STEREOTACTIC BODY RADIOTHERAPY FOR OLIGOPROGRESSIVE OVARIAN CANCER PATIENTS TREATED DURING PARP INHIBITOR MAINTENANCE: EFFICACY AND ADVERSE EVENTS FROM THE EPIMETHEO RETROSPECTIVE STUDY.

PURPOSE: The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of SBRT during PARP inhibitors (PARPi) maintenance, in a series of oligometastatic ovarian cancer (OC) patients. METHODS: Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were: next systemic treatment change-free survival (NEST-FS), and acute and late toxicity; the secondary endpoints were: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression free-survival (PFS), and 2-year overall survival (OS). RESULTS: From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, Niraparib, and Rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, Partial Response, Stable Disease, and Progressive Disease (PD) were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7 to 13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, PFS and OS were 68.1%, 22.5% and 77%, respectively with differences figures between complete and not complete responders. The achievement of CR was found to be correlated with an improvement in LC and OS. CONCLUSIONS: This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

The complex relationship between infertility and female genital tract cancer: A review.

INTRODUCTION: The link between female infertility and gynecological cancer has always been a debated and challenging topic. Although cervical cancer has the worst impact on female fertility, as it is usually diagnosed in patients of reproductive age, endometrial and ovarian cancer are also diagnosed and treated often in relatively younger patients in which fertility preservation is a relevant issue. The aim of this review is to highlight the correlation between therapy for female infertility and the developing cancer's risk and to describe the fertility sparing treatments in gynecological oncology. MATERIAL AND METHODS: A systematic review of the literature through the main scientific search engines (PubMed and Google Scholar) was performed. We selected the most relevant articles based on the largest case series and the latest updates. All selected documents have been listed in the references. RESULTS: Fifty-six relevant articles published between 1996 and 2019 were identified.Results from the available evidence report no significant increased risk of endometrial, cervical, and ovarian cancer in patients having infertility treatments.In young patients diagnosed with gynecological cancer, preservation of fertility is a personalized choice depending on several factors (type, stage, age and desire to conceive, safety of the treatment, and feasibility of fertility sparing surgery). For ovarian cancer FIGO stage IA G1, IA G2 (grade), and IC G1; for endometrial adenocarcinoma grade 1 with no lymphovascular space invasion (LVSI) or myometrial invasion and for early-stage cervical cancer (FIGO stage 2018: IA1-IB1), fertility sparing treatment is possible. The role of fertility sparing treatment with the increase of personalization of therapies therapy is always a theme of discussion and research. CONCLUSION: At present data regarding the risk of gynecological cancers after infertility treatments are reassuring. Careful evaluation of female fertility-sparing options in young women interested by ovarian, endometrial, or cervical tumors should be carried out involving a multidisciplinary team and ensuring safety and efficacy.

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

Objective@#The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). @*Methods@#We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semiquantitative 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 focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher 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 of distant 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 was an 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 decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.

Laparoscopic vs. robotic-assisted laparoscopy in endometrial cancer staging: large retrospective singleinstitution study / 부인종양

Objective@#The aim of this study is to analyze and draw the potential differences between the robotic-assisted surgery (RS) and the laparoscopy (LPS) in endometrial cancer staging. @*Methods@#In this single-institution retrospective study we enrolled 1,221 consecutive clinical stage I–III endometrial cancer patients undergone minimally invasive surgical staging. We compared patients treated by LPS and by RS, on the basis of perioperative and oncological outcomes (disease-free survival [DFS] and overall survival [OS]). A sub-analysis of the highrisk endometrial cancer population was performed in the 2 cohorts. @*Results@#The 2 cohorts (766 treated by LPS and 455 by RS) were homogeneous in terms of 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 LPS vs. 4.8% in RS, p=0.002). Whereas, univariate and multivariate analyses according to DFS and OS confirmed that the surgical approach did not influence the DFS or the OS. In the multivariable 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 univariate and the multivariate confirmed the influence of the age in DFS and OS, independently of the minimally invasive approach. @*Conclusions@#In our large retrospective analysis, we confirmed that the RS and LPS have similar efficacy and safety for endometrial cancer staging also for the high-risk endometrial cancer patients.

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

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.

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

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.

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

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.

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

Objective@#Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the 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 of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. @*Methods@#The survey consisted of a self-administered, anonymous, online questionnaire. Thesurvey 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 of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%–15%), and to perform less radical surgical procedures (20%–25%) during COVID-19 pandemic. @*Conclusions@#National guidelines should be implemented to further promote the safety of patients 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 clinical activity during the COVID-19 outbreak.

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

Objective@#Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the 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 of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. @*Methods@#The survey consisted of a self-administered, anonymous, online questionnaire. Thesurvey 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 of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%–15%), and to perform less radical surgical procedures (20%–25%) during COVID-19 pandemic. @*Conclusions@#National guidelines should be implemented to further promote the safety of patients 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 clinical activity during the COVID-19 outbreak.

ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience / 부인종양

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 (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.

ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience / 부인종양

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.

The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma.

