The Influence of Surgical Complexity and Center Experience on Postoperative Morbidity After Minimally Invasive Surgery in Gynecologic Oncology: Lessons Learned from the ROBOGYN-1004 Trial.

BACKGROUND: This study was a secondary analysis of the ROBOGYN-1004 trial conducted between 2010 and 2015. The study aimed to identify factors that affect postoperative morbidity after either robot-assisted laparoscopy (RL) or conventional laparoscopy (CL) in gynecologic oncology. METHODS: The study used two-level logistic regression analyses to evaluate the prognostic and predictive value of patient, surgery, and center characteristics in predicting severe postoperative morbidity 6 months after surgery. RESULTS: This analysis included 368 patients. Severe morbidity occurred in 49 (28 %) of 176 patients who underwent RL versus 41 (21 %) of 192 patients who underwent CL (p = 0.15). In the multivariate analysis, after adjustment for the treatment group (RL vs CL), the risk of severe morbidity increased significantly for patients who had poorer performance status, with an odds ratio (OR) of 1.62 for the 1-point difference in the WHO performance score (95 % CI 1.06-2.47; p = 0.027) and according to the type of surgery (p < 0.001). A focus on complex surgical acts showed significant more morbidity in the RL group than in the CL group at the less experienced centers (OR, 3.31; 95 % CI 1.0-11; p = 0.05) compared with no impact at the experienced centers (OR, 0.87; 95 % CI 0.38-1.99; p = 0.75). CONCLUSION: The findings suggest that the center's experience may have an impact on the risk of morbidity for patients undergoing complex robot-assisted surgical procedures.

PET-MRI for evaluation of response to radiochemotherapy in patients with locally advanced cervical cancer.

OBJECTIVE: We aimed to analyze the diagnostic test accuracy of positron emission tomography and a magnetic resonance imaging scan (PET-MRI) fusion in evaluating tumor response after radiochemotherapy in patients with locally advanced cervical cancer. METHODS: Patients treated at two institutes between January 2008 and December 2016 were studied retrospectively. Re-evaluation by positron emission tomography (PET) and magnetic resonance imaging (MRI) was performed in a non-concurrent way 4-8 weeks after treatment. A nuclear medicine doctor and a radiologist (subsequently referred as "radiologists"), both experts in gynecological oncology, re-examined the post-treatment MRI and positron emission tomography-computed tomography (PET-CT) separately, and then performed a fusion of these examinations. In this study we describe this "a posteriori fusion methodology", with two levels, enabling limitation of anatomical shifts. The gold standard was anatomical pathology analysis of the surgical specimen, since all patients underwent surgery following this radiological re-evaluation. The radiologists' degree of certainty in their diagnoses, and the impact of fusion on their diagnostic confidence were assessed by the radiologists, using two Likert judgment scales. They also adjudicated on possible changes of interpretation after the fusion. RESULTS: Thirty-one patients were included. The PET-MRI fusion has a sensitivity of 79% and a specificity of 90%. The positive predictive value (PPV) was 94%, and the negative predictive value (NPV) was 69%. In 45% of cases (n=13), radiologists reported an improvement in their degree of certainty in their diagnosis using a Likert judgment scale, due to inspecting the PET and MRI fused. A change in interpretation of tumor response was observed using a Likert judgment scale in 31% of cases. CONCLUSION: PET-MRI fusion improves the radiologist's own diagnostic confidence in assessing response to concurrent radiochemotherapy in locally advanced cervical cancer. More studies using a latest generation hybrid system will be necessary to further compare to MRI and PET-CT.

Robotic Radical Trachelectomy with Primary Vaginal Closure to Spare Fertility in Young Patients with Early-Stage Cervical Cancer.

