Publications by authors named "Alessandra Fabi"

161 Publications

PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy.

NPJ Breast Cancer 2021 May 5;7(1):47. Epub 2021 May 5.

Istituto Nazionale Tumori Fondazione G. Pascale, Napoli, Italy.

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS results in Italy and its impact on treatment decisions. Physicians' treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2- early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.
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http://dx.doi.org/10.1038/s41523-021-00246-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099872PMC
May 2021

Neoadjuvant Chemotherapy in Breast Cancer: An Advanced Personalized Multidisciplinary Prehabilitation Model (APMP-M) to Optimize Outcomes.

J Pers Med 2021 Apr 21;11(5). Epub 2021 Apr 21.

Multidisciplinary Breast Centre, Dipartimento Scienze della Salute della Donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Neoadjuvant chemotherapy is increasingly being employed in the management of breast cancer patients. Efforts and resources have been devoted over the years to the search for an optimal strategy that can improve outcomes in the neoadjuvant setting. Today, a multidisciplinary approach with the application of evidence-based medicine is considered the gold standard for the improvement of oncological results and patient satisfaction. However, several clinical complications and psychological issues due to various factors can arise during neoadjuvant therapy and undermine outcomes. To ensure that health care needs are adequately addressed, clinicians must consider that women with breast cancer have a high risk of developing "unmet needs" during treatment, and often require a clinical intervention or additional care resources to limit possible complications and psychological issues that can occur during neoadjuvant treatment. This work describes a multidisciplinary model developed at "Fondazione Policlinico Universitario Agostino Gemelli" (FPG) in Rome in an effort to optimize treatment, ease the application of evidence-based medicine, and improve patient quality of life in the neoadjuvant setting. In developing our model, our main goal was to adequately meet patient needs while preventing high levels of distress.
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http://dx.doi.org/10.3390/jpm11050324DOI Listing
April 2021

Development of a Digital Research Assistant for the Management of Patients' Enrollment in Oncology Clinical Trials within a Research Hospital.

J Pers Med 2021 Mar 27;11(4). Epub 2021 Mar 27.

Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy.

Clinical trials in cancer treatment are imperative in enhancing patients' survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients' accrual in clinical trials. We developed a specific platform, called "Digital Research Assistant" (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients' records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients' records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient's data and clinical trial's inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.
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http://dx.doi.org/10.3390/jpm11040244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066078PMC
March 2021

Impact of baseline and on-treatment glycemia on everolimus-exemestane efficacy in patients with hormone receptor-positive advanced breast cancer (EVERMET).

Clin Cancer Res 2021 Mar 30. Epub 2021 Mar 30.

Clinical Oncology, University Hospital of Udine.

Purpose: The mTORC1 inhibitor everolimus (EVE) in combination with the aromatase inhibitor exemestane (EXE) is an effective treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (HR+/HER2- aBC). However, EVE can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/AKT/mTORC1 pathway and induce tumor resistance to EVE.

Experimental Design: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first three months of therapy) blood glucose levels on progression-free survival (PFS) in HR+/HER2- aBC patients treated with EVE-EXE.

Results: We evaluated 809 HR+/HER2- aBC patients treated with EVE-EXE as any-line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared to patients who are already hyperglycemic at baseline and experience diabetes during EVE-EXE therapy (mPFS 6.34 vs. 10.32 months; HR 1.76; 95% CI 1.15-2.69; p=0.008).

Conclusions: The impact of on-treatment glycemia on the efficacy of EVE-EXE therapy in HR+/HER2 aBC patients depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in HR+/HER2 aBC patients.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4928DOI Listing
March 2021

Use of rehabilitation pathways in women with breast cancer in the first 12 months of the disease: a retrospective study.

BMC Cancer 2021 Mar 24;21(1):311. Epub 2021 Mar 24.

Psychology Unit, IRCCS Istituto Nazionale Tumori Regina Elena Roma, Rome, Italy.

Background: Breast cancer (BC) presents important physical and psychological challenges that should be appropriately addressed through continuous, integrated and individualized rehabilitation programs after treatment. In this study, we aimed to collect more information on the rehabilitation patterns and utilization of healthcare services by women with BC.

