Andre Lopes

Empty node packet in endometrial cancer: predictors and clinical significance in the sentinel lymph node era

This study aimed to evaluate clinical and pathological factors associated with the occurrence of empty node packets during sentinel lymph node mapping in patients with endometrial cancer. We performed a retrospective cohort study including patients with histologically confirmed endometrial carcinoma who underwent sentinel lymph node mapping between November 2012 and December 2023. An empty node packet was defined as the intra-operative removal of a presumed sentinel node with no lymphoid tissue identified on final pathological examination. Logistic regression models were used to identify independent predictors. Of 489 patients who had sentinel lymph node mapped, 23 (4.7%) had an empty node packet. In the univariate analysis, body mass index and myometrial invasion were significantly associated (p < .05). In the multi-variable analysis, only body mass index remained independently associated (odds ratio 1.075, 95% confidence interval 1.01 to 1.14, p = .022) with an empty node packet. Tumor histology, grade, type of tracer, and surgical approach were not associated. No nodal recurrences occurred in patients with an empty node packet. Empty node packets are uncommon but clinically relevant during sentinel lymph node mapping for endometrial cancer. Higher body mass index was the only independent predictor, underscoring the influence of patient-related factors on mapping accuracy.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

Analysis of Sentinel Lymph Node Adoption Compared to Systematic Lymphadenectomy in Staging Early Endometrial Cancer at a Tertiary Center: An Ambispective Study

ABSTRACTObjectiveThe purpose of this study was to assess the impact of changing endometrial carcinoma staging from systematic lymph node dissection to the sentinel lymph node approach.MethodsThis is an ambispective study including patients with endometrial carcinoma (EC) limited to the uterus (FIGO 2018 IA/IB). From December 2015 to October 2021, a group of patients underwent systematic staging with lymph node dissection (LND). From December 2021 to April 2024, another group of patients underwent surgical staging with the sentinel lymph node‐indocyanine green (SLN) algorithm and pathology ultrastaging analisys. The groups were matched (1 LND: 1 SLN) based on age, body mass index (BMI), tumor type, tumor size, and myometrial invasion. The primary endpoints were lymph node involvement, length of surgery, and complications. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsTwo hundred fifty‐seven patients were surgically treated during the study period (156 in the LND cohort, 101 in the SLN cohort). Propensity score matching revealed two equivalent groups containing 84 patients each. The rate of positive lymph nodes was similar between the LND group (3.6%) and the SLN group (8.3%) (OR: 2.46, 95% CI: 0.61–9.84; p = 0.205). The length of surgery was significantly lower in the SLN group (152.2 ± 51.9 min) compared to the LND group (304 ± 77.8 min) (p &lt; 0.001). Intraoperative blood loss greater than 100 mL was significantly lower in the SLN group (9.5%) compared to the LND group (29.8%) (p &lt; 0.001). CTCAE grades requiring intervention (grades 3, 4, and 5) were higher in the LND group (14.3%) compared to the SLN group (4.8%) (p = 0.049).ConclusionThe transition from LND to SLN approach was similar compared to systematic lymphadenectomy, allowing the reduction of surgical length, blood loss and severity of complications without compromising surgical complications and lymph node positivity.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial)

Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. NCT03366051.

Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes

Few reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian institution over a 10-year period.This retrospective study included 703 patients diagnosed with endometrial cancer who were treated at a public academic tertiary hospital between 2008 and 2018. The following parameters were analyzed: age at diagnosis, race, body mass index, serum CA125 level before treatment; histological type and grade, and surgical stage. Outcomes were reported relative to histological type, surgical staging, serum CA125, lymph-vascular space involvement (LVSI), and lymph-node metastasis. The median patient age at diagnosis was 63 (range, 27-93) years (6.4% were <50 years). Minimally invasive surgeries were performed in 523 patients (74.4%). Regarding histological grade, 468 patients (66.5%) had low-grade endometrioid histology and 449 patients (63.9%) had stage I tumors. Tumors exceeded 2.0 cm in 601 patients (85.5%). Lymphadenectomy was performed in 551 cases (78.4%). LVSI was present in 208 of the patients' tumors (29.5%). Ninety-three patients (13.2%) had recurrent tumors and 97 (13.7%) died from their malignant disease. The robust prognostic value of FIGO stage and lymph node status were confirmed. Other important survival predictors were histological grade and LVSI [overall survival: hazard ratio (HR) = 3.75, p < 0.001 and HR = 2.01, p = 0.001; recurrence: HR = 2.49, p = 0.004 and HR = 3.22, p = 0.001, respectively). Disease-free (p = 0.087) and overall survival (p = 0.368) did not differ significantly between patients with stage II and III disease. These results indicate that prognostic role of cervical involvement should be explored further. This study reports the characteristics and outcomes of endometrial cancer in a large population from a single institution, with systematic surgical staging, a predominance of minimally invasive procedures, and well-documented outcomes. Prognostic factors in the present study population were generally similar to those in other countries, though our patients' tumors were larger than in studies elsewhere due to later diagnosis. Our unexpected finding of similar prognoses of stage II and III patients raises questions about the prognostic value of cervical involvement and possible differences between carcinomas originating in the lower uterine segment versus those originating in the body and fundus. The present findings can be used to guide public policies aimed at improving the diagnosis and treatment of endometrial cancer in Brazil and other similar countries.

