AVAHO

PURPOSE: To establish a program utilizing a multidisciplinary team to address health care disparities and improve outcomes. To develop a process that would streamline our navigation workflow and assist with the identification of barriers to care. Thus, enabling the Cancer Care program to focus on what really matters— - Veterans.

PROBLEM: The Cancer Care program utilized a series of spreadsheets and an Access database to follow the care of Veterans receiving care within Southeast Louisiana Veterans Health Care System (SLVHCS) and for those Veterans being care for in the community. Each navigator has distinct intervals in which they contact or educate their patients for which care must be carefully coordinated. Our team strives to provide a multidisciplinary approach, but our former workflow of 12 years not only restricted us to one user at a time, but it also restricted usage to one service at a time. Our Clinical Nurse Navigators, Cancer Care Social Worker and Registered Nutritionist were creating and utilizing customized spreadsheets via an Excel program which also restricted access within services. These technological constraints further increased potential for negative outcomes and delays in care.

METHOD: Standardize our navigation process and allow for systemic changes within the department. With over 200 patient navigation programs to choose from (Institute for Alternative Futures, 2007); we adopted OncoNav as our navigation software program. OncoNav is oncologyspecific software designed to help Patient Navigators schedule, track, organize, and report their interactions with patients. It is designed to integrate into the Navigator’s workflow, allowing Navigators to quickly view pertinent patient information, add notes, schedule appointments and run patient-specific reports seamlessly from one system. After purchasing and implementing, ONCONAV, staff participated in training and tailored the package to meet the needs unique to our cancer team.

OUTCOME: Enables staff to schedule, track, organize and report interventions. It optimizes a multidisciplinary approach in which the team can provide their respective expert recommendations and interventions in a singular location; easily accessible by all navigation team members.

IMPLICATIONS: Our goal is to promote and help establish our navigation process as best practice that will be utilized across VA networks.

PURPOSE: To establish a program utilizing a multidisciplinary team to address health care disparities and improve outcomes. To develop a process that would streamline our navigation workflow and assist with the identification of barriers to care. Thus, enabling the Cancer Care program to focus on what really matters— - Veterans.

PROBLEM: The Cancer Care program utilized a series of spreadsheets and an Access database to follow the care of Veterans receiving care within Southeast Louisiana Veterans Health Care System (SLVHCS) and for those Veterans being care for in the community. Each navigator has distinct intervals in which they contact or educate their patients for which care must be carefully coordinated. Our team strives to provide a multidisciplinary approach, but our former workflow of 12 years not only restricted us to one user at a time, but it also restricted usage to one service at a time. Our Clinical Nurse Navigators, Cancer Care Social Worker and Registered Nutritionist were creating and utilizing customized spreadsheets via an Excel program which also restricted access within services. These technological constraints further increased potential for negative outcomes and delays in care.

METHOD: Standardize our navigation process and allow for systemic changes within the department. With over 200 patient navigation programs to choose from (Institute for Alternative Futures, 2007); we adopted OncoNav as our navigation software program. OncoNav is oncologyspecific software designed to help Patient Navigators schedule, track, organize, and report their interactions with patients. It is designed to integrate into the Navigator’s workflow, allowing Navigators to quickly view pertinent patient information, add notes, schedule appointments and run patient-specific reports seamlessly from one system. After purchasing and implementing, ONCONAV, staff participated in training and tailored the package to meet the needs unique to our cancer team.

OUTCOME: Enables staff to schedule, track, organize and report interventions. It optimizes a multidisciplinary approach in which the team can provide their respective expert recommendations and interventions in a singular location; easily accessible by all navigation team members.

IMPLICATIONS: Our goal is to promote and help establish our navigation process as best practice that will be utilized across VA networks.

PURPOSE: To establish a program utilizing a multidisciplinary team to address health care disparities and improve outcomes. To develop a process that would streamline our navigation workflow and assist with the identification of barriers to care. Thus, enabling the Cancer Care program to focus on what really matters— - Veterans.

