Monica Verrico - Academia.edu (original) (raw)
Papers by Monica Verrico
Journal of Clinical Medicine
Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypica... more Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted prese...
Cancers
Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhib... more Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes. Material and Methods: The effects of ICIs on 12 aggressive/metastatic PitNETs from the literature were reviewed and analyzed according to tumor characteristics, with the additional description of a silent-Pit1 metastatic tumor responding to pembrolizumab. Results: Most cases were metastatic (10/13: 6 corticotroph, 3 lactotroph, 1 silent Pit1); 3 were aggressive (2 corticotroph, 1 lactotroph). ICIS was used either as monotherapy or in combination. At last follow-up on ICI, a complete response (CR) was present in 3 cases and a partial response (PR) in 2 cases (4/5 metastatic). One sustained stable disease (SD) was reported. Progressive disease (PD) was observed in 7 cases, 3 of them after initial SD (n = 1) or PR (n = 3...
Endocrine
Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention... more Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention, but their clinical role remains unclear. The aim of this study was to evaluate the role of angiogenic markers in NEN aggressiveness and prognosis. We performed a prospective observational study including 46 consecutive patients with proven NENs of pulmonary (45.65%) and gastro-entero-pancreatic (GEP) (54.35%) origin and 29 healthy controls. Circulating pro-angiogenic factors were measured by ELISA assay. ANG2 tissue expression was evaluated in a subgroup of ten patients by immunohistochemistry. The study demonstrated a significantly higher level of ANG2, ANG1, sTIE2, and PROK2 in patients affected by NENs compared to controls. In the NENs’ group we measured that: (i) ANG2 levels were higher in poorly vs well-differentiated NENs: 4.85 (2.75–7.42) vs 3.16 (1.66–6.36) ng/ml, p = 0.046 and in tumor stage 3–4 compared to stage 1–2: 4.24 (2.66–8.72) vs 2.73 (1.53–5.70), p = 0.044; (ii) ANG2 and PROK2 were significantly higher in patents with progressive disease compared to stable disease: ANG2 = 6.26 (3.98–10.99) vs 2.73 (1.65–4.36) pg/ml, p = 0.001; PROK2 = 29.19 (28.42–32.25) vs 28.37 (28.14–28.91) pg/ml, p = 0.035. Immunohistochemistry confirmed ANG2 expression in tumor specimens. We documented higher levels of angiogenic markers in NENs, with an association between ANG2 serum levels and NENs morphology and staging. In both GEP and lung NENs, ANG2 and PROK2 are higher in case of tumor progression, suggesting a potential role as prognostic markers in NENs patients.
Journal of Clinical Oncology
e14529 Background: PD-L1 is the only biomarker that has been accepted to identify patients who co... more e14529 Background: PD-L1 is the only biomarker that has been accepted to identify patients who could potentially benefit from immune checkpoint inhibitors (ICIs) administration, but also PD-L1 negative tumors respond to immunotherapy. However, other biomarkers have been proposed but they are too expensive and actually, there is not a consensus for detection and analytical methods. Thus, there is an urgent need for inexpensive and reproducible tests to better optimize the clinical use of ICIs. Recent findings suggest that host parameters may help to select patients to treat with ICIs: performance status (PS) and some laboratory parameters, such as lactate dehydrogenase (LDH) and blood cells count. Inflammation and inflammatory response have been considered surrogate biomarkers of host immunity. An elevated neutrophil-to-lymphocyte (NLR), myeloid-to-lymphocyte (MLR) and platelet-to-lymphocyte (PLR) ratio have been associated with systemic inflammation and some evidences suggest that t...
Endocrine, 2022
Purpose: Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) a... more Purpose: Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods: A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results: Median age 61 years (13–86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high-power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6–323), median progression-free survival (PFS) was 36.0 months (0.3–323). Female sex correlated with a more indolent disease (T1; N0;...
R e v i e w open access to scientific and medical research Open Access Full Text Article
Purpose Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) an... more Purpose Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results Median age 61 years (13-86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6-323), median progression free survival (PFS) was 36.0 months (0.3-323). Female sex correlated with a more indolent disease (T1; N0; lo...
Recenti progressi in medicina, 2019
Riassunto. L'angiogenesi svolge un ruolo importante sia nei tessuti epiteliali normali sia in... more Riassunto. L'angiogenesi svolge un ruolo importante sia nei tessuti epiteliali normali sia in quelli maligni. Negli ultimi anni questo fenomeno è stato ampiamente studiato in oncologia sperimentale e clinica perché ci sono evidenze che sia coinvolto nella diffusione e nella diffusione metastatica del carcinoma ovarico. Il fattore di crescita dell'endotelio vascolare (vascular endothelial growth factor - VEGF) è l'attore principale nel meccanismo di angiogenesi e svolge un ruolo strategico nella proliferazione e migrazione delle cellule neoplastiche, con un impatto significativo sulla sopravvivenza e sull'outcome clinico. Secondo quanto emerge da molti studi sperimentali e clinici, le nostre conoscenze sulla biologia dell'angiogenesi e del VEGF sono aumentate portando allo sviluppo farmacologico di specifici agenti in grado di targeting VEGF. Questo nuovo campo di indagine offre agli scienziati l'opportunità di testare nuove possibilità terapeutiche nei pazien...
