Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx
To assess the prognostic value of apoptosis, proliferation and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (...
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| Veröffentlicht in: | Oral oncology 2003-07, Vol.39 (5), p.459-469 |
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| creator | GRABENBAUER, Gerhard G SUCKORADA, Olga NIEDOBITEK, Gerald RÖDEL, Franz IRON, Heiner SAUER, Rolf RÖDEL, Claus SCHULTZE-MOSGAU, Stefan DISTEL, Luitpold |
| description | To assess the prognostic value of apoptosis, proliferation and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (50%) involved the tonsils, 23 (27%) the soft palate, and 19 (23%) the base of the tongue. Median age was 52 years (range, 36-73 years). The pT- and pN-categories (UICC 1997) were: T1 (24), T2 (36), T3 (18), T4 (6), N0 (31), N1 (12), N2 (38), NX (8). Histologically clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given with 60 Gy in 6 weeks and single daily fractions of 2 Gy. The expression of the nuclear Ki-67 labeling index (LI) was investigated by immunostaining using the monoclonal antibody MIB 1 and apoptotic carcinoma cells were identified using the terminal deoxynucleotidyltransferase-(TdT)-mediated dUTP nick end labeling (TUNEL) technique. Median follow-up was 43 months (range, 14-132 months). Overall survival, disease-free survival, and locoregional tumor control rates were 59, 70 and 76% at 5 years. Median values for apoptotic index and Ki-67 labeling were 1.6% (range 0-4.7%), and 20% (range, 0-79%), respectively. Apoptotic index |
| doi_str_mv | 10.1016/S1368-8375(03)00005-8 |
| format | Article |
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Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (50%) involved the tonsils, 23 (27%) the soft palate, and 19 (23%) the base of the tongue. Median age was 52 years (range, 36-73 years). The pT- and pN-categories (UICC 1997) were: T1 (24), T2 (36), T3 (18), T4 (6), N0 (31), N1 (12), N2 (38), NX (8). Histologically clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given with 60 Gy in 6 weeks and single daily fractions of 2 Gy. The expression of the nuclear Ki-67 labeling index (LI) was investigated by immunostaining using the monoclonal antibody MIB 1 and apoptotic carcinoma cells were identified using the terminal deoxynucleotidyltransferase-(TdT)-mediated dUTP nick end labeling (TUNEL) technique. Median follow-up was 43 months (range, 14-132 months). Overall survival, disease-free survival, and locoregional tumor control rates were 59, 70 and 76% at 5 years. Median values for apoptotic index and Ki-67 labeling were 1.6% (range 0-4.7%), and 20% (range, 0-79%), respectively. Apoptotic index <or=1.6% had a profound negative impact when associated with higher proliferation rates (5-year disease-free survival: 26%) as compared to all other patients with a balance between apoptosis and proliferation (5-year disease-free survival: 66-86%, P=0.003). Additional significant prognostic factors for disease-free survival were: tumor site (tonsils: 83% vs soft palate: 66% vs base of tongue: 49%, P=0.02), duration of RT (<or=47 days: 83% vs >47 days: 55%, P=0.03), Ki-67 LI (<or=20%: 84% vs >20%: 56%, P=0.006). A significant prognostic impact on locoregional control was noted for the duration of RT (P=0.01), tumor site (P=0.02), and the Ki-67 LI (P=0.02). A low apoptotic index together with higher proliferation rates led to unfavourable local control as low as 25% compared to the patients with higher apoptotic index (70-80%, P=0.009). An imbalance between apoptotic index and proliferation may identify patients with squamous cell carcinoma at high risk for local recurrence after surgery and postoperative RT. Prospective observation of these factors in clinical trials is warranted to further elucidate this phenomenon.