Dose-Dense Nonpegylated Liposomal Doxorubicin and Docetaxel Combination in Breast Cancer: Dose-Finding Study AUTHOR SUMMARY

ABSTRACT Background. Anthracyclines and taxanes are effective drugs in breast cancer (BC), but their toxicity profiles limit their use in combination. A dose-finding study was performed to determine maximum tolerated doses (MTDs) of nonpegylated liposomal doxorubicin (TLC-D99) and docetaxel (DTX) as a dose-dense schedule, to maintain dose intensity, and to limit toxicity, particularly cardiac. Methods. Twenty-four patients were enrolled, 12 with metastatic BC, 5 with locally advanced BC, and 7 with early BC. An intra-and interpatient approach was planned in two sequential steps. In the first step,TLC-D99 was administered at dose levels of 40, 45, and 50 mg/m 2 plus DTX at a fixed dose of 50 mg/m 2 . In the second step,TCL-D99 was administered at the dose established in the first step plus DTX at dose levels of 55, 60, and 65 mg/m 2 . Every treatment cycle was delivered on day 1 every 14 days. Pegylated granulocyte colony-stimulating factor was scheduled on day 2. Dose-limiting toxicities (DLTs) were defined as G4 hematological; G3 nonhematological; $10$20% left ventricular ejection fraction (LVEF) reduction if the final value was ,50% or $50$20% LVEF reduction in 1 patient and symptomatic arrhythmia in another; 2 incidences of G4 neutropenia (8.3%); and 1 occurrence of G3 asthenia (4.2%) were reported. MTDs were not reached. The recommended doses were established as TLC-D99 50 mg/

Dose-Dense Nonpegylated Liposomal Doxorubicin and Docetaxel Combination in Breast Cancer: Dose-Finding Study AUTHOR SUMMARY

ABSTRACT Background. Anthracyclines and taxanes are effective drugs in breast cancer (BC), but their toxicity profiles limit their use in combination. A dose-finding study was performed to determine maximum tolerated doses (MTDs) of nonpegylated liposomal doxorubicin (TLC-D99) and docetaxel (DTX) as a dose-dense schedule, to maintain dose intensity, and to limit toxicity, particularly cardiac. Methods. Twenty-four patients were enrolled, 12 with metastatic BC, 5 with locally advanced BC, and 7 with early BC. An intra-and interpatient approach was planned in two sequential steps. In the first step,TLC-D99 was administered at dose levels of 40, 45, and 50 mg/m 2 plus DTX at a fixed dose of 50 mg/m 2 . In the second step,TLC-D99 was administered at the dose established in the first step plus DTX at dose levels of 55, 60, and 65 mg/m 2 . Every treatment cycle was delivered on day 1 every 14 days. Pegylated granulocyte colony-stimulating factor was scheduled on day 2. Dose-limiting toxicities (DLTs) were defined as G4 hematological; G3 nonhematological; $10$20% left ventricular ejection fraction (LVEF) reduction if the final value was ,50% or $50$20% LVEF reduction in 1 patient and symptomatic arrhythmia in another; 2 incidences of G4 neutropenia (8.3%); and 1 occurrence of G3 asthenia (4.2%) were reported. MTDs were not reached. The recommended doses were established as TLC-D99 50 mg/

Anthracycline-Free Neoadjuvant Treatment in Patients with HER2-Positive Breast Cancer: Real-Life Use of Pertuzumab, Trastuzumab and Taxanes Association with an Exploratory Analysis of PIK3CA Mutational Status

HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results

Secondary endovascular procedures improve overall patency and limb salvage in patients undergoing in situ saphenous vein infragenicular bypass

