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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe clinical value of achieving no evidence of disease (NED) in patients with advanced colorectal cancer (depends on the balance between the duration of the NED state and the toxicity of the treatments to achieve it, particularly with multimodal interventions. This article discusses the rationale for pursuing the NED state and factors to consider in the decision to pursue this goal.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe clinical value of achieving no evidence of disease (NED) in patients with advanced colorectal cancer (CRC) depends on the balance between the duration of the NED state and the toxicity of the treatments to achieve it, particularly with multimodal interventions. Alberto Sobrero, MD, Hospital San Martino, Genova, Italy, discussed the rationale for pursuing the NED state and factors to consider in the decision to pursue this goal.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe chance of achieving NED is marginal with systemic therapy alone but substantial with local approaches. However, local approaches can be toxic and the addition of adjuvant chemotherapy after local treatment is not as effective as it should be. Results of a pooled analysis from two trials of 278 patients with advanced CRC showed that patients treated with surgery and adjuvant 5-fluorouracil (5-FU) chemotherapy had a 7% higher progression-free survival (PFS) rate than those treated with surgery alone (p=0.058) [Mitry E et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008]. Nordlinger et al. [\u003Cem\u003ELancet\u003C\/em\u003E 2008] reported an 8.1% improvement in PFS at 3 years in patients with advanced CRC treated with surgery and perioperative chemotherapy versus surgery alone (HR, 0.77; 95% CI, 0.60 to 1.00; p=0.041; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Another study found no significant difference in disease-free survival between patients treated with 5-FU\/folinic acid (LV5FU) alone versus LV5FU plus irinotecan (HR, 0.89; 95% CI, 0.66 to 1.19) [Ychou M et al. ASCO 2008. Abstract LBA4013].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022PFS at 3 Years: All Eligible Patients.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-728060831\u0022 data-figure-caption=\u0022PFS at 3 Years: All Eligible Patients.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14536\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EPFS at 3 Years: All Eligible Patients.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReprinted from Nordlinger B et al. Perioperative Chemotherapy with FOLFOX4 and Surgery Versus Surgery Alone for Resectable Liver Metastases from Colorectal Cancer (EORTC Intergroup Trial 40983): A Randomised Controlled Trial. \u003Cem\u003EThe Lancet\u003C\/em\u003E;371(9617):1007\u201316. Copyright 2008, with permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EAchieving NED for at least 12 months gives patients hope for a cure, and is considered beneficial and relevant, whereas the value of achieving NED for 6 months is questionable and for \u0026lt;6 months, can be harmful. In a highly selected population of patients treated with surgery for liver metastases, 5- and 10-year survival rates were 40% and 20% for overall survival (OS), and 20% and 10% for relapse-free survival (RFS). Among unselected patients, the actual cure rate ranged from 1% to 4%.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EProf. Sobrero cautioned against using overly aggressive local treatment approaches because of the high rate of failure to achieve a NED state, the typically very short RFS, possible acceleration of the clinical course, treatment complications, and high mortality. Verwaal et al. [\u003Cem\u003EAnn Surg Oncol\u003C\/em\u003E 2005] concluded that the key issue in selecting patients for cytoreduction and adjuvant therapy is selecting patients in whom it is feasible to reach complete cytoreduction. Laparotomy to diagnose peritoneal carcinomatosis provides the best information for selecting such candidates. According to Prof. Sobrero, this is an example of a simplified approach that can be generalized and used to determine the chance of achieving relevant NED, by evaluating the \u201csoundness\u201d of an intervention and the ease of performing the intervention (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022A Simplified Approach to Determine Chance of Achieving Relevant No Evidence of Disease.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-728060831\u0022 data-figure-caption=\u0022A Simplified Approach to Determine Chance of Achieving Relevant No Evidence of Disease.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/29\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14249\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EA Simplified Approach to Determine Chance of Achieving Relevant No Evidence of Disease.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from A Sobrero, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EHigh originality and relevance coupled with low intrinsic and external validity of the results are the classic features and limits of most trials in this patient population. The main hurdles facing clinical trials in this field are poor feasibility and methodology. Trials must be designed to minimize bias (systematic error) and variability (random error). Bias can be minimized by randomization, treatment masking, eligibility criteria, and intention-to-treat analysis. Variability can be minimized by randomization, the number of patients, target delta, and patient stratification. However, these methods of minimizing bias and variability can be difficult to implement in this field.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EProf. Sobrero concluded that achieving the NED condition in patients with advanced CRC is very relevant. Physicians should not deceive themselves and patients but should, instead, aim for plausible results. The goal includes identifying appropriate patients for this approach, recognizing but not being paralyzed by the limitations of clinical trials in this field, and taking into consideration the toxicities associated with local therapy.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/15\/29.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn8hp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn8hp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}