Publications by authors named "Barbara A Jereczek-Fossa"

80 Publications

Semi-Automated Segmentation of Bone Metastases from Whole-Body MRI: Reproducibility of Apparent Diffusion Coefficient Measurements.

Diagnostics (Basel) 2021 Mar 11;11(3). Epub 2021 Mar 11.

Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy.

Using semi-automated software simplifies quantitative analysis of the visible burden of disease on whole-body MRI diffusion-weighted images. To establish the intra- and inter-observer reproducibility of apparent diffusion coefficient (ADC) measures, we retrospectively analyzed data from 20 patients with bone metastases from breast (BCa; = 10; aged 62.3 ± 14.8) or prostate cancer (PCa; = 10; aged 67.4 ± 9.0) who had undergone examinations at two timepoints, before and after hormone-therapy. Four independent observers processed all images twice, first segmenting the entire skeleton on diffusion-weighted images, and then isolating bone metastases via ADC histogram thresholding (ADC: 650-1400 µm/s). Dice Similarity, Bland-Altman method, and Intraclass Correlation Coefficient were used to assess reproducibility. Inter-observer Dice similarity was moderate (0.71) for women with BCa and poor (0.40) for men with PCa. Nonetheless, the limits of agreement of the mean ADC were just ±6% for women with BCa and ±10% for men with PCa (mean ADCs: 941 and 999 µm/s, respectively). Inter-observer Intraclass Correlation Coefficients of the ADC histogram parameters were consistently greater in women with BCa than in men with PCa. While scope remains for improving consistency of the volume segmented, the observer-dependent variability measured in this study was appropriate to distinguish the clinically meaningful changes of ADC observed in patients responding to therapy, as changes of at least 25% are of interest.
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http://dx.doi.org/10.3390/diagnostics11030499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998160PMC
March 2021

Prognostic value of the , , and mutations in oral squamous cell carcinoma: literature review.

Arch Med Sci 2021 13;17(1):207-217. Epub 2020 Nov 13.

Department of Radiotherapy, European Institute of Oncology, IRCCS, Milan, Italy.

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy. The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit α), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the , , and gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.
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http://dx.doi.org/10.5114/aoms.2020.100780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811327PMC
November 2020

Adjuvant radiotherapy in node positive prostate cancer patients: a debate still on. when, for whom?

BJU Int 2021 Apr 25;127(4):454-462. Epub 2020 Sep 25.

Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Objective: To evaluate the impact of adjuvant radiotherapy (aRT) in patients with prostate cancer (PCa) found to have pathological positive lymph nodes (pN1s) after radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) with regard to distant recurrence-free survival (RFS), according to both main tumour pathological characteristics and number of positive lymph nodes. Biochemical RFS, local RFS, overall survival (OS) and acute and late toxicity were assessed as secondary endpoints.

Patients And Methods: A retrospective cohort of 187 consecutive patients with pN1 PCa were treated with aRT at the IEO, European Institute of Oncology IRCCS, Milan, Italy. aRT on the tumour bed and pelvis was administered within 6 months of RP. Androgen deprivation therapy was administered according to the guidelines. Univariate and multivariate Cox regression analyses predicting biochemical RFS, local RFS, distant RFS and OS rates were performed to assess whether the number of pN1s represented an independent prognostic factor. The Youden index was computed to find the optimal threshold for the number of pN1s able to discriminate between patients with or without biochemical and clinical relapse.

Results: At 5 years, local RFS, distant RFS, biochemical RFS and OS were 68%, 71%, 56% and 94%, respectively. The median follow-up was 49 months. The number of pN1s was significantly associated with biochemical RFS, local RFS and distant RFS. The best threshold for discriminating between patients with or without biochemical and clinical relapse was five pN1s. In multivariate analyses, the number of pN1s was confirmed to be an independent predictor of biochemical RFS, local RFS and distant RFS, but not of OS. Multivariate analyses also showed an increased risk of biochemical relapse for increasing values of initial prostate-specific antigen and for patients with tumour vascular invasion. Local and distant RFS were also inversely correlated with significantly reduced risk for International Society of Urological Pathology grade group <3 (group 1 or 2 compared to group 3).

Conclusions: Our data confirmed the encouraging outcomes of patients with pN1 PCa treated with adjuvant treatments and the key role represented by the number of pN1s in predicting biochemical RFS, clinical RFS and distant RFS. Large prospective cohort studies and randomized clinical trials are needed to confirm these results and to identify the subgroup of patients with pN1 PCa who would most benefit from aRT.
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http://dx.doi.org/10.1111/bju.15228DOI Listing
April 2021

National societies' needs as assessed by the ESTRO National Societies Committee survey: A European perspective.

Radiother Oncol 2020 10 7;151:176-181. Epub 2020 Aug 7.

Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Milan, Italy.

Purpose: To determine how ESTRO can collaborate with Radiation Oncology National Societies (NS) according to its mission and values, and to define the new roadmap to strengthen the NS network role in the forthcoming years.

Materials And Methods: The ESTRO NS committee launched a survey addressed to all European National Societies, available online from June 5th to October 30th 2018. Questions were divided into three main sections: (1) general information about NS; (2) relevant activities (to understand the landscape of each NS context of action); (3) relevant needs (to understand how ESTRO can support the NS). Eighty-nine European NS were invited to participate. Respondents were asked to rank ESTRO milestones in order of importance, indicating the level of priority to their society.

