Luigi Mariani

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Lombardy, Italy

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Publications (173)1029.46 Total impact

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    ABSTRACT: Transsphenoidal endoscopic surgery has gained popularity in the last 2 decades and is becoming a standard technique for resection of pituitary adenomas. In contrast to their ENT colleagues, neurosurgical residents have practically no endoscopic experience when they reach the training stage for transsphenoidal procedures. We have developed an affordable method for repetitive training in endoscopic (and microscopic) work in a narrow channel, allowing training of the basic movements needed for resection of pituitary adenoma. In collaboration with colleagues in the ENT Department, Cantonal Hospital St. Gall, and the Technical University of Zurich, a three-dimensional model of the nasal cavity was developed and patented. The Egghead model consists of a 3D synthetic reconstruction of the head nasal cavity and sphenoid sinus. A boiled egg represents the sella. For validation, 17 neurosurgical residents from the Department of Neurosurgery, University Hospital of Basel, and Department of Neurosurgery, Cantonal Hospital of St. Gall, St. Gall, Switzerland, and two experts performed a standardized procedure mimicking a transsphenoidal pituitary procedure by dissecting a corridor to the egg yolk and resecting it, respecting the surrounding egg white. This procedure was performed under both microscopic and video-endoscopic visualization. A score for the precision and speed of the surgical performance was developed and used. The model allows repetitive training of the resection of the egg yolk under sparing of the egg white after careful opening of the shell. The validation data showed a steeper learning curve using the endoscopic technique than performing the same task using the microscope. After three repetitions, the quality of resection was better with the endoscopic technique. Our model, the Egghead, is affordable, offers tactile feedback and allows infinite repetitions in basic training for pituitary surgery. It can be used for training of advanced neurosurgical residents, who thus far have very few possibilities of acquiring endoscopic experience.
    Acta Neurochirurgica 08/2015; DOI:10.1007/s00701-015-2544-z · 1.79 Impact Factor
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    ABSTRACT: Anastomotic leakage is a major cause of morbidity after colorectal surgery. Epidural analgesia is the most effective method for postoperative pain relief after major abdominal surgery. Anyhow, its effect on anastomotic leakage rate is still controversial. This study aimed to compare epidural versus intravenous analgesia as risk factor for anastomotic leakage requiring reoperation in patients undergoing open colorectal surgery for cancer. A retrospective study on 1,474 patients was performed. The Cox proportional hazards model was used to study the relation between primary and secondary factors of risk and anastomotic leakage occurrence within 30 days after elective operation. Overall 30-day anastomotic leakage requiring reoperation was 4.9% (95%CI: 3.8-6.0%). No difference in anastomotic leakage occurrence was observed between the epidural analgesia group and the intravenous analgesia group (Hazard ratio: 0.94; 95%CI: 0.53-1.67%; P = 0.8338). Females had a rate of anastomotic leakage 43% lower than males (P = 0.0301). The diverting stoma resulted to be protective for anastomotic leakage occurrence (P = 0.0052). AL significantly increased postoperative median length of stay but not in-hospital mortality. Epidural analgesia does not influence the AL risk after open colorectal surgery for cancer. J. Surg. Oncol. 2015;9999:XX-XX. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 07/2015; DOI:10.1002/jso.23966 · 2.84 Impact Factor
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    ABSTRACT: Metastasis is the main reason for lung cancer related mortality but little is known about specific determinants of successful dissemination from primary tumors and metastasis initiation. Here we show that CD133+/CXCR4+ cancer initiating cells (CICs) directly isolated from patient-derived xenografts (PDX) of non-small cell lung cancer (NSCLC) are endowed with superior ability to seed and initiate metastasis at distant organs. We additionally report that CXCR4 inhibition successfully prevents the increase of cisplatin-resistant CD133+/CXCR4+ cells in residual tumors and their metastatization. Immunophenotypic analysis of lung tumor cells intravenously injected or spontaneously disseminated to murine lungs, demonstrates the survival advantage and increased colonization ability of a specific subset of CD133+/CXCR4+ with reduced expression of epithelial cell adhesion molecule (EpCAM-), that also shows the greatest in vitro invasive potential. We next prove that recovered