificial intelligence: radiologists' expectations and opinions gleaned from a nationwide online survey.

Radiol Med 2021 Jan 29;126(1):63-71. Epub 2020 Apr 29.

Department of Precision Medicine, University of Campania, Naples, Italy.

Purpose: To report the results of a nationwide online survey on artificial intelligence (AI) among radiologist members of the Italian Society of Medical and Interventional Radiology (SIRM).

Methods And Materials: All members were invited to the survey as an initiative by the Imaging Informatics Chapter of SIRM. The survey consisted of 13 questions about the participants' demographic information, perceived advantages and issues related to AI implementation in radiological practice, and their overall opinion about AI.

Results: In total, 1032 radiologists (equaling 9.5% of active SIRM members for the year 2019) joined the survey. Perceived AI advantages included a lower diagnostic error rate (750/1027, 73.0%) and optimization of radiologists' work (697/1027, 67.9%). The risk of a poorer professional reputation of radiologists compared with non-radiologists (617/1024, 60.3%), and increased costs and workload due to AI system maintenance and data analysis (399/1024, 39.0%) were seen as potential issues. Most radiologists stated that specific policies should regulate the use of AI (933/1032, 90.4%) and were not afraid of losing their job due to it (917/1032, 88.9%). Overall, 77.0% of respondents (794/1032) were favorable to the adoption of AI, whereas 18.0% (186/1032) were uncertain and 5.0% (52/1032) were unfavorable.

Conclusions: Radiologists had a mostly positive attitude toward the implementation of AI in their working practice. They were not concerned that AI will replace them, but rather that it might diminish their professional reputation.
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http://dx.doi.org/10.1007/s11547-020-01205-yDOI Listing
January 2021

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy.

Diagnostics (Basel) 2020 Apr 13;10(4). Epub 2020 Apr 13.

Diagnostic and Interventional Radiology, Department of Translational Research, University of Pisa, Via Roma, 67, 56126 Pisa, Italy.

Immunotherapy with checkpoint inhibitors (ICIs) is becoming standard of practice for an increasing number of cancer types. ICIs enhance T-cell action against the cancer cells. By unbalancing the immune system ICIs may cause dysimmune toxicities, a series of disorders broadly defined immune-related adverse events (irAEs). IrAEs may affect any organ or apparatus and most frequently involve skin, colon, endocrine organs, liver, and lungs. Early identification and appropriate treatment of irAEs can improve patient outcome. The paper aims at reviewing mechanisms of the occurrence of irAEs, the importance of a proper diagnosis and the main pillars of therapy. To provide effective guidance to the comprehension of major irAEs imaging findings will be reviewed.
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http://dx.doi.org/10.3390/diagnostics10040216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235714PMC
April 2020

The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique.

J Transl Med 2020 02 3;18(1):54. Epub 2020 Feb 3.

Department of Medical Sciences and Infective Diseases, Unit of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100, Pavia, Italy.

Background: Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN).

Methods: We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case.

Results: In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases,  > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case.

Conclusions: Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.
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http://dx.doi.org/10.1186/s12967-020-02241-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998829PMC
February 2020

Multimodal T2w and DWI Prostate Gland Automated Registration.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:4427-4430

Multiparametric magnetic resonance imaging (mpMRI) is emerging as a promising tool in the clinical pathway of prostate cancer (PCa). The registration between a structural and a functional imaging modality, such as T2-weighted (T2w) and diffusion-weighted imaging (DWI) is fundamental in the development of a mpMRI-based computer aided diagnosis (CAD) system for PCa. Here, we propose an automated method to register the prostate gland in T2w and DWI image sequences by a landmark-based affine registration and a non-parametric diffeomorphic registration. An expert operator manually segmented the prostate gland in both modalities on a dataset of 20 patients. Target registration error and Jaccard index, which measures the overlap between masks, were evaluated pre- and post- registration resulting in an improvement of 44% and 21%, respectively. In the future, the proposed method could be useful in the framework of a CAD system for PCa detection and characterization in mpMRI.
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http://dx.doi.org/10.1109/EMBC.2019.8856467DOI Listing
July 2019

Traditional Serrated Adenomas on CT Colonography: International Multicenter Experience With This Rare Colorectal Neoplasm.

AJR Am J Roentgenol 2020 02 12;214(2):355-361. Epub 2019 Nov 12.

Department of Radiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792.