Methods: We retrospectively analyzed data from two archives of the Lazio Regional Health System Database to assess rehabilitation patterns in women diagnosed with BC in the Lazio region (Italy) in 2008.

Results: A total of 5538 women diagnosed with BC were considered in the present study. Most patients (81.7%) received outpatient rehabilitative care, consisting mainly of pathology-related interventions and, more rarely, disability-related interventions (mainly motor rehabilitation and rarely cognitive or psychological therapy). Few patients followed an inpatient (1.3%) or an intensive outpatient rehabilitation program (1.0%).

Conclusion: Most patients do not receive adequate rehabilitation care during the first year after diagnosis. More information and better rehabilitation services should be provided to help patients with BC access rehabilitation programs. The study also suggests the importance of psychosocial and cognitive interventions, which is a major unmet need in women with BC.
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http://dx.doi.org/10.1186/s12885-021-07927-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993006PMC
March 2021

Adjuvant chemotherapy after severe myelotoxicity during chemoradiation phase in malignant gliomas. Is it feasibile? Results from AINO study (Italian Association for Neuro-Oncology).

J Neurol 2021 Feb 20. Epub 2021 Feb 20.

Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.

Background: Malignant gliomas (MG) are aggressive brain tumours in adults. The standard of care is concurrent radiation plus temozolomide (TMZ) [chemo-radiotherapy (CRT)] followed by TMZ maintenance up to 6 months. TMZ is considered to have a low toxicity profile, but several studies reported occurrence of severe myelosuppression, especially during the concomitant phase. Toxicity may be prolonged, thus treatment should be discontinued.

Purpose: To evaluate the risk of recurrente myelotoxicity during adjuvant chemotherapy (CT) in patients who recovered from severe myelotoxicity during CRT.

Methods: We retrospectively collected data on patients with MG who developed and recovered from severe myelotoxicity during CRT from eight Italian neuro-oncology centers.

Results: We included 87 patients. Histology was Glioblastoma (GBM) in 78 patients (89.7%); 60% of patients were female. After myelotoxicity recovery, 54 (62%) received treatment. The majority of them (82%, n = 44) received adjuvant TMZ and 18% (n = 10) others treatments. Out of 44 patients who received adjuvant TMZ, 34% experienced the re-occurrence of grade 3-4 myelotoxicity which required permanent CT discontinuation in 6 (13%) cases. Patients who received TMZ or other treatments had longer overall (OS) (adjusted HR 0.46, p = 0.008) and progression free survival (PFS) (adjusted HR 0.57, p = 0.034) than those who remained untreated.

Conclusion: Our study suggests that after severe myelotoxicity the majority of patients received treatment, particularly with TMZ. Only a fraction of patients experienced toxicity recurrence, suggesting that TMZ is well tolerated and had an impact on PFS and OS.
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http://dx.doi.org/10.1007/s00415-021-10438-4DOI Listing
February 2021

CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives.

Cancers (Basel) 2021 Jan 18;13(2). Epub 2021 Jan 18.

Oncology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, Italy.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2-, ABC.
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http://dx.doi.org/10.3390/cancers13020332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830463PMC
January 2021

Loco-regional adjuvant radiation therapy in breast cancer patients with positive axillary lymph-nodes at diagnosis (CN2) undergoing preoperative chemotherapy and with complete pathological lymph-nodes response. Development of GRADE (Grades of recommendation, assessment, Development and Evaluation) recommendation by the Italian Association of radiation therapy and Clinical Oncology (AIRO).

Breast 2021 Feb 2;55:119-127. Epub 2021 Jan 2.

Radiotherapy, Dipartimento di Biomedicina e Prevenzione, Università Degli Studi di Roma Tor Vergata, Rome, Italy.

Objective: To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST).

Material And Methods: Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events.

Results: Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63-1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events.

Conclusions: Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy.
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http://dx.doi.org/10.1016/j.breast.2020.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808946PMC
February 2021

Palbociclib Plus Fulvestrant or Everolimus Plus Exemestane for Pretreated Advanced Breast Cancer with Lobular Histotype in ER+/HER2- Patients: A Propensity Score-Matched Analysis of a Multicenter Retrospective Patient Series.

J Pers Med 2020 Dec 18;10(4). Epub 2020 Dec 18.

