Publications (26)130.72 Total impact
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Article: Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype.
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ABSTRACT: Background We sought to determine biomarker expression differences in head and neck squamous cell cancers (HNSCCs) based on p16/human papillomavirus (HPV) classification. In addition, our aim was to explore how expression of biomarkers is modulated after E6/E7 repression in HPV16(+) oropharyngeal cancer cells.MethodsHPV16(+) and HPV(-) HNSCC cells were infected with retroviruses expressing short hairpin RNA targeting HPV16 E6/E7. Components of the epidermal growth factor receptor (EGFR) pathway before and after E6/E7 gene silencing were analyzed by immunoblotting and qRT-PCR. Protein expression of 13 biomarkers was analyzed using AQUA on a tissue microarray (TMA). The HPV16 status was determined using HPV16 in situ hybridization (ISH).ResultsIn HPV16(+) cells, E6/E7 silencing was associated with PTEN upregulation and reduction of phosphorylated EGFR. Tumors were classified into four categories based on the HPV and p16 status. HPV(+)/p16(+) tumors expressed significantly higher levels of E-cadherin (P = 0.003), PTEN (P = 0.004), lower levels of PI3Kp110 and β-catenin (P = 0.07). There was a significant difference in overall survival (OS, P = 0.016) among the four subsets. The median OS was 24.83 months for p16(-)/HPV(-) patients, 11.63 for p16(-)/HPV(+) patients and was not reached for p16(+)/HPV(-) and p16(+)/HPV(+) groups.Conclusions Aberrant EGFR signaling contributes to malignant conversion of HPV16(+) HNSCC cells. These results validate β-catenin as a distinct biomarker in HPV(+)/p16(+) HNSCC. Wnt signaling inhibitors merit exploration in HPV(+)/p16(+) HNSCC.Annals of Oncology 02/2013; · 6.43 Impact Factor -
Article: Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03).
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ABSTRACT: Background The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC.Patients and methodsOne hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events).ResultsThe median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%).Conclusions Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population.Clinical Trial NumberACTRN12610000845033, www.anzctr.org.au.Annals of Oncology 11/2012; · 6.43 Impact Factor -
Article: Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study.
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ABSTRACT: The ubiquitin-proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients. Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose-dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one-step quantitative RT-PCR for assessment of mRNA expression of UBE2C. High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05). High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts.Annals of Oncology 11/2011; 23(6):1422-7. · 6.43 Impact Factor -
Article: The prognostic significance of p16 overexpression in oropharyngeal squamous cell carcinoma: implications for treatment strategies and future clinical studies.
Annals of Oncology 10/2010; 21(10):1931-4. · 6.43 Impact Factor -
Article: Carboplatin/gemcitabine alternating with carboplatin/pegylated liposomal doxorubicin and carboplatin/cyclophosphamide in platinum-refractory/resistant paclitaxel - pretreated ovarian carcinoma.
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ABSTRACT: In this phase II study the efficacy and toxicity of an alternating chemotherapy regimen was examined in platinum-resistant relapsed epithelial ovarian cancer (EOC) patients. Forty-five patients with platinum-refractory/resistant relapsed EOC, previously treated with carboplatin+paclitaxel+/-epirubicin were included. The regimen was consisted of gemcitabine 800 mg/m(2) (days 1+8) and carboplatin AUC 5, alternating with pegylated liposomal doxorubicin 30 mg/m(2) and carboplatin AUC 5, alternating with carboplatin AUC 5 and cyclophosphamide 600 mg/m(2), every 3 weeks for a total of 9 cycles. Among 38 patients with measurable disease, 39.4% (95% CI: 23.2-55.7) responded (five complete response and 10 partial response), while 30 out of 40 (75%) patients assessable by CA125 criteria had a serological response. Responses were more frequent in patients with platinum-free interval (PFI) 3-6 months than in those with PFI 0-3 months, but this was not statistically-significant. After a median follow-up of 19.5 months (range, 1.0-37+ months) the median progression-free survival was 7.1 months (95% CI: 3.4-10.8) and the median survival (OS) was 18.8 months (95% CI: 15.6-22.0). For patients with PFI 0-3 months PFS was 4.3 (95% CI: 0.8-7.8) months, while for those with PFI 3-6 months PFS was 8.9 (95% CI: 5.3-12.4) months (p=0.062). The regimen was well-tolerated and the main grade 3-4 toxicity was myelosuppression, palmar-plantar erythrodysesthesia, allergy and fatigue. This alternating regimen, including carboplatin, gemcitabine, liposomal doxorubicin and cyclophosphamide, is an active and well-tolerated treatment in platinum relapsed/refractory EOC patients.Gynecologic Oncology 07/2010; 118(1):52-7. · 3.89 Impact Factor -
Article: Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.