OBJECTIVE: Our aim was to present the surgical technique of robotic radical trachelectomy (RRT) for early-stage squamous cell cervical cancer in women with a desire to preserve fertility. DESIGN: A surgical case to illustrate the entire surgical technique of RRT and sentinel lymph node dissection. Institutional Review Board approval was not required for this video presentation. SETTING: University hospital. INTERVENTIONS: A 30-year-old patient with one child and no medical history. Pap smear and cervical biopsy were in favor of high-grade squamous intraepithelial lesion, and a conization procedure allowed the diagnosis of a 15 mm squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] 1B1). An RRT was performed to preserve the fertility of this young patient, after bilateral sentinel lymph node dissection to ensure the absence of nodal metastasis. The trachelectomy specimen was negative at final pathology examination and the disease was confirmed as stage 1B1 (FIGO 2018). There were no surgical complications and no adjuvant treatment was indicated. Fertility-sparing surgery is acceptable for women of childbearing age who want to become pregnant. CONCLUSION: Minimally invasive surgery is safe, effective, and particularly adapted for women who wish to preserve their fertility without compromising oncological outcomes.1-2 This option may be safely proposed in expert centers for tumors smaller than 2 cm, with primary vaginal closure, and without use of a uterine manipulator.3 Complete information about oncological and obstetrical outcomes is mandatory and patients should agree to comply with a close follow-up protocol.

Comparison of SPECT-CT with intraoperative mapping in cervical and uterine malignancies.

INTRODUCTION: The objective was to evaluate whether hybrid imaging combining single photon emission tomography with computed tomography (SPECT/CT) provides additional clinical value for dectection of sentinel lymph nodes (SLNs) compared with intraoperative combined mapping in uterine and cervical malignancies. METHODS: This was a retrospective study of prospectively collected data from patients with stages IA-IB2 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018) or stage I endometrial cancer, who underwent preoperative SPECT/CT for SLN detection. All included patients had dual injection of technetium-99m (99mTc) with patent blue or indocyanine green. RESULTS: A total of 171 patients were included with 468 SLNs detected during surgery: 146/171 patients (85.4%) had both radiotracer and blue injection whereas 25/171 patients (14.6%) had radiotracer and indocyanine green injected. The overall detection rate was 95.3%. The detection rate of SLN mapping was 74.9% for SPECT/CT, 90.6% for 99mTc, 91.8% for blue dye, and 100% for indocyanine green. Bilateral drainage was found in 140 patients (81.9%), detected by 99mTc in 105 patients (61.4%), by blue in 99 patients (67.3%), by indocyanine green in 23 patients (92%), and by SPECT/CT in 62 patients (36.4%). Atypical SLN locations were identified by SPECT/CT in 64 patients (37.4%), by 99mTc in 28 patients (16.4%), by blue in 17 patients (9.9%), and by indocyanine green in 8 patients (4.7%). Sensitivity and negative predictive value of SLN biopsy to detect lymph node metastasis using dual injection of different intraoperative combined techniques were 88.9% and 97.5%, respectively. CONCLUSION: SPECT/CT enhanced topographic delineation of SLN and more accurately identified drainage to atypical locations. Fluorescent SLN mapping using indocyanine green offered the highest SLN detection rate. When indocyanine green was used, SPECT/CT did not increase SLN detection, and did not add further information to improve lymph node localization and removal.

Severe perioperative morbidity after robot-assisted versus conventional laparoscopy in gynecologic oncology: Results of the randomized ROBOGYN-1004 trial.

OBJECTIVE: In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence. METHODS: ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery). RESULTS: Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75-432) minutes and for CL was 145 (33-407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0-2500) and 50 (0-1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6-78.2), no significant differences in overall and disease-free survival were observed between the groups. CONCLUSIONS: RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL.

Prognostic value of lymphovascular space invasion in early-stage cervical cancer.