PROBLEM: The Cancer Care program utilized a series of spreadsheets and an Access database to follow the care of Veterans receiving care within Southeast Louisiana Veterans Health Care System (SLVHCS) and for those Veterans being care for in the community. Each navigator has distinct intervals in which they contact or educate their patients for which care must be carefully coordinated. Our team strives to provide a multidisciplinary approach, but our former workflow of 12 years not only restricted us to one user at a time, but it also restricted usage to one service at a time. Our Clinical Nurse Navigators, Cancer Care Social Worker and Registered Nutritionist were creating and utilizing customized spreadsheets via an Excel program which also restricted access within services. These technological constraints further increased potential for negative outcomes and delays in care.

METHOD: Standardize our navigation process and allow for systemic changes within the department. With over 200 patient navigation programs to choose from (Institute for Alternative Futures, 2007); we adopted OncoNav as our navigation software program. OncoNav is oncologyspecific software designed to help Patient Navigators schedule, track, organize, and report their interactions with patients. It is designed to integrate into the Navigator’s workflow, allowing Navigators to quickly view pertinent patient information, add notes, schedule appointments and run patient-specific reports seamlessly from one system. After purchasing and implementing, ONCONAV, staff participated in training and tailored the package to meet the needs unique to our cancer team.

OUTCOME: Enables staff to schedule, track, organize and report interventions. It optimizes a multidisciplinary approach in which the team can provide their respective expert recommendations and interventions in a singular location; easily accessible by all navigation team members.

IMPLICATIONS: Our goal is to promote and help establish our navigation process as best practice that will be utilized across VA networks.

BACKGROUND: Antineoplastic ordering is high in both complexity and risk for medication errors. Joint Commission and institutional policy recommends computerized prescriber order entry and verification by a pharmacist as a best practice for patient safety. The use of ordering templates minimizes the risk of errors and ensures appropriate supportive care is being provided. The Veterans Affairs electronic medical record does not feature an antineoplastic ordering component; historically, templates have been on paper. The oncology, pharmacy, and clinical informatics departments in our health system formed a team to create electronic antineoplastic ordering templates.

PURPOSE: To evaluate the impact of electronic antineoplastic ordering templates on pharmacy and infusion clinic efficiency and pharmacist interventions.

METHODS: Ordering templates, which included standard dosing and supportive care medications, were developed and activated for prescribers in phases over the course of two years. Immunotherapy and oral oncolytic templates were activated initially, followed by full implementation of the majority of intravenous (IV) ordering templates. Percent of electronic antineoplastic orders, pharmacy processing time, time to first drug delivery, and number of pharmacist encounters and interventions were documented daily for four weeks after initial implementation and for ten weeks after full implementation. Means were compared using unpaired t tests.

RESULTS: After initial implementation, the percentage of electronic antineoplastic orders increased from 0% to 100% for oral antineoplastics and from 0% to 39% for IV orders. After full implementation, IV orders increased to 69% in weeks 1-5 and 96% in weeks 6-10. Mean pharmacy processing time for supportive care medications was 35 minutes initially. This increased briefly after full implementation (weeks 1-5), then decreased to 17 minutes in weeks 6-10 (p<0.01). Delivery of the first medication to the infusion center decreased by 31 minutes at week ten (<0.01). Mean daily pharmacist encounters increased by 28%(<0.01) and documented interventions increased by 22% (<0.01).

IMPLICATIONS: Implementation of electronic antineoplastic ordering templates increased provider order entry, pharmacy and infusion clinic efficiency and pharmacist interventions. These outcomes may translate to improved patient safety and patient access to quality care. Templates developed can serve as a model for other health systems to implement electronic antineoplastic ordering.

BACKGROUND: Antineoplastic ordering is high in both complexity and risk for medication errors. Joint Commission and institutional policy recommends computerized prescriber order entry and verification by a pharmacist as a best practice for patient safety. The use of ordering templates minimizes the risk of errors and ensures appropriate supportive care is being provided. The Veterans Affairs electronic medical record does not feature an antineoplastic ordering component; historically, templates have been on paper. The oncology, pharmacy, and clinical informatics departments in our health system formed a team to create electronic antineoplastic ordering templates.

