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      Nasopharyngeal carcinoma in adults: treatment results after long-term follow-up with special reference to adjuvant interferon-beta in undifferentiated carcinomas

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          Abstract

          Purpose

          Nasopharyngeal carcinomas (NPC) are radiosensitive, and radiotherapy is the standard curative treatment. Furthermore, it has been shown that combined radiochemotherapy improves prognosis in locally advanced stages. Further encouraging results have been obtained with adjuvant interferon-beta after primary radio(chemo)therapy in childhood undifferentiated NPC. Aim of the present study was to evaluate the treatment results after long-term follow-up after radio(chemo)therapy for adult NPC with special reference to patients with undifferentiated carcinomas treated with adjuvant interferon-beta.

          Patients and methods

          From 02/1992 to 07/2008, 26 adult patients with NPC without distant metastases were treated (17 squamous cell carcinomas, 9 undifferentiated carcinomas). The treatment concepts changed over the years: 13 patients were treated with radiotherapy alone, 13 patients received combined radiochemotherapy. Additionally, six patients with undifferentiated carcinomas were treated with adjuvant interferon-beta after radiochemotherapy for 6 months.

          Results

          After a median follow-up of 96 months, 17 patients remain alive. Collectively, our 5-year overall-survival and loco-regional control rates were 74% (radiochemotherapy 81%, radiotherapy alone 68.5%) and 87% (radiochemotherapy 100%, radiotherapy alone 72.7%), respectively. All treatment regimens used were feasible; especially, adjuvant interferon-beta was applied as provided without high grade toxicity. All patients with undifferentiated carcinomas treated with adjuvant interferon-beta stayed alive until the end of the follow-up.

          Conclusion

          In summary, our data affirm that NPC in adults are curable by primary radio(chemo)therapy. Furthermore, our data indicate that adjuvant interferon-beta application in undifferentiated NPC in adults is feasible and shows promising results. Further prospective clinical trials are needed to finally establish adjuvant interferon beta in curative treatment of adult NPC.

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          Most cited references40

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          The causal relation between human papillomavirus and cervical cancer.

          The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
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            Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update.

            Data on human papillomavirus (HPV) type distribution in invasive and pre-invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV-based screening tests. A meta-analyses of HPV type distribution in invasive cervical cancer (ICC) and high-grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74-77%) than in Africa, Asia and South/Central America (65-70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under-represented, and other high-risk HPV types significantly over-represented in HSIL compared to ICC, suggesting differences in type-specific risks for progression. Data on HPV-typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia. Copyright (c) 2007 Wiley-Liss, Inc.
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              Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

              The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.
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                Author and article information

                Contributors
                +49-5513914687 , +49-551396192 , hendrik.wolff@med.uni-goettingen.de , drhawolff@googlemail.com
                Journal
                J Cancer Res Clin Oncol
                Journal of Cancer Research and Clinical Oncology
                Springer-Verlag (Berlin/Heidelberg )
                0171-5216
                1432-1335
                18 July 2009
                January 2010
                : 136
                : 1
                : 89-97
                Affiliations
                [1 ]Department of Radiotherapy and Radiooncology, Universitätsmedizin Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
                [2 ]Department of Otolaryngology, Universitätsmedizin Göttingen, Göttingen, Germany
                [3 ]Department of Pathology, Universitätsmedizin Göttingen, Göttingen, Germany
                [4 ]Department of Haematology and Oncology, Universitätsmedizin Göttingen, Göttingen, Germany
                Article
                640
                10.1007/s00432-009-0640-2
                2779341
                19618214
                9678ec15-d11c-47c7-9393-92c2bf3ea344
                © The Author(s) 2009
                History
                : 16 April 2009
                : 23 June 2009
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag 2010

                Oncology & Radiotherapy
                nasopharyngeal carcinoma,ebv,interferon-beta,radiochemotherapy
                Oncology & Radiotherapy
                nasopharyngeal carcinoma, ebv, interferon-beta, radiochemotherapy

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