OBJECTIVE: Few prognostic factors likely to influence therapeutic management of early-stage cervical cancer are currently recognized. The objective of this study was to determine the prognostic value of lymphovascular space invasion (LVSI) in overall survival of patients with early-stage cervical cancer. METHODS: This is a retrospective study of patients treated for early-stage cervical cancer between January 1996 and December 2013 at Toulouse University Hospital and the Cancer Center Claudius Regaud Institute. Patients were included if they had FIGO 2018 stage IA1, IA2, IB1/2, or IIA1 cervical cancer. All patients had to have had surgery (conization, radical hysterectomy, or radical trachelectomy). The presence of LVSI was evaluated in the initial anatomic pathology reports of the excised tissue. The presence of LVSI was defined by the presence of epithelial tumor cells in the lumen of vessels, lined by endothelial cells. If the data were missing, the slides were reviewed by an expert pathologist. Comparative analyses of patient populations with and without LVSI invasion were performed, as well as analyses of overall and disease-free survival. RESULTS: A total of 158 patients were included in the analysis. Seventy-two (45.6%) patients had LVSI. More patients with LVSI received external radiotherapy in addition to standard treatment than patients without LVSI (53% vs 14%, p<0.0001). The overall survival of patients with LVSI (89.8%) was similar to that of patients without LVSI (91.5%) (p=0.39). For patients without lymph node involvement but with LVSI, disease-free survival at 5 years tended to be higher among those treated with external radiotherapy in addition to standard treatments (92.6% vs 79.8%, difference not tested due to the small number of events). CONCLUSION: Patients with early-stage cervical cancer with LVSI received external radiotherapy more often, and therefore had an overall survival at 5 years identical to patients without LVSI.

Chemoradiotherapy for locally advanced cervix cancer without aortic lymph node involvement: can we consider metabolic parameters of pretherapeutic FDG-PET/CT for treatment tailoring?

PURPOSE: Aim of the study was to assess impact of pretherapeutic FDG-PET/CT metabolic parameters on response to chemoradiotherapy (CRT) and survival in locally advanced cervical cancer (LACC) patients without paraaortic lymph node involvement. METHODS: LACC patients treated with CRT without macrometastatic involvement after paraaortic surgical staging were included. All patients had received at least 45 Gy radiotherapy and five cycles of platinum-based chemotherapy. High-risk histologies were excluded. Two senior nuclear physician experts in gynaecologic oncology reviewed all PET/CT exams, and extracted tumor SUVmax, MTV, and TLG (standardized uptake value, metabolic tumor volume, and total lesion glycolysis respectively). Response to CRT was assessed with a pelvic MRI done after 45 Gy. Medical charts were reviewed for clinical, pathology, and survival data. RESULTS: Ninety-three patients were included in the study. The overall survival (OS) rates at 2 and 5 years were 83.0% [95%CI: 72.5-89.8] and 71.2% [57.5-81.2] respectively. The RFS rates at 2 and 5 years were 72.5% [61.5-80.9] and 64.4% [52.3-74.2] respectively. Higher cervical SUVmax and TLG were significantly associated with poor response to CRT. In multivariate analysis, cervical SUVmax was the main predictive factor for OS. CONCLUSION: Cervical tumor SUVmax was demonstrated to be a non-invasive prognostic biomarker for response to treatment and survival in LACC patients without paraaortic involvement. SUVmax and other PET/CT metabolic parameters require further prospective investigation to help tailoring of local treatment.

Novel Surgical Strategies in the Treatment of Gynecological Malignancies.