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ABSTRACT: Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.Annals of Oncology 03/2010; 21(10):1952-60. · 6.43 Impact Factor -
Article: Gastric metastases originating from breast cancer: report of 8 cases and review of the literature.
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ABSTRACT: Breast cancer metastasis to the stomach is rare. It is very important to distinguish a breast cancer metastasis to the stomach from a primary gastric cancer on the basis of clinical, endoscopic, radiological and histopathological features, in order to administer the appropriate treatment. Eight patients with breast cancer metastasis to the stomach were identified in our database between 1995 and 2008. The clinicopathological data and outcome from the medical records of these patients were then reviewed. The median age at initial breast cancer diagnosis was 59.5 years (range 44-75 years), while the median interval between the primary breast cancer and the gastric involvement was 41 months (range 2-82 months). The primary breast cancer histological subtype was mostly lobular carcinoma. All the biopsy specimens were estrogen receptor (ER), cytokeratin (CK) 7 and gross cystic disease fluid protein-15 (GCDFP-15) positive and CK-20 negative, while two of them (25%) were HER-2-neu positive. All the patients received chemotherapy and two of them were also treated with hormonal treatment. Two patients underwent surgical intervention, while one patient who had gastric involvement as the only metastatic site will proceed to surgical resection of the stomach. All these three patients were alive after 9, 39 and 44 months of follow-up, respectively. The response rate to chemotherapy was 50% (1 complete response [CR], 3 partial responses [PR]), and the median survival was 11 months (range, 1-44+ months). Breast cancer metastasis to the stomach can be differentiated from primary gastric cancer by comparing the biopsies from the gastric metastasis with the original histological slides from the primary breast tumor. Appropriate systemic treatment for metastatic breast carcinoma is the preferred treatment, whereas surgical intervention should be reserved for palliation or may be indicated in cases of solitary resectable gastrointestinal tract metastases.Anticancer research 11/2009; 29(11):4759-63. · 1.73 Impact Factor -
Article: Primary extranodal lymphomas of stomach: clinical presentation, diagnostic pitfalls and management.
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ABSTRACT: Gastrointestinal lymphoma is the most common form of extranodal lymphoma, accounting for 30%-40% of cases. The most commonly involved site is the stomach (60%-75% of cases), followed by the small bowel, ileum, cecum, colon and rectum. The most common histological subtypes are diffuse large B-cell lymphoma (DLBCL) and marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Helicobacter pylori infection has been implicated in the pathogenesis of MALT gastric lymphoma, but its role in gastric diffuse large B-cell non-Hodgkin's lymphoma (NHL) is controversial. The therapeutic approach for patients with gastric NHL has been revised over the last 10 years. Conservative treatment with anthracycline-based chemotherapy alone or in combination with involved-field radiotherapy has replaced gastrectomy as standard therapy in cases with DLBCL. Additionally, MALT lymphomas are mainly treated with antibiotics alone, which can induce lasting remissions in those cases associated with H. pylori infection. Nevertheless, various therapeutic aspects for primary gastric lymphomas are still controversial and several questions remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as H. pylori eradication in histological aggressive subtypes warrants better clarification.Annals of Oncology 12/2008; 19(12):1992-9. · 6.43 Impact Factor -
Article: Optimizing approaches to head-and-neck cancers. Viruses in head-and-neck cancers: prevention and therapy.
