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Importance: Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. Objective: To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). Design, setting, and participants: This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. Exposures: Upfront PRRT or upfront chemotherapy or targeted therapy. Main outcomes and measures: The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. Results: Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P

The coronavirus disease 2019 (COVID-19) pandemic has severely affected cancer care and research by disrupting the prevention and treatment paths as well as the preclinical, clinical, and translational research ecosystem. In Italy, this has been particularly significant given the severity of the pandemic's impact and the intrinsic vulnerabilities of the national health system. However, whilst detrimental, disruption can also be constructive and may stimulate innovation and progress. The Italian Association of Medical Oncology (AIOM) has recognized the impact of COVID-19 on cancer care continuum and research and proposes the '2021 Matera statement' which aims at providing pragmatic guidance for policymakers and health care institutions to mitigate the impact of the global health crisis on Italian oncology and design the recovery plan for the post-pandemic scenario. The interventions are addressed both to the pillars (prevention, diagnosis, treatment, follow-up, health care professionals) and foundations of cancer care (communication and care relationship, system organization, resources, research, networking). The priorities to be implemented can be summarized in the MATERA acronym: Multidisciplinarity; Access to cancer care; Telemedicine and Territoriality; Equity, ethics, education; Research and resources; Alliance between stakeholders and patients.

Medical records are a relevant source for real-world evidence. We introduced patient-reported outcomes (PROs) in clinical practice, demonstrating a significant quality-of-life improvement, compared to usual visit. In this secondary analysis, we describe the agreement between patients' and physicians' reports of 5 symptoms. Our hypothesis was that adoption of PROs questionnaire could significantly improve the agreement.Eligible patients were receiving active anti-cancer treatment. Patients in the control group underwent usual visits (group A), while patients of group B, before each visit, filled a PROs paper questionnaire, to provide information about symptoms and toxicities. No specific instructions were provided to physicians to integrate such information in medical records. Agreement between patient and physician evaluations was assessed by Cohen's κ, calculating under-reporting as proportion of toxicities reported by patients but not recorded by physicians.211 patients (412 visits) have been analyzed. For all symptoms, Cohen's κ was better for group B: emesis (0.25 group A vs. 0.36 group B), diarrhea (0.16 vs. 0.57), constipation (0.07 vs. 0.28), pain (0.22 vs. 0.42), fatigue (0.03 vs. 0.08). For all symptoms, although under-reporting was relevant in both groups, it was lower for group B: emesis (75.49% vs. 60.0%, p=0.031), diarrhea (82.89% vs. 50.0%, p0.001), constipation (92.11% vs. 69.57%, p0.001), pain (59.57% vs. 42.31%, p=0.01), fatigue (82.11% vs. 64.10%, p0.001).Adoption of paper PROs allowed a significant reduction in under-reporting of symptoms, but agreement remained suboptimal. Direct integration of electronic PROs could minimize the issue of under-reporting of medical records, increasing their accuracy.

Emmanuele De Luca,1,2,* Donatella Marino,1,2,* Massimo Di Maio1,2 1Department of Oncology, University of Turin, Torino, Italy; 2Division of Medical Oncology, Ordine Mauriziano Hospital, Torino, Italy*These authors contributed equally to this workCorrespondence: Massimo Di MaioDivision of Medical Oncology, Ordine Mauriziano Hospital, Via Magellano 1, Turin 10128, ItalyTel +39 011 5082032Fax +39 011 5085081Email massimo.dimaio@unito.itAbstract: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and predominantly develops in patients with liver cirrhosis. In patients with advanced disease, such as extra-hepatic extension or portal vein involvement, and with intermediate disease unsuitable for locoregional therapies, systemic therapy is recommended, if liver function and performance status are adequate. Following a decade of negative Phase III trials since the approval of sorafenib, more recently several drugs have proven efficacy both in first line versus sorafenib (lenvatinib) or in second line versus placebo (regorafenib, cabozantinib, ramucirumab). In this review, we summarize the preclinical and clinical evidence supporting the use of ramucirumab, a recombinant IgG1 monoclonal antibody that specifically binds to Vascular Endothelial Growth Factor receptor 2 (VEGFR-2), in HCC. Following the results of the REACH trial, that was negative in the overall study population but identified a subgroup that could benefit from ramucirumab treatment, the REACH-2 trial was a randomized, placebo-controlled trial, designed to assess ramucirumab as second line in patients with alpha-fetoprotein (AFP) ≥ 400 ng/mL. The results of REACH-2 were published in February 2019, leading to Food and Drug Administration and European Medicines Agency approval of the drug as second-line agent for advanced HCC (after sorafenib) in patients with AFP ≥ 400 ng/mL. For the first time in the history of systemic treatments for HCC, a predictive factor of efficacy was identified. In this review, we also discuss the potential clinical development of systemic treatments in HCC, focusing on combination therapies with immunotherapy (following the recent results of the combination of atezolizumab and bevacizumab in the IMbrave 150 clinical trial) and treatment sequences as a way to maximize survival benefit.Keywords: ramucirumab, hepatocellular carcinoma, VEGF, immunotherapy

