[Show abstract][Hide abstract] ABSTRACT: Cancer of unknown primary origin (CUP) had a poor prognosis, determined by clinico-histological characteristics, partly due to the lack of insights on its biology. We screened tumour DNA from 87 patients with CUP for CTNNB1 (coding exons 2,3,4,5), MET (coding exon 18), PIK3CA (coding exons 9,20), KRAS (coding exons 1,2), BRAF (coding exon 15) gene mutations by using dd-sequencing and evaluated their impact on prognosis. Mutated gene incidences in the 87 CUP cases were: KRAS 11 (12.6 %), BRAF 5 (5.7 %), PIK3CA 8 (9 %), MET 6 (6.7 %) and CTNNB1 18 (20.7 %). Several mutations in the KRAS gene were not the commonly encountered mutations in other solid tumours. Activating mutations were observed in 10.2 % in KRAS, 4.5 % in BRAF, 6.6 % in PIK3CA, 4.5 % in MET, and 19.5 % in CTNNB1. Activating mutations in PIK3CA coding exon 9 were inversely correlated with MET coding exon 18 activating mutations (p = 0.036). MET activating mutations were prognostic for poor Progression-Free Survival (median PFS 5 vs 9 months, p = 0.009) and Overall Survival (median OS 7 vs 20 months, p = 0.005). The complex profile of either CTNNB1 or MET mutations also had an adverse prognostic significance (median OS 11 vs 21 months, p = 0.015). No other gene mutation exhibited prognostic significance. In multivariate analysis, poor performance status, male gender, visceral disease and adenocarcinoma histology, but not gene mutations, were independently associated with poor patient outcome. CTNNB1 gene mutations are frequent, and along with MET mutations have an adverse prognostic effect in patients with CUP.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The aim of this study was to assess whether treatment with angiotensin converting enzyme inhibitors (ACEI) can prevent the alteration of left ventricular systolic and diastolic performance in cancer patients treated with different chemotherapy regimens containing epirubicin.
In this prospective study , 68 patients with different malignant tumors treated with epirubicin and perindopril in different chemotherapy protocols (study group), and a gender- and age-matched group of 68 patients with different malignant tumors treated with epirubicin without perindopril in different chemotherapy protocols (control group), were assessed by Doppler echocardiography. Left ventricular systolic function was assessed by measuring left ventricular ejection fraction (EF). Left ventricular diastolic function was assessed by Doppler ultrasound by evaluating the transmitral flow. We also assessed the QTc on the 12 lead electrocardiograms.
At the end of chemotherapy the left ventricular systolic function was less altered in the study group compared to the control group and was superior in the study group (epirubicin+ACEI) compared to the control group (epirubicin alone). We documented a significantly deteriorated left ventricular diastolic function in both groups at the completion of chemotherapy. QTc time in both arms was also significantly prolonged.
In the present echo-Doppler study we documented a preserved left ventricular systolic performance in patients with various malignancies treated with epirubicin plus perindopril. Although co-treatment with ACEI prevented the alteration of systolic performance, it failed to prevent the deterioration of the left ventricular diastolic performance impairment due to poor left ventricular compliance.
Full-text · Article · Dec 2013 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
[Show abstract][Hide abstract] ABSTRACT: Boala neoplazică reprezintă o problemă de sănătate publică mondială,
fiind a doua cauză de deces, după bolile cardio-vasculare. În anul 2000 pe
plan mondial s-au înregistrat 10 milioane de cazuri noi şi 6 milioane de
decese prin cancer (1). Incidenţa cancerului arată o tendinţă de creştere
continuă, astfel încât se prevede că, în anul 2020 numărul cazurilor nou
diagnosticate în întreaga lume să crească cu 1,5 milioane, iar boala
neoplazică să devină principala cauză de deces în ţările dezvoltate.
