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Creation of a National Virtual Tumor Board Through the National TeleOncology Service
Background
There is unequal access to subspecialty oncology expertise across the Veterans Affairs (VA) network. To address this need, the VA established National TeleOncology (NTO), which provides multiple virtual services (asynchronous [electronic consult] and synchronous [phone, video to home, video to facility]) to over 20 VA sites. Beyond these care modalities, a virtual tumor board was conceived to provide a forum for multidisciplinary review of patient cases. We describe the creation of the first NTO virtual tumor board, encompassing malignant hematology diagnoses.
Observations
Tumor boards are considered a standard of care. While challenging to quantify nationally, multiple single institution experiences have established the importance of tumor boards across different measures. A panel of stakeholders were convened to discuss the creation of a virtual tumor board. Best practices and standard operating procedures were created based on guidance from relevant literature and internal VA experience. Participants from specialties including medical oncology, surgical oncology, radiology, pathology, transplant, and palliative care were engaged from eight different VA medical centers across the nation. On March 2, 2022, the initial tumor board was held allowing for synchronous virtual review of patient pathology and imaging. Thus far 6 tumor boards have been convened, reviewing 11 patients originating from 6 different VA sites.
Results
A participant survey was conducted after 4 sessions, which indicated that all who completed the survey (n = 9) found the sessions beneficial or somewhat beneficial, and 55% found the sessions highly applicable to their practice. The most recent tumor board had 33 participants (physicians, nurses, advanced practice practitioners, and pharmacists).
Conclusions
The establishment of a national VA tumor board represents a novel approach to the review of oncology cases across the VA network. The goal of this tumor board is to leverage the diverse knowledge base that exists within the VA to deliver equitable care regardless of veteran location. Along with improving our general understanding of tumor board application, we believe that the NTO tumor board establishes a unique forum for additional tumor types, continued medical education opportunities, and the review of VA clinical trial opportunities.
Background
There is unequal access to subspecialty oncology expertise across the Veterans Affairs (VA) network. To address this need, the VA established National TeleOncology (NTO), which provides multiple virtual services (asynchronous [electronic consult] and synchronous [phone, video to home, video to facility]) to over 20 VA sites. Beyond these care modalities, a virtual tumor board was conceived to provide a forum for multidisciplinary review of patient cases. We describe the creation of the first NTO virtual tumor board, encompassing malignant hematology diagnoses.
Observations
Tumor boards are considered a standard of care. While challenging to quantify nationally, multiple single institution experiences have established the importance of tumor boards across different measures. A panel of stakeholders were convened to discuss the creation of a virtual tumor board. Best practices and standard operating procedures were created based on guidance from relevant literature and internal VA experience. Participants from specialties including medical oncology, surgical oncology, radiology, pathology, transplant, and palliative care were engaged from eight different VA medical centers across the nation. On March 2, 2022, the initial tumor board was held allowing for synchronous virtual review of patient pathology and imaging. Thus far 6 tumor boards have been convened, reviewing 11 patients originating from 6 different VA sites.
Results
A participant survey was conducted after 4 sessions, which indicated that all who completed the survey (n = 9) found the sessions beneficial or somewhat beneficial, and 55% found the sessions highly applicable to their practice. The most recent tumor board had 33 participants (physicians, nurses, advanced practice practitioners, and pharmacists).
Conclusions
The establishment of a national VA tumor board represents a novel approach to the review of oncology cases across the VA network. The goal of this tumor board is to leverage the diverse knowledge base that exists within the VA to deliver equitable care regardless of veteran location. Along with improving our general understanding of tumor board application, we believe that the NTO tumor board establishes a unique forum for additional tumor types, continued medical education opportunities, and the review of VA clinical trial opportunities.
Background
There is unequal access to subspecialty oncology expertise across the Veterans Affairs (VA) network. To address this need, the VA established National TeleOncology (NTO), which provides multiple virtual services (asynchronous [electronic consult] and synchronous [phone, video to home, video to facility]) to over 20 VA sites. Beyond these care modalities, a virtual tumor board was conceived to provide a forum for multidisciplinary review of patient cases. We describe the creation of the first NTO virtual tumor board, encompassing malignant hematology diagnoses.
Observations
Tumor boards are considered a standard of care. While challenging to quantify nationally, multiple single institution experiences have established the importance of tumor boards across different measures. A panel of stakeholders were convened to discuss the creation of a virtual tumor board. Best practices and standard operating procedures were created based on guidance from relevant literature and internal VA experience. Participants from specialties including medical oncology, surgical oncology, radiology, pathology, transplant, and palliative care were engaged from eight different VA medical centers across the nation. On March 2, 2022, the initial tumor board was held allowing for synchronous virtual review of patient pathology and imaging. Thus far 6 tumor boards have been convened, reviewing 11 patients originating from 6 different VA sites.
Results
A participant survey was conducted after 4 sessions, which indicated that all who completed the survey (n = 9) found the sessions beneficial or somewhat beneficial, and 55% found the sessions highly applicable to their practice. The most recent tumor board had 33 participants (physicians, nurses, advanced practice practitioners, and pharmacists).
Conclusions
The establishment of a national VA tumor board represents a novel approach to the review of oncology cases across the VA network. The goal of this tumor board is to leverage the diverse knowledge base that exists within the VA to deliver equitable care regardless of veteran location. Along with improving our general understanding of tumor board application, we believe that the NTO tumor board establishes a unique forum for additional tumor types, continued medical education opportunities, and the review of VA clinical trial opportunities.
Development of an Informatics Infrastructure and Frontend Dashboard for Monitoring Clinical Operations of the National TeleOncology Service
Background
Since inception, the Veterans Affairs (VA) National TeleOncology (NTO) service has monitored clinical operations through data tools produced by the Veterans Health Administration Support Service Center (VSSC). Unfortunately, pertinent data are spread across multiple reports, making it difficult to continually harmonize needed information. Further, the VSSC does not account for NTO’s hub and spoke clinical model, leading to inaccuracies when attempting to analyze unique encounters. To address these challenges, NTO partnered with the VA Salt Lake City Health Care System Informatics, Decision-Enhancement, and Analytic Sciences Center (IDEAS) to develop an informatics architecture and frontend NTO Clinical Operations Dashboard (NCOD). Here, we summarize our dashboard development process and the finalized key reporting components of the NCOD.