OPINION STATEMENT: The main advancement in the surgical treatment of early cervical cancer has been a de-escalation in the radical surgical approach of early stage disease. Similarly, sentinel lymph node detection with cervical tracer injection can be performed alone in microscopic tumors (stage IA) while additional lymphadenectomy is still performed in macroscopic tumors (IB1 and IIA). Parametrial resection has been progressively reduced in tumors less than 2 cm, and simple procedures, conservative (trachelectomy) or not (simple hysterectomy), are currently being evaluated in several phase III trials. Since the preliminary results of the LACC (locally advanced cervical cancer) trial, the value of minimally invasive surgery as the standard approach for the treatment of early stage cervical cancer has been questioned and patients should be aware when discussing the approach for radical hysterectomy. While awaiting the results of ongoing clinical trials comparing radiological and surgical staging in locally advanced cervical cancer patients, surgical staging with paraaortic lymphadenectomy remains the standard of care before definitive chemoradiotherapy in patients with negative aortic PET/TDM. Patients undergoing salvage surgeries for isolated pelvic recurrences of cervical cancer benefit from advanced reconstructive techniques as DIEP flaps and continent reconstructive urinary techniques. In selected patients, a minimally invasive approach can be considered. Surgery is the mainstay of the treatment of endometrial cancer. The major evolution in surgical strategy has occurred in lymph node staging. The standard surgical staging includes pelvic and paraaortic lymph node dissection to the level of the left renal vein. Sentinel lymph node dissection has been validated as a less morbid alternative of systematic lymphadenectomy, indicated in patients with low and intermediate risk of lymph node involvement. In advanced ovarian cancer, complete cytoreduction is the main objective of surgery. To achieve this goal, upper abdominal complex procedures have been developed. Best survival rates are obtained with primary debulking surgery. Exploratory laparoscopy may be performed before cytoreduction to evaluate resectability and thus avoid unnecessary laparotomy. Although systematic pelvic and paraaortic lymphadenectomy is being questioned in patients with advanced ovarian cancer and clinically negative lymph nodes undergoing complete primary debulking surgery, this procedure is still recommended. While waiting publication of the GOG 252 trial, IP chemotherapy after complete CRS is under debate. HIPEC after interval debulking surgery in patients undergoing complete cytoreduction is an intriguing new option. Patients within the first recurrence of ovarian cancer, with score AGO-positive, benefit from a second complete cytoreductive surgery followed by chemotherapy. Ovarian cancer survival rates are higher in specialized high-volume centers, and thus cases should be centralized and quality indicators used.

Para-aortic workup in locally advanced cervical cancer: heterogeneity is still the rule. Results from a retrospective multicenter study.

PURPOSE: We retrospectively studied the different strategies of para-aortic (PA) staging of patients with PA involvement in locally advanced cervical cancer as conducted in eight centers in France and their impact upon survival and management. METHODS: All patients enrolled in this multicenter study presented with cervical cancer with PA involvement. The diagnosis of PA spread was based on imaging assessment of the PA area and/or pathological examination of harvested PA lymph nodes when staging lymphadenectomy was performed. Imaging modalities comprised positron emission tomography (PET), magnetic resonance imaging and/or computed tomography. Survival outcomes were evaluated retrospectively. RESULTS: One hundred and fifteen women were retrospectively studied. Radiological staging was conducted in 101 (87.8 %) patients. PET was performed in 66 patients (57.4 %). Its FN rate was 22.7 % (15/66) and its sensitivity 77.3 %. Para-aortic lymphadenectomy was conducted in a large proportion of patients (67.8 %). Its indications were not restricted to negative radiological workup. The lymphadenectomy rate was significantly higher in patients with earlier stages (p = 0.02) and lower tumor volume (p = 0.01). Treatment consisted of chemoradiation therapy with extended-field radiotherapy in all patients, followed by intracavitary brachytherapy in 94 cases (81.7 %) and completion surgery in 69 cases (60 %). Patients without para-aortic metastasis on radiological examination were more likely to receive all treatment modalities (p = 0.04). CONCLUSION: Despite established recommendations, our results point out the tremendous heterogeneity regarding para-aortic assessment. These differences in management are perhaps related to a recommended therapeutic strategy that does not appear to improve the poor prognosis associated with PA involvement.

Evaluation of the sentinel lymph node algorithm with blue dye labeling for early-stage endometrial cancer in a multicentric setting.

