Publications by authors named "Alessia Di Legge"

10 Publications

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Endometrial cancer off-line staging using two-dimensional transvaginal ultrasound and three-dimensional volume contrast imaging: Intermethod agreement, interrater reliability and diagnostic accuracy.

Gynecol Oncol 2018 09 18;150(3):438-445. Epub 2018 Jul 18.

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Objectives: The aim is to estimate agreement between two-dimensional transvaginal ultrasound (2D-TVS) and three-dimensional volume contrast imaging (3D-VCI) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) of endometrial cancer and to compare the two methods regarding inter-rater reliability and diagnostic accuracy.

Methods: Fifteen ultrasound experts assessed off-line de-identified 3D-VCI volumes and 2D-TVU video clips from 58 patients with biopsy-confirmed endometrial cancer regarding the presence of deep (≥50%) MI and CSI. Video clips and 3D volumes were assessed independently. Interrater reliability was measured using kappa statistics. Histological diagnosis after hysterectomy served as gold standard. Accuracy measurements were correlated to rater experience using Spearman's rank correlation coefficient (ρ).

Results: Agreement between 2D-TVU and 3D-VCI for diagnosing MI was median 76% (range 64-93%) and for CSI median 88% (range 79-97%). Interrater reliability was better for 2D-TVU than for 3D-VCI (Fleiss' kappa 0.41 vs. 0.31 for MI and 0.55 vs. 0.45 for CSI). Median accuracy for diagnosing deep MI was 76% (range 59-84%) with 2D-TVU and 69% (range 52-83%) for 3D-VCI; the corresponding figures for CSI were 88% (range 81-93%) and 86% (range 72-95%). Accuracy was significantly correlated to how many cases the raters assessed annually.

Conclusions: Off-line assessment of MI and CSI in women with endometrial cancer using 3D-VCI has lower interrater reliability and lower accuracy than 2D-TVU video clip assessment. Since accuracy was correlated to the number of cases assessed annually it is advised to centralize these examinations to high-volume centres.
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http://dx.doi.org/10.1016/j.ygyno.2018.06.027DOI Listing
September 2018

Imaging techniques for evaluation of uterine myomas.

Best Pract Res Clin Obstet Gynaecol 2016 Jul 30;34:37-53. Epub 2015 Nov 30.

Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.

Due to their high prevalence and related morbidity, uterine myomas constitute a group of gynecological pathologies largely studied in all clinical, diagnostic, and therapeutic aspects. They have been widely evaluated with a large series of imaging techniques. In fact, ultrasound (also saline infusion sonohysterography) and magnetic resonance imaging (MRI) are considered the optimal methods to assess uterine fibroids in terms of number, volume, echostructure, location, relation with endometrial cavity and uterine layers, vascularization, and differential diagnosis with other benign (adenomyosis) and malignant myometrial pathologies. Nevertheless, further studies are required to fill some gaps such as the absence of a common and sharable sonographic terminology and methodology to scan the myometrium, as well as imaging parameters for differentiation of typical myomas from smooth tumors of unknown malignant potential (STUMP) and leiomyosarcomas.
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http://dx.doi.org/10.1016/j.bpobgyn.2015.11.014DOI Listing
July 2016

Metronomic oral cyclophosphamide (MOC) in the salvage therapy of heavily treated recurrent ovarian cancer patients: a retrospective, multicenter study.

BMC Cancer 2014 Dec 13;14:947. Epub 2014 Dec 13.

Gynecologic Oncology Unit, Catholic University of Campobasso, Campobasso, Italy.

Background: The aim of this multicenter, retrospective study was to evaluate the efficacy and safety of metronomic oral cyclophosphamide (MOC) in heavily treated, relapsed ovarian cancer (ROC) patients.

Methods: oral cyclophosphamide (Endoxan®, Baxter, Italy) was administered at the dose of 50 mg daily, continuously. Treatment-related toxicity and response to treatment were assessed by the NCI-CTC criteria, and RECIST criteria, respectively. Progression-free (PFS), and overall survival (OS) were also assessed.