Methods
The VA Corporate Data Warehouse (CDW) serves as the primary data source for the NCOD. SQL Server Integration Services was used to build the backend data architecture. Data from the CDW were isolated into a staging data mart for reporting purposes using an extract, transform, load (ETL) approach. The frontend user interface was developed using Power BI. We used a participatory approach1 in determining reporting requirements. Stakeholders included the IDEAS dashboard development team and potential end users from NTO, including leadership, program managers, support assistants, and telehealth coordinators.
Results
The NCOD ETL is scheduled to refresh the data nightly to provide end users with a near real-time experience. The NCOD is comprised of the following four data views: clinic availability, team productivity, patient summary, and encounter summary. The clinic availability view summarizes clinic capacity, no shows, overbookings, and percent utilization. Relative value unit- based productivity is summarized in the team productivity view. The patient summary view presents aggregated data for veterans served by NTO, including geographic distribution, with patient-level drill down displaying demographics, cancer characteristics, and treatment history. Lastly, the encounter view displays utilization trends by modality, while accurately accounting for the hub and spoke clinical model.
Conclusions
An informatics architecture and frontend information display that is capable of synthesizing EHR data into a consumable format has been pivotal in obtaining accurate and timely insight into the demand and capacity of services provided by NTO.
- Esquer Rochin MA, Gutierrez-Garcia JO, Rosales JH, Rodriguez LF. Design and evaluation of a dashboard to support the comprehension of the progression.
Background
Since inception, the Veterans Affairs (VA) National TeleOncology (NTO) service has monitored clinical operations through data tools produced by the Veterans Health Administration Support Service Center (VSSC). Unfortunately, pertinent data are spread across multiple reports, making it difficult to continually harmonize needed information. Further, the VSSC does not account for NTO’s hub and spoke clinical model, leading to inaccuracies when attempting to analyze unique encounters. To address these challenges, NTO partnered with the VA Salt Lake City Health Care System Informatics, Decision-Enhancement, and Analytic Sciences Center (IDEAS) to develop an informatics architecture and frontend NTO Clinical Operations Dashboard (NCOD). Here, we summarize our dashboard development process and the finalized key reporting components of the NCOD.
Methods
The VA Corporate Data Warehouse (CDW) serves as the primary data source for the NCOD. SQL Server Integration Services was used to build the backend data architecture. Data from the CDW were isolated into a staging data mart for reporting purposes using an extract, transform, load (ETL) approach. The frontend user interface was developed using Power BI. We used a participatory approach1 in determining reporting requirements. Stakeholders included the IDEAS dashboard development team and potential end users from NTO, including leadership, program managers, support assistants, and telehealth coordinators.
Results
The NCOD ETL is scheduled to refresh the data nightly to provide end users with a near real-time experience. The NCOD is comprised of the following four data views: clinic availability, team productivity, patient summary, and encounter summary. The clinic availability view summarizes clinic capacity, no shows, overbookings, and percent utilization. Relative value unit- based productivity is summarized in the team productivity view. The patient summary view presents aggregated data for veterans served by NTO, including geographic distribution, with patient-level drill down displaying demographics, cancer characteristics, and treatment history. Lastly, the encounter view displays utilization trends by modality, while accurately accounting for the hub and spoke clinical model.
Conclusions
An informatics architecture and frontend information display that is capable of synthesizing EHR data into a consumable format has been pivotal in obtaining accurate and timely insight into the demand and capacity of services provided by NTO.
Background
Since inception, the Veterans Affairs (VA) National TeleOncology (NTO) service has monitored clinical operations through data tools produced by the Veterans Health Administration Support Service Center (VSSC). Unfortunately, pertinent data are spread across multiple reports, making it difficult to continually harmonize needed information. Further, the VSSC does not account for NTO’s hub and spoke clinical model, leading to inaccuracies when attempting to analyze unique encounters. To address these challenges, NTO partnered with the VA Salt Lake City Health Care System Informatics, Decision-Enhancement, and Analytic Sciences Center (IDEAS) to develop an informatics architecture and frontend NTO Clinical Operations Dashboard (NCOD). Here, we summarize our dashboard development process and the finalized key reporting components of the NCOD.
Methods
The VA Corporate Data Warehouse (CDW) serves as the primary data source for the NCOD. SQL Server Integration Services was used to build the backend data architecture. Data from the CDW were isolated into a staging data mart for reporting purposes using an extract, transform, load (ETL) approach. The frontend user interface was developed using Power BI. We used a participatory approach1 in determining reporting requirements. Stakeholders included the IDEAS dashboard development team and potential end users from NTO, including leadership, program managers, support assistants, and telehealth coordinators.
Results
The NCOD ETL is scheduled to refresh the data nightly to provide end users with a near real-time experience. The NCOD is comprised of the following four data views: clinic availability, team productivity, patient summary, and encounter summary. The clinic availability view summarizes clinic capacity, no shows, overbookings, and percent utilization. Relative value unit- based productivity is summarized in the team productivity view. The patient summary view presents aggregated data for veterans served by NTO, including geographic distribution, with patient-level drill down displaying demographics, cancer characteristics, and treatment history. Lastly, the encounter view displays utilization trends by modality, while accurately accounting for the hub and spoke clinical model.
Conclusions
An informatics architecture and frontend information display that is capable of synthesizing EHR data into a consumable format has been pivotal in obtaining accurate and timely insight into the demand and capacity of services provided by NTO.
- Esquer Rochin MA, Gutierrez-Garcia JO, Rosales JH, Rodriguez LF. Design and evaluation of a dashboard to support the comprehension of the progression.