Frontiers in Oncology, 2021
Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrog... more Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metas...
Neuroendocrinology, 2021
The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It ... more The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain reaction, providing an accurate molecular profile of the neoplasm. Diagnostic utility of NETest has been widely demonstrated, while its role in predicting prognosis and treatment response is less studied. This systematic review aims to collect and discuss the available evidence on the prognostic and predictive role of NETest, trying to answer 3 questions, frequently raised in clinical practice. Is NETest able to differentiate stable from progressive disease? Increased NETest levels (at least >40%) correlate with disease progression. Is NETest able to predict tumor progression and tumor response to treatment? Some studies demonstrated that the baseline NETest score >33–40% could predict tumor progression. Moreover, NETest performed after treatment (as peptide receptor radionuclide therapy) could predict treatment...
Breast Cancer Research and Treatment, 2020
We read with great interest the paper recently published by Vriens et al. [1]. Fertility preserva... more We read with great interest the paper recently published by Vriens et al. [1]. Fertility preservation (FP) in young women undergoing chemotherapy for EBC is still an extremely debated topic, worthy of further investigation, although there is evidence to support the use of clinical strategies aimed at the conservation of fertility in these patients. Several studies and consensus papers suggest offering these patients an oncofertility counselling, in order to maintain their reproductive capacity [2, 3]. Unfortunately, we still have few data on the reproductive outcomes in young EBC patients treated with chemotherapy. Vriens’s study enrolled premenopausal patients under the age of 40 (median 31, range 19–40) with stage I–III invasive EBC, treated with adjuvant/neoadjuvant chemotherapy and potentially interested to FP. Authors reported that of 118 counseled women, 34 (29%) chose FP. In our opinion, this rate appears extremely low considering the young age of patients recruited and the probable desire to maintain reproductive capacity too, even if in the study it should be observed a high recovery rate of ovarian function (the 5-year OFR rate was 92% in all the patients and 93% in patients < 30 years old). These results confirm that young age is the main favorable factor for the preservation of ovarian function, suggesting that FP procedures in very young patients can be avoided. However, we do not completely agree with this theory as too many factors are involved in OFR after chemotherapy; among them, it is proper mentioning also the deterioration of the ovarian tissue after long adjuvant hormonal treatments which today are increasingly carried out. Due to the increasingly frequent postponement of decision to have a pregnancy in these patients, it seems illogical to deprive them of current available therapeutic opportunities to maintain reproductive capacity. In our opinion, fertility conserving strategies should always be guaranteed, both for future reproductive needs and for improving QOL. Probably, with a more advanced median age we could have observed higher rates of FP choice, due to the perception of future difficulties in achieving pregnancy. None of the patients received prophylactic Gn-Rh analogs during chemotherapy. Even if the enrollment period was from 2008 to 2015, it should be emphasized that for several years there has been scientific evidence supporting the use of Gn-Rh analogs for preserving ovarian function during chemotherapy for EBC, even if the consent about this preventive treatment is not yet fully shared. After all, the 5-year OFR rate of 92% suggests that prophylactic treatment with GnRH analogs should be probably reserved to patients older than 40 years. Going to evaluate the reproductive outcomes of the patients studied, it emerges as 26 patients gave birth and the 5-year live birth rate was 27% for all the patients undergoing fertility counseling. Currently, few data are available about the reproductive successful in transferring cryopreserved oocytes or embryos after chemotherapy for EBC. Vriens et al. reported that only three patients returned for embryo transfer, with a relatively high rate of spontaneous pregnancies. In this regard, a major limitation of the study concerns the lack of knowledge relating to the desire for patients to become pregnant. Therefore, it seems appropriate in the future to start clinical trials providing systematically the acquisition of this information to better understand the impact of FP on the reproductive outcomes of young women treated for EBC. This comment refers to the article available online at https ://doi. org/10.1007/s1054 9-020-05598 -2.
Journal of Clinical Oncology, 2012
e11514 Background: Anthracycline is very effective in treatment of breast cancer, however it can ... more e11514 Background: Anthracycline is very effective in treatment of breast cancer, however it can cause cardiac toxicity events. nPLD has greater safety profile and comparable efficacy than conventional anthracyclines. We evaluated safety and efficacy, in neoadjuvant setting, of nPLD in pts with LABC. Methods: 11 pts (median age 57 years). Their clinical stage was: stages IIA and IIB 1 pt respectively, IIIB 7 pts, IIIC 2 pts. 8 pts presented at diagnosis with cT4 disease. All pts were treated with nPLD (50 mg/mq, d1q21) plus Docetaxel (75 mg/mq, d1q21) and Cyclophosphamide (500 mg/mq, d1q21); only 1 pt received Cyclophosphamide, nPLD and Trastuzumab. At beginning of therapy, overall population had left ventricular ejection fraction (LVEF) ≥55%. Results: After a median of 4 chemotherapy cycles, we observed following clinical response: stable disease 2 pts (18%); partial response 7 pts (64%); complete response 2 pts (18%). 9 pts were evaluable for radiological response: objective respo...
