Publications by authors named "Laura Pizzuti"

102 Publications

Circulating HPV DNA in the Management of Oropharyngeal and Cervical Cancers: Current Knowledge and Future Perspectives.

J Clin Med 2021 Apr 6;10(7). Epub 2021 Apr 6.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

Human papillomaviruses (HPVs) are associated with invasive malignancies, including almost 100% of cervical cancers (CECs), and 35-70% of oropharyngeal cancers (OPCs). HPV infection leads to clinical implications in related tumors by determining better prognosis and predicting treatment response, especially in OPC. Currently, specific and minimally invasive tests allow for detecting HPV-related cancer at an early phase, informing more appropriately therapeutical decisions, and allowing for timely disease monitoring. A blood-based biomarker detectable in liquid biopsy represents an ideal candidate, and the use of circulating HPV DNA (ct-DNA) itself could offer the highest specificity for such a scope. Circulating HPV DNA is detectable in the greatest part of patients affected by HPV-related cancers, and studies have demonstrated its potential usefulness for CEC and OPC clinical management. Unfortunately, when using conventional polymerase chain reaction (PCR), the detection rate of serum HPV DNA is low. Innovative techniques such as droplet-based digital PCR and next generation sequencing are becoming increasingly available for the purpose of boosting HPV ct-DNA detection rate. We herein review and critically discuss the most recent and representative literature, concerning the role of HPV ctDNA in OPC and CEC in the light of new technologies that could improve the potential of this biomarker in fulfilling many of the unmet needs in the clinical management of OPC and CEC patients.
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http://dx.doi.org/10.3390/jcm10071525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038737PMC
April 2021

Second-line Eribulin in Triple Negative Metastatic Breast Cancer patients. Multicentre Retrospective Study: The TETRIS Trial.

Int J Med Sci 2021 27;18(10):2245-2250. Epub 2021 Mar 27.

Bio-Statistics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.
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http://dx.doi.org/10.7150/ijms.54996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040412PMC
March 2021

Burnout of health care providers during the COVID-19 pandemic: Focus on Medical Oncologists.

Int J Med Sci 2021 26;18(10):2235-2238. Epub 2021 Mar 26.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 00144 Rome, Italy.

The spread of the coronavirus disease 2019 (Covid-19) has challenged hard the national health system worldwide. At any level, the role of health care providers has been rapidly revisited and eventually modified to face the pandemic. The search of the balance between the provision of the most appropriate health-related services and safety of both patients and health care providers has become an indisputable necessity. The consequently increased work load, along with a widespread feeling of intellectual isolation, emotional overload, sense of inadequacy for involvement in tasks and disciplines which are not always familiar have all been proposed as factors related to the onset and/or worsening of the burnout phenomenon. This latter is sadly renown among care givers and is particularly common among medical oncologists. We herein share our perspectives on the burnout phenomenon over the course of the Covid-19 pandemic, with a specific focus on medical oncologists. Results from the most recent and inherent studies are presented and commented in light of hints provided by the experience matured by a quite restricted, still potentially representative, number of professionals figures from the medical oncologists' category. Reasons are proposed to explain the sense of inadequacy currently perceived in relation to the limits imposed by the current pandemic. In more detail, we illustrate the nature and extents of some of the most relevant difficulties in the optimal management of cancer patients and constant efforts towards the scientific upgrade which allows for the improvement of the professional performance. The need for a deeper understanding of the roots and consequences of the Covid-19 pandemic on the mental health of medical oncologists is finally stressed.
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http://dx.doi.org/10.7150/ijms.54025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040416PMC
April 2021

COVID-19 risk in breast cancer patients receiving CDK4/6 inhibitors: literature data and a monocentric experience.

