Carlo Milandri

Staging of Breast Cancer: New Recommended Standard Procedure

AbstractBackground. Staging procedures used to detect metastatic breast cancer at the time of diagnosis are bone scan (BS), chest X-ray (CXR), liver ultrasonography (LUS) and laboratory parameters (LP). These procedures are expensive and not all patients need them. We aimed to identify groups of patients with different risks for metastatic disease. Methods. We reviewed data from 1,218 consecutive cases of breast cancer. Pathological and biological param-eters and instrumental procedures performed at the time of diagnosis and during 6 months of follow-up were recorded. True positive and negative, false positive and negative cases were evaluated. All cases were grouped on the basis of tumour size, nodal involvement, biological characteristics, menopausal status and age. Results. We observed 46 (3.8%) true positive cases with metastatic disease at the time of diagnosis. Documenta-tion relating to BS, CXR and LUS was available for 1,193, 1,206 and 1,206 patients, respectively, with 37 (3.1%), 8 (0.7%) and 10 (0.8%) true positive tests. Logistic regression analysis showed significant odds ratio estimates for pT status and nodal status, thus highlighting the role of these morphological data. These findings suggest that breast cancer patients can be divided into two subgroups: first group pT1-3N0-1, with ≤3 involved nodes, and second group pT1-3N1 with ≥4 involved nodes, pT4 and pN2 (metastases detection rate 1.46 and 10.68%, respectively). In the former group the appropriate procedures of staging would only be laboratory parameters, whereas in the latter group BS, CXR, LUS, LP and tumour markers CEA and CA15.3 would be necessary. Conclusions. The standard staging procedures to detect metastatic disease at breast cancer diagnosis require modification. On the basis of the literature data and our findings, the full staging procedure is appropriate in the second group of patients.

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015

This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.

Phase I Study of Paclitaxel and Uracil plus Tegafur Combination in Patients with Pretreated Metastatic Breast Cancer: Drug Sequencing Based on Preclinical Modelling Studies

Objective: Taxanes and fluoropyrimidines are active in metastatic breast cancer (MBC), and their combination has proven effective in anthracycline-refractory patients. We conducted a phase I study to determine the maximum tolerated dose (MTD) of uracil plus tegafur (UFT) given in combination with leucovorin (LV) and paclitaxel (Pacl) in patients with refractory MBC. Methods: Pacl was infused at a fixed dose of 150 mg/m2 on day 1. UFT, at doses escalated by 50 mg/m2 starting from 200 mg/m2 · day, and LV, at a fixed dose of 90 mg/day, were given orally every 8 h for 11 days (days 3–13). Cohorts of at least 3 patients were treated at each dose level, and if 1 experienced dose-limiting toxicity (DLT), a maximum of 3 additional patients were added at the same dose level. MTD was reached if 2 out of the 6 patients experienced DLT. Results: Sixteen patients were enrolled in the study. The most important toxicity observed was hematological. Nonhematological toxicities were paresthesia and myalgia, asthenia, nausea, and mucositis. DLT occurred in only 1 patient (grade 3 hepatic toxicity). Conclusions: The recommended dose for a subsequent phase II trial is Pacl 150 mg/m2 on day 1, and UFT 300 mg/m2 and LV 90 mg on days 3–13, every 2 weeks.

Breast carcinoma stage in relation to time interval since last mammography: A registry-based study

In the Romagna Region of Italy, mammography screening for breast carcinoma (BC) was implemented as a routine practice in the regular healthcare system. The Romagna Cancer Registry evaluated the effects of self‐selection for mammography on the stage of BC at the time of presentation.

Gemcitabine and Paclitaxel Combination as Second-Line Chemotherapy in Patients With Small-Cell Lung Cancer: A Phase II Study