Journal of Clinical Oncology, 2012
e12510 Background: Despite the important progress in the treatment of solid tumors, high grade gl... more e12510 Background: Despite the important progress in the treatment of solid tumors, high grade gliomas (HGGs) remain neoplasm with poor prognosis, especially when are not radically resected. Here we report the results of a selected population treated with standard schedule of Radiotherapy (RT) + Temozolomide (TMZ) followed by TMZ until progression. Methods: From January 2008 to January 2010, 14 newly diagnosed HGG patients, with median age of 50.6 years (range 27-75 yrs), were enrolled at Oncology Unit of S. Maria Goretti Hospital in Latina (University of Rome “Sapienza”). All patients were not radically resected and with ECOG PS=O. Furthermore patients were selected according to O6 Methyl-Guanine-DNA-Methyl Transferase (MGMT) promoter methylation status. Only methylated patients were included in our study. After surgery, patients received standard treatment with TMZ (75 mg/m2) concomitant with RT (60 Gy total dose). After a break of six weeks, Magnetic Resonance Imaging (MRI) was p...
Journal of Clinical Oncology, 2012
e11039 Background: CT may induce amenorrhea or menopause to a variable extent. These side-effects... more e11039 Background: CT may induce amenorrhea or menopause to a variable extent. These side-effects may impair or impede fertility, cause sexual dysfunction, bone loss and menopausal symptoms in many women. We analyzed incidence of amenorrhea in premenopausal pts affected by BC treated with CT. Methods: In this retrospective study we evaluated the incidence of amenorrhea in 24 premenopausal BC pts (43 median age years) treated with adjuvant A + C +/- T based CT. Overall population (OP) had regular menstrual cycle and no pts began hormone therapy, at the same time. Results: 10 pts (42%) received only A + C, 6 pts (25%) received A + C + T, 8 pts (33%) received A + C and after T. In 22 pts (92%) amenorrhea appeared during CT; in particular, 9/10 pts (90%) treated with A + C , 5/6 pts (83%) with A + C + T and 8/8 pts (100%) with A + C and after T. In OP amenorrhea appeared during first three cycles of CT in 18 pts (82%) and particularly 7 pts (32%) after 1 cycle, 7 pts (32%) after 2 cycle...
Cancer Chemotherapy and Pharmacology, 2019
Purpose Many studies have indicated that the response to therapy and the prognostic impact of a p... more Purpose Many studies have indicated that the response to therapy and the prognostic impact of a pathologic complete response after neoadjuvant treatment differ among breast cancer subtypes. Methods The aim of our study is to evaluate the effect of this treatment on the expression of estrogen and progesterone receptors, human epidermal growth hormone receptor 2 and Ki67 in breast cancer. We identified 125 patients. Results The estrogen receptor modified its expression from positive to negative in 8% patients and from negative to positive in 22%; progesterone in 21% and in 37% cases. Median Ki-67 value was 20.9% at biopsy and 18% after, HER-2 status did not show a remarkable change before or after neoadjuvant chemotherapy (NACT). We have identified a significant reduction in Ki-67 expression levels after chemotherapy in patients with a pathologic response. Detection of pretreatment Ki-67 could identify patients most likely to benefit from NACT. Conclusions NACT can change the status of ER, PgR, and Ki-67 expression in patients with breast adenocarcinoma, but it did not exert a significant effect on HER-2 status; HER-2 amplification appears to be more stable. We have identified a prognostic role for a decreased expression of PgR and Ki-67 after preoperative chemotherapy in breast cancer patients.