Breast J 2021 04 6;27(4):359-362. Epub 2021 Mar 6.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Substantial changes in the management of cancer patients have been required worldwide in response to the COVID-19 pandemic. Beyond the due details on the primitive cancer site and setting at diagnosis, these latter adaptions are most commonly exemplified by a significant reduction in the screening of asymptomatic subjects, delays in elective surgery and radiotherapy for primary tumors, and dose reductions and/or delays in systemic therapy administration. Advanced breast cancer patients with hormonal receptor positive, HER2 negative tumors are usually treated with endocrine therapy combined with CDK 4/6 inhibitors as first- and second-line treatment. During the pandemic, experts' recommendations have suggested the omission or delay of CDK 4/6 inhibitors delivery, or a careful evaluation of their real need due to the hypothesized increased risk of SARS-Cov-2 infection and disease possibly related to neutropenia. The inherent literature is sparse and inconsistent. We herein present data on the use of CDK 4/6 inhibitors during the pandemic. The evidence reported punctually reflects the experience matured at our Institution, a comprehensive cancer centre, on the topic of interest.
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http://dx.doi.org/10.1111/tbj.14204DOI Listing
April 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

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

Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study.

J Exp Clin Cancer Res 2020 Dec 10;39(1):279. Epub 2020 Dec 10.

Medical Oncology, Paolo Giaccone University Hospital, Palermo, Italy.

Background: HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines.

Methods: The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models.

Results: We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in first-line, and 74 and 10 months in 194 pertuzumab-naïve patients (p = 0.0006 and 0.03 for OS and PFS2, respectively).

Conclusions: Our data support the hypothesis that the addition of pertuzumab to trastuzumab reduces the amount of available plasma membrane HER2 receptor, limiting the binding of T-DM1 in cancer cells. This may help interpret the less favorable outcomes of second-line T-DM1 in trastuzumab/pertuzumab pre-treated patients compared to their pertuzumab-naïve counterpart.
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http://dx.doi.org/10.1186/s13046-020-01797-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731769PMC
December 2020

Palliative- and non-palliative indications for glucocorticoids use in course of immune-checkpoint inhibition. Current evidence and future perspectives.

Crit Rev Oncol Hematol 2021 Jan 17;157:103176. Epub 2020 Nov 17.

Department of Clinical and Molecular Medicine, Sapienza - University of Rome, Sant'Andrea Hospital, Rome, Italy.

Immune-checkpoint inhibitors significantly reshaped treatment landscapes in several solid tumors. Concurrently with disease-oriented therapies, cancer patients often require proper management of drug-related adverse events and/or cancer-related symptoms. Glucocorticoids (GC) are a cornerstone of symptom management in advanced cancer care and in the management of immune-related adverse events (irAEs) due to immune-modulating therapies. Moreover, GC are often administered in patients with autoimmune diseases (AID), either alone or in combination with other treatments. While handling of irAEs with GC is supported by multiple guidelines, it is unclear whether GC administration because of pre-existing AID or because of palliative needs is associated with inferior outcomes in cancer patients treated with immune-checkpoint inhibitors (ICIs). When globally considered, the available evidence seems to orient towards less favorable survival outcomes when GC administration is driven by a palliative intent. Conversely, steroid administration for non-palliative intent seems to be associated with stable or negligibly reduced survival outcomes.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103176DOI Listing
January 2021

Neoadjuvant Immune-Checkpoint Blockade in Triple-Negative Breast Cancer: Current Evidence and Literature-Based Meta-Analysis of Randomized Trials.

Cancers (Basel) 2020 Sep 3;12(9). Epub 2020 Sep 3.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

Chemotherapy based on the sequential use of anthracyclines and taxanes has long represented the most efficacious approach in the management of early-stage, triple-negative breast cancer, whose aggressive behavior is widely renowned. This standard chemotherapy backbone was subsequently enriched by the use of carboplatin, based on its association with increased pathologic complete response and efficacy in the metastatic setting. Following the results from the IMpassion130 trial, the recent approval of the immunotherapic agent atezolizumab in combination with chemotherapy as first-line treatment for programmed-death ligand 1-positive, unresectable locally advanced, or metastatic triple-negative breast cancer increasingly fueled the flourishing of trials of immune-checkpoint inhibitors in the early setting. In this work, we review the most recent inherent literature in light of key methodological issues and provide a quantitative summary of the results from phase II-III randomized trials of immunotherapic agents combined with chemotherapy in the setting of interest. Hints regarding future directions are also discussed.
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http://dx.doi.org/10.3390/cancers12092497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565914PMC
September 2020

Efficacy of immunotherapy in lung cancer with co-occurring mutations in NOTCH and homologous repair genes.

