Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors such as aging and obesity tends to become a ...public health issue. However, its immune environment has been less characterized than in other tumors such as breast cancers. NK cells are cytotoxic innate lymphoid cells that are considered as a major anti-tumoral effector cell type which function is drastically altered in tumors which participates to tumor progression. Here we characterize tumor NK cells both phenotypically and functionally in the tumor microenvironment of endometrial cancer. For that, we gathered endometrial tumors, tumor adjacent healthy tissue, blood from matching patients and healthy donor blood to perform comparative analysis of NK cells. First we found that NK cells were impoverished in the tumor infiltrate. We then compared the phenotype of NK cells in the tumor and found that tumor resident CD103
NK cells exhibited more co-inhibitory molecules such as Tigit, and TIM-3 compared to recruited CD103
NK cells and that the expression of these molecules increased with the severity of the disease. We showed that both chemokines (CXCL12, IP-10, and CCL27) and cytokines profiles (IL-1β and IL-6) were altered in the tumor microenvironment and might reduce NK cell function and recruitment to the tumor site. This led to hypothesize that the tumor microenvironment reduces resident NK cells cytotoxicity which we confirmed by measuring cytotoxic effector production and degranulation. Taken together, our results show that the tumor microenvironment reshapes NK cell phenotype and function to promote tumor progression.
Purpose To evaluate the association between dynamic contrast material-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance (MR) imaging with pathologic complete response after preoperative ...combined chemotherapy and radiation therapy for cervical carcinoma and evaluate the risk of local recurrence. Materials and Methods The institutional ethics committee approved the study and waived the requirement to obtain informed consent. The study comprised 52 patients with locally advanced carcinoma, treated first with combined chemotherapy and radiation therapy, who underwent MR imaging before final surgery between June 2011 and July 2015. Three radiologists evaluated conventional, DW, and DCE MR images to identify a complete response. The standard of reference was surgical-pathologic findings. Results An initial increase in signal intensity on DCE MR images that was greater in the cervical lesion than in the myometrium was defined as time-signal intensity curve type B and showed a significant association with incomplete response (P = .0004). DCE MR imaging parameters (ie, maximum slope enhancement, area under the gadolinium concentration-time curve during the first 90 seconds after gadolinium injection AUGC90, and volume transfer constant K
) and a low signal intensity on apparent diffusion coefficient (ADC) maps were significantly associated with an incomplete response (P = .027, P = .041, P = .037, and P = .032, respectively). A mean ADC of 0.0014 m
/sec or less (hazard ratio HR = 8.3), low ADC signal intensity (HR = 7.3), high signal intensity at DW imaging (HR = 7.1), and time-signal intensity curve type B (HR = 4.3) were associated with earlier recurrence (P < .05). Excellent agreement between readers was found for time-signal intensity curve analysis (κ > 0.9) and the following parameters: AUGC90, K
, and maximum slope enhancement (intraclass correlation coefficient, >0.9). Conclusion DCE MR imaging parameters, especially the time-signal intensity curve, and DW imaging are associated with complete response and incomplete response and could potentially help oncologists with management decisions. Moreover, DCE and DW MR imaging could help oncologists accentuate the follow-up for patients with a high risk of local recurrence to assess for recurrence.
RSNA, 2017 Online supplemental material is available for this article.
Purpose
We aimed to investigate the safety, adequacy and oncological outcomes of laparoscopic surgery (LS) and robot-assisted laparoscopic (RALS) approach for the treatment of early-stage ovarian ...cancer.
Methods
We performed a multicentric, retrospective cohort study, enrolling patients affected by early-stage ovarian cancer who underwent laparoscopic management for early-stage ovarian cancer between 2006 and 2014. Surgical, pathologic and oncologic outcome data were analyzed to compare LS and RALS performances for early-stage ovarian cancer management.
Results
39 patients underwent laparoscopic staging for presumed stage I ovarian cancer: 23 underwent LS and 16 underwent RALS. The mean operative time was 281 ± 81 min (LS 288 ± 88 min; RALS 270 ± 72 min;
p
= 0.49). No conversion to laparotomy occurred, and one patient had intraoperative hemorrhage requiring blood transfusion. Four patients (10.2 %) experienced postoperative complications of grade 3 according to the Clavien-Dindo classification. The median hospital stay was 3 days (1–15); the differences were not statistically significant between two groups LS = 4 (1–15); RALS = 3 (1–7);
p
= 0.43. During a mean follow-up period of 19.4 months, tumor recurrence occurred in 3 patients: 2 (8.7 %) in the LS group and 1 (6.25 %) in the RALS group. Overall survival and disease-free survival for the entire cohort were 97.4 and 92.3 %, respectively.
Conclusions
LS and RALS seem to be adequate and feasible for the treatment of early-stage ovarian cancer in terms of the surgical outcomes and oncological safety. Furthermore, in our experience, perioperative outcomes are comparable between LS and RALS making them an acceptable approach in selected patients.
Abstract Aim To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking ...surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma. Methods Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented. Results In the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached. Conclusion The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated.
In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) ...was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence.
ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery).
Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75–432) minutes and for CL was 145 (33–407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0–2500) and 50 (0–1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6–78.2), no significant differences in overall and disease-free survival were observed between the groups.
RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL.
•Robot-assisted laparoscopy was not superior to conventional laparoscopy in terms of morbidity incidence.•Robot-assisted laparoscopy was associated with a longer operating time than conventional laparoscopy.•This is the largest RCT to evaluate robot-assisted laparoscopy vs. conventional laparoscopy in gynecologic cancer.
Several models have been developed to predict nonsentinel lymph node (non-SN) status in patients with breast cancer with sentinel lymph node (SN) metastasis. The purpose of our investigation was to ...compare available models in a prospective, multicenter study.
In a cohort of 561 positive-SN patients who underwent axillary lymph node dissection, we evaluated the areas under the receiver operating characteristic curves (AUCs), calibration, rates of false negatives (FN), and number of patients in the group at low risk for non-SN calculated from nine models. We also evaluated these parameters in the subgroup of patients with micrometastasis or isolated tumor cells (ITC) in the SN.
At least one non-SN was metastatic in 147 patients (26.2%). Only two of nine models had an AUC greater than 0.75. Three models were well calibrated. Two models yielded an FN rate less than 5%. Three models were able to assign more than a third of patients in the low-risk group. Overall, the Memorial Sloan-Kettering Cancer Center nomogram and Tenon score outperform other methods for all patients, including the subgroup of patients with only SN micrometastases or ITC.
Our study suggests that all models do not perform equally, especially for the subgroup of patients with only micrometastasis or ITC in the SN. We point out available evaluation methods to assess their performance and provide guidance for clinical practice.
Cancer stem-like cells (CSC) have been widely studied, but their clinical relevance has yet to be established in breast cancer. Here, we report the establishment of primary breast tumor-derived ...xenografts (PDX) that encompass the main diversity of human breast cancer and retain the major clinicopathologic features of primary tumors. Successful engraftment was correlated with the presence of ALDH1-positive CSCs, which predicted prognosis in patients. The xenografts we developed showed a hierarchical cell organization of breast cancer with the ALDH1-positive CSCs constituting the tumorigenic cell population. Analysis of gene expression from functionally validated CSCs yielded a breast CSC signature and identified a core transcriptional program of 19 genes shared with murine embryonic, hematopoietic, and neural stem cells. This generalized stem cell program allowed the identification of potential CSC regulators, which were related mainly to metabolic processes. Using an siRNA genetic screen designed to target the 19 genes, we validated the functional role of this stem cell program in the regulation of breast CSC biology. Our work offers a proof of the functional importance of CSCs in breast cancer, and it establishes the reliability of PDXs for use in developing personalized CSC therapies for patients with breast cancer.
The aim of the study was to compare the characteristics of procedures for gynecologic cancers conducted with conventional laparoscopy (CL) or robotically assisted laparoscopy (RAL) in the context of ...an enhanced recovery program (ERP).
This is a secondary analysis of prospectively collected data from a cohort study conducted between 2016 (when the ERP was first implemented at the Institut Paoli-Calmettes, a comprehensive cancer center in France) and 2018. We included patients who had undergone minimally invasive surgery for gynecological cancers and followed our ERP. The endpoints were the analysis of postoperative complications, the length of postoperative hospitalization (LPO), and the proportion of combined procedures depending on the approach (RAL or CL). Combined procedures were defined by the association of at least two of the following operative items: hysterectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy.
A total of 362 women underwent either CL (n = 187) or RAL (n = 175) for gynecologic cancers and followed our ERP. The proportion of combined procedures performed by RAL was significantly higher (85/175 48.6%) than that performed by CL (23/187 12.3%; p < 0.001). The proportions of postoperative complications were similar between the two groups (19.4% versus 17.1%; p = 0.59). Logistic regression analysis revealed a statistically insignificant trend in the association of RAL with a reduced likelihood of an LPO > 3 days after adjusting for predictors of prolonged hospitalization (adjusted OR = 0.573 0.236-1.388; p = 0.217).
Experts from our cancer center preferentially choose RAL to perform gynecologic oncological procedures that present elements of complexity. More studies are needed to determine whether this strategy is efficient in managing complex procedures in the framework of an ERP.
Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20-30% of women delay or refuse early ...oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.
Objectives
Enhanced recovery after surgery programs (ERAS) have been proven to decrease the length of hospital stay without increasing readmission rates or complications. However, the patient and ...operative characteristics that improve the chance of a successful early hospital discharge are not well established. The aim of this study was to design a nomogram which could be used before surgery, using the characteristics of patients, to establish who could benefit from early discharge (POD ≤ 2 days).
Methods
This observational study has been prospectively conducted. All the included patients were referred for surgical treatment of gynecologic cancer. We defined two sub-groups of patients on surgical procedure characteristics: isolated procedures (hysterectomy or lymphadenectomy) and combined procedures (at least the association of two procedures).
Results
230 patients were enrolled during the study protocol. 83.9% of patients were treated with a minimally invasive surgery (MIS). 159 patients (69.1%) were discharged on or before POD 2. On multivariate analysis, the surgical approach (open surgery vs. laparoscopy, OR 0.02 (95% CI 0–0.07),
p
< 0.001) and the type of surgery (combined procedure versus isolated procedure, OR 0.41 (95% CI 0.18–0.91),
p
= 0.028) were found to be significant predictors of increased hospital stay. A nomogram has been built for the purpose of predicting eligible patients for early post-operative discharge based on the multivariate analysis results (AUC = 0.86, 95% CI 0.81–0.92).
Conclusion
The use of MIS for isolated procedures in oncologic indications constitutes an independent factor of early discharge in a setting of ERAS. These promising preliminary results still require to be validated on a prospective cohort.
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