CRO Aviano

Aviano, Italy

CRO Aviano

Aviano, Italy
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Alongi F.,Sacro Cuore Don Calabria Cancer Care Center | Arcangeli S.,San Camillo and Forlanini Hospital | Ramella S.,Biomedical University of Rome | Giaj-Levra N.,Sacro Cuore Don Calabria Cancer Care Center | And 9 more authors.
Expert Review of Anticancer Therapy | Year: 2017

Introduction: The integration between radiotherapy and drugs, from chemotherapy to recently available target therapies, continues to have a relevant role in the treatment of locally advanced and metastatic Non-small cell lung cancer (NSCLC). Aim of the present review is to evaluate the promising and emerging application of the best interaction between new drugs and new modalities of radiotherapy. Areas covered: We searched Medline, Google Scholar, PubMed, ProQuest Dissertation, and Theses databases for reports published in English. A study was included when it reported on cancer-related radiotherapy and included patients with NSCLC treated with chemo and/or target therapies. Review articles were excluded from the analysis. Expert commentary: Chemo-radiotherapy still represents the standard of choice in locally advanced NSCLC, while to date the addition of target therapies to chemo-radiotherapy did not demonstrate any robust advantage in this stage of disease. Considering the absence of randomized controlled trials, the role of target therapies in early stage adjuvant NSCLC is not yet recommended in clinical practice. On the contrary, in the setting of oligometastatic and oligoprogressive disease, new molecules demonstrated to be safe and effective, opening to a promising and emerging application of the best interaction between new drugs and new modalities of radiotherapy. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Lee C.K.,University of Sydney | Gurney H.,University of Sydney | Brown C.,University of Sydney | Sorio R.,CRO Aviano | And 12 more authors.
British Journal of Cancer | Year: 2011

Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin-paclitaxel (CP) or carboplatin-liposomal doxorubicin (CPLD).Methods:We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell 4.0 × 10 9 per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS.Results:Of 608 patients with nadir blood and did not receive growth factors, 72% (CP70%, CPLD73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P0.001), but not those experiencing leukopenia (aHR 0.93, P0.54; interaction P0.008).Of 949 patients, 32% (CP62%, CPLD28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P0.0001), but not those with neuropathy (aHR 0.96, P0.81; interaction P0.15). Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. © 2011 Cancer Research UK All rights reserved.


PubMed | Instituto Oncologico Giovanni Paolo II Bari, University of Chieti Pescara, Medical Oncology Unit, Italian National Cancer Institute and 11 more.
Type: | Journal: Frontiers in pharmacology | Year: 2016

Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib-axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93-7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6-17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib ( vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39-13.40 months) vs. 5.46 months (95% CI 4.04-6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95-10.51 months,


PubMed | Sacro Cuore Don Calabria Cancer Care Center, Spedali Civili of Brescia, San Camillo and Forlanini Hospital, CRO Aviano and 2 more.
Type: | Journal: Expert review of anticancer therapy | Year: 2016

The integration between radiotherapy and drugs, from chemotherapy to recently available target therapies, continues to have a relevant role in the treatment of locally advanced and metastatic Non-small cell lung cancer (NSCLC). Aim of the present review is to evaluate the promising and emerging application of the best interaction between new drugs and new modalities of radiotherapy. Areas covered: We searched Medline, Google Scholar, PubMed, ProQuest Dissertation, and Theses databases for reports published in English. A study was included when it reported on cancer-related radiotherapy and included patients with NSCLC treated with chemo and/or target therapies. Review articles were excluded from the analysis. Expert commentary: Chemo-radiotherapy still represents the standard of choice in locally advanced NSCLC, while to date the addition of target therapies to chemo-radiotherapy did not demonstrate any robust advantage in this stage of disease. Considering the absence of randomized controlled trials, the role of target therapies in early stage adjuvant NSCLC is not yet recommended in clinical practice. On the contrary, in the setting of oligometastatic and oligoprogressive disease, new molecules demonstrated to be safe and effective, opening to a promising and emerging application of the best interaction between new drugs and new modalities of radiotherapy.


