Enzo Pasquini

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.

Acute Disseminated Intravascular Coagulation Syndrome in Cancer Patients

Hemostatic abnormalities are rather frequent in cancer patients either in hematological or in solid tumors. Acute disseminated intravascular coagulation (DIC) is a rare coagulopathy in cancer patients, but when it develops it becomes rapidly fatal. Between June 1988 and December 1992 we observed 8 cases of acute DIC occurring in gastric cancer (4 patients), breast cancer (3 patients) and high-grade non-Hodgkin lymphoma (1 patient). In 3 patients affected by gastric carcinoma, acute DIC was the first manifestation of the presence of the tumor, while in the other patients DIC occurred during the course of the disease. All the patients were treated with heparin, fresh frozen plasma and platelet support, but only in 1 patient was a short duration improvement of clinical conditions and coagulation tests recorded. Acute DIC can be the first manifestation of gastric tumors and the presence of the hemorrhagic syndrome associated with thrombocytopenia, hypofibrinogenemia and fibrin/fibrinogen degradation products should initiate a search for gastric carcinoma.

Bolus Fluorouracil and Leucovorin With Oxaliplatin as First-Line Treatment in Metastatic Colorectal Cancer

PURPOSE A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer. PATIENTS AND METHODS Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m(2) on the first day of each course and 5-FU and LV 350 mg/m(2) and 20 mg/m(2), respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses. RESULTS Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m(2). Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m(2) dosage offered improved dose-intensity compared with the initial dosage.

Prospective randomised trial comparing fluorouracil versus doxifluridine for the treatment of advanced colorectal cancer

Doxifluridine (dFUR) is a fluoropyrimidine derivative that has shown activity on a variety of solid tumours. The purpose of this study was to compare its therapeutic effect with a standard fluorouracil (FU) regimen in patients with locally advanced or metastatic colorectal cancer. 222 previously untreated patients were randomised to receive dFUR (4000 mg/m2) or FU (500 mg/m2) daily for 5 days every 28 days. The primary tumour originated in the colon in two-thirds of the cases in both groups; approximately 90% of patients had metastatic extension, and liver involvement was present in 69% of the patients in the dFUR and FU groups. A good performance status (ECOG 0-1) was recorded in 90% of cases in both arms. A median of five cycles was administered to the patients (range 1-12). Only one partial response among 110 patients in the FU arm and one complete response and five partial responses out of 112 evaluable patients in the dFUR group were observed. Time to progression was significantly longer in the dFUR group (P = 0.02); overall survival, while longer in the dFUR arm (48 weeks vs. 39 weeks), was not significantly so (P = 0.08). Toxicity was acceptable in both arms, although grade 3-4 neurological side-effects and leukopenia were more common after dFUR infusion. Despite the low response rate, our results indicate that dFUR may be a superior alternative to FU. The possibility of enhancing significantly the activity of dFUR with biochemical modulators should be further investigated.

Malignant pericardial mesothelioma. Report of two cases, review of the literature and differential diagnosis.

Malignant pericardial mesothelioma is an uncommon variety of a primary malignant cardio-pericardial tumor and it is a highly lethal and fortunately rare cardiac neoplasm. The presentation of pericardial mesothelioma is aspecific and pathologically mesothelioma is not the most common among primary tumors of the pericardium. It is characterized by atypical solid growth of mesothelium with formation of atypical cavities surrounded by fibrous stroma. Antemortem diagnosis is difficult and distant metastases are extremely rare. Radical surgery can be used to treat localized mesothelioma. The treatment for advanced primary pericardial mesothelioma is usually palliative because the tumor is resistant to radiotherapy and chemotherapy. The prognosis is unfavorable. The median survival from the onset of symptoms is six months. In this paper we report two cases of patients with primary mesothelioma of the pericardium without a definite history of asbestos exposure.

Lipoplatin™ Monotherapy: A Phase II Trial of Second-Line Treatment of Metastatic Non-Small-Cell Lung Cancer

Abstract Lipoplatin™ is a liposome encapsulated form of cisplatin. Phase I studies on lipoplatin have demonstrated that the compound has an excellent toxicity profile. Therefore we performed a phase II trial in heavily pre-treated patients with advanced non-small-cell lung cancer (NSClC), performance status 0-2 in which the primary end-point was response rate and secondary endpoints were safety and overall survival. Nineteen patients, average age 64 years old, with stage IV NSClC, were treated with lipoplatin 100 mg/m2 every two weeks, as second line chemotherapy. We observed 1 partial remission (5.2%) and 3 stable diseases (15.9%). time to progression (ttp) was 16 weeks and median overall survival (OS) was 31 weeks (7.2 months). We observed G1-G2 toxicity during chemotherapy, mainly gastrointestinal with nausea and vomiting (4 patients), asthenia (3 patients), mucositis (2 patients) and anemia (4 patients). Our phase II study does not support a more extensive use of lipoplatin in phase III studies. An increase of dosage and a better selection of patients are mandatory to un-derstand the real therapeutic activity of lipoplatin.

Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial: Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5-FU)/folinic acid (LV) followed by docetaxel and cisplatin versus a 5-FU/LV regimen as postoperative treatment for radically resected gastric cancer.

LBA4001 Background: Following radical resection of gastric or gastroesophageal junction (GEJ) adenocarcinoma, a meta-analysis and randomized studies demonstrated better survival in pts treated with fluoropyrimidine regimens compared to surgery alone. ITACA-S trial is a no-profit, multicenter, randomized, open-label, superiority phase III study aimed at evaluating whether a more intensive postoperative chemotherapy improves efficacy, when replace fluoropyrimidine. METHODS Pts radically resected for gastric or GEJ adenocarcinoma, with ≥D1-lymphadenectomy, node involvement (pN+) or pN0 with pT2b-3-4; within 3-8 weeks after surgery were eligible. Treatment consisted in CPT-11 180 mg/m2 on d1, LV 100 mg/m2 d1-2, 5-FU 400-600 mg/m2 d1-2, q14; for 4 cycles (FOLFIRI regimen) followed by docetaxel 75 mg/m2 d1, cisplatin 75 mg/m2 d1, q 21; for 3 cycles (arm A) vs. LV 100 mg/m2 d1-2, 5-FU 400-600 mg/m2 d1-2, q 14 for 9 cycles (arm B). The primary hypothesis on disease-free survival (DFS) requires 636 events (first recurrence or death) to detect an hazard ratio (HR) of 0.80, with 2-sided 5% significance level for the log-rank test and a power of 80%. RESULTS From February 2005 to August 2009, 1,106 pts were randomized and 1,100 were analyzed (562 arm A, 538 arm B; 6 major violations) by 123 Italian centers. By March 2012, with a median follow-up of 49 months (quartile range: 36-62) we observed 558 events for DFS (HR 0.98; 95%CI 0.83-1.16;p=0.83) accounting for 88% of the target number and 440 deaths (HR: 1.00; 95%CI 0.83-1.20;p=0.98). Toxicity was consistent with literature. Given the data observed, both under the original hypothesis and the current trend, the probability to reach a statistically significant results at the target events is <0.0001. CONCLUSIONS Adjuvant chemotherapy in gastric cancer with more intensive regimen did not result in a significant prolongation of DFS and OS when compared to bolus/infusion FU/LV regimen.

Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report

IntroductionSmall cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites.Case presentationWe report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen.ConclusionsIt has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.

Treatment of primary or metastatic pleural effusion with intracavitary cytosine arabinoside and cisplatin: A phase II study

Thirty-three patients with microscopically verified primary or metastatic malignant pleural effusion were studied: 7 had malignant mesothelioma and 26 metastatic pleural disease. The treatment was based on biochemical and clinical studies which show a synergy between cytosine-arabinoside (Ara-C) and cisplatin. These drugs were instilled in the pleural cavity at the dose of 100 mg for Ara-C and 100 mg/m2 for cisplatin. The cavity was drained after 4 h. If it was possible, the treatment was repeated weekly for 3 times and, after a 6-week rest, it could be started again with the same schedule. The overall response rate (complete plus partial remissions) was 74%. Toxicity was mild or moderate. We conclude that the combination of Ara-C and cisplatin is well tolerated and produces a high response rate in the treatment of malignant pleural effusions.

Primary lymphoma of the central nervous system

Primary lymphoma of the central nervous system (CNS) represents a pathology that is no longer considered rare, also in the light of its high correlation with the human immunodeficiency virus (HIV) syndrome reported recently. Often the correct diagnosis of the disease is difficult to reach, owing to the wide spectrum of non-lymphoma pathologies from which it should be differentiated and the invasiveness of some diagnostic techniques. The biologic aggressiveness of the neoplasm often makes a combined radio-chemotherapeutic approach necessary. In contrast, surgical resection does not seem to provide any significant benefit. The clinical experience reported here, together with a review of the most recent literature, lead the authors to suggest the opportunity of treating primary lymphoma of the CNS with the most active and modern chemotherapeutic protocols in association with traditional treatments to obtain an improvement in overall survival.