Six cycles of neoadjuvant chemotherapy followed by cytoreduction in high-grade serous ovarian cancer: prognostic implications of the chemotherapy response score, CA-125, and tumor-infiltrating lymphocytes

To evaluate the prognostic value of the chemotherapy response score, a histopathologic grading system for tumor regression following neoadjuvant chemotherapy, along with post-treatment serum CA-125 levels and tumor-infiltrating lymphocyte density, in patients with high-grade serous ovarian carcinoma treated with 6 cycles of neoadjuvant chemotherapy followed by surgery. This retrospective cohort study included patients with histologically confirmed high-grade serous ovarian carcinoma treated at a single institution between 2008 and 2021. All patients completed 6 cycles of carboplatin- and paclitaxel-based neoadjuvant chemotherapy. The chemotherapy response score was assessed in omental and adnexal specimens and categorized as 1, 2, or 3. Tumor-infiltrating lymphocyte density in pre- and post-treatment samples was classified as low (<10%) or high (≥10%). Associations among the chemotherapy response score, CA-125 levels, tumor-infiltrating lymphocytes, and survival outcomes-including overall survival and disease-free survival-were analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Of 294 patients screened, 110 met the inclusion criteria. In the omentum, 35.6% had a Chemotherapy Response Score of 3, with a median overall survival of 56.7 months (HR 0.34, 95% CI 0.19 to 0.61). In the adnexa, 43.8% had a score of 2, 41.7% had a score of 1, and 14.6% had a score of 3. Median overall survival for adnexal score 2 was 50.6 months, compared to 33.8 months for score 1. Post-treatment CA-125 levels ≤35 U/mL were associated with higher chemotherapy response score categories and improved survival (HR 0.45, 95% CI 0.28 to 0.73). Tumor-infiltrating lymphocyte density ≥10% was more frequent in adnexal score 2 cases (88.5%, p = .006), but tumor-infiltrating lymphocyte levels-both pre- and post-treatment-were not independently associated with overall survival or disease-free survival. The chemotherapy response score and post-treatment CA-125 levels are independent prognostic indicators following 6 cycles of neoadjuvant chemotherapy. Tumor-infiltrating lymphocyte density showed site-specific patterns but lacked independent prognostic significance for survival outcomes.

Cervical Cancer Outcomes in Mozambique: Impact of an International Gynecologic Oncology Training Program

PURPOSE Cervical cancer is the most common cancer among women in Mozambique and is a major health burden. Surgery for cervical cancer is currently performed at only one hospital in the country, Maputo Central Hospital. Before 2020, there were no gynecologists in Mozambique trained to care for women with cervical cancer. In 2017, the International Gynecologic Cancer Society (IGCS) started a gynecologic oncology training program in Mozambique, and in 2020, the first three fellows graduated from this program. The main objective of this study was to report the outcomes of patients with cervical cancer who were treated surgically by the three newly trained Mozambican gynecologic oncologists. METHODS We performed a retrospective chart review of women diagnosed with cervical cancer who underwent surgical treatment by the Mozambican gynecologic oncologists between November 2020 and October 2022. The outcome of interest was survival at 2 years. RESULTS Thirty-three patients underwent radical hysterectomy with pelvic lymphadenectomy for cervical cancer treatment. The median age at diagnosis was 43 years. After surgery, 15 patients (45%) were dispositioned to surveillance and 18 (55%) were referred for adjuvant treatment with radiotherapy and/or chemotherapy. All patients had follow-up data available, with a median follow-up time of 19 months (range, 0.2 to 37.5). Only one patient died, and the overall survival is 95.7% (95% CI, 87.7% to 100%) at 12.7 months. CONCLUSION The IGCS program has provided training to physicians at Maputo Central Hospital, resulting in surgery for cervical cancer being available to patients in Mozambique. This is an important step in the global elimination of cervical cancer.

