Institute for Cancer Research and Treatment IRCCS

Candiolo, Italy

Institute for Cancer Research and Treatment IRCCS

Candiolo, Italy
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Morandi L.,University of Bologna | Righi A.,Rizzoli Orthopaedic Institute | Maletta F.,University of Turin | Rucci P.,University of Bologna | And 7 more authors.
Endocrine-Related Cancer | Year: 2017

Hobnail variant of papillary thyroid carcinoma (HPTC) represents a recently described, aggressive and rare group of thyroid tumors with poorly understood pathogenesis. Molecular data about this group of cancers are few, and a more detailed molecular characterization of these tumors is needed. The main objective of the study is to define a comprehensive molecular typing of HPTC. Eighteen patients affected by HPTC, including eighteen primary tumors and four lymph node metastases, were screened for NRAS, KRAS, HRAS, BRAF, TP53, PIK3CA, hTERT, PTEN, CDKN2A, EGFR, AKT1, CTNNB1 and NOTCH1 gene mutations. Sequencing is conducted on the MiSEQ system, and molecular data are compared with clinical-pathologic data and follow-up. The patients include 14 women and 4 men. Ages range from 23 to 87 years. All 18 primary tumors of HPTC showed ≥30% hobnail features. BRAF and TP53 mutations are by far the most common genetic alterations in primary HPTC (72.2% and 55.6%, respectively), followed by hTERT (44.4%), PIK3CA (27.8%), CTNNB1 (16.7%), EGFR (11.1%), AKT1 (5.5%) and NOTCH1 (5.5%). The mutational pattern in primary tumors and metastasis was usually maintained. Univariate Cox regression analyses with bootstrap procedure indicated a significantly increased mortality risk in patients harboring BRAF mutation and BRAF mutation associated with TP53 and/or PIK3CA mutations. The detection of these multiple mutations appears to allow the identification of a subset of more aggressive tumors within the group and to bear information that should be useful for prognostic stratification of these patients including the planning of adjuvant therapy. © 2017 Society for Endocrinology Printed in Great Britain.


PubMed | Medical Oncology, Institute for Cancer Research and Treatment IRCCS, Italian National Cancer Institute, University of Verona and 13 more.
Type: | Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association | Year: 2016

Although second-line therapy is often considered for advanced gastric cancer patients, the optimal candidates are not well defined.We retrospectively collected baseline parameters, tumour features, and treatment data for 868 advanced gastric cancer patients exposed to multiple treatment lines at 19 Italian centres. Cross-tables and chi-square tests were used to describe categorical features. To predict the impact of clinical variables on progression-free survival and overall survival, Kaplan-Meier and Cox regression analyses were performed.At the start of second-line therapy, median age was 64.8years (25th-75th percentiles: 55.2-71.9years). Overall, 43% of patients received single-agent chemotherapy, 47.4% a doublet, and 7.3% a triplet. Median second-line progression-free survival was 2.8months (25th-75th percentiles: 1.8-5.2months) and median second-line overall survival was 5.6months (25th-75th percentiles: 2.9-10.0months). Multivariate analysis showed that performance status, LDH level, neutrophils/lymphocytes ratio, and progression-free survival in the first-line therapy all impacted on prognosis. Based on these four prognostic factors, a prognostic index was constructed that divided patients into good, intermediate, and poor risk groups; median second-line overall survival for each group was 7.7, 4.5, and 2.0months, respectively (log-rank p<0.0001).Advanced gastric cancer patients with a favourable ECOG performance status, lower LDH levels, and a lower neutrophils/lymphocytes ratio at the start of second-line therapy seem to have better outcomes, regardless of age and intensity of treatment. A longer progression-free survival in the first-line therapy also had positive prognostic value. Our real-life study might help clinicians to identify the patients who may benefit most from a second-line therapy.


Fornaro L.,Unit of Medical Oncology 2 | Vivaldi C.,Unit of Medical Oncology 2 | Cereda S.,San Raffaele Scientific Institute | Leone F.,Institute for Cancer Research and Treatment IRCCS | And 12 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2015

Background: After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. Methods: We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. Results: A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4%), with median PFS and OS of 3.0months and 6.6months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2%), with limited efficacy in unselected patient populations (median PFS: 3.1months; median OS: 6.3months). Conclusions: The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management. © 2015 Fornaro et al.


Rossi V.,Institute for Cancer Research and Treatment IRCCs | Nole F.,Italian National Cancer Institute | Redana S.,Institute for Cancer Research and Treatment IRCCs | Adamoli L.,Italian National Cancer Institute | And 7 more authors.
Breast | Year: 2013

Background: Five to 10% of women with newly diagnosed breast cancer have synchronous metastases ( de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation. Patients and methods: Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation. Results: Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary (". de novo/surgery"). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", ". de novo/surgery" and ". de novo" without surgery (". de novo/no surgery) stage IV breast cancer. However, women with ". de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with ". de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p<0.01). Multivariate analysis confirmed these findings. Conclusion: Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias. © 2013 Elsevier Ltd.


PubMed | University of Turin, Institute for Cancer Research and Treatment IRCCs, Italian National Cancer Institute and University of Milan
Type: Journal Article | Journal: Breast (Edinburgh, Scotland) | Year: 2013

Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation.Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation.Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary (de novo/surgery). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with recurring, de novo/surgery and de novo without surgery (de novo/no surgery) stage IV breast cancer. However, women with de novo/surgery stage IV breast cancer had the longest median OS (60 months), and those with de novo/no surgery stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p<0.01). Multivariate analysis confirmed these findings.Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias.


PubMed | Regina Elena Cancer Institute, Unit of Medical Oncology 2, Institute for Cancer Research and Treatment IRCCS, Italian National Cancer Institute and 5 more.
Type: | Journal: Journal of experimental & clinical cancer research : CR | Year: 2015

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far.We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings.A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months).The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.


Balmativola D.,University of Turin | Marchio C.,University of Turin | Maule M.,University of Turin | Chiusa L.,University of Turin | And 25 more authors.
Breast Cancer Research and Treatment | Year: 2014

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm2 and 18 % of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2− subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2− subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value. © 2014, The Author(s).

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