Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial.

PURPOSE: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC). PATIENTS AND METHODS: Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers. RESULTS: 114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNγ and CXCL10 levels. CONCLUSIONS: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2- MBC.

Primary leiomyosarcoma of the uterine cervix: an unusual case and critical appraisal.

Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnosis is based on pathology and immunohistochemistry. Surgery with a total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the standard. A female patient in her 60s presented with heavy postmenopausal bleeding. Vaginal ultrasound scan and magnetic resonance imaging showed a large strongly vascularized cervical mass with features suspicious of sarcomatous degeneration. Positron Emission Tomography-Computed Tomography (PET-CT) did not reveal any evidence of metastases nor lymphadenopathy, but presence of right hydronephrosis. An abdominal hysterectomy with bilateral salpingo-oophorectomy, and end-to-end anastomosis of the right ureter, was performed. Pathology showed an International Federation of Gynecology and Obstetrics (FIGO)-stage 1B leiomyosarcoma of the uterine cervix. No adjuvant treatment was given. Adjuvant radiotherapy reduces the risk of recurrence but no survival impact. The benefit of adjuvant chemotherapy is questionable given the lack of randomized trials. Multidisciplinary research concerning molecular alterations of the disease is required to determine optimal management strategies with potential novel molecular therapies.

Case report: a robotic-vaginal approach for total vaginectomy and hysterectomy with pelvic sentinel lymph node dissection in primary vaginal melanoma: a 10-step technique and literature review.

Introduction: Primary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly in elderly women. The diagnosis is based on histology and immunohistochemistry of a biopsy. Given the rarity of vaginal melanoma, no standardized treatment guidelines are established; however, surgery is the primary treatment modality in the absence of metastatic disease. Most reports in the literature are retrospective single cases, case series, and population-based studies. The open surgical approach is the main modality reported. Here, we report for the first time a 10-step combined robotic-vaginal technique, with en bloc resection of the uterus and total vagina, for treating clinically early-stage primary vaginal melanoma. In addition, the patient in our case underwent a robotic pelvic bilateral sentinel lymph node dissection. The literature on the surgical approach for vaginal melanoma is reviewed. Case presentation: A 73-year-old woman was referred to our tertiary cancer center and was clinically staged according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging for vaginal cancer as FIGO-stage I (cT1bN0M0) and according to the American Joint Committee on Cancer (AJCC) for (cutaneous) Melanoma Staging as clinical stage IB. Preoperative imaging with magnetic resonance imaging, FDG-positron emission tomography-computed tomography, and ultrasound of the groins did not reveal any adenopathy nor metastases. The patient was planned for a combined vaginal and robotic en bloc total vaginectomy and hysterectomy, as well as a pelvic bilateral sentinel lymph node dissection. Results: The surgical procedure was performed in 10 steps described in this case report. The pathology revealed free surgical margins and negative test results for all sentinel lymph nodes. The postoperative recovery process was uneventful, and the patient was discharged on day 5. Conclusion: The main surgical approach reported for primary early-stage vaginal melanoma is open surgery. A minimally invasive surgical approach, described here as a combined vaginal-robotic en bloc total vaginectomy and hysterectomy, for the surgical treatment of early-stage vaginal melanoma enables precise dissection, low surgical morbidity, and fast recovery for the patient.

Robotic surgery in early and advanced ovarian cancer: Case selection for surgical staging and interval debulking surgery.

