Impact of COVID-19 in gynecologic oncology: a Nationwide Italian Survey of the SIGO and MITO groups

Giorgio Bogani,Giovanni Apolone,Antonino Ditto,Giovanni Scambia,Pierluigi Benedetti Panici,Roberto Angioli,Sandro Pignata,Stefano Greggi,Paolo Scollo,Mezzanzanica Delia,Massimo Franchi,Fabio Martinell 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.6

Objective: Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changesin cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), andthe Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO)promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity ofgynecologist oncologists and to assess the implementation of containment measures againstCOVID-19 diffusion. Methods: The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020,and was closed on April 20, 2020. Results: Overall, 604 participants completed the questionnaire with a response-rate of70%. The results of this survey suggest that gynecologic oncology units had set a proactiveapproach to COVID-19 outbreak. Triage methods were adopted in order to minimizein-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concernedabout COVID-19 outbreak. Although 73% of the participants stated that COVID-19 hasnot significantly modified their everyday practice, 21% declared a decrease of the use oflaparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adoptedspecific protection against COVID-19. Additionally, responders suggested to delay cancertreatment (10%–15%), and to perform less radical surgical procedures (20%–25%) duringCOVID-19 pandemic. Conclusions: National guidelines should be implemented to further promote the safety ofpatients and health care providers. International cooperation is of paramount importance,as heavily affected nations can serve as an example to find out ways to safely preserve clinicalactivity during the COVID-19 outbreak.

Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Vergote, Ignace,Scambia, Giovanni,O'Malley, David M,Van Calster, Ben,Park, Sang-Yoon,del Campo, Josep M,Meier, Werner,Bamias, Aristotelis,Colombo, Nicoletta,Wenham, Robert M,Covens, Al,Marth, Christia Elsevier 2019 LANCET ONCOLOGY Vol.20 No.6

<P><B>Summary</B></P> <P><B>Background</B></P> <P>Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial.</P> <P><B>Methods</B></P> <P>TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m<SUP>2</SUP>) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete.</P> <P><B>Findings</B></P> <P>Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7–34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0–17·6]) and the placebo group (15·0 months [12·6–16·1]) groups (hazard ratio 0·93 [95% CI 0·79–1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] <I>vs</I> placebo 126 [38%]) anaemia (76 [11%] <I>vs</I> 40 [12%]), and leucopenia (81 [12%] <I>vs</I> 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group.</P> <P><B>Interpretation</B></P> <P>Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population.</P> <P><B>Funding</B></P> <P>Amgen.</P>

Author's reply to: What is the prognostic importance of lymphovascular space invasion in the absence of lymph node metastasis for early-stage endometrial cancer?

Lucia Tortorella,Giovanni Scambia,Francesco Fanfani 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.5

-

Surgical therapy of vulvar cancer: how to choose the correct reconstruction?

Stefano Gentileschi,Maria Servillo,Giorgia Garganese,Simona Fragomeni,Francesca De Bonis,Giovanni Scambia,Marzia Salgarello 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.6

Objective: To create a comprehensive algorithmic approach to reconstruction after vulvarcancer ablative surgery, which includes both traditional and perforator flaps, evaluatinganatomical subunits and shape of the defect. Methods: We retrospectively reviewed 80 cases of reconstruction after vulvar cancerablative surgery, performed between June 2006 and January 2016, transferring 101 flaps. Weregistered the possibility to achieve the complete wound closure, even in presence of verycomplex defects, and the postoperative complications. On the basis of these experience,analyzing the choices made and considering the complications, we developed an algorithmto help with the selection of the flap in vulvoperineal reconstruction after oncologic ablativesurgery for vulvar cancer. Results: We employed eight types of different flaps, including 54 traditional fasciocutaneousV-Y flaps, 23 rectus abdominis myocutaneous flaps, 11 anterolateral thigh flaps, three V-Ygracilis myocutaneous flaps, three free style perforators V-Y flaps from the inner thigh, twoLimberg flaps, two lotus flaps, two deep inferior epigastric artery perforator flap, and onesuperficial circumflex iliac artery perforator flap. The structures most frequently involvedin resection were vulva, perineum, mons pubis, groins, vagina, urethra and, more rarely,rectum, bladder, and lower abdominal wall. Conclusion: The algorithm we implemented can be a useful tool to help flap selection. Thekey points in the decision-making process are: anatomical subunits to be covered, overallshape and symmetry of the defect and some patient features such as skin laxity or previousradiotherapy. Perforator flaps, when feasible, must be considered standard in vulvoperinealreconstruction, although in some cases traditional flaps remain the best choice.

