IRCC Institute for Cancer Research and Treatment

Candiolo, Italy

IRCC Institute for Cancer Research and Treatment

Candiolo, Italy
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Moselli N.M.,IRCC Institute for Cancer Research and Treatment | Cruto M.,IRCC Institute for Cancer Research and Treatment | Massucco P.,IRCC Institute for Cancer Research and Treatment | Savojardo M.,IRCC Institute for Cancer Research and Treatment | Debernardi F.,IRCC Institute for Cancer Research and Treatment
Clinical Journal of Pain | Year: 2010

According to international guidelines, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the cornerstone drugs for cancer pain. In clinical practice, severe cancer pain often requires 3 step analgesics and alternative routes of administration, thus NSAIDs are usually abandoned. Our aim was to evaluate feasibility, safety, and efficacy of ketoprofen combined with opioids in long-term continuous subcutaneous infusion (CSI) for cancer pain in a prospective observational open-label pilot study. METHODS: Ketoprofen was added to morphine CSI in 172 consecutive patients (study group, SG). Concomitantly, 48 received opioids CSI without ketoprofen for contraindication to NSAIDs (control group, CG). CSI was delivered through a single-use elastomeric pump refilled weekly. Safety was evaluated according to the number of adverse events and their severity. The measures of efficacy were pain relief (NRS, Numerical Rating Scale), percentage of patients that needed to increase morphine dosage, and median relative increase between weeks 2 and 4. RESULTS: Toxicity typically attributable to NSAIDs were recorded in 4.1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids seems not to influence the risk of gastrointestinal adverse effects. The local side effects related to the CSI regimen were negligible in both the groups. By the fourth week, pain was well controlled (NRS 0 to 2) in 80% of patients receiving ketoprofen compared with 46% of patients without ketoprofen (P<0.01.) Moreover, the percentage of patients needing to increase the morphine dosage (40.5% vs. 68.7% P<0.01) and the relative dose increase (12% vs. 25% P<0.005) were significantly lower in the SG. CONCLUSIONS: Ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain. © 2010 by Lippincott Williams & Wilkins.


Sardanelli F.,University of Milan | Podo F.,Instituto Superiore Of Sanita | Santoro F.,Instituto Superiore Of Sanita | Manoukian S.,Fondazione IRCCS Instituto Nazionale Tumori | And 23 more authors.
Investigative Radiology | Year: 2011

Objectives: To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. Materials and Methods: We enrolled asymptomatic women aged ≥125: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. Results: A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥150 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P ≤ 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥150 years of age. Conclusion: MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50. © 2011 by Lippincott Williams & Wilkins.


Vignati A.,IRCC Institute for Cancer Research and Treatment | Giannini V.,IRCC Institute for Cancer Research and Treatment | Giannini V.,Polytechnic University of Turin | De Luca M.,IRCC Institute for Cancer Research and Treatment | And 8 more authors.
Journal of Magnetic Resonance Imaging | Year: 2011

Purpose: To describe and test a new fully automatic lesion detection system for breast DCE-MRI. Materials and Methods: Studies were collected from two institutions adopting different DCE-MRI sequences, one with and the other one without fat-saturation. The detection pipeline consists of (i) breast segmentation, to identify breast size and location; (ii) registration, to correct for patient movements; (iii) lesion detection, to extract contrast-enhanced regions using a new normalization technique based on the contrast-uptake of mammary vessels; (iv) false positive (FP) reduction, to exclude contrast-enhanced regions other than lesions. Detection rate (number of system-detected malignant and benign lesions over the total number of lesions) and sensitivity (system-detected malignant lesions over the total number of malignant lesions) were assessed. The number of FPs was also assessed. Results: Forty-eight studies with 12 benign and 53 malignant lesions were evaluated. Median lesion diameter was 6 mm (range, 5-15 mm) for benign and 26 mm (range, 5-75 mm) for malignant lesions. Detection rate was 58/65 (89%; 95% confidence interval [CI] 79%-95%) and sensitivity was 52/53 (98%; 95% CI 90%-99%). Mammary median FPs per breast was 4 (1st-3rd quartiles 3-7.25). Conclusion: The system showed promising results on MR datasets obtained from different scanners producing fat-sat or non-fat-sat images with variable temporal and spatial resolution and could potentially be used for early diagnosis and staging of breast cancer to reduce reading time and to improve lesion detection. Further evaluation is needed before it may be used in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.


