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Accuracy of Detecting Residual Disease After Cross Neoadjuvant Chemoradiotherapy for Esophageal Cancer (preSANO Trial): Rationale and Protocol.

Noordman BJ, Shapiro J, Spaander MC, Krishnadath KK, van Laarhoven HW, van Berge Henegouwen MI, Nieuwenhuijzen GA, van Hillegersberg R, Sosef MN, Steyerberg EW, Wijnhoven BP, van Lanschot JJ, SANO study gro - JMIR Res Protoc (2015)

Bottom Line: These results provide a rationale to reconsider and study the timing and necessity of esophagectomy in (all) patients after application of the CROSS regimen.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.The first patient was enrolled on July 23, 2013, and results are expected in January 2016.

View Article: PubMed Central - HTML - PubMed

Affiliation: Erasmus MC - University Medical Center Rotterdam, Department of Surgery, Rotterdam, Netherlands. b.noordman@erasmusmc.nl.

ABSTRACT

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 randomized 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 prospective, 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 (random) 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 (random) 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 randomized trial comparing nCRT plus standard surgery versus chemoradiotherapy plus "surgery as needed" will be conducted (SANO trial).

Trial registration: Netherlands Trial Register: NTR4834; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4834 (archived by Webcite at http://www.webcitation.org/6Ze7mn67B).

No MeSH data available.


Related in: MedlinePlus

Expected distribution of patients (based partly on CROSS trial data).All numbers are based on an inclusion of 120 patients. CI: confidence interval; CRE: clinical response evaluation; nCRT: neoadjuvant chemoradiotherapy; N: number of patients; TRG: tumor regression grade, as measured by the modified TRG system of Chirieac. Of the 45 patients who will undergo a postponed resection following CRE-II, 15 patients are expected to have a pathologically incomplete response (at least TRG2).
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figure2: Expected distribution of patients (based partly on CROSS trial data).All numbers are based on an inclusion of 120 patients. CI: confidence interval; CRE: clinical response evaluation; nCRT: neoadjuvant chemoradiotherapy; N: number of patients; TRG: tumor regression grade, as measured by the modified TRG system of Chirieac. Of the 45 patients who will undergo a postponed resection following CRE-II, 15 patients are expected to have a pathologically incomplete response (at least TRG2).

Mentions: As was seen in the previous CROSS trial approximately 40% of the included patients will have TRG3 or TRG4 residual tumor in the resection specimen [18]. With a total inclusion of 120 patients, approximately 45 patients will have TRG3 or TRG4 residual tumor. We consider 45 patients a sufficiently large sample for determining the accuracy of individual and/or combined diagnostic tests. In order to estimate the distribution of 120 patients planned to be included, data were used from the CROSS trial as indicated in Figure 2. Furthermore, several assumptions were made:


Accuracy of Detecting Residual Disease After Cross Neoadjuvant Chemoradiotherapy for Esophageal Cancer (preSANO Trial): Rationale and Protocol.

Noordman BJ, Shapiro J, Spaander MC, Krishnadath KK, van Laarhoven HW, van Berge Henegouwen MI, Nieuwenhuijzen GA, van Hillegersberg R, Sosef MN, Steyerberg EW, Wijnhoven BP, van Lanschot JJ, SANO study gro - JMIR Res Protoc (2015)

Expected distribution of patients (based partly on CROSS trial data).All numbers are based on an inclusion of 120 patients. CI: confidence interval; CRE: clinical response evaluation; nCRT: neoadjuvant chemoradiotherapy; N: number of patients; TRG: tumor regression grade, as measured by the modified TRG system of Chirieac. Of the 45 patients who will undergo a postponed resection following CRE-II, 15 patients are expected to have a pathologically incomplete response (at least TRG2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526968&req=5

figure2: Expected distribution of patients (based partly on CROSS trial data).All numbers are based on an inclusion of 120 patients. CI: confidence interval; CRE: clinical response evaluation; nCRT: neoadjuvant chemoradiotherapy; N: number of patients; TRG: tumor regression grade, as measured by the modified TRG system of Chirieac. Of the 45 patients who will undergo a postponed resection following CRE-II, 15 patients are expected to have a pathologically incomplete response (at least TRG2).
Mentions: As was seen in the previous CROSS trial approximately 40% of the included patients will have TRG3 or TRG4 residual tumor in the resection specimen [18]. With a total inclusion of 120 patients, approximately 45 patients will have TRG3 or TRG4 residual tumor. We consider 45 patients a sufficiently large sample for determining the accuracy of individual and/or combined diagnostic tests. In order to estimate the distribution of 120 patients planned to be included, data were used from the CROSS trial as indicated in Figure 2. Furthermore, several assumptions were made:

Bottom Line: These results provide a rationale to reconsider and study the timing and necessity of esophagectomy in (all) patients after application of the CROSS regimen.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.The first patient was enrolled on July 23, 2013, and results are expected in January 2016.

View Article: PubMed Central - HTML - PubMed

Affiliation: Erasmus MC - University Medical Center Rotterdam, Department of Surgery, Rotterdam, Netherlands. b.noordman@erasmusmc.nl.

ABSTRACT

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 randomized 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 prospective, 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 (random) 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 (random) 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 randomized trial comparing nCRT plus standard surgery versus chemoradiotherapy plus "surgery as needed" will be conducted (SANO trial).

Trial registration: Netherlands Trial Register: NTR4834; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4834 (archived by Webcite at http://www.webcitation.org/6Ze7mn67B).

No MeSH data available.


Related in: MedlinePlus