***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background Results from the recent CROSS trial showed that neoadjuvant chemoradiotherapy ( nCRT ) significantly increased survival as compared to surgery alone in patients with potentially curable esophageal cancer . Furthermore , in the nCRT arm 49 % of patients with a squamous cell carcinoma ( SCC ) and 23 % of patients with an adenocarcinoma ( AC ) had a pathologically complete response in the resection specimen . These results provide a rationale to reconsider and study the timing and necessity of esophagectomy in ( all ) patients after application of the CROSS regimen . Objective We propose a “ surgery as needed ” approach after completion of nCRT . In this approach , patients will undergo active surveillance after completion of nCRT . Surgical resection would be offered only to those patients in whom residual disease or a locoregional recurrence is highly suspected or proven . However , before a surgery as needed approach in oesophageal cancer patients ( SANO ) can be tested in a r and omized controlled trial , we aim to determine the accuracy of detecting the presence or absence of residual disease after nCRT ( preSANO trial ) . Methods This study is set up as a prospect i ve , single arm , multicenter , diagnostic trial . Operable patients with potentially curable SCC or AC of the esophagus or esophagogastric junction will be included . Approximately 4 - 6 weeks after completion of nCRT all included patients will undergo a first clinical response evaluation ( CRE-I ) including endoscopy with ( r and om ) conventional mucosal biopsies of the primary tumor site and of any other suspected lesions in the esophagus and radial endo-ultrasonography ( EUS ) for measurement of tumor thickness and area . Patients in whom no locoregional or disseminated disease can be proven by cytohistology will be offered a postponed surgical resection 6 - 8 weeks after CRE-I ( ie , approximately 12 - 14 weeks after completion of nCRT ) . In the week preceding the postponed surgical resection , a second clinical response evaluation ( CRE-II ) will be planned that will include a whole body PET-CT , followed again by endoscopy with ( r and om ) conventional mucosal biopsies of the primary tumor site and any other suspected lesions in the esophagus , radial EUS for measurement of tumor thickness and area , and linear EUS plus fine needle aspiration of PET-positive lesions and /or suspected lymph nodes . The main study parameter is the correlation between the clinical response assessment during CRE-I and CRE-II and the final pathological response in the resection specimen . Results The first patient was enrolled on July 23 , 2013 , and results are expected in January 2016 . Conclusions If this preSANO trial shows that the presence or absence of residual tumor can be predicted reliably 6 or 12 weeks after completion of nCRT , a r and omized trial comparing nCRT plus st and ard surgery versus chemoradiotherapy plus “ surgery as needed ” will be conducted ( SANO trial ) . Trial Registration Netherl and s Trial Register : NTR4834 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=4834 ( archived by Webcite at http://www.webcitation.org/6Ze7mn67B ) Purpose R and omized trials examining neoadjuvant chemoradiotherapy followed by surgical resection ( nCRT-S ) and definitive CRT ( dCRT ) for esophageal cancer ( EC ) patients are hampered by use of nonst and ard treatment paradigms . Outcomes of nCRT-S versus dCRT in a more common patient population are lacking . We investigated local control and survival , evaluated clinical factors associated with endpoints , and assessed patterns of failure between these cohorts . Methods We retrospectively analyzed 130 patients with locally advanced EC receiving either dCRT or nCRT-S at our institution from 2000–2012 . Inclusion criteria were curatively treated nonmetastatic EC , Karnofsky performance status ≥70 % , and receipt of concomitant CRT . Patients were excluded if receiving < 41 Gy neoadjuvantly or < 50 Gy definitively . Kaplan – Meier analysis was used to evaluate local recurrence ( LR ) , progression-free survival ( PFS ) , and overall survival ( OS ) . Univariate and multivariate Cox proportional hazards modeling addressed factors associated with outcomes . Patterns of failure were enumerated as local , regional , or distant . Results Mean follow-up was 34.2 months . The 3‑year LR was 10.8 % in the nCRT-S group and 21.5 % in the dCRT group ( p = 0.266 ) . Median PFS were 15.6 and 14.9 months , respectively ( p = 0.549 ) . Median OS were 20.6 and 25.9 months , respectively ( p = 0.81 ) . On univariate and multivariate analysis , none of the investigated factors was associated with outcomes , although node-positive disease showed a trend for worse OS and PFS . Most common failures in both groups were distant ( dCRT 31.2 % vs. nCRT-S 21.6 % ) followed by local in-field recurrences  ( dCRT 26.9 % vs. nCRT-S 10.8 % ) . Conclusions In this institutional analysis , no significant differences regarding outcomes and patterns of failure were observed between nCRT-S and dCRT.ZusammenfassungZielR and omisierte Studien , welche die neoadjuvante