J Immunother Cancer 2020 08;8(2)

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy

Background: Immune checkpoint inhibitors (ICIs) provide significant survival benefits in non-small cell lung cancer (NSCLC). Nevertheless, while some patients obtain a prolonged benefit, a non-negligible fraction of patients experiences an ultrarapid disease progression. Identifying specific molecular backgrounds predicting opposite outcomes is instrumental to optimize the use of these agents in clinical practice.

Methods: We carried out an observational study with prospective design envisioning targeted next-generation sequencing (NGS) with an approved assay in 55 patients with metastatic NSCLC (Rome cohort), of whom 35 were treated with ICIs. Data from three clinically comparable datasets were collected and combined into a metadataset containing 779 patients. The datasets were related to the Memorial Sloan Kettering Cancer Center (MSKCC) cohort (tissue-based NGS) and the randomized phase II and III POPLAR and OAK trials (blood-based NGS).

Results: In patients treated with ICIs in the Rome cohort, co-occurring mutations in NOTCH1-3 and homologous repair (HR) genes were associated with durable clinical benefit. Using the MSKCC/POPLAR/OAK metadaset, we confirmed the relationship between the NOTCH/HR signature and longer progression-free survival (PFS) in ICI-treated patients (multivariate Cox: HR 0.51, 95% CI 0.34 to 0.76, p=0.001). The NOTCH/HR genomic predictor was also associated with longer survival (log-rank p=0.008), despite patients whose tumors carried the NOTCH/HR signature had higher metastatic burden as compared with their negative counterpart. Finally, we observed that this genomic predictor was also associated with longer survival in patients with other tumor types treated with ICIs (n=1311, log-rank p=0.002).

Conclusions: Co-occurring mutations in the NOTCH and HR pathways are associated with increased efficacy of immunotherapy in advanced NSCLC. This genomic predictor deserves further investigation to fully assess its potential in informing therapeutic decisions.
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http://dx.doi.org/10.1136/jitc-2020-000946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409965PMC
August 2020

Case report: 5-year progression free survival and complete liver response in a patient with metastatic breast cancer treated with everolimus plus exemestane.

Medicine (Baltimore) 2020 Jul;99(31):e21211

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome.

Rationale: Within a rapidly expanding therapeutic armamentarium, the combination of everolimus (Eve) plus exemestane (Exe) utility needs to be reinstated in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC).

Patient Concerns: We herein report on a patient affected by HR+ HER2- MBC treated with radical surgery after neoadjuvant chemotherapy, who relapsed early on adjuvant tamoxifen, progressed rapidly on first line anastrozole, and failed treatment with third line capecitabine.

Diagnoses: Metastatic luminal breast cancer progressed under standard endocrine therapy and chemotherapy.

Interventions: Third line with Eve plus Exe was given after chemotherapy.

Outcomes: Patient experienced a 5-year progression free interval.

Lessons: Eve plus Exe remains a valid option in HR+HER2- MBC.
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http://dx.doi.org/10.1097/MD.0000000000021211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402792PMC
July 2020

Neoadjuvant Endocrine Therapy in Breast Cancer: Current Knowledge and Future Perspectives.

Int J Mol Sci 2020 May 16;21(10). Epub 2020 May 16.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.

In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.
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http://dx.doi.org/10.3390/ijms21103528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278946PMC
May 2020

The Agnostic Role of Site of Metastasis in Predicting Outcomes in Cancer Patients Treated with Immunotherapy.

Vaccines (Basel) 2020 Apr 28;8(2). Epub 2020 Apr 28.

Department of Clinical and molecular oncology, University of Rome "Sapienza", 00185 Rome, Italy.

