Lymph Node Status and TS Gene Expression Are Prognostic Markers in Stage II/III Rectal Cancer After Neoadjuvant Fluorouracil-Based Chemoradiotherapy
According to the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group, preoperative combined fluorouracil (FU) -based long-term chemoradiotherapy (CT/RT) is recommended for patients with International Union Against Cancer (UICC) stage II/III rectal cancer. However, despite the local benefit...
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| Veröffentlicht in: | Journal of clinical oncology 2006-09, Vol.24 (25), p.4062-4068 |
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| creator | LIERSCH, Torsten LANGER, Claus GHADIMI, B. Michael KULLE, Bettina AUST, Daniela E BARETTON, Gustavo B SCHWABE, Wolfgang HÄUSLER, Peter BECKER, Heinz JAKOB, Christiane |
| description | According to the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group, preoperative combined fluorouracil (FU) -based long-term chemoradiotherapy (CT/RT) is recommended for patients with International Union Against Cancer (UICC) stage II/III rectal cancer. However, despite the local benefit of neoadjuvant treatment, the overall prognostic value remains uncertain in comparison with adjuvant CT/RT. Furthermore, the prognostic value of molecular biomarkers, such as thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD), all of which are involved in the FU metabolism, is unknown in neoadjuvant settings. We assessed the impact of standardized preoperative CT/RT and intratumoral TS, TP, and DPD levels on patient outcome.
Forty patients with rectal cancer pretherapeutic UICC stage II/III, receiving preoperative FU-based CT/RT (CAO/ARO/AIO-94 trial) followed by standardized surgery, including total mesorectal excision, were investigated. Downsizing, downstaging, tumor regression, as well as TS, TP, and DPD gene expression of post-treatment surgical specimens were correlated with disease-free survival (DFS) and overall survival (OS).
Significant downsizing (P < .001) and downstaging (P = .001) were achieved with preoperative CT/RT. During a median follow-up of 49 months (95% CI, 43 to 58 months), the cancer recurrence rate was 28.2%. DFS and OS were significantly increased in patients with downstaging (P < .001 and P = .003, respectively), compared with patients without downstaging. All patients who developed cancer recurrence had a persistent positive lymph node status after preoperative CT/RT (P < .001) and a significantly higher TS gene expression (P = .035) compared with those patients without recurrence.
Persistent positive lymph node status and high intratumoral TS expression after preoperative CT/RT are predictive of an unfavorable prognosis in rectal cancer UICC stage II/III. |
| doi_str_mv | 10.1200/JCO.2005.04.2739 |
| format | Article |
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Forty patients with rectal cancer pretherapeutic UICC stage II/III, receiving preoperative FU-based CT/RT (CAO/ARO/AIO-94 trial) followed by standardized surgery, including total mesorectal excision, were investigated. Downsizing, downstaging, tumor regression, as well as TS, TP, and DPD gene expression of post-treatment surgical specimens were correlated with disease-free survival (DFS) and overall survival (OS).
Significant downsizing (P < .001) and downstaging (P = .001) were achieved with preoperative CT/RT. During a median follow-up of 49 months (95% CI, 43 to 58 months), the cancer recurrence rate was 28.2%. DFS and OS were significantly increased in patients with downstaging (P < .001 and P = .003, respectively), compared with patients without downstaging. All patients who developed cancer recurrence had a persistent positive lymph node status after preoperative CT/RT (P < .001) and a significantly higher TS gene expression (P = .035) compared with those patients without recurrence.