Serrated polyps include hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas (TSAs). Hyperplastic polyps and sessile serrated polyps account for approximately 99% of all serrated lesions; TSAs are rare. However, both sessile serrated polyps and TSAs are now recognized as precursor lesions to carcinogenesis, representing approximately one-fourth of all sporadic colorectal cancers. We report what is, to our knowledge, the first series describing the characteristics of CTAs on CT colonography (CTC). An international, multicenter, retrospective review of CT colonography-detected TSAs diagnosed between 2008 and 2018 was conducted. Data collected included patient demographics and data from CTC, optical colonoscopy, and pathologic analysis. A total of 67 proven TSAs in 58 patients (mean age, 67 years) were identified. The majority (66%) were located in the distal colon (descending colon, sigmoid colon, and rectum), and their mean size was 19 mm (range, 3-80 mm). Small (< 10 mm) TSAs typically had a simple sessile or pedunculated morphologic appearance, whereas large (≥ 10 mm) TSAs tended to be more lobulated and irregular, pedunculated, or carpetlike. The majority (88%) showed at least some contrast medium surface coating. We report what we believe to be the first multicenter experience describing the characteristics of TSAs on CTC. Unlike sessile serrated lesions, TSAs are more often left-sided and tend to be more lobulated and irregular. However, like sessile serrated polyps, most TSAs show contrast medium surface coating. Detection of these rare lesions on CTC is important, given their malignant potential.
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http://dx.doi.org/10.2214/AJR.19.21882DOI Listing
February 2020

Dematerialisation of patient's informed consent in radiology: insights on current status and radiologists' opinion from an Italian online survey.

Radiol Med 2019 Sep 2;124(9):846-853. Epub 2019 Apr 2.

Department of Radiology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.

Purpose: To assess the current status of patient's informed consent (PIC) management at radiological centres and the overall opinion of radiologist active members of the Italian Society of Medical Radiology (SIRM) about PIC dematerialisation through an online survey.

Methods And Materials: All members were invited to join the survey as an initiative by the Imaging Informatics Chapter of SIRM. The survey consisted of 11 multiple-choice questions about participants' demographics, current local modalities of PIC acquisition and storage, perceived advantages and disadvantages of PIC dematerialisation over conventional paper-based PIC, and overall opinion about PIC dematerialisation.

Results: A total of 1791 radiologists (amounting to 17.4% of active SIRM members for the year 2016) joined the survey. Perceived advantages of PIC dematerialisation were easier and faster PIC recovery (96.5%), safer storage and conservation (94.5%), and reduced costs (90.7%). Conversely, the need to create dedicated areas for PIC acquisition inside each radiological unit (64.0%) and to gain preliminary approval for the use of advanced digital signature tools from patients (51.8%) were seen as potential disadvantages. Overall, 94.5% of respondents had a positive opinion about PIC dematerialisation.

Conclusion: Radiologists were mostly favourable to PIC dematerialisation. However, concerns were raised that its practical implementation might face hurdles due to its complexity in current real life working conditions.
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http://dx.doi.org/10.1007/s11547-019-01033-9DOI Listing
September 2019

Radiological Wheeler staging system: a retrospective cohort analysis to improve the local staging of prostate cancer with multiparametric MRI.

Minerva Urol Nefrol 2019 Jun 17;71(3):264-272. Epub 2019 Jan 17.

Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Background: The knowledge of tumor location and extension can allow a modulated radical prostatectomy in order to minimize positive surgical margins and reduce functional morbidity after surgery in patients with prostate cancer (PCa). Multiparametric (mp) magnetic resonance imaging (MRI) could allow the assessment of tumor extension and of its relationship with external structures. Aim of this study is to propose a new radiological Wheeler (rW) staging system applied to mp-MRI, based on the pathologic staging system (pW) for the local assessment of PCa.

Methods: This retrospective single-center multi-reader study included consecutive patients with PCa and preoperative mp-MRI, who underwent non-nerve sparing radical prostatectomy. Three radiologists reported on all examinations and classified each selected lesion according to imaging criteria following rW. Whole-mount histological sections were used as the reference standard. An experienced pathologist classified the extent of prostatic capsular invasion of each PCa according to the pW. Each histological section was scanned for comparison with mp-MRI findings. The rate of PCa correctly classified by radiologists using the pW was assessed. To evaluate the accuracy of mp-MRI in the discrimination between T2 and T3 PCa, the AUC was computed.

Results: One-hundred and five patients with a total of 195 PCa foci were included in the study. 130/195 tumors with a clear overlap between mp-MRI and surgical specimens were selected. The sensitivity of the most experienced reader was lower than that of the other two readers (48.6% vs. 68.6% and 62.9%, P>0.09) while specificity and PPV were higher (95.8% vs. 79.0% and 57.9%, P<0.001; 81.0% vs. 54.6% and 35.5%, P<0.041; respectively). The AUC values for the most and the intermediate experienced readers in the detection of extracapsular extension were in the range 0.72-0.74.

Conclusions: The rW staging system has low accuracy in predicting each single pW class, while accuracy was over 80% for experienced readers in the identification of organ-confined (T2 stage class) tumors and non-organ confined cases (T3 stage class).
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http://dx.doi.org/10.23736/S0393-2249.19.03248-XDOI Listing
June 2019

Radiomics and liquid biopsy in oncology: the holons of systems medicine.