Results: A total of 58 out of 89 NS (65.2%) from 31 European countries completed the questionnaire. The majority of NS ranked "Optimal patient care to cure cancer and to reduce treatment-related toxicity" as the highest level of priority. This aligns well with the ESTRO vision 2030 "Optimal health for all together." NS also indicated a high need for more consensus guidelines and exchange of best practices, access to high quality accredited education, implementation of the ESTRO School Core Curriculum at the national level, and defining quality indicators and standard in Radiation Oncology, improved communication and increased channelling of information.

Conclusion: The results of this survey will be used to strengthen the relations between ESTRO and European NS to promote and develop initiatives to improve cancer care.
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http://dx.doi.org/10.1016/j.radonc.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410806PMC
October 2020

Machine Learning-Based Models for Prediction of Toxicity Outcomes in Radiotherapy.

Front Oncol 2020 5;10:790. Epub 2020 Jun 5.

Division of Radiotherapy, IEO European Institute of Oncology IRCCS, Milan, Italy.

In order to limit radiotherapy (RT)-related side effects, effective toxicity prediction and assessment schemes are essential. In recent years, the growing interest toward artificial intelligence and machine learning (ML) within the science community has led to the implementation of innovative tools in RT. Several researchers have demonstrated the high performance of ML-based models in predicting toxicity, but the application of these approaches in clinics is still lagging, partly due to their low interpretability. Therefore, an overview of contemporary research is needed in order to familiarize practitioners with common methods and strategies. Here, we present a review of ML-based models for predicting and classifying RT-induced complications from both a methodological and a clinical standpoint, focusing on the type of features considered, the ML methods used, and the main results achieved. Our work overviews published research in multiple cancer sites, including brain, breast, esophagus, gynecological, head and neck, liver, lung, and prostate cancers. The aim is to define the current state of the art and main achievements within the field for both researchers and clinicians.
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http://dx.doi.org/10.3389/fonc.2020.00790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289968PMC
June 2020

Corrigendum to 'EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees' [European Urology 77 (2020) 223-250].

Authors:
J Alfred Witjes Marek Babjuk Joaquim Bellmunt H Maxim Bruins Theo M De Reijke Maria De Santis Silke Gillessen Nicholas James Steven Maclennan Juan Palou Tom Powles Maria J Ribal Shahrokh F Shariat Theo Van Der Kwast Evanguelos Xylinas Neeraj Agarwal Tom Arends Aristotle Bamias Alison Birtle Peter C Black Bernard H Bochner Michel Bolla Joost L Boormans Alberto Bossi Alberto Briganti Iris Brummelhuis Max Burger Daniel Castellano Richard Cathomas Arturo Chiti Ananya Choudhury Eva Compérat Simon Crabb Stephane Culine Berardino De Bari Willem De Blok Pieter J L De Visschere Karel Decaestecker Konstantinos Dimitropoulos Jose L Dominguez-Escrig Stefano Fanti Valerie Fonteyne Mark Frydenberg Jurgen J Futterer Georgios Gakis Bogdan Geavlete Paolo Gontero Bernhard Grubmüller Shaista Hafeez Donna E Hansel Arndt Hartmann Dickon Hayne Ann M Henry Virginia Hernandez Harry Herr Ken Herrmann Peter Hoskin Jorge Huguet Barbara A Jereczek-Fossa Rob Jones Ashish M Kamat Vincent Khoo Anne E Kiltie Susanne Krege Sylvain Ladoire Pedro C Lara Annemarie Leliveld Estefania Linares-Espinós Vibeke Løgager Anja Lorch Yohann Loriot Richard Meijer M Carmen Mir Marco Moschini Hugh Mostafid Arndt-Christian Müller Christoph R Müller James N'Dow Andrea Necchi Yann Neuzillet Jorg R Oddens Jan Oldenburg Susanne Osanto Wim J G Oyen Luís Pacheco-Figueiredo Helle Pappot Manish I Patel Bradley R Pieters Karin Plass Mesut Remzi Margitta Retz Jonathan Richenberg Michael Rink Florian Roghmann Jonathan E Rosenberg Morgan Rouprêt Olivier Rouvière Carl Salembier Antti Salminen Paul Sargos Shomik Sengupta Amir Sherif Robert J Smeenk Anita Smits Arnulf Stenzl George N Thalmann Bertrand Tombal Baris Turkbey Susanne Vahr Lauridsen Riccardo Valdagni Antoine G Van Der Heijden Hein Van Poppel Mihai D Vartolomei Erik Veskimäe Antoni Vilaseca Franklin A Vives Rivera Thomas Wiegel Peter Wiklund Peter-Paul M Willemse Andrew Williams Richard Zigeuner Alan Horwich

Eur Urol 2020 Jul 21;78(1):e48-e50. Epub 2020 May 21.

Emeritus Professor, The Institute of Cancer Research, London, UK.

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http://dx.doi.org/10.1016/j.eururo.2020.03.017DOI Listing
July 2020

Effects of MRI image normalization techniques in prostate cancer radiomics.

Phys Med 2020 Mar 18;71:7-13. Epub 2020 Feb 18.

Division of Radiotherapy, European Institute of Oncology IRCCS, via Ripamonti 435, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, via Ripamonti 435, Milan, Italy.