disseminated cells from lungs of PDX bearing mice enriched for CD133+/CXCR4+/EpCAM- CICs are highly tumorigenic and metastatic. Importantly, microenvironment stimuli eliciting EMT, including signals from cancer-associated fibroblasts, are able to increase the dissemination potential of lung cancer cells through the generation of CD133+/CXCR4+/EpCAM- subset. These findings also have correlates in patient samples where disseminating CICs are enriched in metastatic lymphnodes (20-fold, p=0.006) and their detection in primary tumors is correlated with poor clinical outcome (DFS p=0.03; OS p=0.05). Overall these results highlight the importance of specific cellular subsets in the metastatic process, the need for in depth characterization of disseminating tumor cells and the potential of therapeutic strategies targeting both primary tumor and tumor-microenvironment interactions. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 07/2015; DOI:10.1158/0008-5472.CAN-14-3781 · 9.28 Impact Factor
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    ABSTRACT: Hope is crucial for patients with cancer. We explored the determinants of hope in patients with cancer using a questionnaire administered over the course of 1 day to an unselected sample of patients at an Italian cancer center. A team of oncologists, statisticians, and chaplains developed a questionnaire with medical, psychological, spiritual, and religious content. A cross-sectional study was conducted on 320 patients who answered the questionnaire. In the group of participants, 92.8% had a religious belief. Women, patients with limited formal education, and believers were more hopeful. Patients placed trust in God, their partners and children, scientific research, and doctors. On univariate and multivariate analysis, hope was found sensitive to patients' sharing their experiences with others (including family and friends), their positive perception of the people around them, and their relationship with doctors and nurses. If validated in further studies, these results support the notion that a patient with cancer's sense of hope is sensitive to the quality of relationships with caregivers. This may be important to health care organization and resource allocation.
    05/2015; DOI:10.5301/tj.5000366
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    ABSTRACT: Approximately one-third of the metastatic germ cell tumors (GCT) in patients are classified as intermediate-risk metastatic GCT, and available guidelines recommend the same treatment of poor-risk cases. Yet the prognosis of these patients is heterogeneous, and consequently refining the intensity of treatment is warranted. We aimed to address the heterogeneity of this category by providing a proof of principle for reclassification attempt. Data on consecutive patients with intermediate-risk metastatic GCT and who received treatment at Fondazione INT Milano in the time frame between February 1980 and March 2014 were collected. Cox regression analyses were done, evaluating potential prognostic factors for overall survival (OS, primary end point) to first-line therapy. Each factor was evaluated in a multivariable model. Recursive partitioning was performed to define prognostic risk groups. A total of 224 patients were suitable for the present analysis. Median age was 26 years (interquartile range: 22-31), 11 patients (4.9%) had a retroperitoneal primary tumor, 6 yielded seminomatous histology, 85 (37.9%) had lung metastases, and 58 (25.9%) had bulky (i.e.,≥10cm) retroperitoneal lymph nodes. Patients received cisplatin, bleomycin, and etoposide (PEB, n = 199) or vinblastine (PVB, n = 23); however, 2 patients received other treatments. Median follow-up was 135 months (interquartile range: 81-223). Globally, 5-year progression-free survival and OS rates were 72.8% (95% CI: 67.1-79.0) and 86.2% (81.7-91.0), respectively. In the multivariable model for OS, elevated alfa fetoprotein (AFP) level was the only significant prognostic factor (hazard ratio = 1.48, 95% CI: 1.12-1.96). The 2 separate prognostic groups with differential OS outcomes were identified based on the cutoff level of 6,200IU/ml. The 10-year OS rate was 55.6% (95% CI: 36.6-84.3), and it was 86.7% (95% CI: 82.0-91.7) for those with AFP levels more than (n = 19, 8.5%) and less than (n = 205, 91.5%) the cutoff, respectively. A small fraction of patients with highly elevated AFP levels have an OS approximating the poor prognostic category, whereas most of them are close to good-risk cases. This might have implications to select outlier patients for clinical trials and molecular characterization. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 05/2015; 33(7). DOI:10.1016/j.urolonc.2015.04.008 · 3.36 Impact Factor
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    ABSTRACT: A correlation between osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal β-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.