Stasi M.,IRCC Institute for Cancer Research and Treatment | Bresciani S.,IRCC Institute for Cancer Research and Treatment | Miranti A.,IRCC Institute for Cancer Research and Treatment | Maggio A.,IRCC Institute for Cancer Research and Treatment | And 2 more authors.
Medical Physics | Year: 2012

Purpose: The aim of this work is to investigate the predictive power of a common conventional intensity modulated radiation therapy (IMRT) quality assurance (QA) performance metric, the gamma passing rate (GP), through the analysis of the sensitivity and of the correlation between GP and different dose discrepancies between planned dose-volume histogram (DVH) and perturbed DVH. The perturbed DVH is calculated by using a dedicated software, 3DVH (Sun Nuclear Corporation, Melbourne, FL), which is able to modify the dose distribution calculated by the treatment planning system (TPS) according to the dose discrepancies detected with planar measurements in order to predict the delivered 3D dose distribution in the patient. Methods: Twenty-seven high-risk prostate cancer (PP) patients and 15 head and neck (HN) cancer patients, treated with IMRT technique, were analyzed. Pretreatment verifications were performed for all patients' plans by acquiring planar dose distributions of each treatment field with 2D-diode array. Measured dose distributions were compared to the calculated ones using the gamma index (GI) method applying both global (Van Dyk) and local normalization, and GP were generated for each pair of planar doses using the following acceptance criteria: 11, 22, and 33 mm. Planar dose distributions acquired during pretreatment verifications, together with patients DICOM RT plan, RT structure set, and RT dose files from TPS were loaded into the 3DVH software. Percentage dose differences (DE) between DVHs, obtained by TPS and by 3DVH, were calculated; statistical correlation between DE and GP was studied by using Pearsons correlation coefficient (r). This analysis was performed, for each patient, on planning target volumes and on some typical organs at risk of the prostatic and head and neck anatomical district. The sensitivity was calculated to correctly identify the pretreatment plans with high dose errors and to quantify the incidence of false negatives, on varying the gamma index method. Results: Analysis of DE vs GP showed that there were only weak correlations (Pearsons r-values 0.8). The results also showed numerous instances of false negatives (cases where high IMRT QA passing rates did not imply good agreement in anatomy dose metrics) and the reverse, mainly for the 33 mm global gamma passing rate. Conclusions: The lack of correlation between conventional IMRT QA performance metrics gamma passing rates and dose errors in DVHs values and the low sensitivity of 33 mm global gamma method show that the most common published acceptance criteria have disputable predictive power for per-patient IMRT QA. © 2012 American Association of Physicists in Medicine.


Esposito A.,Instituto Europeo Of Oncologia | Bardelli A.,University of Turin | Bardelli A.,IRCC Institute for Cancer Research and Treatment | Bardelli A.,FIRC Institute of Molecular Oncology IFOM | And 8 more authors.
Cancer Treatment Reviews | Year: 2014

Circulating cell-free DNA represents a non-invasive biomarker, as it can be isolated from human plasma, serum and other body fluids. Circulating tumor DNA shed from primary and metastatic cancers may allow the non-invasive analysis of the evolution of tumor genomes during treatment and disease progression through 'liquid biopsies'. The serial monitoring of tumor genotypes, which are instable and prone to changes under selection pressure, is becoming increasingly possible. The "liquid biopsy" provide novel biological insights into the process of metastasis and may elucidate signaling pathways involved in cell invasiveness and metastatic competence.This review will focus on the clinical utility of circulating cell free DNA in main solid tumors, including genetic and epigenetic alterations that can be detected. © 2013 Elsevier Ltd.


Martini M.,IRCC Institute for Cancer Research and Treatment | Martini M.,Molecular Biotechnology Center | Russo M.,IRCC Institute for Cancer Research and Treatment | Lamba S.,University of Turin | And 11 more authors.
Cancer Research | Year: 2013

Colorectal cancers (CRC) are commonly classified into those with microsatellite instability and those that are microsatellite stable (MSS) but chromosomally unstable. The latter are characterized by poor prognosis and remain largely intractable at the metastatic stage. Comprehensive mutational analyses have revealed that the mixed lineage kinase 4 (MLK4) protein kinase is frequently mutated in MSS CRC with approximately 50% of the mutations occurring in KRAS- or BRAF-mutant tumors. This kinase has not been characterized previously and the relevance of MLK4 somatic mutations in oncogenesis has not been established. We report that MLK4-mutated alleles in CRC are constitutively active and increase the transformation and tumorigenic capacity of RAS-mutated cell lines. Gene expression silencing or targeted knockout of MLK4 impairs the oncogenic properties of KRAS- and BRAF-mutant cancer cells both in vitro and in xenograftmodels. In establishing the role of MLK4 in intracellular signaling, we show it directly phosphorylates MEK1 (MAP2K1) and that MEK/ERK (MAPK1) signaling is impaired in MLK4 knockout cells. These findings suggest that MLK4 inhibitors may be efficacious in KRAS- and BRAF-mutated CRCs and may provide a new opportunity for targeting such recalcitrant tumors. © 2012 AACR.


Guiot C.,University of Turin | Garibaldi E.,IRCC Institute for Cancer Research and Treatment | Gabriele D.,University of Turin | Gabriele P.,IRCC Institute for Cancer Research and Treatment
Proceedings of the 2012 5th International Advanced Research Workshop on In Silico Oncology and Cancer Investigation - The TUMOR Project Workshop, IARWISOCI 2012 | Year: 2012

Prostate tumor (PT) normally has an indolent course during the first 10 to 15 years. Tumor progression and its clinical management, in the elderly patients, is therefore becoming a social problem, and the feasibility of non-therapeutic approaches, such as the Wait & Watch (W&W) one, requires a better understanding of the tumor natural history. Our model aims at connecting physical, biological and statistical knowledge in order to validate empirical views and to propose to clinicians a simple and effective 'therapy-simulator', based on a large experimental sample, helping them in the difficult goal of personalizing patients' therapy. © 2012 ICCS-NTUA.


