31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Long-term results of transcervical, intrauterine ultrasound-guided radiofrequency ablation of uterine fibroids with the Sonata System: a retrospective follow-up study

BACKGROUND: The Sonata System is a new minimally invasive, transcervical, uterine-sparing treatment option for fibroids with a mainly intramural location. The device combines intrauterine ultrasonography with radiofrequency ablation. Long-term follow-up data are still lacking. OBJECTIVE: This study aimed to evaluate long-term outcomes of the Sonata System in terms of surgical reintervention and to identify factors predicting surgical reintervention. Moreover, patient satisfaction, fibroid size reduction, and complication rate were evaluated. STUDY DESIGN: We performed a retrospective single-center cohort study of 53 women who underwent Sonata treatment between December 2011 and April 2019. Medical chart review was conducted to collect data on surgical reintervention and patient, fibroid, and surgery characteristics. The follow-up period lasted from date of initial surgery until April 2020. In addition, women filled out a questionnaire at a single time point (April 2020) containing questions about surgical reintervention and patient satisfaction. Kaplan–Meier analysis was used to determine cumulative reintervention rates and median time without reintervention. Univariate Cox regression analyses were performed to identify factors predicting surgical reintervention. RESULTS: Median follow-up period was 36 months (interquartile range, 22–58). Twenty-four women (45.3%) underwent a surgical reintervention, of which most were hysteroscopic myomectomies (45.8%). Surgical reintervention rates as determined by Kaplan–Meier analysis at 1-year and 2-year follow-up were 24.5% and 39.8%, respectively. Eventually, 7 women (13.2%) underwent a hysterectomy after the Sonata treatment. Univariate Cox regression analyses were performed, but did not show a significant association between surgical reintervention and age, preoperative fibroid size, type of ablated fibroid, number of ablated fibroids, and presence of other fibroids that could not be ablated during the Sonata procedure. Median fibroid diameter was 41 mm (interquartile range, 29–50) before and 29 mm (interquartile range, 20–40) after treatment (Z=−5.01; P<.001; 95% confidence interval, −13.0 to 7.0). Thirty-four women (69.4%) were satisfied with the treatment effect, and 42 women (85.7%) would recommend the Sonata treatment to other women. No device-related complications occurred. CONCLUSION: The Sonata System is a safe and minimally invasive treatment option for women suffering from (partly) intramural fibroids. The findings of this long-term follow-up study support counseling women for treatment with the Sonata System. More prospective studies with long-term follow-up are needed to investigate for which type and size of uterine fibroid the Sonata System is of most value

The (cost) effectiveness of procedural sedation and analgesia versus general anaesthesia for hysteroscopic myomectomy, a multicentre randomised controlled trial: PROSECCO trial, a study protocol

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The (cost) effectiveness of procedural sedation and analgesia versus general anaesthesia for hysteroscopic myomectomy, a multicentre randomised controlled trial : PROSECCO trial, a study protocol

BACKGROUND: In women with abnormal uterine bleeding, fibroids are a frequent finding. In case of heavy menstrual bleeding and presence of submucosal type 0-1 fibroids, hysteroscopic resection is the treatment of first choice, as removal of these fibroids is highly effective. Hysteroscopic myomectomy is currently usually performed in the operating theatre. A considerable reduction in costs and a higher patient satisfaction are expected when procedural sedation and analgesia with propofol (PSA) in an outpatient setting is applied. However, both safety and effectiveness - including the necessity for re-intervention due to incomplete resection - have not yet been evaluated. METHODS: This study is a multicentre randomised controlled trial with a non-inferiority design and will be performed in the Netherlands. Women > 18 years with a maximum of 3 symptomatic type 0 or 1 submucosal fibroids with a maximum diameter of 3.5 cm are eligible to participate in the trial. After informed consent, 205 women will be randomised to either hysteroscopic myomectomy using procedural sedation and analgesia with propofol in an outpatient setting or hysteroscopic myomectomy using general anaesthesia in a clinical setting in the operating theatre. Primary outcome will be the percentage of complete resections, based on transvaginal ultrasonography 6 weeks postoperatively. Secondary outcomes are cost effectiveness, menstrual blood loss (Pictorial blood assessment chart), quality of life, pain, return to daily activities/work, hospitalization, (post) operative complications and re-interventions. Women will be followed up to one year after hysteroscopic myomectomy. DISCUSSION: This study may demonstrate comparable effectiveness of hysteroscopic myomectomy under procedural sedation and analgesia versus general anaesthesia in a safe and patient friendly environment, whilst achieving a significant cost reduction. TRIAL REGISTRATION: Dutch trial register, number NTR5357 . Registered 11th of August 2015