The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m−2 (D) with the combination of docetaxel 80 mg m−2 and epirubicin 75 mg m−2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n=26) and D arms (n=25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy.

This article analyzes the interaction between changes in tariff protection, informality, inequality and aggregate income. First, we describe some new empirical evidence on informality, the formal/informal wage gap and trade openness in Latin American countries. Then we present a simple model characterized by three (empirically based) assumptions: (1) agents consume both formal and informal goods; (2) the government uses tariff revenues to purchase formal goods; (3) informality is a voluntary phenomenon. The model predicts that tariff reduction increases informality and wage inequality and that the maximization of income requires a positive level of tariff protection. The model's results are shown to be consistent with the empirical evidence concerning Latin American countries.

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

Background Large randomised clinical trials and systematic reviews substantiate that tamoxifen is ineffective in improving survival of patients with hepatocellular carcinoma (HCC). However, a recent report suggested that the drug might prolong survival among patients with well preserved liver function. The aim of this paper is to validate this hypothesis. Methods We used the updated database of the phase 3 randomised CLIP-1 trial that compared tamoxifen with supportive therapy. Primary endpoint was overall survival. Treatment arms were compared within strata defined according to the Okuda stage and the CLIP-score. Survival differences were tested by the Log-rank test. Results Tamoxifen was not effective in prolonging survival in Okuda I-II subgroup (p = 0.501). Median survival times were equal to 16.8 (95%CI 12.7–18.5) months for tamoxifen and 16.8 (95%CI 13.5–22.4) months for the control arms; 1-year survival probabilities were equal to 58.8% (95%CI 51.7–65.8) and 59.4 (95%CI 52.5–66.2), respectively. Similar results were observed in the better CLIP subgroup (score 0/1), without evidence of difference between the two treatment arms (p = 0.734). Median survival times were equal to 29.2 (95%CI 20.1–36.4) months with tamoxifen and 29.0 (95%CI 23.3–35.2) months without; 1-year survival probabilities were equal to 80.9% (95%CI 72.5–89.3) with tamoxifen and 77.1% (95%CI 68.6–85.7) for the control arm. Conclusion The recent suggestion that tamoxifen might be effective in the subgroup of patients with better prognosis is not supported by a reanalysis of the CLIP-1 trial. Tamoxifen should no longer be considered for the treatment of HCC patients and future trials of medical treatment should concentrate on different drugs.

The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established.Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P

C-erbB2 is over-expressed or amplified in many carcinomas. We assessed the relationship between erb-B2 immunoreactivity, and its predictive role in progression-free survival and treatment outcome in patients with cervical carcinoma. Sections from 65 cervical carcinoma were immunostained with antibody to p185 erbB2. Immunoreactive ErbB2 was found in 25 patients (38%) [+ 15 pts. (23%); ++ 10 pts. (15%)]. There were no correlation with age, performance status, grading and histology. Erb-B2 immunoreactivity significantly correlated with stage of the disease. Positive immunoreactivity was found in 63%, 44%, 14% and 0% of stage I, II, III and IV carcinomas, (p = 0.0045). Progression-free survival was longer in erb-B2 positive patients without reaching significance. No correlation was found between erbB2 and response to radiotherapy or chemotherapy. In conclusion, a significant proportion of stage I and II cervical cancer express erb-B2 compared to more advanced stages. Expression of the oncogene does not appear to be related to prognosis or treatment outcome.

