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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.

Supplementary Figures S1-S10 and Tables S1-S3

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.

Introduction: To use positron emission tomography coupled with computed tomography (18FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all 18FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox9s proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (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

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.

IntroductionThe 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.MethodsThis 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.ResultsA 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% for99mTc, 91.8% for blue dye, and 100% for indocyanine green. Bilateral drainage was found in 140 patients (81.9%), detected by99mTc 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.ConclusionSPECT/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.

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.

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. 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. University hospital. 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. 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.

Identify a group with a high risk of postoperative complications after deep bowel endometriosis surgery. We conducted a retrospective study on patients treated from 2012 to 2018 in two departments of gynecological surgery at the Toulouse University Hospital, France. The postoperative complications were evaluated in relation to the surgical management, associated with or without non-digestive surgical procedures, initial disease and patient's characteristics. 164 patients were included. A postoperative complication occurred in 37.8% (n = 62) of the cases and required a secondary surgery in 18.3% (n = 30) of the cases. In the univariate analysis, the risk of postoperative complications increased significantly in the presence of segmental resection, disease progression, and associated urinary tract procedure or vaginal incision. In the multivariate analysis, the risk of overall postoperative complications was associated with the surgical management (p = 0.013 and 0.017) and particularly in the presence of segmental resection [Odds Ratio (OR): 20.87; CI 95% (1.96–221.79)]. The risk of rectovaginal fistula increased in the presence of segmental resection [OR: 22.71; CI 95% (2.74–188.01)] as well as in vaginal incision [OR: 19.67; CI 95% (2.43–159.18); p = 0.005]. The risk of overall postoperative complications and rectovaginal fistula in particular increases significantly in the presence of vaginal incision, segmental resection and urinary tract procedures after deep bowel endometriosis surgery.

International audience; 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.

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.

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. 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. 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. 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.

Key Clinical Message Lower-limb bone metastases are uncommon in low-grade endometrial carcinoma, and are mostly located on the axial skeleton. Here, we present a rare case of bilateral femur metastases in low-grade endometrial carcinoma and performed a review of the current literature.

Objectives The role of additional surgery in patients responding to radiation and chemotherapy for locally advanced cervical cancer is controversial. The goal of this study was to compare disease-free survival (DFS) and overall survival (OS) of two groups of patients, with or without additional surgery. Study design One hundred and eleven patients with advanced cervical cancer who responded to chemoradiotherapy followed by brachytherapy were included in a retrospective, multicenter series. Results Of the patients who had completion surgery (Group 1), 22.4% (15/67) had recurrence compared with 36.4% (16/44) of those who did not have surgery (Group 2). The difference is statistically significant ( p = 0.01). The relative risk of disease progression or death was 0.41 (95% confidence interval 0.20–0.85) ( p = 0.01) in favor of completion surgery. After multivariate analysis, only age, pathology and initial tumor size remained significant (respectively p = 0.003, p = 0.001 and p = 0.03). Among the locations of recurrence in Group 1, 46.7% were pelvic (7/15) compared with 56.2% in Group 2 (9/16). In Group 1, 16.4% (11/67) of the patients died of disease compared to 20.4% (9/44) in Group 2. Of these, 45.4% (5/11) in Group 1 died after pelvic recurrence as compared to 77.8% (7/9) in Group 2. Conclusion Completion surgery does not improve OS but may improve DFS. There is no consensus regarding completion surgery in advanced cervical cancer with a good response to the standard treatment but we think it is safer to propose it.

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. 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. 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). 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.

We retrospectively studied the therapeutic significance of extended-field radiotherapy combined with concurrent platinum-based chemotherapy for the management of cervical carcinoma with paraaortic spread. Treatment response and survival outcomes were evaluated. One hundred and fifteen women were retrospectively studied. Radiological staging was conducted in 101 (87.8%) patients and paraaortic lymphadenectomy in 78 (67.8%). Patterns of treatment comprised chemoradiation therapy (100%), intracavitary brachytherapy (81.7%), completion surgery (60%) and neoadjuvant chemotherapy (4.3%). Four-year overall and disease-free survivals were 32.7% and 28.8%, respectively. Progression and relapse mostly involved the locoregional area and distant organs, rather than the paraaortic area. Advanced FIGO stage at baseline was the most significant prognostic factor (HR=3.02, p=0.01). Despite systematic extended-field chemoradiation therapy, paraaortic involvement in cervical cancer is associated with poor survival outcomes. The patterns of progression and recurrence suggest the existence of occult metastatic disease at presentation. Additional systemic treatment might thus be beneficial.

ObjectivesSentinel 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.MethodsSixty-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.ResultsSentinel 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 lymphadenectomiesConclusionOur 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.

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.

Introduction:The aim of this study was to compare 18 fluoro-2deoxy-d-glucose-positron emission tomography (FDG-PET) after chemoradiation to histological findings after lymphadenectomy and radical hysterectomy and thus evaluate if FDG-PET could avoid surgery when negative.Methods:Twenty-one patients with locally advanced cervical cancer treated by chemoradiation, brachytherapy, and adjuvant surgery were prospectively enrolled. 18 Fluoro-2deoxy-d-glucose-PET was realized 5 weeks after concomitant chemoradiation and compared with histology.Results:18 Fluoro-2deoxy-d-glucose-PET assessed residual cervical involvement after chemoradiation with a sensitivity of 27.3%, specificity of 90%, and positive predictive value (PPV) of 75%. The negative predictive value (NPV) and the false-negative rate (FN) were 50%. Among patients with no evidence of disease on FDG-PET but with residual involvement on histology, 75% had residual involvement size under10 mm.For residual pelvic lymph node involvement, the specificity was 100%, NPV was 83.3%, and FN rate was 16.7%.For residual paraaortic lymph node involvement, specificity and sensitivity were 100%, but only 1 patient was concerned. Considering all the lymph node locations, sensitivity was 20%, specificity 100%, PPV 100%, and NPV 90%.Considering all localizations for each patient, control FDG-PET had a 30% sensitivity, 87% specificity, 80% PPV, and 43% NPV. False-negative rate was 43%.Conclusion:The aim of this study was to evaluate if control FDG-PET might avoid surgery for patients with a negative screening. Although FDG-PET is an interesting diagnostic test for residual lymph node involvement evaluation, it seems not accurate enough to be the only element of the surgery's indication. However, our sample size was too small to definitely conclude.