Radiochemotherapie ( CRT ) einschließlich konsekutiver Operation ( nCRT-S ) mit der definitiven Radiochemotherapie ( dCRT ) für Ösophaguskarzinom(EC)-Patienten vergleichen , sind aufgrund nicht st and ardgerechter Beh and lungskonzepte nur eingeschränkt in die Praxis übertragbar . Zum Vergleich nCRT-S vs. dCRT mit aktueller St and ardtherapie liegen kaum Erkenntnisse vor . Verglichen wurden lokale Kontrolle/Überleben , klinische Einflussfaktoren auf das Outcome und Rezidivmuster dieser beiden Gruppen . Method enWir untersuchten retrospektiv 130 Patienten mit lokal fortgeschrittenem EC , die i m Zeitraum 2000–2012 in unserer Klinik mit dCRT oder nCRT-S beh and elt worden waren . Einschlusskriterien waren ein kuratives Beh and lungskonzept bei nichtmetastasiertem EC , ein Karnofsky-Index ≥70 % und die simultane CRT . Patienten mit einer Gesamtdosis von < 41 Gy ( neoadjuvant ) bzw . < 50 Gy ( definitiv ) wurden ausgeschlossen . Eine Kaplan-Meier-Analyse wurde zur Beurteilung von Lokalrezidiven ( LR ) , progressionsfreiem Überleben ( PFS ) und Gesamtüberleben ( OS ) durchgeführt , eine univariate/multivariate Cox-Regression zur Analyse klinischer Einflussfaktoren auf das Outcome . Rezidive wurden als lokal , regional oder distant klassifiziert . ErgebnisseDas mittlere Follow-Up betrug 34,2 Monate . Die 3‑Jahres-LR-Raten lagen bei 10,8 % für nCRT-S und 21,5 % für dCRT ( p = 0,266 ) . Das mediane PFS betrug 15,6 bzw . 14,9 Monate ( p = 0,549 ) , das mediane OS 20,6 bzw . 25,9 Monate ( p = 0,81 ) . Univariate und multivariate Analysen zeigten keine klinischen Faktoren mit signifikantem Einfluss auf das Outcome , wenngleich nodal-positive Patienten i m Trend ein schlechteres OS und PFS aufwiesen . Rezidive traten in beiden Gruppen meist als Fernmetastasen ( dCRT 31,2 % vs. nCRT-S 21,6 % ) auf oder als In-field-Lokalrezidive ( dCRT 26,9 % vs. nCRT-S 10,8 % ) .SchlussfolgerungIm untersuchten Patientenkollektiv waren i m Hinblick auf Outcome und Rezidivmuster keine signifikanten Unterschiede festzustellen nach neoadjuvanter Radiochemotherapie plus Operation bzw . nach definitiver Radiochemotherapie Esophageal cancer is the sixth most common cause of cancer deaths worldwide . Adenocarcinoma is more common in North America and Western European countries , originating mostly in the lower third of the esophagus , which often involves the esophagogastric junction ( EGJ ) . Recent r and omized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer . Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas . Multidisciplinary team management is essential for patients with esophageal and EGJ cancers . This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This study aim ed to determine whether 18F-FDG PET response after induction chemotherapy before concurrent chemoradiotherapy can identify patients with esophageal adenocarcinoma who may benefit from subsequent esophagectomy . Methods : We identified and analyzed 220 patients with esophageal adenocarcinoma who had received induction chemotherapy before chemoradiotherapy , with or without surgery , with curative intent ; all underwent 18F-FDG PET scanning before and after induction chemotherapy . 18F-FDG PET responders were defined as patients who achieved complete response ( CR ) after induction chemotherapy ( maximum SUV ≤ 3.0 ) . The predictive value of 18F-FDG PET response for patient outcomes was evaluated . Results : Overall , 86 patients had bimodality therapy ( BMT ; induction chemotherapy + chemoradiotherapy ) and 134 had trimodality therapy ( TMT ; induction chemotherapy + chemoradiotherapy with surgery ) . Forty-eight patients ( 21.8 % ) achieved an 18F-FDG  PET CR after induction chemotherapy . 18F-FDG PET CR was found to correlate with overall survival ( OS ) and progression-free survival ( PFS ) in BMT patients . For TMT patients , 18F-FDG PET CR predicted pathologic response ( P = 0.003 ) but not survival . Among 18F-FDG PET nonresponders , TMT patients had significantly better survival than did BMT patients ( P < 0.001 ) . However , among 18F-FDG PET responders , BMT patients had OS ( P = 0.201 ) and PFS ( P = 0.269 ) similar to that of TMT patients . After propensity score-matched analysis , 18F-FDG PET responders treated with BMT versus TMT still had comparable OS and PFS , but TMT was associated with better locoregional control . Conclusion : 18F-FDG PET response to induction chemotherapy could be a useful imaging biomarker to identify patients with esophageal adenocarcinoma who could benefit from subsequent esophagectomy after chemoradiotherapy . Compared with BMT , TMT can significantly improve survival in 18F-FDG PET nonresponders . However , outcomes for 18F-FDG PET responders were similar after either treatment ( BMT or TMT ) . Prospect i ve validation of these findings is warranted BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery  , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was 
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Conclusion These meta-analyses do not show clear survival advantage for TMT over dCRT .
Only a non-significant trend towards better survival was seen , assuming comparable patient groups at baseline .