Experimental and Molecular Therapeutics, 2019
Analysis of circulating tumor cells ( CTCs) and circulating cell-free DNA (cfDNA), detected in pe... more Analysis of circulating tumor cells ( CTCs) and circulating cell-free DNA (cfDNA), detected in peripheral blood of patients, is an extraordinary novel strategy to identify and study NSCLC patients, in order to obtain prognostic and predictive molecular informations with a simple, non invasive and sensitive method. Liquid biopsy therefore offers a new source of cancer cells and cancer-derived materials in order to test more personalized treatment. With two PCR-based next generation sequencing (NGS) approaches we evaluated 45 patients with not squamous NSCLC ; in eighteen pts ( 40 % ) almost one genomic mutation was detected among 56 different genes analyzed with NGS. Median age of patients was 69 years ( 55-78) and 14 (73%) were males. Altogether, 11 genes were mutated with a panel of 56 genes analyzed (19,6% ) . The most frequent mutations occurred in KRAS, TP53, MET,KDR, KIT, SMAD4 and MET genes. Several patients expressed many mutations and the most frequent detected concerned gen c-Kit ( 22%). Other mutations concerned the following genes : TP53 ( 16 % ), MET/KDR. / SMAD4/KRas ( 44%). Other genomic alterations concerned the following genes: JACK3 (5%); APC(5%); ERBB4(5%); CTNNB! (5%); EGFR (5%). Altogheter the response to therapy was higher among patients with mutation of Smad 4 gene and lower in patients with mutations of KIT gene. All side effects occurred with target therapy was categorized according to the Common Terminology Criteria for Adverse Events, 4.0 version. An increase of gastroenteric (G3/G4) and hematologic toxicity (G3/G4) was observed in patients with Kit mutations. In our study this correlation was observed mainly during treatment with Tyrosine Kinase Inhibitors (TKIs ).Evaluating Progression Free Survival (PFS) in all the patients recruited in the study, a median PFS of 12.5, 11.5, 4 and 9 months was observed respectively in patients with mutations of KIT, SMAD4, TP53 and MET. In this study, all the genetic alterations analyzed and highlighted were related to the response to chemotherapeutic treatments and possible tyrosine kinase inhibitory treatments in terms of PFS and toxicity. Note: This abstract was not presented at the meeting. Citation Format: Silverio Tomao, Monica Verrico, Luigi Rossi, Iacobelli Stefano. Predictive therapeutic value of NGS with liquid biopsy in metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3334.
Journal of Clinical Oncology, 2014
ABSTRACT Background: Neutropenia (N) is a common chemotherapy (CT) related adverse event and febr... more ABSTRACT Background: Neutropenia (N) is a common chemotherapy (CT) related adverse event and febrile N (FN) often requires hospitalization, being associated with morbidity and mortality. Primary prophylaxis with G-CSF is a common strategy to avoid the onset of FN. Methods: Retrospectively, we evaluated efficacy and safety of daily injections of L (263 μg) from day 5 to 9 (5 total injections) compared with a single injection of P (6 mg) on day 2 in 55 NMBC pts (median age 55 years) during 6 cycles of FEC100 (group A) or 3 cycles of FEC100 followed by further 3 cycles of D100 (group B). Incidence of N, FN and bone pain (BP) (NRS >7) were evaluated. In group A: 35 pts (median age 54 years) received 6 cycles of FEC100. At every cycle, 17 pts received L, while 18 pts one dose of P. In group B: 20 pts (median age 55.5 years) underwent 3 cycles of FEC100 plus 3 of D100. At every cycle, 12 and 8 pts received L and P, respectively. Results: In overall population incidence of N-G3/G4 was 54.5%. In group A: G3/G4-N was 50% and 58% in P and L arm, respectively. One case of FN occurred in P arm. During first cycle, incidence of G3/G4-N was 33% and 41% in P and L arms, respectively; no G3/G4-N occurred during the last cycle. Incidence of BP was 11% in both arms. CT reduction occurred in 50% and 29% in P and L arm, respectively. In group B: G3/G4-N was 25% in P arm and 83% in L arm. No case of FN occurred in both arms. During first cycle, incidence of G3/G4-N was 0% in P and 50% in L arm; while during last cycle no G3/G4-N occurred in the P arm and 25% in L arm. 37% and 50% of pts experienced BP in P and L arm, respectively. CT dose reductions were necessary in 50% of P arm and 58% of L arm. Conclusions: P showed an higher efficacy than L for preventing G3/G4-N in both groups, also in the first cycle, even if the only FN occurred in a patient who was assuming P. There was a higher frequency of BP for L arm in FEC100-D100. In pts assuming FEC100 incidence of CT dose reduction was higher in P arm, while those assuming FEC100-D100 the incidence was higher in L arm.
Journal of Clinical Oncology, 2014
e12000 Background: Transitory or definitive amenorrhea (A) is a related side effect, specifically... more e12000 Background: Transitory or definitive amenorrhea (A) is a related side effect, specifically affecting young women diagnosed with breast cancer and treated with adjuvant chemotherapy (CT). Premature ovarian failure (POF) is often related to increased morbidity and mortality for heart disease and osteoporosis. In this study we analyzed the incidence of CIA in PBC patients and the correlation between their BMI and occurrence of A. Methods: 32 PBC patients, median age 44, were treated with adjuvant FEC±D. BMI was evaluated in all women. At accrual all the pts had normal menstrual activity (MA) and nobody received concomitant endocrine therapy. Results: 18 patients received FEC and 14 patients received FEC+D. In 27 patients A occurred during CT: in 89% of pts with FEC and 86% with FEC+D. In 62% of pts A occurred within first three cycles of CT. CIA occurred within the first two doses in 15/32 pts: in 44% treated with FEC and 50% with FEC+D. MA reappeared at the end of CT in 12% of pts (median age 44 year...