PURPOSE: To evaluate the impact of electronic antineoplastic ordering templates on pharmacy and infusion clinic efficiency and pharmacist interventions.

METHODS: Ordering templates, which included standard dosing and supportive care medications, were developed and activated for prescribers in phases over the course of two years. Immunotherapy and oral oncolytic templates were activated initially, followed by full implementation of the majority of intravenous (IV) ordering templates. Percent of electronic antineoplastic orders, pharmacy processing time, time to first drug delivery, and number of pharmacist encounters and interventions were documented daily for four weeks after initial implementation and for ten weeks after full implementation. Means were compared using unpaired t tests.

RESULTS: After initial implementation, the percentage of electronic antineoplastic orders increased from 0% to 100% for oral antineoplastics and from 0% to 39% for IV orders. After full implementation, IV orders increased to 69% in weeks 1-5 and 96% in weeks 6-10. Mean pharmacy processing time for supportive care medications was 35 minutes initially. This increased briefly after full implementation (weeks 1-5), then decreased to 17 minutes in weeks 6-10 (p<0.01). Delivery of the first medication to the infusion center decreased by 31 minutes at week ten (<0.01). Mean daily pharmacist encounters increased by 28%(<0.01) and documented interventions increased by 22% (<0.01).

IMPLICATIONS: Implementation of electronic antineoplastic ordering templates increased provider order entry, pharmacy and infusion clinic efficiency and pharmacist interventions. These outcomes may translate to improved patient safety and patient access to quality care. Templates developed can serve as a model for other health systems to implement electronic antineoplastic ordering.

BACKGROUND: Antineoplastic ordering is high in both complexity and risk for medication errors. Joint Commission and institutional policy recommends computerized prescriber order entry and verification by a pharmacist as a best practice for patient safety. The use of ordering templates minimizes the risk of errors and ensures appropriate supportive care is being provided. The Veterans Affairs electronic medical record does not feature an antineoplastic ordering component; historically, templates have been on paper. The oncology, pharmacy, and clinical informatics departments in our health system formed a team to create electronic antineoplastic ordering templates.

PURPOSE: To evaluate the impact of electronic antineoplastic ordering templates on pharmacy and infusion clinic efficiency and pharmacist interventions.

METHODS: Ordering templates, which included standard dosing and supportive care medications, were developed and activated for prescribers in phases over the course of two years. Immunotherapy and oral oncolytic templates were activated initially, followed by full implementation of the majority of intravenous (IV) ordering templates. Percent of electronic antineoplastic orders, pharmacy processing time, time to first drug delivery, and number of pharmacist encounters and interventions were documented daily for four weeks after initial implementation and for ten weeks after full implementation. Means were compared using unpaired t tests.

RESULTS: After initial implementation, the percentage of electronic antineoplastic orders increased from 0% to 100% for oral antineoplastics and from 0% to 39% for IV orders. After full implementation, IV orders increased to 69% in weeks 1-5 and 96% in weeks 6-10. Mean pharmacy processing time for supportive care medications was 35 minutes initially. This increased briefly after full implementation (weeks 1-5), then decreased to 17 minutes in weeks 6-10 (p<0.01). Delivery of the first medication to the infusion center decreased by 31 minutes at week ten (<0.01). Mean daily pharmacist encounters increased by 28%(<0.01) and documented interventions increased by 22% (<0.01).

IMPLICATIONS: Implementation of electronic antineoplastic ordering templates increased provider order entry, pharmacy and infusion clinic efficiency and pharmacist interventions. These outcomes may translate to improved patient safety and patient access to quality care. Templates developed can serve as a model for other health systems to implement electronic antineoplastic ordering.

BACKGROUND: Cancer treatment with immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs). Incidence and onset time of irAEs vary across therapies and trials. There is lack of data regarding irAEs in veterans. The aim of this study was to evaluate irAEs in a real-world veteran population to assess the safety of ICIs.