Aromatase inhibitors (AI) have become a cornerstone of adjuvant treatment for postmenopausal patients with estrogen receptor (ER)- positive early breast cancer. This chapter reviews the available evidence on endocrine effects of AI. Pharmacological activity of AI produces estradiol suppression, which represents the only known mechanism of action of such drugs, determining both side effects and antineoplastic efficacy. Overall, all third-generation AI (anastrozole, exemestane, letrozole) produce a significant suppression of estradiol levels, but there are some data suggesting that this effect might be less extensive than commonly thought and there are few comparative data to verify whether estradiol suppression varies with different AI. The most frequent side effects, related to estradiol suppression and reported in largescale clinical trials of adjuvant treatment with AI, are gynecological symptoms (less frequent and less severe than with tamoxifen, with the exception of vaginal dryness) and musculoskeletal symptoms (worse than with tamoxifen, which even has a positive effect on bone health). Disorders of lipid metabolism and cardiovascular side effects are less frequent. Among the latter, thromboembolism is less frequent with AI than with tamoxifen. There are many issues still of interest for clinical research on endocrine effects of AI. For example, it seems of utmost importance to verify whether endocrine effects might be predictive of AI efficacy and help to select the patients who can derive the greatest benefit from treatment with these drugs.

This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.

Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. Methods: Patients received maintenance olaparib capsules (400mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 336 very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P < 0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i) pain self-assessment should be part of oncological clinical practice; (ii) pain control should be a primary goal in clinical practice and in clinical trials; (iii) physicians should receive more training in pain management; (iv) analgesic treatment deserves greater attention in protocols of anticancer treatment. © 2004 Cancer Research UK.

SARS-CoV2 infection, responsible for the COVID-19 disease, can determine cardiac as well as respiratory injury. In COVID patients, viral myocarditis can represent an important cause of myocardial damage. Clinical presentation of myocarditis is heterogeneous. Furthermore, the full diagnostic algorithm can be hindered by logistical difficulties related to the transportation of COVID-19 patients in a critical condition to the radiology department. Our aim was to study longitudinal systolic cardiac function in patients with COVID-19-related myocarditis with echocardiography and to compare these findings with cardiac magnetic resonance (CMR) results. Patients with confirmed acute myocarditis and age- and gender-matched healthy controls were enrolled. Both patients with COVID-19-related myocarditis and healthy controls underwent standard transthoracic echocardiography and speckle-tracking analysis at the moment of admission and after 6 months of follow-up. The data of 55 patients with myocarditis (mean age 46.4 ± 15.3, 70% males) and 55 healthy subjects were analyzed. The myocarditis group showed a significantly reduced global longitudinal strain (GLS) and sub-epicardial strain, compared to the control (p < 0.001). We found a positive correlation (r = 0.65, p < 0.0001) between total scar burden (TSB) on CMR and LV GLS. After 6 months of follow-up, GLS showed marked improvements in myocarditis patients on optimal medical therapy (p < 0.01). Furthermore, we showed a strong association between baseline GLS, left ventricular ejection fraction (LVEF) and TSB with LVEF at 6 months of follow-up. After a multivariable linear regression analysis, baseline GLS, LVEF and TSB were independent predictors of a functional outcome at follow-up (p < 0.0001). Cardiac function and myocardial longitudinal deformation, assessed by echocardiography, are associated with TSB at CMR and have a predictive value of functional recovery in the follow-up.

