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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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 role of postoperative radiation therapy in stage III non\u2013small cell lung cancer treatment remains undetermined. Multidisciplinary discussion with up-front stratification in potentially resectable or unresectable disease is of key importance. Factors such as surgery type and hospital volume are key to surgical outcomes.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Estage III non\u2013small cell lung cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eadjuvant chemotherapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eneoadjuvant chemotherapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einduction chemotherapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epostoperative radiation therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Echemoradiation therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einduction chemoradiation therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoncology clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eadjuvant\/neoadjuvant therapy\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPatients with stage III non\u2013small cell lung cancer (NSCLC) are a heterogeneous group at high risk for local and distant relapse. It is generally agreed that optimal treatment selection occurs in a multidisciplinary team setting after optimal staging. Adjuvant chemotherapy is now considered the standard of care for patients with resectable disease; the NSCLC Collaborative Group meta-analysis concluded that adjuvant chemotherapy improved survival in locally advanced NSCLC irrespective of whether it was performed after surgery alone or after surgery plus radiation therapy (RT) [NSCLC Meta-analyses Collaborative Group. \u003Cem\u003ELancet.\u003C\/em\u003E 2010]. The role of neoadjuvant or adjuvant RT, however, remains controversial. A landmark meta-analysis of 9 randomized trials with \u0026gt;\u20052000 patients concluded that postoperative RT (PORT) was detrimental in patients with early-stage, completely resected NSCLC but that its role in patients with N2 disease was unclear [PORT Meta-analysis Trialists Group. \u003Cem\u003ECochrane Database Syst Rev.\u003C\/em\u003E 2003].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EC\u00e9cile Le P\u00e9choux, MD, Institut Gustave-Roussy, Villejuif, France, reviewed the evidence concerning the role of neoadjuvant or adjuvant RT in improving outcomes for patients with stage III disease. She noted that patient selection and treatment have changed considerably since the publication of the PORT meta-analysis. In addition, neoadjuvant or adjuvant chemotherapy has become the standard of care; surgical and RT techniques have improved; and positron emission tomography scanning is being used to refine patient selection.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EProf Le P\u00e9choux summarized the results of 4 large randomized trials of neoadjuvant RT and 2 of PORT in patients with stage III NSCLC, none of which showed a survival benefit (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). In the most recently completed trial\u2014SAKK 16\/00 [Pless M et al. \u003Cem\u003EAnn Oncol.\u003C\/em\u003E 2014; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00030771\u0026amp;atom=%2Fspmdc%2F15%2F8%2F20.atom\u0022\u003ENCT00030771\u003C\/a\u003E]\u2014RT increased rates of response, complete resection, and pathologic complete response but failed to improve local control, event-free survival, or overall survival. In a 2005 update of the PORT meta-analysis, there was an 18% relative increase in the risk of death for PORT when compared with surgery alone [Burdett S, Stewart L. \u003Cem\u003ELung Cancer.\u003C\/em\u003E 2005]. A 2013 update using new statistical methodology found that the effect of PORT varied by stage and nodal status [Burdett et al. \u003Cem\u003ELung Cancer.\u003C\/em\u003E 2013], but Prof Le P\u00e9choux stated that this analysis was underpowered.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16313\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16313\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16313\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003ERCTs of Neoadjuvant or Adjuvant RT in Patients With Stage III NSCLC\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAlthough findings from meta-analyses do not support a role for RT after complete resection, excess toxicity, poor local control, and the use of older techniques may have contributed to excess mortality, she said. Population-based studies have found superior 5-year survival in completely resected N2 patients who received PORT when compared with patients who received surgery alone or surgery plus chemotherapy [Mikell JL et al. \u003Cem\u003EJ Thorac Oncol\u003C\/em\u003E. 2015; Robinson CG et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2015], but these studies cannot be considered robust evidence in favor of PORT, she said.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EBoth preoperative RT and PORT, however, have been shown to reduce local recurrence rates [Pless et al. \u003Cem\u003EAnn Oncol.