Immune checkpoint inhibitors have revolutionized treatment and outcome of melanoma and many other solid malignancies including non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Unfortunately, only a minority of patients have a long-term benefit, while the remaining demonstrate primary or acquired resistance. Recently, it has been demonstrated that the prevalence of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) varies based on the anatomical site of metastases. In particular, liver seems to have more immunosuppressive microenvironment while both the presence of lymph nodal disease and lung metastases seem to have the highest prevalence of PD-L1 and TILs. The aim of the present study is to investigate the possible role of site of metastases as a predictive factor for response or resistance to immunotherapy in several types of cancer. In this multicenter retrospective study, we enrolled patients with metastatic NSCLC, melanoma, RCC, urothelial, merkel carcinoma, and colon cancer who received immunotherapy from April 2015 to August 2019. Major clinicopathological parameters were retrieved and correlated with patients' survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision-making process. A total of 291 patients were included in this study. One hundred eighty-seven (64%) patients were male and 104 (36%) female. The tumor histology was squamous NSCLC in 56 (19%) patients, non-squamous NSCLC in 99 (34%) patients, melanoma in 101 (35%) patients, RCC in 28 (10%) patients, and other tumors in the remaining 7 (2%) patients. The number of metastatic sites was 1 in 103 patients (35%), 2 in 104 patients (36%) and 3 in 84 patients (29%). Out of 183 valuable patients, the entity of response was complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD) in 15, 53, 31, and 79 patients, respectively. Using an univariate analysis (UVA), tumor burden ( = 0.0004), the presence of liver ( = 0.0009), bone ( = 0.0016), brain metastases ( < 0.0001), the other metastatic sites ( = 0.0375), the number of metastatic sites ( = 0.0039), the histology ( = 0.0034), the upfront use of immunotherapy ( = 0.0032), and Eastern Cooperative Oncology Group (ECOG) Perfomance status (PS) ≥ 1 ( < 0.0001) were significantly associated with poor overall survival (OS). Using a multivariate analysis (MVA) the presence of liver ( = 0.0105) and brain ( = 0.0026) metastases, the NSCLC diagnosis ( < 0.0001) and the ECOG PS ( < 0.0001) resulted as significant prognostic factors of survival. Regarding the progression free survival (PFS), using a UVA of the tumor burden ( = 0.0004), bone ( = 0.0098) and brain ( = 0.0038) metastases, the presence of other metastatic sites ( = 0.0063), the number of metastatic sites ( = 0.0007), the histology ( = 0.0007), the use of immunotherapy as first line ( = 0.0031), and the ECOG PS ≥ 1 ( ≤ 0.0001) were associated with a lower PFS rate. Using an MVA, the presence of brain ( = 0.0088) and liver metastases ( = 0.024) and the ECOG PS ( < 0.0001) resulted as predictors of poor PFS. Our study suggests that the site of metastases could have a role as prognostic and predictive factor in patients treated with immunotherapy. Indeed, regardless of the histology, the presence of liver and brain metastases was associated with a shorter PFS and OS, but these results must be confirmed in further studies. In this context, a deep characterization of microenvironment could be crucial to prepare patients through novel strategies with combination or sequential immunotherapy in order to improve treatment response.
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http://dx.doi.org/10.3390/vaccines8020203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349154PMC
April 2020

The Impact of Locoregional Treatment on Response to Nivolumab in Advanced Platinum Refractory Head and Neck Cancer: The Need Trial.

Vaccines (Basel) 2020 Apr 20;8(2). Epub 2020 Apr 20.

Department of Clinical and Molecular Medicine, University of Rome "Sapienza", 00161 Rome, Italy.

Background: Previous locoregional treatment could affect the response to nivolumab in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). The aim of this study is to evaluate the impact of the clinicopathological characteristics and previous treatment in predicting early progression to nivolumab in a real-world population.

Methods: This is an observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received nivolumab 240 mg every 2 weeks from October 2018 to October 2019. We analyzed the association between previous treatment, clinicopathological characteristics, and early progression (within 3 months).

Results: Data from 61 pts were reviewed. Median age was 67 years (30-82). Forty-two pts (69%) received previous locoregional treatment. Early progression to nivolumab occurred in 36 pts (59%), while clinical benefit (stable disease and partial response) was achieved in 25 pts (41%). Early progression to nivolumab was significantly associated to previous locoregional treatment both at univariate and multivariate analysis ( = 0.005 and = 0.048, respectively).

Conclusion: nivolumab in R/M HNSCC is burdened with a high early progression rate. Previous wide neck dissection and high dose radiotherapy may compromise the efficacy of nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.
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http://dx.doi.org/10.3390/vaccines8020191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349768PMC
April 2020

Observational Multicenter Study on the Prognostic Relevance of Coagulation Activation in Risk Assessment and Stratification in Locally Advanced Breast Cancer. Outline of the ARIAS Trial.