- Esquer Rochin MA, Gutierrez-Garcia JO, Rosales JH, Rodriguez LF. Design and evaluation of a dashboard to support the comprehension of the progression.
Myeloid Neoplasm Masquerading as Hypereosinophilia and Sweet Syndrome
Introduction
Hypereosinophilia can be seen in many medical conditions, including myeloproliferative disorders, and can lead to serious complications if untreated. Sweet syndrome is a rare and painful cutaneous inflammatory condition that has been linked to underlying malignancies.
Case Presentation
A 72-year-old male presented with 6-month history of painful maculopapular rash, night sweats, fever, and weight loss. He was treated with antibiotics and steroids with no improvement. A skin biopsy demonstrated neutrophilic dermatosis consistent with sweet syndrome. Laboratory studies a showed hemoglobin 7.1g/dl, WBC 12.9x103/uL, 30% eosinophils, absolute eosinophil count 3x109/L, and normal platelets. Infectious and immunological work up was negative. CT scan revealed splenomegaly. Bone marrow biopsy showed 100% hypercellularity, trilineage atypia, eosinophils 43% (normal, 1-5%) and 3-4% blasts positive for CD34 and CD117. FISH studies detected loss of PDGFRB signal, cytogenetics revealed a complex karyotype. He was diagnosed with a high-risk (based on IPSS-R) MDS/MPN cross-over with peripheral eosinophilia and is planned to undergo HSCT.
Discussion
Hematologic malignancies are associated with several paraneoplastic syndromes including sweet syndrome, also known as acute febrile neutrophilic dermatosis. The literature describes sweet syndrome occurring mostly with AML but can also be seen with other malignancies like MDS and solid tumor. The distinction between sweet syndrome and infectious or immune-mediated rash can be challenging as it requires histopathologic evaluation and is usually mistreated. Hypereosinophilia is defined as persistent eosinophil count of at least 1.5x109/L. It can be idiopathic or associated with allergic, rheumatologic, infectious, or neoplastic conditions. Clonal hypereosinophilia is most frequently associated with chronic myeloid neoplasms such as myeloproliferative neoplasm (MPN) or overlapping MDS/MPN, and more less frequently with AML. Hypereosinophilia related to hematological malignancies has been linked to gene rearrangements involving PDGFRA, PDGFRB, FGFR1, and JAK2. Patients with documented rearrangements or mutations in PDGFRB are treated with imatinib, which is a potent kinase inhibitor. However, patients with high-risk MDS/MPN with associated eosinophilia are typically treated as MDS and should undergo allogenic HSCT if eligible.
Conclusions
Both hypereosinophlia and sweet syndrome have been linked to myeloid neoplasms. Early recognition of either phenomenon as a paraneoplastic syndrome is important for early diagnosis and treatment.
Introduction
Hypereosinophilia can be seen in many medical conditions, including myeloproliferative disorders, and can lead to serious complications if untreated. Sweet syndrome is a rare and painful cutaneous inflammatory condition that has been linked to underlying malignancies.
Case Presentation
A 72-year-old male presented with 6-month history of painful maculopapular rash, night sweats, fever, and weight loss. He was treated with antibiotics and steroids with no improvement. A skin biopsy demonstrated neutrophilic dermatosis consistent with sweet syndrome. Laboratory studies a showed hemoglobin 7.1g/dl, WBC 12.9x103/uL, 30% eosinophils, absolute eosinophil count 3x109/L, and normal platelets. Infectious and immunological work up was negative. CT scan revealed splenomegaly. Bone marrow biopsy showed 100% hypercellularity, trilineage atypia, eosinophils 43% (normal, 1-5%) and 3-4% blasts positive for CD34 and CD117. FISH studies detected loss of PDGFRB signal, cytogenetics revealed a complex karyotype. He was diagnosed with a high-risk (based on IPSS-R) MDS/MPN cross-over with peripheral eosinophilia and is planned to undergo HSCT.
Discussion
Hematologic malignancies are associated with several paraneoplastic syndromes including sweet syndrome, also known as acute febrile neutrophilic dermatosis. The literature describes sweet syndrome occurring mostly with AML but can also be seen with other malignancies like MDS and solid tumor. The distinction between sweet syndrome and infectious or immune-mediated rash can be challenging as it requires histopathologic evaluation and is usually mistreated. Hypereosinophilia is defined as persistent eosinophil count of at least 1.5x109/L. It can be idiopathic or associated with allergic, rheumatologic, infectious, or neoplastic conditions. Clonal hypereosinophilia is most frequently associated with chronic myeloid neoplasms such as myeloproliferative neoplasm (MPN) or overlapping MDS/MPN, and more less frequently with AML. Hypereosinophilia related to hematological malignancies has been linked to gene rearrangements involving PDGFRA, PDGFRB, FGFR1, and JAK2. Patients with documented rearrangements or mutations in PDGFRB are treated with imatinib, which is a potent kinase inhibitor. However, patients with high-risk MDS/MPN with associated eosinophilia are typically treated as MDS and should undergo allogenic HSCT if eligible.
Conclusions
Both hypereosinophlia and sweet syndrome have been linked to myeloid neoplasms. Early recognition of either phenomenon as a paraneoplastic syndrome is important for early diagnosis and treatment.
Introduction
Hypereosinophilia can be seen in many medical conditions, including myeloproliferative disorders, and can lead to serious complications if untreated. Sweet syndrome is a rare and painful cutaneous inflammatory condition that has been linked to underlying malignancies.