\u003C\/em\u003E 2014; Le P\u00e9choux C. \u003Cem\u003EOncologist\u003C\/em\u003E. 2011]. Technical advances may enhance the ability of RT to improve local relapse-free survival, disease-free survival, and possibly overall survival. New evidence to reassess the role of PORT using modern radiation techniques may emerge from the international randomized LUNG ART trial [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00410683\u0026amp;atom=%2Fspmdc%2F15%2F8%2F20.atom\u0022\u003ENCT00410683\u003C\/a\u003E], Prof Le P\u00e9choux said. In this ongoing phase 3 study, an expected enrollment of 700 patients with completely resected N2 NSCLC will be randomized to receive conformal mediastinal PORT or no PORT. Patients may also receive neoadjuvant or adjuvant chemotherapy. The trial\u2019s primary end point is disease-free survival.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EPaul De Leyn, MD, PhD, University Hospitals Leuven, Leuven, Belgium, offered a surgeon\u2019s perspective on improving long-term outcomes for patients with stage III disease. Definitive upfront stratification of tumors\u2014as resectable, potentially resectable with an increased risk of incomplete resection, or unresectable\u2014is crucial, he said. According to Prof De Leyn, good survival rates and acceptable morbidity and mortality have been achieved with induction chemotherapy or chemoradiotherapy in selected patients with potentially resectable tumors with an increased risk of incomplete resection.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EProf De Leyn reviewed the evidence from several studies involving patients with potentially resectable N2 disease and one study of patients with unresectable disease, all of whom underwent surgery following induction chemotherapy or chemoradiation therapy (CRT; \u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E). In the German Lung Cancer Cooperative Group study [Thomas M et al. \u003Cem\u003ELancet Oncol.\u003C\/em\u003E 2008], preoperative CRT increased postsurgical mortality compared with preoperative chemotherapy, primarily due to increased rates of empyema and bronchial insufficiency. The evidence does not support a role for induction CRT for N2 disease, Prof De Leyn said. For Pancoast tumors, however, induction CRT is the standard of care. For stage III tumors deemed unresectable at baseline assessment, the EORTC 8947 trial [van Meerbeeck JP et al. \u003Cem\u003EJ Natl Cancer Inst.\u003C\/em\u003E 2007] demonstrated that induction chemotherapy will not render an unresectable tumor resectable, Prof De Leyn said. He recommended that patients whose tumors are deemed unresectable should receive immediate CRT.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16314\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16314\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16314\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-11\u0022 class=\u0022first-child\u0022\u003EStudies of Potentially Resectable or Baseline Unresectable Stage III (N2) NSCLC\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EBoth types of surgery and hospital surgical volume have been shown to influence outcomes. In a systematic review and meta-analysis of 27 studies published between 1990 and 2010, right pneumonectomy following neoadjuvant therapy was associated with significantly higher 30-day (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.02) and 90-day (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.03) mortality compared with left pneumonectomy; 90-day mortality for all pneumonectomies was also higher than 30-day mortality [Kim et al. \u003Cem\u003EJ Thorac Cardiovasc Surg\u003C\/em\u003E. 2012]. Prof De Leyn noted that these findings highlight the need for careful patient selection for pneumonectomy and reporting of 90-day mortality.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EIn regard to surgical volume, Bach and colleagues reported in 2001 that 44% of patients who had surgery at the highest volume centers survived 5 years postsurgery, compared with 33% of patients treated at the lowest volume centers (\u003Cem\u003EP\u2005\u003C\/em\u003E\u0026lt;\u2005.001). A 2013 analysis of data on \u0026gt;\u2005134\u2005000 patients with NSCLC diagnosed in England between 2004 and 2008 found that high procedure volume was strongly associated with improved survival, a higher resection rate, and a higher percentage of resections in patients with higher levels of comorbidity [L\u00fcchtenborg M et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EIn conclusion, evidence reviewed in this session showed that unanswered questions still surround the role of PORT in the treatment of patients with stage III NSCLC, that the role of induction CRT is dependent on tumor resectability, and that type of surgery and hospital surgical volume are important factors in surgical outcomes.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\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\/15\/8\/20.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_openurl.js?nzlnjp\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_tables.js?nzlnjp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}