Cancers (Basel) 2020 Apr 1;12(4). Epub 2020 Apr 1.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 00144 Rome, Italy.

A hypercoagulable state may either underlie or frankly accompany cancer disease at its onset or emerge in course of cancer development. Whichever the case, hypercoagulation may severely limit administration of cancer therapies, impose integrative supporting treatments and finally have an impact on prognosis. Within a flourishing research pipeline, a recent study of stage I-IIA breast cancer patients has allowed the development of a prognostic model including biomarkers of coagulation activation, which efficiently stratified prognosis of patients in the study cohort. We are now validating our risk assessment tool in an independent cohort of 108 patients with locally advanced breast cancer with indication to neo-adjuvant therapy followed by breast surgery. Within this study population, we will use our tool for risk assessment and stratification in reference to 1. pathologic complete response rate at definitive surgery, intended as our primary endpoint, and 2. rate of thromboembolic events, intended as our secondary endpoint. Patients' screening and enrollment procedures are currently in place. The trial will be shortly enriched by experimental tasks centered on next-generation sequencing techniques for identifying additional molecular targets of treatments which may integrate current standards of therapy in high-risk patients.
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http://dx.doi.org/10.3390/cancers12040849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226579PMC
April 2020

Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine. Real-world evidence.

J Cell Physiol 2020 11 15;235(11):7900-7910. Epub 2020 Jan 15.

Medical Oncology Unit, Belcolle Hospital, Viterbo, Italy.

Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5-24.9, 25-29.9, and 30.0-34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p = .15), while BMI ≥ 30 was associated with worse OS (p = .003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p = .001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p = .03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile.
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http://dx.doi.org/10.1002/jcp.29445DOI Listing
November 2020

Eribulin in Triple Negative Metastatic Breast Cancer: Critic Interpretation of Current Evidence and Projection for Future Scenarios.

J Cancer 2019 12;10(24):5903-5914. Epub 2019 Oct 12.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy.

Triple negative breast cancer (TNBC) is characterized by distinctive biological features that confer an aggressive clinical behavior. In TNBC patients, the absence of well-defined driver pathways such as hormonal receptor expression or hyperactivation of the human epidermal growth factor receptor 2 (HER2) significantly reduce the spectrum of therapeutic options, which are currently mainly confined to chemotherapy. Thus far, median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. However, the heterogeneity recently revealed at a gene expression level inside the TNBC family may help inform therapeutic decisions concerning the use of chemotherapy and hopefully lead the way to novel targeted options that include immunotherapy. Eribulin, a halichondrin class antineoplastic drug, is currently recommended for treatment of HER2 negative metastatic or recurrent breast cancer (BC) previously exposed to anthracyclines and taxanes, also for patients with a TNBC. It is currently indicated from the second line of treatment. In this review, we aim to analyze a wide range of cumulated evidence on eribulin use in TNBC including preclinical studies, intervention and observational clinical trials. Data from the real-world setting and the emerging evidence increasingly substantiating the rationale for combinations with new generation treatment strategies, e.g., PARP-inhibitors, immune checkpoint inhibitors, will be also discussed.
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http://dx.doi.org/10.7150/jca.35109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856581PMC
October 2019

Highly durable response to capecitabine in patient with metastatic estrogen receptor positive breast cancer: A case report.

Medicine (Baltimore) 2019 Sep;98(37):e17135

IRCCS - Regina Elena Cancer Institute, Division of Medical Oncology 2.

Rationale: In estrogen receptor-positive HER2-negative (ER+HER2-) metastatic breast cancer, chemotherapy should be offered only to patients who develop endocrine resistance or have a rapid disease progression. However, the correct sequence of chemotherapy administration is still debated.

Patient Concerns: We report the case of a 49-year-old woman with ER+ HER2- metastatic breast cancer who experienced an exceptionally long response to capecitabine administered as second-line therapy following a first-line anthracycline-based chemotherapy.

Diagnoses: The patient was diagnosed with ER+ HER2- metastatic breast cancer with massive liver involvement and mediastinal lymph nodes metastasis.