Pearls and Potential Pitfalls for Correct Diagnosis of Ovarian Cystadenofibroma in MRI: A Pictorial Essay

Avesani Giacomo,Caliolo Gianluca,Gui Benedetta,Petta Federica,Panico Camilla,Viviana La Manna,Moro Francesca,Testa Antonia Carla,Scambia Giovanni,Manfredi Riccardo 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.11

Ovarian cystadenofibroma is a benign ovarian tumor that is characterized by a consistent percentage of masses, which remain indeterminate in ultrasonography and require magnetic resonance (MR) investigation; they may mimic borderline or malignant lesions. Three main morphologic patterns, resembling different ovarian neoplasms, can be identified in cystadenofibromas: multilocular solid lesions, unilocular cystic lesions with parietal thickening, and purely cystic masses. However, a cystoadenofibroma has typical features, such as T2-weighted hypointensity associated with no restrictions in diffusion-weighted imaging (the so-called “dark-dark appearance”) and progressive post-contrast enhancement (type I perfusion curve). The purpose of this study was to review the features of ovarian cystadenofibromas in MR imaging and to suggest pearls and pitfalls regarding their correct diagnosis.

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.

Laparoscopic vs. robotic-assisted laparoscopy in endometrial cancer staging: large retrospective single institution study

Emanuele Perrone,Ilaria Capasso,Tina Pasciuto,Alessandro Gioè,Salvatore Gueli Alletti,Stefano Restaino,Giovanni Scambia,Francesco Fanfani 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.3

Objective: The aim of this study is to analyze and draw the potential differences between therobotic-assisted surgery (RS) and the laparoscopy (LPS) in endometrial cancer staging. Methods: In this single-institution retrospective study we enrolled 1,221 consecutive clinicalstage I–III endometrial cancer patients undergone minimally invasive surgical staging. Wecompared patients treated by LPS and by RS, on the basis of perioperative and oncologicaloutcomes (disease-free survival [DFS] and overall survival [OS]). A sub-analysis of the high risk endometrial cancer population was performed in the 2 cohorts. Results: The 2 cohorts (766 treated by LPS and 455 by RS) were homogeneous in termsof perioperative and pathological data. We recorded differences in number of relapse/progression (11.7% in LPS vs. 7% in RS, p=0.008) and in number of deaths (9.8% in LPSvs. 4.8% in RS, p=0.002). Whereas, univariate and multivariate analyses according to DFSand OS confirmed that the surgical approach did not influence the DFS or the OS. In themultivariable analysis the association of the age and grading was significant for DFS and OS. In the sub-analysis of the 426 high risk EC patients (280 in LPS and 146 in RS) the univariateand the multivariate confirmed the influence of the age in DFS and OS, independently of theminimally invasive approach. Conclusions: In our large retrospective analysis, we confirmed that the RS and LPS havesimilar efficacy and safety for endometrial cancer staging also for the high-risk endometrialcancer patients.

Pharmacokinetics of cisplatin during open and minimally-invasive secondary cytoreductive surgery plus HIPEC in women with platinum-sensitive recurrent ovarian cancer: a prospective study

Marco Petrillo,Massimo Zucchettii,Stefano Cianci,Lavinia Morosi,Carlo Ronsini,Andrea Colombo,Maurizio D'Incalci,Giovanni Scambia,Anna Fagotti 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.4

Objective: Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS).Methods: Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit.Results: Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 μg/mL vs. Cmax=4.057 μg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 μg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054).Conclusions: We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01539785

Immunotherapy-Related Imaging Findings in Patients with Gynecological Malignancies: What Radiologists Need to Know

Russo Luca,Avesani Giacomo,Gui Benedetta,Trombadori Charlotte Marguerite Lucille,Salutari Vanda,Perri Maria Teresa,Di Paola Valerio,Rodolfino Elena,Scambia Giovanni,Manfredi Riccardo 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.8

Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.

Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer

Lucia Tortorella,Stefano Restaino,Gianfranco Zannoni,Giuseppe Vizzielli,Vito Chiantera,Serena Cappuccio,Alessandro Gioè,Eleonora La Fera,Giorgia Dinoi,Giuseppe Angelico,Giovanni Scambia,Francesco Fanf 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.2

Objective: The aim of this study is to analyze the prognostic role of lymph-vascular spaceinvasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low riskendometrial cancer (EC). Methods: We enrolled patients who underwent surgery for endometrial cancer between2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, withmyometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi quantitative way, according to a 3-tiered scoring system in absent, focal and substantial. Results: Among 524 patients, any positive LVSI was found in 57 patients (10.9%) with focalLVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated tohigher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions(p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment(6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6%in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6%in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate ofdistant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival(hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI wasan independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure(HR=10.6, p=0.006). Conclusions: Substantial LVSI represents the strongest independent risk factor for decreasedsurvival and distant relapse, indicating a role for potential hematogenous dissemination.