Search

Lessons Learned Background The objectives of this study were to compare the safety profiles of sodium levofolinate (Na-Lev) and calcium levofolinate (Ca-Lev) in combination with 5-fluorouracil (5-FU) in the FOLFIRI regimen and to measure the organizational impact of the introduction of Na-Lev on drug production and administration. Methods The study opened in November 2015 and closed in August 2019. Patients with gastrointestinal cancers who were candidates for treatment with the FOLFIRI regimen were included in this nonrandomized study. Age ≥18 years, life expectancy Results Sixty patients were enrolled, 30 in each arm. Patient characteristics were balanced. Grade (G)1–2 adverse events occurred in 18 (60.0%) and 19 (63.4%) patients of Na-Lev and Ca-Lev cohorts, respectively, whereas G3–4 adverse events occurred in 12 (40.0%) and 11 (36.6%) patients, respectively. The use of Na-Lev enabled us to save approximately 13 minutes for drug preparation and 2 hours for treatment administration, per patient per cycle. Conclusion Na-Lev showed a reassuring toxicity profile and a favorable impact on drug preparation and administration.

In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1–65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8–13.2) and 14.3 (95% CI 12.0–18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6–33.0), and the R0 resection rate was 13.7% (95% CI 5.8–21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19–9 were associated with improved OS and PFS. Concerning OS, log(CA19–9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02–1.42), p = 0.027. For ECOG PS 0, HR was 1.00, for PS 1, HR was 2.69 (95% CI 1.46–4.96), for PS 2, HR was 4.18 (95% CI 0.90–19.46), p = 0.003. Low CA19–9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52–0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.

to examine the factors that, in the context of the current pandemic, have influenced the conduct of a randomized clinical trial on hydroxychloroquine in Italy.the trend of enrolment in the PROTECT study, "A randomized study with Hydroxychloroquine versus observational support for prevention or early phase treatment of Coronavirus disease (COVID-19)" (Eudract number: 2020-001501-24, NCT04363827), conducted in the period from May to September 2020, was analysed to evaluate the possible association of the enrolment rate with the amount of information published in the national and local press on hydroxychloroquine.the PROTECT clinical study is an Italian interventional superiority study, open label, with cluster randomization, aimed at evaluating whether treatment with hydroxychloroquine can reduce the percentage of symptomatic subjects compared to observation only in a population of subjects exposed to SARS-CoV-2 virus consisting of cohabitants/contacts of COVID-19 patients and asymptomatic or paucisymptomatic subjects diagnosed with COVID-19.the number of asymptomatic or paucisymptomatic COVID-19 patients and the number of contacts/cohabitants of COVID-19 patients enrolled in the Protect study from May to September 2020.from May to September 2020, the number of patients diagnosed with COVID-19 enrolled in the PROTECT clinical trial showed a decrease consistent with the number of news on hydroxychloroquine appearing in the national and local press, starting from the time when the first criticisms of the efficacy of hydroxychloroquine were made known; the number of contacts/cohabitants of COVID-19 patients showed a more marked and more timely decrease.in the context determined by the current COVID-19 pandemic, conducting a controlled clinical trial is strongly influenced by public opinion on scientific issues. Adherence to a clinical study can become highly problematic and invalidate the possibility of answering a scientific question and the validity of a project. In the current pandemic situation, randomized controlled trials may not always be the optimal tool to reach the expected scientific evidence, due to a number of problems. It is preferable to use a sequential or adaptive design. Furthermore, study protocols should implement innovative approaches that also include the involvement of participants in the decision-making process. In any case, the influence of public information on scientific issues is an extremely important factor to consider in the design of clinical trials in exceptional situations such as a pandemic.

Aims: We created a new index (Multi Inflammatory Index, MII) composed of an inflammatory index [neutrophil-to lymphocyte-ratio (NLR): MII-1; platelet-to-lymphocyte ratio (PLR): MII-2; or systemic immune-inflammation index (SII): MII-3] and C-reactive protein (CRP). Our aim was to evaluate the prognostic and/or predictive capacity of the MII in the randomized ITACa (Italian Trial in Advanced Colorectal Cancer) study on patients with metastatic colorectal cancer undergoing first-line chemotherapy. Methods: Between November 2007 and March 2012, baseline NLR, PLR; SII and CRP were available for 131 patients, 66 receiving chemotherapy plus bevacizumab and 65 receiving chemotherapy alone. Results: Patients with low (Conclusion: All MII indexes appear to be useful as prognostic markers. Trial registration ClinicalTrials.gov identifier: NCT01878422 (registration date: 07/06/2013) https://clinicaltrials.gov/ct2/show/NCT01878422