Interventions: This patient was treated with capecitabine 1000 mg/mq bid given intermittently for 14 days within a 21-day cycle as a second-line therapy following a rapid progression on letrozole treatment given as a maintenance therapy.

Outcomes: Our patient experienced a progression-free survival (PFS) >3 years with an exceptionally good quality of life (QoL).

Lessons: In ER+HER2- metastatic breast cancer patients, capecitabine monochemotherapy in second line may be associated with a particularly satisfactory PFS and no impact in terms of QoL. Future studies focused on biomarkers with predictive ability may help select patients who represent the best candidates to this treatment.
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http://dx.doi.org/10.1097/MD.0000000000017135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750334PMC
September 2019

Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting.

Ther Adv Med Oncol 2019 18;11:1758835919853192. Epub 2019 Aug 18.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Background: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT).

Methods: Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered.

Results: The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature ( = 0.011). In models of Ki-67 reduction, 'luminal B' subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant ( < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival ( = 0.027) and overall survival ( = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades ( < 0.05 for both).

Conclusions: We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.
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http://dx.doi.org/10.1177/1758835919853192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700857PMC
August 2019

Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer.

Cells 2019 07 19;8(7). Epub 2019 Jul 19.

Center for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.

Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.
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http://dx.doi.org/10.3390/cells8070750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678306PMC
July 2019

Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting.

Int J Cancer 2020 04 7;146(7):1917-1929. Epub 2019 Aug 7.

Department of Medical Oncology, Policlinico Universitario "A. Gemelli", Rome, Italy.

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients.
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http://dx.doi.org/10.1002/ijc.32583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027476PMC
April 2020

Mutations in the KEAP1-NFE2L2 Pathway Define a Molecular Subset of Rapidly Progressing Lung Adenocarcinoma.

J Thorac Oncol 2019 11 16;14(11):1924-1934. Epub 2019 Jul 16.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy. Electronic address:

Introduction: Molecular characterization studies revealed recurrent kelch like ECH associated protein 1 gene (KEAP1)/nuclear factor, erythroid 2 like 2 gene (NFE2L2) alterations in NSCLC. These genes encode two interacting proteins (a stress response pathway [SRP]) that mediate a cytoprotective response to oxidative stress and xenobiotics. Nevertheless, whether KEAP1/NFE2L2 mutations have an impact on clinical outcomes is unclear.

Methods: We performed amplicon-based next-generation sequencing to characterize the SRP in patients with metastatic NSCLC (Regina Elena National Cancer Institute cohort [n = 88]) treated with first-line chemotherapy. Mutations in the DNA damage response (tumor protein p53 gene [TP53], ATM serine/threonine kinase gene [ATM], and ATR serine/threonine kinase gene [ATR]) were concomitantly analyzed. In lung adenocarcinoma (LAC), we also determined the expression of phosphorylated ataxia telangiectasia mutated kinase and ataxia telangiectasia and Rad3-related protein. Two independent cohorts (the Memorial Sloan Kettering Cancer Center cohort and The Cancer Genome Atlas cohort) with data from approximately 1400 patients with advanced LAC were used to assess the reproducibility of the results.

Results: In the Regina Elena National Cancer Institute cohort, patients whose tumors carried mutations in the KEAP1/NFE2L2 pathway had significantly shorter progression-free survival and overall survival than their wild-type counterparts did (log-rank p = 0.006 and p = 0.018, respectively). This association was driven by LAC in which KEAP1/NFE2L2 mutations were overrepresented in fast progressors and associated with an increased risk of disease progression and death. LACs carrying KEAP1/NFE2L2 mutations were characterized by elevated expression of phosphorylated ataxia telangiectasia mutated (pATM) kinase and ataxia telangiectasia and Rad3-related (pATR) protein in association with a pattern of mutual exclusivity with TP53 alterations. The relationship between KEAP1/NFE2L2 mutations and shorter survival was validated in the Memorial Sloan Kettering Cancer Center cohort (n = 1256) (log-rank p < 0.001) and in The Cancer Genome Atlas cohort (n = 162) (log-rank p = 0.039).