    Gastric Cancer 04/2015; DOI:10.1007/s10120-015-0495-y · 4.83 Impact Factor
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    ABSTRACT: The mutation status of KIT or PDGFRA notoriously affects the response of advanced gastrointestinal stromal tumors (GISTs) to tyrosine kinase inhibitors. Conversely, it is currently still unclear whether mutation status impinges on the prognosis of localized, untreated GISTs. Hence, at present, this variable is not included in decision making for adjuvant therapy. A series of 451 primary localized GISTs were analyzed for KIT, PDGFRA, and BRAF mutations. Univariable and multivariable analyses and a backward selection procedure were used to assess the impact of mutation status on overall survival and to identify prognostically homogenous groups. Mutation was a significant prognostic indicator of overall survival in naive, localized GISTs (P<0.001): KIT-mutated patients had a worse outcome than PDGFRA-mutated or triple-negative (KIT, PDGFRA, BRAF wild-type) cases. Multivariable Cox regression models allowed us to identify 3 molecular risk groups: group I exhibited the best outcome and included PDGFRA exon 12, BRAF, and KIT exon 13-mutated cases; group II, of intermediate clinical phenotype (HR=3.06), included triple-negative, KIT exon 17, PDGFRA exon 18 D842V, and PDGFRA exon 14-mutated cases; group III displayed the worst outcome (hazard ratio=4.52), and comprised KIT exon 9 and exon 11 and PDGFRA exon 18 mutations apart from D842V. This study highlights the prognostic impact of mutation status on the natural course of GIST and suggests that the molecular prognostic grouping may complement the conventional clinicopathologic risk stratification criteria in decision making for adjuvant therapy.
    The American journal of surgical pathology 04/2015; 39(7). DOI:10.1097/PAS.0000000000000418 · 4.59 Impact Factor
  • Federico Bozzetti · Luigi Mariani
    Nutrition 03/2015; DOI:10.1016/j.nut.2015.03.002 · 3.05 Impact Factor
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    ABSTRACT: Survival estimates with first-line treatment for patients with metastatic poor prognosis germ cell tumors (GCT) are still suboptimal in the literature. We conducted a retrospective study to evaluate the outcome of patients referred to our tertiary cancer center. A retrospective analysis was conducted on patients who received at least first-line chemotherapy at our center. Distribution of clinical characteristics was evaluated in the periods < 1997, 1997 to 2001, 2001 to 2006, and 2007 to 2013. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariable and multivariable Cox models with prespecified clinical variables were undertaken for PFS and OS. All tests and confidence intervals were 2-sided and set at a P = .05 level of significance. Between 1982 and 2013, 168 patients were identified. The median age was 27 years (interquartile range [IQR], 22-34). The presence of liver, bone, or brain metastases trended to greater incidence from 1997 onward (27.5% < 1997 to 55.6% in 2007-2013; χ(2)P = .054). Median follow-up was 102 (IQR, 63-166) months. Global 5-year PFS was 48.5% (95% confidence interval [CI], 41.5-56.8) and OS was 63.2% (95% CI, 56.0-71.2). In multivariable analysis, treatment period was not significantly associated with either PFS (overall P = .229) or OS (overall P = .216). In this single-center series of consecutive poor prognosis GCT we could observe greater PFS and OS than the historical estimates. This observation was independent from the period of treatment. Based on the present results, studies focused on improving the outcome in the sole poor-risk cohort should be discouraged. Results were biased by their retrospective quality. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Genitourinary Cancer 02/2015; DOI:10.1016/j.clgc.2015.02.002 · 1.69 Impact Factor