</description><identifier>ISSN: 1368-8375</identifier><identifier>EISSN: 1879-0593</identifier><identifier>DOI: 10.1016/S1368-8375(03)00005-8</identifier><identifier>PMID: 12747970</identifier><language>eng</language><publisher>Oxford: Elsevier</publisher><subject>Adult ; Aged ; Apoptosis - physiology ; Biological and medical sciences ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - radiotherapy ; Carcinoma, Squamous Cell - surgery ; Cell Division - physiology ; Combined Modality Therapy ; Female ; Humans ; Male ; Medical sciences ; Middle Aged ; Oropharyngeal Neoplasms - pathology ; Oropharyngeal Neoplasms - radiotherapy ; Oropharyngeal Neoplasms - surgery ; Otorhinolaryngology. Stomatology ; Palatal Neoplasms - pathology ; Palatal Neoplasms - radiotherapy ; Palatal Neoplasms - surgery ; Survival Analysis ; Tongue Neoplasms - pathology ; Tongue Neoplasms - radiotherapy ; Tongue Neoplasms - surgery ; Tonsillar Neoplasms - pathology ; Tonsillar Neoplasms - radiotherapy ; Tonsillar Neoplasms - surgery ; Treatment Failure ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>Oral oncology, 2003-07, Vol.39 (5), p.459-469</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c335t-d40786370ff9be2c1618f77bbcf7334f3fff210f05bb19ee0fc0193892e37bb43</citedby><cites>FETCH-LOGICAL-c335t-d40786370ff9be2c1618f77bbcf7334f3fff210f05bb19ee0fc0193892e37bb43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14749784$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12747970$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GRABENBAUER, Gerhard G</creatorcontrib><creatorcontrib>SUCKORADA, Olga</creatorcontrib><creatorcontrib>NIEDOBITEK, Gerald</creatorcontrib><creatorcontrib>RÖDEL, Franz</creatorcontrib><creatorcontrib>IRON, Heiner</creatorcontrib><creatorcontrib>SAUER, Rolf</creatorcontrib><creatorcontrib>RÖDEL, Claus</creatorcontrib><creatorcontrib>SCHULTZE-MOSGAU, Stefan</creatorcontrib><creatorcontrib>DISTEL, Luitpold</creatorcontrib><title>Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx</title><title>Oral oncology</title><addtitle>Oral Oncol</addtitle><description>To assess the prognostic value of apoptosis, proliferation and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (50%) involved the tonsils, 23 (27%) the soft palate, and 19 (23%) the base of the tongue. Median age was 52 years (range, 36-73 years). The pT- and pN-categories (UICC 1997) were: T1 (24), T2 (36), T3 (18), T4 (6), N0 (31), N1 (12), N2 (38), NX (8). Histologically clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given with 60 Gy in 6 weeks and single daily fractions of 2 Gy. The expression of the nuclear Ki-67 labeling index (LI) was investigated by immunostaining using the monoclonal antibody MIB 1 and apoptotic carcinoma cells were identified using the terminal deoxynucleotidyltransferase-(TdT)-mediated dUTP nick end labeling (TUNEL) technique. Median follow-up was 43 months (range, 14-132 months). Overall survival, disease-free survival, and locoregional tumor control rates were 59, 70 and 76% at 5 years. Median values for apoptotic index and Ki-67 labeling were 1.6% (range 0-4.7%), and 20% (range, 0-79%), respectively. Apoptotic index <or=1.6% had a profound negative impact when associated with higher proliferation rates (5-year disease-free survival: 26%) as compared to all other patients with a balance between apoptosis and proliferation (5-year disease-free survival: 66-86%, P=0.003). Additional significant prognostic factors for disease-free survival were: tumor site (tonsils: 83% vs soft palate: 66% vs base of tongue: 49%, P=0.02), duration of RT (<or=47 days: 83% vs >47 days: 55%, P=0.03), Ki-67 LI (<or=20%: 84% vs >20%: 56%, P=0.006). A significant prognostic impact on locoregional control was noted for the duration of RT (P=0.01), tumor site (P=0.02), and the Ki-67 LI (P=0.02). A low apoptotic index together with higher proliferation rates led to unfavourable local control as low as 25% compared to the patients with higher apoptotic index (70-80%, P=0.009). An imbalance between apoptotic index and proliferation may identify patients with squamous cell carcinoma at high risk for local recurrence after surgery and postoperative RT. Prospective observation of these factors in clinical trials is warranted to further elucidate this phenomenon.