The variance in intensities of MRI scans is a fundamental impediment for quantitative MRI analysis. Intensity values are not only highly dependent on acquisition parameters, but also on the subject and body region being scanned. This warrants the need for image normalization techniques to ensure that intensity values are consistent within tissues across different subjects and visits. Many intensity normalization methods have been developed and proven successful for the analysis of brain pathologies, but evaluation of these methods for images of the prostate region is lagging. In this paper, we compare four different normalization methods on 49 T2-w scans of prostate cancer patients: 1) the well-established histogram normalization, 2) the generalized scale normalization, 3) an extension of generalized scale normalization called generalized ball-scale normalization, and 4) a custom normalization based on healthy prostate tissue intensities. The methods are compared qualitatively and quantitatively in terms of behaviors of intensity distributions as well as impact on radiomic features. Our findings suggest that normalization based on prior knowledge of the healthy prostate tissue intensities may be the most effective way of acquiring the desired properties of normalized images. In addition, the histogram normalization method outperform the generalized scale and generalized ball-scale methods which have proven superior for other body regions.
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http://dx.doi.org/10.1016/j.ejmp.2020.02.007DOI Listing
March 2020

Modified-BEP Chemotherapy in Patients With Germ-Cell Tumors Treated at a Comprehensive Cancer Center.

Am J Clin Oncol 2020 06;43(6):381-387

Medical Division of Urogenital and Head and Neck Cancer.

Objectives: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain patients. In an attempt to reduce bleomycin-toxicity, we developed a modified-BEP (mBEP) regimen.

Materials And Methods: Between August 2008 and February 2018, 182 unselected mainly testicular GCT patients (39 with adjuvant purpose and 143 with curative purpose) received a tri-weekly 5-day hospitalization schedule with bleomycin 15 U intravenous (IV) push on day 1 and 10 U IV continuous infusion over 12 hours on days 1 to 3, cisplatin 20 mg/m IV, and etoposide 100 mg/m IV on days 1 to 5. Pulmonary toxicity was assessed through chest computed tomography scan and clinical monitoring.

Results: Median number of mBEP cycles was 3 (range: 1 to 4). In the curative setting, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system, 112, 21, and 9 patients had good-risk, intermediate-risk, and poor-risk class, respectively; 66 (46%) patients had complete response (CR), 67 (47%) had partial response (52 of whom became CR afterwards), 6 (4%) had stable disease (that in 3 became CR afterwards), 3 (2%) progressed, and 1 (1%) died of brain stroke. At a median follow-up of 2.67 years (interquartile range: 1.23-5.00 y), 1 and 5-year overall survival and progression-free survival were 99% and 95%, and 90% and 88%, respectively. In the entire patient population, there was grade 3/4 neutropenia in 92 patients (51%), febrile neutropenia in 11 patients (6%), grade 1/2 nausea in 74 patients (41%), and no death due to pulmonary toxicity.

Conclusion: In GCT patients, our mBEP-schedule would suggest an effective treatment modality without suffering meaningful pulmonary toxicity.
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http://dx.doi.org/10.1097/COC.0000000000000679DOI Listing
June 2020

Palliative radiation therapy in bladder cancer: a matter of dose, techniques and patients' selection.

Ann Palliat Med 2019 Nov;8(5):786-789

Division of Radiotherapy, IEO, European Institute of Oncology IRCCS, Milan, Italy.

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http://dx.doi.org/10.21037/apm.2019.11.02DOI Listing
November 2019

Radiotherapy in the treatment of extracranial hemangiopericytoma/solitary fibrous tumor: Study from the Rare Cancer Network.

Radiother Oncol 2020 03 2;144:114-120. Epub 2019 Dec 2.

Dept. Of Radiation Oncology, Centre A. Lacassagne, Nice, France; Dept. of Radiation Oncology, Centre F. Baclesse, Caen, France.

Background And Purpose: The role of radiotherapy (RT) in the treatment of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) is still under debate. We aimed at investigating whether radiotherapy can improve the results in patients operated for extracranial HPC/SFT.

Materials And Methods: Data from patients with HPC/SFT, treated from 1982 to 2012, were retrospectively reviewed within the Rare Cancer Network framework. Actuarial local control (LC), disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) were calculated with Kaplan-Meyer method. Patient and tumor parameters were analyzed by univariate and multivariate analysis.

Results: Of 114 HPC/SFT, 58 (50.9%) occurred in the extremities/superficial trunk and 56 (49.1%) in intra-thoracic/retroperitoneum. Seventy-eight patients (68.4%) underwent surgery only (Sx), and 36 (31.6%) Sx and RT (Sx + RT). Median RT dose was 60 Gy (range 45-68.4 Gy) in 1.6-2.2 Gy fractions. In the extremities/superficial trunk group of patients, actuarial 5-year LC rates were 50.4% after Sx and 91.6% after Sx + RT (p < 0.0001) for LC, and 50.4% after Sx and 83.1% after Sx + RT (p = 0.008) for DFS. In the intra-thoracic/retroperitoneum group of patients, actuarial 5-year rates were 89.3% after Sx and 77.8% after Sx + RT (p = 0.99) for LC, and 73.8% after Sx and 77.8% after Sx + RT (p = 0.93) for DFS. At multivariate analysis, the addition of RT resulted in better LC and DFS in the whole series. The advantage was confirmed for LC in the group of patients affected by extremity/superficial trunk tumors.