Purpose\ud This paper illustrates a conceptual model for a new patient-reported outcome measure (PROM) aimed at measuring financial toxicity (FT) in oncological setting in Italy, where citizens are provided universal healthcare coverage.\ud \ud Methods\ud Focus groups with overall 34 patients/caregivers in three different Italian centers (from Northern, Centre, and Southern Italy) and an open-ended survey with 97 medical oncologists were undertaken. Transcripts from focus groups and the open-ended survey were analyzed to identify themes and links between themes. Themes from the qualitative research were supplemented with those reported in the literature; concepts identified formed the basis for item development that were then tested through the importance analysis (with 45 patients) and the cognitive debriefing (with other 45 patients) to test relevance and comprehension of the first draft PRO instrument.\ud \ud Results\ud Ten domains were extracted by analyzing 156 concepts generated from focus groups and the open-ended survey. After controlling for redundancy, 55 items were generated and tested through the importance analysis. After controlling comprehension and feasibility through cognitive debriefing interviews, a first version of the questionnaire consisting of 30 items was devised.\ud \ud Conclusions\ud This qualitative study represents the first part of a study conducted to develop a new PROM to assess FT in Italy, by using a bottom-up approach that makes the most of patients’ experiences and the health system analysis.\ud \ud Trial registration\ud clinicaltrials.gov NCT03473379 first posted on March 22, 2018.

Aims The aim of this study was to investigate prospectively the effect of sacubitril/valsartan in advanced heart failure (HF) patients in waiting list for heart transplantation (HT) and the effect on physical frailty (PF). Methods and results We treated 37 consecutive patients with advanced HF with sacubitril/valsartan. Patients were followed up until HT, device implant, or last follow‐up visit after 2 years of follow‐up. At baseline, mean New York Heart Association (NYHA) class was 3.1 ± 0.4, with 64.9% in NYHA III and 35.1% NYHA IIIB. Left ventricular ejection fraction was 23.5 ± 5.8%, VO2 max was 10.3 ± 2.3 mL/kg/min, cardiac index was 2.3 ± 0.5 L/min/m2, and N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) was 4943.0 ± 5326.8 pg/mL. After a mean follow‐up of 17.1 ± 4.4 months, no deaths were observed, but NYHA class improved significantly with 56.8% in NYHA II, 40.5% in NYHA III, and 2.7% in NYHA IIIB (P < 0.001). VO2 max and 6 min walk test (6MWT) increased, whereas pulmonary systolic blood pressure, E/E′, VE/VCO2 slope, and NT‐pro‐BNP decreased. At right heart catheterization performed after 1 year of follow‐up, cardiac index and pulmonary vascular resistance remained stable, while a decrease in systolic pulmonary artery pressure and pulmonary capillary wedge pressure is observed. Furosemide dosage decrease from 102.7 ± 69.4 to 78.7 ± 66.3 mg (P = 0.040). PF decreased from 3.35 ± 1.0 at baseline to 1.57 ± 1.3 at the end of follow‐up (P < 0.001), with a reduction in all PF domains. Conclusions Our study showed a rapid improvement in PF in HT waiting list patients treated with sacubitril/valsartan. The improvement in all PF domains was paralleled by VO2 and 6MWT increase and together with an NT‐pro‐BNP reduction constant over the follow‐up.

Humans drive in a holistic fashion which entails, in particular, understanding dynamic road events and their evolution. Injecting these capabilities in autonomous vehicles can thus take situational awareness and decision making closer to human-level performance. To this purpose, we introduce the ROad event Awareness Dataset (ROAD) for Autonomous Driving, to our knowledge the first of its kind. ROAD is designed to test an autonomous vehicle's ability to detect road events, defined as triplets composed by an active agent, the action(s) it performs and the corresponding scene locations. ROAD comprises videos originally from the Oxford RobotCar Dataset, annotated with bounding boxes showing the location in the image plane of each road event. We benchmark various detection tasks, proposing as a baseline a new incremental algorithm for online road event awareness termed 3D-RetinaNet. We also report the performance on the ROAD tasks of Slowfast and YOLOv5 detectors, as well as that of the winners of the ICCV2021 ROAD challenge, which highlight the challenges faced by situation awareness in autonomous driving. ROAD is designed to allow scholars to investigate exciting tasks such as complex (road) activity detection, future event anticipation and continual learning. The dataset is available at https://github.com/gurkirt/road-dataset; the baseline can be found at https://github.com/gurkirt/3D-RetinaNet., IEEE Transactions on Pattern Analysis and Machine Intelligence, 45 (1), ISSN:0162-8828, ISSN:1939-3539

