A Prospective Cohort Study Comparing Colorimetric and Fluorescent Imaging for Sentinel Lymph Node Mapping in Endometrial Cancer.

BACKGROUND: This prospective cohort study aimed to assess sentinel lymph node (SLN) mapping using isosulfan blue (ISB) compared with ISB plus indocyanine green (ICG) and near-infrared imaging (NIR) for patients with endometrial cancer. METHODS: In this study, 200 patients with endometrial cancer underwent SLN assessments and were randomized to ISB + ICG (n = 180) or ISB alone (n = 20). Blue dye determinations were recorded for all 200 cases followed by NIR imaging of ICG for 180 randomized subjects. All the patients underwent robotically assisted hysterectomy with pelvic ± aortic lymphadenectomy. RESULTS: The mean age of the patients was 64.5 ± 8.4 years, and the mean body mass index (BMI) was 33 ± 7.6 kg/m2. The histologies were endometrioid G1 (43%), G2 (30%), G3 (7%), and type 2 (20%). The mean time from dye injection to initiation of mapping was 13.4 ± 6.2 min, and the time to removal of SLN was 17.4 ± 11.2 min. Detection of SLN for the 20 ISB control cases did not differ from that for the 180 ISB + ICG cases (p > 0.05). The rates of SLN detection for ISB + ICG/NIR (n = 180) versus ISB (n = 200) were as follows: bilateral (83.9 vs. 40%), unilateral (12.2 vs. 36%), and none (3.9 vs. 24%) (p < 0.001). The median SLN per case was 2 (range 0-4). Positive SLNs were found in 21.1% (n = 38) of the ISB + ICG cases compared with 13.5% (n = 27) of the ISB cases (p = 0.056). The false-negative rate for SLN biopsy was 2.5% (95% confidence interval, 0.1-14.7%). In 61% (25/41) of the node-positive cases, SLN was the only positive lymph node (LN). Isolated tumor cells were found in 39.5% (15/38) of the SLN metastasis cases compared with 26.7% (4/15) of the non-SLN metastasis cases (p = 0.528). CONCLUSIONS: In this prospective study, ISB + ICG and NIR detected more SLNs and more LN metastases than ISB alone. Assessment of SLN with ICG + ISB/NIR imaging had excellent sensitivity for detection of metastasis and no safety issues.

Prognostic Significance of the Standardized Uptake Value of Pretherapeutic 18F-Labeled 2-Fluoro-2-Deoxyglucose Positron Emission Tomography/Computed Tomography in Patients With Locally Advanced Cervical Cancer.

OBJECTIVES: To determine the prognostic significance of the pretreatment and posttreatment maximum standardized uptake value (SUVmax) of F-labeled 2-fluoro-2-deoxyglucose positron emission tomography (PET)/computed tomography imaging in patients with stage IB2-IVA cervical cancer. METHODS: This was a retrospective review of cervical cancer patients with International Federation of Gynecology and Obstetrics stages IB2-IVA, from March 2008 to April 2014. All patients had pretreatment and posttreatment PET imaging and received primary whole pelvic radiation therapy with concurrent radiosensitizing chemotherapy, followed by intracavitary brachytherapy. Of the 58 patients who met the inclusion criteria, 31 patients (group A) showed no evidence of disease at last follow-up, and 27 patients (group B) presented with recurrence/persistence of disease. RESULTS: The mean pretreatment SUVmax in group A was 17.65 ± 7.82 versus 18.8 ± 7.77 in group B (P = 0.577). The mean posttreatment SUVmax between the groups was 0.85 ± 1.83 versus 6.05 ± 3.01 (P < 0.001), respectively. The mean difference between pretreatment and posttreatment SUVmax was 17.73 ± 7.50 in group A versus 13.29 ± 7.15 in group B (P = 0.045). In group A, 80.7% of patients demonstrated no posttreatment hypermetabolic activity on PET imaging versus 11.1% in group B. Of the patients who experienced treatment failure, the site of failure was pelvic in 25.9%, distant in 44.4%, and both pelvic and distant in 29.6%. CONCLUSIONS: No threshold was identified for the pretreatment SUVmax relative to the risk of recurrence. However, distinct correlations were found between the risk of recurrence, percent reduction in SUVmax, and the observation of residual hypermetabolic activity. This finding may help identify candidates for sequential chemotherapy.

Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.

OBJECTIVES: To compare the performance of sentinel lymph node (SLN) mapping with staging lymphadenectomy versus staging lymphadenectomy alone for the detection of metastasis and the use of adjuvant therapies in patients with endometrial cancer. METHODS: All patients with apparent early-stage endometrial cancer (n=780) who underwent robotic-assisted hysterectomy with pelvic±aortic lymphadenectomy from July-2006 to June-2013 were compared [pelvic±aortic lymphadenectomy (n=661) versus SLN-mapped cases with pelvic±aortic lymphadenectomy (n=119)]. Isosulfan-blue and indocyanine-green with near-infrared imaging were used for SLN mapping. Clinico-pathological data, FIGO stage, GOG risk category, and adjuvant therapies were compared. RESULTS: Non-mapped and mapped cases were comparable with respect to BMI, histology, depth-of-invasion, and lympho-vascular space invasion. The mapped group had more pelvic lymph node (LN) harvested compared to non-mapped group (26.4±10.5 vs. 18.8±8.5, p<0.001). Aortic LN yields were identical for both groups (9.0±5.6 vs. 9.0±6.0). The mapped group had more LN metastasis detected (30.3% vs. 14.7%, p<0.001), more stage IIIC (30.2% vs. 14.5%, p<0.001), more GOG high-risk cases (32.8% vs. 21.8%, p=0.013), and received more chemotherapy+radiation (28.6% vs. 16.3%, p<0.003). The SLN was the only metastasis in 18 (50%) mapped cases with positive nodes. The SLN false negative rate was 1/36 (2.8%). Micrometastases or isolated tumor cells were identified in 22/35 (62.9%) SLN metastases. Multivariate analysis demonstrated that SLN mapping imparted a significant effect on the detection of metastatic disease [adjusted OR=3.29, p<0.001]. CONCLUSIONS: The performance of SLN mapping with staging lymphadenectomy increased the detection of lymph node metastasis and was associated with more use of adjuvant therapies.

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer.

Studies have shown enhanced survival of ovarian cancer patients in which the tumors are infiltrated with tumor infiltrating lymphocytes and natural killer cells showing the importance of immune surveillance and recognition in ovarian cancer. Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFNα-2b) in a xenograft mouse model of ovarian cancer. SKOV3-AF2 ovarian cancer cells were injected intra-peritoneally (IP) into athymic nude mice. On day 7 post-tumor cell injection, mice were injected IP with peripheral blood mononuclear cells (PBMC; 5 × 10(6) PBMC) and cytokine combinations [IL-2 ± pegylated-IFNα-2b (IFN)]. Cytokine injections were continued weekly for IFN (12,000 U/injection) and thrice weekly for IL-2 (4000 U/injection). Mice were euthanized when they became moribund due to tumor burden at which time tumor and ascitic fluid were measured and collected. Treatment efficacy was measured by improved survival at 8 weeks and overall survival by Kaplan-Meier analysis. We observed that the mice tolerated all treatment combinations without significant weight loss or other apparent illness. Mice receiving PBMC plus IL-2 showed improved median survival (7.3 weeks) compared to mice with no treatment (4.2 weeks), IL-2 (3.5 weeks), PBMC (4.0 weeks), or PBMC plus IL-2 and IFN (4.3 weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5 weeks, p > 0.05). We demonstrate that cytokine-stimulated cellular immune therapy with PBMC and IL-2 was well tolerated and resulted in survival advantage compared to untreated controls and other cytokine combinations in the nude-mouse model.

Robotic transperitoneal infra-renal aortic lymphadenectomy in early-stage endometrial cancer.

OBJECTIVES: To assess the clinical performance of robotic-assisted infra-renal aortic lymphadenectomy (IRL) using a single center-docked approach for patients with endometrial cancer. METHODS: Robotic-assisted hysterectomy with pelvic and aortic lymphadenectomy was performed in 97 clinical stage I endometrial cancer (EC) patients with the intent to remove infra-renal aortic lymph nodes. Peri-operative data was contemporaneously accessioned and a retrospective database analysis was performed to examine clinical outcomes. RESULTS: IRL versus infra-mesenteric artery (IMA) dissections were accomplished in 88 (90.7%) and nine (9.3%) cases, respectively. There were no laparotomy conversions. Histology included 20.6% G1, 41.2% G2, and 38.1% G3 (endometrioid and Type II histologies). Forty-four (45.4%) cases had >50% depth-of-invasion and 43 (44.3%) cases had lymphovascular space invasion. Lymph node metastases were detected in 39 (40.2%) cases [37 (38.1%) pelvic, 16 (16.5%) pelvic+aortic, two (2.1%) isolated aortic lymph nodes]. Aortic metastasis was identified in 16/37 (43.2%) pelvic node positive cases, and 6/34 (17.7%) IRL cases with positive pelvic nodes had infra-renal metastasis, yet normal aortic nodes below the IMA. Harvested aortic lymph nodes for IRL exceeded IMA cases (15.9±6.3 vs. 8.9±4.6; p<0.01). Mean BMI for IMA cases exceeded IRL cases (37.4±3.3 vs. 31.4±7.1kg/m(2); p<0.001). Twenty-five (81%) patients with BMI >35kg/m(2) underwent successful IRL (range 36-47kg/m(2)) compared to 95% of cases <35kg/m(2) (p=0.03). CONCLUSIONS: IRL was accomplished in 95% of EC patients with BMI <35kg/m(2) and 81% with BMI >35kg/m(2) using a single center-docked approach. A strict 35kg/m(2) BMI cut-off for avoiding IRL is therefore not advised.