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Bone metastases (BM) are still the main cause of morbidity in cancer patients because of skeletal-related events (SREs) that reduce quality of life. They have also led to increased social and healthcare costs. At present, data available on BM are insufficient. This was a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 months’ follow-up. Information on patients at the first diagnosis of BM, including demographics and characteristics of the primary tumor and BM. Data were periodically updated by participating centres and reviewed by the coordinator centre. From October 2014 to July 2019, 618 patients with BM from solid tumors were enrolled and 220 were eligible for the present study. Median age was 62 years (range 26–86). Median follow-up was 34 months (range 6–149). At the time of enrolment, 109 (50%) had only BM (BOM) and 109 (50%) had concomitant visceral lesions and BM (BVM). Median time-to-first BM was 47 months (range 0–312) in BOM and 78.6 months in BVM patients. Disease-free interval differed on the basis of BC molecular subtype and stage. Ninety-eight BM patients had at least on SRE. Zoledronate was used in 69.1% of cases and denosumab in 28.3%. First-line treatment was hormone-based (50.7%), chemotherapy-based (38.7%) or chemotherapy- + hormone therapy-based (9.7%). Median progression-free and overall survival were 15.1 months (95% CI 12.6–18.4) and 66.8 months (95% CI 52.1–79.2), respectively. Our prospective study could substantially help to better understand the natural history of BM from BC.