Annals of Oncology 09/2008; 19 Suppl 7:vii189-94. · 6.43 Impact Factor -
Article: Primary ovarian lymphoma: report of two cases and review of the literature.
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ABSTRACT: Ovarian lymphoma is a rare entity. Clinicians should be aware of its clinical manifestations and management since surgery alone often is not adequate treatment. Here, we present two cases of ovarian lymphoma and discuss what is known about ovarian lymphoma.Journal of chemotherapy (Florence, Italy) 09/2008; 20(4):513-7. · 1.08 Impact Factor -
Article: Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression.
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ABSTRACT: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 7 (hk7) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. A tissue array composed of 150 advanced-stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of kallikrein 7 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred and twenty eight of 150 cases had sufficient tissue for AQUA. In univariate survival analysis, low tumor hk7 expression was associated with better outcome for overall survival (OS) and disease-free survival in 3 years (P values 0.032 and 0.037, respectively). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor hk7 expression level was the most significant predictor variable for OS (95% confidence interval 0.125-0.729, P = 0.007). High tumor hk7 protein expression is associated with inferior patient outcome in ovarian cancer. hk7 may represent a promising prognostic factor in ovarian cancer.Annals of Oncology 08/2008; 19(7):1271-7. · 6.43 Impact Factor -
Article: Carboplatin and paclitaxel in advanced or metastatic endometrial cancer.
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ABSTRACT: The purpose of this study was to evaluate the activity and toxicity of carboplatin and paclitaxel combination in advanced or recurrent endometrial carcinoma. Forty-seven eligible patients with measurable advanced or recurrent endometrial carcinoma were treated with carboplatin [area under the curve (AUC) 5] and paclitaxel 175 mg/m(2) every 3 weeks for 6-9 cycles or until disease progression or unacceptable toxicity. There were 10 complete responses (CRs) (21%) and 19 partial responses (PRs) (41%) for an overall response rate (RR) of 62% (29 patients) (95% confidence interval [CI], 47-76%). The median progression-free survival (PFS) was 15 months (95% CI, 7.3-22.7 months) and the median overall survival (OS) was 25 months (95% CI, 19.0-31.0 months). No difference was found in RR and OS in patients with primary advanced disease and those with recurrent tumors. Similarly, no difference was found in PFS and OS for patients with serous/clear tumors and those with endometrioid tumors. Toxicity was generally mild except for myelotoxicity. Neutropenia grade 3/4 was recorded in 36% of patients and 6% experienced febrile neutropenia. One patient each developed grade 4 thrombocytopenia and anemia. Grade 3 sensory neuropathy was recorded in 6% of patients. The combination of carboplatin and paclitaxel appears to have activity in advanced or recurrent endometrial carcinoma with an acceptable toxicity profile.Gynecologic Oncology 06/2008; 109(2):250-4. · 3.89 Impact Factor -
Article: Granulosa cell tumor of the ovary.
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ABSTRACT: Ovarian granulosa cell tumors (GCTs) are uncommon neoplasms that arise from the sex-cord stromal cells of the ovary. GCTs are characterized by long natural history and their tendency to recur years after the initial diagnosis. They present with symptoms and signs due to estradiol secretion, including vaginal bleeding and precocious puberty. Occasionally, tumor rupture causes abdominal pain and hemoperitoneum. GCT is usually associated with a mass on pelvic examination which is subsequently confirmed with imagine techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging and debulking surgery. In patients with stage I disease and those in reproductive age a more conservative unilateral salpingo-oophorectomy is indicated. In postmenopausal women and those with more advanced disease a total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment. The most important prognostic factor associated with a higher risk of relapse is the stage of disease. The role of post-operative chemo- or radiotherapy in stage I disease and those with completely resected tumor has not been defined. Nevertheless, the use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy should be considered for patients with advanced, recurrent or metastatic disease and the BEP (bleomycin, etoposide, cisplatin) is the currently preferable regimen. Although overall response rate (RR) is high, the impact on disease-free or overall survival is unknown. Due to their tendency to recur years after the initial diagnosis, prolonged surveillance is essential.Cancer Treatment Reviews 03/2008; 34(1):1-12. · 6.05 Impact Factor -
Article: Analysis of p53 protein expression levels on ovarian cancer tissue microarray using automated quantitative analysis elucidates prognostic patient subsets.
