Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors
Purpose To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Pati...
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| Veröffentlicht in: | International journal of radiation oncology, biology, physics biology, physics, 2014-07, Vol.89 (3), p.547-555 |
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| creator | Nakamura, Takatoshi, MD, PhD Yamashita, Keishi, MD, PhD Sato, Takeo, MD, PhD Ema, Akira, MD Naito, Masanori, MD, PhD Watanabe, Masahiko, MD, PhD, FACS |
| description | Purpose To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS ( P =.0019) and OS ( P =.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT ( P =.0065) and tumor location ( P =.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence ( P |
| doi_str_mv | 10.1016/j.ijrobp.2014.03.007 |
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Methods and Materials The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS ( P =.0019) and OS ( P =.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT ( P =.0065) and tumor location ( P =.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence ( P <.0001), which occurred most commonly in the lung. Conclusions NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2014.03.007</identifier><identifier>PMID: 24929164</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject><![CDATA[Adult ; Aged ; Aged, 80 and over ; Agranulocytosis - etiology ; Analysis of Variance ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Camptothecin - administration & dosage ; Camptothecin - adverse effects ; Camptothecin - analogs & derivatives ; Chemoradiotherapy - adverse effects ; Chemoradiotherapy - methods ; Diarrhea - etiology ; Disease-Free Survival ; Dose Fractionation ; Drug Administration Schedule ; Drug Combinations ; Female ; Fluorouracil - administration & dosage ; Hematology, Oncology and Palliative Medicine ; Humans ; Leucovorin - administration & dosage ; Leukopenia - etiology ; LUNGS ; Male ; Middle Aged ; MULTIVARIATE ANALYSIS ; Neoadjuvant Therapy - adverse effects ; Neoadjuvant Therapy - methods ; Neoplasm Staging ; NEOPLASMS ; Organoplatinum Compounds - administration & dosage ; Oxonic Acid - administration & dosage ; Oxonic Acid - adverse effects ; PATIENTS ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; RADIOTHERAPY ; Rectal Neoplasms - mortality ; Rectal Neoplasms - pathology ; Rectal Neoplasms - therapy ; RECTUM ; SURGERY ; Tegafur - administration & dosage ; Tegafur - adverse effects ; Treatment Outcome]]></subject><ispartof>International journal of radiation oncology, biology, physics, 2014-07, Vol.89 (3), p.547-555</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-56940897d8ecb80b324d50a8599355e9519e2cf23ccd5c1b9d39e5af9fc6fb7f3</citedby><cites>FETCH-LOGICAL-c445t-56940897d8ecb80b324d50a8599355e9519e2cf23ccd5c1b9d39e5af9fc6fb7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijrobp.2014.03.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24929164$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22420339$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamura, Takatoshi, MD, PhD</creatorcontrib><creatorcontrib>Yamashita, Keishi, MD, PhD</creatorcontrib><creatorcontrib>Sato, Takeo, MD, PhD</creatorcontrib><creatorcontrib>Ema, Akira, MD</creatorcontrib><creatorcontrib>Naito, Masanori, MD, PhD</creatorcontrib><creatorcontrib>Watanabe, Masahiko, MD, PhD, FACS</creatorcontrib><title>Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS ( P =.0019) and OS ( P =.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT ( P =.0065) and tumor location ( P =.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence ( P <.0001), which occurred most commonly in the lung. Conclusions NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Agranulocytosis - etiology</subject><subject>Analysis of Variance</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Camptothecin - administration & dosage</subject><subject>Camptothecin - adverse effects</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Chemoradiotherapy - adverse effects</subject><subject>Chemoradiotherapy - methods</subject><subject>Diarrhea - etiology</subject><subject>Disease-Free Survival</subject><subject>Dose Fractionation</subject><subject>Drug Administration Schedule</subject><subject>Drug Combinations</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Leucovorin - administration & dosage</subject><subject>Leukopenia - etiology</subject><subject>LUNGS</subject><subject>Male</subject><subject>Middle Aged</subject><subject>MULTIVARIATE ANALYSIS</subject><subject>Neoadjuvant Therapy - adverse effects</subject><subject>Neoadjuvant Therapy - methods</subject><subject>Neoplasm Staging</subject><subject>NEOPLASMS</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Oxonic Acid - administration & dosage</subject><subject>Oxonic Acid - adverse effects</subject><subject>PATIENTS</subject><subject>Radiology</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>RADIOTHERAPY</subject><subject>Rectal Neoplasms - mortality</subject><subject>Rectal Neoplasms - pathology</subject><subject>Rectal Neoplasms - therapy</subject><subject>RECTUM</subject><subject>SURGERY</subject><subject>Tegafur - administration & dosage</subject><subject>Tegafur - adverse effects</subject><subject>Treatment