Papers by Francesco Legge
F1000 - Post-publication peer review of the biomedical literature, 2012
BACKGROUND-The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that pl... more BACKGROUND-The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. METHODS-We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. RESULTS-Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and
Purpose:We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) su... more Purpose:We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) subsets [CD3, CD4,CD8, CD25, and T cell receptor (TCR)-~ ^ expressing cells] and tryptase-positive mast cells in cervical tumors. Circulating levels of cytokines [interleukin (IL)-1h, IL-10, tumor necrosis factor-a, IL-6, and IL-12] and angiogenesis-modulating factors (vascular endothelial growth factor and endostatin) have also been analyzed. Experimental Design: Cervical tumor biopsies and blood samples were obtained at the time of diagnosis and after10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assayswere used to assess the expression of biological factors in tumor tissue and circulating levels of cytokines and angiogenic molecules. Results:We showed a statistically significant increase in the percentage of TIL expressing the TCR-~ chain after celecoxib treatment: indeed, in cases exposed to celecoxib, the percenta...
F1000 - Post-publication peer review of the biomedical literature, 2011
Journal of Cancer Research and Clinical Oncology
Objective The aim of this retrospective study was to compare surgical and survival outcome in onl... more Objective The aim of this retrospective study was to compare surgical and survival outcome in only patients with early-stage UCSs managed by laparotomic surgery (LPT) versus minimally invasive surgery (MIS). Methods Data were retrospectively collected in four Italian different institutions. Inclusion criteria were UCS diagnosis confirmed by the definitive histological examination, and stage I or II according to the FIGO staging system. Results Between August 2000 and March 2019, the data relative to 170 patients bearing UCSs were collected: of these, 95 were defined as early-stage disease (stage I–II) based on the histological report at the primary surgery, and thus were included in this study. Forty-four patients were managed by LPT, and 51 patients were managed by MIS. The operative time was lower in the MIS group versus the LPT group (p value 0.021); the median estimated blood loss was less in the MIS group compared to the median of LPT group (p value
International Journal of Gynecologic Cancer
IntroductionRecurrence of endometrial cancer is an important clinical challenge, with median surv... more IntroductionRecurrence of endometrial cancer is an important clinical challenge, with median survival rarely exceeding 12 months. The aim of this study was to analyze patterns of endometrial cancer recurrence and associations of these patterns with clinical outcome.MethodsThe study included patients with endometrial cancer who underwent primary surgical treatment with or without adjuvant treatment between July 2004 and June 2017 at the Gynaecologic Oncology Unit of one of three tertiary hospitals of the Catholic University Network in Italy with complete follow-up data available. Information on the date and pattern of recurrence was retrieved for each relapse. Post-relapse survival was recorded as the time from the date of recurrence to the date of death or last follow-up. Survival probabilities were compared using log rank tests, and associations of clinico-pathological characteristics with post-relapse survival were tested using Cox’s regression models.ResultsA total of 1503 patien...
International Journal of Gynecological Cancer
ObjectiveThe aim of this retrospective study was to assess the surgical and oncological outcome o... more ObjectiveThe aim of this retrospective study was to assess the surgical and oncological outcome of 3 different surgical approaches (laparotomy, laparoscopy, and robotic surgery) in the treatment of early-stage cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1.MethodsAll patients with a histologically confirmed diagnosis of early-stage cervical cancer, FIGO stage IB1, who underwent abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy, or robotic radical hysterectomy with or without pelvic and aortic lymphadenectomy were included in the study. A review of the literature was conducted.ResultsThree hundred forty-one patients, between January 2001 and December 2016, were included in this study: 101 patients were submitted to ARH, 152 to laparoscopic radical hysterectomy, and 88 to robotic radical hysterectomy. In 97% and 11.5% of cases, bilateral pelvic and aortic lymph node dissections were performed, respectively. The 3 groups wer...
American journal of obstetrics and gynecology, Jan 2, 2018
Vaginal cuff dehiscence following hysterectomy is considered an infrequent but potentially devast... more Vaginal cuff dehiscence following hysterectomy is considered an infrequent but potentially devastating complication. Different possible techniques for cuff closure have been proposed to reduce this threatening adverse event. The aim of the present randomized study was to compare laparoscopic and transvaginal suture of the vaginal vault at the end of a total laparoscopic hysterectomy, in terms of incidence of vaginal dehiscence and vaginal cuff complications. Factors associated with vaginal dehiscence were also analyzed. This article presents the results of the interim analysis of the trial. Patients undergoing total laparoscopic hysterectomy for benign indications were randomized at the time of colpotomy to receive vaginal closure through transvaginal vs laparoscopic approach using a 1:1 ratio. Allocation concealment was obtained using a password-protected randomization database. Monopolar energy for colpotomy was set at 60W. Vaginal closure was performed with a single-layer running...