Background andObjectives: Current guidelines on cardiac rehabilitation (CR) suggest moderate-intensity physical activity after acute coronary syndrome (ACS). Recent report have shown that high-intensity interval training (HIIT) could be more effective than moderate-intensity continuous training (MCT) in improving cardiac performance. Our aim was to analyze the effects of HIIT protocol after ACS on advanced echocardiographic parameters of myocardial function. Materials and Methods: In total, 75 patients with recent ACS, with or without ST segment elevation, were enrolled and compared with a control group of 50 age- and sex-comparable healthy subjects. Patients were randomized to perform a MCT training or HIIT-based rehabilitation program. A complete echocardiographic evaluation, including left ventricular (LV) and left atrial (LA) global longitudinal strain (GLS) and myocardial work (MW) through speckle-tracking analysis, was performed for all patients, before and after cardiac rehabilitation training. A cardiopulmonary exercise testing (CPET) was also performed at the end of the rehabilitation program. Results: Patients who followed the HIIT rehabilitation program showed improved LV diastolic function compared to the MCT group (E/e’: 3.4 ± 3.1 vs. 6.4 ± 2.8, respectively, p < 0.01). Similarly, LV systolic function showed significant improvement in the group of patients performing HIIT (ejection fraction: 53.1 ± 6.4 vs. 52.3 ± 5.4%, p < 0.01; GLS: −17.8 ± 3.8 vs. −15.4 ± 4.3, p < 0.01). In addition, LA strain was improved. MW efficiency was also increased in the HIIT group (91.1 ± 3.3 vs. 87.4 ± 4.1%, p < 0.01), and was closely related to peak effort measurements expressed in peak VO2 by CPET. Conclusions: In patients with recent ACS, the HIIT rehabilitation program determined reverse cardiac remodeling, with the improvement of diastolic and systolic function, assessed by standard echocardiography. In addition, cardiac deformation index as GLS, LA strain and MW efficiency improved significantly after HIIT, and were associated with functional capacity during effort.

Background and objectives: Pre-existing atrial fibrillation (AF) is a frequent comorbidity in hospitalized patients with COVID-19; however, little is still known about its prognostic role in infected patients. The aim of our study was to evaluate whether the pre-existing AF as comorbidity would contribute to increase the risk for severe forms of COVID-19, worse prognosis, or even higher mortality. Materials and Methods: We retrospectively evaluated all consecutive COVID-19 patients admitted to the emergency department of nine Italian Hospitals from 1 March to 30 April 2020.The prevalence and the type of pre-existing AF have been collected. The correlation between the history and type of AF and the development of severe ARDS and in-hospital mortality has been evaluated. Results: In total, 467 patients (66.88 ± 14.55 years; 63% males) with COVID-19 were included in the present study. The history of AF was noticed in 122 cases (26.1%), of which 12 (2.6%) with paroxysmal, 57 (12.2%) with persistent and 53 (11.3%) with permanent AF. Among our study population, COVID-19 patients with AF history were older compared to those without AF history (71.25 ± 12.39 vs. 65.34 ± 14.95 years; p < 0.001); however, they did not show a statistically significant difference in cardiovascular comorbidities or treatments. Pre-existing AF resulted in being independently associated with an increased risk of developing severe ARDS during the hospitalization; in contrast, it did not increase the risk of in-hospital mortality. Among patients with AF history, no significant differences were detected in severe ARDS and in-hospital mortality between patients with permanent and non-permanent AF history. Conclusions: Pre-existing AF is a frequent among COVID-19 patients admitted to hospital, accounting up to 25% of cases. It is independently associated with an increased risk of severe ARDS in hospitalized COVID-19 patients; in contrast, it did not affect the risk of death. The type of pre-existing AF (permanent or non-permanent) did not impact the clinical outcome.

