Alejandra Martinez

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

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. 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 ( 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 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.

Pocket memo based on the ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma: definition of prognostic risk groups

Intraepithelial tumor-infiltrating lymphocytes shape loco-regional PET/CT spread of locally advanced cervical cancer

Data suggest an association between positron emission tomography/CT (PET/CT) metabolic metrics and tumor microenvironment in several malignancies, and a potential role of PET/CT to monitor response to immunotherapy. To evaluate the correlation between tumor loco-regional extension and tumor-infiltrating lymphocyte infiltration in locally advanced cervical cancer prior to concurrent chemo-radiotherapy.The secondary objective was to assess the association between tumor-infiltrating lymphocytes and PET/CT metabolic metrics. Patients with locally advanced cervical cancer and negative para-aortic extensions on PET/CT were included. Two senior nuclear medicine physicians specializing in gynecologic oncology reviewed all PET/CT exams, and extracted tumor maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis, as well as pelvic lymph node involvement. One senior gynecologic oncology pathologist assessed intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. Intraepithelial tumor-infiltrating lymphocytes were categorized following previous studies as 1%. The cut-off for stromal tumor-infiltrating lymphocytes was chosen empirically: intermediate 60%. 86 patients were included. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with tumor metabolic metrics. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with maximum standard uptake value (p=0.16), or metabolic tumor volume (p=0.19). Tumors with <1% intraepithelial tumor-infiltrating lymphocytes score were associated with a higher MRI tumor size (≥ median) (63.3% vs 39.3%, p=0.04). Patients with pelvic lymph node uptake were significantly more frequent in patients with high stromal tumor-infiltrating lymphocytes score (≥60%) (61.5% vs 31.7%, p=0.009). Poor or absent intraepithelial tumor-infiltrating lymphocytes were associated with more advanced disease at diagnosis and larger tumor size. Tumor-infiltrating lymphocytes were not associated with tumor metabolic activity. Intraepithelial and stroma tumor-infiltrating lymphocytes are not redundant and should be assessed separately. Further work is needed to evaluate the association between tumor metabolic profile and immune populations, including different T-cell subtypes for patient selection for immunotherapy strategies.

PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells

Tumor antigen-specific CD4 T cells accumulate at tumor sites, evoking their involvement in antitumor effector functions in situ. Contrary to CD8 cytotoxic T lymphocyte exhaustion, that of CD4 T cells remains poorly appreciated. Here, using phenotypic, transcriptomic, and functional approaches, we characterized CD4 T cell exhaustion in patients with head and neck, cervical, and ovarian cancer. We identified a CD4 tumor-infiltrating lymphocyte (TIL) population, defined by high PD-1 and CD39 expression, which contained high proportions of cytokine-producing cells, although the quantity of cytokines produced by these cells was low, evoking an exhausted state. Terminal exhaustion of CD4 TILs was instated regardless of TIM-3 expression, suggesting divergence with CD8 T cell exhaustion. scRNA-Seq and further phenotypic analyses uncovered similarities with the CD8 T cell exhaustion program. In particular, PD-1hiCD39+ CD4 TILs expressed the exhaustion transcription factor TOX and the chemokine CXCL13 and were tumor antigen specific. In vitro, PD-1 blockade enhanced CD4 TIL activation, as evidenced by increased CD154 expression and cytokine secretion, leading to improved dendritic cell maturation and consequently higher tumor-specific CD8 T cell proliferation. Our data identify exhausted CD4 TILs as players in responsiveness to immune checkpoint blockade.

Transdiaphragmatic and transxiphoid cardiophrenic lymph node resection step-by-step in advanced ovarian cancer

Surgical approach of the left upper quadrant for ovarian cancer in 10 steps

Effect of tumor burden and radical surgery on survival difference between upfront, early interval or delayed cytoreductive surgery in ovarian cancer

We sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0). This retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC-IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3-4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score. Five hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score 10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS. The benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.