Case Presentation
A 72-year-old male presented with 6-month history of painful maculopapular rash, night sweats, fever, and weight loss. He was treated with antibiotics and steroids with no improvement. A skin biopsy demonstrated neutrophilic dermatosis consistent with sweet syndrome. Laboratory studies a showed hemoglobin 7.1g/dl, WBC 12.9x103/uL, 30% eosinophils, absolute eosinophil count 3x109/L, and normal platelets. Infectious and immunological work up was negative. CT scan revealed splenomegaly. Bone marrow biopsy showed 100% hypercellularity, trilineage atypia, eosinophils 43% (normal, 1-5%) and 3-4% blasts positive for CD34 and CD117. FISH studies detected loss of PDGFRB signal, cytogenetics revealed a complex karyotype. He was diagnosed with a high-risk (based on IPSS-R) MDS/MPN cross-over with peripheral eosinophilia and is planned to undergo HSCT.
Discussion
Hematologic malignancies are associated with several paraneoplastic syndromes including sweet syndrome, also known as acute febrile neutrophilic dermatosis. The literature describes sweet syndrome occurring mostly with AML but can also be seen with other malignancies like MDS and solid tumor. The distinction between sweet syndrome and infectious or immune-mediated rash can be challenging as it requires histopathologic evaluation and is usually mistreated. Hypereosinophilia is defined as persistent eosinophil count of at least 1.5x109/L. It can be idiopathic or associated with allergic, rheumatologic, infectious, or neoplastic conditions. Clonal hypereosinophilia is most frequently associated with chronic myeloid neoplasms such as myeloproliferative neoplasm (MPN) or overlapping MDS/MPN, and more less frequently with AML. Hypereosinophilia related to hematological malignancies has been linked to gene rearrangements involving PDGFRA, PDGFRB, FGFR1, and JAK2. Patients with documented rearrangements or mutations in PDGFRB are treated with imatinib, which is a potent kinase inhibitor. However, patients with high-risk MDS/MPN with associated eosinophilia are typically treated as MDS and should undergo allogenic HSCT if eligible.
Conclusions
Both hypereosinophlia and sweet syndrome have been linked to myeloid neoplasms. Early recognition of either phenomenon as a paraneoplastic syndrome is important for early diagnosis and treatment.
Gastrointestinal Stromal Tumor Arising From the Small Intestine in a Heart Transplant Recipient on Hemodialysis and Chronic Immunosuppression: A Case Report
Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors with worse prognosis if arising from the small bowel. Surgery remains the mainstay of treatment for patients with resectable tumors. Imatinib has become the standard treatment in cKIT-positive GISTs with significant morbidity in neoadjuvant, adjuvant, and palliative settings. There are limited data on efficacy and safety of imatinib in dialysis patients, and chemotherapy dosing is challenging in dialysis patients with multiple comorbidities.
Presentation
A 68-year-old male with a history of orthotopic heart transplantation on sirolimus with prednisone, cardiac allograft vasculopathy, plus ESRD on peritoneal dialysis (PD), presented with lower abdominal pain and fever. Abdominal imaging revealed a right lower quadrant (RLQ) mass with concern for bowel perforation.
Diagnosis and Treatment
The patient underwent exploratory laparoscopy with small bowel resection, excision of the mesenteric small bowel mass, drainage and washout of intraabdominal abscess, removal of PD catheter, and transition to hemodialysis. Pathology revealed a 14.5-cm high-grade GIST with mixed spindle and epithelioid types involving the ileal wall and mesentery, consistent with pT4 primary tumor and stage IIIB disease. Molecular testing was positive for c-KIT and DOG-1 mutations.
After a prolonged recovery, repeat abdominal imaging demonstrated metastatic liver disease and a new RLQ lesion. The patient was started on palliative imatinib 100 mg daily with subsequent increase to 200 mg daily. He was monitored closely for toxicities but reported only mild nausea controlled with ondansetron. Hemodialysis was continued 3 times per week. Follow up scans 3 months later showed improvement in RLQ mass and hepatic lesions. The patient remains on the current dose 15 months after the diagnosis.
Conclusion
To our knowledge, this is the first case of a small intestinal GIST in a heart transplant recipient treated with dose-reduced imatinib with concurrent dialysis and immunosuppression. Treatment decision-making was complex given concern for cardiotoxicity with pre-existing cardiac disease and drug-drug interactions with immunosuppressive agents. While some literature suggests standard dose imatinib with dialysis, no large-scale studies evaluated pharmacokinetics of imatinib with creatinine clearance < 20 mL/min. There is a need for further studies to determine dosing strategies for such patients.
Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors with worse prognosis if arising from the small bowel. Surgery remains the mainstay of treatment for patients with resectable tumors. Imatinib has become the standard treatment in cKIT-positive GISTs with significant morbidity in neoadjuvant, adjuvant, and palliative settings. There are limited data on efficacy and safety of imatinib in dialysis patients, and chemotherapy dosing is challenging in dialysis patients with multiple comorbidities.
Presentation
A 68-year-old male with a history of orthotopic heart transplantation on sirolimus with prednisone, cardiac allograft vasculopathy, plus ESRD on peritoneal dialysis (PD), presented with lower abdominal pain and fever. Abdominal imaging revealed a right lower quadrant (RLQ) mass with concern for bowel perforation.
Diagnosis and Treatment
The patient underwent exploratory laparoscopy with small bowel resection, excision of the mesenteric small bowel mass, drainage and washout of intraabdominal abscess, removal of PD catheter, and transition to hemodialysis. Pathology revealed a 14.5-cm high-grade GIST with mixed spindle and epithelioid types involving the ileal wall and mesentery, consistent with pT4 primary tumor and stage IIIB disease. Molecular testing was positive for c-KIT and DOG-1 mutations.
After a prolonged recovery, repeat abdominal imaging demonstrated metastatic liver disease and a new RLQ lesion. The patient was started on palliative imatinib 100 mg daily with subsequent increase to 200 mg daily. He was monitored closely for toxicities but reported only mild nausea controlled with ondansetron. Hemodialysis was continued 3 times per week. Follow up scans 3 months later showed improvement in RLQ mass and hepatic lesions. The patient remains on the current dose 15 months after the diagnosis.