METHODS: This is a retrospective study of United States veterans who received at least one ICI dose from 1/1/14 to 10/31/19 at VA Long Beach Healthcare System (VALBHS). The primary objectives are to describe the incidence of irAEs and time to onset after ICI therapy. The secondary objectives are to identify factors that may predict irAE occurrence and to compare the incidence and time to irAE onset at VALBHS to literature data. The irAEs evaluated were diarrhea/colitis, kidney injury, pneumonitis, thyroid disorder, and transaminitis, as defined by the National Comprehensive Cancer Network (NCCN) guidelines. Statistical analysis was performed using Fisher’s exact test, Mann-Whitney U test, and logistic regression where appropriate.

RESULTS: Of 140 evaluable patients, 31 experienced 1 or more irAEs, for a total of 37 irAEs. Baseline characteristics among patients with irAEs versus patients with no irAEs were not statistically significant except for thoracic cancer (19.4% vs. 45%, p=0.01) and number of ICI doses received (median 9 vs. 5 doses, =0.01), respectively. There were 5 incidences of diarrhea/colitis, 5 kidney injury, 2 pneumonitis, 17 thyroid disorder, and 8 transaminitis. Severity ranged from grade 1-3. The median time to irAE onset was 18 weeks (range, 1-78 weeks). The factors examined (age, gender, race, cancer type, ICI drug class, and number of ICI doses received) did not significantly predict irAE occurrence (B<0.436, >0.21). When compared to literature data, VALBHS had broadly similar irAE incidence rates, but patients generally had a longer time to irAE onset.

CONCLUSION: Incidence of irAEs in the veteran population at VALBHS is generally consistent with the literature. The longer time to irAE onset in the study underscores the importance of ongoing monitoring during ICI therapy, as irAEs can happen anytime and there were no patient factors that helped predict occurrence.

BACKGROUND: Cancer treatment with immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs). Incidence and onset time of irAEs vary across therapies and trials. There is lack of data regarding irAEs in veterans. The aim of this study was to evaluate irAEs in a real-world veteran population to assess the safety of ICIs.

METHODS: This is a retrospective study of United States veterans who received at least one ICI dose from 1/1/14 to 10/31/19 at VA Long Beach Healthcare System (VALBHS). The primary objectives are to describe the incidence of irAEs and time to onset after ICI therapy. The secondary objectives are to identify factors that may predict irAE occurrence and to compare the incidence and time to irAE onset at VALBHS to literature data. The irAEs evaluated were diarrhea/colitis, kidney injury, pneumonitis, thyroid disorder, and transaminitis, as defined by the National Comprehensive Cancer Network (NCCN) guidelines. Statistical analysis was performed using Fisher’s exact test, Mann-Whitney U test, and logistic regression where appropriate.

RESULTS: Of 140 evaluable patients, 31 experienced 1 or more irAEs, for a total of 37 irAEs. Baseline characteristics among patients with irAEs versus patients with no irAEs were not statistically significant except for thoracic cancer (19.4% vs. 45%, p=0.01) and number of ICI doses received (median 9 vs. 5 doses, =0.01), respectively. There were 5 incidences of diarrhea/colitis, 5 kidney injury, 2 pneumonitis, 17 thyroid disorder, and 8 transaminitis. Severity ranged from grade 1-3. The median time to irAE onset was 18 weeks (range, 1-78 weeks). The factors examined (age, gender, race, cancer type, ICI drug class, and number of ICI doses received) did not significantly predict irAE occurrence (B<0.436, >0.21). When compared to literature data, VALBHS had broadly similar irAE incidence rates, but patients generally had a longer time to irAE onset.

CONCLUSION: Incidence of irAEs in the veteran population at VALBHS is generally consistent with the literature. The longer time to irAE onset in the study underscores the importance of ongoing monitoring during ICI therapy, as irAEs can happen anytime and there were no patient factors that helped predict occurrence.