Peritoneal cancer index: laparoscopic evaluation of peritoneal carcinomatosis from gynecological origin

How should we stage and tailor treatment strategy in locally advanced cervical cancer? Imaging versus para-aortic surgical staging

Para-aortic lymph node status at initial assessment is the most important prognostic factor and a key point for the therapeutic strategy in patients with locally advanced cervical cancer. Undiagnosed lymph node metastasis is a major clinical problem as the finding of positive para-aortic lymph nodes leads to treatment modification, with a possible impact on disease free survival. When aortic lymph node disease is discovered, radiotherapy is extended to the para-aortic area, and other treatment modalities may be considered. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is the most accurate imaging examination to assess para-aortic extension in patients with locally advanced cervical cancer. The gold standard to identify para-aortic extension remains histologic evaluation of the lymph nodes. Indeed, PET/CT fails to detect approximately 10-15% of patients with negative PET/CT aortic nodes who have lymph node metastasis on pathologic staging. Patients with positive pelvic lymph nodes have para-aortic extension in 25-30% of cases, and surgical staging will lead to treatment modification and probably to improved para-aortic and distant control. Surgical staging also avoids unnecessary toxicity associated with extended field radiation in approximately 75% of patients with pelvic lymph node metastasis. The best modality to identify para-aortic extension is histological evaluation of the lymph nodes, but the survival benefit of surgical staging remains controversial. On the other hand, current studies include a majority of patients without pelvic lymph node spread, who are likely to be those who will benefit the least from surgical staging.

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

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. 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. 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). 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.

Tumour and pelvic lymph node metabolic activity on FDG-PET/CT to stratify patients for para-aortic surgical staging in locally advanced cervical cancer

The aim of our study was to comprehensively evaluate the most valuable metabolic parameters of cervical tumours and pelvic lymph nodes (PLN) by FDG-PET/CT to predict para-aortic lymph node (PALN) metastasis and stratify patients for surgical staging. The study included patients with locally advanced cervical cancer, negative PALN uptake on preoperative FDG-PET/CT, and para-aortic lymphadenectomy. Two senior nuclear medicine physicians expert in gynaecologic oncology reviewed all PET/CT exams, and extracted tumour SUVmax, MTV, and TLG, as well as PLN. Prognostic parameters of PALN involvement were identified using ROC curves and logistic regression analysis. One hundred and twenty-five consecutive locally advanced cervical cancer patients were included. The FDG-PET/CT false-negative rate was, respectively, 27.7% (13/47) and 5.1% (4/78) in patients with and without FDG-PET/CT PLN uptake. The AUC of cervical tumour size, SUVmax, MTV, and TLG was, respectively, 0.75 (0.62-0.87), 0.59 (0.44-0.76), 0.75 (0.60-0.90), and 0.71 (0.56-0.86). The AUC of PLN size, SUVmax, SUVmean, PLN SUVmax/Tumour SUVmax ratio, MTV, and TLG was, respectively, 0.57 (0.37-0.78), 0.82 (0.68-0.95), 0.77 (0.61-0.94), 0.85 (0.72-0.98), 0.69 (0.51-0.87), and 0.74 (0.57-0.91). The metabolic parameter showing the best trade-off between sensitivity and specificity to predict PALN involvement was the ratio between PLN and tumour SUVmax. The risk of PALN metastasis in FDG-PET/CT negative PLN patients is very low, so para-aortic lymphadenectomy does not seem justified. In patients with preoperative PLN uptake on FDG-PET/CT, surgical staging led to treatment modification in more than 25% of cases and should therefore be performed. Patients with more than one positive PLN and high PLN metabolic activity are at high risk of para-aortic extension and recurrence. Further prospective evaluation is required to consider intensified treatment modalities without prior PALN dissection.

