Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study

Background: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry. Methods: Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival. Findings: Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1–3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2–28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9–87·7%), and 5-year disease-specific survival was 94% (91–96%). Interpretation: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare. Funding: European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant

Percival: A searchable secret-split datastore

Maintaining information privacy is challenging when sharing data across a distributed long-term datastore. In such applications, secret splitting the data across independent sites has been shown to be a superior alternative to fixed-key encryption; it improves reliability, reduces the risk of insider threat, and removes the issues surrounding key management. However, the inherent security of such a datastore normally precludes it from being directly searched without reassembling the data; this, however, is neither computationally feasible nor without risk since reassembly introduces a single point of compromise. As a result, the secret-split data must be pre-indexed in some way in order to facilitate searching. Previously, fixed-key encryption has also been used to securely pre-index the data, but in addition to key management issues, it is not well suited for long term applications. To meet these needs, we have developed Percival: a novel system that enables searching a secret-split datastore while maintaining information privacy. We leverage salted hashing, performed within hardware security modules, to access prerecorded queries that have been secret split and stored in a distributed environment; this keeps the bulk of the work on each client, and the data custodians blinded to both the contents of a query as well as its results. Furthermore, Percival does not rely on the datastore's exact implementation. The result is a flexible design that can be applied to both new and existing secret-split datastores. When testing Percival on a corpus of approximately one million files, it was found that the average search operation completed in less than one second

Percival: A searchable secret-split datastore

Maintaining information privacy is challenging when sharing data across a distributed long-term datastore. In such applications, secret splitting the data across independent sites has been shown to be a superior alternative to fixed-key encryption; it improves reliability, reduces the risk of insider threat, and removes the issues surrounding key management. However, the inherent security of such a datastore normally precludes it from being directly searched without reassembling the data; this, however, is neither computationally feasible nor without risk since reassembly introduces a single point of compromise. As a result, the secret-split data must be pre-indexed in some way in order to facilitate searching. Previously, fixed-key encryption has also been used to securely pre-index the data, but in addition to key management issues, it is not well suited for long term applications. To meet these needs, we have developed Percival: a novel system that enables searching a secret-split datastore while maintaining information privacy. We leverage salted hashing, performed within hardware security modules, to access prerecorded queries that have been secret split and stored in a distributed environment; this keeps the bulk of the work on each client, and the data custodians blinded to both the contents of a query as well as its results. Furthermore, Percival does not rely on the datastore's exact implementation. The result is a flexible design that can be applied to both new and existing secret-split datastores. When testing Percival on a corpus of approximately one million files, it was found that the average search operation completed in less than one second