Manzoni M.,Science Oncologia |
Mariucci S.,Science Oncologia |
Delfanti S.,Science Oncologia |
Rovati B.,Science Oncologia |
And 5 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012
Background: Bevacizumab has shown consistent clinical efficacy in metastatic colorectal cancer (mCRC), but some patients respond better than others. Thus, it is crucial to identify biomarkers that permit the recognition of potentially responsive subjects and to spare toxicity in those who are unlikely benefit from treatment. Methods: In 24 mCRC patients undergoing Bevacizumab-based first-line treatment, we assessed by multiparameter flow cytometry changes in circulating endothelial cell (CEC) number, their apoptotic fraction (APO-CEC) and their mutual relationship. Data were compared with those from a group of 21 healthy subjects. Results: CECs and APO-CECs were higher in patients versus controls (p = 0.01 and p>0.05, respectively). The increase in CECs at the 3rd cycle in complete response (CR) patients was statistically significant (p = 0.048). A better progression-free survival was evidenced in patients that showed an increase in CECs at the 6th cycle (p = 0.009). Regarding the changes in CECs and APO-CECs, a strong correlation was evidenced, at baseline, both in the global population (0.002; r: 0.53) and in the CR subgroup (p: 0.02; r: 0.77). In the partial response + stable and progression disease (SD + PD) subgroup, this correlation was highly significant at the 6th cycle (p: 0.001; r: 0.83). Conclusions: We confirmed the predictive role of an increase in CECs in mCRC patients treated with Bevacizumab- based therapy and showed that modifications in CECs and APO-CECs are independent factors. This underlines the relevance of a simultaneous quantitative and functional evaluation of these biomarkers in view of their possible diagnostic utility. © Springer-Verlag 2012.
Pedrazzoli P.,Science Oncologia |
Comoli P.,Pediatric Hematology Oncology |
Montagna D.,University of Pavia |
Demirer T.,Uludag University
Bone Marrow Transplantation | Year: 2012
Among the novel biological therapeutics that will increase our ability to cure human cancer in years to come, adoptive cellular therapy is one of the most promising approaches. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. The results obtained with tumor-infiltrating lymphocytes therapy for melanoma, and virus-specific CTLs for EBV-associated malignancies are encouraging in terms of both ability to obtain clinical benefit and limited toxicity profile. In both settings, objective responses were obtained in at least 50% of treated patients. However, improvements to the clinical protocols, in terms of better patient selection and timing of administration, as well as cell product quality and availability, are clearly necessary to further ameliorate outcome, and logistical solutions are warranted to extend T-cell therapy beyond academic centers. In particular, there is a need to simplify cell production, in order to decrease costs and ease preparation. Promising implementations are underway, including harnessing the therapeutic potential of T cells transduced with TCRs directed against shared tumor antigens, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells. © 2012 Macmillan Publishers Limited.
PubMed | U.O. Ematologia con Trapianto di Midollo Osseo e Terapia Intensiva, Science Oncologia, U.O. Ematologia e CTMO, University of Houston and U.O. Multidisciplinare di Patologia Mammaria
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2015
As of today, the level of individualization of cancer therapies has reached a level that 20 years ago would be considered visionary. However, most of the diagnostic, prognostic, and therapy-predictive procedures which aim to improve the overall level of personalization are based on the evaluation of tumor tissue samples, therefore requiring surgical operations with consequent low compliance for patients and high costs for the hospital. Hence, the research of a panel of circulating indicators which may serve as source of information about tumor characteristics and which may be obtainable by a simple withdrawal of peripheral blood today represents a growing field of interest. This review aims to objectively summarize the characteristics of the currently available breast cancer circulating biomarkers, also providing an overview about the multitude of novel potential soluble predictors which are still under evaluation. Specifically, the usefulness of a so-called liquid biopsy will be discussed in terms of improvements of diagnosis, prognosis, and therapy-prediction, but an overview will be given also on the potentiality of the molecular characterization arising from the isolation of circulating biomarkers and cells. Although this review will focus on the specific case of the breast, in the future liquid biopsies will hopefully be available for virtually any type of neoplasms.
Miglietta L.,Instituto Nazionale per la Ricerca sul Cancro |
Vanella P.,Instituto Nazionale per la Ricerca sul Cancro |
Canobbio L.,Divisione di Oncologia Medica |
Naso C.,Science Oncologia |
And 4 more authors.
Oncology | Year: 2010
Purpose: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. Patients and Methods: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≥15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. Results: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. Conclusions: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index. © 2011 S. Karger AG, Basel.
Miglietta L.,Science Oncologia Medica A |
Morabito F.,Unita di Emato Oncologia |
Provinciali N.,Divisione di Oncologia Medica |
Canobbio L.,Divisione di Oncologia Medica |
And 6 more authors.