The use of liquid biopsy in the clinical management of colorectal cancer (CRC) patients is not yet a routine clinical practice, although it could give important information for tumor baseline characterization and for monitoring during treatment. In this retrospective exploratory study, we examined plasma-circulating tumor DNA (ctDNA) in a series of 27 metastatic CRC patients receiving chemotherapy plus bevacizumab as firstline treatment, both at baseline and at progression. All patients were characterized for RAS and BRAF status on tumor tissue before the start of treatment: 70% of patients were RAS-mutated(16 KRAS, 3 NRAS),15% were BRAF mutated and 15% were RAS/BRAF wild-type. Detection of ctDNA mutations were performed using Oncomine™Colon cfDNA Assay on Ion GeneStudio™ S5 System (Thermofisher). All mutations observed in the tissue were identified also in the baseline ctDNA, excluding one BRAF mutated case that was not detected in the ctDNA. Additional mutations on TP53, APC, PIK3CA, FBXW7 were detected respectively in 11, 12, 3 and 2 cases. TP53 mutations were identified also in 3 RAS/BRAF wild-type cases. Baseline RAS/BRAF variant allele frequency (VAF) lower than 10% was found associated with longer progression free survival (PFS) (log-rank p-value=0.027) (Table 1). At progression, 80% of patients carried the same mutations identified at baseline, and 7 cases carried additional mutations of TP53. Predominantly mutations has a lower VAF at progression with respect to baseline, however RAS/BRAF VAF at progression was found not associated with PFS. In conclusion, we report a concordance-rate >96% between ctDNA and tissue demonstrating the high sensibility of liquid biopsy for detection of mutations in metastatic CRC. Thus, ctDNA could be useful for monitoring of minimal residual disease and tumor heterogeneity during therapeutic treatment. These data, if confirmed in a larger cohort, might support the use of liquid biopsy in the clinical management of CRC patients. Table 1.Relationships between RAS/BRAF mutation VAF and progression free survival during treatmentTimeConditionN. of casesMedian PFS (range), daysχ2p-valueBaselineVAF10%11373 (41-719)ProgressionVAF10%8412 (41-843) Citation Format: Milena Urbini, Giorgia Marisi, Alessandro Passardi, Chiara Molinari, Matteo Canale, Laura Matteucci, Gianluca Tedaldi, Giovanni Martinelli, Giovanni L. Frassineti, Ulivi Paola. Liquid biopsy for molecular characterization and monitoring in patients with metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 541.

Objective Neoadjuvant chemotherapy plus interval debulking surgery is growing treatment strategy for advanced ovarian cancer patients with unresectable disease. Here, we aimed to assess predictors of surgical unresectability and survival of patients submitted to neoadjuvant chemotherapy plus interval debulking surgery. Methods Data of consecutive 193 patients undergoing neoadjuvant chemotherapy plus interval debulking surgery were retrospectively evaluated in four Italian oncologic centers. RECIST 1.1 guidelines were used to assess response to neoadjuvant chemotherapy. Survival outcomes were evaluated using Kaplan-Meier and Cox proportional hazard models. Results Overall, 155 (80.3%) and 38 (19.7%) patients had optimal and non-optimal cytoreduction at the time of interval debulking surgery. Via multivariate analysis, age (OR: 2.87 (95%CI: 1.29, 6.36) per 10-year increase) and radiological response to neoadjuvant chemotherapy (OR: 48.1 (95%CI: 6.33, 365.3)) impact on the inability to perform a complete cytoreduction. Patients having complete or partial response experienced a significant better disease-free survival than patients having stable or progressive disease at radiological examination (median disease-free survival 16.8 vs. 11.0 months; HR: 0.42 (95%CI: 0.09, 0.78); p = .001). Radiological response did not predict for overall survival (p = .719). Conclusions RECIST1.1 response criteria might be helpful to predict surgical resectability and disease-free survival of advanced stage ovarian cancer patients undergoing neoadjuvant chemotherapy plus interval debulking surgery.

