Agnès Laplanche

Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN-γ-free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN-γ-Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN-γ-Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN-γ-Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN-γ-Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC.

PURPOSE: To define the optimal initial management and the best extent of surgery that would optimize margins on primary retroperitoneal sarcomas (RPS). PATIENTS AND METHODS: A total of 382 patients with primary RPS were analyzed. Sixty-five patients had a simple resection of the tumor, 120 patients had a complete compartmental resection (systematic resection of noninvolved contiguous organs), 130 patients had a contiguously involved organ resection, 21 patients had a systematic re-excision, 38 patients had an incomplete gross resection, and eight patients had a biopsy alone. Radiotherapy and chemotherapy were administered to 121 and 145 patients, respectively. RESULTS: One, 3-, and 5-year overall survival (OS) rates were 86% (95% CI, 0.82 to 0.89), 66% (95% CI, 0.61 to 0.71), and 57% (95% CI, 0.51 to 0.62), respectively. Median overall survival was 6 years. In the multivariate analysis, high grade, tumor rupture, gross residual disease, and positive margins were associated with decreased OS. Low grade, no tumor rupture, negative histologic margins, a high number of patients undergoing operation per center, and compartmental resection compared with standard procedures were associated with decreased abdominal recurrences. Compartmental resection is a significant variable, predicting a 3.29-fold lower rate of abdominal recurrence compared with simple complete resection. CONCLUSION: Complete compartmental surgery without tumor rupture should be performed when possible to achieve clear margins. This surgery should be performed in a high-volume center. The role of adjuvant treatments should be evaluated in a randomized trial in association with this optimal surgery.

A multivariate analysis of the prognostic factors was carried out on a series of 546 differentiated thyroid cancers followed for 8 to 40 years. For survival, the highest risk factor was associated with age; tumors diagnosed in patients younger than 45 years had higher relapse-free survival (RFS) and total survival (TS) rates and a slower growth rate. In children, although the RFS and TS at 15 years were high, they decreased later. The second independent prognostic factor was histology. There was no difference between papillary and follicular well-differentiated (FWD) tumors, but follicular moderately differentiated (FMD) had lower TS and RFS. Among FMD cancers, relapses occurred earlier and the interval between relapse and death was shorter. The third factor was sex. Tumors tended to disseminate more in male than in female patients. The survival rate after relapse was the same, however, suggesting that the growth rates are not different. The presence of palpable lymph nodes also had a significant independent impact on both TS and RFS. Patients treated after 1960 have a better outcome than patients treated earlier, although they did not differ in age distribution, histologic characteristics, sex ratio, or incidence of palpable lymph nodes. The distribution of time intervals between treatment and relapse was not compatible with an exponential failure time model but fit with a log-logistic model. Relapses can occur as late as 30 years or more after initial treatment. Elevated levels of circulating thyroglobulin have been observed in about 12% of the patients who had been in complete remission for longer than 20 years.

PURPOSE: To compare the respective sensitivity of somatostatin receptor scintigraphy (SRS), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of liver metastases from well-differentiated gastroenteropancreatic endocrine tumor (WDGEP ET) patients. To define predictive factors for "high-sensitivity SRS." PATIENTS AND METHODS: Sixty-four patients with WDGEP ET underwent SRS with abdominal single-photon emission computed tomography (SPECT), spiral CT, and 1.5-T MRI within a 15-day interval, the order of which was randomized. Two readers analyzed images of each modality, blindly and independently. RESULTS: Hepatic metastases were present in 40 of the 64 patients and confirmed by pathology after liver biopsy or surgery in 32 and eight patients, respectively. SRS, CT, and MRI detected a total of 204, 325, and 394 metastases, respectively. The number of detected metastases was significantly higher with MRI than with CT (P = .02) and SRS (P < 10(-4)) and higher with CT than with SRS (P < 10(-4)). SRS was negative in seven patients with a positive CT and/or MRI. More lesions were detected in 10 patients by SPECT compared with static views. The median metastasis size was significantly correlated (P = .04) with the sensitivity of SRS. CONCLUSION: MRI seems to have an edge over CT and SRS for the detection of liver metastases from endocrine tumors. We recommend the systematic performance of liver MRI at WDGEP ET initial staging and before major therapeutic events. The low performance of SRS was mainly explained by the impact of the metastasis size on the detection capacity of SRS.