Conclusion: Addition of RT to Sx could improve the prognosis, in terms of LC and DFS, essentially in patients with extremities/superficial trunk tumor locations.
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http://dx.doi.org/10.1016/j.radonc.2019.11.011DOI Listing
March 2020

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Authors:
J Alfred Witjes Marek Babjuk Joaquim Bellmunt H Maxim Bruins Theo M De Reijke Maria De Santis Silke Gillessen Nicholas James Steven Maclennan Juan Palou Tom Powles Maria J Ribal Shahrokh F Shariat Theo Van Der Kwast Evanguelos Xylinas Neeraj Agarwal Tom Arends Aristotle Bamias Alison Birtle Peter C Black Bernard H Bochner Michel Bolla Joost L Boormans Alberto Bossi Alberto Briganti Iris Brummelhuis Max Burger Daniel Castellano Richard Cathomas Arturo Chiti Ananya Choudhury Eva Compérat Simon Crabb Stephane Culine Berardino De Bari Willem De Blok Pieter J L De Visschere Karel Decaestecker Konstantinos Dimitropoulos Jose L Dominguez-Escrig Stefano Fanti Valerie Fonteyne Mark Frydenberg Jurgen J Futterer Georgios Gakis Bogdan Geavlete Paolo Gontero Bernhard Grubmüller Shaista Hafeez Donna E Hansel Arndt Hartmann Dickon Hayne Ann M Henry Virginia Hernandez Harry Herr Ken Herrmann Peter Hoskin Jorge Huguet Barbara A Jereczek-Fossa Rob Jones Ashish M Kamat Vincent Khoo Anne E Kiltie Susanne Krege Sylvain Ladoire Pedro C Lara Annemarie Leliveld Estefania Linares-Espinós Vibeke Løgager Anja Lorch Yohann Loriot Richard Meijer M Carmen Mir Marco Moschini Hugh Mostafid Arndt-Christian Müller Christoph R Müller James N'Dow Andrea Necchi Yann Neuzillet Jorg R Oddens Jan Oldenburg Susanne Osanto Wim J G Oyen Luís Pacheco-Figueiredo Helle Pappot Manish I Patel Bradley R Pieters Karin Plass Mesut Remzi Margitta Retz Jonathan Richenberg Michael Rink Florian Roghmann Jonathan E Rosenberg Morgan Rouprêt Olivier Rouvière Carl Salembier Antti Salminen Paul Sargos Shomik Sengupta Amir Sherif Robert J Smeenk Anita Smits Arnulf Stenzl George N Thalmann Bertrand Tombal Baris Turkbey Susanne Vahr Lauridsen Riccardo Valdagni Antoine G Van Der Heijden Hein Van Poppel Mihai D Vartolomei Erik Veskimäe Antoni Vilaseca Franklin A Vives Rivera Thomas Wiegel Peter Wiklund Andrew Williams Richard Zigeuner Alan Horwich

Eur Urol 2020 02 19;77(2):223-250. Epub 2019 Nov 19.

Emeritus Professor, The Institute of Cancer Research, London, UK.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

Setting: Online Delphi survey and consensus conference.

Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

Outcome Measurements And Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

Results And Limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

Patient Summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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http://dx.doi.org/10.1016/j.eururo.2019.09.035DOI Listing
February 2020

Sexual function recovery after robot-assisted radical prostatectomy: Outcomes from an Italian referral centre and predicting nomogram.

Andrologia 2019 Nov 18;51(10):e13385. Epub 2019 Aug 18.

Division of Urology, European Institute of Oncology, IRCCS, Milan, Italy.

Aims of this study were to assess sexual recovery after robotic-assisted radical prostatectomy (RARP) and to build a nomogram predicting 1-year sexual function. From May 2015 to July 2016, all patients eligible for RARP at our institution were invited to enter the study. The Expanded Prostate cancer Index Composite (EPIC) questionnaire was administered pre-operatively, then at 45 days, and at 3, 6, 9, and 12 months post-operatively. According to sexual function scores, patients were divided into four classes. Multivariate analysis was used to investigate the influence of patient- and disease-related features on sexual recovery. A total of 643 patients were included. Age was associated with baseline potency (p < .0001). Bioptic Gleason score (GS; p = .0002), American Society of Anesthesiologists (ASA) score ( = .002ASA Physical Status Classification System ) and Charlson Comorbidity Index (CCI; p = .02) were negatively associated with potency. Baseline sexual function was associated with potency recovery. A nomogram resulted from fitting a proportional odds logistic model for ordinal outcomes, with 1-year sexual function as a dependent variable and baseline sexual potency, age, body mass index (BMI), clinical stage, biopsy GS, initial prostate-specific antigen (iPSA), ASA score, and CCI as predictors. After further validation, this nomogram could be a useful tool for the pre-operative counselling.
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http://dx.doi.org/10.1111/and.13385DOI Listing
November 2019

Comparison of Outcomes and Toxicity Between Extreme and Moderate Radiation Therapy Hypofractionation in Localized Prostate Cancer: A Propensity Score Analysis.

Int J Radiat Oncol Biol Phys 2019 11 1;105(4):735-744. Epub 2019 Aug 1.

Department of Radiation Oncology, European Institute of Oncology, IRCCS, Milan, Italy; Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hematoncology, University of Milan, Milan, Italy.

Purpose: To compare clinical outcomes and toxicities of 2 radiation therapy (RT) schemes for localized prostate cancer (PCa): extreme hypofractionation (EH; fractions of 6.5-7 Gy to a total dose of 32.5-35 Gy) and the moderate hypofractionation (MH; 26 fractions of 2.7 Gy to a total dose of 70.2 Gy). A propensity score method was used to compare the EH-RT and MH-RT groups.

Methods And Materials: Our analysis included a total of 421 patients divided in 2 groups: 227 treated with MH-RT and 194 treated with EH-RT (43 and 30 months median follow-up, respectively). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate proportional hazard Cox models were used to compare the 2 groups, mainly for gastrointestinal and genitourinary toxicity and secondarily for clinical progression-free survival, biochemical progression-free survival, and overall survival.

Results: Considering the whole population, acute genitourinary and gastrointestinal greater than grade 1 was significantly more frequent in the whole MH-RT group (P < .001 and P < .002, respectively). A borderline significantly greater late genitourinary was confirmed with the multivariate analysis (P = .07). Concerning tumor outcome, no statistically significant differences were observed. After propensity score matching, 226 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups.