Results: 54 patients were analyzed: 20 patients (37.0%) were considered primarily platinum refractory/resistant, while 34 patients (63.0%) were defined as platinum sensitive; 79.6% of patients had received ≥2 previous lines before starting MOC. The objective response rate (ORR) was 20.4%. Eleven patients (20.4%) experienced stable disease and 8 of them had a response duration ≥6 months. A total of 32 patients (59.2.%) progressed during treatment. Median PFS was 4 months, and the 12-month PFS rate was 19.6%; median OS was 13 months, and the 12-month OS rate was 51.5% . Patients responding to MOC showed a more favorable PFS (median = 17 months) compared to patients with stabilization (median = 6 months) or progression of disease (median = 3 months) (p value = 0.0001). Median OS of responding patients was 30 months compared to 11 months in cases achieving stabilization, or progression of disease (median = 8 months) (p value = 0.0001). Only 1 patient experienced grade 3 anemia. Non-hematological grade 3 toxicity was registered in 2 patients.

Conclusions: MOC could provide a valid alternative in terms of risk/benefit ratio in the palliative treatment of heavily treated ROC patients.
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http://dx.doi.org/10.1186/1471-2407-14-947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301460PMC
December 2014

Clinical utility of trabectedin for the treatment of ovarian cancer: current evidence.

Onco Targets Ther 2014 12;7:1273-84. Epub 2014 Jul 12.

Gynecologic Oncology Unit, Department of Oncology, Catholic University of Rome, Italy.

Among the pharmaceutical options available for treatment of ovarian cancer, attention has been increasingly focused on trabectedin (ET-743), a drug which displays a unique mechanism of action and has been shown to be active in several human malignancies. Currently, single agent trabectedin is approved for treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, and in association with pegylated liposomal doxorubicin for treatment of patients with relapsed partially platinum-sensitive ovarian cancer. This review aims at summarizing the available evidence about the clinical role of trabectedin in the management of patients with epithelial ovarian cancer. Novel perspectives coming from a better understanding of trabectedin mechanisms of action and definition of patients subgroups likely susceptible to benefit of trabectedin treatment are also presented.
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http://dx.doi.org/10.2147/OTT.S51550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103925PMC
July 2014

Imaging techniques for the evaluation of cervical cancer.

Best Pract Res Clin Obstet Gynaecol 2014 Jul 4;28(5):741-68. Epub 2014 May 4.

Department of Radiology, University of Verona, "G.B. Rossi" Hospital, Verona, Italy.

Improvements in the treatment of cervical carcinoma have made it possible to offer optimal and personalised treatment. Cervical cancer staging is based on clinical examination and histological findings. Many diagnostic methods are used in clinical practice. Magnetic resonance imaging is considered the optimal method for staging cervical carcinoma because of its high accuracy in assessing local extension of disease and distant metastases. Ultrasound has gained increased attention in recent years; it is faster, cheaper, and more widely available than other imaging techniques, and is highly accurate in detecting tumour presence and evaluating local extension of disease. Magnetic resonance imaging and ultrasound are often used together with computed tomography or positron emission tomography combined with computed tomography to assess the whole body, a more accurate detection of pathological lymph nodes and metabolic information of the disease.
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http://dx.doi.org/10.1016/j.bpobgyn.2014.04.009DOI Listing
July 2014

Which imaging technique should we use in the follow up of gynaecological cancer?

Best Pract Res Clin Obstet Gynaecol 2014 Jul 2;28(5):769-91. Epub 2014 May 2.

Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Rome, Italy.