BACKGROUND: Cancer treatment with immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs). Incidence and onset time of irAEs vary across therapies and trials. There is lack of data regarding irAEs in veterans. The aim of this study was to evaluate irAEs in a real-world veteran population to assess the safety of ICIs.

METHODS: This is a retrospective study of United States veterans who received at least one ICI dose from 1/1/14 to 10/31/19 at VA Long Beach Healthcare System (VALBHS). The primary objectives are to describe the incidence of irAEs and time to onset after ICI therapy. The secondary objectives are to identify factors that may predict irAE occurrence and to compare the incidence and time to irAE onset at VALBHS to literature data. The irAEs evaluated were diarrhea/colitis, kidney injury, pneumonitis, thyroid disorder, and transaminitis, as defined by the National Comprehensive Cancer Network (NCCN) guidelines. Statistical analysis was performed using Fisher’s exact test, Mann-Whitney U test, and logistic regression where appropriate.

RESULTS: Of 140 evaluable patients, 31 experienced 1 or more irAEs, for a total of 37 irAEs. Baseline characteristics among patients with irAEs versus patients with no irAEs were not statistically significant except for thoracic cancer (19.4% vs. 45%, p=0.01) and number of ICI doses received (median 9 vs. 5 doses, =0.01), respectively. There were 5 incidences of diarrhea/colitis, 5 kidney injury, 2 pneumonitis, 17 thyroid disorder, and 8 transaminitis. Severity ranged from grade 1-3. The median time to irAE onset was 18 weeks (range, 1-78 weeks). The factors examined (age, gender, race, cancer type, ICI drug class, and number of ICI doses received) did not significantly predict irAE occurrence (B<0.436, >0.21). When compared to literature data, VALBHS had broadly similar irAE incidence rates, but patients generally had a longer time to irAE onset.

CONCLUSION: Incidence of irAEs in the veteran population at VALBHS is generally consistent with the literature. The longer time to irAE onset in the study underscores the importance of ongoing monitoring during ICI therapy, as irAEs can happen anytime and there were no patient factors that helped predict occurrence.

INTRODUCTION: Methylene blue (MB) has recently gained traction as an adjunctive therapy in the management of vasoplegia. Due to risk of inducing oxidative hemolysis its use should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Although rare, drug induced oxidative hemolysis can still occur in patients without G6PD deficiency. In this report, we describe a case of severe oxidative hemolysis in a G6PD sufficient adult following administration of a large dose of MB.

CASE REPORT: A 78-year-old male with a history of coronary artery disease was admitted for coronary artery bypass graft surgery. Patient underwent surgery without any major complications. Post operatively however he developed severe shock refractory to multiple vasopressors and inotropes. A presumptive diagnosis of vasoplegia was made for which the patient was given multiple boluses of MB. Hemodynamics improved thus the patient was started on a MB infusion. Approximately 24 hours later the patient was noted to have an acute drop in his hemoglobin from 9.9 to 8.0 g/dl. He was transfused multiple units of blood with only transient improvements in his hemoglobin. Physical exam and imaging revealed no evidence of bleeding. Additional workup was notable for an LDH of 7222 U/L and an elevated bilirubin raising concern for hemolytic anemia.

Review of his peripheral smear was notable for the presence of numerous bite cells. A diagnosis of oxidative hemolytic anemia secondary to MB administration was made. MB infusion was discontinued and within 48 hours the patient’s LDH normalized and hemoglobin had stabilized. A quantitative G6PD test ordered during the acute hemolytic period and was reported as normal. Due to the possibility of a falsely normal result in the setting of active hemolysis, G6PD testing was repeated two months following discharge and was also normal.

CONCLUSIONS: Methylene blue can be a lifesaving medication in the setting of severe vasoplegia. However, clinicians should be aware of the possibility of inducing severe oxidative hemolytic anemia even in G6PD sufficient patients when giving this agent in large doses. Management of oxidative hemolysis secondary to MB is supportive care with prompt discontinuation resulting in resolution of hemolysis.