Persistent positive lymph node status and high intratumoral TS expression after preoperative CT/RT are predictive of an unfavorable prognosis in rectal cancer UICC stage II/III.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.2005.04.2739</identifier><identifier>PMID: 16943523</identifier><language>eng</language><publisher>Baltimore, MD: American Society of Clinical Oncology</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - metabolism ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Chemotherapy, Adjuvant ; Dihydrouracil Dehydrogenase (NADP) - metabolism ; Disease-Free Survival ; Female ; Fluorouracil - administration & dosage ; Fluorouracil - metabolism ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Medical sciences ; Middle Aged ; Neoadjuvant Therapy - methods ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms - drug therapy ; Rectal Neoplasms - enzymology ; Rectal Neoplasms - pathology ; Rectal Neoplasms - radiotherapy ; Rectal Neoplasms - therapy ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Thymidine Phosphorylase - metabolism ; Thymidylate Synthase - metabolism ; Treatment Outcome ; Tumors</subject><ispartof>Journal of clinical oncology, 2006-09, Vol.24 (25), p.4062-4068</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-e84d9287969041763cb2a7c69aca4d0773866e0af224b03d1704d453e8c73ff53</citedby><cites>FETCH-LOGICAL-c359t-e84d9287969041763cb2a7c69aca4d0773866e0af224b03d1704d453e8c73ff53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3716,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18107112$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16943523$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LIERSCH, Torsten</creatorcontrib><creatorcontrib>LANGER, Claus</creatorcontrib><creatorcontrib>GHADIMI, B. Michael</creatorcontrib><creatorcontrib>KULLE, Bettina</creatorcontrib><creatorcontrib>AUST, Daniela E</creatorcontrib><creatorcontrib>BARETTON, Gustavo B</creatorcontrib><creatorcontrib>SCHWABE, Wolfgang</creatorcontrib><creatorcontrib>HÄUSLER, Peter</creatorcontrib><creatorcontrib>BECKER, Heinz</creatorcontrib><creatorcontrib>JAKOB, Christiane</creatorcontrib><title>Lymph Node Status and TS Gene Expression Are Prognostic Markers in Stage II/III Rectal Cancer After Neoadjuvant Fluorouracil-Based Chemoradiotherapy</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>According to the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group, preoperative combined fluorouracil (FU) -based long-term chemoradiotherapy (CT/RT) is recommended for patients with International Union Against Cancer (UICC) stage II/III rectal cancer. However, despite the local benefit of neoadjuvant treatment, the overall prognostic value remains uncertain in comparison with adjuvant CT/RT. Furthermore, the prognostic value of molecular biomarkers, such as thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD), all of which are involved in the FU metabolism, is unknown in neoadjuvant settings. We assessed the impact of standardized preoperative CT/RT and intratumoral TS, TP, and DPD levels on patient outcome.
Forty patients with rectal cancer pretherapeutic UICC stage II/III, receiving preoperative FU-based CT/RT (CAO/ARO/AIO-94 trial) followed by standardized surgery, including total mesorectal excision, were investigated. Downsizing, downstaging, tumor regression, as well as TS, TP, and DPD gene expression of post-treatment surgical specimens were correlated with disease-free survival (DFS) and overall survival (OS).
Significant downsizing (P < .001) and downstaging (P = .001) were achieved with preoperative CT/RT. During a median follow-up of 49 months (95% CI, 43 to 58 months), the cancer recurrence rate was 28.2%. DFS and OS were significantly increased in patients with downstaging (P < .001 and P = .003, respectively), compared with patients without downstaging. All patients who developed cancer recurrence had a persistent positive lymph node status after preoperative CT/RT (P < .001) and a significantly higher TS gene expression (P = .035) compared with those patients without recurrence.
Persistent positive lymph node status and high intratumoral TS expression after preoperative CT/RT are predictive of an unfavorable prognosis in rectal cancer UICC stage II/III.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - metabolism</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Chemotherapy, Adjuvant</subject><subject>Dihydrouracil Dehydrogenase (NADP) - metabolism</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Fluorouracil - metabolism</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy - methods</subject><subject>Neoplasm Staging</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Radiotherapy, Adjuvant</subject><subject>Rectal Neoplasms - drug therapy</subject><subject>Rectal Neoplasms - enzymology</subject><subject>Rectal Neoplasms - pathology</subject><subject>Rectal Neoplasms - radiotherapy</subject><subject>Rectal Neoplasms - therapy</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Thymidine Phosphorylase - metabolism</subject><subject>Thymidylate Synthase - metabolism</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU9v00AUxC0EoqFw54T2Apyc7j977WNqtcUotIgWidvqZf0cb7C9ZtduyffgA-MokXp5c_nNPGkmit4zumSc0ouvxd1y1mRJ5ZIrkb-IFizhKlYqSV5GC6oEj1kmfp1Fb0LYUcpkJpLX0RlLcykSLhbRv_W-Gxpy6yok9yOMUyDQV-Thntxgj-Tq7-AxBOt6svJIvnu37V0YrSHfwP9GH4jtD74tkrK8KMuS_EAzQksK6A16sqrH-d6ig2o3PUI_kut2ct5NHoxt40sIWJGiwc55qKwbG_Qw7N9Gr2poA7476Xn08_rqofgSr-9uymK1jo1I8jHGTFY5z1Se5lQylQqz4aBMmoMBWVGlRJamSKHmXG6oqJiispKJwMwoUdeJOI8-HXMH7_5MGEbd2WCwbaFHNwWdZhkVPFczSI-g8S4Ej7UevO3A7zWj-rCEnpfQhyU0lfqwxGz5cMqeNh1Wz4ZT9TPw8QRAMNDWfm7MhmcuY1Qxxmfu85Fr7LZ5sh516KBt51iud8bx-V-iJU25-A-YLp50</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>LIERSCH, Torsten</creator><creator>LANGER, Claus</creator><creator>GHADIMI, B. 