Objectives Hydroxychloroquine has shown to have antiviral activity in vitro against coronaviruses, specifically SARS-CoV-2. It is believed to block virus infection by increasing endosomal pH required for virus cell fusion and glycosylation of viral surface proteins. In addition to its antiviral activity, hydroxychloroquine has an immune-modulating activity that may synergistically enhance its antiviral effect in vivo, making it a potentially promising drug for the prevention and the cure of SARS-CoV-19. However, randomized controlled trials are needed to assess whether it can be used safely to treat COVID-19 patients or to prevent infection. The main objective of the present study is to evaluate the efficacy of hydroxychloroquine for (I) the prevention of COVID-19 or related symptoms in SARS-CoV-2-exposed subjects, such as as household members/contacts of COVID-19 patients and (II) the treatment of early-phase asymptomatic or paucisymptomatic COVID-19 patients. Trial design This is a controlled, open label, cluster-randomized, superiority trial with parallel group design. Subjects will be randomized either to receive hydroxychloroquine or to observation (2:1). Participants SARS-CoV-2-exposed subjects, including household members and/or contacts of COVID-19 patients and healthcare professionals (Group 1) or patients with COVID-19 (positive PCR test on a rhinopharyngeal or oropharyngeal swab for SARS-CoV-2), asymptomatic or paucisymptomatic in home situations who are not undergoing treatment with any anti COVID-19 medication (Group 2), will be enrolled. Paucisymptomatic patients are defined as patients with a low number of mild symptoms. All subjects must be aged ≥18 years, male or female, must be willing and able to give informed consent and must not have any contraindications to take hydroxychloroquine (intolerance or previous toxicity for hydroxychloroquine/chloroquine, bradycardia or reduction in heart rhythm with arrhythmia, ischemic heart disease, retinopathy, congestive heart failure with use of diuretics, favism or glucose-6-phosphate dehydrogenase (G6PD) deficiency, diabetes type 1, major comorbidities such as advanced chronic kidney disease or dialysis therapy, known history of ventricular arrhythmia, any oncologic/hematologic malignancy, severe neurological and mental illness, current use of medications with known significant drug-drug interactions, and known prolonged QT syndrome or current use of drugs with known QT prolongation). The study is monocentric and will be conducted at Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS. Subjects will be enrolled from a large epidemic region (North-Central Italy). The Public Health Departments of several Italian regions will collaborate by identifying potentially eligible subjects. Intervention and comparator The participants will be randomized (2:1 randomization) to receive either hydroxychloroquine (Arm A) or to Observation (Arm B). Hydroxychloroquine will be administered with the following schedule: Group1: A loading dose hydroxychloroquine 400 mg twice daily on day 1, followed by a weekly dose of hydroxychloroquine 200 mg twice daily on days 8, 15 and 22, for a total of one month of treatment. Group 2: A loading dose hydroxychloroquine 400 mg twice daily on day 1 followed by 200 mg twice daily for a total of 5-7 days. The comparator in this trial is observation given that currently neither treatment is administered to asymptomatic or paucisymptomatic subjects, nor prophylaxis is available for contacts. Hydroxychloroquine will be shipped to subjects within 24 hours of randomization. Given the extraordinary nature of the COVID-19 pandemic, only telephonic interviews will be carried out and electronic Patient Reported Outcomes (ePRO) completed. During treatment, each subject will be contacted every other day for the first week and weekly thereafter (Group 2) or weekly (Group 1) by a study physician to assess early onset of any COVID-19 symptom or any adverse reaction to hydroxychloroquine and to check subject compliance. Furthermore, all subjects will receive periodic ePROs which may be completed through smartphone or tablets to record drug self-administration and onset of any symptom or adverse event. All subjects will be followed up for a total of 6 months by periodic telephonic interviews and ePROs. Main outcomes The primary endpoint/outcome measure for this trial is: for Group 1, the proportion of subjects who become symptomatic and/or swab-positive in each arm within one month of randomization; for Group 2, the proportion of subjects who become swab-negative in each arm within 14 days of randomization. Randomization All household members and/or contacts of each COVID-19 index case, and the COVID-19 patient himself/herself, fulfilling all inclusion criteria will be grouped into a single cluster and this cluster will be randomized (2:1) to either arm A or arm B. Information on each subject will be recorded in specific data records. Randomization lists will be stratified according to the following factors regarding COVID-19 index cases: 1. COVID-19 risk level on the basis of province of residence (high vs. low/intermediate); 2. Index case is a healthcare professional (yes vs.no) 3. Index case with COVID-19 treatment (yes vs. no) An independent statistician not otherwise involved in the trial will generate the allocation sequence, and COVID-19 response teams will be unaware of the allocation of clusters. Randomization will be performed through an interactive web-based electronic data-capturing database. An Independent Data Monitoring Committee has been established. Blinding (masking) This study is open label. Numbers to be randomized (sample size) For Group 1, a sample size of about 2000 SARS-CoV-2-exposed subjects such as household members and/or contacts of COVID-19 patients will take part in the study. Assuming around 1.5-2.0 asymptomatic household members and/or contacts for each COVID-19 patient, we expect to identify approximately 1000-1300 COVID-19 index cases to be randomized. An interim analysis on efficacy is planned using standard alpha-spending function. For Group 2, sufficient power for primary objective (negative swab within 14 days of randomization) will be reached given a sample size of 300 asymptomatic or paucisymptomatic COVID-19 subjects in home situations not treated for COVID-19 (25%-30% of about 1000-1300 expected index cases). Since up to date reduced evidence about COVID-19 infection epidemiology, the continuous update of diagnostic and therapeutic approaches, the sample size estimation could be updated after a one third of population will be recruited and eventually modified according to a substantial protocol amendment. An interim analysis at 100 enrolled COVID-19 patients is planned. We have planned a Generalized Estimating Equation analysis, which is more efficient than a cluster level analysis, to take advantage of subject-specific covariates. The above reported sample size analysis is therefore to be considered conservative. Trial Status The current version of the PROTECT trial protocol is ‘Final version, 15 April 2020’. The study started on 9th May 2020. The first patient was enrolled on 14th May 2020. Recruitment is expected to last through September 2020. Trial registration The PROTECT trial is registered in the EudraCT database (no. 2020-001501-24) and in ClinicalTrials.gov (NCT04363827), date of registration 24 April 2020. Full protocol The full PROTECT protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol (Protocol final version, 15th April 2020). The study protocol has been reported in accordance with Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