OBJECTIVES: Sentinel lymph node (SLN) removal may be a midterm between no and full pelvic dissection in early endometrial cancer. Whereas the use of blue dye alone in SLN detection has a poor accuracy, its integration in an SLN algorithm may yield better results and overcome hurdles such as the requirement of nuclear medicine facility. METHODS: Sixty-six patients with clinical stage I endometrial cancer were prospectively enrolled in a multicentre study between May 2003 and June 2009. Patent blue was injected intraoperatively into the cervix. We retrospectively assessed the accuracy of a previously described SLN algorithm consisting of the following sequence: (1) pelvic node area is inspected for removal of all mapped SLN and (2) excision of every suspicious non-SLN, (3) in the absence of mapping in a hemipelvis, a standard ipsilateral lymphadenectomy is then performed. RESULTS: Sentinel nodes were identified in 41 patients (62.1%), mostly in interiliac and obturator areas. None was detected in the para-aortic area. Detection was bilateral in 23 cases (56.1%). Seven patients (10.6%) had positive nodes. The false-negative rate was 40% using SLN detection alone. When the algorithm was applied, the false-negative rate was 14.3%. The use of a SLN algorithm would have avoided 53% of lymphadenectomies CONCLUSION: Our multicentric evaluation validates the use of a SLN algorithm based on blue-only sentinel node mapping in early-stage endometrial cancer. The application of such SLN algorithm should be evaluated in a prospective context and might lead to decrease unnecessary lymphadenectomies.

Evaluation of the impact of the COVID-19 lockdown on the quality of life of patients monitored for cancer who practice an adapted physical activity: rugby for health.

PURPOSE: The benefits of regular physical exercise on the tolerability of cancer treatments, quality of life and survival rates post-diagnosis have been demonstrated but all supervised physical activities have been interrupted due to the global health crisis and the need for lockdown to halt the spread of SARS-CoV-2. To reintroduce activities post-lockdown, we wanted to assess the impact of the COVID-19 lockdown on the quality of life and the psychological status of patients who practice an adapted physical activity such as rugby for health. METHODS: The evaluation was conducted in two phases: an initial self-questionnaire comprised of 42 questions sent to all participants to assess the impact of lockdown and a second assessment phase in the presence of the participants. We assessed anthropometric data, functional fitness parameters, quality of life and the psychosocial status of the subjects. The data were compared to pre-lockdown data as part of a standardised follow-up procedure for patients enrolled in the programme. RESULTS: 105/120 (87.5%) individuals responded to the rapid post-lockdown survey analysis. In 20% of the cases, the patients reported anxiety, pain, a decline in fitness and a significant impact on the tolerability of cancer treatments. Twenty-seven patients agreed to participate in the individual analysis. Following lockdown, there was a significant decrease in the intensity of physical activity (p = 8.223e-05). No post-lockdown changes were noted in the assessments that focus on the quality of life and the level of psychological distress. Conversely, there was a significant correlation between the total of high energy expended during lockdown and the quality of life (p = 0.03; rho = 0.2248) and the level of psychological distress post-lockdown (p = 0.05; rho = - 0.3772). CONCLUSION: Lockdown and reduced physical activity, particularly leisure activities, did not impact the overall health of the patients. However, there was a significant correlation with the level of physical activity since the higher the level of physical activity, the better the quality of life and the lower the level of psychological distress.

Evaluation of a trainer phantom in the learning phase of sentinel lymph node identification in breast cancer.