BACKGROUND: Secondary interventions strongly improves patency and limb salvage rates in patients undergoing infrainguinal vein bypass. The aim of this study was to evaluate the influence of secondary endovascular procedures performed during the follow-up on patency and limb salvage in patients with critical limb-threatening ischemia (CLTI) undergoing in situ saphenous vein infragenicular bypass. METHODS: From January 2018 to December 2019 541 patients in 43 centers have been enrolled into the LIMBSAVE registry (treatment of critical Limb IschaeMia with infragenicular Bypass adopting in situ SAphenous VEin technique). In all patients a strict surveillance program with Duplex scan was established (1, 3, 6, 9, 12, 18, 24 months). During the follow-up indications for endovascular procedures were anastomotic stenoses, improvement of run-in (iliac stenosis) or run-off (tibial vessels' stenoses or occlusions). Two-year estimated outcomes in terms of overall patency, and limb salvage were analyzed by life-table analysis (Kaplan-Meier test). Outcomes obtained in patients undergoing endovascular procedure (Group-endo) were compared by means of Gehan-Breslow-Wilcoxon Test with those obtained in patients with no secondary RESULTS: Two groups were homogeneous in terms of demographics and intraprocedural details. Overall mean duration of follow-up was 12.1 months (range 1-24). During the follow-up period (>30 days) 55 endovascular procedures were performed in 49 patients (9.1%) (Group-endo). Most of endovascular procedures (37/55, 67.3%) was performed to treat stenoses at proximal or distal anastomosis. Secondary endovascular procedures (40/55, 72.7%) were predominantly performed within 6 months from the index procedure. Estimated 2-year overall patency (97.9% vs. 85.2%, P=0.05), and limb salvage (100% vs. 93.9%, P=0.05) rates were significantly better in Group-endo. CONCLUSIONS: Secondary endovascular procedures in patients with CLTI undergoing in situ saphenous infragenicular bypass significantly improve the rates of overall patency and limb salvage in the mid-term period. improve overall patency and limb salvage in patients undergoing in situ saphenous vein infragenicular bypass. J Cardiovasc Surg 2023;64:430-6. DOI

Factors Affecting Patency of In Situ Saphenous Vein Bypass: Two Year Results from LIMBSAVE (Treatment of critical Limb Ischaemia with infragenicular Bypass adopting in situ SAphenous VEin technique) Registry

objective: the aim was to demonstrate contemporary outcomes of in situ saphenous vein bypass using a valvulotome.methods: analysis of two year outcomes of a multicentre registry based on the treatment of critical limb ischaemia with infragenicular bypass adopting in situ SAphenous VEin technique (LIMBSAVE). Between January 2018 and december 2019, 541 patients in 43 centres were enrolled. In all patients an innovative valvulotome was used. early outcomes were assessed. two year outcomes according to KaplaneMeier curves in terms of patency and limb salvage were evaluated. Associations between patient and procedure variables were analysed with univariable and multivariable analyses.results: In all cases, a valvulotome was able to lyse the valves. vein injury due to the in situ technique was 3.5%. Thirty day mortality and major amputation rates were 3% and 0.9%, respectively. Mean follow up was 12.1 months. Two year estimated primary patency, primary assisted patency, secondary patency, and limb salvage were 69.1%, 81.4%, 86.5%, and 94.5%, respectively. multivariable analysis showed an association between pre-operative vein diameter < 3 mm and lower primary patency (hazard ration [HR] 14.3, p <.001), primary assisted patency (HR 9.4, p = .002), secondary patency (HR 7.2, p =. 07), and limb salvage (HR 7.8, p = .005) rates. distal anastomosis to a tibial or foot vessel was also associated with lower primary patency (HR 4.8, p = .033), and primary assisted patency (HR 6, p = .011) rates. Use of a suprafascial tributary collateral as a graft was associated with lower primary patency (HR 6.7, p = .013), and primary assisted patency (HR 4.2, p = .042) rates.conclusion: vein diameter < 3 mm, distal anastomosis on a tibial or foot vessel, and use of a suprafascial tributary collateral as a graft were significantly associated with loss of patency and limb loss during follow up

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

Background: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Società Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). Methods: A questionnaire consisting of 26 statements was developed, validated by an 18-member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when ≥70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. Results: Two-hundred-forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first-round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). Conclusions: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available

RIvaroxaban and VAscular Surgery (RIVAS): insights from a multicenter, worldwide web-based survey

no abstract availabl