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    ABSTRACT: Background The prognostic impact of early metabolic response by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) after 2 cycles of first-line chemotherapy is still unrecognized in metastatic transitional cell carcinoma (TCC). Patients and Methods Patients with metastatic TCC receiving the modified combination of methotrexate, vinblastine, doxorubucin, and cisplatin (MVAC), according to Institutional protocol, underwent computed tomography (CT) and FDG-PET at baseline, a restaging with PET after 2 cycles only (PET2), and a CT (± FDG-PET) at the end of treatment and during follow up. Progression-free (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method; univariable (UVA) and multivariable (MVA) Cox models were fitted. Pre-specified variables were the presence of visceral metastases, nodal or soft tissue disease, and early PET response. Results In the time-frame 05/2010-10/2012, 31 patients with ECOG-PS 0 received the modified MVAC regimen, every 3 weeks. Six patients (19.3%) had a complete (CR) and 17 (54.8%) a partial metabolic response (PR), 4 had stable disease (SD), 4 progressed. PET2 responders had a median (95% confidence interval [CI]) progression-free survival (PFS) of 8 (7-11) months compared to 3 (2-5) months of patients without response (p=0.024). They also had a significant benefit in 8-month PFS (p<0.001 at Klein test) and 15-month overall survival (OS, p=0.016). PET2 response was significant for PFS in both UVA and MVA (p=0.027 and p=0.023, respectively). Conclusion PET response after 2 cycles of first-line chemotherapy was associated with longer PFS and OS in advanced TCC and warrants further investigation in the field, compared to early CT.
    Clinical Genitourinary Cancer 12/2014; 12(6). DOI:10.1016/j.clgc.2014.03.007 · 1.69 Impact Factor
  • Federico Bozzetti · Luigi Mariani
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    ABSTRACT: Objective The results achieved through the Enhanced Recovery After Surgery (ERAS) approach in the gastrointestinal surgery has led to its enthusiastic acceptance also in pancreatic surgery. However the ERAS programme also involves an early oral feeding that is not always feasible after pancreatoduodenectomy. We investigated in the literature whether the difficulty with an early oral feeding was adequately balanced by a perioperative enteral or parenteral nutritional support as recommended by the ESPEN Guidelines in these patients or whether these recommendations have lost value in the “bundle” of the ERAS. Methods We reanalyzed both ESPEN guidelines and literature regarding ERAS programme in surgical pancreatic patients. Results There was a high prevalence of malnutrition (and consequently of postoperative complications) in pancreatic cancer patients, and there is evidence that many of these patients should be candidate for a perioperative nutritional support according to the ESPEN guidelines. The start of oral fluid and solid feeding was quite variable in literature reporting the use of ERAS in pancreatic cancer surgery, with consistent gap between the recommended and the effective start of both the feedings. The use of nasogastric/jejunal tube or of a needle-catheter jejunostomy was discouraged by the ERAS guidelines but their use can prove beneficial in patients who are recognized at high risk for postoperative complications according to the scores available in literature. Conclusion The current practice of the ERAS programme in these patients appears to neglect some ESPEN recommendations. On the contrary both ESPEN and ERAS recommendations could combine together with a supplemental benefit for the patient.
