Giacomo Corrado

Conservative surgical management of stage IA endometrial carcinoma for fertility preservation

OBJECTIVE To describe an innovative method to preserve fertility in young women with stage IA endometrial cancer with use of hysteroscopic resection followed by administration of 160 mg of megestrol acetate. DESIGN Prospective study. SETTING Division of Gynecologic Oncology, Catholic University of the Sacred Heart, and the Endoscopic Gynecologic Unit, Nuova Villa Claudia, Rome, Italy. PATIENT(S) Six young patients with stage IA endometrial cancer. INTERVENTION(S) Conservative resectoscopic treatment using a three-step technique in which each step is characterized by a pathologic analysis: the removal of the tumor (step 1), the removal of the endometrium adjacent to the tumor (step 2), and the removal of the myometrium underlying the tumor (step 3). MAIN OUTCOME MEASURE(S) Therapy of stage IA endometrial cancer and pregnancy. RESULT(S) The conservative surgery was effective because results of transvaginal ultrasound examination and diagnostic hysteroscopy with target biopsies at 3, 6, 9, and 12 months after surgery were negative for atypia or malignancy. Moreover, four out of six patients (66%) achieved childbearing. CONCLUSION(S) This method, under a close postsurgical follow-up, might represent a novel therapeutic option for those women with stage IA endometrial cancer who wish to preserve fertility.

Impact of Interval Debulking Surgery on Clinical Outcome in Primary Unresectable FIGO Stage IIIc Ovarian Cancer Patients

Objectives: To report the results of neoadjuvant chemotherapy (NACT) and the impact of interval debulking surgery (IDS) on clinical outcomes of patients considered unresectable at primary surgery. Methods: Retrospective analysis was carried out on 73 consecutive stage IIIc ovarian cancer patients treated with platinum-based NACT followed by IDS. Their clinical outcomes were compared with those of 111 consecutive stage IIIc ovarian cancer patients treated with primary cytoreduction followed by platinum-based adjuvant chemotherapy. Results: Patients who underwent successful IDS had a more favorable prognosis than those who did not in terms of time to progression (TTP) (p = 0.00001), and overall survival (OS) (p = 0.0001). On the other hand, in the group of patients that underwent successful IDS, no differences in survival outcomes were observed between patients with no residual disease and patients with macroscopic residual disease <2 cm after IDS (p = n.s.). Conclusions: NACT followed by successful IDS can achieve good results in terms of survival outcomes in a high percentage of chemoresponsive IIIc ovarian cancer patients classified as unresectable at primary surgery. These results are in fact inferior to those achievable with optimal primary cytoreduction; however, they were quite similar to those seen with suboptimal primary cytoreduction.

Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multi-institutional series.

OBJECTIVE The aim of this study is to analyze the safety, adequacy, perioperative and survival figures in a large series of laparoscopic staging of patients with apparent early stage ovarian malignancies (ESOM). PATIENTS AND METHODS Retrospective data from seven gynecologic oncology service databases were searched for ESOM patients undergoing immediate laparoscopic staging or delayed laparoscopic staging after an incidental diagnosis of ESOM. Between May 2000 and February 2014, 300 patients were selected: 150 had been submitted to immediate laparoscopic staging (Group 1), while 150 had undergone delayed laparoscopic staging (Group 2) of ESOM. All surgical, pathologic, and oncologic outcome data were analyzed in each group and a comparison between the two was carried out. RESULTS Longer operative time, higher blood loss, more frequently spillage/rupture of ovarian capsule and conversion to laparotomy occurred in Group 1. No significant differences of post-operative complications were observed between the two groups. Histological data revealed more frequently serous tumors (0.06), Grade 3 (p=0.0007) and final up-staging (p=0.001) in Group 1. Recurrence and death of disease were documented in 25 (8.3%), and 10 patients (3.3%%), respectively. The 3-year disease free survival (DFS) and overall survival (OS) rates were 85.1%, and 93.6%, respectively in the whole series. There was no difference between Group 1 and Group 2 in terms of DFS (p value=0.39) and OS (p value=0.27). CONCLUSION In this very large multi-institutional study, it appears that patients with apparent ESOM can safely undergo laparoscopic surgical management.