Comprehensive Cancer Center, UOC di Oncologia Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO-FUL) with everolimus plus exemestane (EVE-EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO-FUL and 26 with EVE-EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE-EXE compared with PALBO-FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35-0.96; = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE-EXE compared to PALBO-FUL (6.0 vs. 4.6 months, = 0.04). This retrospective analysis suggests that EVE-EXE is more effective than PALBO-FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence.
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http://dx.doi.org/10.3390/jpm10040291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766166PMC
December 2020

The Experience of Oncology Healthcare Providers in the Central Italy during the COVID-19 Lockdown.

Cancers (Basel) 2020 Oct 18;12(10). Epub 2020 Oct 18.

Psyconcology Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

While the emotional response of healthcare providers during the COVID-19 pandemic has been extensively investigated in countries in the Far-East, little is known about the psychological impact and the associated emotional distress of healthcare providers in Italy, especially with regard to different regions. The aim of the "VIRARE" survey, which was addressed to all the healthcare providers in the Lazio region (central Italy) and, in particular, to those working in the oncology field, is to analyze their opinion on the impact and management of the pandemic, to better understand the level of their psychological distress. A global good psychological response of healthcare providers to the pandemic has emerged, independently from their different occupations in the oncology field. Healthcare providers show a high degree of resilience, identifying the major causes of distress the difficulty of the management of this situation, the obstacles in their working activity and expressing a high degree of dissatisfaction with how Italian institutions handled this situation. This survey also provides a direct comparison between COVID-19-infected (or directly in contact with COVID-19-infected patients) and uninfected healthcare providers, identifying the sub-category of infected professionals that reported signs of depression as particularly vulnerable.
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http://dx.doi.org/10.3390/cancers12103031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603147PMC
October 2020

p53 and BLC2 Immunohistochemical Expression Across Molecular Subtypes in 1099 Early Breast Cancer Patients With Long-Term Follow-up: An Observational Study.

Clin Breast Cancer 2020 12 13;20(6):e761-e770. Epub 2020 May 13.

Biostatistics and Bioinformatic Unit, Scientific Direction, IRCCS, Regina Elena National Cancer Institute, Rome, Italy.

Introduction: p53 and antiapoptotic B-cell leukemia/lymphoma 2 (BLC2) have been proposed as prognostic markers for early breast cancer (BC), although their relationship with conventional parameters and patient prognosis, as well as their distribution within the molecular BC subtypes remains uncertain.

Patients And Methods: In this observational study, we analyzed the immunohistochemical expression of p53 and BLC2 in 1099 early BC patients surgically treated between 2000 and 2006 and followed for at least 5 years, also considering their association with pathologic factors and molecular subtypes, as well as their influence on disease-free survival.

Results: p53 and BLC2 are distributed differently across molecular subtypes (P < .0001); in particular, p53 positivity and BLC2 negativity seems to be associated with more aggressive conventional tumor phenotypes. Moreover, BLC2 negativity seems to be a significant discriminating factor for disease-free survival (P = .003) according to Kaplan-Meier analysis, while p53 seems to have no discriminating effect. Among patients with discordant p53/BLC2 phenotype, the combination p53BLC2 seems to be associated with the worst outcomes (P = .007) and significantly influenced the clinical course of node-negative patients treated only with hormone therapy (P = .004).

Conclusion: These two biomarkers, in addition to conventional pathologic factors and molecular subtype, could help define the risk and outcome of BC.
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http://dx.doi.org/10.1016/j.clbc.2020.05.005DOI Listing
December 2020

Nanoparticle albumin-bound paclitaxel/liposomal-encapsulated doxorubicin in HER2-negative metastatic breast cancer patients.

Future Oncol 2020 Aug 5;16(22):1629-1637. Epub 2020 Jun 5.

Medical Oncology 1, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.