Journal of minimally invasive gynecology, Jan 12, 2018
To investigate the feasibility, safety, and short-term outcomes of robotic surgery (RS) for gynec... more To investigate the feasibility, safety, and short-term outcomes of robotic surgery (RS) for gynecologic oncologic indications (cervical, endometrial, and ovarian cancer) in elderly patients, especially women age 65 to 74 years (elderly group [EG]) compared with women age ≥75 years (very elderly group [VEG]). Retrospective cohort study (Canadian Task Force classification II-2). Catholic University of the Sacred Heart, Rome, Italy. Between May 2013 and April 2017, 204 elderly and very elderly patients underwent RS procedures for gynecologic malignancies. The median age was 71 years (range, 65-74 years) in the EG and 77 years (range, 75-87 years) in the VEG. The incidence of cardiovascular disease was higher in the VEG (p = .038). The EG and VEG were comparable in terms of operative time, blood loss, and need for blood transfusion. Almost all (98.5%) of the patients underwent total/radical hysterectomy, 109 patients (55.6% of the EG vs 48.3% of the VEG) underwent pelvic lymphadenectomy...
Journal of minimally invasive gynecology
The primary aim of this study was to evaluate the feasibility, efficacy, and safeness of nerve-sp... more The primary aim of this study was to evaluate the feasibility, efficacy, and safeness of nerve-sparing laparoscopic colposacropexy performed with a minimally invasive approach by using 2.9-mm Percuvance percutaneous surgical system (PSS; The Percuvance System; Teleflex Inc., Wayne, PA). The secondary aim was to investigate the technical performance of these instruments as needle holder in the placement of the mesh. The final aim was to establish the rate of prolapse recurrence. Step-by-step video demonstration of the surgical technique. The Internal Department Committee approved this study. The patient was adequately informed about the possible risks and benefits of this experimental technique, and a written consent agreeing to undergo the described procedure was signed. Nerve-sparing laparoscopic colposacropexy with positioning of two polypropylene titanized meshes and concomitant subtotal hysterectomy and salpingo-oophorectomy entirely performed with a 2.9-mm PSS. Pelvic organ pro...
International Journal of Radiation Oncology*Biology*Physics, 2016
A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of... more A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort received higher doses (60 Gy in 2.4-Gy fractions). Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity-free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). This clinical study showed the feasibility of this technique and its good profile in terms of acute and late toxicity at the recommended doses even in aged and frail patients.
Clinical Cancer Research, Sep 1, 2001
Purpose: The aim of the study was to investigate if a short-term administration of high-dose Tamo... more Purpose: The aim of the study was to investigate if a short-term administration of high-dose Tamoxifen (Tam) could affect the expression of biologically relevant biochemical parameters in cervical cancer tissue. Experimental Design: The study was conducted in 24 patients with histologically confirmed cervical tumors. Biopsies were obtained by colposcopy on day 0 in all patients, who then received either 80 mg/die or 160 mg/die for 5 consecutive days until the second biopsy was obtained. Immunohistochemistry was performed with antiestrogen receptor (ER), anti-Ki67, anticaspase cleavage product of keratin 18 (M30), and anti-CD31 monoclonal antibodies. Results: Eleven (45.8%) of 24 cervical tumors were ER positive. The percentage of Ki67-positive tumor cells in pre-Tam biopsies was significantly higher than the percentage in the corresponding posttreatment biopsies (z ؍ 4.29, P ؍ 0.0001). No difference in the pretreatment percentage of Ki67-positive cells according to ER status was found. The percentage of M30 positivity was higher in post-Tam than in pre-Tam biopsies. Microvessel density values in pre-Tam biopsies were significantly higher than corresponding values in posttreatment tissues (z ؍ ؊3.72, P ؍ 0.0002). The reduction in the percentage of Ki67-positive tumors was significantly (z ؍ 3.58, P ؍ 0.0003) higher in ER-positive than in ER-negative tumors, whereas no difference in Taminduced reduction of microvessel density values according to ER status (z ؍ ؊0.18, P ؍ 0.85) was found. Tam treatment did not induce any change of M30 positivity in ER-positive tumors, whereas in ER-negative tumors, it produced a significant (P ؍ 0.015) increase in the percentage of M30positive cells in post-Tam versus pre-Tam biopsies. Conclusions: A short-term treatment with Tam at doses 4-8-fold higher than those in conventional schemes is associated with modifications of biological parameters associated with tumor cell proliferation, apoptosis, and neoangiogenesis in cervical cancer.