OBJECTIVE: During the last decade several case series have been published on robotic surgery in early and advanced stage ovarian cancer. Although most studies lack a significant oncological follow-up, more importantly criteria for patient selection for both robotic surgical staging (R-SS) and robotic interval debulking surgery (R-IDS) are not well defined. The objective of this study was to assess the surgical and oncological outcomes, using well-defined selection criteria, between robotic and open surgery in early and advanced stage ovarian cancer. STUDY DESIGN: Single-center retrospective case cohort study including 96 ovarian cancer patients. For early stage ovarian cancer, patients were selected for R-SS after laparoscopic salpingo-oophorectomy of a suspicious adnexal mass. For advanced stage ovarian cancer, only patients receiving neoadjuvant chemotherapy and IDS were included in the study. Exclusion criteria were the presence of residual peritoneal disease after NACT and/or patients requiring additional complex surgical procedures. RESULTS: For early stage ovarian cancer, similar median operative times were seen between R-SS and open surgical staging (O-SS), 132 min and 120 min respectively. Pelvic/para-aortic lymph node yield was similar between R-SS and O-SS, 22/11 nodes and 18/8 nodes respectively. Surgical upstaging occurred in 11.5% in the R-SS group and in 27.6% in the O-SS group. In advanced stage ovarian cancer, the BMI was significantly higher in the R-IDS group compared to the O-IDS group (27.8 vs 23.5; p =.006). The median follow was 52 months in the R-IDS group and 31 months in the O-IDS group. Recurrent disease occurred in 42.9% of the R-IDS group and in 45% of the O-IDS group. The length of hospitalization was significantly longer in the O-SS and O-IDS group (p <.00001). CONCLUSION: Patients with clinically early stage ovarian cancer, confirmed after laparoscopic removal of a suspicious adnexal mass, are candidates for R-SS whilst maintaining similar surgical and oncological outcome measures as O-SS. In advanced ovarian cancer, suitable candidates for R-IDS are those who receive NACT with good response and no residual peritoneal disease, especially in patients with a high BMI, but large prospective randomized trials with well-defined criteria are needed.

Robotic Staging of Cervical Cancer With Simultaneous Detection of Primary Pelvic and Secondary Para-Aortic Sentinel Lymph Nodes: Reproducibility in a First Case Series.

Objective: Discrepancies exist among international guidelines on the surgical staging of para-aortic lymph nodes in locally advanced cervical cancer (LACC), varying from considering a para-aortic lymph node dissection, at least up to the inferior mesenteric artery, to a complete para-aortic lymph node dissection. In this study, we aim to assess the reproducibility of our recently reported robotic technique using indocyanine green for identifying besides primary pelvic sentinel lymph nodes (SLNs), secondary para-aortic SLNs in a first case-cohort of cervical cancer patients. Methods: A retrospective case series of LACC patients with/without suspicious pelvic lymph nodes (LNs) on imaging (including two patients with an additional suspicious para-aortic LN) is reported. All patients underwent a robotic pelvic SLN and para-aortic sentinel/nonsentinel LN dissection using the da Vinci Xi platform. Indocyanine green was used as a fluorescent tracer, at a concentration of 1.9 mg/mL, and injected as 0.5 mL in each quadrant of the cervix. Results: In a total of 10 cases, primary pelvic SLNs (90% bilateral) with subsequent secondary para-aortic SLNs were identified in all cases. Lower para-aortic SLNs were present in all cases, and upper para-aortic SLNs were found in 9 out of 10 cases. The mean age of the cervical cancer patients was 49.8 years (SD ± 6.89), and the mean body mass index (BMI; kg/m2) was 23.96 (SD ± 4.60). The median total operative time was 105.5 min (range: 89-141 min). The mean numbers of primary pelvic SLNs and secondary lower and upper para-aortic SLNs were 3.10 (SD ± 1.10), 2.90 (SD ± 0.74), and 2.30 (SD ± 1.57), respectively. The median number of total para-aortic LNs (PALNs) dissected per patient was 11.5. Six patients had positive primary pelvic SLNs, and two had secondary positive para-aortic SLNs. The nonsentinel para-aortic LNs were negative in all cases. There were no intra- or postoperative complications. Conclusion: Our preliminary experience demonstrates the reproducibility of identifying, besides primary pelvic SLNs, secondary lower and upper para-aortic SLNs during robotic staging in LACC. A surgical approach limiting a complete para-aortic LN dissection could reduce the potential risks and morbidity associated with this procedure. To determine the sensitivity and negative predictive value of this new surgical approach, and whether the lower para-aortic SLNs under the inferior mesenteric artery are representative of the whole para-aortic region, large prospective observational studies are needed in LACC and/or those with suspicious pelvic LNs but apparent normal para-aortic LNs on imaging.

Bone scan alterations in aromatase inhibitor-treated patients.

We report bone scan changes in 3 patients receiving aromatase inhibitors as adjuvant treatment for postmenopausal hormone receptor-positive breast cancer. Compared with bone scans before treatment, repeated scans after at least 10 months of aromatase inhibitor treatment showed increased activity in the peripheral skeleton and the skull. In 2 patients, these alterations could be correlated with increased markers of bone turnover. They probably result from high bone turnover induced by estrogen depletion caused by aromatase inhibitors. This effect should be taken into account in the differential diagnosis of a bone scan pattern suggestive of hyperparathyroidism, which was ruled out.