Efficacy and fertility outcomes of levonorgestrel-releasing intra-uterine system treatment for patients with atypical complex hyperplasia or endometrial cancer: a retrospective study

Umberto Leone Roberti Maggiore,Fabio Martinelli,Giulia Dondi,Giorgio Bogani,Valentina Chiappa,Maria Teresa Evangelista,Viola Liberale,Antonino Ditto,Simone Ferrero,Francesco Raspagliesi 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.4

Objective: To investigate the efficacy of levonorgestrel-releasing intra-uterine system (LNG-IUS) treatment in patients affected by atypical complex hyperplasia/endometrial cancer (ACH/EC) wishing to preserve their fertility and to present fertility outcomes of those patients who actively tried to conceive. Methods: Data of consecutive women with ACH/EC who underwent fertility-sparing treatment using LNG-IUS were retrospectively evaluated. Results: Overall, 48 patients and the mean (±standard deviation) length of follow-up was 82.6±47.2 months. Among patients with ACH, 25/28 (89.3%) had a complete response (CR), 2/28 (7.1%) had a partial response (PR) and 1/28 (3.6%) had a progressive disease (PD). Mean (±standard deviation) time to CR was 6.7±4.0 months. Among patients with G1 EC, 13/16 (81.3%) had a CR, 1/16 (6.3%) had a PR and 2/16 (12.5%) had a PD. Mean (±standard deviation) time to CR was 5.0±2.9 months. Among patients with G2 EC, 3/4 (75.0%) had a CR and 1/4 (25.0%) had a PD. Mean (±standard deviation) time to CR was 4.0±0 months. Only 19 (39.6%) patients who had CR actually attempted to conceive. Eleven (57.9%) women tried to conceive naturally while 8 (42.1%) women underwent an in vitro fertilization (IVF). Fourteen (73.7%) patients wishing to conceive achieved a pregnancy (6 spontaneously and 8 through IVF). Conclusions: Fertility-sparing treatment of patient with ACH/EC with LNG-IUS achieves high regression rates and good fertility outcomes. Future larger multi-institutional studies should be designed to confirm these preliminary findings.

The detrimental effect of adopting interval debulking surgery in advanced stage low-grade serous ovarian cancer

Giorgio Bogani,Umberto Leone Roberti Maggiore,Biagio Paolini,Antonino Diito,Fabio Martinelli,Domenica Lorusso,Francesco Raspagliesi 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.1

Objective: To examine outcomes of patients having treatments for newly diagnosed advanced stage low-grade serous ovarian cancer (LGSC). Methods: We conducted a retrospective case series of women affected by advanced stage (stage IIIB or more) LGSC undergoing surgery in a single oncologic center between January 2000 and December 2017. Survival outcomes were assessed using Kaplan-Meier and Cox models. Results: Data of 72 patients were retrieved. Primary cytoreductive surgery was attempted in 68 (94.4%) patients: 19 (27.9%) had residual disease (RD) >1 cm after primary surgery. Interval debulking surgery (IDS) was attempted in 15 of these 19 (78.9%) patients and the remaining 4 patients having not primary debulking surgery. Twelve out of 19 (63.1%) patients having IDS had RD. After a mean (±standard deviation) follow-up was 61.6 (±37.2) months, 50 (69.4%) and 22 (30.5%) patients recurred and died of disease, respectively. Via multivariate analysis, non-optimal cytoreduction (hazard ratio [HR]=2.79; 95% confidence interval [CI]=1.16–6.70; p=0.021) and International Federation of Obstetrics and Gynecologists (FIGO) stage IV (HR=3.15; 95% CI=1.29–7.66; p=0.011) were associated with worse disease-free survival. Via multivariate analysis, absence of significant comorbidities (HR=0.56; 95% CI=0.29–1.10; p=0.093) and primary instead of IDS (HR=2.95; 95% CI=1.12–7.74; p=0.027) were independently associated with an improved overall survival. Conclusion: LGSC is at high risk of early recurrence. However, owing to the indolent nature of the disease, the majority of patients are long-term survivors. Further prospective studies and innovative treatment modalities are warranted to improve patients care.

Lynch syndrome – Muir-Torre variant: implication in gynecologic oncology

Giorgio Bogani,Umberto Leone Roberti Maggiore,Francesco Raspagliesi 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

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Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer: a Gynecologic Cancer Inter-Group (GCIG) study

Francesca Falcone,Umberto Leone Roberti Maggiore,Violante Di Donato,Anna Myriam Perrone,Luigi Frigerio,Giuseppe Bifulco,Stephan Polterauer,Paolo Casadio,Gennaro Cormio,Valeria Masciullo,Mario Malzoni 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.5