To investigate the toxicity of nab-paclitaxel (wNP)/nonpegylated liposome-encapsulated doxorubicin (wNPLD) combination in HER2-negative metastatic breast cancer (MBC) patients as first-line treatment. Phase I, single-arm study in metastatic breast cancer patients naive to previous chemotherapy for advanced disease. A 3 + 3 dose-escalation design was used to determine the safety. Primary endpoints were the identification of dose-limiting toxicity and maximum tolerated dose. In total, 12 patients (mean age: 52 years; median metastatic sites: 2) were enrolled and 97 cycles were completed. Maximum tolerated dose was wNP + wNPLD 25 mg/m. The most common adverse events were neutropenia, nausea, diarrhea and mucositis. The objective response rate was 68% (response mean duration: 12.6 months). wNP/wNPLD combination constitutes an active regimen with mild toxicity.
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http://dx.doi.org/10.2217/fon-2019-0742DOI Listing
August 2020

Italian consensus and recommendations on diagnosis and treatment of low-grade gliomas. An intersociety (SINch/AINO/SIN) document.

J Neurosurg Sci 2020 Aug 29;64(4):313-334. Epub 2020 Apr 29.

Department of Neuro-Oncology, Città della Salute e della Scienza, University of Turin, Turin, Italy.

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.
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http://dx.doi.org/10.23736/S0390-5616.20.04982-6DOI Listing
August 2020

Is There Still a Role for Endocrine Therapy Alone in HR+/HER2- Advanced Breast Cancer Patients? Results from the Analysis of Two Data Sets of Patients Treated with High-Dose Fulvestrant as First-Line Therapy in the Real-World Setting: The EVA and GIM-13 AMBRA Studies.

Breast Care (Basel) 2020 Feb 17;15(1):30-37. Epub 2019 Apr 17.

Oncology Unit, Ospedale Moriggia Pelascini, Gravedona, Italy.

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting.

Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies).

Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35-82) for the EVA and 57.8 years (range 35.0-82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1-48) and 12.4 months (range 2.9-70.0) in the two data sets, respectively.

Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.
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http://dx.doi.org/10.1159/000495469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098305PMC
February 2020

Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study.

BMC Cancer 2020 Mar 19;20(1):232. Epub 2020 Mar 19.

Breast Medical Oncology Division, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.

Background: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle.

Methods: In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined.

Results: Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65-0.50 for no CINV events on cycles 3 and 4).

Conclusion: The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle.

Trial Registration: This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.
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http://dx.doi.org/10.1186/s12885-020-6707-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081578PMC
March 2020

[Application of narrative medicine in oncological clinical practice: impact on health care professional.]

Recenti Prog Med 2020 03;111(3):154-159

Servizio di Epidemiologia e Registro Tumori, IRCCS Istituto Nazionale Tumori Regina Elena, Roma.

Introduction: Narrative medicine makes explicit the experience of disease and enhances the subjective view in the cure. In addition, the narrative approach involves personal experience and emotional resonances of the health care professional leading him to redefine the values in terms of health and disease. The IMPERO study aims to explore the personal "life experience" of health care professionals involved in studies exploring a new methodological clinical approach: the use of a digital narrative diary in collecting and integrating theme-oriented narration in clinical practice.

Methods: Qualitative study based on the interviews of three health care professionals (two oncologists and one nurse) involved in the AMENO study. The main topic of the interviews was the "perceived" and the intimate experience of each health care professional, particularly on the meaning and the role regarding their personal and professional experience while coping with patients narration. The analysis of data focuses on three aspects: a) the health care professionals' point of view using the diary as a tool for narrative-based medicine; b) the work environment as a framework for the use of the digital diary; c) the mental construction concerning the meaning of the tool and its preliminary use in clinical practice.

Results: The diary is appreciate as a tool for the application of narrative-based medicine; the reading/writing format is considered of high quality and suitable for clinical practice processes. The narration drives a change in the patient-health care professional relationship: the patient is valued as an "individual". An atmosphere of empathy and greater intimacy is created. The perceptions developed over the years of clinical practice, which reflect personal and professional concepts (knowledge and individual believes in illness, health, healing, etc.), influence the perception of the narrative instrument and its clinical use. The work context influences the use of the diary, limiting its potential. Narrative medicine is a way of reorganizing the criteria that contribute in defining the quality of patient care by focusing on the patient-health care professional relationship.

Discussion: The approach of narrative medicine must be reviewed in the light of the relational systemic theory which allows us to understand several aspects: the training in narrative medicine itself, the acquisition of professional skills by practitioners, and the organizational development of the institutions (the organizational structures but also the values and professional culture of work).
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http://dx.doi.org/10.1701/3315.32857DOI Listing
March 2020

T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study.