Avanzo M.,CRO Aviano | Trovo M.,CRO Aviano | Stancanello J.,General Electric | Jena R.,University of Cambridge | And 4 more authors.
Physica Medica | Year: 2015

Purpose: To reduce the fraction number in Partial Breast Irradiation (PBI) with initial prescription of 40 Gy in 10 fractions using radiobiological models with specific focus on risk of moderate/severe radiation-induced fibrosis (RIF) and report clinical results. Methods and materials: 68 patients (patient group A) were treated with 40 Gy in 10 fractions delivered by field-in-field, forward-planned IMRT. Isotoxic regimens with decreasing number of fractions were calculated using Biological Effective Dose (BED) to the breast. Risk for RIF in hypofractionated treatment was predicted by calculating NTCP from DVHs of group A rescaled to fractions and dose of novel regimens. Moderate/severe RIF was prospectively scored during follow-up. Various NTCP models, with and without incomplete repair correction, were assessed from difference to observed incidence of RIF. In order to verify the value for α/β of 3 Gy assumed for breast, we fitted α/β to observed incidences of moderate/severe RIF. Results: Treatments with 35 Gy/7f and 28 Gy/4f were selected for the fraction reduction protocol. 75 patients (group B) were treated in 35 Gy/7f. Incidence of moderate/severe RIF was 5.9% in group A, 5.3% in group B. The NTCP model with correction for incomplete repair had lowest difference from observed RIF. The α/β obtained from fitting was 2.8 (95%CIs 1.1-10.7) Gy. Conclusions: The hypofractionated regimen was well tolerated. The model for NTCP corrected for incomplete repair was the most accurate and an assumed α/β value of 3 Gy is consistent with our patient data. The hypofractionation protocol is continuing with patients treated with 28 Gy/4f. © 2015 Associazione Italiana di Fisica Medica.


Locatelli S.L.,Humanitas Cancer Center | Locatelli S.L.,University of Milan | Cleris L.,Fondazione IRCCS Instituto Nazionale Tumori | Stirparo G.G.,Humanitas Cancer Center | And 10 more authors.
Leukemia | Year: 2014

Relapsed/refractory Hodgkin's lymphoma (HL) is an unmet medical need requiring new therapeutic options. Interactions between the histone deacetylase inhibitor Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L-540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic inhibition of cell growth (range, 70-80%) and a marked increase in cell death (up to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury. Gene expression profiling indicated that the synergistic effects of Givinostat/Sorafenib treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib-induced ROS production, mitochondrial injury, activation of BH3-only protein BIM and cell death. Knockdown experiments identified BIM as a key signaling molecule that mediates Givinostat/Sorafenib-induced oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor burden (P<0.0001), a 5- to 15-fold increase in BIM expression (P≤0.0001) and a fourfold increase in tumor necrosis in Givinostat/Sorafenib-treated animals compared with mice that received single agents. These results provide a rationale for exploring Givinostat/Sorafenib combination in relapsed/refractory HL. © 2014 Macmillan Publishers Limited.


PubMed | CRO Aviano
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

18012 Background: Recent evidences supported the benefit of Rituxan in combination with chemotherapy in CD20+ NHL. Further maintenance therapy with Rituxan resulted in improved event free survival in R-FL and R-MC NHL. In this study we assessed the tolerability and the activity in terms of clinical and molecular remission of Rituxan after ABMT in R-FL or R-MC NHL.The pts in response after salvage treatment (R-DHAOX) underwent to high dose chemotherapy (HDC) with the scheme BEAM-R and further were treated with maintenance therapy with rituximab 375 mg/mFrom June 2002 to January 2007, 34 pts were enrolled. 21 were male (M) and 13 female (F). Median age was 51 (30-66). 23 ( 68%) pts were R-FL G1-G2, 10 (29%) R-MC and 1 a transformed follicular (TF). The stage was III for 8 (24%) and IV for 26 (76%) pts. 24 (70%) pts were previous treated with rituxan and 32 (94%) with anthracyclines schedules. CD34+ harvest was after 4These data suggested that the use of rituxan in combination with HDC is an effective in vivo purging method. HDC and maintenance immunotherapy with rituxan is an approach well tolerated and highly effective for R-FL and R-MC NHL. No significant financial relationships to disclose.


