Oncologic outcomes in the era of modern radiation therapy using FIGO 2018 staging system for cervical cancer.

BACKGROUND: The recently published ASTRO cervical cancer guidelines recommend the use of modern radiotherapy. Imaging is now incorporated in the updated FIGO 2018 staging with a new stage IIIC. This study aims to evaluate the oncologic outcomes and predictors of survival using FIGO 2018 staging in a cohort of patients treated in an era of high-precision image-guided radiotherapy. METHODS: We performed a retrospective cohort study of 216 adult cervical cancer patients treated with definitive chemoradiotherapy between 2010 and 2018. Eligible patients had non-metastatic cervical cancer treated at a single academic institution. All patients had pre-treatment MRI and CT/PET. Treatment protocol consisted of external beam intensity-modulated radiotherapy and 3D image-guided brachytherapy. Kaplan-Meier curves were used for survival analysis. Multivariate cox proportional-hazards model was performed to identify potential prognostic factors. RESULTS: Median age at diagnosis was 50 and median BMI was 26.4 kg/m2. Median follow-up time was 44.3 months. Five-year overall survival (OS), disease-free survival and loco-regional disease-free survival rates were 76.8%, 68.5% and 82.6%, respectively. FIGO 2018 showed better OS discrimination compared to FIGO 2009 classification. OS was increasingly worse with positive pelvic and para-aortic nodes (p < 0.001). In a multivariate prediction model, performance status (p = 0.044) and FIGO 2018 classification (stage III p = 0.016; stage IVA p = 0.010) were predictors of mortality; FIGO 2018 classification (stage III p = 0.003; stage IVA p = 0.001) was a predictor of any recurrence; MRI tumor diameter (p ≤ 0.001) and nodal metastases (p = 0.024) were predictors of loco-regional recurrence. CONCLUSIONS: Integration of state-of-the-art imaging in cervical cancer staging and in radiotherapy planning leads to good loco-regional control rates, however distant recurrence remains an important issue. FIGO 2018 staging better reflects patient prognosis, highlighting the need for new treatment strategies for stage IIIC cervical cancer.

Distinct Histologic, Immunohistochemical and Clinical Features Associated With Serous Endometrial Intraepithelial Carcinoma Involving Polyps.

The origin of serous endometrial intraepithelial carcinoma (SEIC) is debated, due to its premalignant and independently malignant nature. It often arises next to endometrial serous carcinoma (ESC), with a propensity for polypoid growth. We aimed to better characterize this discrepancy by analyzing the clinical, histologic, and immunohistochemical features of polypoid carcinoma associated with SEIC (P-SEIC), and compared them with usual endometrial serous carcinoma without SEIC (UESC). Consecutive patients with P-SEIC were recruited and compared with UESC controls from our institutional research center. Clinical, histologic, and immunohistochemical (IHC, ER, PR, P53, Napsin-A, WT1, P16) were analyzed. BRCA testing results and familial history were also extracted from clinical databases. Welch T test, Pearson χ, and Fisher exact test were performed in SPSS version 23. A total of 37 P-SEIC and 25 UESC were the basis of a case-control study. P-SEIC was associated with more bilateral ovarian involvement (P=0.026), yet showed lower rates of myometrial invasion (P=0.002). P-SEIC showed a statistically different IHC profile: p53+, p16+, ER+, PR+, and WT-1+, and high rates of Napsin-A, while UESC was p53+, p16+, WT-1-, Napsin-A-, with lower rates of ER and PR. We also identified 2 patients who received prophylactic salpingo-oophorectomy for BRCA mutations and who subsequently developed P-SEIC with its unique IHC pattern. Our results suggest different underlying expression profiles and possibly diverging molecular signatures between both P-SEIC and UESC. If confirmed in further molecular studies, it could lead to a distinct molecular subclass.

Green versus blue: Randomized controlled trial comparing indocyanine green with methylene blue for sentinel lymph node detection in endometrial cancer.

OBJECTIVE: To ascertain the increase in detection rate of sentinel lymph node (SLN) associated with the use of indocyanine green (ICG) in comparison with methylene blue dye in women with endometrial cancer. METHODS: For this randomized controlled trial, all patients underwent SLN mapping after injection of blue dye on one side of the cervix and ICG on the other side. Randomization was for the side (right vs. left) on which ICG was used so that each patient's contralateral hemipelvis (HP) served as a control to her ipsilateral HP. We performed a two-tailed, normal-approximate McNemar test for paired-matched data. The primary endpoint was the difference in SLN detection rate for each HP according to the dye used. RESULTS: This trial included 132 patients, and 46 patients underwent robotic-assisted surgery while 86 had standard laparoscopic surgery. Successful detection of SLN was 90.9% using ICG and 64.4% using blue dye (p < 0.0001). There were no differences in the duration of the SLN procedure (median 10 min per HP) and number of SLN per HP (mean 1.2) according to the dye used. The SLN detection rates for either dye were very similar whether the surgical approach was robotic (mean BMI 45) or laparoscopic (mean BMI 29). Crossover of dye to the contralateral HP was present in 3% of cases. CONCLUSION: The use of ICG instead of blue dye results in a 26.5% (95% CI 17.4%-35.6%) increase of SLN detection rates per HP in women with endometrial cancer.

Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study.

BACKGROUND: Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed. METHODS: The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin-paclitaxel-treated population (validation cohort 3 [V3], n=320). FINDINGS: From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5-29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1-3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4-4·0, p=0·0009) with a GVS of 2; 4·1 (2·5-7·0, p<0·0001) for a GVS of 3; 5·5 (3·3-9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7-17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8-18·7] vs 40·8 [32·0-45·6] months; HR 2·8 [95% CI 2·2-3·7]; p<0·0001); V2 (11·9 [95% CI 8·8-18·1] vs 40·8 [32·0-45·6] months, HR 3·5 [2·5-4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8-31·8] vs 43·0 [40·6-49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001). INTERPRETATION: The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains. FUNDING: French National Cancer Institute. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Error reporting from the da Vinci surgical system in robotic surgery: A Canadian multispecialty experience at a single academic centre.

INTRODUCTION: The goal of the study is to evaluate and report on the third-generation da Vinci surgical (Si) system malfunctions. METHODS: A total of 1228 robotic surgeries were performed between January 2012 and December 2015 at our academic centre. All cases were performed by using a single, dual console, four-arm, da Vinci Si robot system. The three specialties included urology, gynecology, and thoracic surgery. Studied outcomes included the robotic surgical error types, immediate consequences, and operative side effects. Error rate trend with time was also examined. RESULTS: Overall robotic malfunctions were documented on the da Vinci Si systems event log in 4.97% (61/1228) of the cases. The most common error was related to pressure sensors in the robotic arms indicating out of limit output. This recoverable fault was noted in 2.04% (25/1228) of cases. Other errors included unrecoverable electronic communication-related in 1.06% (13/1228) of cases, failed encoder error in 0.57% (7/1228), illuminator-related in 0.33% (4/1228), faulty switch in 0.24% (3/1228), battery-related failures in 0.24% (3/1228), and software/hardware error in 0.08% (1/1228) of cases. Surgical delay was reported only in one patient. No conversion to either open or laparoscopic occurred secondary to robotic malfunctions. In 2015, the incidence of robotic error rose to 1.71% (21/1228) from 0.81% (10/1228) in 2014. CONCLUSIONS: Robotic malfunction is not infrequent in the current era of robotic surgery in various surgical subspecialties, but rarely consequential. Their seldom occurrence does not seem to affect patient safety or surgical outcome.