scholarly journals Proof-of-concept study: Homomorphically encrypted data can support real-time learning in personalized cancer medicine

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Silvia Paddock ◽  
Hamed Abedtash ◽  
Jacqueline Zummo ◽  
Samuel Thomas
Keyword(s):  
Real World ◽  
Drug Exposure ◽  
Homomorphic Encryption ◽  
Unmet Need ◽  
Learning System ◽  
Administrative Claims ◽  
Use Case ◽  
Proof Of Concept ◽  
Cancer Treatments ◽  
Concept Study

Abstract Background The successful introduction of homomorphic encryption (HE) in clinical research holds promise for improving acceptance of data-sharing protocols, increasing sample sizes, and accelerating learning from real-world data (RWD). A well-scoped use case for HE would pave the way for more widespread adoption in healthcare applications. Determining the efficacy of targeted cancer treatments used off-label for a variety of genetically defined conditions is an excellent candidate for introduction of HE-based learning systems because of a significant unmet need to share and combine confidential data, the use of relatively simple algorithms, and an opportunity to reach large numbers of willing study participants. Methods We used published literature to estimate the numbers of patients who might be eligible to receive treatments approved for other indications based on molecular profiles. We then estimated the sample size and number of variables that would be required for a successful system to detect exceptional responses with sufficient power. We generated an appropriately sized, simulated dataset (n = 5000) and used an established HE algorithm to detect exceptional responses and calculate total drug exposure, while the data remained encrypted. Results Our results demonstrated the feasibility of using an HE-based system to identify exceptional responders and perform calculations on patient data during a hypothetical 3-year study. Although homomorphically encrypted computations are time consuming, the required basic computations (i.e., addition) do not pose a critical bottleneck to the analysis. Conclusion In this proof-of-concept study, based on simulated data, we demonstrate that identifying exceptional responders to targeted cancer treatments represents a valuable and feasible use case. Past solutions to either completely anonymize data or restrict access through stringent data use agreements have limited the utility of abundant and valuable data. Because of its privacy protections, we believe that an HE-based learning system for real-world cancer treatment would entice thousands more patients to voluntarily contribute data through participation in research studies beyond the currently available secondary data populated from hospital electronic health records and administrative claims. Forming collaborations between technical experts, physicians, patient advocates, payers, and researchers, and testing the system on existing RWD are critical next steps to making HE-based learning a reality in healthcare.

scholarly journals Lenvatinib as an Initial Treatment in Patients with Intermediate-stage Hepatocellular Carcinoma Beyond up-to-seven Criteria and Child-Pugh A Liver Function: A Proof-of-Concept Study

2019 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephan Chan ◽  
Tomohiro Minami ◽  
Hirokazu Chishina ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Unmet Need ◽  
Intermediate Stage ◽  
Proof Of Concept ◽  
Concept Study

Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.

Real-world neo-adjuvant with or without adjuvant treatment patterns among pancreatic ductal adenocarcinoma patients in the U.S.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16217-e16217
Author(s):  
Prakash Navaratnam ◽  
Monica Chase ◽  
Howard Steven Friedman ◽  
Seongjung Joo ◽  
Michael J. Pishvaian
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Adjuvant Treatment ◽  
Real World ◽  
Unmet Need ◽  
Treatment Patterns ◽  
Ductal Adenocarcinoma ◽  
Administrative Claims ◽  
Surgery Patient ◽  
To Receive ◽  
The U.S

e16217 Background: The vast majority of pancreatic ductal adenocarcinoma (PDAC) patients have unresectable disease at diagnosis, with only about 20% presenting with either resectable or borderline resectable tumors and who may receive adjuvant with or without neo-adjuvant treatment with surgery. This study seeks to characterize these treatment patterns in the real-world setting. Methods: This was a retrospective observational study to evaluate adjuvant treatment of PDAC patients, with or without neo-adjuvant treatment in the U.S. Patients with at least two medical claims with a primary diagnosis for PDAC between 2016 to 2019 were identified in the Truven MarketScan administrative claims database. A surgical resection within 3 months of any primary PDAC coded medical encounter was the index event, with patients required to be continuously enrolled for at least 3 months before and 6 months after the surgery. Patient demographics and treatment patterns (chemotherapy, radiotherapy, and chemoradiation) were evaluated over the pre-index (3 months) and post-index (3 and 6 months) observation windows. Neo-adjuvant and adjuvant treatment patterns were reported for the overall population and also stratified by age and sex. Results: 737 patients met the selection criteria with a majority (n=520, 71%) being <65 years old and 53% females (n=387). 65% (n=478) of patients received adjuvant chemotherapy during the 6-month post-index compared with 28% (n=207) receiving neo-adjuvant treatment. In the neo-adjuvant setting, patients were likely to receive leucovorin+fluorouracil+irinotecan+oxaliplatin (FOLFIRINOX; 43%, n=88) followed by gemcitabine+pacitaxel (18%, n=37), across all patients, as well as stratified by age or sex. Among patients that received adjuvant but did not receive neo-adjuvant treatment, patients were likely to receive gemcitabine monotherapy (35%, n=112) followed by gemcitabine+capecitabine (GEMCAP; 23%, n=72). Among adjuvant patients that had received neo-adjuvant treatment, the most common chemotherapy regimens were gemcitabine monotherapy (22%, n=35), GEMCAP (18%, n=29) and FOLFIRINOX (16%, n=26). For patients ≥ 65 years old, the most common adjuvant regimen was gemcitabine monotherapy (n=62, 29%) whereas for patients <65, the most common regimens were GEMCAP (25%, n=90) and gemcitabine monotherapy (16%, n=85). Gemcitabine monotherapy (41%; n=118 of 453) was the main adjuvant regimen for patients with index dates of 2016-2017 but for those with index dates of 2018-2019 the most common was FOLFIRINOX (34%; n=64 of 284) followed by GEMCAP (18%; n=35 of 284). Conclusions: The majority (70%) of patients that underwent PDAC resection surgery did not receive neo-adjuvant treatment and about a third of patients did not receive any adjuvant treatment. These results suggest an unmet need in the management of PDAC.

The Secret Life of Schema in Web Protocols, API's and Software Type Systems

2017 ◽  
Author(s):  
David Lee
Keyword(s):  
Real World ◽  
Multiple Representations ◽  
Type Systems ◽  
Work Flow ◽  
Use Case ◽  
Proof Of Concept ◽  
Experimental Proof ◽  
Reverse Engineer ◽  
Data Schema ◽  
Rest Api

In this publication, I describe some of the results of several years’ research and experimentation in the field of Web API Protocols (JSON/XML/Media over HTTP) and Software APIs tracing the migration of ‘Schema’ into software class definitions, annotations, formal and semi-formal markup document types describing their structure and usefulness. Using a specific use case as a representative example, I demonstrate the rationale, steps and results of an experimental proof of concept. The proof of concept utilizes a wide variety of easily available techniques and tools rarely used together in a work-flow to reverse engineer a REST API from its behavior. It involves coupled transformations of data, schema, and software, through multiple representations utilizing tools from otherwise disparate domains to produce a largely auto-generated application to aid in a real world business problems.

scholarly journals Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1084 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephan Chan ◽  
Tomohiro Minami ◽  
Hirokazu Chishina ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Unmet Need ◽  
Intermediate Stage ◽  
Proof Of Concept ◽  
Concept Study

Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child–Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were −2.61 to −2.61 for 30 patients in the lenvatinib group (p = 0.254) and −2.66 to −2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child–Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.

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