Conclusions: EH-RT yields a decreased risk of acute or late toxicities compared with MH-RT, and oncologic outcomes were comparable. Our data indicate that EH-RT might be considered as a treatment modality of choice for select patients with PCa.
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http://dx.doi.org/10.1016/j.ijrobp.2019.07.027DOI Listing
November 2019

Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Crit Rev Oncol Hematol 2019 Jun 1;138:24-28. Epub 2019 Apr 1.

Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy.

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.
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http://dx.doi.org/10.1016/j.critrevonc.2019.03.014DOI Listing
June 2019

Patient specific outcomes of charged particle therapy for hepatocellular carcinoma - A systematic review and quantitative analysis.

Radiother Oncol 2019 03 2;132:127-134. Epub 2019 Jan 2.

Danish Center for Particle Therapy, Aarhus University Hospital, Denmark.

Hepatocellular carcinoma (HCC) is a raising condition world-wide. Most of patients are ineligible for surgery at diagnosis due to the advanced stage of the disease or poor medical condition of the patient. Charged particle therapy (CPT) is a radiotherapy modality showing promising results. The aim of this systematic review was to summarize current knowledge on patient-specific outcomes of CPT for HCC, including overall survival, local control, the effect of radiation dose and the toxicity burden. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After comprehensive database search 17 cohorts (16 studies, 1516 patients) were included into qualitative and quantitative analyses; 11 of 16 studies were retrospective. Eleven studies were on protons, 2 studies were on protons and carbon ions and 4 on carbon ions alone, were identified. Median BED10 (biologically equivalent dose) range was 68.75-122.5 GyE. Mean weighted overall survival across studies was 86%, 62%, 59% and 35% at 1, 2, 3 and 5 years, respectively. Mean weighted local control was 86%, 89%, 87% and 89% at 1, 2, 3 and 5 years, respectively. Adjusted morbidity rates were: 54% for acute G1-2 toxicities and 6% for acute ≥G3 toxicities; 9% for late G1-2 toxicities and less than 4% for late ≥G3 toxicities. There was no treatment-associated mortality. CONCLUSIONS: CPT offers high local control, acceptable overall survival and low post-treatment morbidity. Quality of findings, especially on toxicities, is decreased by incomplete reporting and retrospective designs of available studies. Therefore, there is a strong need for better reporting and prospective studies.
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http://dx.doi.org/10.1016/j.radonc.2018.12.012DOI Listing
March 2019

Nutritional Intervention for Nonsurgical Head and Neck Cancer Patients Treated with Radiation Therapy: Results from a Prospective Stepped-Wedge Clinical Protocol.

Nutr Cancer 2018 10 1;70(7):1051-1059. Epub 2018 Oct 1.

a Department of Radiotherapy , European Institute of Oncology , Milan, Italy.

Aim: To evaluate the impact on weight loss (WL) of a standardized nutritional stepped-wedge protocol on consecutive head and neck cancer (HNC) patients treated with curative radiotherapy (RT).

Methods: We prospectively collected data of patients followed by a trained dietitian and treated according to a pre-defined stepped-wedge protocol. Patients with swallowing defect at the baseline and WL >10% 3 months prior to the beginning of RT were excluded from the analysis. Nutritional status was assessed at the baseline and weekly during the course of RT. Fluid and caloric intake were assessed through a 24-h recall.

Results: Between May 2010 and March 2011, 42 patients treated were evaluated. Median overall treatment time was 52.5 days. WL per CTCAE 4.03 was G0, G1 and G2 in 23 (55%), 14 (33%) and 5 (12%) patients, respectively. Thirty-five (83%) patients did not require enteral nutrition. About 90% of patients completed RT without interruption of oral feeding.

Conclusions: Despite the high toxicity profile of curative RT in HN, we proposed a standardized stepped-wedge protocol allowing to prevent severe WL in most of our patients. Further larger prospective studies are warranted to validate our approach and to achieve consensus on nutritional intervention in this subset of patients.
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http://dx.doi.org/10.1080/01635581.2018.1497187DOI Listing
October 2018

Equipment, staffing, and provision of radiotherapy in Lombardy, Italy: Results of three surveys performed between 2012 and 2016.

Tumori 2018 Oct 9;104(5):352-360. Epub 2018 Jul 9.

35 Radiation Oncology Center, IEO Scientific Direction, Milan, Italy.

Introduction:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent.

Methods:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources.

Results:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014).

Conclusions:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.
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http://dx.doi.org/10.1177/0300891618784800DOI Listing
October 2018

"Give me five" ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach.

Med Oncol 2018 May 10;35(6):96. Epub 2018 May 10.

Department of Radiotherapy, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35 Gy in 5 fractions, while 25 patients (13%) received 32.5 Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9-12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2 ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan-Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7 ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients' quality of life and potential overall health system and social benefits.
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http://dx.doi.org/10.1007/s12032-018-1155-yDOI Listing
May 2018

Radiotherapy Plus Total Androgen Block Radiotherapy Plus LHRH Analog Monotherapy for Non-metastatic Prostate Cancer.

Anticancer Res 2018 05;38(5):3139-3143

Division of Radiotherapy, European Institute of Oncology, Milan, Italy.

Background/aim: Patients with locally advanced prostate cancer are generally treated with radiotherapy (RT) which can be combined with hormonal therapy. RT plus monotherapy with luteinizing hormone-releasing hormone (LHRH) analog triptorelin was compared to RT plus total androgen block (TAB).

