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Beksac M.,Ankara University | Cavenagh J.,St. Bartholomew's Hospital | Cavo M.,Institute of Hematology and Medical Oncology | Delforge M.,University Hospital Leuven | And 19 more authors.
Oncologist | Year: 2011

The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that have been published or presented at congresses up to the end of 2010 and assesses their impact on treatment practices. © AlphaMed Press.


Ludwig H.,Wilhelminenspital | Avet-Loiseau H.,Institute Of Biologie | Boccadoro M.,University of Turin | Cavenagh J.,St. Bartholomew's Hospital | And 17 more authors.
Oncologist | Year: 2012

The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies. ©AlphaMed Press.


Ludwig H.,Wilhelminenspital | Beksac M.,Ankara University | Boccadoro M.,University of Turin | Cavenagh J.,St. Bartholomew's Hospital | And 19 more authors.
Oncologist | Year: 2010

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents. ©AlphaMed Press.


Ceriani L.,Oncology Institute of Southern Switzerland | Martelli M.,University of Rome La Sapienza | Zinzani P.L.,Institute of Hematology and Medical Oncology | Ferreri A.J.M.,San Raffaele Scientific Institute | And 16 more authors.
Blood | Year: 2015

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cut-off values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567. © 2015 by The American Society of Hematology.


Ludwig H.,Hematology and Palliative Care | Sonneveld P.,Erasmus Medical Center | Davies F.,Royal Marsden Hospital | Boccadoro M.,University of Turin | And 15 more authors.
Oncologist | Year: 2014

The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. © AlphaMed Press.


PubMed | University of Turin, University of Southampton, Instituto Nazionale Tumori Giovanni Paolo II IRCCS, University of Chile and 8 more.
Type: | Journal: International journal of radiation oncology, biology, physics | Year: 2016

To assess the predictive value of Among 125 patients prospectively enrolled in the IELSG-26 study, 88 were eligible for central review of PET/CT scans after completion of RT. Responses were evaluated using the 5-point Deauville scale at the end of induction R-CHT and after consolidation RT. According to the Lugano classification, a complete metabolic response (CMR) was defined by a Deauville score (DS) 3.The CMR (DS1, -2, or -3) rate increased from 74% (65 patients) after R-CHT to 89% (78 patients) after consolidation RT. Among the 10 patients (11%) with persistently positive scans, the residual uptake after RT was slightly higher than the liver uptake in 6 patients (DS4; 7%) and markedly higher in 4 patients (DS5; 4%): these patients had a significantly poorer 5-year progression-free survival and overall survival. At a median follow-up of 60months (range, 35-107months), no patients with a CMR after RT have relapsed. Among the 10 patients who did not reach a CMR, 3 of the 4 patients (positive predictive value, 75%) with DS5 after RT had subsequent disease progression (within the RT volume in all cases) and died. All patients with DS4 had good outcomes without recurrence.All the patients obtaining a CMR defined as DS3 remained progression-free at 5years, confirming the excellent negative predictive value of the Lugano classification criteria in primary mediastinal large B-cell lymphoma patients. The few patients with DS4 also had an excellent outcome, suggesting that they do not necessarily require additional therapy, because the residual


PubMed | Hematology Unit, Medical Oncology Unit, University of Southampton, Azienda Ospedaliera Papardo and 7 more.
Type: Clinical Trial | Journal: Blood | Year: 2015

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567.


Gascon P.,Institute of Hematology and Medical Oncology
Transfusion Alternatives in Transfusion Medicine | Year: 2012

Erythropoiesis-stimulating agents (ESAs) are widely used in oncology to correct the anemia associated with chemotherapy, although only 50-70% of patients show an optimal response, mostly because of functional iron deficiency (FID). As intravenous (IV) iron can overcome this FID, it has become an important adjunct to obtaining and maintaining adequate hemoglobin levels in patients with cancer receiving chemotherapy. In fact, six out of seven published randomized, controlled trials performed in cancer patients have demonstrated that IV iron given concomitantly to ESAs induces a faster and much more robust response than with ESAs alone. The possibility that giving only IV iron can also produce adequate hemoglobin responses requires further studies. However, there still exists some reluctance among many oncologists to use IV iron because of the poor safety profile observed in the past with the old iron preparations, in particular high-molecular-weight iron dextran. As the efficacy and safety of the new iron preparations have been proven, the use of IV iron should be considered in the management of anemia secondary to chemotherapy treatments. © 2012 Medical Education Global Solutions.


PubMed | Institute of Hematology and Medical Oncology
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

15062 Background: At moment chemotherapy treatment of liver metasteses from colorectal cancer is not differentiated between synchronous and methacronous disease. We studied the gene expression profiling of liver metastases in order to identify some molecular differences for differentiating the systemic therapies in these two clinical setting.We collected fresh tissues specimens from 18 patients. We studied 9 synchronous and 7 metachronous lesions with Affymetrix platform. RNA was extracted from frozen tumor specimens, labelled and hybridized to HG-U133Plus 2.0 Affymetrix arrays. Raw data were background-subtracted, normalized and summarized with the RMA algorithm. Routine quality controls were performed. Probes poorly expressed or not differential in all the samples were excluded from further analysis. A moderated t-statistic test was used to identify genes differentially expressed setting the significance threshold at p <0.01. All the analyses were performed with R and Bioconductor packages. PCA analysis and hierarchical clustering was performed with TIGR MeV and functional classification of differential genes with EASE tool.Supervised analysis identified 245 probes differentially expressed between synchronous and metachronous metastases. Synchronous lesions overexpress COX2, FLT1 and Cyr61 that are strongly implicated in the metastatic process, as cell adhesion, response to wounding, cell motility, immune response, angiogenesis and matrix remodelling. While metachronous lesions overexpress EGFR and genes related to its signaling pathway such as Jak1, PI3K, Jun. Realtime-PCR determinations of these molecules are on going in order to confirm the microarray data.Some interesting differences of gene expression profiling were found between synchronous and metachronous metastases. It may suggest that medical treatments of patients affected by metastatic colorectal cancer should be differentiated considering the different biological background, for example based on EGFr pathway inhibition for metachronous mestastases and on angiogenesis inhibition for synchronous metastases.The present results need to be confirmed in larger series and investigated in clinical trials. No significant financial relationships to disclose.

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