Persistent postoperative ascites successfully identified and treated with laparoscopic indocyanine green fluorescence

Role of systematic pelvic and para‐aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high‐grade serous ovarian carcinoma

AbstractIntroductionWe analyzed the role of systematic pelvic and para‐aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high‐grade serous ovarian carcinoma.Materials and MethodsWe retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin‐paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC‐IVB high‐grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin‐paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression‐free and overall survivals were analyzed using the Kaplan–Meier method.ResultsTotally, 132 patients with FIGO IIIC‐IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4–70.1) and 61.2 (21.4–101.0) months (p = 0.934); the corresponding disease‐free survival was 8.1 (6.2–10.1) and 8.3 (5.1–11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence.ConclusionsSystematic lymphadenectomy after six NACT cycles may have no influence on survival.

Expanding Cervical Cancer Screening in Mozambique: Challenges Associated With Diagnosing and Treating Cervical Cancer

PURPOSE Mozambique has one of the highest burdens of cervical cancer globally. Treatment options are few as most women present with advanced disease, and there are limited trained health professionals and health care resources. The objective of this study was to describe the outcomes of women diagnosed with invasive cancer as part of the Mozambican women undergoing cervical cancer screening with human papillomavirus (HPV) testing in conjunction with family planning services (MULHER) study. MATERIALS AND METHODS Women age 30-49 years were prospectively enrolled in the MULHER study and offered screening with primary HPV testing followed by treatment of screen-positive women with thermal ablation or excision as appropriate. Women with cervical examination findings suspicious for cancer were referred to one of the three gynecologic oncologists in the country. RESULTS Between January 2020 and January 2023, 9,014 women underwent cervical cancer screening and 30 women were diagnosed with cervical cancer. In this cohort, four patients (13.3%) had early-stage disease, 18 (60.0%) had locally advanced disease, one (3.3%) had distant metastatic disease, and seven (23.3%) did not have staging information available. Five patients (16.6%) died without receiving oncologic treatment, and seven patients (23.3%) are still awaiting treatment. Of the remaining 18 patients, three (17.6%) underwent surgery and four (23.5%) received radiotherapy. Eleven (36.7%) patients received only chemotherapy. CONCLUSION As cervical screening programs are implemented in low-resource settings, there will likely be an increase in the number of women diagnosed with invasive cervical cancer. Our results in Mozambique demonstrate the need to increase access to advanced surgery, radiation, and palliative care services.

Reconsidering adjuvant radiotherapy in intermediate-risk cervical cancer: findings from the CIRCOL study group

To evaluate survival outcomes associated with intermediate-risk factors in patients who underwent radical hysterectomy for cervical cancer, with a focus on the role of adjuvant radiotherapy. A multicenter retrospective cohort database comprising 1280 patients who underwent radical hysterectomy for cervical cancer was analyzed. For inclusion, patients had tumors ≤4 cm (International Federation of Gynecology and Obstetrics 2018 stages Ia2-Ib2) and were treated surgically between January 2000 and December 2017. Patients with lymph node metastasis, positive surgical margins, or parametrial involvement were excluded. Intermediate-risk factors were defined as tumor size >2 cm to ≤4 cm, stromal invasion ≥10 mm, and presence of lymphovascular space invasion. A total of 759 patients met inclusion criteria, of whom 158 (20.8%) received external beam radiotherapy. Patients who received external beam radiotherapy were older, more often underwent open surgery, and exhibited a higher incidence of adverse pathological features, including larger tumors, deeper stromal invasion, and lymphovascular space invasion. In multivariate analysis, tumor size >2 cm (HR 5.25, 95% CI 1.86 to 14.8) and stromal invasion ≥10 mm (HR 2.68, 95% CI 1.14 to 6.30) were independently associated with increased recurrence risk. No variables were independently associated with cancer-specific mortality. The presence of ≥2 intermediate-risk factors significantly increased the risk of recurrence (HR 3.48, 95% CI 2.05 to 5.91) and cancer-related death (HR 2.47, 95% CI 1.04 to 2.89), regardless of radiotherapy use. Tumor size and depth of stromal invasion were associated with increased recurrence risks. Adjuvant radiotherapy was not associated with improved survival outcomes in patients with intermediate-risk features.

Comparison of Two-Position and Four-Position Cervical Injection Techniques for Sentinel Lymph Node Mapping in Endometrial Cancer Using Methylene Blue

This clinical trial evaluates lymph node mapping in newly diagnosed endometrial cancer patients undergoing surgery. The standard technique uses a 2-point methylene blue cervical injection. The study aims to determine if increasing injection points improves mapping success.

Sentinel Node Mapping in High Risk Endometrial Cancer

This study will evaluate the role of systematic lymphadenectomy after sentinel node (SLN) mapping in high risk endometrial cancer (high grade histologies or deep myometrial invasion). The participants will be randomized in a non-inferiority controlled trial in 2 groups: SLN mapping or SLN mapping followed by systematic lymphadenectomy.