Cyclophosphamide "metronomic" chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer.

BackgroundEvaluation of the clinical efficacy and tolerance of metronomic chemotherapy as salvage therapy in a young patient with advanced, platinum resistant, ovarian carcinoma and bad performance status.Case presentationWe tried palliative chemotherapy with daily low dose oral cyclophosphamide with a patient suffering from stage IIIC ovarian cancer that responded to daily cyclophosphamide (CTX) after no response to chemotherapy with paclitaxel and carboplatin as first line and progression after second line with topotecan.The progression-free survival time on daily low dose oral cyclophosphamide treatment was 65 months without side effects. She was well during the chemotherapy and lived a normal working and social life.ConclusionWe think that use of low dose of oral CTX should be investigated further as a strategy against tumour progression after standard chemotherapy in patients who are platinum resistant with poor performance status.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

The lymphatic drainage of the uterine cervix in adult fresh cadavers: anatomy and surgical implications.

OBJECTIVE To investigate the differences of the amount of paracervical lymphatic structures removed when performing classical type III, modified type II and nerve-sparing radical hysterectomy (RH). MATERIAL AND METHODS Open macroscopic or laparoscopic pelvic dissections in 18 fresh adult female cadavers after lymphatic channels and nodes staining by Lipiodol dye solution injection of the uterine cervix. RESULTS We distinguished three different lymphatic pathways: 1) the supraureteral paracervical pathway (vascular portion of paracervix-uterine artery and superficial uterine vein), identified in 96% of cases, and removed in all types of RH, 2) the infraureteral paracervical pathway (vascular portion of paracervix-deep uterine vein), identified in 22% of cases, and removed by type III and nerve-sparing RH, and 3) the neural paracervical pathway (nervous portion of paracervix), identified in 7% of cases, and removable only by type III RH. No evidence of stained lymphatic structures running into the vesicouterine and uterosacral ligaments was found. CONCLUSION Nerve-sparing RH offers the most effective ratio between oncological safety and surgical-related complications, and would be particularly useful in patients with high risk of paracervical involvement while our results suggest caution in the use of modified type II RH in patients at low-moderate risk of paracervical involvement, unless the use of adjuvant radiotherapy, because of the large amount of potentially lymph-bearing paracervical tissue leaved in situ. Classical type III RH affords the complete resection of all paracervical lymphatic pathways potentially draining the cervix, however this procedure implies a high risk of lesions of the autonomous nerves of pelvic organs.

Pegylated liposomal doxorubicin in the management of ovarian cancer.

Among the pharmaceutical options available for treatment of ovarian cancer, much attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation, which entraps conventional doxorubicin in a bilayer lipidic sphere surrounded by a polyethylene glycol layer, prolongs the persistence of the drug in the circulation and potentiates intratumor drug accumulation. These properties enable this drug to sustain its very favorable toxicity profile and to be used safely in combination with other drugs. PLD has been already approved for treatment of advanced ovarian cancer patients failing first-line platinum-based treatment. Moreover, phase III trials have been already completed, and results are eagerly awaited, which hopefully will expand the range of PLD clinical application in this neoplasia both in front-line treatment, and in the salvage setting in combination with other drugs. Moreover, attempts are continuing to enable this drug to be combined with novel cytotoxic drugs and target-based agents. This review aims at summarizing the available evidence and the new perspectives for the clinical role of PLD in the management of patients with epithelial ovarian cancer.

Prognostic role of Ca125 response criteria and RECIST criteria: Analysis of results from the MITO-3 phase III trial of gemcitabine versus pegylated liposomal doxorubicin in recurrent ovarian cancer