Patients And Methods: A retrospective study was carried out on patients with locally advanced prostate cancer comparing RT plus monotherapy versus RT plus TAB.

Results: For overall survival, no differences between patients receiving RT with monotherapy and those treated with TAB were observed. A trend favoring use of TAB was found for progression-free survival. No differences in late gastrointestinal and genitourinary toxicities were reported.

Conclusion: This study suggests that monotherapy with LHRH is as effective as TAB, which is important in selecting appropriate treatment considering that TAB can have higher risks of adverse events and reduce the quality of life of patients.
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http://dx.doi.org/10.21873/anticanres.12576DOI Listing
May 2018

Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases.

Med Oncol 2018 Apr 18;35(5):75. Epub 2018 Apr 18.

Division of Radiotherapy, European Institute of Oncology, Ripamonti 435, 20141, Milan, Italy.

To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan-Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0-67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.
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http://dx.doi.org/10.1007/s12032-018-1137-0DOI Listing
April 2018

A Qualitative Investigation on Patient Empowerment in Prostate Cancer.

Front Psychol 2017 26;8:1215. Epub 2017 Jul 26.

Applied Research Division for Cognitive and Psychological Science, European Institute of OncologyMilan, Italy.

Men with prostate cancer often describe low levels of empowerment. eHealth interventions may represent useful tools to deliver care and education and to meet patients' needs within an empowerment framework. In order to design a platform for cancer patients' empowerment within the H2020 iManageCancer project, the perspective of the target population for the platform was assessed. The present study aims to assess the qualitative experience of prostate cancer patients during treatment in order to provide insights for clinical practice with a particular focus on the design of a web platform to promote cancer patients' empowerment. Ten patients undergoing radiation therapy treatment took part in a semi-structured interview to explore different aspects of patient empowerment. Four main thematic areas were addressed: patient-healthcare providers' communication, decision-making, needs, and resources. A qualitative approach using thematic analysis was followed. Half of the patients reported little to no possibility to share information and questions with healthcare providers. With regards to decision-making, the role of healthcare providers was perceived as directive/informative, but half of the patients perceived to assume an active role in at least one interaction. Difficulties and needs included the choice of the specialist or of the structure after diagnosis, clinicians' support in self-management, surgical consequences, and side effects, preparation for radiation therapy. Resources included family and social support both from a practical and from an emotional perspective, coping style, and work schedule management. These results suggest that relations with healthcare providers should be supported, especially immediately after diagnosis and after surgery. Support to self-management after surgery and at the beginning of radiation therapy treatment also constitutes a priority. The adoption of a personalized approach from the beginning of prostate cancer care flow may promote patient empowerment, overcoming the aforementioned needs and mobilizing resources. The social network represents an important resource that could be integrated in interventions. These considerations will be taken into account in the design of a cancer self-management platform aiming to increase patients' empowerment.
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http://dx.doi.org/10.3389/fpsyg.2017.01215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526923PMC
July 2017

Voxel-based analysis unveils regional dose differences associated with radiation-induced morbidity in head and neck cancer patients.

Sci Rep 2017 08 3;7(1):7220. Epub 2017 Aug 3.

Institute of Biostructures and Bioimaging, National Research Council (CNR), Naples, Italy.

The risk of radiation-induced toxicity in patients treated for head and neck (HN) cancer with radiation therapy (RT) is traditionally estimated by condensing the 3D dose distribution into a monodimensional cumulative dose-volume histogram which disregards information on dose localization. We hypothesized that a voxel-based approach would identify correlations between radiation-induced morbidity and local dose release, thus providing a new insight into spatial signature of radiation sensitivity in composite regions like the HN district. This methodology was applied to a cohort of HN cancer patients treated with RT at risk of radiation-induced acute dysphagia (RIAD). We implemented an inter-patient elastic image registration framework that proved robust enough to match even the most elusive HN structures and to provide accurate dose warping. A voxel-based statistical analysis was then performed to test regional dosimetric differences between patients with and without RIAD. We identified a significantly higher dose delivered to RIAD patients in two voxel clusters in correspondence of the cricopharyngeus muscle and cervical esophagus. Our study goes beyond the well-established organ-based philosophy exploring the relationship between radiation-induced morbidity and local dose differences in the HN region. This approach is generally applicable to different HN toxicity endpoints and is not specific to RIAD.
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http://dx.doi.org/10.1038/s41598-017-07586-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543173PMC
August 2017

Can the Day 0 CT-scan predict the post-implant scanning? Results from 136 prostate cancer patients.

Phys Med 2017 Aug 23;40:66-71. Epub 2017 Jul 23.

Departments of Radiotherapy, European Institute of Oncology, Milan, Italy; University of Milan, Milan, Italy.

Purpose: Post-implant CT-scanning is an essential part of permanent prostate brachytherapy. However, the evaluation of post-implant CT dosimetry is not straightforward due to the edema that can modify the dose to the prostate and to the organs at risk. The aim of this study is to evaluate the impact of the timing of the post-implant CT-scan on the dosimetric results and to verify if the Day 0 scan findings can predict Day 50 scanning.

Methods: 136 consecutive patients who received monotherapy with I-125 implants were selected for this study. Two sets of 8 dosimetric quality parameters corresponding to 2 different CT-scans (Day 0 and Day 50) were calculated and compared. The dosimetric parameters included are the percentage volume of the post-implant prostate receiving 80%, 100% and 150% of the prescribed dose, the doses covering 80% and 90% of the prostate volume and the Dose Homogeneity Index. The values of the dose covering 1cm of the rectum and urethra were assessed.