INTRODUCTION: Methylene blue (MB) has recently gained traction as an adjunctive therapy in the management of vasoplegia. Due to risk of inducing oxidative hemolysis its use should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Although rare, drug induced oxidative hemolysis can still occur in patients without G6PD deficiency. In this report, we describe a case of severe oxidative hemolysis in a G6PD sufficient adult following administration of a large dose of MB.

CASE REPORT: A 78-year-old male with a history of coronary artery disease was admitted for coronary artery bypass graft surgery. Patient underwent surgery without any major complications. Post operatively however he developed severe shock refractory to multiple vasopressors and inotropes. A presumptive diagnosis of vasoplegia was made for which the patient was given multiple boluses of MB. Hemodynamics improved thus the patient was started on a MB infusion. Approximately 24 hours later the patient was noted to have an acute drop in his hemoglobin from 9.9 to 8.0 g/dl. He was transfused multiple units of blood with only transient improvements in his hemoglobin. Physical exam and imaging revealed no evidence of bleeding. Additional workup was notable for an LDH of 7222 U/L and an elevated bilirubin raising concern for hemolytic anemia.

Review of his peripheral smear was notable for the presence of numerous bite cells. A diagnosis of oxidative hemolytic anemia secondary to MB administration was made. MB infusion was discontinued and within 48 hours the patient’s LDH normalized and hemoglobin had stabilized. A quantitative G6PD test ordered during the acute hemolytic period and was reported as normal. Due to the possibility of a falsely normal result in the setting of active hemolysis, G6PD testing was repeated two months following discharge and was also normal.

CONCLUSIONS: Methylene blue can be a lifesaving medication in the setting of severe vasoplegia. However, clinicians should be aware of the possibility of inducing severe oxidative hemolytic anemia even in G6PD sufficient patients when giving this agent in large doses. Management of oxidative hemolysis secondary to MB is supportive care with prompt discontinuation resulting in resolution of hemolysis.

INTRODUCTION: Methylene blue (MB) has recently gained traction as an adjunctive therapy in the management of vasoplegia. Due to risk of inducing oxidative hemolysis its use should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Although rare, drug induced oxidative hemolysis can still occur in patients without G6PD deficiency. In this report, we describe a case of severe oxidative hemolysis in a G6PD sufficient adult following administration of a large dose of MB.

CASE REPORT: A 78-year-old male with a history of coronary artery disease was admitted for coronary artery bypass graft surgery. Patient underwent surgery without any major complications. Post operatively however he developed severe shock refractory to multiple vasopressors and inotropes. A presumptive diagnosis of vasoplegia was made for which the patient was given multiple boluses of MB. Hemodynamics improved thus the patient was started on a MB infusion. Approximately 24 hours later the patient was noted to have an acute drop in his hemoglobin from 9.9 to 8.0 g/dl. He was transfused multiple units of blood with only transient improvements in his hemoglobin. Physical exam and imaging revealed no evidence of bleeding. Additional workup was notable for an LDH of 7222 U/L and an elevated bilirubin raising concern for hemolytic anemia.

Review of his peripheral smear was notable for the presence of numerous bite cells. A diagnosis of oxidative hemolytic anemia secondary to MB administration was made. MB infusion was discontinued and within 48 hours the patient’s LDH normalized and hemoglobin had stabilized. A quantitative G6PD test ordered during the acute hemolytic period and was reported as normal. Due to the possibility of a falsely normal result in the setting of active hemolysis, G6PD testing was repeated two months following discharge and was also normal.

CONCLUSIONS: Methylene blue can be a lifesaving medication in the setting of severe vasoplegia. However, clinicians should be aware of the possibility of inducing severe oxidative hemolytic anemia even in G6PD sufficient patients when giving this agent in large doses. Management of oxidative hemolysis secondary to MB is supportive care with prompt discontinuation resulting in resolution of hemolysis.