Clin Breast Cancer 2020 04 14;20(2):e181-e187. Epub 2019 Nov 14.

Department of Medical Oncology, Ospedale Policlinico San Martino, University of Genova, Genoa, Italy; Department of Internal Medicine and Medical Specialties, University of Genova, Genoa, Italy.

Background: T-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy.

Patients And Methods: Eligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS.

Results: Of 445 patients with HER2 metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals [CI], 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%.

Conclusions: Our results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.
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http://dx.doi.org/10.1016/j.clbc.2019.09.001DOI Listing
April 2020

Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial.

Int J Cancer 2020 07 4;147(1):160-169. Epub 2019 Dec 4.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genoa, Italy.

Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52-1.89; OS: HR, 0.95; 95% CI 0.37-2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.
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http://dx.doi.org/10.1002/ijc.32789DOI Listing
July 2020

Should All Patients With HR-Positive HER2-Negative Metastatic Breast Cancer Receive CDK 4/6 Inhibitor As First-Line Based Therapy? A Network Meta-Analysis of Data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT Trials.

Cancers (Basel) 2019 Oct 26;11(11). Epub 2019 Oct 26.

Division of Medical Oncology1, IRCCS Regina Elena National Cancer Institute, 00128 Rome, Italy.

: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (-) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach.

Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed.

Results: First-line treatment options in HR+/HER2- MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53-0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53-0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47-0.86 for abemaciclib + AI) and patient's characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors.

Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics.
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http://dx.doi.org/10.3390/cancers11111661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896062PMC
October 2019

Correction to: Phase II study of weekly carboplatin in pretreated adult malignant gliomas.

J Neurooncol 2019 Oct;145(1):189

Division of Medical Oncology, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.

In the original article, the names of authors Mariantonia Carosi and Tatiana Koudriavtseva were incorrectly captured, and author Francesco Cognetti's affiliation was incorrect. The information is correctly shown here.
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http://dx.doi.org/10.1007/s11060-019-03285-xDOI Listing
October 2019

[LHRH analogs: current role in early and advanced breast cancer treatment of premenopausal patients.]

Recenti Prog Med 2019 Jul-Aug;110(7):347-355

Oncologia Medica 1, Istituto Nazionale Tumori Regina Elena, Roma.

LHRH analogues (LHRHa) are used in the treatment of breast cancer that occurs in young women. Amenorrhoea induced by chemotherapy correlates with a reduced risk of recurrence disease. In premenopausal women, analogous LHRHs are used to suppress ovarian estrogen production, raising estrogen hormone levels to post-menopausal values and improving patient outcomes. Two large clinical studies have investigated the role of complete estrogen blockage in adjuvant hormonal treatment of premenopausal patients. Both studies showed the clinical benefit of ovarian suppression treatment, mainly associated with non-steroidal aromatase inhibitor exemestane in high-risk patients. In the recent years, hormonal treatments made available in clinical practice have considerably prolonged the median survival of patients suffering from endocrine-responsive metastatic breast cancer. Even in the premenopausal setting, CDK4/6 inhibitors in association with endocrine therapy have shown a marked improvement in patient outcomes. The safety and efficacy of this new class of drugs demonstrated in the MONALEESA-7 study in premenopausal women and in the premenopausal subgroups of the PALOMA-3 and MONARCH 2 studies support the use of hormone therapy and analogous LHRH combined with CDK 4/6 inhibitor in patients in premenopausal. Finally, LHRH analogues have been extensively studied in strategies for maintaining ovarian function and fertility preservation during adjuvant chemotherapy in younger patients.
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http://dx.doi.org/10.1701/3197.31747DOI Listing
January 2020

Neurocognitive evaluation in older adult patients affected by glioma.

J Geriatr Oncol 2020 05 2;11(4):701-708. Epub 2019 Jul 2.

Neuro-Oncology Unit, I.R.C.C.S. Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.

Background: Glioblastoma (GBM) has an increasing incidence and dismal prognosis in older adults. This study evaluated neurocognitive status of an older adult population with GBM and its correlation with clinical and demographical variables.

Methods: Each patient underwent an extended neuropsychological evaluation by means of a battery of standardized tests describing eight cognitive domains: global function; verbal learning; short- and long-term memory (LTM); executive functions (EFs); abstract reasoning (AR); attention; and visuo-constructional abilities (CA).