În ultimele decenii s-a înregistrat îmbunătăţirea supravieţuirii la cinci
ani a bolnavilor neoplazici, de la 40% în 1960, la 60% în anii 2000 (1),
astfel încât se poate afirma că pentru o parte din bolnavi, cancerul a devenit
o boală curabilă, iar pentru alţii o boală cronică, motiv pentru care atenţia se
îndreaptă în zilele noastre spre cunoaşterea şi încercarea de a preveni
efectele adverse ale tratamentelor antitumorale, mai ales a celor induse de
[Show abstract][Hide abstract] ABSTRACT: Background Hypothesising that cancer of unknown primary (CUP) may harbour unique characteristics, we present a translational study of
the immunohistochemical expression and clinical correlation of key PTEN/AKT pathway molecules.
Full-text · Article · May 2012 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial.
Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients).
Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT.
IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.
Full-text · Article · Apr 2011 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of capecitabine (Xeloda) as rescue treatment (2nd, 3rd and 4th line) in patients with relapsed nasopharyngeal carcinoma (NPC) in a phase II study.
Between 5/2002-11/2005, 23 relapsed NPC patients (17 locoregional relapse, 3 metastatic, 3 locoregional + metastatic) received capecitabine 2500 mg/m(2)/d, days 1-14 every 3 weeks, until progression or for a maximum of 6 cycles.
Patient characteristics: 23 patients (14 men, 9 women) with median age 46 years (range 15-59); ECOG performance status 1 n=21, 2 n=2; histology: undifferentiated carcinoma (WHO type III) n=21, non-keratinizing epidermoid carcinoma (WHO type II), n=2. Capecitabine was given as 2nd--(13 patients), 3rd--(7 patients), and 4th--(3 patients) line chemotherapy. Previous chemotherapy regimes were epirubicin + cisplatin, paclitaxel + carboplatin, paclitaxel + 5-fluorouracil and leucovorin (5-FU/LV) or methotrexate. 104 cycles were given (median 5, range 2-6). Two (9%) patients achieved complete response (CR); 9 (39%) partial response (PR); 9 (39%) stable disease (SD) and 3 (13%) progressed (PD). Toxicity was mild without toxic deaths or grade 4 toxicities. The most frequent toxicities (grades 1-3) were anemia (38%), hand-foot syndrome (23%), leukopenia (13%) and diarrhea (7%). Median follow-up was 10 months (range 2-44). Median overall survival was not reached at 18 months and actuarial one-year survival was 62% (95% confidence interval/CI: 41-80). Median progression-free survival was 14 months.
Capecitabine is active in relapsed NPC patients, achieving 48% objective responses, with mild toxicity. It is an attractive therapy to be administered in an outpatient setting.
No preview · Article · Jan 2008 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
[Show abstract][Hide abstract] ABSTRACT: Although extremely rare, the primitive lung hemangiopericytoma in adults is similar to hemangiopericytomas with other soft tissue localizations. Although generally benign and curable after radical surgery, it might also have a malignant clinical course with dissemination in both lungs, infiltration of vital organs (heart, pulmonary artery), extension to the adjacent tissues, and even pulmonary metastases. The treatment of choice is the complete tumor resection with negative surgical margins after excision. Certain histologic features might indicate a malignant potential. The clinical outcome of patients is variable: some are cured after radical surgery and others might present relapse and recurrences that necessitate a second intervention, radiation therapy, and/or chemotherapy. Over the years, the conventionally-defined hemangiopericytoma concept has evolved because of the nonspecific histologic growth pattern (characteristic monotonous appearance, moderate or high cellularity, and a well-developed branching vascular pattern) shared by numerous, unrelated benign or malignant lesions. Hemangiopericytoma is no longer considered a specific entity but rather as a characteristic growth pattern; in the heterogeneous group of hemangiopericytoma-like neoplasms, many lesion categories have been individualized and defined. We report an uncommon case of primitive lung tumor exhibiting hemangiopericytoma-like features, with an aggressive, fatal clinical course. Because of the major histologic overlap between solitary fibrous tumor and hemangiopericytoma and lack of clear classification criteria, we encountered difficulty in including this case in a known clinical entity; primitive solitary fibrous tumor of the lung, which mimics lung hemangiopericytoma, seemed to be the most plausible diagnosis. We discuss the case particularities and the radiologic and pathologic correlations.