Results: All the dosimetric parameters of the Day 50 were higher than those of the Day 0 scan. Linear functions were obtained that calculate D and V values at Day 50 based on the Day 0 findings. Rectal and urethral parameters tended to be underestimated on Day 0 CT-scan relative to Day 50 based dosimetry.

Conclusions: Predicting the Day 50 dosimetry from the Day 0 scan could be a possible alternative to a Day 50 scan only in specific situations, but with a degree of uncertainty in the predicted values.
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http://dx.doi.org/10.1016/j.ejmp.2017.07.011DOI Listing
August 2017

Physicists' views on hadrontherapy: a survey of members of the Italian Association of Medical Physics (AIFM).

Tumori 2017 Sep 8;103(5):430-437. Epub 2017 Jul 8.

Medical Physics Unit, Department of Diagnostic Imaging and Radiotherapy, Fondazione IRCCS National Cancer Institute, Milan - Italy.

Background: This study was based on a survey to investigate perceptions of hadrontherapy of the members of the Italian Association of Medical Physics (AIFM). The survey was digitally submitted to the 991 members between the end of January and the beginning of April 2016.

Methods: A 19-item questionnaire was designed focusing on advantages and disadvantages of hadrontherapy, current status and possible future improvements, and need and opportunities for future investments in Italy and abroad. Information about professional qualifications, main fields of clinical involvement and specific competencies of the respondents was also collected.

Results: The survey was completed by 121 AIFM members (response rate 12.2%). In the answers collected, it was shown that medical physicists expressed interest in hadrontherapy mainly for reasons of personal interest rather than for professional needs (90% ± 2.5% vs. 52% ± 4.3% of the respondents, respectively), with a good knowledge of the related basic aspects as well as of the pros and cons of its application. However, poor knowledge of the current status of hadrontherapy was observed among the medical physicists not directly involved at a professional level, who were less than 3% of the physicists working in radiotherapy.

Conclusions: In light of these results, the implementation of new training and education initiatives should be devised to promote a deeper and global knowledge of hadrontherapy-related issues, not only from a theoretical point of view but also in practical terms. Moreover, a close collaboration between highly specialized medical physicists employed in hadrontherapy centers and others in oncology hospitals should be -encouraged.
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http://dx.doi.org/10.5301/tj.5000654DOI Listing
September 2017

Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression.

Med Oncol 2017 Jun 27;34(6):107. Epub 2017 Apr 27.

Department of Radiotherapy, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.
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http://dx.doi.org/10.1007/s12032-017-0965-7DOI Listing
June 2017

Comparison between model-predicted tumor oxygenation dynamics and vascular-/flow-related Doppler indices.

Med Phys 2017 May 13;44(5):2011-2019. Epub 2017 Apr 13.

Department of Electronics, Information and Bioengineering (DEIB), Politecnico di Milano University, Piazza Leonardo da Vinci, 32 - 20133, Milan, Italy.

Purpose: Mathematical modeling is a powerful and flexible method to investigate complex phenomena. It discloses the possibility of reproducing expensive as well as invasive experiments in a safe environment with limited costs. This makes it suitable to mimic tumor evolution and response to radiotherapy although the reliability of the results remains an issue. Complexity reduction is therefore a critical aspect in order to be able to compare model outcomes to clinical data. Among the factors affecting treatment efficacy, tumor oxygenation is known to play a key role in radiotherapy response. In this work, we aim at relating the oxygenation dynamics, predicted by a macroscale model trained on tumor volumetric data of uterine cervical cancer patients, to vascularization and blood flux indices assessed on Ultrasound Doppler images.

Methods: We propose a macroscale model of tumor evolution based on three dynamics, namely active portion, necrotic portion, and oxygenation. The model parameters were assessed on the volume size of seven cervical cancer patients administered with 28 fractions of intensity modulated radiation therapy (IMRT) (1.8 Gy/fraction). For each patient, five Doppler ultrasound tests were acquired before, during, and after the treatment. The lesion was manually contoured by an expert physician using 4D View (General Electric Company - Fairfield, Connecticut, United States), which automatically provided the overall tumor volume size along with three vascularization and/or blood flow indices. Volume data only were fed to the model for training purpose, while the predicted oxygenation was compared a posteriori to the measured Doppler indices.

Results: The model was able to fit the tumor volume evolution within 8% error (range: 3-8%). A strong correlation between the intrapatient longitudinal indices from Doppler measurements and oxygen predicted by the model (about 90% or above) was found in three cases. Two patients showed an average correlation value (50-70%) and the remaining two presented poor correlations. The latter patients were the ones featuring the smallest tumor reduction throughout the treatment, typical of hypoxic conditions. Moreover, the average oxygenation value predicted by the model was close to the average vascularization-flow index (average difference: 7%).

Conclusions: The results suggest that the modeled relation between tumor evolution and oxygen dynamics was reasonable enough to provide realistic oxygenation curves in five cases (correlation greater than 50%) out of seven. In case of nonresponsive tumors, the model failed in predicting the oxygenation trend while succeeded in reproducing the average oxygenation value according to the mean vascularization-flow index. Despite the need for deeper investigations, the outcomes of the present work support the hypothesis that a simple macroscale model of tumor response to radiotherapy is able to predict the tumor oxygenation. The possibility of an objective and quantitative validation on imaging data discloses the possibility to translate them as decision support tools in clinical practice and to move a step forward in the treatment personalization.
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http://dx.doi.org/10.1002/mp.12192DOI Listing
May 2017

High-Risk Prostate Cancer and Radiotherapy: The Past and the Future. A Benchmark for a New Mixed Beam Radiotherapy Approach.