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ABSTRACT: p53 protein is regarded as a valuable prognostic marker in cancer with a potential use as a molecular target. Here, we sought to determine the prognostic value of p53 in ovarian cancer using a novel method of compartmentalized in situ protein analysis. A tissue array composed of 141 advanced stage ovarian cancers uniformly treated was constructed. For evaluation of p53 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). High nuclear p53 expression levels were associated with better outcome for overall survival (OS) (P = 0.0023) and disease-free survival (P = 0.0338) at 5-years. High cytoplasmic p53 expression levels were associated with better outcome for OS (P = 0.0002). In multivariable analysis, high nuclear and high cytoplasmic p53 level with International Federation of Gynecology and Obstetrics (FIGO) stage were the most significant predictor variables for OS and high nuclear p53 level with FIGO stage were the significant predictor variables for disease-free survival. Assessment of the prognostic value of p53 protein levels using conventional immunohistochemistry is limited by the nonquantitative nature of the method. AQUA provides precise estimation of p53 protein levels and was able to elucidate the association of p53 protein levels and ovarian cancer prognosis.Annals of Oncology 05/2007; 18(4):709-15. · 6.43 Impact Factor -
Article: Cisplatin-based chemotherapy for merkel cell carcinoma of the skin.
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ABSTRACT: Merkel cell carcinoma (MCC), a rare tumor of the skin with aggressive behavior, is usually fatal when advanced disease is present. The role of chemotherapy (CT) in the treatment of patients with MCC is unclear. Over 15 years, 9 patients with locally advanced or metastatic disease were treated with carboplatin (CBDCA) (300 mg/m(2) of AUC 5 on Day 1) and etoposide (VP-16) (100 mg/m(2) on Days 1-3) every 3 weeks. As second-line CT, cisplatin (CDDP) (60-100 mg/m(2)), ifosfamide (IFO) (3-5 g/m(2)) and epirubicin (EPI) (30-50 mg/m(2)) were utilized. Of the 3 patients who received adjuvant therapy, one achieved complete response after 108+ months with second-line chemotherapy and radiotherapy, despite a brief relapse; 2 patients remain disease-free after 84+ and 108+ months. Of the 6 patients with locally advanced or metastatic disease who were treated with first-line chemotherapy, one (16.6 percent) achieved a complete response and 3 (50 percent) achieved partial response, for an overall response rate of 66.6 percent. Two patients (one with complete and one with partial response) received subsequent radiotherapy, following which complete response was achieved. Of the 2 complete responders, one patient remains disease-free after 56+ months. The median overall survival from the time of initial diagnosis for the whole group was 56 months (range 15-114 months); the median overall survival from the initiation of chemotherapy was 18 months (range 6-108+). Local recurrences and soft tissue metastases responded better than visceral metastases. Patients with partial response and no response had rapid disease progression and fatality, despite second-line chemotherapy and/or radiotherapy. MCC appears to be chemosensitive but can progress rapidly with fatal outcomes. Although the rarity of these tumors precludes randomized trials, a common treatment plan should be utilized by those treating MCC. This may allow some conclusions regarding the optimum treatment of patients with MCC to be drawn in the future.Cancer Investigation 01/2007; 24(8):780-5. · 1.85 Impact Factor -
Article: Automated quantitative analysis of DCC tumor suppressor protein in ovarian cancer tissue microarray shows association with beta-catenin levels and outcome in patients with epithelial ovarian cancer.