Cancer Chemotherapy and Pharmacology, Apr 11, 2007
Gemcitabine (2&am... more Gemcitabine (2',2'-difluorodeoxycytidine) (GEM) has been demonstrated to be active in the salvage setting of ovarian cancer (OC) patients. A 57-year-old woman, with a diagnosis of FIGO Stage IIIC clear cell OC, judged inoperable to optimal residual tumor, was administered neo-adjuvant chemotherapy with carboplatin/paclitaxel/topotecan, and cytoreduction. After 5 months the patient progressed, and pegylated liposomal doxorubicin was started with rapid progression. GEM (1,000 mg/m2, d1,8,15, q28) was then started, and a complete clinical response was documented after seven cycles of treatment, and was maintained for 9 months; at progression fourth line carboplatin was attempted but 1 month after the last course of carboplatin, progression occurred, and the patient was re-challenged with GEM obtaining a partial response, of 6 months duration. Currently, the patient is still under treatment, without any complaints relative to her quality of life/specific symptoms. We described the case of a drug resistant clear cell ovarian cancer showing a selective susceptibility only to GEM at first administration and at re-challenge. Moreover, this case expressed a molecular profile very likely to support high tumour cell sensitivity to GEM.
Oncology Letters, 2016
The present study investigated the combination of levonorgestrel-releasing intrauterine device (L... more The present study investigated the combination of levonorgestrel-releasing intrauterine device (LNG-IUD) insertion and palliative radiotherapy (RT) as a potential approach for treating frail, elderly endometrial cancer (EC) patients considered unfit for curative oncological treatments. The inclusion criteria were an age of ≥65 years, pathological confirmation of a uterine neoplasm, a Charlson comorbidity index (CCI) value of ≥4 and the presence of vaginal bleeding. Patients underwent intrauterine insertion of an LNG-IUD, and thereafter, received a total dose of 30 Gy at 3 Gy per fraction, over 10 days. The clinical target volume (CTV) was defined as the uterus and disease-involved tissues in the pelvis plus a 1-cm margin. The planning target volume was obtained by adding a 1-cm isotropic margin to the CTV. A total of 9 patients with EC (median age, 85 years; Eastern Cooperative Oncology Group performance status ≥2, ≥88.8%; obesity, 55.5%; median CCI, 5) received an LNG-IUD plus RT. An early complete resolution of bleeding was documented in 8 patients (88.8%), while the remaining patient experienced a marked improvement. The median duration of bleeding control was 18 months, while the 2-year actuarial rate of bleeding-free survival was 53.3% (median follow-up time, 20 months; range, 9-60 months). No LNG-IUD-or severe RT-related complications were documented. Overall, a high rate of bleeding remission, durable bleeding-free survival in face of the easy intrauterine insertion of an LNG-IUD and a negligible toxicity profile of the complete treatment were documented in this study, indicating a requirement for further investigation in a larger series.
Journal of minimally invasive gynecology, Jan 27, 2015
This is a prospective, phase II study aimed at assessing the feasibility rate of laparoscopic rad... more This is a prospective, phase II study aimed at assessing the feasibility rate of laparoscopic radical surgery in locally advanced cervical cancer (LACC) patients administered chemoradiation (CT/RT). FIGO Stage IB2-III patients were evaluated for accrual at the Gynecologic Oncology Unit of the Catholic University (Rome/Campobasso). Neo-adjuvant CT/RT included whole pelvic irradiation (total dose 45.0-50.4 Gy) combined with cisplatin and 5-fluorouracil. Objective response to treatment was evaluated according to RECIST criteria; laparoscopic radical hysterectomy (RH) plus pelvic ± aortic lymphadenectomy was attempted within 6-8 weeks from CT/RT. The feasibility of laparoscopic RH, as well as the rate, pattern, and severity of early and late post-operative complications were analyzed. Between January 2010 and October 2013, 58 patients were enrolled into the study. After CT/RT, 23 patients (39.6%) underwent Type B2 RH, while 31 cases (53.4%) underwent Type C1 RH, and 4 cases (6.9%) were ...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2011
Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian... more Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy.
Cancer Chemotherapy and Pharmacology, 2007
Gemcitabine (2&am... more Gemcitabine (2',2'-difluorodeoxycytidine) (GEM) has been demonstrated to be active in the salvage setting of ovarian cancer (OC) patients. A 57-year-old woman, with a diagnosis of FIGO Stage IIIC clear cell OC, judged inoperable to optimal residual tumor, was administered neo-adjuvant chemotherapy with carboplatin/paclitaxel/topotecan, and cytoreduction. After 5 months the patient progressed, and pegylated liposomal doxorubicin was started with rapid progression. GEM (1,000 mg/m2, d1,8,15, q28) was then started, and a complete clinical response was documented after seven cycles of treatment, and was maintained for 9 months; at progression fourth line carboplatin was attempted but 1 month after the last course of carboplatin, progression occurred, and the patient was re-challenged with GEM obtaining a partial response, of 6 months duration. Currently, the patient is still under treatment, without any complaints relative to her quality of life/specific symptoms. We described the case of a drug resistant clear cell ovarian cancer showing a selective susceptibility only to GEM at first administration and at re-challenge. Moreover, this case expressed a molecular profile very likely to support high tumour cell sensitivity to GEM.
F1000 - Post-publication peer review of the biomedical literature, 2009
F1000 - Post-publication peer review of the biomedical literature, 2008
F1000 - Post-publication peer review of the biomedical literature, 2010
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Papers by Francesco Legge