Clin Genitourin Cancer 2017 06 18;15(3):376-383. Epub 2017 Jan 18.

Scientific Direction, European Institute of Oncology, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.

Background: The prognosis for patients with high-risk prostate cancer is poor. No consensus exists on the most effective treatment. The aim of this retrospective study was to identify the biochemical progression-free survival and the toxicity profile of patients with localized high-risk prostate cancer treated with external beam radiation therapy. These results will constitute a benchmark for a prospective "mixed beam" trial: a boost with carbon ions followed by a pelvic photon intensity-modulated radiotherapy (NCT02672449 [clinicaltrials.gov]).

Patients And Methods: We retrospectively reviewed the data of 76 patients treated in our institution with photon radiation therapy according to the inclusion criteria of the future "mixed beam" trial: cT3a and/or serum prostate-specific antigen > 20 ng/mL and/or Gleason score of 8 to 10, cN0 cM0. Toxicity, and biochemical and clinical progression-free survival were assessed.

Results: Seventy-six patients fulfilled our criteria. The median follow-up was 30.2 months (range, 7.2-61.1). Biochemical progression was observed in 22 patients (28.9%) after a median time of 20.2 months (range, 5-58.1) from the end of radiotherapy. Sixteen patients had clinical progression, in all the cases preceded by biochemical progression. Fifty-seven patients (75%) are alive with no evidence of disease, 13 (17.1%) are alive with clinically evident disease, 6 died (3 of prostate disease 3.9%).

Conclusion: Our results suggest that a more aggressive treatment is necessary. Local treatment intensification based on the "mixed beam" approach combining carbon ions (with its known radiobiological advantages) and photons might represent a promising strategy in high-risk prostate cancer and it will be investigated with our prospective clinical trial.
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http://dx.doi.org/10.1016/j.clgc.2017.01.007DOI Listing
June 2017

Phase II multi-institutional clinical trial on a new mixed beam RT scheme of IMRT on pelvis combined with a carbon ion boost for high-risk prostate cancer patients.

Tumori 2017 May 2;103(3):314-318. Epub 2016 Dec 2.

Scientific Direction, European Institute of Oncology, Milan - Italy.

Purpose: Definition of the optimal treatment schedule for high-risk prostate cancer is under debate. A combination of photon intensity modulated radiotherapy (IMRT) on pelvis with a carbon ion boost might be the optimal treatment scheme to escalate the dose on prostate and deliver curative dose with respect to normal tissue and quality of dose distributions. In fact, carbon ion beams offer the advantage to deliver hypofractionated radiotherapy (RT) using a significantly smaller number of fractions compared to conventional RT without increasing risks of late effects.

Methods: This study is a prospective phase II clinical trial exploring safety and feasibility of a mixed beam scheme of carbon ion prostate boost followed by photon IMRT on pelvis. The study is designed to enroll 65 patients with localized high-risk prostate cancer at 3 different oncologic hospitals: Istituto Europeo di Oncologia, Fondazione IRCCS Istituto Nazionale dei Tumori, and Centro Nazionale di Adroterapia Oncologica. The primary endpoint is the evaluation of safety and feasibility with acute toxicity scored up to 1 month after the end of RT. Secondary endpoints are treatment early (3 months after the end of RT) and long-term tolerability, quality of life, and efficacy.

Results: The study is not yet recruiting; in silico studies are ongoing and we expect to start recruitment by 2017.

Conclusions: The present clinical trial aims at improving the current treatment for high-risk prostate cancer, evaluating safety and feasibility of a new RT mixed-beam scheme including photons and carbon ions. Encouraging results are coming from carbon ion facilities worldwide on the treatment of different tumors including prostate cancers. Carbon ions combine physical properties allowing for high dose conformity and advantageous radiobiological characteristics. The proposed mixed beam treatment has the advantage to combine a photon high conformity standard of care IMRT phase with a hypofractionated carbon ion RT boost delivered in a short overall treatment time.
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http://dx.doi.org/10.5301/tj.5000587DOI Listing
May 2017

Extreme hypofractionation for early prostate cancer: Biology meets technology.

Cancer Treat Rev 2016 Nov 29;50:48-60. Epub 2016 Aug 29.

Division of Radiation Oncology, European Institute of Oncology, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.

The aim of this review is to present the available radiobiological, technical and clinical data about extreme hypofractionation in primary prostate cancer radiotherapy. The interest in this technique is based on the favourable radiobiological characteristics of prostate cancer and supported by advantageous logistic aspects deriving from short overall treatment time. The clinical validity of short-term treatment schedule is proven by a body of non-randomised studies, using both isocentric (LINAC-based) or non-isocentric (CyberKnife-based) stereotactic body irradiation techniques. Twenty clinical studies, each enrolling more than 40 patients for a total of 1874 treated patients, were revised in terms of technological setting, toxicity, outcome and quality of life assessment. The implemented strategies for the tracking of the prostate and the sparing of the rectal wall have been investigated with particular attention. The urinary toxicity after prostate stereotactic body irradiation seems slightly more pronounced as compared to rectal adverse events, and this is more evident for late occurring events, but no worse as respect to conventional fractionation schemes. As far as the rate of severe acute toxicity is concerned, in all the available studies the treatment was globally well tolerated. While awaiting long-term data on efficacy and toxicity, the analysed studies suggest that the outcome profile of this approach, alongside the patient convenience and reduced costs, is promising. Forty-eight ongoing clinical trials are also presented as a preview of the expectation from the near future.
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http://dx.doi.org/10.1016/j.ctrv.2016.08.005DOI Listing
November 2016