Follow-up routines after gynaecological cancer vary. The optimal approach is unknown, and no randomised-controlled trials comparing surveillance protocols have been published. In this chapter, we summarise the diagnostic performance of ultrasound, computed tomography, and magnetic resonance imaging in the follow up of women treated for ovarian or uterine cancers. Computed tomography is today the standard imaging method for the follow up of women treated for endometrial, cervical, or ovarian cancer. Six-monthly or annual follow-up examinations have not been shown to positively affect survival. Instead, a combination of transvaginal and transabdominal ultrasound examination with clinical examination might be a more cost-effective strategy for early detection of recurrence. Positron-emission tomography might play a role in women with clinical or serological suspicion of recurrence but without evidence of disease at conventional diagnostic imaging. To create guidelines, more studies, preferably randomised-controlled trials, on follow-up strategies are needed.
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http://dx.doi.org/10.1016/j.bpobgyn.2014.04.008DOI Listing
July 2014

Early-stage cervical cancer: tumor delineation by magnetic resonance imaging and ultrasound - a European multicenter trial.

Gynecol Oncol 2013 Mar 28;128(3):449-53. Epub 2012 Sep 28.

Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden.

Objective: To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard.

Patients And Methods: Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2-IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion<2/3 (superficial) or ≥2/3 (deep), and parametrial invasion.

Results: Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (>4cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (<2cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as <2cm, or >4cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p<0.001) and parametrial invasion (p<0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy.

Conclusion: US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion.
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http://dx.doi.org/10.1016/j.ygyno.2012.09.025DOI Listing
March 2013

Phase 2 trial of nonpegylated doxorubicin (Myocet) as second-line treatment in advanced or recurrent endometrial cancer.

Int J Gynecol Cancer 2011 Nov;21(8):1446-51

Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.

Background: Advanced or recurrent endometrial cancer is associated with a poor prognosis, and results obtained with systemic therapy are far from being impressive. Myocet is an interesting formulation of citrate conjugated doxorubicin encapsulated in nonpegylated liposomes. This phase 2 study was designed to evaluate the objective response rate and the toxicity profile of Myocet in women with advanced or recurrent endometrial cancer.

Methods: Patients with diagnosis of advanced or recurrent endometrial cancer failing 1 previous carboplatin-paclitaxel chemotherapy were enrolled. Myocet was administered at the dose of 60 mg/m intravenously on day 1 every 4 weeks.

Results: Eighteen patients were enrolled in our institution from September 2007 to January 2010. No complete or partial response was observed. Stable disease was registered in 5 patients (27.5%). Median time to progression was 9 weeks. Median time to death was 24 weeks. Grade 3/4 anemia was reported in 2 patients (11%). Grade 3/4 neutropenia was observed in 16.5% and 44% of patients, respectively. The major nonhematologic toxicities (grades 3/4) were fatigue (22%), nausea, and vomiting (5.5%).

Conclusions: Myocet presents no activity, and only few stabilizations of disease of limited duration in this recurrent endometrial carcinoma population previously treated with platinum-taxane chemotherapy are reported.
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http://dx.doi.org/10.1097/IGC.0b013e31822d754eDOI Listing
November 2011

Emerging drugs for ovarian cancer.

Expert Opin Emerg Drugs 2010 Dec 7;15(4):635-52. Epub 2010 Jul 7.

Catholic University of the Sacred Heart, Department of Gynecologic Oncology, Largo Agostino Gemelli 8, IT-00168 Rome.

Importance Of The Field: Ovarian cancer has the highest mortality of all female reproductive tract cancers, which reflects both the absence of proven ovarian cancer screening tests and the development of drug-resistant cancer cell. Apart from varying the dosages, schedules, mode of delivery and combinations of existing drugs, efforts must continue to identify signaling pathways in tumor cells sufficiently different from normal cells that can be a target for maximizing tumor kill and minimizing toxicity.

Areas Covered In This Review: Some of the most important cellular pathways are analyzed and discussed and the most interesting clinical trials, both closed and ongoing, described.

What The Reader Will Gain: The reader will gain a panoramic vision of all the most active drugs in clinical investigations in ovarian cancer. The reader will also better understand what the unresolved problems of molecular research are and how complicated the process 'from the bench to the bedside' is.

Take Home Message: It is only with a strong commitment, cooperation and collaboration from the international ovarian cancer community that significant improvement in patient outcomes can be attained beyond the marginal gains achieved so far.
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http://dx.doi.org/10.1517/14728214.2010.502888DOI Listing
December 2010
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