No preview · Article · Oct 2007 · Clinical Lung Cancer
[Show abstract][Hide abstract] ABSTRACT: Anthracyclines confer an increased risk of cardiotoxicity. The authors evaluated left ventricular (LV) performance in patients treated with epirubicin. Sixty-eight patients with malignancies (study group), treated with epirubicin < or = 450 mg/m2, and a matched control group of 68 cancer patients who had not started chemotherapy were evaluated by Doppler echocardiography. The authors assessed LV diastolic function by measuring the transmitral flow: the maximal velocity of the E and A waves, the Emax/Amax ratio, the pressure half time of E wave (PHT), and the isovolumic relaxation time (IVRT). Global LV ejection fraction (LVEF) was estimated to determine the systolic performance. The authors documented alterations of the LV diastolic performance in the study group by finding a significant decrease in Emax, whereas Amax was significantly increased. Prolonged PHT and IVRT were also certified in the epirubicin-treated group compared with controls. No significant variation in LVEF between the 2 groups was detected.
[Show abstract][Hide abstract] ABSTRACT: Paraneoplastic syndromes are frequently detected in many small cell lung cancer (SCLC) patients. In the present paper we report 2 cases of patients diagnosed with SCLC, in whom 2 distinct endocrine paraneoplastic syndromes were identified during diagnosis. In the first patient, severe hyponatremia and renal sodium loss with inappropriate antidiuresis was found during routine laboratory tests. Serum antidiuretic hormone (ADH) level was within normal limits, but the atrial natriuretic peptide (ANP) level was elevated. The second case presented with severe hypercalcemia secondary to an excessive parathormone (PTH) secretion. We discuss the 2 cases and review the literature.
No preview · Article · Jul 2007 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
[Show abstract][Hide abstract] ABSTRACT: To evaluate and compare the left ventricular performance in female patients with breast cancer treated with chemotherapy (CT) and either left or right thoracic irradiation (RT), using Doppler echocardiography.
Thirty-four patients with cancer of the left breast treated with surgical resection, adjuvant EC CT (epirubicin and cyclophosphamide) and conventionally fractionated left thoracic RT (study group) and a gender-and age-matched group of 34 patients with cancer of the right breast also treated with surgical resection, adjuvant EC CT and right thoracic RT (control group), were studied by echocardiography. Assessed were the left ventricular systolic performance by measuring the global ejection fraction (EF) and the shortening fraction (SF). Left ventricular diastolic performance was assessed by measuring the Doppler transmitral flow: the maximal velocity of the E wave (rapid filling/ Emax) and A wave (atrial filling/Emax) were measured. The ratio of Emax/Amax, the pressure half-time (PHT) of the E wave and the isovolumic relaxation time (IVRT) were also calculated.
The left ventricular diastolic performance was altered in the study group which showed a significant decrease (p <0.001) of Emax. A wave was significantly increased in the study group compared with the control group (p <0.001. The mitral E/A ratio was subunitary in both groups but more depressed in the study group. The E wave PHT was more prolonged in the study group compared to the control group (p <0.001). The IVRT was prolonged in the study group compared with the controls (p <0.05). The left ventricular systolic performance was within normal limits in both groups.
Our Doppler echocardiography study documented an impaired left ventricular diastolic performance in patients with cancer of the left breast treated with fractionated thoracic RT and CT. This impairment is due to poor left ventricular compliance.
No preview · Article · Jul 2007 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
[Show abstract][Hide abstract] ABSTRACT: To determine the efficacy, toxicity and survival of concurrent therapy with vinorelbine and a platinum compound with radiotherapy (RT), followed by consolidation chemotherapy with the same drugs, for locally advanced non small cell lung cancer (NSCLC).
Fifty-seven patients with stage III NSCLC were included in this phase II study: median age 56 years (range 44-71), males / females 49/8, ECOG performance status (PS) 1/2=27/30, stage IIIA/ IIIB 11/46, squamous cell carcinoma 44, adenocarcinoma 7, adenoid cystic carcinoma 1 and large cell carcinoma 5. Treatment consisted of 2 cycles of chemotherapy with vinorelbine and cisplatin or carboplatin, given concurrently with RT, followed by 2-4 more cycles of consolidation chemotherapy with the same drugs. Twenty-two patients received amifostine for radio- and chemoprotection.
