PubMed | Medical Oncology, Institute for Cancer Research and Treatment IRCCS, Italian National Cancer Institute, University of Verona and 13 more.
Type: | Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association | Year: 2016
Although second-line therapy is often considered for advanced gastric cancer patients, the optimal candidates are not well defined.We retrospectively collected baseline parameters, tumour features, and treatment data for 868 advanced gastric cancer patients exposed to multiple treatment lines at 19 Italian centres. Cross-tables and chi-square tests were used to describe categorical features. To predict the impact of clinical variables on progression-free survival and overall survival, Kaplan-Meier and Cox regression analyses were performed.At the start of second-line therapy, median age was 64.8years (25th-75th percentiles: 55.2-71.9years). Overall, 43% of patients received single-agent chemotherapy, 47.4% a doublet, and 7.3% a triplet. Median second-line progression-free survival was 2.8months (25th-75th percentiles: 1.8-5.2months) and median second-line overall survival was 5.6months (25th-75th percentiles: 2.9-10.0months). Multivariate analysis showed that performance status, LDH level, neutrophils/lymphocytes ratio, and progression-free survival in the first-line therapy all impacted on prognosis. Based on these four prognostic factors, a prognostic index was constructed that divided patients into good, intermediate, and poor risk groups; median second-line overall survival for each group was 7.7, 4.5, and 2.0months, respectively (log-rank p<0.0001).Advanced gastric cancer patients with a favourable ECOG performance status, lower LDH levels, and a lower neutrophils/lymphocytes ratio at the start of second-line therapy seem to have better outcomes, regardless of age and intensity of treatment. A longer progression-free survival in the first-line therapy also had positive prognostic value. Our real-life study might help clinicians to identify the patients who may benefit most from a second-line therapy.
PubMed | Sloan Kettering Cancer Center, Medical Oncology and Hematology Unit and University of Bologna
Type: Review | Journal: Liver cancer | Year: 2016
Western and Eastern perspectives on therapeutic guidelines for hepatocellular carcinoma (HCC) have many commonalities but may also differ in certain aspects, as described in this article. In view of the limited therapeutic options for advanced HCC, evidence-based therapies are few, and thus there is a dependence on consensus-based guidelines. This article focuses on the Italian Association for the Study of the Liver guidelines and the Japanese approaches to therapy, while drawing attention to certain controversies from other academic bodies where applicable and appropriate.
PubMed | Humanitas Clinical and Research Center, Karolinska Institutet, Marche Polytechnic University, Medical Oncology and Hematology Unit and 6 more.
Type: Journal Article | Journal: Clinical and experimental immunology | Year: 2016
The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC)>070 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between PSC and CC. After the validation phase, miR-200c was found to be expressed differentially in PSC versus controls, whereas miR-483-5p and miR-194 showed deregulated expression in CC compared with controls. We also demonstrate a difference in the expression of miR-222 and miR-483-5p in CC versus PSC. Combination of these specific miRNAs further improved the specificity and accuracy of diagnosis. This study provides a basis for the use of miRNAs as biomarkers for the diagnosis of PSC and CC.
PubMed | University of Udine, Azienda Ospedaliero Universitaria Pisana, Medical Oncology and Hematology Unit, Polo Oncologico and 4 more.
Type: Journal Article | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2015
The prognosis of brain metastases (BM) in colorectal cancer (CRC) is extremely poor, but the incidence is increasing. The performance of existing prognostic classifications such as recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) has never been evaluated in this specific setting. Moreover, the development of nomograms for estimating survival in such patients could be extremely helpful for treating physicians.Between 2000 and 2013, data from 227 patients with BM from CRC were collected at 8 Italian institutions. Overall survival (OS) was estimated with the Kaplan-Meier method and statistical comparison between curves was performed using the log-rank test. The discriminative ability for OS of RPA and GPA was assessed by the Harrell C-index from univariable Cox models. Putative prognostic factors for OS were also studied by multivariable Cox analysis, using the Harrell C index to evaluate the model discriminative ability. After a backward variable selection, a nomogram was developed to predict median survival time from individual patient- and tumor-related characteristics. The nomogram was externally validated on an independent series.After a median follow-up of 59 months, fifty percent of patients were still at risk at 5 months. The C index was 0.594 and 0.607 for the RPA and GPA classifications, respectively. The C-index associated with the final multivariable Cox model used for developing the nomogram was 0.643; the favorable prognostic factors for survival were lower age (p=0.061), better Karnofsky performance status (p<0.001), supratentorial site of BM (p<0.001), and lower number of BM (p=0.035). The C index evaluated on the validation series was 0.733, even better than in the development series; also, the calibration of nomogram predictions was good.The C-index associated to the nomogram model was slightly higher than that obtained for the RPA and GPA classifications. Most importantly, the very satisfactory results of nomogram validation on the external series, make us confident that our instrument may assist in prognostic assessment, treatment decision making, and enrollment into clinical trials.
PubMed | Medical Oncology, Fondazione Instituto Nazionale Tumori IRCCS, Medical Oncology Unit, Medical Oncology and Hematology Unit and 6 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems.TOSCA [Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data.From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34).TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations.NCT00646607.
