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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. Source

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). Source

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. Source

Bresciani S.,Institute for Cancer Research and Treatment IRCCS | Dia A.D.,Institute for Cancer Research and Treatment IRCCS | Maggio A.,Institute for Cancer Research and Treatment IRCCS | Cutaia C.,Institute for Cancer Research and Treatment IRCCS | And 3 more authors.
Medical Physics | Year: 2013

Purpose: Pretreatment patient plan verification with gamma index (GI) metric analysis is standard procedure for intensity modulated radiation therapy (IMRT) treatment. The aim of this paper is to evaluate the variability of the local and global gamma index obtained during standard pretreatment quality assurance (QA) measurements for plans performed with Tomotherapy unit. The QA measurements were performed with a 3D diode array, using variable passing criteria: 3%/3 mm, 2%/2 mm, 1%/1 mm, each with both local and global normalization. Methods: The authors analyzed the pretreatment QA results for 73 verifications; 37 were prostate cancer plans, 16 were head and neck plans, and 20 were other clinical sites. All plans were treated using the Tomotherapy Hi-Art System. Pretreatment QA plans were performed with the commercially available 3D diode array ArcCHECK™. This device has 1386 diodes arranged in a helical geometry spaced 1 cm apart. The dose measurements were acquired on the ArcCHECK™ and then compared with the calculated dose using the standard gamma analysis method. The gamma passing rate (%GP), defined as the percentage of points satisfying the condition GI < 1, was calculated for different criteria (3%/3 mm, 2%/2 mm, 1%/1 mm) and for both global and local normalization. In the case of local normalization method, the authors set three dose difference threshold (DDT) values of 2, 3, and 5 cGy. Dose difference threshold is defined as the minimum absolute dose error considered in the analysis when using local normalization. Low-dose thresholds (TH) of 5% and 10% were also applied and analyzed. Results: Performing a paired-t-test, the authors determined that the gamma passing rate is independent of the threshold values for all of the adopted criteria (5%TH vs 10%TH, p > 0.1). Our findings showed that mean %GPs for local (or global) normalization for the entire study group were 93% (98%), 84% (92%), and 66% (61%) for 3%/3 mm, 2%/2 mm, and 1%/1 mm criteria, respectively. DDT was equal to 2 cGy for the local normalization analysis cases. The authors observed great variability in the resulting %GP. With 3%/3 mm gamma criteria, the overall passing rate with local normalization was 4.6% less on the average than with global one, as expected. The wide difference between %GP calculated with global or local approach is also confirmed by an unpaired t-test statistical analysis. Conclusions: The variability of %GP obtained confirmed the necessity to establish defined agreement criteria that could be universal and comparable between institutions. In particular, while the gamma passing rate does not depend on the choice of threshold, the choice of DDT strongly influences the gamma passing rate for local calculations. The difference between global and local %GP was statistically significant for prostate and other treatment sites when DDT was changed from 2 to 3 cGy. © 2013 American Association of Physicists in Medicine. Source

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