    Nutrition 11/2014; 30(11-12). DOI:10.1016/j.nut.2014.03.002 · 3.05 Impact Factor
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    ABSTRACT: Purpose To explore patterns of failure and postrelapse outcome of patients with retroperitoneal sarcoma primarily treated by extended resection. Methods All consecutive patients with primary retroperitoneal sarcoma, treated between January 2002 and December 2011 at two European sarcoma centers were included. Five-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastases (DM) were calculated. Multivariate analyses for OS and CCI of LR and DM were performed. Postrelapse OS was investigated. Results A total of 377 patients were identified. Median follow-up from the time of primary surgery was 44 months [interquartile range (IQR) 27–82]. Five-year OS was 64 % [95 % confidence interval (CI) 0.588, 0710]. CCI of LR and DM were 23.6 % (95 % CI 18.9, 29.4) and 21.9 % (95 % CI 17.6, 27.3), respectively. OS, CCI of LR and DM were 87, 18 % and 0 for well-differentiated liposarcoma; 54, 44 and 9 % for grade II dedifferentiated liposarcoma; 41,33, and 44 % for grade III dedifferentiated liposarcoma; 58, 5, and 55 % for leiomyosarcoma; and 85, 4, and 17 % for solitary fibrous tumor, respectively. Seventy-six patients developed LR. Median postrelapse follow-up was 27 months (IQR 10–58). Twenty-one patients (27 %) underwent a second surgical resection (complete in 18), while 55 (73 %) did not (22 multifocal, 17 inoperable, 16 other causes). Median postrelapse OS was 17 months (IQR 7–31). Well-differentiated liposarcoma histology and disease-free interval predicted postrelapse OS, while surgical resection did not. Conclusions When primary extended surgery limits LR, histologic subtype and grade determine the outcome. At recurrence, a second surgery is of limited benefit.
    Annals of Surgical Oncology 10/2014; 22(5). DOI:10.1245/s10434-014-4130-7 · 3.94 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):2852-2852. DOI:10.1158/1538-7445.AM2014-2852 · 9.28 Impact Factor
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    ABSTRACT: Extracorporeal photochemotherapy (ECP) is a treatment approved by the FDA for cutaneous T-cell lymphoma, and it is currently used off-label for graft-versus-host disease (GvHD) and other conditions. In agreement with good practices for the therapeutic use of human cells, quality control has to be performed to validate the ECP procedure with the off-line technique. Since no gold-standard biological test is available, we assessed the apoptosis generated in the ECP bag using a flow cytometric analysis. Thirty-one ECP procedures performed on 13 patients with chronic GvHD were studied by monitoring the induction of mononuclear cell (MNC) apoptosis using annexin V/propidium iodide double staining; residual lymphocyte proliferation to standard mitogens was also measured in 17 of the procedures. The kinetics of apoptosis was analyzed at different times in MNCs untreated or treated with 8-methoxy-psoralen plus ultraviolet A; the variation (ΔAPOPTOSIS) after 24 h revealed the efficacy of the treatment. In 88.6% of the 31 ECP procedures, ΔAPOPTOSIS was >15% (the “alerting” threshold for ΔAPOPTOSIS was set at 15% on the basis of our data); in the remainder (19.4%), the increment in apoptosis was lower. In four procedures, the proliferation assay was useful for assessing the effect of ECP on the apheretic bag. In conclusion, both flow cytometric assays enabled a biologically significant result to be obtained. In our opinion, the apoptosis test—being faster and easier than the proliferation test—could be a reliable way to validate ECP procedures. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Clinical Apheresis 09/2014; 30(3). DOI:10.1002/jca.21357 · 1.58 Impact Factor
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    ABSTRACT: Background Knowledge of the expression of molecular drivers and potentially druggable targets may enhance prognostic classification of metastatic urothelial carcinoma (UC). Materials and Methods We analyzed archival tissue from patients with UC undergoing first-line chemotherapy for locally-advanced (LA) and metastatic (M) disease between the years 2000 and 2013. The following biomarkers were evaluated by immunohistochemistry (IHC): ERCC1, EGFR, HER2, VEGFR-3, PDGFRα, p53, p63. Expression of ERCC1, EGFR, and HER2 was dichotomized as positive (2+,3+) or negative (≤1+). Cox regression models evaluated the association of biomarker expression with progression-free (PFS) and overall survival (OS), after controlling for known prognostic factors. Results Since 06/2009, tissues of 88 cases (27 LA, 61 M) have been stained. Rates