Survival Nomograms after Curative Neoadjuvant Chemotherapy and Radical Surgery for Stage IB2-IIIB Cervical Cancer

Claudia Marchetti,Francesca De Felice,Anna Di Pinto,Alessia Romito,Angela Musella,Innocenza Palaia,Marco Monti,Vincenzo Tombolini,Ludovico Muzii,PierLuigi Benedetti Panici 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose The purpose of this study was to develop nomograms for predicting the probability of overall survival (OS) and progression-free survival (PFS) in locally advanced cervical cancer treated with neoadjuvant chemotherapy and radical surgery. Materials and Methods Nomograms to predict the 5-year OS rates and the 2-year PFS rates were constructed. Calibration plots were constructed, and concordance indices were calculated. Evaluated variables were body mass index, age, tumor size, tumor histology, grading, lymphovascular space invasion, positive parametria, and positive lymph nodes. Results In total 245 patients with locally advanced cervical cancer who underwent neoadjuvant chemotherapy and radical surgery were included for the construction of the nomogram. The 5-year OS and PFS were 72.6% and 66%, respectively. Tumor size, grading, and parametria status affected the rate of OS, whereas tumor size and positive parametria were the main independent PFS prognostic factors. Conclusion We constructed a nomogram based on clinicopathological features in order to predict 2-year PFS and 5-year OS in locally advanced cervical cancer primarily treated with neoadjuvant chemotherapy followed by radical surgery. This tool might be particularly helpful for assisting in the follow-up of cervical cancer patients who have not undergone concurrent chemoradiotherapy.

ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience

Giulia Amadio,Claudia Marchetti,Emanuele Rocco Villani,Domenico Fusco,Francesca Stollagli,Carolina Bottoni,Mariagrazia Distefano,Giuseppe Colloca,Giovanni Scambia,Anna Fagotti 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.1

Objective: Bevacizumab maintenance following platinum-based chemotherapy is an effective treatment for epithelial ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition. Methods: This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (<65 years, group 1) and elderly (≥65 years, group 2). A binary logistic model was applied to correlate clinical variables and severe (grade ≥3) toxicity risk. Results: Overall, 283 patients with EOC were included, with 72 (25.4%) older patients compared with 211 (74.6%) younger women. Bevacizumab had been administered to 234 patients (82.7%) as first-line treatment and in 49 (17.3%) with recurrent disease. At diagnosis, elderly patients presented with at least one comorbidity and were taking at least 1 medication in 84.7% and 80.6% of the cases respectively, compared with correspondingly 47.4% and 37.4% in group 1 (p<0.001). Nonetheless, the occurrence of serious (grade ≥3) adverse events did not increase among the older group. Creatinine serum levels >1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity. Conclusions: Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk.

Diatom Allantoin Synthase Provides Structural Insights into Natural Fusion Protein Therapeutics

Oh, Juntaek,Liuzzi, Anastasia,Ronda, Luca,Marchetti, Marialaura,Corsini, Romina,Folli, Claudia,Bettati, Stefano,Rhee, Sangkee,Percudani, Riccardo American Chemical Society 2018 ACS CHEMICAL BIOLOGY Vol.13 No.8

<P>Humans have lost the ability to convert urate into the more soluble allantoin with the evolutionary inactivation of three enzymes of the uricolytic pathway. Restoration of this function through enzyme replacement therapy can treat severe hyperuricemia and Lesch-Nyhan disease. Through a genomic exploration of natural gene fusions, we found that plants and diatoms independently evolved a fusion protein (allantoin synthase) complementing two human pseudogenes. The 1.85-Å-resolution crystal structure of allantoin synthase from the diatom <I>Phaeodactylum tricornutum</I> provides a rationale for the domain combinations observed in the metabolic pathway, suggesting that quaternary structure is key to the evolutionary success of protein domain fusions. Polyethylene glycol (PEG) conjugation experiments indicate that a PEG-modified form of the natural fusion protein provides advantages over separate enzymes in terms of activity maintenance and manufacturing of the bioconjugate. These results suggest that the combination of different activities in a single molecular unit can simplify the production and chemical modification of recombinant proteins for multifunctional enzyme therapy.</P> [FIG OMISSION]</BR>

Tumor Infiltrating Lymphocytes in Ovarian Cancer

Gasparri, Maria Luisa,Attar, Rukset,Palaia, Innocenza,Perniola, Giorgia,Marchetti, Claudia,Donato, Violante Di,Farooqi, Ammad Ahmad,Papadia, Andrea,Panici, Pierluigi Benedetti Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

Comparison of Anogenital Distance and Correlation with Vulvo-vaginal Atrophy: A Pilot Study on Premenopausal and Postmenopausal Women

( Lavinia Domenici ),( Angela Musella ),( Carlotta Bracchi ),( Francesca Lecce ),( Michele Carlo Schiavi ),( Vanessa Colagiovanni ),( Violante Di Donato ),( Claudia Marchetti ),( Federica Tomao ),( In 대한폐경학회 2018 대한폐경학회지 Vol.24 No.2

Objectives: Anogenital distance (AGD) represents the space between labia posterior commissure and anus. This was pilot study to investigate how menopause and so lack of oestrogens affects AGD. Methods: A total of 109 patients were enrolled. AGD was measured in lithotomy position using sterile paper ruler. Anogenital index (AGI) was used to control 2 variables of height and weight (body mass index, kg/m2). Vaginal health index (VHI) was used to evaluate vaginal wellness. Female sexual function index (FSFI) questionnaire was administered to all women to evaluate the impact of menopause on their sexual function. Results: AGD (30.87 ± 2.98 vs. 17.57 ± 2.18; P = 0.0001) and AGI (1.40 ± 0.21 vs. 0.70 ± 0.15; P = 0.0001) were both significantly lower in the postmenopausal group. Postmenopausal women were affected by vulvovaginal atrophy (VVA) significantly. Thus, VHI scores were dramatically worse in postmenopausal group (23.95 ± 1.28 vs. 10.75 ± 3.41; P = 0.0001) as well as FSFI results (32.68 ± 2.25 vs. 19.78 ± 5.46; P = 0.0001). Conclusions: This study confirms that AGD in post-menopausal women was significantly shorter than AGD in premenopausal women, correlating with an increase of VVA and sexual impairment. Changes of AGD and AGI demonstrated to predict hormonal changes that may occur after menopause. (J Menopausal Med 2018;24:108-112)