Grade 3 or 4 toxicities were neutropenia and esophagitis in 19% of the patients each, and gastrointestinal toxicity in 17% of the patients. Of the 55 patients evaluable for response, 23.64% achieved complete response (CR) and 40% partial response (PR) (overall response rate 63.64%). Progression-free survival curves showed 1- and 2-year values of 42% and 21%, respectively, and median time to progression 10.5 months. The 1- and 2- year disease-specific survival was 58% and 29%, and the median overall survival 15 months.
Preliminary analysis indicates that concurrent vinorelbine and a platinum compound with RT followed by consolidation chemotherapy with the same drugs for advanced stage III NSCLC is well tolerated, has considerable activity and positive impact on survival.
No preview · Article · Jan 2007 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
[Show abstract][Hide abstract] ABSTRACT: In the present study the left ventricular diastolic and systolic functions were evaluated in patients treated with lower total doses of epirubicin using Doppler echocardiography.
Seventeen patients with different malignant tumors treated with epirubicin up to 450 mg/m(2) (study group), and a gender-and age-matched group of 29 patients diagnosed with tumors, who had not started treatment yet (control group), were assessed by echocardiography. Left ventricular diastolic function was assessed by measuring the Doppler transmitral flow. We measured the maximal velocity of the E wave (rapid filling) and A wave (atrial filling). The ratio of Emax/Amax, the pressure half time (PHT) of the E wave and the iso-volumic relaxation time (IVRT) were also calculated. The left ventricular systolic performance was assessed by measuring the global ejection fraction (EF).
The left ventricular diastolic performance was altered in the study group. In this group we noticed a significant decrease ( p < 0.001) of Emax. A wave was significantly increased in the study group compared to the control group ( p < 0.001). The mitral E/A ratio was subunitary in the study group. The E wave PHT was prolonged in the epirubicin-treated group in comparison to the controls (p<0.001). The IVRT was prolonged in the study group in comparison to the controls (p<0.05). The left ventricular systolic performance was not significantly altered in the study group compared to the control group. Although the EF was lower in the study group the difference did not reach statistical significance.
Our Doppler echocardiography study documented an impaired left ventricular diastolic performance in patients with various malignancies treated with lower total doses of epirubicin. This impairment is due to poor left ventricular compliance.
No preview · Article · Jan 2005 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose: This multicenter phase II study was conducted to investigate the activity and toxicity of a combination of paclitaxel and carboplatin delivered on an outpatient basis in relapsed/ metastatic nasopharyngeal carcinoma patients. Patients and methods: Patients aged ≥18 years with histologically proven recurrent or metastatic nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and a life expectancy of ≥12 weeks were eligible. Measurable disease outside prior radiotherapy ports was required, unless a subsequent progression of the lesion was documented. An interval of ≥12 months was required between the previous chemotherapy (neoadjuvant, concurrent chemoradiotherapy or adjuvant) and study entry. Prior radiotherapy or surgery were allowed. All patients had adequate bone marrow (WBC > 4000/mL, platelets >100000/mL), hepatic (bilirubin <1,5 mg/dL, SGPT <1.5×N), and renal function (serum creatinine <1.5 mg/dL or creatinine clearance >60 mL/min). Chemotherapy consisted of paclitaxel 175 mg/m 2, given as a 3-hour infusion, followed by carboplatin dosed to an area under the concentration-time curve (AUC) of 6 mg*min/mL, administered every 21 days. Results: 40 patients entered the study. There were 3 complete responders (CR) and 8 partial responders (PR), for an overall response rate (ORR) of 27.5% (95% confidence interval - C.I.: 14.5-44). Median time to progression (TTP) was 3.5 months, and median survival was 11.5 months. Grade 3-4 toxicity included leucopenia (17.5% of the patients), anaemia (17.5%), thrombocytopenia (10%), neutropenia (7.5%), and peripheral neuropathy (2.5%). Conclusion: These data indicate that the combination of paclitaxel and carboplatin can be safely administered on an outpatient basis, but it is only moderately active against relapsed/metastatic nasopharyngeal carcinoma patients.