Ibatici A.,Medical Oncology and Hematology Unit |
Caviggioli F.,University of Milan |
Valeriano V.,University of Milan |
Quirici N.,University of Milan |
And 6 more authors.
Aesthetic Plastic Surgery | Year: 2014
Background: Autologous fat grafting is a widely adopted surgical technique in both the reconstructive and aesthetic fields. This study aimed to compare centrifuged lipoaspirates harvested and refined by the Coleman technique with noncentrifuged lipoaspirates in terms of cell number and viability, phenotypic profile, and clonogenic and proliferative potential of adipose-derived stem cell (ADSC) populations.Methods: For each patient, both a centrifuged sample using the Coleman’s technique and a noncentrifuged sample of adipose tissue were collected. Adipose-derived stem cells from both the centrifuged fraction (CF) and the noncentrifuged fraction (NCF) were isolated. The recovered ADSCs were used to set up flow cytometry analysis, colony-forming units–fibroblast (CFU-F) assays, and ADSC cultures.Results: The number of recovered cells was variable among the different donors but significantly higher in the CF donors. Cell viability, determined by the Trypan Blue dye assay, always exceeded 95 %, in both the CF and NCF fractions. Analysis of the putative ADSC subpopulations showed a significant enrichment of the mesenchymal and endothelial progenitors in CF compared with NCF. No differences in the clonogenic efficiency of the ADSC samples were observed when the same number of cells were plated from each fraction. On the contrary, when equal fat volumes were compared, the colony-forming ability of CF was always significantly higher than that of its NCF counterparts.Conclusions: This is the first study to comprehensively characterize the impact of Coleman’s technique on the quality of lipoaspirates, showing that centrifugation is safe and feasible and does not impair cell viability, can augment the content in ADSC and the frequency of CFU-F, and reduces the number of proinflammatory blood cells.No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266. © 2014, Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery.
Rimassa L.,Medical Oncology and Hematology Unit |
Pressiani T.,Medical Oncology and Hematology Unit |
Boni C.,Medical Oncology |
Carnaghi C.,Medical Oncology and Hematology Unit |
And 13 more authors.
Oncologist | Year: 2013
Background. Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated. Methods. Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600mgtwice daily (n49) or best supportive care (n52). The primary end point was progression-free survival (PFS). Time to progression, overall survival,andsafetywerealso evaluated. Results. The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%). Conclusions. Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials © AlphaMed Press 2013.
PubMed | Medical Oncology and Hematology Unit
Type: Journal Article | Journal: The International journal of biological markers | Year: 2015
Inhibition of angiogenesis is an effective treatment option for metastatic colorectal cancer. Predictive biomarkers to select patients who are most likely to benefit from this therapeutic strategy are lacking. We conducted a pilot, retrospective biomarker study in a cohort of metastatic colorectal cancer patients treated with bevacizumab. The objectives of this study were to evaluate the prognostic value of biomarker expression in metastases and to compare their expression in paired tumor specimens.Eligible patients were treated with a bevacizumab-containing therapy; from these patients, tumor tissue from metastases was available. PTEN, PI3K p110a, c-MET, and CAIX were analyzed by immunohistochemistry.Forty-two patients received bevacizumab, 13 (31%) with first-line and 29 (69%) with second-line chemotherapy. Expression of CAIX, PI3K p110a, and c-MET in metastases did not predict objective response. PTEN loss was associated with response to treatment (p=0.02) and this association remained significant after adjusting for prognostic variables (p=0.006). However, no association with survival outcomes was found. In 32 patients (76%) with available paired specimens, we observed an equal expression between primary tumors and corresponding metastases in 75% of cases for CAIX in epithelial tumor cells, 56% for CAIX in stromal cells, 63% for PTEN, and 87% for c-MET.PTEN loss in metastases appears to be associated with response to bevacizumab-based therapy. However, larger studies are necessary to confirm the potential role of the PI3K/AKT/mTOR pathway in modulating the therapeutic effect of bevacizumab. Tumor heterogeneity should be taken into consideration when analyzing tumor tissues for biomarker studies.
PubMed | Medical Oncology and Hematology Unit
Type: Clinical Trial, Phase III | Journal: Tumori | Year: 2015
In the last decades the management of hepatocellular carcinoma (HCC) has undergone significant changes following the introduction of novel therapies such as sorafenib, which have improved patient survival. Nevertheless, HCC is still the third most common cause of cancer-related death worldwide. The evidence-based therapy for advanced HCC that is unsuitable for locoregional treatment is limited to sorafenib, with no second-line option available. This article focuses on the development of the MET inhibitor tivantinib in HCC as a promising treatment option for patients who failed sorafenib. A randomized, placebo-controlled phase II study showed activity of tivantinib in patients with high MET expression. Based on these results, the METIV-HCC phase III study in second-line treatment for MET-high patients was initiated to demonstrate the survival advantage of tivantinib compared to placebo.
PubMed | Medical Oncology and Hematology Unit, IRCCS Clinical and Research Institute Humanitas, IRCCS Humanitas Clinical Institute and University of Milan
Type: Journal Article | Journal: Experimental cell research | Year: 2015
cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1. In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.