Conclusion: These findings suggest that a mutant SRP represents a negative prognostic/predictive factor in metastatic LAC and that KEAP1/NFE2L2 mutations may define a molecular subtype of chemotherapy-resistant and rapidly progressing LAC.
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http://dx.doi.org/10.1016/j.jtho.2019.07.003DOI Listing
November 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

Trastuzumab-related cardiotoxicity in patients with nonlimiting cardiac comorbidity.

Breast J 2019 05 1;25(3):444-449. Epub 2019 Apr 1.

Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.

Background: Significant and symptomatic cardiac comorbidity is a contraindication to adjuvant trastuzumab in breast cancer patients. However, some patients with asymptomatic, nonlimiting cardiac comorbidity and normal baseline left ventricular ejection fraction (LVEF) receive adjuvant trastuzumab in the clinical practice. We sought to describe the tolerability of trastuzumab in these patients.

Patients And Methods: Retrospective analysis of patients with baseline asymptomatic, nonlimiting cardiac comorbidity receiving adjuvant trastuzumab at six Institutions between July 2007 and January 2016.

Results: Thirty-seven patients with HER2-positive, surgery treated breast cancer at high risk of relapse were studied. Median age was 64 years (range 36-82), median baseline LVEF 61% (range 50%-85%). Thirteen patients (35%) received trastuzumab with adjuvant anthracycline and taxane-based regimens, 19 (51%) with taxane-based, three (8%) with off-label vinorelbine and two (5%) with off-label endocrine therapy. Most frequent cardiac comorbidities were ischemic heart disease (35%), valvular disease (30%), atrial fibrillation (19%), and conduction disorders (14%). Nine patients (24.3%) experienced a cardiac event: congestive heart failure (one patient, 3%), asymptomatic LVEF reduction (six patients, 16%), and rhythm disturbances (two patients, 5%). Trastuzumab had to be discontinued either permanently (five patients, 14%) or temporarily (two patients, 5%). At the time of last follow-up visit, all patients showed LVEF within normal limits, except one who had experienced a symptomatic cardiac event (LVEF value at last follow-up 46%).

Conclusions: Caution is needed in patients with significant ongoing cardiovascular risk factors, but when adjuvant trastuzumab is deemed beneficial on breast cancer outcomes, nonlimiting cardiac comorbidity should not preclude treatment.
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http://dx.doi.org/10.1111/tbj.13240DOI Listing
May 2019

A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab.

J Transl Med 2019 03 27;17(1):99. Epub 2019 Mar 27.

Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.

Background: The advent of immune checkpoint inhibitors (ICIs) has considerably expanded the armamentarium against non-small cell lung cancer (NSCLC) contributing to reshaping treatment paradigms in the advanced disease setting. While promising tissue- and plasma-based biomarkers are under investigation, no reliable predictive factor is currently available to aid in treatment selection.

Methods: Patients with stage IIIB-IV NSCLC receiving nivolumab at Sant'Andrea Hospital and Regina Elena National Cancer Institute from June 2016 to July 2017 were enrolled onto this study. Major clinicopathological parameters were retrieved and correlated with patients' survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision making process.

Results: A total of 102 patients were included in this study. The median age was 69 years (range 44-85 years), 69 (68%) were male and 52% had ECOG PS 0. Loco-regional/distant lymph nodes were the most commonly involved site of metastasis (71%), followed by lung parenchyma (67%) and bone (26%). Overall survival (OS) in the whole patients' population was 83.6%, 63.2% and 46.9% at 3, 6 and 12 months, respectively; while progression-free survival (PFS) was 66.5%, 44.4% and 26.4% at 3, 6 and 12 months, respectively. At univariate analysis, age ≥ 69 years (P = 0.057), ECOG PS (P < 0.001), the presence of liver (P < 0.001), lung (P = 0.017) metastases, lymph nodes only involvement (P = 0.0145) were significantly associated with OS and ECOG PS (P < 0.001) and liver metastases (P < 0.001), retained statistical significance at multivariate analysis. A prognostic nomogram based on three variables (liver and lung metastases and ECOG PS) was built to assign survival probability at 3, 6, and 12 months after nivolumab treatment commencement.