of positive IHC/number evaluable were as follows: ERCC1: 30/66 (45%); HER2: 24/52 (46%); EGFR: 31/54 (57%); VEGFR-3: 50/66 (76%); PDGFRα: 10/63 (16%); p53: 25/56 (45%); p63: 46/53 (87%). In the multivariable model, PDGFRα was significantly prognostic for poorer PFS (HR: 2.53, 95%CI, 1.01-6.37, p=0.047) and trended to significance for poorer OS (HR: 2.66, 95%CI, 0.96-7.42, p=0.060) while VEGFR-3 was significantly prognostic for both better PFS (HR: 0.33, 95%CI, 0.15-0.74, p=0.007) and OS (HR: 0.36, 95%CI, 0.15-0.85, p=0.019). The c-index of the model was 0.67 and 0.68 for the two endpoints, respectively. Conclusions Tumor VEGFR-3 and PDGFRα expression appeared to confer a divergent prognostic impact. These data underscore the hurdles in defining the role of angiogenesis as a molecular driver and therapeutic target, as well as the controversial role of IHC to guide therapeutic decision-making.
    Clinical Genitourinary Cancer 08/2014; 13(2). DOI:10.1016/j.clgc.2014.08.002 · 1.69 Impact Factor
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    ABSTRACT: Purpose: Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients. Patients and Methods: Data from 2,243 patients with thin melanoma were retrieved from prospectively maintained databases at six centers. Kaplan-Meier survival and crude cumulative incidences of recurrence were estimated, and competing risks were taken into account. Multivariable Cox regression was used to investigate survival predictors. Results: Median follow-up was 124 months (interquartile range, 106 to 157 months); 12-year overall survival was 85.3% (95% CI, 83.4% to 87.2%). Median times to local, regional, and distant recurrence were 79, 78, and 107 months, respectively. Relapse was significantly related to age, Breslow thickness, mitotic rate (MR), ulceration, lymphovascular invasion (LVI), and regression; incidence was lower and subgroup differences were less marked for distant metastasis than for regional relapse. The worst prognosis categories were age older than 60 years, Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, presence of LVI, and regression ≥ 50%. Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, and LVI (all P = .001) were significantly associated with sentinel node positivity. Age, MR, ulceration, LVI, regression, and sentinel node status were independent predictors of survival and were used to construct a nomogram to predict 12-year overall survival. The nomogram was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.88). Conclusion: Our findings suggest including LVI and regression as new prognostic factors in the melanoma staging system. The nomogram appears useful for risk stratification in clinical management and for recruiting patients to clinical trials.
    Journal of Clinical Oncology 07/2014; 32(23). DOI:10.1200/JCO.2013.54.2340 · 18.43 Impact Factor
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    ABSTRACT: Aims The purpose of this observational study was to evaluate disease free survival (DFS), overall survival (OS), and local recurrence rate (LRR) in patients submitted to Class II RH compared with Class III RH in early FIGO stage cervical cancer (ECC). Materials and Methods We investigated 127 patients with CC admitted to the National Cancer Institute of Milan from June 2001 to October 2011 treated with Class II RH, and compared them with 202 patients operated with Class III RH between March 1980 and March 2001. A total of 329 patients were collected. Results Median follow-up time was 91 months (IQ range:58-196). Five-year OS and DFS estimates were 89.5% (95%CI: 86.0-93.2%) and 85.6% (95%CI: 81.6-89.7%), respectively. Estimates of effect of surgical treatment (Class III RH versus Class II RH) on OS showed a HR of death= 3.38 (95%CI: 1.18-9.63, P=0.0228), at univariable Cox analysis, and a HR= 3.08 (95%CI: 0.96-9.93; P= 0.0595) at multivariable analysis. For DFS, a HR of relapse=2.51 (95%CI 1.10-5.72; P=0.0290) comparing Class III vs Class II was found at multivariable analysis. Overall recurrence rate was 12.8%, whilst it was 16.3% for Class III and 7.1% for Class II respectively. Conclusions The present data suggest that the outcomes of Class II RH are comparable in terms of LRR and OS to those of Class III RH, according to literature data. The opportunity of extending the indication to all women with ECC needs further investigations. Clearer data are warranted by prospective controlled studies
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 07/2014; 40(7). DOI:10.1016/j.ejso.2014.02.229 · 2.89 Impact Factor
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    ABSTRACT: Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis.