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Michael ; KULLE, Bettina ; AUST, Daniela E ; BARETTON, Gustavo B ; SCHWABE, Wolfgang ; HÄUSLER, Peter ; BECKER, Heinz ; JAKOB, Christiane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-e84d9287969041763cb2a7c69aca4d0773866e0af224b03d1704d453e8c73ff53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - metabolism</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Chemotherapy, Adjuvant</topic><topic>Dihydrouracil Dehydrogenase (NADP) - metabolism</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - metabolism</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoadjuvant Therapy - methods</topic><topic>Neoplasm Staging</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Radiotherapy, Adjuvant</topic><topic>Rectal Neoplasms - drug therapy</topic><topic>Rectal Neoplasms - enzymology</topic><topic>Rectal Neoplasms - pathology</topic><topic>Rectal Neoplasms - radiotherapy</topic><topic>Rectal Neoplasms - therapy</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Michael</creatorcontrib><creatorcontrib>KULLE, Bettina</creatorcontrib><creatorcontrib>AUST, Daniela E</creatorcontrib><creatorcontrib>BARETTON, Gustavo B</creatorcontrib><creatorcontrib>SCHWABE, Wolfgang</creatorcontrib><creatorcontrib>HÄUSLER, Peter</creatorcontrib><creatorcontrib>BECKER, Heinz</creatorcontrib><creatorcontrib>JAKOB, Christiane</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>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LIERSCH, Torsten</au><au>LANGER, Claus</au><au>GHADIMI, B. Michael</au><au>KULLE, Bettina</au><au>AUST, Daniela E</au><au>BARETTON, Gustavo B</au><au>SCHWABE, Wolfgang</au><au>HÄUSLER, Peter</au><au>BECKER, Heinz</au><au>JAKOB, Christiane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lymph Node Status and TS Gene Expression Are Prognostic Markers in Stage II/III Rectal Cancer After Neoadjuvant Fluorouracil-Based Chemoradiotherapy</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2006-09-01</date><risdate>2006</risdate><volume>24</volume><issue>25</issue><spage>4062</spage><epage>4068</epage><pages>4062-4068</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>According to the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group, preoperative combined fluorouracil (FU) -based long-term chemoradiotherapy (CT/RT) is recommended for patients with International Union Against Cancer (UICC) stage II/III rectal cancer. However, despite the local benefit of neoadjuvant treatment, the overall prognostic value remains uncertain in comparison with adjuvant CT/RT. Furthermore, the prognostic value of molecular biomarkers, such as thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD), all of which are involved in the FU metabolism, is unknown in neoadjuvant settings. We assessed the impact of standardized preoperative CT/RT and intratumoral TS, TP, and DPD levels on patient outcome.
Forty patients with rectal cancer pretherapeutic UICC stage II/III, receiving preoperative FU-based CT/RT (CAO/ARO/AIO-94 trial) followed by standardized surgery, including total mesorectal excision, were investigated. Downsizing, downstaging, tumor regression, as well as TS, TP, and DPD gene expression of post-treatment surgical specimens were correlated with disease-free survival (DFS) and overall survival (OS).
Significant downsizing (P < .001) and downstaging (P = .001) were achieved with preoperative CT/RT. During a median follow-up of 49 months (95% CI, 43 to 58 months), the cancer recurrence rate was 28.2%. DFS and OS were significantly increased in patients with downstaging (P < .001 and P = .003, respectively), compared with patients without downstaging. All patients who developed cancer recurrence had a persistent positive lymph node status after preoperative CT/RT (P < .001) and a significantly higher TS gene expression (P = .035) compared with those patients without recurrence.
Persistent positive lymph node status and high intratumoral TS expression after preoperative CT/RT are predictive of an unfavorable prognosis in rectal cancer UICC stage II/III.</abstract><cop>Baltimore, MD</cop><pub>American Society of Clinical Oncology</pub><pmid>16943523</pmid><doi>10.1200/JCO.2005.04.2739</doi><tpages>7</tpages></addata></record> |
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| ispartof | Journal of clinical oncology, 2006-09, Vol.24 (25), p.4062-4068 |
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| source | MEDLINE; American Society of Clinical Oncology Online Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Aged Antineoplastic Combined Chemotherapy Protocols - metabolism Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Biomarkers, Tumor - metabolism Chemotherapy, Adjuvant Dihydrouracil Dehydrogenase (NADP) - metabolism Disease-Free Survival Female Fluorouracil - administration & dosage Fluorouracil - metabolism Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Lymphatic Metastasis Male Medical sciences Middle Aged Neoadjuvant Therapy - methods Neoplasm Staging Predictive Value of Tests Prognosis Radiotherapy, Adjuvant Rectal Neoplasms - drug therapy Rectal Neoplasms - enzymology Rectal Neoplasms - pathology Rectal Neoplasms - radiotherapy Rectal Neoplasms - therapy Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Thymidine Phosphorylase - metabolism Thymidylate Synthase - metabolism Treatment Outcome Tumors |
| title | Lymph Node Status and TS Gene Expression Are Prognostic Markers in Stage II/III Rectal Cancer After Neoadjuvant Fluorouracil-Based Chemoradiotherapy |
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