Prevention and Management of Hormonal Crisis during Theragnosis with LU-DOTA-TATE in Neuroendocrine Tumors. A Systematic Review and Approach Proposal.

Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTR) on their cell surface. The first-line pharmacological treatment for inoperable metastatic functioning well-differentiated NETs are somatostatin analogs. On second line, Lu-DOTA-TATE (177Lu-DOTA0 Tyr 3 octreotate) has shown stabilization of the disease and an increase in progression free survival, as well as effectiveness in controlling symptoms and increasing quality of life. The management of functional NETs before and during LU-DOTA-TATE treatment is specially challenging, as several complications such as severe carcinoid and catecholamine crisis have been described. The aim of this review is to establish practical guidance for the management and prevention of the most common hormonal crises during radionuclide treatment with Lu-DOTA-TATE: carcinoid syndrome (CS) and catecholamine hypersecretion, as well as to provide a brief commentary on other infrequent metabolic complications. To establish a practical approach, a systematic review was performed. This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and conducted using MEDLINE (accessed from PubMed), Google Scholar and ClinicalTrials.gov. Literature searches found 449 citations, and finally nine were considered for this systematic review.

Sentinel lymph node technique in early-stage ovarian cancer (SENTOV): a phase II clinical trial.

OBJECTIVE: Early-stage ovarian cancer might represent an ideal disease scenario for sentinel lymph node application. Nevertheless, the published experience seems to be limited. Our objective was to assess the feasibility and safety concerns of sentinel lymph node biopsy in patients with clinical stage I-II ovarian cancer. METHODS: We conducted a prospective cohort study of 20 patients with histologically confirmed ovarian cancer. 99mTc and indocyanine green were injected into both the utero-ovarian and infundibulopelvic ligament stump, if they were present, during surgical staging. An intraoperative gamma probe and near-infrared fluorescence imaging were used to detect the sentinel lymph nodes. Inclusion criteria included: >18 years of age, suspicious adnexal mass (unilateral or bilateral) at ultrasound and CT imaging or confirmed ovarian tumor after previous surgery (unilateral or bilateral salpingo-oophorectomy with or without hysterectomy). Adverse events were recorded through postoperative day 30. The primary trial end point was to report adverse events related to the technique, including the use of 99mTc and ICG intraperitoneally, as well as the feasibility of the technique. RESULTS: A total of 20 patients were included in the analysis. Sentinel lymph nodes were detected in 14/15 (93%) pelvic and all 20 (100%) para-aortic regions. Five patients did not have utero-ovarian injection because of prior hysterectomy. The mean time from injection to sentinel lymph node resection was 53±15 min (range; 30-80). The mean number of harvested sentinel lymph nodes was 2.2±1.5 (range; 0-5) lymph nodes in the pelvis and 3.3±1.8 (range; 1-7) lymph nodes in the para-aortic region. There were no adverse intraoperative events, nor any within the 30 days of follow-up related with the technique. CONCLUSION: Sentinel lymph node mapping in early-stage ovarian cancer is feasible without major intraoperative or < 30 days safety concerns. (NCT03452982). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03452982.

Sentinel Lymph Node Technique in Apparent Early Ovarian Cancer: Laparoscopic Technique.

STUDY OBJECTIVE: To demonstrate the feasibility of laparoscopic sentinel lymph node technique in presumed early-stage ovarian cancer. DESIGN: Video illustrating the laparoscopic performance of the sentinel lymph node technique in ovarian cancer. SETTING: The Oncologic Gynecology Department at the University Hospital La Fe. PATIENTS: Candidates for the technique presented an apparent early stage ovarian cancer. The technique was performed in the context of a clinical trial called SENTOV (NCT03452982). INTERVENTIONS: To date, lymphadenectomy is recommended after the diagnosis of apparent early-stage ovarian cancer as part of the surgical staging. Minimally invasive surgery can be considered for the purpose of restaging [1]. Up to 14% of the patients are upstaged because of positive lymph nodes after pelvic and para-aortic lymphadenectomy [2]. Regarding low-grade tumors, a lower rate of lymph node involvement has been reported [3]. Sentinel lymph node technique has been reported to be feasible in a recent pilot study [4]. Two clinical trials (Sentinel Lymph Node in Early Ovarian Cancer and Sentine Lymph Node in Early Ovarian Cancer) are currently ongoing to clarify the use of sentinel lymph node technique in early ovarian cancer. The injection points were at the infundibulopelvic and ovarian ligament stumps. Two hundred microliters of saline solution containing 37 MBq of technetium-99m nanocolloid followed by 0.5 mL of indocyanine green (ICG) was injected subperitoneally. We used a 27 G needle at each injection point. Immediately after injection and also at 15 and 30 minutes after injection, the operative field was checked guided by the acoustic signal of the gamma probe and the near-infrared camera. We performed a minimum dissection looking for the sentinel lymph node or nodes in the pelvic and para-aortic region. Any lymph node with a remarkable radioactivity count as high as 10 times the background and/or dyed with ICG was considered a sentinel lymph node and was harvested separately. A systematic surgical staging was performed after the sentinel lymph node procedure was completed. Because of its small size, the ICG molecule is not caught in the lymph node valve system and keeps migrating when performing lymphography. An exhaustive direct view of the dye path is required to avoid misleading detection of the real sentinel lymph node. This theoretical problem is resolved by the use of the 99mTC-nanocolloid. This tracer gets trapped into the lymph node valve system because of its molecular size and does not keep migrating as does ICG. As such, a combination of both methods is proposed. CONCLUSION: Laparoscopic performance of sentinel lymph node technique in ovarian cancer seems to achievable. Between 2017 and 2019, this procedure was performed in 30 patients (13 laparoscopic), in the context of our pilot experience [4] and the Sentinel Lymph Node in Early Ovarian Cancer clinical trial (NCT03452982).