Conclusion
To our knowledge, this is the first case of a small intestinal GIST in a heart transplant recipient treated with dose-reduced imatinib with concurrent dialysis and immunosuppression. Treatment decision-making was complex given concern for cardiotoxicity with pre-existing cardiac disease and drug-drug interactions with immunosuppressive agents. While some literature suggests standard dose imatinib with dialysis, no large-scale studies evaluated pharmacokinetics of imatinib with creatinine clearance < 20 mL/min. There is a need for further studies to determine dosing strategies for such patients.
Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors with worse prognosis if arising from the small bowel. Surgery remains the mainstay of treatment for patients with resectable tumors. Imatinib has become the standard treatment in cKIT-positive GISTs with significant morbidity in neoadjuvant, adjuvant, and palliative settings. There are limited data on efficacy and safety of imatinib in dialysis patients, and chemotherapy dosing is challenging in dialysis patients with multiple comorbidities.
Presentation
A 68-year-old male with a history of orthotopic heart transplantation on sirolimus with prednisone, cardiac allograft vasculopathy, plus ESRD on peritoneal dialysis (PD), presented with lower abdominal pain and fever. Abdominal imaging revealed a right lower quadrant (RLQ) mass with concern for bowel perforation.
Diagnosis and Treatment
The patient underwent exploratory laparoscopy with small bowel resection, excision of the mesenteric small bowel mass, drainage and washout of intraabdominal abscess, removal of PD catheter, and transition to hemodialysis. Pathology revealed a 14.5-cm high-grade GIST with mixed spindle and epithelioid types involving the ileal wall and mesentery, consistent with pT4 primary tumor and stage IIIB disease. Molecular testing was positive for c-KIT and DOG-1 mutations.
After a prolonged recovery, repeat abdominal imaging demonstrated metastatic liver disease and a new RLQ lesion. The patient was started on palliative imatinib 100 mg daily with subsequent increase to 200 mg daily. He was monitored closely for toxicities but reported only mild nausea controlled with ondansetron. Hemodialysis was continued 3 times per week. Follow up scans 3 months later showed improvement in RLQ mass and hepatic lesions. The patient remains on the current dose 15 months after the diagnosis.
Conclusion
To our knowledge, this is the first case of a small intestinal GIST in a heart transplant recipient treated with dose-reduced imatinib with concurrent dialysis and immunosuppression. Treatment decision-making was complex given concern for cardiotoxicity with pre-existing cardiac disease and drug-drug interactions with immunosuppressive agents. While some literature suggests standard dose imatinib with dialysis, no large-scale studies evaluated pharmacokinetics of imatinib with creatinine clearance < 20 mL/min. There is a need for further studies to determine dosing strategies for such patients.
Team-based Genetic Consultation: An Effective System of Care for Delivery of Precision Oncology Services
Objectives
US Department of Veterans Affairs (VA) patients with genetics referrals are 1.5 times more likely to have multiple cancer screening and preventive procedures if they completed their genetic consultations, but only when completed under a VA traditional model staffed by a team of clinical geneticists and genetic counselors versus a VA nontraditional, centralized telehealth model staffed by genetic counselors working independently. We sought to understand the reasons for these differences in cancer screening and prevention uptake.
Methods
We reviewed randomly selected medical records of patients with cancer genetics referrals stratified by model (142 records from each model). We conducted semi-structured interviews with 15 genetics providers and 36 referring clinicians from 13 VA facilities using purposive sampling. We analyzed annotated medical records and interview transcripts using a rapid assessment process. We characterized annotations as personalized recommendations (eg, begin colonoscopy at age 30 then every 1-2 years), options (eg, consider bilateral mastectomy), and generic messages (eg, refer to guidelines or another provider).
Results
Cancer screening or prevention was documented in 80 traditional-model records (141 annotations) and 106 nontraditional-model records (143 annotations). Personalized recommendations comprised 69% (97/141) of annotations within traditional-model records and 30% (43/143) within nontraditional-model records. Generic messages comprised 17% (24/141) of annotations in traditional-model records and 51% (73/143) in nontraditional-model records. From interview data, referring clinicians expected a broad range of services from genetics providers, including management and screening recommendations, and stated their role was to follow through on recommendations made. Under the traditional model, geneticists formulated recommendations documented by genetic counselors. Under the nontraditional model, scope of practice limited how genetic counselors addressed cancer screening and prevention.
Conclusions/Impacts
Personalized recommendations were typical of traditional-model records, whereas nontraditional-model records usually had generic messages. Compared with the nontraditional model, the traditional model was more patient-centered and better meets expectations of referring clinicians, which might explain in part the differences in patient uptake of cancer screening and preventive procedures.
As the demand for genetic services grows, the VA should promote team-based care under the traditional model for a more patient-centered, coordinated, and effective system of care for precision oncology.
Objectives
US Department of Veterans Affairs (VA) patients with genetics referrals are 1.5 times more likely to have multiple cancer screening and preventive procedures if they completed their genetic consultations, but only when completed under a VA traditional model staffed by a team of clinical geneticists and genetic counselors versus a VA nontraditional, centralized telehealth model staffed by genetic counselors working independently. We sought to understand the reasons for these differences in cancer screening and prevention uptake.
Methods
We reviewed randomly selected medical records of patients with cancer genetics referrals stratified by model (142 records from each model). We conducted semi-structured interviews with 15 genetics providers and 36 referring clinicians from 13 VA facilities using purposive sampling. We analyzed annotated medical records and interview transcripts using a rapid assessment process. We characterized annotations as personalized recommendations (eg, begin colonoscopy at age 30 then every 1-2 years), options (eg, consider bilateral mastectomy), and generic messages (eg, refer to guidelines or another provider).
Results
Cancer screening or prevention was documented in 80 traditional-model records (141 annotations) and 106 nontraditional-model records (143 annotations). Personalized recommendations comprised 69% (97/141) of annotations within traditional-model records and 30% (43/143) within nontraditional-model records. Generic messages comprised 17% (24/141) of annotations in traditional-model records and 51% (73/143) in nontraditional-model records. From interview data, referring clinicians expected a broad range of services from genetics providers, including management and screening recommendations, and stated their role was to follow through on recommendations made. Under the traditional model, geneticists formulated recommendations documented by genetic counselors. Under the nontraditional model, scope of practice limited how genetic counselors addressed cancer screening and prevention.