High mortality rates in elderly patients or in those with underlying chronic illnesses and/or a compromised immune system is a peculiar feature of COVID-19 infection. The possible coexistence of a cancer and COVID-19 infection in the same individual prompted concerns regarding their synergistic effect on prognosis. In order to balance patients’ needs with the risks related to the infection, the question oncologists have asked from the beginning of the first wave of the pandemic has been: ‘how can we deal with COVID-19 infection in cancer patients?’ In pursuing its mission, the Associazione Italiana Oncologia Medica (AIOM) has made every possible effort to support cancer patients, health care professionals and institutions in the decision-making processes the pandemic has engendered within this scenario. The relevant documents as well as the educational and institutional initiatives the AIOM has taken are reported in this article.

For decades metastatic squamous cell carcinoma of the anus (SCCA)has been considered a rare disease with very limited treatment options and a dismal prognosis. Prior to 2017, no data from prospective studies on the management of metastatic SCCA were available with scant information from retrospective analyses and few treatment options. Recently, InterAAct trial showed an advantage of carboplatin plus paclitaxel over the historical standard of care represented by cisplatin plus 5-fluorouracil. Unfortunately, there is no established second-line treatment after progression to first-line platinum-based chemotherapy. Interestingly, a better understanding of the immunobiology of the neoplasm and the strict association between HPV/HIV infection and tumor microenvironment led to the development of immunotherapies. Emerging evidence suggests that the use of anti-PD1/PD-L1 agents could lead to promising antitumor activity in a subgroup of patients with pre-treated anal cancer, opening new therapeutic scenarios. Here, we will focus on completed clinical trials evaluating immunotherapy in patients with (SCCA), pointing out the future perspectives and possible biomarkers of response.

Introduction: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID-19. The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. Materials and methods: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. Results: 414 hospitalized patients with COVID-19 (66.9±15.0years, 61.1% male) were included in the present study. During a median follow-up of 28days (IQR: 12-45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new-onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in-hospital mortality (RR: 2.55; P:.003). Conclusions: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients.

Little is still known about the clinical features associated with the occurrence of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus disease 2019 (COVID-19). The aim of the present study was to describe the prevalence of pre-admission antithrombotic therapies in patients with COVID-19 and to investigate the potential association between antithrombotic therapy and ARDS, as disease clinical presentation, or in-hospital mortality. We enrolled 192 consecutive patients with laboratory-confirmed COVID-19 admitted to emergency department of five Italian hospitals. The study population was divided in two groups according to the evidence of ARDS at chest computed tomography at admission. Propensity score weighting adjusted regression analysis was performed to assess the risk ARDS at admission, and death during hospitalization, in patients treated or not with antiplatelet and anticoagulant agents. ARDS was reported in 73 cases (38 %), who showed more likely hypertension compared to those without ARDS (57.8 % vs 49.6 %; P = 0.005). Thirty-five patients (18.5 %) died during the hospitalization. Not survived COVID-19 patients showed a statistically significant increased age (77 ± 8.31 vs 65.57 ± 8.31; P = 0.001), hypertension (77.1 % vs 53.5 %; P = 0.018) and coronary artery disease prevalence (28.6 % vs 10.2 %; P = 0.009). Both unadjusted and adjusted regression analyses showed no difference in the risk of ARDS at admission, or death during hospitalization, between patients treated or not with antiplatelets or anticoagulants. Pre-admission antithrombotic therapy, both antiplatelet and anticoagulant, does not seem to show a protective effect in severe forms of COVID-19 with ARDS at presentation and rapidly evolving toward death.