Results: We assessed 79 patients with GBM (median age: 74 years). Out of this initial sample, a subgroup of seventeen patients with six-month median time underwent a follow-up test session. 46 out of the 79 patients (58.2%) presented multi-domain cognitive impairment, 24 patients (30.3%) showed single-domain cognitive impairment and only seven (9%) showed no cognitive impairment. Kaplan Meier estimator showed that patients with AR deficit had a poorer prognosis in terms of progression-free survival and overall survival (p < .001). At the multivariate analysis AR (deficit vs non; hazard ratio (HR) = 5.07, 95%; confidence interval (CI): 1.91-13.46; p < .001) was correlated with disease progression and overall survival, AR (deficit vs non; HR = 7.24, 95% CI: 2.58-20.32; p < .001). Eight out of seventeen patients who underwent follow-up test session showed cognitive improvement, five resulted in further deterioration, and four patients remained stable. LTM, EF, and CA were the most affected functions at follow-up, while verbal learning was the most improved one in patients with cognitive improvement.

Conclusions: Cognitive functioning evaluation should be included among the standard clinical endpoints in the treatment of older adult neuro-oncology patients.
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http://dx.doi.org/10.1016/j.jgo.2019.06.015DOI Listing
May 2020

Phase II study of weekly carboplatin in pretreated adult malignant gliomas.

J Neurooncol 2019 Aug 4;144(1):211-216. Epub 2019 Jul 4.

Division of Medical Oncology, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.

Purpose: Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas.

Methods: This was a single-arm, phase II study. Eligibility criteria included progressive or recurrent glioma after radiotherapy and chemotherapy-based treatments and Karnofsky performance status (KPS) > 60.

Results: Thirty-two patients (median age 43.5 years) were enrolled to receive weekly carboplatin monotherapy in an intravenous method of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival was 2.3 months while overall survival was 5.5 months. Pre-treatment with corticosteroids (i.e. dexamethasone) was associated to clinical benefit in 43.8% of patients. Patients achieving clinical benefit exhibited a longer progression-free survival (4.6 vs. 1.5 months; p > 0.001) and overall survival (7.9 vs. 3.2 months; p = 0.041) compared with those not achieving clinical benefit.

Conclusions: Our findings show that single agent, weekly, intravenous administration of carboplatin may have a role in patients with recurrent glioma and suggest that pre-treatment with corticosteroids may confer survival benefit.
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http://dx.doi.org/10.1007/s11060-019-03223-xDOI Listing
August 2019

The HERBA Study: A Retrospective Multi-Institutional Italian Study on Patients With Brain Metastases From HER2-Positive Breast Cancer.

Clin Breast Cancer 2019 08 18;19(4):e501-e510. Epub 2019 May 18.

Unità di Oncologia Medica, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy. Electronic address:

Background: There is no sufficient evidence to establish a standard of care for patients with brain metastases (BM) from HER2 breast cancer (BC). The aim of this study was to assess the impact of local and systemic treatments on the outcome of patients diagnosed with BM from HER2 BC over a period of 10 years, from 2005 to 2014.

Patients And Methods: Data of 154 patients were retrospectively collected at 14 Italian institutions through a specifically designed database.

Results: Median overall survival (OS) was 24.5 months. Patients receiving surgery/stereotactic radiosurgery experienced longer OS compared to those receiving whole-brain radiotherapy or no treatment (33.5 vs. 11.4 months; hazard ratio = 0.34; 95% confidence interval, 0.22-0.52; P < .001). Interestingly, whole-brain radiotherapy did not improve OS compared to no treatment (11.4 vs. 9.8 months; hazard ratio = 0.99; 95% confidence interval, 0.62-1.62; P = .99). HER2-targeted therapy was associated with better OS compared to systemic therapy without HER2-targeted therapy or no systemic therapy (27.5 vs. 5.4 months; hazard ratio = 0.26; 95% confidence interval, 0.17-0.41; P < .001). At multivariate analysis stratified by local treatments, systemic therapy, Karnofsky performance status, and neurologic symptoms significantly affected OS. Age, number of BM, steroid therapy, number of previous lines of systemic therapy, status of extracranial disease, and period of diagnosis had no significant impact on OS.