Objective: ‘The Endometrial Cancer Conservative Treatment (E.C.Co.). A multicentre archive’is a worldwide project endorsed by the Gynecologic Cancer Inter-Group, aimed at registeringconservatively treated endometrial cancer (EC) patients. This paper reports the oncologicaland reproductive outcomes of intramucous, G2, endometrioid EC patients from this archive. Methods: Twenty-three patients (Stage IA, G2, endometrioid EC) were enrolled betweenJanuary 2004 and March 2019. Primary and secondary endpoints were, respectively, completeregression (CR) and recurrence rates, and pregnancy and live birth rates. Results: A median follow-up of 35 months (9–148) was achieved. Hysteroscopic resection(HR) plus progestin was adopted in 74% (17/23) of cases. Seventeen patients showed CR(median time to CR, 6 months; 3-13). Among the 6 non-responders, one showed persistenceand 5 progressed, all submitted to definitive surgery, with an unfavorauble outcome in one. The recurrence rate was 41.1%. Ten (58.8%) complete responders attempted to conceive, ofwhom 3 achieved at least one pregnancy with a live-birth. Two out of the 11 candidate patientsunderwent definitive surgery, while the remaining 9 have so far refused. To date, 22 patientsshow no evidence of disease, and one is still alive with disease. Conclusions: Fertility-sparing treatment seems to be feasible even in G2 EC, although cautionshould be kept considering the potential pathological undergrading or non-endometrioid histology misdiagnosis. The low rate of attempt to conceive and of compliance to definitivesurgery underline the need for a ‘global’ counselling extended to the follow-up period.

Current landscape and future perspective of sentinel node mapping in endometrial cancer

Giorgio Bogani,Francesco Raspagliesi,Umberto Leone Roberti Maggiore,Andrea Mariani 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.6

Endometrial cancer (EC) represents the most common gynecological neoplasm in developed countries. Surgery is the mainstay of treatment for EC. Although EC is characterized by a high prevalence several features regarding its management are still unclear. In particular the execution of lymphadenectomy is controversial. The recent introduction of sentinel node mapping represents the mid-way between the execution and omission of node dissection in EC patients. In the present review we discuss the emerging role of sentinel node mapping in EC. In addition, we discussed how type of tracers utilized and site of injection impacted on sentinel node detection rates. Future perspective regarding EC management are also discussed.

Oncologic effectiveness of nerve-sparing radical hysterectomy in cervical cancer

Antonino Ditto,Giorgio Bogani,Umberto Leone Roberti Maggiore,Fabio Martinelli,Valentina Chiappa,Carlos Lopez,Stefania Perotto,Domenica Lorusso,Francesco Raspagliesi 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.3

Objective: Nerve-sparing radical hysterectomy (NSRH) was introduced with the aim to reduce pelvic dysfunctions related to conventional radical hysterectomy (RH). Here, we sought to assess the effectiveness and safety of NSRH in a relatively large number of the patients of cervical cancer (CC) patients undergoing either primary surgery or neoadjuvant chemotherapy (NACT) followed by surgery. Methods: Outcomes of consecutive patients undergoing NSRH and of a historical cohort of patients undergoing conventional RH were retrospectively reviewed. Results: This study included 325 (49.8%) and 327 (50.2%) undergoing NSRH and RH, respectively. Via a multivariable model, nodal status was the only factor predicting for DFS (hazard ratio [HR]=2.09; 95% confidence interval [CI]=1.17–3.73; p=0.01). A trend towards high risk of recurrence was observed for patients affected by locally advanced cervical cancer (LACC) undergoing NACT followed by surgery (HR=2.57; 95% CI=0.95–6.96; p=0.06). Type of surgical procedures (NSRH vs. RH) did not influence risk of recurrence (p=0.47). Similarly, we observed that the execution of NSRH rather than RH had not a detrimental effect on OS (HR=1.19; 95% CI=0.16–9.01; p=0.87). Via multivariable model, no factor directly correlated with OS. No difference in early complication rates was observed between the study groups. Conversely, a significant higher number of late complications was reported in RH versus NSRH groups (p=0.02). Conclusion: Our data suggested that NSRH upholds effectiveness of conventional RH, without increasing recurrence and complication rates but improving pelvic dysfunction rates.

Minimally invasive surgery improves short-term outcomes of nerve-sparing radical hysterectomy in patients with cervical cancer: a propensity-matched analysis with open abdominal surgery

Giorgio Bogani,Diego Rossetti,Antonino Ditto,Fabio Martinelli,Valentina Chiappa,Chiara Leone,Umberto Leone Roberti Maggiore,Domenica Lorusso,Francesco Raspagliesi 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.2