Conclusions/Impacts
Personalized recommendations were typical of traditional-model records, whereas nontraditional-model records usually had generic messages. Compared with the nontraditional model, the traditional model was more patient-centered and better meets expectations of referring clinicians, which might explain in part the differences in patient uptake of cancer screening and preventive procedures.
As the demand for genetic services grows, the VA should promote team-based care under the traditional model for a more patient-centered, coordinated, and effective system of care for precision oncology.
Objectives
US Department of Veterans Affairs (VA) patients with genetics referrals are 1.5 times more likely to have multiple cancer screening and preventive procedures if they completed their genetic consultations, but only when completed under a VA traditional model staffed by a team of clinical geneticists and genetic counselors versus a VA nontraditional, centralized telehealth model staffed by genetic counselors working independently. We sought to understand the reasons for these differences in cancer screening and prevention uptake.
Methods
We reviewed randomly selected medical records of patients with cancer genetics referrals stratified by model (142 records from each model). We conducted semi-structured interviews with 15 genetics providers and 36 referring clinicians from 13 VA facilities using purposive sampling. We analyzed annotated medical records and interview transcripts using a rapid assessment process. We characterized annotations as personalized recommendations (eg, begin colonoscopy at age 30 then every 1-2 years), options (eg, consider bilateral mastectomy), and generic messages (eg, refer to guidelines or another provider).
Results
Cancer screening or prevention was documented in 80 traditional-model records (141 annotations) and 106 nontraditional-model records (143 annotations). Personalized recommendations comprised 69% (97/141) of annotations within traditional-model records and 30% (43/143) within nontraditional-model records. Generic messages comprised 17% (24/141) of annotations in traditional-model records and 51% (73/143) in nontraditional-model records. From interview data, referring clinicians expected a broad range of services from genetics providers, including management and screening recommendations, and stated their role was to follow through on recommendations made. Under the traditional model, geneticists formulated recommendations documented by genetic counselors. Under the nontraditional model, scope of practice limited how genetic counselors addressed cancer screening and prevention.
Conclusions/Impacts
Personalized recommendations were typical of traditional-model records, whereas nontraditional-model records usually had generic messages. Compared with the nontraditional model, the traditional model was more patient-centered and better meets expectations of referring clinicians, which might explain in part the differences in patient uptake of cancer screening and preventive procedures.
As the demand for genetic services grows, the VA should promote team-based care under the traditional model for a more patient-centered, coordinated, and effective system of care for precision oncology.
Duty to Assist: Assisting Veterans With Exposures to Hazardous Materials
Background
Veterans are not well informed of the presumptive conditions associated with toxic exposures endured during military service. A quality improvement project was created to increase awareness. The purpose of this project was to: Raise awareness of presumptive conditions associated with Agent Orange, Camp LeJeune contaminated water and Southwest Asia Burn Pit (fine particulate) exposure, to notify veterans how to initiate the disability benefits application process, and to inform veterans and providers of new changes in legislation (ie, Blue Water and Southwest Asia).
Methods
Using the Cancer Registry, the cancer access coordinator identified veterans with a diagnosis on each of the 3 presumptive condition lists for Agent Orange, Camp Lejeune, and Southwest Asia. These lists were then forwarded to informatics who further screened for military service history. Informative mailers were then sent to the identified veterans, alerting them to their potential eligibility for disability benefits. In addition, the mailers informed veterans how to initiate the benefits application process, how to schedule Disability Benefit Questionnaire (DBQ) exams to expedite the process, as well as contact information for local Veteran’s Service Commission (VSC) and the Veterans Benefits Administration (VBA) for further assistance. These letters were also distributed throughout the medical facility and was shared at cancer committee meetings to increase provider awareness.
Results
In 2021, 604 veterans were identified as potentially eligible for disability benefits and were contacted via mailer. As a result, 153 veterans have been granted service-connected benefits for their identified condition. An additional 91 mailers have been sent since January 2022.
Conclusions
Utilizing this simple practice increases both veteran and provider awareness of presumptive conditions, and aids in veterans receiving the disability compensation they are entitled to. In addition, this practice improves the overall quality of care the veterans receive through the VA and gives us a chance to give back to our veterans.
Background
Veterans are not well informed of the presumptive conditions associated with toxic exposures endured during military service. A quality improvement project was created to increase awareness. The purpose of this project was to: Raise awareness of presumptive conditions associated with Agent Orange, Camp LeJeune contaminated water and Southwest Asia Burn Pit (fine particulate) exposure, to notify veterans how to initiate the disability benefits application process, and to inform veterans and providers of new changes in legislation (ie, Blue Water and Southwest Asia).
Methods
Using the Cancer Registry, the cancer access coordinator identified veterans with a diagnosis on each of the 3 presumptive condition lists for Agent Orange, Camp Lejeune, and Southwest Asia. These lists were then forwarded to informatics who further screened for military service history. Informative mailers were then sent to the identified veterans, alerting them to their potential eligibility for disability benefits. In addition, the mailers informed veterans how to initiate the benefits application process, how to schedule Disability Benefit Questionnaire (DBQ) exams to expedite the process, as well as contact information for local Veteran’s Service Commission (VSC) and the Veterans Benefits Administration (VBA) for further assistance. These letters were also distributed throughout the medical facility and was shared at cancer committee meetings to increase provider awareness.
Results
In 2021, 604 veterans were identified as potentially eligible for disability benefits and were contacted via mailer. As a result, 153 veterans have been granted service-connected benefits for their identified condition. An additional 91 mailers have been sent since January 2022.