Journal of Clinical Medicine
Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypica... more Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted prese...
Cancers
Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhib... more Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes. Material and Methods: The effects of ICIs on 12 aggressive/metastatic PitNETs from the literature were reviewed and analyzed according to tumor characteristics, with the additional description of a silent-Pit1 metastatic tumor responding to pembrolizumab. Results: Most cases were metastatic (10/13: 6 corticotroph, 3 lactotroph, 1 silent Pit1); 3 were aggressive (2 corticotroph, 1 lactotroph). ICIS was used either as monotherapy or in combination. At last follow-up on ICI, a complete response (CR) was present in 3 cases and a partial response (PR) in 2 cases (4/5 metastatic). One sustained stable disease (SD) was reported. Progressive disease (PD) was observed in 7 cases, 3 of them after initial SD (n = 1) or PR (n = 3...
Endocrine
Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention... more Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention, but their clinical role remains unclear. The aim of this study was to evaluate the role of angiogenic markers in NEN aggressiveness and prognosis. We performed a prospective observational study including 46 consecutive patients with proven NENs of pulmonary (45.65%) and gastro-entero-pancreatic (GEP) (54.35%) origin and 29 healthy controls. Circulating pro-angiogenic factors were measured by ELISA assay. ANG2 tissue expression was evaluated in a subgroup of ten patients by immunohistochemistry. The study demonstrated a significantly higher level of ANG2, ANG1, sTIE2, and PROK2 in patients affected by NENs compared to controls. In the NENs’ group we measured that: (i) ANG2 levels were higher in poorly vs well-differentiated NENs: 4.85 (2.75–7.42) vs 3.16 (1.66–6.36) ng/ml, p = 0.046 and in tumor stage 3–4 compared to stage 1–2: 4.24 (2.66–8.72) vs 2.73 (1.53–5.70), p = 0.044; (ii) ANG2 and PROK2 were significantly higher in patents with progressive disease compared to stable disease: ANG2 = 6.26 (3.98–10.99) vs 2.73 (1.65–4.36) pg/ml, p = 0.001; PROK2 = 29.19 (28.42–32.25) vs 28.37 (28.14–28.91) pg/ml, p = 0.035. Immunohistochemistry confirmed ANG2 expression in tumor specimens. We documented higher levels of angiogenic markers in NENs, with an association between ANG2 serum levels and NENs morphology and staging. In both GEP and lung NENs, ANG2 and PROK2 are higher in case of tumor progression, suggesting a potential role as prognostic markers in NENs patients.
Journal of Clinical Oncology
e14529 Background: PD-L1 is the only biomarker that has been accepted to identify patients who co... more e14529 Background: PD-L1 is the only biomarker that has been accepted to identify patients who could potentially benefit from immune checkpoint inhibitors (ICIs) administration, but also PD-L1 negative tumors respond to immunotherapy. However, other biomarkers have been proposed but they are too expensive and actually, there is not a consensus for detection and analytical methods. Thus, there is an urgent need for inexpensive and reproducible tests to better optimize the clinical use of ICIs. Recent findings suggest that host parameters may help to select patients to treat with ICIs: performance status (PS) and some laboratory parameters, such as lactate dehydrogenase (LDH) and blood cells count. Inflammation and inflammatory response have been considered surrogate biomarkers of host immunity. An elevated neutrophil-to-lymphocyte (NLR), myeloid-to-lymphocyte (MLR) and platelet-to-lymphocyte (PLR) ratio have been associated with systemic inflammation and some evidences suggest that t...
Endocrine, 2022
Purpose: Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) a... more Purpose: Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods: A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results: Median age 61 years (13–86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high-power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6–323), median progression-free survival (PFS) was 36.0 months (0.3–323). Female sex correlated with a more indolent disease (T1; N0;...
R e v i e w open access to scientific and medical research Open Access Full Text Article
Purpose Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) an... more Purpose Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results Median age 61 years (13-86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6-323), median progression free survival (PFS) was 36.0 months (0.3-323). Female sex correlated with a more indolent disease (T1; N0; lo...
Recenti progressi in medicina, 2019
Riassunto. L'angiogenesi svolge un ruolo importante sia nei tessuti epiteliali normali sia in... more Riassunto. L'angiogenesi svolge un ruolo importante sia nei tessuti epiteliali normali sia in quelli maligni. Negli ultimi anni questo fenomeno è stato ampiamente studiato in oncologia sperimentale e clinica perché ci sono evidenze che sia coinvolto nella diffusione e nella diffusione metastatica del carcinoma ovarico. Il fattore di crescita dell'endotelio vascolare (vascular endothelial growth factor - VEGF) è l'attore principale nel meccanismo di angiogenesi e svolge un ruolo strategico nella proliferazione e migrazione delle cellule neoplastiche, con un impatto significativo sulla sopravvivenza e sull'outcome clinico. Secondo quanto emerge da molti studi sperimentali e clinici, le nostre conoscenze sulla biologia dell'angiogenesi e del VEGF sono aumentate portando allo sviluppo farmacologico di specifici agenti in grado di targeting VEGF. Questo nuovo campo di indagine offre agli scienziati l'opportunità di testare nuove possibilità terapeutiche nei pazien...