// Alessandro Passardi 1, * , Emanuela Scarpi 2, * , Luigi Cavanna 3 , Monia Dall’Agata 2 , Davide Tassinari 4 , Silvana Leo 5 , Ilaria Bernardini 6 , Fabio Gelsomino 7 , Stefano Tamberi 8 , Alba A. Brandes 9 , Elena Tenti 10 , Roberto Vespignani 11 , Giovanni L. Frassineti 1 , Dino Amadori 1 , Ugo De Giorgi 1 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy 3 Medical Oncology Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy 4 Department of Oncology, Infermi Hospital, Rimini, Italy 5 Medical Oncology Unit, Vito Fazzi Hospital, Lecce, Italy 6 Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy 7 Oncology Unit, University Hospital Modena, Modena, Italy 8 Oncology Unit, Degli Infermi Hospital, Faenza, Italy 9 Department of Medical Oncology, Azienda USL, Bellaria Hospital - IRCCS Institute of Neurological Sciences, Bologna, Italy 10 Oncology Pharmacy Laboratory, IRST IRCCS, Meldola, Italy 11 IT Service, IRST IRCCS, Meldola, Italy * These authors have contributed equally to this work Correspondence to: Emanuela Scarpi, e-mail: emanuela.scarpi@irst.emr.it Keywords: metastatic colorectal cancer, bevacizumab, SII NLR PLR, prognosis Received: February 24, 2016 Accepted: April 04, 2016 Published: April 21, 2016 ABSTRACT Background: To investigate the role of pre-treatment inflammatory indexes (II) as predictors of prognosis and treatment efficacy in patients with metastatic colorectal cancer mCRC randomized onto the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) with or without bevacizumab (Bev). Results: In the overall population, PFS and OS were higher in patients with low SII ( p = .015 and .002, respectively), low NLR ( p = .0001 and

Andrea Casadei Gardini,1,* Emanuela Scarpi,2,* Elena Orlandi,3 Davide Tassinari,4 Silvana Leo,5 Ilaria Bernardini,6 Fabio Gelsomino,7 Stefano Tamberi,8 Silvia Ruscelli,1 Roberto Vespignani,9 Sonia Ronconi,10 Giovanni Luca Frassineti,1 Dino Amadori,1 Alessandro Passardi1 1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy; 3Medical Oncology Department, Piacenza Hospital, Piacenza, Italy; 4Department of Oncology, City Hospital, Rimini, Italy; 5Medical Oncology Unit, Vito Fazzi Hospital, Lecce, Italy; 6Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy; 7Department of Oncology and Hematology, Division of Oncology, University Hospital Modena, Italy; 8Oncolgy Unit, Degli Infermi Hospital, Faenza, Italy; 9IT Service, IRST IRCCS, Meldola, Italy; 10Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy *These authors contributed equally to this work Background: The aim of this study was to investigate the role of pre-treatment aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) + bevacizumab (B) or CT alone. Patients and methods: Patients randomly received CT+B or CT alone as first-line therapy. CT consisted of either FOLFOX4 or FOLFIRI at the clinician’s discretion. Results: Out of the 284 patients enrolled, increased ALRI levels were associated with shorter PFS and OS (p