Conclusion: Patients with BM from HER2 BC treated with surgery/stereotactic radiosurgery as local treatment and HER2-targeted therapy as systemic treatment experienced the best outcomes. Patients with low Karnofsky performance status and neurologic symptoms had poor survival.
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http://dx.doi.org/10.1016/j.clbc.2019.05.006DOI Listing
August 2019

The unmet need for oncofertility preservation in women: Results of a survey by different oncological specialists in Lazio, Italy.

Curr Probl Cancer 2019 12 17;43(6):100479. Epub 2019 May 17.

Psyco-Oncology Service, Regina Elena National Cancer Institute, Rome, Italy.

In recent years, we have witnessed a growing interest in the prevention of the loss of reproductive efficacy in young women as a result of cancer or its treatments. Indeed, recent studies have shown that loss of fertility impacts deeply on young women and sometimes may be even more stressful than the cancer diagnosis itself. In fact, the risk of treatment-associated infertility and premature menopause is a major concern for patients. Nevertheless, the approach to fertility preservation in women diagnosed with cancer is far from being standardized, and counseling strategies are poorly adopted in clinical practice. In Italy, the federal structure of public health makes it difficult to refer patients to local referral centers experienced in fertility preservation. In particular, a need exists to identify oncologists in the Lazio region specialized in fertility preservation and those facilities who are able to counsel patients regarding their sexuality. For these reasons, the Lazio section of Italian Association of Medical Oncology has led an oncofertility and oncosexuality survey to assess deficiencies in the path to start fertility preservation procedures and to help patients with cancer-related sexual problems. In total, 273 healthcare providers participated in the survey. Overall, the participants had a low interest in their patients' infertility problems, which led to a poor referral of patients to fertility preservation centers. This behavior demonstrated by healthcare providers is attributed to the necessity to rapidly start oncological treatments, the lack of knowledge of referral centers, and the little experience in tackling the subject with the patients. The interviewees also recognize communication difficulties related to lack of information on issues, absence of rehabilitations paths, and embarrassment.
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http://dx.doi.org/10.1016/j.currproblcancer.2019.05.002DOI Listing
December 2019

Treating advanced breast cancer with metronomic chemotherapy: what is known, what is new and what is the future?

Onco Targets Ther 2019 23;12:2989-2997. Epub 2019 Apr 23.

Medical Oncology Unit, Azienda ULSS 3 Serenissima, Mirano-Dolo, Italy.

The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed breast cancer patients present with metastatic disease, and 30%-50% of those diagnosed at earlier stages will subsequently progress to mBC. In terms of ongoing management for advanced/metastatic breast cancer after failure of hormonal therapy, there is a high medical need for new treatment options that prolong the interval to the start of intensive cytotoxic therapy, which is often associated with potentially serious side effects and reduced quality of life. Oral chemotherapeutic agents such as capecitabine and vinorelbine have demonstrated efficacy in patients with mBC, with prolonged disease control and good tolerability. Use of oral chemotherapy reduces the time and cost associated with treatment and is often more acceptable to patients than intravenous drug delivery. Metronomic administration of oral chemotherapy is therefore a promising treatment strategy for some patients with mBC and inhibits tumor progression via multiple mechanisms of action. Ongoing clinical trials are investigating metronomic chemotherapy regimens as a strategy to prolong disease control with favorable tolerability. This article provides an overview of metronomic chemotherapy treatment options in mBC, with perspectives on this therapy from a panel of experts.
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http://dx.doi.org/10.2147/OTT.S189163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485034PMC
April 2019

A multicenter real-world study of bevacizumab in heavily pretreated malignant gliomas: clinical benefit is a plausible end point?

Future Oncol 2019 May 12;15(15):1717-1727. Epub 2019 Apr 12.

Neuroncology Unit, IRCCS Regina Elena National Cancer Institute, via Elio Chianesi 53 00144, Rome, Italy.

This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG).  The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.
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http://dx.doi.org/10.2217/fon-2018-0826DOI Listing
May 2019

Open Kyphoplasty for Metastatic Spine Disease: A Retrospective Clinical Series.

World Neurosurg 2019 Jul 2;127:e751-e760. Epub 2019 Apr 2.

Department of Neurosurgery, IRCSS National Cancer Institute "Regina Elena", Rome, Italy.