OBJECTIVES The aim of the study was to investigate i) the association between the Ca125 based and the RECIST assessed response in recurrent ovarian cancer patients enrolled in a Phase III randomized trial (MITO-3) comparing salvage treatment with pegylated liposomal doxorubicin (PLD) versus gemcitabine (GEM); ii) the correlation between the early modifications of Ca125 levels during treatment and the RECIST assessed response; iii) the prognostic value of response based on Ca125 and the RECIST criteria. METHODS Assessment of response was performed by the RECIST and the GCIG criteria. The prognostic impact of the response by the RECIST criteria and the GCIG criteria was analyzed by the landmark method. RESULTS Overall, of 30 cases defined as responders on the basis of the GCIG criteria, 20 resulted as responders according to the RECIST criteria (NPV=66.7%); conversely, 93.7% of the cases considered not responders based on the GCIG criteria were defined as unresponsive at RECIST evaluation. Early modifications of Ca125 levels were not completely predictive of the ultimate RECIST defined response. Overall survival (OS) was longer in RECIST defined responders versus non responders, although the statistical significance was not reached (p value=0.092); conversely, median OS was significantly longer in GCIG defined responders than in non responding patients (p value=0.0059). In multivariate analysis, the GCIG assessed response maintained its independent association with OS. CONCLUSIONS GCIG criteria for tumor response could replace the conventional assessment of response in the decision making process relative to the discontinuation or prolongation of the salvage treatment in ovarian cancer.

Laparoscopic vs. open treatment of endometrial cancer in the elderly and very elderly: An age-stratified multicenter study on 1606 women

UNLABELLED Objective To investigate in depth the effect of increasing age on the peri-operative outcomes of laparoscopic treatment for endometrial cancer, compared to open surgery, with stratification of patients according to the different definitions of elderly age used in the literature. METHODS Data of consecutive patients who underwent surgery for endometrial cancer staging at six centers were reviewed and analyzed according to surgical approach (laparoscopic or open), different definitions of elderly and very elderly age (≥65years, ≥75years, ≥80years), and class of age (<65; ≥65-<75; ≥75-80; ≥80years). Multivariable analysis to correct for possible confounders and propensity-score matching to minimize selection bias were used. RESULTS A total of 1606 patients were included: 938 and 668 patients received laparoscopic and open surgery, respectively. With increasing age, fewer patients received laparoscopy (P<0.001 with ANOVA). The percentage of patients who received lymphadenectomy declined significantly in both groups for age ≥80years. Blood transfusions, incidence and severity of post-operative complications, and hospital stay were significantly lower among patients who had laparoscopy both in younger (<65years) and elderly (whether defined as ≥65 or ≥75years) patients, with no effect of age on any of the characteristics analyzed ( ANOVA P>0.05). The same tendency was observed among very-elderly patients (≥80years). Multivariable and propensity score-matched analysis confirmed these findings. CONCLUSIONS Laparoscopy for staging endometrial cancer retains its advantages over open surgery even in elderly and very-elderly patients. Our data strongly suggest that minimally-invasive surgery is advantageous even among subjects ≥80years.

Role of comorbidities in locally advanced cervical cancer patients administered preoperative chemoradiation: Impact on outcome and treatment-related complications

AIMS The study aimed at describing the prevalence, and pattern of comorbidities, as well as their clinical role in a large series of locally advanced cervical cancer (LACC) patients triaged to preoperative chemoradiation. METHODS The Charlson index (CCI), and the ACE27 index were used to retrospectively evaluate comorbidities in 258 LACC patients: life tables were computed by the Kaplan-Meier method; multivariate analysis was performed by Coxs regression model. RESULTS A CCI score = 0 was documented in 225 patients (87.2%), while 24 patients (9.3%) had a CCI score = 1, and only 9 patients (3.5%) had a CCI score ≥ 2. An ACE27 score = 0 was documented in 170 patients (65.9%), and was 1 in 59 patients (22.8%), 2 in 24 patients (9.3%) and 3 in 5 patients (2%). There was no association between the presence of comorbidities and clinico-pathological variables with the exception of a direct association with older age. There was no difference in the distribution of comorbid cases according to the extent of hysterectomy and lymphadenectomy. DFS or OS curves did not differ in patients with or without comorbidities according to both indexes. No difference in the distribution of patients with comorbidities according to presence of complications was documented. CONCLUSIONS The role of comorbidities in the decision-making process relative to the enrollment of LACC patients into this trimodal therapeutic strategy needs to be established in specifically designed prospective trials.