BACKGROUND Although small-cell lung cancer is a chemosensitive malignancy, most patients rapidly relapse. Results of second-line treatment are generally poor. We conducted a phase II study to evaluate the activity and toxicity of a combination of gemcitabine and paclitaxel as second-line chemotherapy. PATIENTS AND METHODS Eligible patients were refractory or relapsed small-cell lung cancer, with an Eastern Cooperative Oncology Group performance status of 0-2 and measurable disease. Paclitaxel was administered at 135 mg/m(2) days 1 and 8 immediately followed by gemcitabine at 1000 mg/m(2) every 3 weeks up to 6 courses. Restaging of disease was scheduled every 3 courses. RESULTS Forty-one patients were enrolled. The median age was 65 years. Nineteen patients were considered refractory (progressive disease during or within 90 days from completion of first-line treatment), whereas 22 patients were chemotherapy sensitive. A total of 135 courses was administered (range, 1-6; median, 3). Nine patients achieved a partial remission (partial response, 22%), and 10 patients had stable disease (24%), with a disease control rate (partial response + stable disease) of 46%: in 12 (55%) of 22 patients who were sensitive and in 7 (37%) of 19 patients with refractory disease, respectively. All partial responses but one were observed in the sensitive group. The median duration of response was 5 months. The most-frequent severe toxicities were neutropenia grade 3-4 and neurologic grade 3 in 24% and 7% of delivered courses, respectively. CONCLUSIONS The combination of gemcitabine and paclitaxel investigated in our study achieved a high disease control rate, but the schedule we adopted appeared to be quite toxic.

Acute hiatal hernia: a late complication following gastrectomy.

Introduction We describe a case of acute hiatal hernia during chemotherapy, in a female patient previously treated with gastrectomy. Case presentation After gastric resection, the patient underwent chemotherapy, developing important emetic symptoms. A radiograph of the abdomen was performed because of acute epigastrial pain and it showed a marked left diaphragm elevation. A CT scan carried out 24 hours later identified an occlusion with herniation in the left hemi thorax. Subsequent surgical investigation resulted in a diagnosis of hiatal hernia with volvulus. Conclusions This case represents a rare, late complication occurring after gastrectomy.

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

BackgroundDocetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.MethodsPatients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m2on day 1 and gemcitabine 900 mg/m2 on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).ResultsThe objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.ConclusionOur results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.Trial registration numberIOR 162 02

Abstract 4901: Preliminary investigation of circulating NSCLC cells using dielectrophoresis-based instrumentation

Aims: The study of rare cell populations is an extremely important field in cancer research. Our main aim was to carry out a preliminary investigation into a new technological platform capable of identifying and studying rare tumor cells in whole blood samples from patients with advanced cancer. Methods: The study was performed using DEPArray™, a new dielectrophoresis-based instrumentation capable of detecting, examining and sorting circulating tumor cells (CTCs) in a very small quantity (microliters) of enriched whole blood. Analyses were conducted on 3 blood samples from patients with EGFR-mutated metastatic NSCLC and on 15 samples composed of A549 cells spiked into the whole blood of healthy donors. Whole blood starting volume was 7.5 ml. After Ficoll-Paque centrifugation, tumor cells were immunomagnetically enriched via EpCam positive selection or CD45 negative depletion and then fixed and stained with Hoechst and fluorescent conjugated antibodies against CD45 and pan-cytokeratin. Cell recovery was followed by EGFR gene mutation evaluation through sequence analysis. Results: Preliminary data showed that DEPArray™ detected, isolated and sorted enriched CTCs with 100% purity, with no lymphocyte contamination in subsequent analyses. Single or multiple cell sorting was possible, making it simple to perform different downstream molecular assays. In particular, the EGFR gene mutation status of NSCLC was studied to find out whether mutations were present or whether gene status remained that observed in the primary tumor tissue. Although it was decided to work on fixed cells during the investigation of this first set of samples, DEPArray™ is also capable of sorting live cells with high specificity. Conclusions: The study of infrequent tumor or tumor-related cells such as circulating tumor cells, cancer stem cells and/or circulating endothelial cells is an increasingly important area of research from both a preclinical and clinical point of view. A growing number of studies have evaluated different methods and variables involved in the detection of rare cells, in particular CTCs, but there is still no general consensus on the most accurate method to use. DEPArray™ is an innovative dielectrophoresis-based instrument capable of identifying, manipulating and sorting rare live and fixed cells with extremely high purity. Although the most accurate markers to discriminate between normal epithelial cells and tumor cells have yet to be defined, DEPArray™ has already proven to be extremely versatile in the field of rare cell studies, introducing new possibilities such as 100%-pure retrieval of live cells and furthering its potential as a promising new strategy for cancer cell detection and characterization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4901. doi:10.1158/1538-7445.AM2011-4901