The (cost) effectiveness of procedural sedation and analgesia versus general anaesthesia for hysteroscopic myomectomy, a multicentre randomised controlled trial : PROSECCO trial, a study protocol

BACKGROUND: In women with abnormal uterine bleeding, fibroids are a frequent finding. In case of heavy menstrual bleeding and presence of submucosal type 0-1 fibroids, hysteroscopic resection is the treatment of first choice, as removal of these fibroids is highly effective. Hysteroscopic myomectomy is currently usually performed in the operating theatre. A considerable reduction in costs and a higher patient satisfaction are expected when procedural sedation and analgesia with propofol (PSA) in an outpatient setting is applied. However, both safety and effectiveness - including the necessity for re-intervention due to incomplete resection - have not yet been evaluated. METHODS: This study is a multicentre randomised controlled trial with a non-inferiority design and will be performed in the Netherlands. Women > 18 years with a maximum of 3 symptomatic type 0 or 1 submucosal fibroids with a maximum diameter of 3.5 cm are eligible to participate in the trial. After informed consent, 205 women will be randomised to either hysteroscopic myomectomy using procedural sedation and analgesia with propofol in an outpatient setting or hysteroscopic myomectomy using general anaesthesia in a clinical setting in the operating theatre. Primary outcome will be the percentage of complete resections, based on transvaginal ultrasonography 6 weeks postoperatively. Secondary outcomes are cost effectiveness, menstrual blood loss (Pictorial blood assessment chart), quality of life, pain, return to daily activities/work, hospitalization, (post) operative complications and re-interventions. Women will be followed up to one year after hysteroscopic myomectomy. DISCUSSION: This study may demonstrate comparable effectiveness of hysteroscopic myomectomy under procedural sedation and analgesia versus general anaesthesia in a safe and patient friendly environment, whilst achieving a significant cost reduction. TRIAL REGISTRATION: Dutch trial register, number NTR5357 . Registered 11th of August 2015

Looking at Zagreb: The Italian State as a Popularizer of Contemporary Art

In 1965, at the 12th International Conference of Critics, Artists and Art Scholars, held in Rimini, Verucchio and San Marino and devoted to the theme Art and Technology, Italian art critic Giulio Carlo Argan declared that Yugoslavia had overcome the problem of the relationship between art and technology. His statement concerned to the cultural milieu of Zagreb that Argan had known from the early Sixties. In the same year, Palma Bucarelli, the chief curator of the Rome National Gallery, attended the Brezovica conference held for Nova tendencija 3, to present a project in which the museum had a significant role as a state institution that had to encourage contemporary art in order to free artists from the pressures of the art market and private art galleries. In 1963, another art scholar, Umbro Apollonio, the curator of the Venice Biennale Archive for Contemporary Arts who had directly participated in the Venice exhibition Nuova tendenza 2, claimed that Italian Public Art School needed a new relationship between teaching and industries. My presentation aims to highlight how Argan, Bucarelli, Apollonio and other Italian scholars hoped for the state to intervene in the Italian art system and also how their ideas were inspired by the Croatian political and cultural situation of the 1960s