Soft tissue sarcoma (STS) is a rare malignancy of mesenchymal origin classified into more than 50 different subtypes with distinct clinical and pathologic features. Despite the poor prognosis in the majority of patients, only modest improvements in treatment strategies have been achieved, largely due to the rarity and heterogeneity of these tumors. Therefore, the discovery of new prognostic and predictive biomarkers, together with new therapeutic targets, is of enormous interest. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor that commonly loses its function via mutation, deletion, transcriptional silencing, or protein instability, and is frequently downregulated in distinct sarcoma subtypes. The loss of PTEN function has consequent alterations in important pathways implicated in cell proliferation, survival, migration, and genomic stability. PTEN can also interact with other tumor suppressors and oncogenic signaling pathways that have important implications for the pathogenesis in certain STSs. The aim of the present review is to summarize the biological significance of PTEN in STS and its potential role in the development of new therapeutic strategies.

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

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

Survival in clinical stage I endometrial cancer with single vs. multiple positive pelvic nodes: results of a multi-institutional Italian study / 부인종양

OBJECTIVE: To investigate survival outcomes in endometrioid endometrial cancer (EEC) patients with single vs. multiple positive pelvic lymph nodes. METHODS: We performed a retrospective evaluation of all consecutive patients with histologically proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 EEC who underwent primary surgical treatment between 2004 and 2014 at seven Italian gynecologic oncology referral centers. Patients with pre- or intra-operative evidence of extra-uterine disease (including the presence of bulky nodes) and patients with stage IIIC2 disease were excluded, in order to obtain a homogeneous population. RESULTS: Overall 140 patients met the inclusion criteria. The presence of >1 metastatic pelvic node was significantly associated with an increased risk of recurrence and mortality, compared to only 1 metastatic node, at both univariate (recurrence: hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.2–3.99; p=0.01; mortality: HR=2.8; 95% CI=1.24–6.29; p=0.01) and multivariable analysis (recurrence: HR=1.91; 95% CI=1.02–3.56; p=0.04; mortality: HR=2.62; 95% CI=1.13–6.05; p=0.02) and it was the only independent predictor of prognosis in this subset of patients. Disease-free survival (DFS) and disease-specific survival (DSS) were significantly longer in patients with only 1 metastatic node compared to those with more than 1 metastatic node (p=0.008 and 0.009, respectively). CONCLUSION: The presence of multiple metastatic nodes in stage IIIC1 EEC represents an independent predictor of worse survival, compared to only one positive node. Our data suggest that EEC patients may be categorized according to the number of positive nodes.

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

OBJECTIVE: To create a comprehensive algorithmic approach to reconstruction after vulvar cancer ablative surgery, which includes both traditional and perforator flaps, evaluating anatomical subunits and shape of the defect. METHODS: We retrospectively reviewed 80 cases of reconstruction after vulvar cancer ablative surgery, performed between June 2006 and January 2016, transferring 101 flaps. We registered the possibility to achieve the complete wound closure, even in presence of very complex defects, and the postoperative complications. On the basis of these experience, analyzing the choices made and considering the complications, we developed an algorithm to help with the selection of the flap in vulvoperineal reconstruction after oncologic ablative surgery for vulvar cancer. RESULTS: We employed eight types of different flaps, including 54 traditional fasciocutaneous V-Y flaps, 23 rectus abdominis myocutaneous flaps, 11 anterolateral thigh flaps, three V-Y gracilis myocutaneous flaps, three free style perforators V-Y flaps from the inner thigh, two Limberg flaps, two lotus flaps, two deep inferior epigastric artery perforator flap, and one superficial circumflex iliac artery perforator flap. The structures most frequently involved in 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. The key points in the decision-making process are: anatomical subunits to be covered, overall shape and symmetry of the defect and some patient features such as skin laxity or previous radiotherapy. Perforator flaps, when feasible, must be considered standard in vulvoperineal reconstruction, although in some cases traditional flaps remain the best choice.

Preoperative chemoradiotherapy in locally advanced cervical cancer: long-term outcome and complications.

OBJECTIVE: To demonstrate the efficacy and feasibility of preoperative chemoradiotherapy in a consecutive series of 100 locally advanced cervical cancer (LACC) patients. METHODS: Between October 1997 and December 2004, 100 LACC patients were consecutively staged and treated at the Catholic University of the Sacred Heart of Rome. Radiotherapy was administered to the whole pelvic region (1.8 Gy/day, totaling 39.6 Gy) in combination with cisplatin (20 mg/m(2)) and 5-FU (1000 mg/m(2)) (both on days 1-4 and 27-30). Radical surgery was performed 5-6 weeks after the end of the treatment. RESULTS: A clinical complete or partial response was observed in 96 patients (56 and 40, respectively). Radical surgery was performed in 95 patients and an overall complication rate of 12.6% was observed in the early postoperative time. At pathological examination, 43 of 95 patients (45.2%) undergoing radical surgery showed complete response to treatment, 28 patients (29.5%) only had a microscopic disease, 18 patients (19%) had a partial response and 6 (6.3%) had no change of disease. With a median follow-up time of 25 months, the 5-year disease-free survival was 76% and the 5-year overall survival was 78%. CONCLUSIONS: These data confirm the possibility of achieving encouraging rates of local control and OS in LACC patients submitted to chemoradiation plus surgery, with a low rate of toxicity and complications.