Frontiers in Oncology, 2021
Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrog... more Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metas...
Neuroendocrinology, 2021
The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It ... more The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain reaction, providing an accurate molecular profile of the neoplasm. Diagnostic utility of NETest has been widely demonstrated, while its role in predicting prognosis and treatment response is less studied. This systematic review aims to collect and discuss the available evidence on the prognostic and predictive role of NETest, trying to answer 3 questions, frequently raised in clinical practice. Is NETest able to differentiate stable from progressive disease? Increased NETest levels (at least >40%) correlate with disease progression. Is NETest able to predict tumor progression and tumor response to treatment? Some studies demonstrated that the baseline NETest score >33–40% could predict tumor progression. Moreover, NETest performed after treatment (as peptide receptor radionuclide therapy) could predict treatment...
Breast Cancer Research and Treatment, 2020
We read with great interest the paper recently published by Vriens et al. [1]. Fertility preserva... more We read with great interest the paper recently published by Vriens et al. [1]. Fertility preservation (FP) in young women undergoing chemotherapy for EBC is still an extremely debated topic, worthy of further investigation, although there is evidence to support the use of clinical strategies aimed at the conservation of fertility in these patients. Several studies and consensus papers suggest offering these patients an oncofertility counselling, in order to maintain their reproductive capacity [2, 3]. Unfortunately, we still have few data on the reproductive outcomes in young EBC patients treated with chemotherapy. Vriens’s study enrolled premenopausal patients under the age of 40 (median 31, range 19–40) with stage I–III invasive EBC, treated with adjuvant/neoadjuvant chemotherapy and potentially interested to FP. Authors reported that of 118 counseled women, 34 (29%) chose FP. In our opinion, this rate appears extremely low considering the young age of patients recruited and the probable desire to maintain reproductive capacity too, even if in the study it should be observed a high recovery rate of ovarian function (the 5-year OFR rate was 92% in all the patients and 93% in patients < 30 years old). These results confirm that young age is the main favorable factor for the preservation of ovarian function, suggesting that FP procedures in very young patients can be avoided. However, we do not completely agree with this theory as too many factors are involved in OFR after chemotherapy; among them, it is proper mentioning also the deterioration of the ovarian tissue after long adjuvant hormonal treatments which today are increasingly carried out. Due to the increasingly frequent postponement of decision to have a pregnancy in these patients, it seems illogical to deprive them of current available therapeutic opportunities to maintain reproductive capacity. In our opinion, fertility conserving strategies should always be guaranteed, both for future reproductive needs and for improving QOL. Probably, with a more advanced median age we could have observed higher rates of FP choice, due to the perception of future difficulties in achieving pregnancy. None of the patients received prophylactic Gn-Rh analogs during chemotherapy. Even if the enrollment period was from 2008 to 2015, it should be emphasized that for several years there has been scientific evidence supporting the use of Gn-Rh analogs for preserving ovarian function during chemotherapy for EBC, even if the consent about this preventive treatment is not yet fully shared. After all, the 5-year OFR rate of 92% suggests that prophylactic treatment with GnRH analogs should be probably reserved to patients older than 40 years. Going to evaluate the reproductive outcomes of the patients studied, it emerges as 26 patients gave birth and the 5-year live birth rate was 27% for all the patients undergoing fertility counseling. Currently, few data are available about the reproductive successful in transferring cryopreserved oocytes or embryos after chemotherapy for EBC. Vriens et al. reported that only three patients returned for embryo transfer, with a relatively high rate of spontaneous pregnancies. In this regard, a major limitation of the study concerns the lack of knowledge relating to the desire for patients to become pregnant. Therefore, it seems appropriate in the future to start clinical trials providing systematically the acquisition of this information to better understand the impact of FP on the reproductive outcomes of young women treated for EBC. This comment refers to the article available online at https ://doi. org/10.1007/s1054 9-020-05598 -2.
Journal of Clinical Oncology, 2012
e11514 Background: Anthracycline is very effective in treatment of breast cancer, however it can ... more e11514 Background: Anthracycline is very effective in treatment of breast cancer, however it can cause cardiac toxicity events. nPLD has greater safety profile and comparable efficacy than conventional anthracyclines. We evaluated safety and efficacy, in neoadjuvant setting, of nPLD in pts with LABC. Methods: 11 pts (median age 57 years). Their clinical stage was: stages IIA and IIB 1 pt respectively, IIIB 7 pts, IIIC 2 pts. 8 pts presented at diagnosis with cT4 disease. All pts were treated with nPLD (50 mg/mq, d1q21) plus Docetaxel (75 mg/mq, d1q21) and Cyclophosphamide (500 mg/mq, d1q21); only 1 pt received Cyclophosphamide, nPLD and Trastuzumab. At beginning of therapy, overall population had left ventricular ejection fraction (LVEF) ≥55%. Results: After a median of 4 chemotherapy cycles, we observed following clinical response: stable disease 2 pts (18%); partial response 7 pts (64%); complete response 2 pts (18%). 9 pts were evaluable for radiological response: objective respo...