Objective: Symptomatic metastatic spine disease (MSD), is a challenging disease involving 3%-20% of patients with bone metastases. Different surgical options are available and must be tailored to the general and neurologic conditions of the patients. Open kyphoplasty (OKP) refers to decompressive hemilaminectomy, associated with a contralateral percutaneous kyphoplasty, and in some cases, to a posterior stabilization. The aim of the study was to critically review our experience during the last decade with OKP in patients with cancer.

Methods: Fifty-three patients with cancer underwent OKP for symptomatic MSD. The Tokuhashi score and Spinal Instability Neoplastic Score were calculated for each patient. Length of hospital stay, perioperative complications, incidence of adjacent-level fractures, and median survival after surgery were evaluated. Karnofsky Performance Status, visual analog scale, and Dennis Pain Score were calculated preoperatively, postoperatively, and at last follow-up.

Results: Median Tokuhashi score and Spinal Instability Neoplastic Score were 10 and 10, respectively. The mean volume of filling material inserted was 3.6 mL. Median operative time was 180 minutes. Complications included 8 leakages (15%), 2 permanent motor deficits (3.8%), and 2 asymptomatic pulmonary embolisms (3.8%). Mean length of hospital stay was 7 days. A significant improvement was observed in Karnofsky Performance Status, visual analog scale score, and Dennis Pain Score (P < 0.0001). Median follow-up was 16 months and overall survival 22 months.

Conclusions: OKP was an effective treatment of symptomatic MSDs in selected oncologic patients with low Tokuhashi scores. It relieved lateral epidural compressions, expanded indications of palliative surgery in patients who were not otherwise surgical candidates, and rapidly dealt with cement leakages.
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http://dx.doi.org/10.1016/j.wneu.2019.03.258DOI Listing
July 2019

Comorbidities in elderly patients with glioblastoma: a field-practice study.

Future Oncol 2019 Mar 18;15(8):841-850. Epub 2019 Jan 18.

Neuro-Oncology Unit, 'Regina Elena' National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.

Aim: This single-center study evaluated the effect of comorbidities on progression-free and overall survival in elderly patients with glioblastoma multiforme (GBM).

Patients & Methods: Comorbid conditions were identified in each patient with the modified version of the cumulative illness rating scale (CIRS).

Results:  Total of 118 patients with GBM were enrolled. An age of >75 years at diagnosis, high CIRS, comorbidity index and performance status play a predictive role on survival.

Conclusion: Comorbidities play an important prognostic role in elderly patients with GBM, a factor too often neglected in clinical practice. If the prognostic role of comorbidity measured by CIRS on outcome will be confirmed, it would be interesting to add it in the algorithm for treatment choice in elderly GBM patients.
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http://dx.doi.org/10.2217/fon-2018-0524DOI Listing
March 2019

RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.

J Exp Clin Cancer Res 2019 Jan 8;38(1):12. Epub 2019 Jan 8.

Unit of Endocrinology and Metabolic Diseases, Department of Systems Medicine, CTO A. Alesini Hospital, ASL Roma 2, University Tor Vergata, Via San Nemesio, 21, 00145, Rome, Italy.

RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, different studies have elucidated its specific role in mammary gland physiology and hormone-driven epithelial proliferation during pregnancy. Of note, several data suggest that progesterone induces mammary RANKL expression in mice and humans. In turn, RANKL controls cell proliferation in breast epithelium under physiological conditions typically associated with higher serum progesterone levels, such as luteal phase of the menstrual cycle and pregnancy. Hence, RANKL/RANK system can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression. Expression of RANKL, RANK, and OPG has been detected in breast cancer cell lines and in human primary breast cancers. To date, dysregulation of RANKL/RANK/OPG system at the skeletal level has been widely documented in the context of metastatic bone disease. In fact, RANKL inhibition through the RANKL-blocking human monoclonal antibody denosumab represents a well-established therapeutic option to prevent skeletal-related events in metastatic bone disease and adjuvant therapy-induced bone loss in breast cancer. On the other hand, the exact role of OPG in breast tumorigenesis is still unclear. This review focuses on molecular mechanisms linking RANKL/RANK/OPG system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings.
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http://dx.doi.org/10.1186/s13046-018-1001-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325760PMC
January 2019