Conclusions
Utilizing this simple practice increases both veteran and provider awareness of presumptive conditions, and aids in veterans receiving the disability compensation they are entitled to. In addition, this practice improves the overall quality of care the veterans receive through the VA and gives us a chance to give back to our veterans.
Background
Veterans are not well informed of the presumptive conditions associated with toxic exposures endured during military service. A quality improvement project was created to increase awareness. The purpose of this project was to: Raise awareness of presumptive conditions associated with Agent Orange, Camp LeJeune contaminated water and Southwest Asia Burn Pit (fine particulate) exposure, to notify veterans how to initiate the disability benefits application process, and to inform veterans and providers of new changes in legislation (ie, Blue Water and Southwest Asia).
Methods
Using the Cancer Registry, the cancer access coordinator identified veterans with a diagnosis on each of the 3 presumptive condition lists for Agent Orange, Camp Lejeune, and Southwest Asia. These lists were then forwarded to informatics who further screened for military service history. Informative mailers were then sent to the identified veterans, alerting them to their potential eligibility for disability benefits. In addition, the mailers informed veterans how to initiate the benefits application process, how to schedule Disability Benefit Questionnaire (DBQ) exams to expedite the process, as well as contact information for local Veteran’s Service Commission (VSC) and the Veterans Benefits Administration (VBA) for further assistance. These letters were also distributed throughout the medical facility and was shared at cancer committee meetings to increase provider awareness.
Results
In 2021, 604 veterans were identified as potentially eligible for disability benefits and were contacted via mailer. As a result, 153 veterans have been granted service-connected benefits for their identified condition. An additional 91 mailers have been sent since January 2022.
Conclusions
Utilizing this simple practice increases both veteran and provider awareness of presumptive conditions, and aids in veterans receiving the disability compensation they are entitled to. In addition, this practice improves the overall quality of care the veterans receive through the VA and gives us a chance to give back to our veterans.
Online tool IDs people with genetic mutations linked to cancer
(PGVs) in a diverse spectrum of cancer susceptibility genes.
The PREMMplus online tool was developed and validated by researchers at the Dana-Farber Cancer Institute, Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.
The study was published online in the Journal of Clinical Oncology.
“Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling,” senior author Sapna Syngal, MD, MPH, with Dana-Farber/Brigham and Women’s Hospital, Boston, said in an institution news release.
Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.
“At a time when there’s a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they’re most needed – helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found,” Dr. Syngal says.
Online tool
The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual’s likelihood of harboring a PGV in 19 cancer susceptibility genes.
A PREMMplus score of 2.5% or greater had a 89%-94% sensitivity and > 97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined “category A” high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.
These PGVs “represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines,” the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.
The ability of PREMMplus to identify individuals with PGVs in “moderate-penetrance” cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still “quite strong” (84%-90% sensitivity and > 93% NPV), the study team reports.
In an interview, Dr. Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).
“Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate,” Dr. Syngal explained.
The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.
Dr. Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.
With the second version, the doctor and patient would fill out the information together during an office visit.
PREMMplus would be free for the individual patient or provider.
“What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing,” Dr. Syngal told this news organization.
“For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they’re going to use it,” Dr. Syngal said.
Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
(PGVs) in a diverse spectrum of cancer susceptibility genes.
The PREMMplus online tool was developed and validated by researchers at the Dana-Farber Cancer Institute, Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.
The study was published online in the Journal of Clinical Oncology.
“Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling,” senior author Sapna Syngal, MD, MPH, with Dana-Farber/Brigham and Women’s Hospital, Boston, said in an institution news release.
Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.
“At a time when there’s a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they’re most needed – helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found,” Dr. Syngal says.
Online tool
The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual’s likelihood of harboring a PGV in 19 cancer susceptibility genes.
A PREMMplus score of 2.5% or greater had a 89%-94% sensitivity and > 97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined “category A” high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.
These PGVs “represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines,” the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.
The ability of PREMMplus to identify individuals with PGVs in “moderate-penetrance” cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still “quite strong” (84%-90% sensitivity and > 93% NPV), the study team reports.
In an interview, Dr. Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).
“Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate,” Dr. Syngal explained.
The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.
Dr. Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.
With the second version, the doctor and patient would fill out the information together during an office visit.
PREMMplus would be free for the individual patient or provider.
“What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing,” Dr. Syngal told this news organization.
“For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they’re going to use it,” Dr. Syngal said.
Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
(PGVs) in a diverse spectrum of cancer susceptibility genes.
The PREMMplus online tool was developed and validated by researchers at the Dana-Farber Cancer Institute, Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.
The study was published online in the Journal of Clinical Oncology.
“Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling,” senior author Sapna Syngal, MD, MPH, with Dana-Farber/Brigham and Women’s Hospital, Boston, said in an institution news release.
Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.
“At a time when there’s a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they’re most needed – helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found,” Dr. Syngal says.
Online tool
The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual’s likelihood of harboring a PGV in 19 cancer susceptibility genes.
A PREMMplus score of 2.5% or greater had a 89%-94% sensitivity and > 97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined “category A” high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.
These PGVs “represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines,” the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.
The ability of PREMMplus to identify individuals with PGVs in “moderate-penetrance” cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still “quite strong” (84%-90% sensitivity and > 93% NPV), the study team reports.
In an interview, Dr. Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).
“Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate,” Dr. Syngal explained.
The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.
Dr. Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.
With the second version, the doctor and patient would fill out the information together during an office visit.
PREMMplus would be free for the individual patient or provider.
“What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing,” Dr. Syngal told this news organization.
“For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they’re going to use it,” Dr. Syngal said.
Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
Intera Oncology recalls hepatic artery infusion pumps for possible life-threatening issue
Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.
Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.
The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.
The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.
Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.
A version of this article first appeared on Medscape.com.
Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.
Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.
The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.
The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.
Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.
A version of this article first appeared on Medscape.com.
Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.
Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.
The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.
The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.
Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.
A version of this article first appeared on Medscape.com.