How to avoid peritoneal tumor spillage during total abdominal hysterectomy in uterine cancers with cervical invasion

Vulvar and clitoral reconstruction using bilateral Singapore island perforator flap after anterior vulvectomy

Perineal resection and anorectal amputation with perforator flap reconstruction by a dorsal approach in prone Jackknife position

Anterior pelvic exenteration and laterally extended pelvic resection: a step by step procedure

Metabolic activity determines survival depending on the level of lymph node involvement in cervical cancer

Abstract Background To assess the impact of PET/CT functional parameters on survival, locoregional, and distant failure according to the most distant level of lymph node [18F]FDG uptake in patients with locally advanced cervical cancer (LACC). Methods Retrospective study including 148 patients with LACC treated with concurrent chemoradiotherapy after PET/CT and para-aortic lymph node (PALN) surgical staging. Two senior nuclear medicine physicians reviewed all PET/CT exams and retrieved tumor and lymph node metabolic parameters: SUVmax, MTV, TLG. Oncological outcomes according to metabolic parameters and level of lymph node spread on PET/CT were assessed. Results In patients without lymph node uptake on PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 5.14 95%CI = [2.15–12.31]), OS (HR = 6.10 95%CI = [1.89–19.70]), and time to distant (HR = 4.73 95%CI = [1.55–14.44]) and locoregional recurrence (HR = 5.18 95%CI = [1.72–15.60]). In patients with pelvic lymph node (PLN) uptake but without PALN uptake on [18F]FDG-PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 3.17 95%CI = [1.02–9.83]) and OS (HR = 3.46 95%CI = [0.96–12.50]), and the number of PLN fixations was associated with DFS (HR = 1.30 95%CI = [1.10–1.53]), OS (HR = 1.35 95%CI = [1.11–1.64]), and time to distant (HR = 1.35 95%CI = [1.08–1.67]) and locoregional recurrence (HR = 1.31 95%CI = [1.08–1.59]). There was no significant association between cervical tumor metabolic or lymph node metrics and survival outcome in patients with PALN uptake. Conclusions Cervical MTV is more accurate than SUVmax to predict survival outcome in patients with locoregional disease confined to the pelvis and should be implemented in routine clinical practice. Prognostic value of metabolic metrics disappears with PALN uptake, which is associated with distant failure in nearly half of patients. Graphical Abstract

The prognostic value of tumor-infiltrating lymphocytes in vulvovaginal melanoma

To assess the relation between immune microenvironment, survival, and clinicopathological characteristics. This study was a retrospective, single-center, observational study. Patients with a vulvovaginal melanoma and available archived material were included. All cases underwent pathology review, tumor-infiltrating lymphocyte quantification, and next-generation sequencing analysis, when feasible. Clinical data included demographic, treatment, and prognostic data. Forty-two patients were selected during the study period, but 13 were finally excluded owing to unavailable formalin-fixed, paraffin-embedded material or unknown follow-up data. Twelve of 19 cases (63.2%) had at least one genetic mutation, 3/18 (16.7%) had BRAF, 3/18 (16.7%) had c-KIT mutation, and 4/17 (23.5%) had NRAS mutations. High stromal tumor-infiltrating lymphocytes were identified in 13/28 patients (46.4%), and brisk tumor-infiltrating lymphocytes in 17/28 patients (60.7%). A density of stromal tumor-infiltrating lymphocytes >40% and brisk distribution were the single clinicopathologic factor associated with increased disease-free survival. The study showed that brisk tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes were a marker for disease progression, and for response to immunotherapy strategies. To validate these findings on a larger scale, further research is warranted through a multicenter study with a larger cohort and additional genetic and translational analysis.

Comparing the Efficacy of Surgery Staging and Image Staging of Locally Advanced Cervical Cancer

The study is a domestic multicenter, prospective, non-randomized controlled concurrent trial. It will be assessed whether surgery staging on locally advanced cervical cancer is superior to image staging for improving progression-free survival and overall survival.