</description><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - radiotherapy</subject><subject>Carcinoma, Squamous Cell - surgery</subject><subject>Cell Division - physiology</subject><subject>Combined Modality Therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oropharyngeal Neoplasms - pathology</subject><subject>Oropharyngeal Neoplasms - radiotherapy</subject><subject>Oropharyngeal Neoplasms - surgery</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Palatal Neoplasms - pathology</subject><subject>Palatal Neoplasms - radiotherapy</subject><subject>Palatal Neoplasms - surgery</subject><subject>Survival Analysis</subject><subject>Tongue Neoplasms - pathology</subject><subject>Tongue Neoplasms - radiotherapy</subject><subject>Tongue Neoplasms - surgery</subject><subject>Tonsillar Neoplasms - pathology</subject><subject>Tonsillar Neoplasms - radiotherapy</subject><subject>Tonsillar Neoplasms - surgery</subject><subject>Treatment Failure</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>1368-8375</issn><issn>1879-0593</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc-OFCEQxonRuOvoI2jqolkPrdB0D81xs_HPJpt4UM8EmCKL6QYW6NV5Hx9UZnbM1oWq5FfFl-8j5DWjHxhl24_fGd9O3cTFeEH5e9pq7KYn5JxNQnZ0lPxp6_8jZ-RFKb8ODBvpc3LGejEIKeg5-Xu9GD3rYBEM1t-IAVKOs3eYdfUxgA470CmmGosvsOh94yBjSTEUb2YEFzPUjLouGCo47ec1I2hXMUOKpcZ0PHXftvTOx3rbxrQHH6DcrXqJawGL8wxWZ-tDXDREB42CmGO61Xkf_rwkz5yeC746vRvy8_OnH1dfu5tvX66vLm86y_lYu91AxbTlgjonDfaWbdnkhDDGOsH54LhzrmfU0dEYJhGps5RJPskeeaMGviHvHu42C-5WLFUtvhzE6YBNpxK8l838sYHjA2hzLCWjUyn7pWlVjKpDPOoYjzp4ryhXx3jatCFvTh-sZsHd49Ypjwa8PQG6WD273JLx5ZEbxCDFNPB_z26dnw</recordid><startdate>20030701</startdate><enddate>20030701</enddate><creator>GRABENBAUER, Gerhard G</creator><creator>SUCKORADA, Olga</creator><creator>NIEDOBITEK, Gerald</creator><creator>RÖDEL, Franz</creator><creator>IRON, Heiner</creator><creator>SAUER, Rolf</creator><creator>RÖDEL, Claus</creator><creator>SCHULTZE-MOSGAU, Stefan</creator><creator>DISTEL, Luitpold</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20030701</creationdate><title>Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx</title><author>GRABENBAUER, Gerhard G ; SUCKORADA, Olga ; NIEDOBITEK, Gerald ; RÖDEL, Franz ; IRON, Heiner ; SAUER, Rolf ; RÖDEL, Claus ; SCHULTZE-MOSGAU, Stefan ; DISTEL, Luitpold</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-d40786370ff9be2c1618f77bbcf7334f3fff210f05bb19ee0fc0193892e37bb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - radiotherapy</topic><topic>Carcinoma, Squamous Cell - surgery</topic><topic>Cell Division - physiology</topic><topic>Combined Modality Therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oropharyngeal Neoplasms - pathology</topic><topic>Oropharyngeal Neoplasms - radiotherapy</topic><topic>Oropharyngeal Neoplasms - surgery</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Palatal Neoplasms - pathology</topic><topic>Palatal Neoplasms - radiotherapy</topic><topic>Palatal Neoplasms - surgery</topic><topic>Survival Analysis</topic><topic>Tongue Neoplasms - pathology</topic><topic>Tongue Neoplasms - radiotherapy</topic><topic>Tongue Neoplasms - surgery</topic><topic>Tonsillar Neoplasms - pathology</topic><topic>Tonsillar Neoplasms - radiotherapy</topic><topic>Tonsillar Neoplasms - surgery</topic><topic>Treatment Failure</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GRABENBAUER, Gerhard G</creatorcontrib><creatorcontrib>SUCKORADA, Olga</creatorcontrib><creatorcontrib>NIEDOBITEK, Gerald</creatorcontrib><creatorcontrib>RÖDEL, Franz</creatorcontrib><creatorcontrib>IRON, Heiner</creatorcontrib><creatorcontrib>SAUER, Rolf</creatorcontrib><creatorcontrib>RÖDEL, Claus</creatorcontrib><creatorcontrib>SCHULTZE-MOSGAU, Stefan</creatorcontrib><creatorcontrib>DISTEL, Luitpold</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Oral oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GRABENBAUER, Gerhard G</au><au>SUCKORADA, Olga</au><au>NIEDOBITEK, Gerald</au><au>RÖDEL, Franz</au><au>IRON, Heiner</au><au>SAUER, Rolf</au><au>RÖDEL, Claus</au><au>SCHULTZE-MOSGAU, Stefan</au><au>DISTEL, Luitpold</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx</atitle><jtitle>Oral oncology</jtitle><addtitle>Oral Oncol</addtitle><date>2003-07-01</date><risdate>2003</risdate><volume>39</volume><issue>5</issue><spage>459</spage><epage>469</epage><pages>459-469</pages><issn>1368-8375</issn><eissn>1879-0593</eissn><abstract>To assess the prognostic value of apoptosis, proliferation and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (50%) involved the tonsils, 23 (27%) the soft palate, and 19 (23%) the base of the tongue. Median age was 52 years (range, 36-73 years). The pT- and pN-categories (UICC 1997) were: T1 (24), T2 (36), T3 (18), T4 (6), N0 (31), N1 (12), N2 (38), NX (8). Histologically clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given with 60 Gy in 6 weeks and single daily fractions of 2 Gy. The expression of the nuclear Ki-67 labeling index (LI) was investigated by immunostaining using the monoclonal antibody MIB 1 and apoptotic carcinoma cells were identified using the terminal deoxynucleotidyltransferase-(TdT)-mediated dUTP nick end labeling (TUNEL) technique. Median follow-up was 43 months (range, 14-132 months). Overall survival, disease-free survival, and locoregional tumor control rates were 59, 70 and 76% at 5 years. Median values for apoptotic index and Ki-67 labeling were 1.6% (range 0-4.7%), and 20% (range, 0-79%), respectively. Apoptotic index <or=1.6% had a profound negative impact when associated with higher proliferation rates (5-year disease-free survival: 26%) as compared to all other patients with a balance between apoptosis and proliferation (5-year disease-free survival: 66-86%, P=0.003). Additional significant prognostic factors for disease-free survival were: tumor site (tonsils: 83% vs soft palate: 66% vs base of tongue: 49%, P=0.02), duration of RT (<or=47 days: 83% vs >47 days: 55%, P=0.03), Ki-67 LI (<or=20%: 84% vs >20%: 56%, P=0.006). A significant prognostic impact on locoregional control was noted for the duration of RT (P=0.01), tumor site (P=0.02), and the Ki-67 LI (P=0.02). A low apoptotic index together with higher proliferation rates led to unfavourable local control as low as 25% compared to the patients with higher apoptotic index (70-80%, P=0.009). An imbalance between apoptotic index and proliferation may identify patients with squamous cell carcinoma at high risk for local recurrence after surgery and postoperative RT. Prospective observation of these factors in clinical trials is warranted to further elucidate this phenomenon.</abstract><cop>Oxford</cop><pub>Elsevier</pub><pmid>12747970</pmid><doi>10.1016/S1368-8375(03)00005-8</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult Aged Apoptosis - physiology Biological and medical sciences Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - radiotherapy Carcinoma, Squamous Cell - surgery Cell Division - physiology Combined Modality Therapy Female Humans Male Medical sciences Middle Aged Oropharyngeal Neoplasms - pathology Oropharyngeal Neoplasms - radiotherapy Oropharyngeal Neoplasms - surgery Otorhinolaryngology. Stomatology Palatal Neoplasms - pathology Palatal Neoplasms - radiotherapy Palatal Neoplasms - surgery Survival Analysis Tongue Neoplasms - pathology Tongue Neoplasms - radiotherapy Tongue Neoplasms - surgery Tonsillar Neoplasms - pathology Tonsillar Neoplasms - radiotherapy Tonsillar Neoplasms - surgery Treatment Failure Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
| title | Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx |
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