Conclusion: We developed a nomogram based on easily available and inexpensive clinical factors showing a good performance in predicting individual OS probability among NSCLC patients treated with nivolumab. This prognostic device could be valuable to clinicians in more accurately driving treatment decision in daily practice as well as enrollment onto clinical trials.
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http://dx.doi.org/10.1186/s12967-019-1847-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437908PMC
March 2019

A case of 20-week abortion in a rare communicating rudimentary horn of a misinterpreted unicornuate uterus, incorrectly diagnosed as bicornuate: A serious hazard!

Eur J Obstet Gynecol Reprod Biol 2019 Apr 27;235:133-135. Epub 2019 Feb 27.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.

Female genital malformations, as the unicornuate uterus, are deviations from normal anatomy that could impair the reproductive potential of a woman or her health. We present a rare case of a 20-week spontaneous abortion in a 24 years old patient affected by a misunderstood unicornuate uterus with communicating rudimentary horn, previously diagnosed as bicornuate, and for this reason subjected to induction of abortive labor, using mifepristone and gemeprost. Following the ultrasound exam and MRI, performed due to the failure of the abortive procedure, revealed the diagnosis of unicornuate uterus with (not clear) communicating accessory horn pregnancy, then treated with laparotomy. 3D-ultrasonography, and above all MRI, should be performed in all those cases of suspected uterine anomalies, especially in presence of pregnancy or abortion, with the aim of avoiding wrong treatments, which leads to a high risk of uterine rupture. In this case, given the uncertainty of imaging exams performed in such an advanced second trimester of pregnancy, only the surgical approach was able to discover the real communication.
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http://dx.doi.org/10.1016/j.ejogrb.2019.02.018DOI Listing
April 2019

Long-Term Safety and Real-World Effectiveness of Trastuzumab in Breast Cancer.

J Clin Med 2019 Feb 18;8(2). Epub 2019 Feb 18.

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy.

Trastuzumab is a milestone in the treatment of human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), in both the early and metastatic settings. Over the last two decades, clinical trials have established the good safety profile of trastuzumab. Cardiotoxicity remains the most frequent adverse event, more commonly exemplified by an asymptomatic decline in the left ventricular ejection fraction rather than congestive heart failure. Results from several long-term (>5 years) safety analyses have been recently published, with the inherent evidence substantially confirming the findings from previous trials. The clinical experience gained over the years in the use of trastuzumab has also fueled a number of observational studies focused on the effectiveness of this drug in the real-world settings. We herein reviewed the evidence available from tree major databases, namely, PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), to explore and critically discuss key issues related to the long-term safety and effectiveness of trastuzumab in clinical practice.
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http://dx.doi.org/10.3390/jcm8020254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406268PMC
February 2019

Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients.

Breast 2019 Apr 2;44:33-38. Epub 2019 Jan 2.

Department of Medical, Oral and Biotechnological Sciences and CeSI-MeT, G. D'Annunzio University, Chieti, Italy.

The immune system seems to play a fundamental role in breast cancer responsiveness to chemotherapy. We investigated two peripheral indicators of immunity/inflammation, i.e. neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in order to reveal a possible relationship with pathological complete response (pCR) in patients with early or locally advanced breast cancer treated with neoadjuvant chemotherapy (NACT). We retrospectively analyzed 373 consecutive patients affected by breast cancer and candidates to NACT. The complete blood cell count before starting NACT was evaluated to calculate NLR and PLR. ROC curve analysis determined threshold values of 2.42 and 104.47 as best cut-off values for NLR and PLR, respectively. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ 2 or Fisher's exact test as appropriate. Univariate and multivariate analyses were performed using a logistic regression model. NLR and PLR were not significantly associated with pCR if analyzed separately. However, when combining NLR and PLR, patients with a NLR/PLR profile achieved a significantly higher rate of pCR compared to those with NLR and/or PLR (OR 2.29, 95% CI 1.22-4.27, p 0.009). Importantly, the predictive value of NLR/PLR was independent from common prognostic factors such as grading, Ki67, and molecular subtypes. The combination of NLR and PLR may reflect patients' immunogenic phenotype. Low levels of both NLR and PLR may thus indicate a status of immune system activation that may predict pCR in breast cancer patients treated with NACT.
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http://dx.doi.org/10.1016/j.breast.2018.12.014DOI Listing
April 2019