BACKGROUND: The concept of a learning phase is difficult to implement in a university setting, as it is unacceptable to subject a patient who requires only lymphadenectomy to axillary dissection for the purpose of training surgeons. We therefore sought to evaluate intraoperative sentinel node detection using a phantom, the Senti-Trainer. Learning phases on the Senti-Trainer and detection rate were assessed in order to determine whether the proficiency of surgeons in training improved with the number of procedures. METHODS: Twenty residents each performed 30 detection procedures of a sentinel node on the silicon phantom. Each resident was evaluated at each procedure, and an observation report was made every five procedures. Evaluation was single-blind as the surgeons did not know the result of the previous detection and were aware of the results only after the thirtieth procedure. RESULTS: The mean detection rate was 75% during the first procedure and reached 95% (or 5% detection errors) at the 30th procedure (p<0.0001; OR=6.33 with a 95% CI=[2.31; 17.33]). Proficiency in sentinel lymph node (SLN) identification also increased with the number of procedures performed. The ability to localize SLN improved during the learning phase with the increasing number of procedures performed. Mean detection time during the 30 procedures was 150 s (range: 115-210 s). CONCLUSIONS: Training on a phantom showed that this is a valuable teaching tool that enables surgeons to become familiar with gamma probes. It cannot replace the clinical training phase, but is an important aid to proficiency in intraoperative detection.

Virilising ovarian tumour: a case associating a Sertoli-Leydig cell tumour and a Brenner tumour.

Ovarian Sertoli-Leydig cell tumours (SLCT), also termed arrhenoblastomas, are the most frequent virilising tumours in women of reproductive age. Very rare secretory Brenner tumours (BT) have been described, generally after the menopause. A 31-year-old woman sought medical advice for secondary amenorrhoea, progressive hirsutism and a 5-year history of virilisation syndrome with clitoromegaly. Testosterone was markedly high (285 ng/dl, N<85) with moderate elevation of delta 4-androstenedione (D4AD) (311 ng/dl, N <270), dehydroepiandrosterone sulfate (DHEAS) (366 µg/dl, N <340) and 17-hydroxyprogesterone (17OHP) (275 ng/dl). LH was 9 IU/l, FSH 4.3 IU/l, estradiol 60 pg/ml and progesterone 314 ng/100 ml. Cortisol was decreased (1.3 µg/dl) after the dexamethasone suppression test. Pelvic MRI showed a 5-cm right ovarian tumour with a 2.5 cm nodular component and cystic areas, and two nodules measuring 11 mm and 15 mm above the right and left ovaries. After right ovariectomy by laparoscopy, pathological examination concluded on a 3-cm SLCT and a 2-cm BT; the nodules above the ovaries were dysembryoplastic cysts. Postoperatively, testosterone level was normal after 24 h (26 ng/dl), estradiol and progesterone rapidly decreased, cyclic secretion then resumed and the patient menstruated at day 27. To our knowledge, this is the first report of an ovarian tumour associating a Sertoli-Leydig cell tumour and a Brenner tumour in a patient with virilisation syndrome which resolved after ovariectomy.

Performance of Multiparametric Functional Imaging to Assess Peritoneal Tumor Burden in Ovarian Cancer.

PURPOSE: The aim of the study was to evaluate the clinical utility of pretreatment 18F-FDG PET/CT with quantitative evaluation of peritoneal metabolic cartography in relation to staging laparoscopy for ovarian carcinomatosis. PATIENTS AND METHODS: A retrospective review of prospectively collected data from 84 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IIIC to IV ovarian cancer was carried out. All patients had a double-blinded 18F-FDG PET/CT review. Discriminant capacity of metabolic parameters to identify peritoneal carcinomatosis in the 13 abdominal regions according to the peritoneal cancer index was estimated with area under the receiver operating characteristic curve (AUC). RESULTS: The metabolic parameter showing the best trade-off between sensitivity and specificity to predict peritoneal extension compared with peritoneal cancer index score was the metabolic tumor volume (MTV), with a Spearman ρ equal to 0.380 (P < 0.001). The AUC of MTV to diagnose peritoneal involvement in the upper abdomen (regions 1, 2, and 3) ranged from 0.740 to 0.765. MTV AUC values were lower in the small bowel regions (9-12), ranging from 0.591 to 0.681, and decreased to 0.487 in the pelvic region 6. 18F-FDG PET/CT also improved the detection of extra-abdominal disease, upstaging 35 patients (41.6%) from stage IIIC to IV compared with CT alone and leading to treatment modification in more than one third of patients. CONCLUSIONS: 18F-FDG PET/CT metrics are highly accurate to reflect peritoneal tumor burden, with variable diagnostic value depending on the anatomic region. MTV is the most representative metabolic parameter to assess peritoneal tumor extension.