Insights Imaging 2018 Dec 14;9(6):915-924. Epub 2018 Nov 14.

Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Radiomics is a process of extraction and analysis of quantitative features from diagnostic images. Liquid biopsy is a test done on a sample of blood to look for cancer cells or for pieces of tumourigenic DNA circulating in the blood. Radiomics and liquid biopsy have great potential in oncology, since both are minimally invasive, easy to perform, and can be repeated in patient follow-up visits, enabling the extraction of valuable information regarding tumour type, aggressiveness, progression, and response to treatment. Both methods are in their infancy, with major evidence of application in lung and gastrointestinal cancer, while still undergoing evaluation in other cancer types. In this paper, the main oncologic applications of radiomics and liquid biopsy are reviewed, and a synergistic approach incorporating both tests for cancer diagnosis and follow-up is discussed within the context of systems medicine. TEACHING POINTS: • Radiomics is a process of extraction and analysis of quantitative features from diagnostic images. • Most clinical applications of radiomics are in the field of oncologic imaging. • Radiomics applies to all imaging modalities. • A cluster of radiomic features is a "radiomic signature". • Machine learning may improve the efficacy of radiomics analysis.
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http://dx.doi.org/10.1007/s13244-018-0657-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269342PMC
December 2018

Deep Learning Electronic Cleansing for Single- and Dual-Energy CT Colonography.

Radiographics 2018 Nov-Dec;38(7):2034-2050

From the 3D Imaging Research Lab, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 25 New Chardon St, Suite 400C, Boston, MA 02114 (R.T., J.J.N., N.K., T.H., H.Y.); Department of Information Science and Technology, National Institute of Technology, Oshima College, Yamaguchi, Japan (R.T.); Department of Medical Physics and Engineering, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan (J.O.); Department of Medical Physics, University of Applied Sciences Giessen, Giessen, Germany (N.K.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (S.H.K.); Department of Surgical Sciences, University of Torino, Turin, Italy (D.R.); and Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-Istituto di Ricovero e Cura a Carattere Scientifico (FPO-IRCCS), Candiolo, Turin, Italy (D.R.).

Electronic cleansing (EC) is used for computational removal of residual feces and fluid tagged with an orally administered contrast agent on CT colonographic images to improve the visibility of polyps during virtual endoscopic "fly-through" reading. A recent trend in CT colonography is to perform a low-dose CT scanning protocol with the patient having undergone reduced- or noncathartic bowel preparation. Although several EC schemes exist, they have been developed for use with cathartic bowel preparation and high-radiation-dose CT, and thus, at a low dose with noncathartic bowel preparation, they tend to generate cleansing artifacts that distract and mislead readers. Deep learning can be used for improvement of the image quality with EC at CT colonography. Deep learning EC can produce substantially fewer cleansing artifacts at dual-energy than at single-energy CT colonography, because the dual-energy information can be used to identify relevant material in the colon more precisely than is possible with the single x-ray attenuation value. Because the number of annotated training images is limited at CT colonography, transfer learning can be used for appropriate training of deep learning algorithms. The purposes of this article are to review the causes of cleansing artifacts that distract and mislead readers in conventional EC schemes, to describe the applications of deep learning and dual-energy CT colonography to EC of the colon, and to demonstrate the improvements in image quality with EC and deep learning at single-energy and dual-energy CT colonography with noncathartic bowel preparation. RSNA, 2018.
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http://dx.doi.org/10.1148/rg.2018170173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276077PMC
September 2019

Cost-effectiveness of colorectal cancer screening programmes using sigmoidoscopy and immunochemical faecal occult blood test.

J Med Screen 2019 06 4;26(2):76-83. Epub 2018 Sep 4.

1 SSD Epidemiology, screening unit - CPO, University Hospital "Città della Salute e della Scienza", Turin, Italy.

Objective: Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme.

Methods: Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed.

Results: Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10-17% CRC incidence reduction) and cost-effective vs. no screening (ICER <€1000 per life-year saved). FS and FS + FIT were the only cost-saving strategies, with FS least expensive (€15 saving per person invited). FS + FIT and FS were the only non-dominated strategies. FS + FIT were more effective and cost-effective than FS (ICER €1217 per life-year saved). The residual marginal uncertainty was mainly related to parameters inherent to FIT effectiveness and adherence.

Conclusions: Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.
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http://dx.doi.org/10.1177/0969141318789710DOI Listing
June 2019

Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer.

Cancer Cell 2018 07;34(1):148-162.e7

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan 20162, Italy.

Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients. ctDNA profiles and lesion-specific radiographic reports revealed organ- or metastasis-private evolutionary patterns. When radiologic assessments documented progressive disease in target lesions, response to HER2 blockade was retained in other metastases. Genomic and functional analyses on samples and cell models from eight metastases of a patient co-recruited to a postmortem study unveiled lesion-specific evolutionary trees and pharmacologic vulnerabilities. Lesion size and contribution of distinct metastases to plasma ctDNA were correlated.
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http://dx.doi.org/10.1016/j.ccell.2018.06.004DOI Listing
July 2018

A cloud-based computer-aided detection system improves identification of lung nodules on computed tomography scans of patients with extra-thoracic malignancies.

Eur Radiol 2019 Jan 15;29(1):144-152. Epub 2018 Jun 15.

Department of Radiology at Candiolo Cancer Institute-FPO, IRCCS, Strada Provinciale 142 km 3.95, 10060, Candiolo, Turin, Italy.

Objectives: To compare unassisted and CAD-assisted detection and time efficiency of radiologists in reporting lung nodules on CT scans taken from patients with extra-thoracic malignancies using a Cloud-based system.

Materials And Methods: Three radiologists searched for pulmonary nodules in patients with extra-thoracic malignancy who underwent CT (slice thickness/spacing 2 mm/1.7 mm) between September 2015 and March 2016. All nodules detected by unassisted reading were measured and coordinates were uploaded on a cloud-based system. CAD marks were then reviewed by the same readers using the cloud-based interface. To establish the reference standard all nodules ≥ 3 mm detected by at least one radiologist were validated by two additional experienced radiologists in consensus. Reader detection rate and reporting time with and without CAD were compared. The study was approved by the local ethics committee. All patients signed written informed consent.

Results: The series included 225 patients (age range 21-90 years, mean 62 years), including 75 patients having at least one nodule, for a total of 215 nodules. Stand-alone CAD sensitivity for lesions ≥ 3 mm was 85% (183/215, 95% CI: 82-91); mean false-positive rate per scan was 3.8. Sensitivity across readers in detecting lesions ≥ 3 mm was statistically higher using CAD: 65% (95% CI: 61-69) versus 88% (95% CI: 86-91, p<0.01). Reading time increased by 11% using CAD (296 s vs. 329 s; p<0.05).

Conclusion: In patients with extra-thoracic malignancies, CAD-assisted reading improves detection of ≥ 3-mm lung nodules on CT, slightly increasing reading time.

Key Points: • CAD-assisted reading improves the detection of lung nodules compared with unassisted reading on CT scans of patients with primary extra-thoracic tumour, slightly increasing reading time. • Cloud-based CAD systems may represent a cost-effective solution since CAD results can be reviewed while a separated cloud back-end is taking care of computations. • Early identification of lung nodules by CAD-assisted interpretation of CT scans in patients with extra-thoracic primary tumours is of paramount importance as it could anticipate surgery and extend patient life expectancy.
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http://dx.doi.org/10.1007/s00330-018-5528-6DOI Listing
January 2019

Computer-based self-training for CT colonography with and without CAD.

Eur Radiol 2018 Nov 23;28(11):4783-4791. Epub 2018 May 23.

Department of Surgical Science, University of Turin, 10124, Turin, Italy.

Objectives: To determine whether (1) computer-based self-training for CT colonography (CTC) improves interpretation performance of novice readers; (2) computer-aided detection (CAD) use during training affects learning.

Methods: Institutional review board approval and patients' informed consent were obtained for all cases included in this study. Twenty readers (17 radiology residents, 3 radiologists) with no experience in CTC interpretation were recruited in three centres. After an introductory course, readers performed a baseline assessment test (37 cases) using CAD as second reader. Then they were randomized (1:1) to perform either a computer-based self-training (150 cases verified at colonoscopy) with CAD as second reader or the same training without CAD. The same assessment test was repeated after completion of the training programs. Main outcome was per lesion sensitivity (≥ 6 mm). A generalized estimating equation model was applied to evaluate readers' performance and the impact of CAD use during training.

Results: After training, there was a significant improvement in average per lesion sensitivity in the unassisted phase, from 74% (356/480) to 83% (396/480) (p < 0.001), and in the CAD-assisted phase, from 83% (399/480) to 87% (417/480) (p = 0.021), but not in average per patient sensitivity, from 93% (390/420) to 94% (395/420) (p = 0.41), and specificity, from 81% (260/320) to 86% (276/320) (p = 0.15). No significant effect of CAD use during training was observed on per patient sensitivity and specificity, nor on per lesion sensitivity.

Conclusions: A computer-based self-training program for CTC improves readers' per lesion sensitivity. CAD as second reader does not have a significant impact on learning if used during training.

Key Points: • Computer-based self-training for CT colonography improves per lesion sensitivity of novice readers. • Self-training program does not increase per patient specificity of novice readers. • CAD used during training does not have significant impact on learning.
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http://dx.doi.org/10.1007/s00330-018-5480-5DOI Listing
November 2018