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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

Study algorithm.1. During the pretreatment workup, it suffices when a “partial body” F18-FDG PET-CT of the esophagus will be performed (to test for avidity of the primary lesion); if it is preferred to make a “whole-body” PET-CT not only after, but also before the neoadjuvant chemoradiotherapy in order to detect distant metastases at an earlier stage, the indication for performing an external US with FNA of the neck can be limited to those patients who have a suspected lymph node on the PET-CT [23]. In the period after neoadjuvant therapy, 1 whole-body F18-FDG PET-CT will be performed either at CRE-I (for the clinically noncomplete responders) or at CRE-II (for the clinically complete responders at CRE-I). 2. EUS with FNA of suspected lymph nodes only during CRE-II, not during CRE-I.CRE: clinical response evaluation; CT: computed tomography; EUS: endoscopic ultrasonography; FNA: fine-needle aspiration; nCRT: neoadjuvant chemoradiotherapy; EGD: esophagogastroduodenoscopy; PET: positron-emission tomography; US: ultrasonography.
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figure1: Study algorithm.1. During the pretreatment workup, it suffices when a “partial body” F18-FDG PET-CT of the esophagus will be performed (to test for avidity of the primary lesion); if it is preferred to make a “whole-body” PET-CT not only after, but also before the neoadjuvant chemoradiotherapy in order to detect distant metastases at an earlier stage, the indication for performing an external US with FNA of the neck can be limited to those patients who have a suspected lymph node on the PET-CT [23]. In the period after neoadjuvant therapy, 1 whole-body F18-FDG PET-CT will be performed either at CRE-I (for the clinically noncomplete responders) or at CRE-II (for the clinically complete responders at CRE-I). 2. EUS with FNA of suspected lymph nodes only during CRE-II, not during CRE-I.CRE: clinical response evaluation; CT: computed tomography; EUS: endoscopic ultrasonography; FNA: fine-needle aspiration; nCRT: neoadjuvant chemoradiotherapy; EGD: esophagogastroduodenoscopy; PET: positron-emission tomography; US: ultrasonography.

Mentions: We plan to include individuals from a population of operable patients with potentially curable SCC or AC of the esophagus or esophagogastric junction. All patients who are planned to undergo nCRT according to the CROSS regimen [18] followed by surgical resection are eligible to participate. Patients with dementia or altered mental status prohibiting the understanding and giving of informed consent will be excluded from participation in this study. Patients will undergo conventional pretreatment selection (including at least a “partial body” F18-FDG positron emission tomography-computed tomography (PET-CT) to assess the avidity of the primary tumor process; Figure 1 and Table 1).


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)

Study algorithm.1. During the pretreatment workup, it suffices when a “partial body” F18-FDG PET-CT of the esophagus will be performed (to test for avidity of the primary lesion); if it is preferred to make a “whole-body” PET-CT not only after, but also before the neoadjuvant chemoradiotherapy in order to detect distant metastases at an earlier stage, the indication for performing an external US with FNA of the neck can be limited to those patients who have a suspected lymph node on the PET-CT [23]. In the period after neoadjuvant therapy, 1 whole-body F18-FDG PET-CT will be performed either at CRE-I (for the clinically noncomplete responders) or at CRE-II (for the clinically complete responders at CRE-I). 2. EUS with FNA of suspected lymph nodes only during CRE-II, not during CRE-I.CRE: clinical response evaluation; CT: computed tomography; EUS: endoscopic ultrasonography; FNA: fine-needle aspiration; nCRT: neoadjuvant chemoradiotherapy; EGD: esophagogastroduodenoscopy; PET: positron-emission tomography; US: ultrasonography.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

figure1: Study algorithm.1. During the pretreatment workup, it suffices when a “partial body” F18-FDG PET-CT of the esophagus will be performed (to test for avidity of the primary lesion); if it is preferred to make a “whole-body” PET-CT not only after, but also before the neoadjuvant chemoradiotherapy in order to detect distant metastases at an earlier stage, the indication for performing an external US with FNA of the neck can be limited to those patients who have a suspected lymph node on the PET-CT [23]. In the period after neoadjuvant therapy, 1 whole-body F18-FDG PET-CT will be performed either at CRE-I (for the clinically noncomplete responders) or at CRE-II (for the clinically complete responders at CRE-I). 2. EUS with FNA of suspected lymph nodes only during CRE-II, not during CRE-I.CRE: clinical response evaluation; CT: computed tomography; EUS: endoscopic ultrasonography; FNA: fine-needle aspiration; nCRT: neoadjuvant chemoradiotherapy; EGD: esophagogastroduodenoscopy; PET: positron-emission tomography; US: ultrasonography.
Mentions: We plan to include individuals from a population of operable patients with potentially curable SCC or AC of the esophagus or esophagogastric junction. All patients who are planned to undergo nCRT according to the CROSS regimen [18] followed by surgical resection are eligible to participate. Patients with dementia or altered mental status prohibiting the understanding and giving of informed consent will be excluded from participation in this study. Patients will undergo conventional pretreatment selection (including at least a “partial body” F18-FDG positron emission tomography-computed tomography (PET-CT) to assess the avidity of the primary tumor process; Figure 1 and Table 1).

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