Journal of Clinical Oncology, 2012
e12510 Background: Despite the important progress in the treatment of solid tumors, high grade gl... more e12510 Background: Despite the important progress in the treatment of solid tumors, high grade gliomas (HGGs) remain neoplasm with poor prognosis, especially when are not radically resected. Here we report the results of a selected population treated with standard schedule of Radiotherapy (RT) + Temozolomide (TMZ) followed by TMZ until progression. Methods: From January 2008 to January 2010, 14 newly diagnosed HGG patients, with median age of 50.6 years (range 27-75 yrs), were enrolled at Oncology Unit of S. Maria Goretti Hospital in Latina (University of Rome “Sapienza”). All patients were not radically resected and with ECOG PS=O. Furthermore patients were selected according to O6 Methyl-Guanine-DNA-Methyl Transferase (MGMT) promoter methylation status. Only methylated patients were included in our study. After surgery, patients received standard treatment with TMZ (75 mg/m2) concomitant with RT (60 Gy total dose). After a break of six weeks, Magnetic Resonance Imaging (MRI) was p...
Journal of Clinical Oncology, 2012
e11039 Background: CT may induce amenorrhea or menopause to a variable extent. These side-effects... more e11039 Background: CT may induce amenorrhea or menopause to a variable extent. These side-effects may impair or impede fertility, cause sexual dysfunction, bone loss and menopausal symptoms in many women. We analyzed incidence of amenorrhea in premenopausal pts affected by BC treated with CT. Methods: In this retrospective study we evaluated the incidence of amenorrhea in 24 premenopausal BC pts (43 median age years) treated with adjuvant A + C +/- T based CT. Overall population (OP) had regular menstrual cycle and no pts began hormone therapy, at the same time. Results: 10 pts (42%) received only A + C, 6 pts (25%) received A + C + T, 8 pts (33%) received A + C and after T. In 22 pts (92%) amenorrhea appeared during CT; in particular, 9/10 pts (90%) treated with A + C , 5/6 pts (83%) with A + C + T and 8/8 pts (100%) with A + C and after T. In OP amenorrhea appeared during first three cycles of CT in 18 pts (82%) and particularly 7 pts (32%) after 1 cycle, 7 pts (32%) after 2 cycle...
Cancer Chemotherapy and Pharmacology, 2019
Purpose Many studies have indicated that the response to therapy and the prognostic impact of a p... more Purpose Many studies have indicated that the response to therapy and the prognostic impact of a pathologic complete response after neoadjuvant treatment differ among breast cancer subtypes. Methods The aim of our study is to evaluate the effect of this treatment on the expression of estrogen and progesterone receptors, human epidermal growth hormone receptor 2 and Ki67 in breast cancer. We identified 125 patients. Results The estrogen receptor modified its expression from positive to negative in 8% patients and from negative to positive in 22%; progesterone in 21% and in 37% cases. Median Ki-67 value was 20.9% at biopsy and 18% after, HER-2 status did not show a remarkable change before or after neoadjuvant chemotherapy (NACT). We have identified a significant reduction in Ki-67 expression levels after chemotherapy in patients with a pathologic response. Detection of pretreatment Ki-67 could identify patients most likely to benefit from NACT. Conclusions NACT can change the status of ER, PgR, and Ki-67 expression in patients with breast adenocarcinoma, but it did not exert a significant effect on HER-2 status; HER-2 amplification appears to be more stable. We have identified a prognostic role for a decreased expression of PgR and Ki-67 after preoperative chemotherapy in breast cancer patients.