Moselli N.M.,IRCC Institute for Cancer Research and Treatment | Baricocchi E.,IRCC Institute for Cancer Research and Treatment | Ribero D.,Ospedale Mauriziano Umberto i | Sottile A.,IRCC Institute for Cancer Research and Treatment | And 2 more authors.
Annals of Surgical Oncology | Year: 2011

Background: The intraoperative epidural analgesia (EA) has the potential to reduce stress response to surgical trauma which induces a transient immunoactivation that has a negative impact on the outcome. This study investigates the effect of intraoperative EA versus intravenous analgesia (IA) on the immune function. Methods: A total of 35 consecutive patients candidated to undergo major surgery for colon cancer were randomly assigned to intraoperative EA (n = 18) or IA (n = 17). Blood samples for TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, and GM-CSF were obtained before surgery (T pre), 3 h (T 3h), and 24 h (T 24h) after skin incision. Data on postoperative complications were prospectively collected and analyzed. Results: In the EA group, IL-4 increased from T pre to T 3h and from T 3h to T 24h, IL-10 increased from T pre to T 3h and persisted unmodified thereafter. At all time-points, IL-4 and IL-10 serum levels were significantly higher than those in the IA group. Conversely, in the IA group, IL-4 and IL-10 serum levels did not change while all other cytokines levels were significantly higher compared with the EA group. In particular, IL-6 progressively reached a 7-fold increase of its basal value at T 24h. Complications were significantly more common in IA patients (13 of 17) compared with EA patients (7 of 18) (P = .024). Conclusions: Our results indicate that in cancer patients undergoing major elective colon surgery, the EA attenuates the surgery-induced proinflammatory response and the typical postoperative transient immunosuppression and seems associated with a reduced rate of postoperative complications compared with IA. © 2011 Society of Surgical Oncology.


PubMed | IRCC Institute for Cancer Research and Treatment
Type: Journal Article | Journal: Journal of magnetic resonance imaging : JMRI | Year: 2011

To describe and test a new fully automatic lesion detection system for breast DCE-MRI.Studies were collected from two institutions adopting different DCE-MRI sequences, one with and the other one without fat-saturation. The detection pipeline consists of (i) breast segmentation, to identify breast size and location; (ii) registration, to correct for patient movements; (iii) lesion detection, to extract contrast-enhanced regions using a new normalization technique based on the contrast-uptake of mammary vessels; (iv) false positive (FP) reduction, to exclude contrast-enhanced regions other than lesions. Detection rate (number of system-detected malignant and benign lesions over the total number of lesions) and sensitivity (system-detected malignant lesions over the total number of malignant lesions) were assessed. The number of FPs was also assessed.Forty-eight studies with 12 benign and 53 malignant lesions were evaluated. Median lesion diameter was 6 mm (range, 5-15 mm) for benign and 26 mm (range, 5-75 mm) for malignant lesions. Detection rate was 58/65 (89%; 95% confidence interval [CI] 79%-95%) and sensitivity was 52/53 (98%; 95% CI 90%-99%). Mammary median FPs per breast was 4 (1st-3rd quartiles 3-7.25).The system showed promising results on MR datasets obtained from different scanners producing fat-sat or non-fat-sat images with variable temporal and spatial resolution and could potentially be used for early diagnosis and staging of breast cancer to reduce reading time and to improve lesion detection. Further evaluation is needed before it may be used in clinical practice.


PubMed | IRCC Institute for Cancer Research and Treatment
Type: Evaluation Studies | Journal: The Clinical journal of pain | Year: 2010

According to international guidelines, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the cornerstone drugs for cancer pain. In clinical practice, severe cancer pain often requires 3 step analgesics and alternative routes of administration, thus NSAIDs are usually abandoned. Our aim was to evaluate feasibility, safety, and efficacy of ketoprofen combined with opioids in long-term continuous subcutaneous infusion (CSI) for cancer pain in a prospective observational open-label pilot study.Ketoprofen was added to morphine CSI in 172 consecutive patients (study group, SG). Concomitantly, 48 received opioids CSI without ketoprofen for contraindication to NSAIDs (control group, CG). CSI was delivered through a single-use elastomeric pump refilled weekly. Safety was evaluated according to the number of adverse events and their severity. The measures of efficacy were pain relief (NRS, Numerical Rating Scale), percentage of patients that needed to increase morphine dosage, and median relative increase between weeks 2 and 4.Toxicity typically attributable to NSAIDs were recorded in 4.1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids seems not to influence the risk of gastrointestinal adverse effects. The local side effects related to the CSI regimen were negligible in both the groups. By the fourth week, pain was well controlled (NRS 0 to 2) in 80% of patients receiving ketoprofen compared with 46% of patients without ketoprofen (P<0.01.) Moreover, the percentage of patients needing to increase the morphine dosage (40.5% vs. 68.7% P<0.01) and the relative dose increase (12% vs. 25% P<0.005) were significantly lower in the SG.Ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain.

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