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ABSTRACT: The deleted in colorectal cancer (DCC) protein, the product of DCC tumor suppressor gene, is frequently altered in cancer. Preclinical data demonstrate that DCC regulates beta-catenin levels. Here, we sought to determine the association of DCC with beta-catenin protein levels, clinicopathological parameters and patient outcome in ovarian cancer using a method of in situ compartmentalized protein analysis. A tissue array composed of 150 advanced-stage ovarian cancers, treated with surgical debulking and platinum-paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). One hundred and twelve patients (74%) had sufficient tissue for AQUA. The median follow-up time for the entire cohort was 33 months. Patients with low nuclear DCC expression had a 3-year progression-free survival (PFS) rate of 0% compared with 33% of those with high DCC expression (P = 0.0067). In multivariate analysis, low nuclear DCC expression level retained its prognostic significance for PFS. Between DCC and beta-catenin, a significant relationship was found, where tumors with low DCC had low beta-catenin and vice versa (P = 0.003). Low nuclear DCC levels predict for poor patient outcome in epithelial ovarian cancer. DCC may exert its antitumor function, in part, through regulation of beta-catenin levels.Annals of Oncology 01/2007; 17(12):1797-802. · 6.43 Impact Factor -
Article: Optimal therapy for platinum-resistant recurrent ovarian cancer: doxorubicin, gemcitabine or topotecan?
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ABSTRACT: Ovarian cancer is more fatal than all the other gynaecological malignancies combined. Although most patients respond to first-line combination chemotherapy, the vast majority (50-75%) of patients with advanced disease will relapse. The management of patients with recurrent ovarian cancer is based on their response profile to platinum: patients with platinum-sensitive disease can be rechallenged with platinum-based chemotherapy, whereas the management of patients with platinum-resistant or -refractory disease remains an area of active investigation. In this review, the data for second-line therapy in this latter group of patients will be summarised and recommendations for their optimal management will be made.Expert Opinion on Pharmacotherapy 07/2006; 7(8):975-87. · 3.20 Impact Factor -
Article: Functional asplenia in a patient with Rothmann-Makai syndrome: a pathogenetic relationship?
Rheumatology 01/2006; 44(12):1588. · 4.06 Impact Factor -
Article: Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer.
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ABSTRACT: Functional inactivation of p16 is an early and frequent event in head and neck squamous cell cancers. In this study, we sought to determine whether p16 expression is of prognostic importance in oropharyngeal squamous cell carcinoma. p16 protein expression was evaluated by immunohistochemistry in a tissue microarray composed of 123 oropharyngeal squamous cell cancers with a mean patient follow-up time of 33 months. p16 overexpression was associated with more advanced Tumor-Node-Metastasis stage and higher histologic grade. Despite this association with unfavorable features, p16 overexpression was associated with decreased 5-year local recurrence rates (11 versus 53%) and increased 5-year disease-free survival (62 versus 19%) and overall survival (60 versus 21%). In multivariate analysis, p16 expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. In patients with oropharyngeal squamous cell carcinoma, overexpression of p16 as determined by immunohistochemistry is associated with significantly improved prognosis and lower local recurrence rates.Clinical Cancer Research 10/2004; 10(17):5684-91. · 7.74 Impact Factor -
Article: Cisplatin, fluorouracil, and leucovorin induction chemotherapy followed by concurrent cisplatin chemoradiotherapy for organ preservation and cure in patients with advanced head and neck cancer: long-term follow-up.
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ABSTRACT: The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.Journal of Clinical Oncology 09/2004; 22(15):3061-9. · 18.37 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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ΓΕΝ.ΝΟΣΟΚΟΜΕΙΟ ΑΛΕΞΑΝΔΡΑ
Athens, Attiki, Greece
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2006–2011
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Attikon University Hospital
Athens, Attiki, Greece
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2004–2008
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Yale-New Haven Hospital
New Haven, CT, USA -
Yale University
New Haven, CT, USA
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2007
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Harokopion University of Athens
Athens, Attiki, Greece
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