Background The risk of death in patients affected by ST-elevation segment myocardial infarction (STEMI) is well known, but more data are required to define the in-hospital mortality in special subsets. We sought to assess the prognostic value of indicators in patients with large anterior STEMI as a first acute coronary event, undergoing percutaneous coronary intervention (PCI) and intra-aortic balloon pump (IABP). Methods and results We evaluated 48 consecutive large anterior STEMI patients admitted as first acute coronary event, undergoing in acute phase both PCI and IABP. Patient demographics, clinical, noninvasive and invasive findings, together with in-hospital complications, were collected. Moreover, findings obtained after a 24-month follow-up were reported. The primary endpoint was in-hospital mortality, whereas the secondary endpoints were out of hospital mortality, rehospitalization for heart failure or reinfarction, and New York Heart Association (NYHA) class at least 2 at follow-up visit. The univariate analysis showed a significant association with symptom to balloon, left anterior descending coronary artery, myocardial blush grade, and wall motion score index. Results of the multivariable analysis revealed the strongest predictive power for in-hospital mortality of proximal left anterior descending coronary artery (odds ratio: 6.9; 95% confidence interval: 1.1-67.7) and of myocardial blush grade 0-1 (odds ratio: 5.5; 95% confidence interval: 1.0-38.8). In-hospital death occurred in 13 patients (27% of total cases), whereas, at follow-up, the mean of survival was 66.7 ± 7.0%. Conclusion The patients with large anterior STEMI as a first acute coronary event, undergoing PCI and IABP, had a very high in-hospital mortality, whereas the mortality rate over the follow-up period was lower. The involvement of a large territory at risk and the ineffective treatment in terms of myocardial reperfusion were the main predictors of in-hospital mortality.

// Lucia Kim 1,12,* , Mauro Saieg 1,13,* , Massimo Di Maio 2,14,* , Ciro Gallo 3,* , Charles Butts 4 , Fortunato Ciardiello 5 , Ronald Feld 6 , Dengxiao Cheng 6 , Vittorio Gebbia 7 , Marco Angelo Burgio 8 , Yasmin Alam 9 , Simona Signoriello 3 , Antonio Rossi 10 , Natasha Leighl 6 , Paolo Maione 10 , Alessandro Morabito 2 , Geoffrey Liu 6,** , Ming-Sound Tsao 1,** , Francesco Perrone 2,** and Cesare Gridelli 10,11,** 1 Department of Pathology, University Health Network, Princess Margaret Cancer Center and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 2 National Cancer Institute, G. Pascale Foundation, IRCCS, Naples, Italy 3 Department of Mental Health and Preventive Medicine, Chair of Statistics, Second University of Naples, Naples, Italy 4 Medical Oncology, Cross Cancer Institute, Edmonton, Canada 5 Medical Oncology, Second University, Naples, Italy 6 Division of Hematology and Oncology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada 7 Medical Oncology, Casa di Cura La Maddalena, Palermo, Italy 8 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy 9 Medical Oncology, Windsor Regional Cancer Centre, Windsor, Canada 10 Department of Oncology/Hematology, Division of Medical Oncology, “S.G. Moscati” Hospital, Avellino, Italy 11 On behalf of the TORCH Investigators 12 Department of Pathology, Inha University School of Medicine, Incheon, South Korea 13 Santa Casa Medical School, Sao Paulo, SP, Brazil 14 University of Turin, Turin, Italy * Co-first author ** Co-last author Correspondence to: Cesare Gridelli, email: // Keywords : NSCLC, EGFR TKI, biomarker analysis, predictive factors, prognostic factors Received : November 09, 2016 Accepted : February 01, 2017 Published : February 25, 2017 Abstract Background: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. Methods: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting. Progression-free survival (PFS) was the primary end-point, overall survival, response rate and side effects (diarrhoea and skin toxicity) were secondary end-points. Interactions between biomarkers and treatment were studied with multivariable models (either Cox model or logistic regression). Statistical analyses accounted for multiple comparisons. Results: At least one biomarker was assessed in 324 out of 760 patients in the TORCH study. EGFR mutation was more common in female ( P = 0.0001), East Asians ( P < 0.0001) and never smoker ( P < 0.0001) patients; low MET protein expression by IHC (H-score