Objectives: Nerve-sparing radical hysterectomy has been implemented in order to reduce pelvic floor dysfunctions in women undergoing radical surgery for cervical cancer. Here, we aimed to investigate if the adoption of laparoscopic surgery impacts on patients' outcomes. Methods: Data of consecutive patients affected by cervical cancer who had laparoscopic nerve-sparing radical hysterectomy were matched 1:1 with an historical cohort of patients undergoing open procedure. A propensity-score matched algorithm was applied. Results: Thirty-five patients' pairs (70 patients: 35 undergoing laparoscopic vs. 35 undergoing open abdominal nerve-sparing radical hysterectomy) were included. Demographic and baseline oncologic characteristics were balanced between groups. Patients undergoing laparoscopic surgery had similar operative time than patients undergoing open abdominal procedures (249 [±91.5] vs. 223 [±65.0] minutes; p=0.066). Laparoscopic approach correlated with lower blood loss (30.5 [±11.0] vs. 190 [90.4] mL; p<0.001) and shorter hospital stay (3.2 [±1.2] vs. 5.4 [2.0] days; p=0.023). Patients undergoing laparoscopy experienced a lower 30-day pelvic floor dysfunction rate than patients having open surgery. Moreover, they experienced shorter recovery of bladder function than patients having open procedures (median, 7 vs. 9 days; p=0.004, log-rank test). Conclusion: Laparoscopic approach resulted in a faster recovery of bladder function in comparison to open surgery for patients undergoing nerve-sparing radical hysterectomy.

Artificial intelligence weights the importance of factors predicting complete cytoreduction at secondary cytoreductive surgery for recurrent ovarian cancer

Giorgio Bogani,Diego Rossetti,Antonino Ditto,Fabio Martinelli,Valentina Chiappa,Lavinia Mosca,Umberto Leone Roberti Maggiore,Stefano Ferla,Domenica Lorusso,Francesco Raspagliesi 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

Objective: Accumulating evidence support that complete cytoreduction (CC) at the time of secondary cytoreductive surgery (SCS) improves survival in patients affected by recurrent ovarian cancer (ROC). Here, we aimed to determine whether artificial intelligence (AI) might be useful in weighting the importance of clinical variables predicting CC and survival. Methods: This is a retrospective study evaluating 194 patients having SCS for ROC. Using artificial neuronal network (ANN) analysis was estimated the importance of different variables, used in predicting CC and survival. ANN simulates a biological neuronal system. Like neurons, ANN acquires knowledge through a learning-phase process and allows weighting the importance of covariates, thus establishing how much a variable influences a multifactor phenomenon. Results: Overall, 82.9% of patients had CC at the time of SCS. Using ANN, we observed that the 3 main factors driving the ability of achieve CC included: disease-free interval (DFI) (importance: 0.231), retroperitoneal recurrence (importance: 0.178), residual disease at primary surgical treatment (importance: 0.138), and International Federation of Gynecology and Obstetrics (FIGO) stage at presentation (importance: 0.088). Looking at connections between different covariates and overall survival (OS), we observed that DFI is the most important variable influencing OS (importance: 0.306). Other important variables included: CC (importance: 0.217), and FIGO stage at presentation (importance: 0.100). Conclusion: According to our results, DFI should be considered as the most important factor predicting both CC and OS. Further studies are needed to estimate the clinical utility of AI in providing help in decision making process.

A score system for complete cytoreduction in selected recurrent ovarian cancer patients undergoing secondary cytoreductive surgery: predictors- and nomogram-based analyses

Giorgio Bogani,Elena Tagliabue,Mauro Signorelli,Antonino Ditto,Fabio Martinelli,Valentina Chiappa,Lavinia Mosca,Ilaria Sabatucci,Umberto Leone Roberti Maggiore,Domenica Lorusso,Francesco Raspagliesi 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.3

Objective: To test the applicability of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Memorial Sloan Kettering (MSK) criteria in predicting complete cytoreduction (CC) in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer (ROC). Methods: Data of consecutive patients undergoing SCS were reviewed. The Arbeitsgemeinschaft Gynäkologische Onkologie OVARian cancer study group (AGO-OVAR) and MSK criteria were retrospectively applied. Nomograms, based on AGO criteria, MSK criteria and both AGO and MSK criteria were built in order to assess the probability to achieve CC at SCS. Results: Overall, 194 patients met the inclusion criteria. CC was achieved in 161 (82.9%) patients. According to the AGO-OVAR criteria, we observed that CC was achieved in 87.0% of patients with positive AGO score. However, 45 out of 71 (63.4%) patients who did not fulfilled the AGO score had CC. Similarly, CC was achieved in 87.1%, 61.9% and 66.7% of patients for whom SCS was recommended, had to be considered and was not recommended, respectively. In order to evaluate the predictive value of the AGO-OVAR and MSK criteria we built 2 separate nomograms (c-index: 0.5900 and 0.5989, respectively) to test the probability to achieve CC at SCS. Additionally, we built a nomogram using both the aforementioned criteria (c-index: 0.5857). Conclusion: The AGO and MSK criteria help identifying patients deserving SCS. However, these criteria might be strict, thus prohibiting a beneficial treatment in patients who do not met these criteria. Further studies are needed to clarify factors predicting CC at SCS.