PubMed | CRO Aviano
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

10611 Background: Most recurrences after breast conserving surgery for cancer occur in the tissues around the original tumour. Wound-fluid has been shown to induce proliferation of breast carcinoma cells. We investigated whether intraoperative radiotherapy (IORT) using the targeted intraoperative radiotherapy (Targit) technique changes the effect of surgical wound fluid on the behaviour of breast cancer cells.Preoperative peripheral blood serums (A) and wound fluid (B) (first 24 hourss drainage) from 30 unselected patients undergoing breast conserving surgery with (14) or without (16) IORT using the Targit technique was collected, processed and stored at -80C. The breast carcinoma cell lines (MDA-MB231, MDA-MB-45 and SKBR-3) were used to evaluate the activity of A and B on cell proliferation (MTT-FACS analysis) and motility (chemotaxis) and invasion (Matrigel).Wound fluid stimulated cell proliferation, cell motility and cell invasion significantly more than the preoperative serum from the same patient. Targit did not influence the effect of wound fluid on cell proliferation. However, Targit abrogated the effect wound fluid on cell motility and cell invasion.This work demonstrates that wound fluid after surgery for breast cancer stimulates cancer cell growth and motility. Targit appears to significantly abrogate the effect on cancer cell migration and invasion. This outcome may confer more benefits than could be expected from the tumoricidal activity of radiotherapy, and may stimulate the development of novel peri-operative treatments directed at compensating the possible harmful effects of surgery. No significant financial relationships to disclose.


PubMed | Humanitas Cancer Center Humanitas Clinical and Research Center, Fondazione IRCCS Instituto Nazionale Tumori, Instituto Superiore Of Sanita, CRO Aviano and University of Milan
Type: Journal Article | Journal: Leukemia | Year: 2014

Relapsed/refractory Hodgkins lymphoma (HL) is an unmet medical need requiring new therapeutic options. Interactions between the histone deacetylase inhibitor Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L-540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic inhibition of cell growth (range, 70-80%) and a marked increase in cell death (up to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury. Gene expression profiling indicated that the synergistic effects of Givinostat/Sorafenib treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib-induced ROS production, mitochondrial injury, activation of BH3-only protein BIM and cell death. Knockdown experiments identified BIM as a key signaling molecule that mediates Givinostat/Sorafenib-induced oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor burden (P<0.0001), a 5- to 15-fold increase in BIM expression (P < 0.0001) and a fourfold increase in tumor necrosis in Givinostat/Sorafenib-treated animals compared with mice that received single agents. These results provide a rationale for exploring Givinostat/Sorafenib combination in relapsed/refractory HL.


PubMed | CRO Aviano, University of Udine, General Electric and University of Cambridge
Type: Journal Article | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2015

To reduce the fraction number in Partial Breast Irradiation (PBI) with initial prescription of 40Gy in 10 fractions using radiobiological models with specific focus on risk of moderate/severe radiation-induced fibrosis (RIF) and report clinical results.68 patients (patient group A) were treated with 40Gy in 10 fractions delivered by field-in-field, forward-planned IMRT. Isotoxic regimens with decreasing number of fractions were calculated using Biological Effective Dose (BED) to the breast. Risk for RIF in hypofractionated treatment was predicted by calculating NTCP from DVHs of group A rescaled to fractions and dose of novel regimens. Moderate/severe RIF was prospectively scored during follow-up. Various NTCP models, with and without incomplete repair correction, were assessed from difference to observed incidence of RIF. In order to verify the value for / of 3Gy assumed for breast, we fitted / to observed incidences of moderate/severe RIF.Treatments with 35Gy/7f and 28Gy/4f were selected for the fraction reduction protocol. 75 patients (group B) were treated in 35Gy/7f. Incidence of moderate/severe RIF was 5.9% in group A, 5.3% in group B. The NTCP model with correction for incomplete repair had lowest difference from observed RIF. The / obtained from fitting was 2.8 (95%CIs 1.1-10.7) Gy.The hypofractionated regimen was well tolerated. The model for NTCP corrected for incomplete repair was the most accurate and an assumed / value of 3Gy is consistent with our patient data. The hypofractionation protocol is continuing with patients treated with 28Gy/4f.

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