Liver metastasectomy for metastatic breast cancer patients: A single institution retrospective analysis

The liver represents the first metastatic site in 5\u201312% of metastatic breast cancer (MBC) cases. In absence of reliable evidence, liver metastasectomy (LM) could represent a possible therapeutic option for selected MBC patients (patients) in clinical practice. A retrospective analysis including MBC patients who had undergone an LM after a multidisciplinary Tumor Board discussion at the Hepatobiliary Surgery Unit of Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS in Rome, between January 1994 and December 2019 was conducted. The primary endpoint was overall survival (OS) after a MBC-LM; the secondary endpoint was the disease-free interval (DFI) after surgery. Forty-nine MBC patients underwent LM, but clinical data were only available for 22 patients. After a median follow-up of 71 months, median OS and DFI were 67 months (95% CI 45\u2013103) and 15 months (95% CI 11\u201346), respectively. At univariate analysis, the presence of a negative resection margin (R0) was the only factor that statistically significantly influenced OS (78 months versus 16 months; HR 0.083, p < 0.0001) and DFI (16 months versus 5 months; HR 0.17, p = 0.0058). A LM for MBC might represent a therapeutic option for selected patients. The radical nature of the surgical procedure performed in a high-flow center and after a multidisciplinary discussion appears essential for this therapeutic option

Postdemokratie und Engaged Citizenship. Optionen zivilgesellschaftlichen Protests am Beispiel des europäischen Attac-Netzwerkes

Der Beitrag thematisiert das europäische Attac-Netzwerk als eine Lernplattform, über die sich engaged European citizenship im als postdemokratisch beschriebenen Kontext konsti­tuiert. Dem diskursiven Erfolg, der die Kritik des Neoliberalismus und einige Forderungen von Attac in eine Mainstream-Position versetzt, steht dabei die Tatsache gegenüber, dass bislang jeglicher realpolitische Niederschlag dieser Kritiken und Forderungen aussteht. Aus dem Fallbeispiel ergeben sich grundsätzliche Überlegungen zu folgenden Fragen: Wie lassen sich gegenwärtige Dilemmata für Engaged Citizenship (eine engagierte BürgerInnenschaft) in Europa vor dem Hintergrund der Postdemokratie-These verstehen? Welches Licht werfen weitere Ansätze, etwa eine gouvernementalistische Perspektive, auf die beschriebenen Bildungsprozesse? (DIPF/Orig.)The article deals with the European Attac network as a learning platform through which engaged European citizenship is constituted in a context described as post-democratic: The discursive success, which puts the critique of neoliberalism and some of Attac‘s claims in a mainstream position, is confronted with the fact that these critiques and claims have not found any expression in politics yet. Fundamental considerations have emerged from this case study concerning the following questions: How can current dilemmas for engaged citizenship in Europe be understood against the background of the post-democratic thesis? What kind of light do further approaches, such as a governmentalist perspective, shed upon the described education processes? (DIPF/Orig.

Prognostic Factors Influencing Tumor Response, Locoregional Control and Survival, in Melanoma Patients with Multiple Limb In-transit Metastases Treated with TNF alpha-based Isolated Limb Perfusion

Background: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF alpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNF alpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable close (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNF alpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFa was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNF alpha-based ILP and identify prognostic factors for response, locoregional control and survival. Patients and Methods: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>= 10 nodules :53 cm or fewer nodules with a diameter > 3 cm) in 42.5% of the patients and unresectable in 33%. Forty patients were treated with a TNFa dosage of > 1 mg and 73 with 1 mg. Patients with tumors in the tipper and lower limbs were submitted to ILP via axillary and iliac vessels, respectively. TNF alpha was injected in the arterial line of an extracorporeal circuit at the pre-established close, followed by melphalan (13 and 10 mg/l of limb volume for the upper and lower limbs, respectively) 30 minutes later. Results: Complete responses (CR) and partial responses (PR) were 63% and 24.5%, respectively, with an objective response (OR) of 87.5%. No change (NC) was observed in only 12.5% of the patients. Upon multivariate analysis, only bulky disease maintained its independent value for tumor response with an odds ratio of 4.07 and a p-value of 0.02. The 5-year locoregional disease-free survival was 42.7%. Upon multivariate analysis, the only prognostic factors were stage, age and bulky disease. The 5-year overall survival was 49%. Multivariate analysis showed that only, sex, stage and CR maintained their independent values. Conclusion: TNF alpha-based ILP was proven to be an effective treatment for melanoma patients with in-transit metastases. The TNF alpha dosage of 1 mg was as effective as 3-4 mg, with lower toxicity and cost. We propose that TNF alpha and melphalan-based ILP should be employed for bulky tumors or after failure of melphalan-based ILP

Upfront HIPEC and bevacizumab-containing adjuvant chemotherapy in advanced epithelial ovarian cancer

INTRODUCTION: In advanced epithelial ovarian cancer patients, the standard of care is primary debulking surgery, followed by first-line chemotherapy often with bevacizumab addiction. In this context, some experiences have shown that a comprehensive treatment approach to surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) could improve the prognosis. OBJECTIVE: This is a study aimed to explore the feasibility of primary debulking surgery and HIPEC upfront followed by first-line therapy with bevacizumab. STUDY DESIGN: Phase II monocentric, open label, non-randomised and single-arm study. Forty patients affected by advanced ovarian cancer submitted to primary debulking surgery with HIPEC were enrolled in the study. After surgery, all patients underwent systemic chemotherapy with bevacizumab addiction. RESULTS: Complete cytoreduction (RT\u2009=\u20090) was achieved in all cases. Treatment-related early complications were observed in 23 patients and in 15 cases were G1-G2. Major complications were reported in 8 patients. No postoperative death was recorded. Subsequent chemotherapy was administered in all cases. Median time between surgery and first cycle of chemotherapy was 42\u2009days (range 30-76). Concomitant bevacizumab was administered in 34 patients (85%). Maintenance with bevacizumab was feasible in 33 patients (82.5%) and its withdrawal was necessary for 1 patient (2.5%) due to G3 hypertension. CONCLUSION: Our data suggest that HIPEC can be safely introduced in the upfront therapy of advanced ovarian cancer

Dabrafenib-Trametinib and Radiotherapy for Oligoprogressive BRAF Mutant Advanced Melanoma

The clinical management of metastatic melanoma has been changed by BRAF (BRAFi) and MEK inhibitors (MEKi), which represent a standard treatment for BRAF-mutant melanoma. In oligoprogressive melanoma patients with BRAF mutations, target therapy can be combined with loco-regional radiotherapy (RT). However, the association of BRAF/MEK inhibitors and RT needs to be carefully monitored for potential increased toxicity. Despite the availability of some reports regarding the tolerability of RT + target therapy, data on simultaneous RT and BRAFi/MEKi are limited and mostly focused on the BRAFi vemurafenib. Here, we report a series of metastatic melanoma patients who received fractioned RT regimens for oligoprogressive disease in combination with the BRAFi dabrafenib and the MEKi trametinib, which have continued beyond progression. None of the cases developed relevant adverse events while receiving RT or interrupted dabrafenib and trametinib administration. These cases suggest that a long period of dabrafenib/trametinib interruption during radiotherapy for oligoprogressive disease can be avoided. Prospective trials are warranted to assess the efficacy and safety of the contemporary administration of BRAF/MEK inhibitors and radiotherapy for oligoprogressive disease