    Clinical Genitourinary Cancer 06/2014; 13(1). DOI:10.1016/j.clgc.2014.06.014 · 1.69 Impact Factor
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    ABSTRACT: Background: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting. Methods: We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28). Results: Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes. Conclusion: TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease. © 2014 S. Karger AG, Basel.
    Oncology 06/2014; 86(5-6):289-294. DOI:10.1159/000360088 · 2.61 Impact Factor
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    ABSTRACT: Background The contribution of postchemotherapy pelvic (PLND) or retroperitoneal lymphadenectomy (RPLND) on survival in patients with advanced and metastatic urothelial carcinoma (UC) is still unclear. Patients and Methods Between September 1986 and May 2012, 157 patients with locally advanced or metastatic urothelial cancer received first-line chemotherapy consisting of the modified methotrexate, vinblastine, doxorubicin, and cisplatin (mMVAC), according to our policy. Patients having subdiaphragmatic nodal disease/local recurrence only and experiencing at least a stable disease were selected. Fifty-nine patients were identified, 28 of whom underwent surgery, 31 started consolidation chemotherapy±radiotherapy or observation. The prognostic effect of candidate factors upon survival was evaluated by using Cox proportional hazard regression models. Results A total of 14 PLND and 14 RPLND were identified after achieving a complete response (CR, N=7) or a partial response-stable disease (PR+SD, N=21). Median follow-up was 88 months (IQR: 24-211). Median progression-free (PFS) survival was 18 (95%CI, 11-not estimated) and 11 (95%CI, 5-19) months, respectively in favor of surgical cohort and curves were statistically different (log-rank test p=0.009). On multivariate analysis, post-chemotherapy surgery was significantly prognostic for both PFS and OS and response to chemotherapy (PR/SD vs CR) was prognostic for PFS and trended to significance for OS. A model including these two factors showed a bootstrap-corrected Harrel C statistics for PFS and OS of 0.65 and 0.68, respectively. Conclusions In well selected patients with UC like those achieving a clinical benefit with chemotherapy and having nodal metastatic disease there was a survival advantage by removing disease residuals.
    Clinical Genitourinary Cancer 06/2014; 13(1). DOI:10.1016/j.clgc.2014.06.003 · 1.69 Impact Factor

Publication Stats

8k Citations
1,029.46 Total Impact Points


  • 1993–2015
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • • s.c. Medicina Oncologica 1
      • • s.c. Medicina Nucleare
      • • s.c. Pediatria Oncologica
      Milano, Lombardy, Italy
  • 2013
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy
  • 2005–2013
    • CRO Centro di Riferimento Oncologico di Aviano
      • • Division of Medical Oncology A
      • • Department of Surgery
      • • Division of Experimental Oncology 1
      Aviano, Friuli Venezia Giulia, Italy
  • 2006–2010
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1993–2010
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 2009
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 2005–2006
    • University of Milan
      Milano, Lombardy, Italy
  • 2004–2006
    • IEO - Istituto Europeo di Oncologia
      • Division of Epidemiology and Biostatistics
      Milano, Lombardy, Italy