European Journal of Surgical Oncology | Year: 2013
Background Ki-67 expression has gained attention as a breast cancer prognostic factor, however its significance in the remaining malignant cells after neoadjuvant chemotherapy (NAC) has been rarely examined. This investigation, extension and analysis of a previously reported cohort of patients, evaluates the significance of Ki-67 and estrogen receptor (ER) expression after NAC in LABC (locally advanced breast cancer). Patients and methods clinical stage, tumor size, clinical and pathological lymph node involvement, Ki-67, ER, progesterone receptor (PgR), HER2 expression, grading and clinical response were evaluated before and after NAC in 110 patients with LABC. Ki-67 expression was assessed both in pre and post-therapy histological samples, using >15% positive cells as cut-off value to distinguish high from low Ki-67 expressing tumors. Results six patients (5.45%) attained pCR after NAC. A significant relationship between elevated post-CT Ki-67 and ER expression was showed at Cox multivariate analysis of disease free survival (DFS). On univariate analysis high post-chemotherapy Ki-67 and ER status were associated with worse survival; at multivariate model included these results were confirmed. Based on these two parameters, a prognostic model identified two different groups: low risk (low postchemotherapy Ki-67 and ER positive, or either high post-chemotherapy Ki-67 or ER negative), and high risk (high post-chemotherapy Ki-67 and ER negative). The low risk group showed a good prognosis (median OS still not reached), while the high risk group had a worse OS (median 41 months). Conclusions Ki-67 value after NAC and ER status could predict a worse prognosis among LABC patients treated with NAC. © 2013 Elsevier Ltd. All rights reserved.
Numico G.,Science Oncologia |
Silvestris N.,Instituto Oncologico |
Russi E.G.,Science Radioterapia Oncologica
Frontiers in Bioscience - Scholar | Year: 2011
Initial research showed that EGFR targeting through known single agents, both monoclonal antibodies and small-molecule tyrosine-kinase inhibitors, applied to patients with refractory head and neck cancer, resulted in low response rates and short median survival times. However, the combination of Cetuximab with radiotherapy in patients with locally advanced disease and with a combination of platinum and fluorouracil in the setting of relapsed and/or metastatic disease resulted in a sharp improvement compared to standard therapy. Cetuximab entered clinical practice in both indications. Other anti- EGFR drugs, although showing activity, have not demonstrated an improvement of the results of standard therapy. Unfortunately, no molecular parameter emerged as a useful tool in predicting activity, thus impairing clinical applications. Only skin rash was repeatedly shown to be related with drug activity. Although generally well tolerated, class and drug specific toxicities can be troublesome and require knowledge and expertise for an optimal management. Further research is needed in order to find the best ways of integrating the anti-EGFR strategy with current standards of care.
Tampellini M.,SCDU Oncologia |
Ottone A.,SCDU Oncologia |
Alabiso I.,Science Oncologia |
Baratelli C.,SCDU Oncologia |
And 4 more authors.
Tumor Biology | Year: 2015
Serum marker evaluation is an easily available prognostic indicator that may help clinicians to discriminate patients with an aggressive disease; there are few and small-sized studies exploring the prognostic role of baseline carcinoembryonic antigen (CEA) values and their variations during first-line therapy, and even fewer data are available for carbohydrate antigen 19–9 (CA 19-9). Our aim was to analyze the role of those prognostic markers to exploit them in daily clinical practice. Data of 892 patients with marker determination before and 3 and/or 6 months during therapy were extracted from two institutional databases. Patients were grouped according to single marker variation as always negative (G0), decreasing (G1), stable (G2), or increasing (G3). We evaluated the progression-free survival (PFS) and the overall survival (OS) of all the patents and correlated them with CEA and CA 19-9 values. A concordance between response to therapy and marker decrease was evident in 50.2 % and in 34.4 % of the patients for CEA and CA 19-9. Patients with low CEA or CA 19-9 baseline values had a longer PFS (15.1 vs. 10.5; 13.6 vs. 10.2 months) and OS (32.0 vs. 22.3; 30.5 vs. 20.1 months). The same results of PFS and OS were obtained by analyzing the data of the four different groups. Multivariate analyses confirmed the independent prognostic role of CEA and CA 19-9. Baseline CEA and CA 19-9 levels and their kinetics demonstrated to be independent prognostic factors. CA 19-9 dosage is not recommended; a possible role of CA 19-9 in patients with negative CEA could be worth further evaluation. © 2014, International Society of Oncology and BioMarkers (ISOBM).