Background: We assessed the real-life clinical impact of bone health management in patients with breast cancer (BC) receiving adjuvant endocrine therapy at an Italian Osteoncology Center. Methods: Pre- and post-menopausal women undergoing adjuvant endocrine therapy for early-stage BC who came to our institute for their first bone health evaluation from January 2011 to June 2016 were considered in this retrospective observational study. Results: 1125 pre- and post-menopausal early-stage BC patients (209 and 916, respectively) were evaluated. Median age was 61 years (range 26&ndash, 88). In the pre-menopausal group, spinal x-ray revealed that 10 patients (4.7%) had a morphometric vertebral fracture. Higher age (OR: 1.14, 95% CI: 1.01&ndash, 1.29) and bone mineral density (BMD) &le, &minus, 2.5 (OR: 14.45, 95% CI: 1.70&ndash, 122.67) were associated with a higher risk of bone fracture. The overall frequency of bone fracture was 17.6% (n = 161) in post-menopausal patients and a lower risk for bone fractures was associated with tamoxifen or other treatments (OR: 0.25, 95% CI: 0.12&ndash, 0.53), presence of back pain (OR: 1.65, 95% CI: 1.16&ndash, 2.36), lower BMD (OR: 2.09 in patients with T-score &le, 2.5, 95% CI: 1.21&ndash, 3.59) and lower vitamin D levels (OR: 1.57 in patients with &le, 10 ng/mL, 95% CI: 1.05&ndash, 2.34) in univariate analysis. Conclusion: Our findings confirm that bone health management should be an integral part of long-term cancer care.

Background Computerized decision support systems (CDSSs) are computer programs that provide doctors with person-specific, actionable recommendations, or management options that are intelligently filtered or presented at appropriate times to enhance health care. CDSSs might be integrated with patient electronic health records (EHRs) and evidence-based knowledge. Methods/Design The Computerized DEcision Support in ONCOlogy (ONCO-CODES) trial is a pragmatic, parallel group, randomized controlled study with 1:1 allocation ratio. The trial is designed to evaluate the effectiveness on clinical practice and quality of care of a multi-specialty collection of patient-specific reminders generated by a CDSS in the IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) hospital. We hypothesize that the intervention can increase clinician adherence to guidelines and, eventually, improve the quality of care offered to cancer patients. The primary outcome is the rate at which the issues reported by the reminders are resolved, aggregating specialty and primary care reminders. We will include all the patients admitted to hospital services. All analyses will follow the intention-to-treat principle. Discussion The results of our study will contribute to the current understanding of the effectiveness of CDSSs in cancer hospitals, thereby informing healthcare policy about the potential role of CDSS use. Furthermore, the study will inform whether CDSS may facilitate the integration of primary care in cancer settings, known to be usually limited. The increasing use of and familiarity with advanced technology among new generations of physicians may support integrated approaches to be tested in pragmatic studies determining the optimal interface between primary and oncology care. Trial registration ClinicalTrials.gov, NCT02645357

Introduction Despite the growing number of oral agents available for cancer treatment, their efficacy may be reduced due to the lack of adherence, inappropriate adverse event self-management and arbitrary dose adjustment. The management of anticancer therapies could exponentially benefit from the introduction of mobile health technologies in a highly integrated electronic oncology system. Methods and analysis We plan to customise and fine-tune an existing monitoring TreC platform used in different chronic diseases in the oncology setting. This project follows a multistep approach with two major purposes: 1. participatory design techniques driven by Health Literacy and Patient Reported Outcomes principles in order to adapt the system to the oncology setting involving patients and healthcare providers; 2. a prospective training-validation, interventional, non-pharmacological, multicentre study on a series of consecutive patients with cancer (20 and 60 patients in the training and validation steps, respectively) in order to assess system capability, usability and acceptability. The novel Onco-TreC 2.0 is expected to contribute to improving the adherence and safety of cancer care, promoting patient empowerment and patient–doctor communication. Ethics and dissemination Ethical approval was obtained from the Independent Ethics Committees of the participating institutions (CEIIAV protocol Number 2549/2015; reference Number 1315-PU). Informed consent will be obtained from all study participants. Findings will be disseminated through peer-reviewed journals, conferences and event presentations. Trial registration number ClinicalTrials.gov (NCT02921724); (Pre-results). Other study ID Number: IRST100.18.

e13075Background: BM are still the main cause of morbidity and morbility in cancer patients, mostly due to their complications defined as skeletal-related event (SRE). SRE reduce patients’quality o...