Experimental and Molecular Therapeutics, 2019
Analysis of circulating tumor cells ( CTCs) and circulating cell-free DNA (cfDNA), detected in pe... more Analysis of circulating tumor cells ( CTCs) and circulating cell-free DNA (cfDNA), detected in peripheral blood of patients, is an extraordinary novel strategy to identify and study NSCLC patients, in order to obtain prognostic and predictive molecular informations with a simple, non invasive and sensitive method. Liquid biopsy therefore offers a new source of cancer cells and cancer-derived materials in order to test more personalized treatment. With two PCR-based next generation sequencing (NGS) approaches we evaluated 45 patients with not squamous NSCLC ; in eighteen pts ( 40 % ) almost one genomic mutation was detected among 56 different genes analyzed with NGS. Median age of patients was 69 years ( 55-78) and 14 (73%) were males. Altogether, 11 genes were mutated with a panel of 56 genes analyzed (19,6% ) . The most frequent mutations occurred in KRAS, TP53, MET,KDR, KIT, SMAD4 and MET genes. Several patients expressed many mutations and the most frequent detected concerned gen c-Kit ( 22%). Other mutations concerned the following genes : TP53 ( 16 % ), MET/KDR. / SMAD4/KRas ( 44%). Other genomic alterations concerned the following genes: JACK3 (5%); APC(5%); ERBB4(5%); CTNNB! (5%); EGFR (5%). Altogheter the response to therapy was higher among patients with mutation of Smad 4 gene and lower in patients with mutations of KIT gene. All side effects occurred with target therapy was categorized according to the Common Terminology Criteria for Adverse Events, 4.0 version. An increase of gastroenteric (G3/G4) and hematologic toxicity (G3/G4) was observed in patients with Kit mutations. In our study this correlation was observed mainly during treatment with Tyrosine Kinase Inhibitors (TKIs ).Evaluating Progression Free Survival (PFS) in all the patients recruited in the study, a median PFS of 12.5, 11.5, 4 and 9 months was observed respectively in patients with mutations of KIT, SMAD4, TP53 and MET. In this study, all the genetic alterations analyzed and highlighted were related to the response to chemotherapeutic treatments and possible tyrosine kinase inhibitory treatments in terms of PFS and toxicity. Note: This abstract was not presented at the meeting. Citation Format: Silverio Tomao, Monica Verrico, Luigi Rossi, Iacobelli Stefano. Predictive therapeutic value of NGS with liquid biopsy in metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3334.
Journal of Clinical Oncology, 2014
ABSTRACT Background: Neutropenia (N) is a common chemotherapy (CT) related adverse event and febr... more ABSTRACT Background: Neutropenia (N) is a common chemotherapy (CT) related adverse event and febrile N (FN) often requires hospitalization, being associated with morbidity and mortality. Primary prophylaxis with G-CSF is a common strategy to avoid the onset of FN. Methods: Retrospectively, we evaluated efficacy and safety of daily injections of L (263 μg) from day 5 to 9 (5 total injections) compared with a single injection of P (6 mg) on day 2 in 55 NMBC pts (median age 55 years) during 6 cycles of FEC100 (group A) or 3 cycles of FEC100 followed by further 3 cycles of D100 (group B). Incidence of N, FN and bone pain (BP) (NRS >7) were evaluated. In group A: 35 pts (median age 54 years) received 6 cycles of FEC100. At every cycle, 17 pts received L, while 18 pts one dose of P. In group B: 20 pts (median age 55.5 years) underwent 3 cycles of FEC100 plus 3 of D100. At every cycle, 12 and 8 pts received L and P, respectively. Results: In overall population incidence of N-G3/G4 was 54.5%. In group A: G3/G4-N was 50% and 58% in P and L arm, respectively. One case of FN occurred in P arm. During first cycle, incidence of G3/G4-N was 33% and 41% in P and L arms, respectively; no G3/G4-N occurred during the last cycle. Incidence of BP was 11% in both arms. CT reduction occurred in 50% and 29% in P and L arm, respectively. In group B: G3/G4-N was 25% in P arm and 83% in L arm. No case of FN occurred in both arms. During first cycle, incidence of G3/G4-N was 0% in P and 50% in L arm; while during last cycle no G3/G4-N occurred in the P arm and 25% in L arm. 37% and 50% of pts experienced BP in P and L arm, respectively. CT dose reductions were necessary in 50% of P arm and 58% of L arm. Conclusions: P showed an higher efficacy than L for preventing G3/G4-N in both groups, also in the first cycle, even if the only FN occurred in a patient who was assuming P. There was a higher frequency of BP for L arm in FEC100-D100. In pts assuming FEC100 incidence of CT dose reduction was higher in P arm, while those assuming FEC100-D100 the incidence was higher in L arm.
Journal of Clinical Oncology, 2014
e12000 Background: Transitory or definitive amenorrhea (A) is a related side effect, specifically... more e12000 Background: Transitory or definitive amenorrhea (A) is a related side effect, specifically affecting young women diagnosed with breast cancer and treated with adjuvant chemotherapy (CT). Premature ovarian failure (POF) is often related to increased morbidity and mortality for heart disease and osteoporosis. In this study we analyzed the incidence of CIA in PBC patients and the correlation between their BMI and occurrence of A. Methods: 32 PBC patients, median age 44, were treated with adjuvant FEC±D. BMI was evaluated in all women. At accrual all the pts had normal menstrual activity (MA) and nobody received concomitant endocrine therapy. Results: 18 patients received FEC and 14 patients received FEC+D. In 27 patients A occurred during CT: in 89% of pts with FEC and 86% with FEC+D. In 62% of pts A occurred within first three cycles of CT. CIA occurred within the first two doses in 15/32 pts: in 44% treated with FEC and 50% with FEC+D. MA reappeared at the end of CT in 12% of pts (median age 44 year...