Comandone A.,Science Oncologia |
Boglione A.,Science Oncologia
Recenti Progressi in Medicina | Year: 2015
GIST (gastrointestinal stromal tumor) are the most common mesenchymal tumors in gastrointestinal tract and are thought to derive from the cells of Cajal or their precursors that have a constitutional mutation in KIT and PDGFRA genes. There are KIT and PDGFRA genes mutations detected before the start of therapy that are believed to be related to GIST pathogenesis and some secondary mutations causing drug resistance and progression of disease. The most common KIT mutations are detected in exon 11 (66-71[%]), exon 9 (10-13[%]), exon 13,14,17 (1[%] each). PDGFRA mutations (8[%]) are described in exon 18 (5-6[%]), 12 (1[%]) and 14 (1[%]). No mutations are detected in 5-10[%] of tumors and those subtypes are called wild type GIST (WT). Imatinib mesilate is a selective inhibitor of KIT and PDGFRA with an antityrosine kinase activity (TKI) used in advanced or metastatic GIST as well as in adjuvant setting after complete resection of neoplasm. Imatinib has radically changed the therapy and prognosis of GIST, but sensitivity of the disease is different on the basis of leading mutations. GIST KIT exon 11 mutated manifests response rate in 80[%] of cases, exon 9 in 40[%] and GIST WT in 14[%]. PDGFRA shows a mild sensitivity to drug (66[%]) except the exon 18 D842 V mutation which is totally resistant. Unfortunately up to 15[%] of GIST have a primary resistance to imatinib that means progression of the disease within 6-12 months after the start of therapy. Another 40-50[%] of GIST develops a secondary resistance after >24 months of TKI treatment. Biopsy of progressing GIST shows multiple clonal origins with distinct mutational changes. Secondary resistance occurs almost exclusively in KIT mutated GIST with the appearances of T670I gatekeeper secondary mutation and less common in 14, 17, 18 exons. After progression of disease second line therapy is represented by sunitinib malate that overcomes the most common resistant mutations excepted PGDFRA D842V. Again, after few months of treatment, new different mutations appear and the disease progresses. Regorafenib is the third line therapy but too few data relates mutational status and regorafenib activity. In adjuvant setting only imatinib has a role. Two important studies (the USA ACOSOG Z 9001 and the German-Scandinavian study) fail to demonstrate that a specific mutation can predict a better DFS and OS in treated patients. On the contrary, volume of the tumor, number of mitosis and site of GIST are strong prognostic and predictive factors. In conclusion mutational analysis in GIST is at present more useful in metastatic setting than in adjuvant therapy. The insurgence of primary and secondary mutations during therapy is a fundamental step for disease progression.
Fatigoni S.,Science Oncologia |
Fumi G.,Science Oncologia |
Roila F.,Science Oncologia
Recenti Progressi in Medicina | Year: 2015
Cancer-related fatigue (CRF) is a very common and distressing symptom experienced by most cancer patients, during and after treatments and also at the end of life. There is no accepted definition of CRF, because it is a multifaceted symptom that involves multiple biopsycho-social aspects. Several scales for assessing CRF have been used, unidimensional or multidimensional, but there is no agreement regarding the best instrument to measure CRF. Concerning the CRF treatment, pharmacologic and non-pharmacologic interventions have been used. Phar-macologic therapies have been evaluated in few randomized clinical trials: corticosteroids demonstrated a superior efficacy to the placebo in terminal cancer patients; psychostimulants (methylfenidate, dexamphetamine, modafinil), antidepressant (paroxetine), acetilcholinesterase inhibitors (donepezil), l-carnitine and coenzyme Q10generally have reported negative results. Non-pharmacologic interventions (physical exercise, psychosocial interventions and other integrative interventions, such as yoga, ginseng, acupuncture) have been evaluated in several randomized and non-randomized studies, but with many methodological limitations. Therefore, the most effective non-pharmacological intervention remains unclear and the effect sizes are small. Further research is needed to delineate the optimal definition, measurement and treatment of CRF.
PubMed | Science Oncologia
Type: Journal Article | Journal: Journal of the National Cancer Institute. Monographs | Year: 2015
The efficacy of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation for breast cancer (BC) has been an area of intense controversy among the medical oncology community. Over the last decade, due to the presentation of negative results from early randomized studies, this approach has not longer been considered an option by the vast majority of medical oncologists. This article is aimed to clarify what happened and where we are now in this not exhausted field.We critically revised the published literature regarding HDC in the setting of high-risk BC, including a recent meta-analysis using individual patient data from 15 randomized studies.A significant benefit by HDC in recurrence-free survival has been clearly documented in unselected patient populations. In HER2-negative population, particularly in the triple-negative disease, a positive effect of intensified therapy in overall survival is biologically plausible and supported by clinical evidence. Over the years HDC with support of adequate number of stem cells has become a safe treatment modality.The administration of higher doses of chemotherapy with stem cell support may still represent a therapeutic option (and not a recommendation) in selected BC patients. This approach should be investigated further.