High inter-patient variability and high spatial heterogeneity are features of colorectal cancer (CRC). This may influence the molecular characterization of tumor tissue, now mandatory for patients with metastatic CRC who are candidates for treatment with an anti-EGFR mAb, as false-negative results can occur, leading to non optimal therapy. Moreover, temporal molecular heterogeneity during treatment is known to influence the response to therapy and prognosis. We present a literature overview of advances made in characterizing molecular heterogeneity in CRC, underlining that the analysis of liquid biopsy could represent an efficient non-invasive tool to overcome the problem. We believe that understanding CRC heterogeneity is fundamental for a more accurate diagnosis, for selecting the best targets to ensure prolonged antitumor response, and for monitoring minimal residual disease and the onset of resistance to therapy, all essential components of successful personalized treatment.

ObjectiveThe aim of the study was to evaluate outcomes of patients with unresectable advanced ovarian cancer experiencing complete response (CR) to neoadjuvant chemotherapy.MethodsData of consecutive patients undergoing neoadjuvant chemotherapy plus interval debulking surgery (IDS) were retrospectively reviewed in 4 Italian centers. Using a propensity-matching algorithm, we compared data of patients achieving CR with neoadjuvant chemotherapy (no macroscopic either microscopic residual disease (RD) at the time of IDS) with patients achieving partial response (PR). This latter group was stratified by the presence of RD (RD = 0 vs RD > 0).ResultsOverall, 193 had IDS after neoadjuvant chemotherapy: 25 (13%), 81 (41.9%), and 74 (38.3%) patients had CR, PR with RD of 0, and PR with RD of more than 0, respectively. In addition, 13 (6.7%) patients had no macroscopic disease detected at DS but just microscopic disease at pathological examination. For the study purpose, 25 patients achieving CR were matched (1:2) with 50 patients having PR and RD of 0 and 50 patients having PR and RD of more than 0. As the result of propensity matching, baseline characteristics were similar between groups. Comparing survival outcomes of patients having CR and PR with RD of 0, we observed that type of response to chemotherapy did not influence disease-free (hazard ratio = 1.53 [95% confidence interval = 0.88–2.66], P = 0.127) and overall (hazard ratio = 1.74 [95% confidence interval = 0.76–4.01], P = 0.189) survivals. Patients achieving CR experienced significantly better disease-free survival (P = 0.004) and a trend toward better overall survival (P = 0.06) than patients achieving PR with RD of more than 0 at IDS.ConclusionsComplete cytoreduction might mitigate the difference in response to neoadjuvant chemotherapy. The presence of RD at IDS is associated with worse survival outcomes.

ObjectivesNeoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) may be a valuable treatment option in advanced ovarian cancer when primary cytoreduction is not feasible. However, a consensus on the ideal number of NACT cycles is still lacking. In the present investigation, we aimed to evaluate how number of cycles of NACT influenced patients' outcomes.MethodsData of consecutive patients undergoing NACT and IDS were retrospectively reviewed in 4 Italian centers, and survival outcomes were evaluated.ResultsOverall, 193 patients were included. Cycles of NACT were 3, 4, and at least 5 in 77 (40%), 74 (38%), and 43 (22%) patients, respectively. Patients undergoing 3 cycles experienced a similar disease-free survival (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.89–1.65; P = 0.20) but an improved overall survival (HR, 1.64; 95% CI, 1.05–2.4; P = 0.02) in comparison to patients receiving at least 4 cycles. Five-year overall survival was 46% and 31% for patients having 3 and at least 4 cycles. Ten-year overall survival was 26% and 18% for patients having 3 and at least 4 cycles (HR, 1.70; 95% CI, 1.13–2.55; P = 0.009). Using multivariate analysis, we observed that only Eastern Cooperative Oncology Group performance status correlated with overall survival (HR, 1.76; 95% CI, 1.2–2.49; P = 0.001). In addition, a trend toward worse overall survival was observed for patients with residual disease at IDS (HR, 1.29; 95% CI, 0.98–1.70; P = 0.06) and patients receiving at least 4 cycles (HR, 1.76; 95% CI, 0.95–3.22; P = 0.06).ConclusionOur data underline the potential implication of number of cycles of NACT before IDS. Further prospective studies are warranted to assess this correlation.

This paper focuses on the notion of experience, whose conceptual analysis seems to be often neglected or at least not sufficiently made explicit in the current discourse on Everyday Aesthetics. In our investigation this notion will be tackled, in particular, through the lens of such concepts as Erlebnis, Erfahrung, and Lebenswelt, which are drawn from the continental philosophical tradition. Purpose of the paper is to present a provisional framework aimed at clarifying that a more accurate conceptualization of experience allows for a better contemporary reflection on the aesthetics of everyday life.