Evolocumab benefits accrue with longer follow-up: FOURIER OLE
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022
Ketogenic Diet and Cancer: A Case Report and Feasibility Study at VA Central California Healthcare System
Background
Ketogenic diet (KD) is a high-fat and low carbohydrate diet that has been reported as a treatment option for patients with cancer. KD creates a metabolic state in which blood glucose levels are reduced and ketone bodies are elevated. Cancer cells are unable to use ketone bodies for energy and metabolism due to mitochondrial dysfunction. We published the efficacy of KD in patients with cancer after failure of chemotherapy. 1 This case report is presented to evaluate the feasibility of KD concurrent with chemoimmunotherapy.
Case Report
Patient is a 69-year-old male who presented with iron deficiency anemia in 2018. Colonoscopy and biopsy showed colon adenocarcinoma. He underwent resection which confirmed stage IIIC disease. He received adjuvant treatment with FOLFOX but quickly developed pancreatic and omental metastasis. He was started on FOLFIRI + bevacizumab followed by pancreatic mass resection in 2019. Molecular testing revealed wild type KRAS, positive BRAF V600E, and high MSI. He received encorafenib + cetuximab until disease progression. Treatment was changed to pembrolizumab until PET scan showed progression. His CEA increased to 1031 in January 2021. He was subsequently started on KD concurrent with trifluridine + tipiracil + bevacizumab. He progressed after 10 months. Therapy was changed to ipilimumab + nivolumab with continuation of KD. He was strictly adherent to KD with low Glucose Ketone Index of 8.2 (confirming ketosis) but in 2022 his GKI level started to rise. His CEA, however, significantly decreased to 20 in March 2022 and PET scan showed stable disease. He presently is on maintenance nivolumab + KD while maintaining an excellent quality of life by EORTC QLQ scores.
Conclusions
The use of KD concurrently with chemotherapy and immunotherapy is still under investigation. Our case report shows that KD is tolerable with treatment and can possibly contribute to controlling progression of metastatic cancer. We are starting an investigator initiative KD trial that received a grant from R&D at VACCHCS. We will present the study protocol in poster presentation.
1. Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System]. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y
Background
Ketogenic diet (KD) is a high-fat and low carbohydrate diet that has been reported as a treatment option for patients with cancer. KD creates a metabolic state in which blood glucose levels are reduced and ketone bodies are elevated. Cancer cells are unable to use ketone bodies for energy and metabolism due to mitochondrial dysfunction. We published the efficacy of KD in patients with cancer after failure of chemotherapy. 1 This case report is presented to evaluate the feasibility of KD concurrent with chemoimmunotherapy.
Case Report
Patient is a 69-year-old male who presented with iron deficiency anemia in 2018. Colonoscopy and biopsy showed colon adenocarcinoma. He underwent resection which confirmed stage IIIC disease. He received adjuvant treatment with FOLFOX but quickly developed pancreatic and omental metastasis. He was started on FOLFIRI + bevacizumab followed by pancreatic mass resection in 2019. Molecular testing revealed wild type KRAS, positive BRAF V600E, and high MSI. He received encorafenib + cetuximab until disease progression. Treatment was changed to pembrolizumab until PET scan showed progression. His CEA increased to 1031 in January 2021. He was subsequently started on KD concurrent with trifluridine + tipiracil + bevacizumab. He progressed after 10 months. Therapy was changed to ipilimumab + nivolumab with continuation of KD. He was strictly adherent to KD with low Glucose Ketone Index of 8.2 (confirming ketosis) but in 2022 his GKI level started to rise. His CEA, however, significantly decreased to 20 in March 2022 and PET scan showed stable disease. He presently is on maintenance nivolumab + KD while maintaining an excellent quality of life by EORTC QLQ scores.
Conclusions
The use of KD concurrently with chemotherapy and immunotherapy is still under investigation. Our case report shows that KD is tolerable with treatment and can possibly contribute to controlling progression of metastatic cancer. We are starting an investigator initiative KD trial that received a grant from R&D at VACCHCS. We will present the study protocol in poster presentation.
Background
Ketogenic diet (KD) is a high-fat and low carbohydrate diet that has been reported as a treatment option for patients with cancer. KD creates a metabolic state in which blood glucose levels are reduced and ketone bodies are elevated. Cancer cells are unable to use ketone bodies for energy and metabolism due to mitochondrial dysfunction. We published the efficacy of KD in patients with cancer after failure of chemotherapy. 1 This case report is presented to evaluate the feasibility of KD concurrent with chemoimmunotherapy.
Case Report
Patient is a 69-year-old male who presented with iron deficiency anemia in 2018. Colonoscopy and biopsy showed colon adenocarcinoma. He underwent resection which confirmed stage IIIC disease. He received adjuvant treatment with FOLFOX but quickly developed pancreatic and omental metastasis. He was started on FOLFIRI + bevacizumab followed by pancreatic mass resection in 2019. Molecular testing revealed wild type KRAS, positive BRAF V600E, and high MSI. He received encorafenib + cetuximab until disease progression. Treatment was changed to pembrolizumab until PET scan showed progression. His CEA increased to 1031 in January 2021. He was subsequently started on KD concurrent with trifluridine + tipiracil + bevacizumab. He progressed after 10 months. Therapy was changed to ipilimumab + nivolumab with continuation of KD. He was strictly adherent to KD with low Glucose Ketone Index of 8.2 (confirming ketosis) but in 2022 his GKI level started to rise. His CEA, however, significantly decreased to 20 in March 2022 and PET scan showed stable disease. He presently is on maintenance nivolumab + KD while maintaining an excellent quality of life by EORTC QLQ scores.
Conclusions
The use of KD concurrently with chemotherapy and immunotherapy is still under investigation. Our case report shows that KD is tolerable with treatment and can possibly contribute to controlling progression of metastatic cancer. We are starting an investigator initiative KD trial that received a grant from R&D at VACCHCS. We will present the study protocol in poster presentation.
1. Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System]. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y
1. Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System]. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y