Outcome</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks-O0zAQxiMEYsvCGyBkiQuXFP9NYw5IKGLZShWL2K7EzXKcSevQ2Fk7WakPwvvibAsHLpzm8ptvZr5vsuw1wUuCSfG-W9ou-HpYUkz4ErMlxqsn2YKUK5kzIX48zRaYFThnCb7IXsTYYYwJWfHn2QXlkkpS8EX26yt43XTTg3YjqvbQ-6Abq0frHdruIejhiO6idTtUeWemECBxtzlB2jVoHazzIxjtkHXoO5hRH1ClnYHwAa37QZsRJZ2Nd7t8C6FH1cE6axJ0M43G9xAfZb4Fv3M-jtagq9TiQ3yZPWv1IcKrc73M7q4-b6vrfHPzZV192uSGczHmopAcl3LVlGDqEteM8kZgXQopkwMgBZFATUuZMY0wpJYNkyB0K1tTtPWqZZfZ25PuPF1FY9Mxe-OdS6coSjnFjMlEvTtRQ_D3E8RR9TYaOBy0Az9FRUTyGTNKaEL5CTXBxxigVUOwvQ5HRbCaY1OdOsWm5tgUZirFltrenCdMdQ_N36Y_OSXg4wmA5MaDhTAvC8noxoZ518bb_034V8Ccs_gJR4idn4JLTiuiIlVY3c6vM38O4RhTKUr2Gw_KwLE</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Nakamura, Takatoshi, MD, PhD</creator><creator>Yamashita, Keishi, MD, PhD</creator><creator>Sato, Takeo, MD, PhD</creator><creator>Ema, Akira, MD</creator><creator>Naito, Masanori, MD, PhD</creator><creator>Watanabe, Masahiko, MD, PhD, FACS</creator><general>Elsevier Inc</general><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><scope>OTOTI</scope></search><sort><creationdate>20140701</creationdate><title>Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors</title><author>Nakamura, Takatoshi, MD, PhD ; Yamashita, Keishi, MD, PhD ; Sato, Takeo, MD, PhD ; Ema, Akira, MD ; Naito, Masanori, MD, PhD ; Watanabe, Masahiko, MD, PhD, FACS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-56940897d8ecb80b324d50a8599355e9519e2cf23ccd5c1b9d39e5af9fc6fb7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Agranulocytosis - etiology</topic><topic>Analysis of Variance</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Camptothecin - administration & dosage</topic><topic>Camptothecin - adverse effects</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Chemoradiotherapy - adverse effects</topic><topic>Chemoradiotherapy - methods</topic><topic>Diarrhea - etiology</topic><topic>Disease-Free Survival</topic><topic>Dose Fractionation</topic><topic>Drug Administration Schedule</topic><topic>Drug Combinations</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Leucovorin - administration & dosage</topic><topic>Leukopenia - etiology</topic><topic>LUNGS</topic><topic>Male</topic><topic>Middle Aged</topic><topic>MULTIVARIATE ANALYSIS</topic><topic>Neoadjuvant Therapy - adverse effects</topic><topic>Neoadjuvant Therapy - methods</topic><topic>Neoplasm Staging</topic><topic>NEOPLASMS</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Oxonic Acid - administration & dosage</topic><topic>Oxonic Acid - adverse effects</topic><topic>PATIENTS</topic><topic>Radiology</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>RADIOTHERAPY</topic><topic>Rectal Neoplasms - mortality</topic><topic>Rectal Neoplasms - pathology</topic><topic>Rectal Neoplasms - therapy</topic><topic>RECTUM</topic><topic>SURGERY</topic><topic>Tegafur - administration & dosage</topic><topic>Tegafur - adverse effects</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakamura, Takatoshi, MD, PhD</creatorcontrib><creatorcontrib>Yamashita, Keishi, MD, PhD</creatorcontrib><creatorcontrib>Sato, Takeo, MD, PhD</creatorcontrib><creatorcontrib>Ema, Akira, MD</creatorcontrib><creatorcontrib>Naito, Masanori, MD, PhD</creatorcontrib><creatorcontrib>Watanabe, Masahiko, MD, PhD, FACS</creatorcontrib><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><collection>OSTI.GOV</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakamura, Takatoshi, MD, PhD</au><au>Yamashita, Keishi, MD, PhD</au><au>Sato, Takeo, MD, PhD</au><au>Ema, Akira, MD</au><au>Naito, Masanori, MD, PhD</au><au>Watanabe, Masahiko, MD, PhD, FACS</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>89</volume><issue>3</issue><spage>547</spage><epage>555</epage><pages>547-555</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>Purpose To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS ( P =.0019) and OS ( P =.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT ( P =.0065) and tumor location ( P =.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence ( P <.0001), which occurred most commonly in the lung. Conclusions NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24929164</pmid><doi>10.1016/j.ijrobp.2014.03.007</doi><tpages>9</tpages></addata></record> |
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| ispartof | International journal of radiation oncology, biology, physics, 2014-07, Vol.89 (3), p.547-555 |
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| subjects | Adult Aged Aged, 80 and over Agranulocytosis - etiology Analysis of Variance Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Camptothecin - administration & dosage Camptothecin - adverse effects Camptothecin - analogs & derivatives Chemoradiotherapy - adverse effects Chemoradiotherapy - methods Diarrhea - etiology Disease-Free Survival Dose Fractionation Drug Administration Schedule Drug Combinations Female Fluorouracil - administration & dosage Hematology, Oncology and Palliative Medicine Humans Leucovorin - administration & dosage Leukopenia - etiology LUNGS Male Middle Aged MULTIVARIATE ANALYSIS Neoadjuvant Therapy - adverse effects Neoadjuvant Therapy - methods Neoplasm Staging NEOPLASMS Organoplatinum Compounds - administration & dosage Oxonic Acid - administration & dosage Oxonic Acid - adverse effects PATIENTS Radiology RADIOLOGY AND NUCLEAR MEDICINE RADIOTHERAPY Rectal Neoplasms - mortality Rectal Neoplasms - pathology Rectal Neoplasms - therapy RECTUM SURGERY Tegafur - administration & dosage Tegafur - adverse effects Treatment Outcome |
| title | Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors |
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