Results of surgery after concurrent chemoradiotherapy in advanced cervical cancer: comparison of extended hysterectomy and extrafascial hysterectomy.

OBJECTIVES: The primary objective of this study was to compare disease-free survival (DFS) and overall survival (OS) of patients with and without completion surgery. The secondary objective was to compare DFS and OS of patients who had had systematic simple extrafascial hysterectomy or extended hysterectomy. The other objectives were to compare early and late complications with and without completion surgery and between the various surgical techniques. METHODS: One hundred seventy-one patients with advanced cervical cancer were included in a retrospective, multicenter series. RESULTS: The rate of pelvic control was 81.29% in our study after chemoradiotherapy, but histological residual cervical tumor persisted in nearly half of cases (49.71%). After a mean follow-up of 33 months, OS and DFS were not significantly higher in surgically treated patients, nor was the complication rate higher. Overall survival and DFS were not better after radical hysterectomy than after extrafascial hysterectomy. Statistically significant predictors of survival were clinical stage, tumor size, node extension, and residual tumor after chemoradiotherapy. CONCLUSION: There is no consensus regarding the maximal residual tumor volume after chemoradiotherapy suitable for surgery as there is no reliable imaging yet. Therefore, extrafascial hysterectomy with bilateral pelvic lymphadenectomy seems as a reasonable option if there are histological factors suggesting poor prognosis.

ROBOT-ASSISTED ABDOMINAL LAPAROSCOPIC RADICAL TRACHELECTOMY FOR EARLY STAGE CERVICAL CANCER :Case report with surgical intervention.

BACKGROUND: Vaginal radical trachelectomy to preserve fertility in women with early stage cervical cancer was first described by Dargent in 1994. Nowadays, robot-assisted abdominal laparoscopic radical is a new alternative. We want to share our first experience of robot-assisted radical trachelectomy. TECHNIQUE: We report the case of a 28 years-old women with an early stage cervical cancer (1B1) and has a wish for preserved fertility (no anterior pregnancy). She undergoes a robot-assisted laparoscopic radical trachelectomy. We divide the technique into 10 surgical steps. EXPERIENCE: The duration of the surgery was : 4H30 with a bleeding < 100cc. The post operative period was simple without complications. Since the intervention, we perform 3 more robot-assisted radical trachelectomy. None of them have a complication during the surgery and the post operative period was simple. CONCLUSION: Robot-assisted laparoscopic radical trachelectomy is a safe and acurate technique. We want to share our recent experience by sharing this video. The surgeon in our hospipal are used to pratic robot-assisted laparoscopic. However, it was our first robot-assisted laparoscopic radical trachelectomy. Thus we would like to demonstrate the feasibility and the reproducibility of this technique.

18F-FDG PET/CT Identifies Predictors of Survival in Patients with Locally Advanced Cervical Carcinoma and Paraaortic Lymph Node Involvement to Allow Intensification of Treatment.

Our objective was to use 18F-FDG PET/CT to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and paraaortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynecologic oncology reviewed all 18F-FDG PET/CT scans. Metabolic parameters including SUVmax, metabolic tumor volume, and total lesion glycolysis (TLG) were determined for the primary tumor, pelvic lymph nodes, and PALNs. Associations between these parameters and overall survival (OS) were assessed with the Cox proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% confidence interval, 40.8-68.0). When adjusted for age, stage, and histology, pelvic lymph node TLG, PALN TLG, and PALN SUVmax were significantly associated with OS (P < 0.005). Conclusion:18F-FDG PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.

Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies.

Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor-specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison with their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor-specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated patients with head and neck cancer. Our results showed that PD-1 blockade-mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors.