Fluorescence imaging for real-time detection of breast cancer tumors using IV injection of indocyanine green with non-conventional imaging: a systematic review of preclinical and clinical studies of perioperative imaging technologies.

BACKGROUND: This review summarizes the available data on the effectiveness of indocyanine green fluorescence imaging (ICG-FI) for real-time detection of breast cancer (BC) tumors with perioperative imaging technologies. METHODS: PubMed and Scopus databases were exhaustively searched for publications on the use of the real-time ICG-FI evaluation of BC tumors with non-conventional breast imaging technologies. RESULTS: Twenty-three studies were included in this review. ICG-FI has been used for BC tumor identification in 12 orthotopic animal tumor experiences, 4 studies on animal assessment, and for 7 human clinical applications. The BC tumor-to-background ratio (TBR) was 1.1-8.5 in orthotopic tumor models and 1.4-3.9 in animal experiences. The detection of primary human BC tumors varied from 40% to 100%. The mean TBR reported for human BC varied from 2.1 to 3.7. In two studies evaluating BC surgical margins, good sensitivity (93.3% and 100%) and specificity (60% and 96%) have been reported, with a negative predictive value of ICG-FI to predict margin involvement intraoperatively of 100% in one study. CONCLUSIONS: The use of ICG-FI as a guiding tool for the real-time identification of BC tumors and for the assessment of tumor boundaries is promising. There is great variability between the studies with regard to timing and dose. Further evidence is needed to assess whether ICG-guided BC surgery may be implemented as a standard of care.

Prognostic Impact of Mesenteric Lymph Node Status on Digestive Resection Specimens During Cytoreductive Surgery for Ovarian Peritoneal Metastases.

BACKGROUND: The most common mode of ovarian cancer (OC) spread is intraperitoneal dissemination, with the peritoneum as the primary site of metastasis. Cytoreductive surgery (CRS) with chemotherapy is the primary treatment. When necessary, a digestive resection can be performed, but the role of mesenteric lymph nodes (MLNs) in advanced OC remains unclear, and its significance in treatment and follow-up evaluation remains to be determined. This study aimed to evaluate the prevalence of MLN involvement in patients who underwent digestive resection for OC peritoneal metastases (PM) and to investigate its potential prognostic value. METHODS: This retrospective, descriptive study included patients who underwent CRS with curative intent for OC with PM between 1 January 2007 and 31 December 2020. The study assessed MLN status and other clinicopathologic features to determine their prognostic value in relation to overall survival (OS) and progression-free survival (PFS). RESULTS: The study enrolled 159 women with advanced OC, 77 (48.4%) of whom had a digestive resection. For 61.1% of the patients who underwent digestive resection, MLNs were examined and found to be positive in 56.8%. No statistically significant associations were found between MLN status and OS (p = 0.497) or PFS ((p = 0.659). CONCLUSIONS: In anatomopathologic studies, MLNs are not systematically investigated but are frequently involved. In the current study, no statistically significant associations were found between MLN status and OS or PFS. Further prospective studies with a systematic and standardized approach should be performed to confirm these findings.

Effectiveness of Carbon Localization for Invasive Breast Cancer: An Institutional Experience.

Introduction: The final oncological and aesthetic results of breast-conserving surgery (BCS) are influenced by the precise localization of breast cancer (BC) tumors and by the quality of the intraoperative margin assessment technique. This study aimed to assess the effectiveness of the carbon localization (CL) technique by determining the success rate of BC identification and the proportion of adequate complete resection of BC lesions. Methods: We conducted a cross-sectional retrospective study of patients treated with primary BCS for invasive BC who underwent CL of their BC lesion at the Jules Bordet Institute between January 2015 and December 2017. Descriptive statistics with categorical and continuous variables were used. The success rate of tumor identification and the rate of adequate excision were calculated using the test of percentages for independent dichotomous data. Results: This study included 542 patients with 564 nonpalpable BC lesions. The median pathological tumor size was 12 mm. Of these, 460 were invasive ductal carcinomas. Most of the tumors were of the luminal subtype. CL was performed using ultrasound guidance in 98.5% of cases. The median delay between CL and surgery was 5 days, with 46% of the patients having CL one day before surgery. The lumpectomy weighed 38 g on average, with a median diameter of the surgical sample at 6 cm and a median volume of 44 cm3 (6-369). One-stage complete resection was successfully performed in 93.4% of cases. In 36% of cases, an intraoperative re-excision was performed, based on intraoperative macroscopic pathological margin evaluation. The tumor was identified in 98.9% of cases in the breast surgical specimen. Conclusion: This study demonstrated high success rates for BC tumor identification (99%) and one-stage complete resection (93.4%) after BCS and CL. These results show that CL is an effective, simple, and inexpensive localization technique for successful excision of BC lesions during BCS.

Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery.

BACKGROUND: Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any "peritoneal scar-like tissues" (PST) during CRS, hasn't been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC. METHODS: This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients' variables, were studied. RESULTS: In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS. CONCLUSION: Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts.

Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry.

BACKGROUND: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial. METHODS: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical). RESULTS: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%. CONCLUSIONS: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

Breast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery. Trial Registration Number: NCT04551495 (ClinicalTrials.gov).

The Impact of Temporal Variation in ICG Administration on Axillary Node Identification During Reverse Mapping Procedures.

ICG with other tracers can be injected pre and/or per operatively to identify the axillary Lymph Nodes (LN) draining the breast cancer (the SLN nodes) and/or the ipsilateral arm (the ARM nodes). to evaluate the impact on this temporal variable-variation on the identification of these ARM LN. Material and methods: One hundred and nine women, who were scheduled to undergo, either lumpectomy with selective lymphadenectomy (SLN), or mammary surgery (either lumpectomy, or mastectomy) with complete axillary node dissection (CALND) for a histologically proven mammary tumor, had administered the day before the surgery one subcutaneous injection of ICG in the first interdigital space of the ipsilateral hand (pre-op subgroup (SLN=28 and CALND=15), or the same day as the surgery (per op subgroup (SLN=26 and CALND= 20). The fluorescent characteristics of the SLN and/or axillary LN were then analyzed and compared between the two subgroups. Results: Basic characteristics were not significantly different between the pre and per op subgroups. The percentage of patients found with fluorescent SLN (28%), the percentage of patients with fluorescent LN in CALND (74.5%), or the percentage of LN fluorescent in CALND (38.5%) did not differ significantly too. Conclusion: Injection of ICG in the first interdigital space of the hand of operated side performed one day before the surgery or the same day as the surgery has no significant influence in our study on detection of the arm nodes. The timing of ICG injection is an independent variable with no effect on the results; this allows the injection to be performed either the day before the surgery or the day of the surgery.

Inferior epigastric artery lymph nodes: A pathway for systemic dissemination from peritoneal carcinomatosis?

BACKGROUND AND OBJECTIVES: We report, for the first time in the literature, a metastatic lymphatic pathway along the inferior epigastric vessels, through the inferior epigastric lymph nodes (IELNs), in patients with peritoneal carcinomatosis (PC). Interestingly, these lymph nodes (LNs) in the anterior retroperitoneum were not detectable on preoperative imaging. They may, however, represent a pertinent systemic dissemination pathway for PC. PATIENTS AND METHODS: In patients undergoing indocyanine green-fluorescence imaging during cytoreductive surgery for PC, an incidental finding of a hyperfluorescent LN, harboring metastatic tumorous cells, around the inferior epigastric artery was made. RESULTS: In three out of five patients with clear fluorescent hotspot, the harvested LN was harboring metastatic cancerous cells. None of these nodes, whether negative or positive, was visible on any preoperative imaging modalities. A protocol to sample, in a systematic manner, the IELN in patients with PC, is currently being devised at our institution. CONCLUSION: These lymphatic nodes basin and channels might reveal to be a potential passage from peritoneal metastasis to the extraperitoneal lymphatic compartment, representing an independent pathway for cancerous cell dissemination. This will bring us to further investigate the prevalence and the prognostic significance of these LNs.

Ex vivo indocyanine green fluorescence imaging for the detection of lymph node involvement in advanced-stage ovarian cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the ex vivo detection of metastatic lymph nodes (LNs) in advanced stage ovarian cancer (AOC). METHODS: Paraffin-embedded LNs from patients included in a previous ICG-FI study (Protocol NCT01834469) were further assessed for fluorescence. Intravenous injection of ICG was delivered intraoperatively. Tumor-to-background ratios (TBRs) were calculated. RESULTS: A total of 675 LNs from 19 patients were analyzed. The mean LN number per patient was 29.3 (median: 24; range 2-77). Seventy-three LNs were malignant (10.8%), 602 were benign (89.2%). The mean TBR of all LNs was 1.5 (SD 0.8). With a cut-off TBR of 1.3, the sensitivity, specificity, positive predictive, and negative predictive values of ICG-FI for retroperitoneal LNs were 80%, 41%, 2.8%, and 99%, respectively. On univariate analysis, only the fluorescence ratio (TBR ≥ 1.3) was correlated with malignancy at pathology (P = 0.03). No predictive factors of pathological LN status were found on multivariate analysis. CONCLUSIONS: Ex vivo ICG-FI of retroperitoneal LNs in AOC had good sensitivity but poor specificity. However, its high negative predictive value could make it an appropriate complementary tool to focus pathological analysis on fluorescent LNs.

ICG-fluorescence imaging for detection of peritoneal metastases and residual tumoral scars in locally advanced ovarian cancer: A pilot study.

BACKGROUND AND OBJECTIVES: No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue. METHODS: Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS. RESULTS: A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%. CONCLUSIONS: ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC.

Inflammatory Stroma of Lymphoepithelioma-like Carcinoma of the Cervix: Immunohistochemical Study of 3 Cases and Review of the Literature.

The aim of this study was to characterize the inflammatory infiltrate of the lymphoepithelioma-like carcinoma, a variant of squamous cell carcinoma clinically associated with a good prognosis. Immunohistochemistry was used to characterize 3 cases of lymphoepithelioma-like carcinoma in the uterine cervix, diagnosed over a period of 3 yr. The patients were between 30 and 50 yr old. Their cervical smears had shown atypical squamous cells of unknown significance or high-grade squamous intraepithelial lesions, and the initial cervical biopsy showed high-grade cervical intraepithelial neoplasia (CIN3) or squamous cell carcinoma. All patients underwent a Wertheim operation, 2 of which were preceded by a cervicectomy. Microscopically, all tumors were characterized by poorly defined sheets of undifferentiated squamous cells with a syncytial pattern and a dense background of infiltrating lymphocytes. Immunohistochemical analysis revealed that the lymphocytes were predominantly CD3 and CD8 T cells. The tumor lobules contained isolated CD8 T cells, whereas CD4 T cells and CD20 B cells surrounded the tumor lobules. CD56 NK cells and CD79 B cells were scattered in the tumor tissue. An in situ hybridization staining for Epstein-Barr encoding region was negative but all cases were immunohistochemically positive for P16. Follow-up varied between 2 mo and 2.7 yr. All 3 patients were disease free. Lymphoepithelioma-like carcinoma of the uterine cervix is a variant of squamous cell carcinoma, known for its better prognosis. The good prognosis of this tumor is potentially explained by the high levels of infiltrating CD8 T cells.

The impact of breast MRI workup on tumor size assessment and surgical planning in patients with early breast cancer.

BACKGROUND: The size and focality of the primary tumor in breast cancer (BC) influence therapeutic decision making. The purpose of this study was to evaluate whether preoperative breast magnetic resonance imaging (MRI) is helpful for the assessment of tumor size and surgical planning in early BC. METHODS: We performed a retrospective review of a prospectively collected database of 174 patients treated at a single institution for invasive BC who had complete documentation of the tumor size from mammography (MMG), ultrasonography (US), and MRI. RESULTS: A total of 186 breast tumors were analyzed. Mean tumor size varied by imaging method: 14.7 mm by MMG, 13.8 mm by US, and 17.9 mm by MRI. The concordance between breast imaging techniques (BIT) and final pathology with a cutoff ≤ 2 mm was 34.8% for MRI, 32.1% for US, and 27.2% for MMG. US and MMG underestimated while MRI and MMG overestimated the real tumor size. Concordance was the same in premenopausal women for MRI and US at 35%, while concordance was higher in postmenopausal women for MRI. Correlations between size determined by BIT and histopathological size were best with MRI (0.59), compared to US (0.56) or MMG (0.42). Intrinsic subtypes of BC had different concordances according to imaging method, but no significant associations were found. MRI examination revealed additional lesions in 13.8% of patients, 69% of these lesions were malignant. MRI changed the surgical plan in 15 patients (8.6%), and the rate of mastectomy increased by 6.9%. CONCLUSIONS: MRI estimates BC tumor size more accurately than US or MMG, but a significant overestimation exists. Complementary MRI examination improved the concordance for tumor size between BIT and final pathology in 16.7%. MRI did not alter surgical planning for most patients and allowed more appropriate treatment for 8% of them.

Evaluation of the perceptions and cosmetic satisfaction of breast cancer patients undergoing totally implantable vascular access device (TIVAD) placement.

PURPOSE: Totally implantable vascular access devices (TIVADs) are widely used to administer chemotherapy to cancer patients. While great progress has been made with respect to breast surgical reconstruction to take into account both aesthetics and patients' perceptions of body integrity, these aspects have not been considered with regard to the impact of TIVAD. In order to address this practice gap, we have adapted our TIVAD implantation technique to improve cosmetic results. The aim of this study was to assess breast cancer patients' comfort level and aesthetic satisfaction with regard to TIVAD insertion. METHODS: Patients with breast cancer admitted for chemotherapy at an outpatient clinic completed a previously validated survey evaluating three main domains: symptoms (pain, discomfort) related to the TIVAD itself in daily activity, information received before and during the surgical procedure, and cosmetic aspects regarding the port insertion site (scar, port, and catheter location). RESULTS: Between September 2010 and June 2011, 232 patients were evaluated. Cosmetic satisfaction with scar location was high (93.3 %). Information given to patients before and during the procedure had a major impact on both symptom perception in daily activity and on cosmetic satisfaction. CONCLUSIONS: Obtaining a more aesthetic scar by placing the TIVAD in the deltopectoral groove contributed to a high rate of cosmetic satisfaction. Furthermore, the relevance of information given to patients before and/or during surgery had a major impact on symptom perception. Therefore, we suggest including a pre-operative information session in the care pathway.

Interval Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First-Line Treatment for Advanced Ovarian Carcinoma: A Feasibility Study.

OBJECTIVES: We conducted a phase 2 trial to assess the feasibility of interval cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in patients with stage III and IV pleural ovarian carcinoma in first-line treatment with no macroscopic residual disease after surgery. METHODS: Patients could be treated either with primary CS with HIPEC followed by 6 conventional cycles of chemotherapy or with 3 or 4 cycles of neoadjuvant chemotherapy before CS with HIPEC and 3 postoperative chemotherapy cycles. Hyperthermic intraperitoneal chemotherapy was performed with cisplatin (50 mg/m) for 60 minutes, only in case of complete cytoreduction. RESULTS: Nineteen patients were included in the study, and they all underwent neoadjuvant chemotherapy before CS. Sixteen patients underwent complete CS with HIPEC. There was no mortality, and morbidity of CS with HIPEC was acceptable. The HIPEC procedure did not prevent the administration of the standard first-line treatment. In the 16 patients who underwent CS with HIPEC, the outcomes were very good. CONCLUSION: Our study shows an acceptable toxicity of adding HIPEC to the standard first-line treatment in patients with stage III ovarian carcinoma treated with interval CS. Further studies are needed to confirm the role of HIPEC in the treatment of ovarian carcinoma.

Prognostic value of preoperative serological biomarkers in patients undergoing cytoreductive surgery for ovarian cancer peritoneal metastases.

Objectives: Peritoneal metastases of ovarian cancer (PMOC) are common at initial presentation. Cytoreductive surgery (CRS) of curative intent has been proven to be efficient in increasing the overall survival (OS) and the disease-free survival (DFS) of these patients. Nevertheless, CRS is associated with high postoperative morbidity, which makes patient selection a major concern. Appropriate prognostic factors that can predict patient outcomes after surgery are still lacking. Preoperative biomarkers and their ratios have been shown to be predictive of patient prognosis for various solid tumors. We aimed to study their correlation with the prognosis of patients undergoing CRS for PMOC. Methods: This retrospective study included patients with PMOC operated by CRS. Preoperative biomarkers and other clinicopathological characteristics were studied to determine their prognostic value in terms OS and DFS. Results: 216 patients were included. Patients with preoperative hemoglobin (Hb) <11.7 g/dL had a poorer prognosis in terms of OS (p=0.0062) and DFS (p=0.0077). Additionally, increased neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) >0.32, and platelet-to-lymphocyte ratio (PLR) >214.5 were associated with worse OS (p=0.022, p=0.0028, and p=0.0018, respectively) and worse DFS (p=0.028, p=0.003, and p=0.019, respectively). Multivariate analysis showed that the variables mentioned above were independent predictive factors for OS and DFS. Conclusions: Preoperative Hb level, NLR, MLR, and PLR are prognostic factors for OS and DFS in PMOC patients operated by curative CRS.

Axillary Surgical Attitude Changing with Retrospective Application of ACOSOG Z0011 Eligible Criteria: An Institutional Evaluation.

Objective: Sentinel lymph node biopsy (SLNB) represents the gold standard for axillary surgical staging. The aim of this study was to assess the proportion of axillary lymph node dissection (ALND) that could be avoided after retrospective application of the ACOSOG Z0011 criteria and to evaluate the shortterm complications associated with axillary surgery. Materials and Methods: We reviewed breast cancer (BC) patients treated by primary breast-conserving surgery from 2012 to 2015. The percentage of SLNB vs ALND performed before and after the application of the ACOSOG Z0011 criteria was calculated. Complications were analyzed using crosstabs, with p<0.05 considered significant. Results: Two hundred fifty one patients with a median age of 59.3 years were included. BC tumors had a median size of 13 mm and were mostly unifocal (83.9%). There were 30.3% with 1-2 metastatic lymph nodes (MLN). ALND was performed in 44.2%. The patients with 1-2 MLN, had only SLNB in 14.5% of cases. By applying the ACOSOG Z0011 criteria, ALND would have been avoided in 40.2% of patients. At least one postoperative complication was reported after SLNB or ALND for 45.7% and 74.7% of patients respectively. Seroma was the most frequent complication, and occurred in 29.3% of cases after SLNB and in 59.5% after ALND. Conclusion: SNLB is the most commonly used axillary surgical staging procedure in this series (55.8%). With a retrospective application of the ACOSOG Z0011 criteria in our population, ALND could have been avoided for 40.2% patients. Post-operative complications rate was higher after ALND, with a seroma rate at 59.5%.

Uterine embryonal rhabdomyosarcoma in adult women: a case report on the challenging diagnosis and treatment.

BACKGROUND: Uterine embryonal rhabdomyosarcoma (uERMS) in adult women is a very rare malignant entity. The study aim was to report a case of adult uERMS and to discuss the implications of histopathological diagnosis on the treatment and prognosis. CASE PRESENTATION: We present here the clinicopathological features of a uERMS case in an adult woman. The study has been approved by the institutional Ethics Committee and an informed consent has been obtained (IJB∕CE3005). A 45-year-old woman presented to her gynecologist with intermenstrual bleedings and polypoid cervical mass (initially interpreted as benign polyp). A second biopsy was sent to our Department of Pathology at the Jules Bordet Institute, Brussels, Belgium for revision and was reinterpreted as botryoid-type uERMS. The patient underwent a total hysterectomy. The final pathology confirms a 3 cm cervical ERMS, and a simple surveillance was decided by our multidisciplinary team. Six months later, pelvic magnetic resonance imaging control showed a recurrence in the right pelvic lymph nodes. Multi-drug chemotherapy and radiotherapy were done before surgical resection. Pathological examination of the resected pelvic mass confirmed uERMS recurrence of 60 mm, with large zones of necrosis and the presence of cartilaginous structures. The patient is free of disease 60 months after diagnosis. CONCLUSIONS: Adult uERMS is rare and the pathological examination is the main element for diagnosis and treatment. It is often confused with other benign entities, at least at the time of diagnosis. ERMS should be included in the differential diagnosis of cervical and uterine polyp of adult women. Long-term survival is possible with a multimodal therapy approach.

Deep epigastric lymph nodes implication in patients' recurrence pattern after cytoreductive surgery in ovarian peritoneal metastases.

INTRODUCTION: Although complete cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) offers a good prognosis in patients with peritoneal metastasis of ovarian cancer (PMOC), recurrences are quite common. These recurrences can be intra-abdominal or systemic in nature. Our objective was to study and illustrate the global recurrence pattern in patients operated for PMOC, shedding light on a previously overlooked lymphatic basin at the level of the epigastric artery, the deep epigastric lymph nodes (DELN) basin. PATIENTS AND METHODS: This was a retrospective study including patients with PMOC who underwent surgery with curative-intent, from 2012 until 2018, at our cancer center, and who presented with any type of disease recurrence on follow-up. CT-scans, MRIs and PET-scans were reviewed in order to determine solid organs and lymph nodes (LN) recurrences. RESULTS: During the study period, 208 patients underwent CRS ± HIPEC, 115 (55.3%) presented with organ or lymphatic recurrence over a median follow-up of 81 months. Sixty percent of these patients had radiologically enlarged LN involvement. The pelvis/pelvic peritoneum was the most common intra-abdominal organ recurrence site (47%), while the retroperitoneal LN was the most common lymphatic recurrence site (73.9%). Previously overlooked DELN were found in 12 patients, with 17.4% implication in lymphatic basin recurrence patterns. CONCLUSION: Our study revealed the potential role of the DELN basin, previously overlooked in the systemic dissemination process of PMOC. This study sheds light on a previously unrecognized lymphatic pathway, as an intermediate checkpoint or relay, between the peritoneum, an intra-abdominal organ, and the extra-abdominal compartment.

First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial.

BACKGROUND: Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in. METHODS: The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2-6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery. RESULTS: Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37-69. All patients received SBRT and underwent surgery 2-4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4-5 AE were documented. Overall cosmetical breast evaluation after surgery was 'excellent' in four patients and 'good' in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3. CONCLUSIONS: This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial. TRIAL REGISTRATION NUMBER: NCT03875573.