BACKGROUND: Oral antineoplastic therapy (OAT) use among Veterans is rising significantly. Through the MISSION/CHOICE Act, Veterans can receive Veterans Affairs (VA)-funded hematology/oncology care from non-VA community providers. These providers can prescribe high-risk, high-cost OATs which the VA then dispenses. However, Veterans receiving hematology/ oncology treatment in rural and community settings often lack access to comprehensive medication management, increasing their risk for suboptimal care.

SYNTHESIS OF RELEVANT LITERATURE: A survey performed within VISN 19 revealed Veterans on OATs prescribed by community providers receive inadequate monitoring and follow-up. Clinical pharmacist- driven medication management programs are established in a variety of clinical settings, including for patients taking OATs for hematologic and oncologic malignancies. Additionally, the American Society of Clinical Oncology (ASCO) considers medically integrated dispensing of OATs, often through hematology/ oncology pharmacist-driven medication management programs, a quality standard.

INTERVENTION(S) PROVIDED: The VA CARES program provides a dedicated clinical pharmacy specialist (CPS) for all phases of OAT treatment prescribed by community providers. During the OAT initiation phase, the CPS ensures appropriate indication and dosing, reviews baseline laboratory results, and performs a thorough drug-drug interaction analysis. The CPS also performs baseline patient assessment and education through a telephone encounter. During the OAT maintenance phase, the CPS ensures necessary monitoring occurs (e.g., labs are drawn and results are within appropriate limits), and schedules regular follow-up encounters with the patient to assess knowledge, adherence, toxicities, and need for OAT refills.

OUTCOME OF THE INTERVENTION/SITUATION: In the first three months, VA CARES enrolled sixteen patients with a total of nineteen community care prescriptions (sixteen for OATs, three for broad-spectrum antifungals). The CPS performed thirty-eight encounters and twenty-nine interventions. The majority of interventions included detection and/or prevention of drug-drug interactions (n=15), followed by prevention of adverse events (n=5). Other interventions included drug not indicated (n=3), alternative therapy suggested (n=2), limited-quantity dispensed (n=1), and unnecessary consultation prevented (n=1). Total cost avoidance and savings in three months were estimated at $52,013.

IMPLICATIONS: A CPS-driven medication management program for Veterans receiving OATs through the MISSION/CHOICE Act is associated with clinical and economic benefits.

BACKGROUND: Oral antineoplastic therapy (OAT) use among Veterans is rising significantly. Through the MISSION/CHOICE Act, Veterans can receive Veterans Affairs (VA)-funded hematology/oncology care from non-VA community providers. These providers can prescribe high-risk, high-cost OATs which the VA then dispenses. However, Veterans receiving hematology/ oncology treatment in rural and community settings often lack access to comprehensive medication management, increasing their risk for suboptimal care.

SYNTHESIS OF RELEVANT LITERATURE: A survey performed within VISN 19 revealed Veterans on OATs prescribed by community providers receive inadequate monitoring and follow-up. Clinical pharmacist- driven medication management programs are established in a variety of clinical settings, including for patients taking OATs for hematologic and oncologic malignancies. Additionally, the American Society of Clinical Oncology (ASCO) considers medically integrated dispensing of OATs, often through hematology/ oncology pharmacist-driven medication management programs, a quality standard.

INTERVENTION(S) PROVIDED: The VA CARES program provides a dedicated clinical pharmacy specialist (CPS) for all phases of OAT treatment prescribed by community providers. During the OAT initiation phase, the CPS ensures appropriate indication and dosing, reviews baseline laboratory results, and performs a thorough drug-drug interaction analysis. The CPS also performs baseline patient assessment and education through a telephone encounter. During the OAT maintenance phase, the CPS ensures necessary monitoring occurs (e.g., labs are drawn and results are within appropriate limits), and schedules regular follow-up encounters with the patient to assess knowledge, adherence, toxicities, and need for OAT refills.

OUTCOME OF THE INTERVENTION/SITUATION: In the first three months, VA CARES enrolled sixteen patients with a total of nineteen community care prescriptions (sixteen for OATs, three for broad-spectrum antifungals). The CPS performed thirty-eight encounters and twenty-nine interventions. The majority of interventions included detection and/or prevention of drug-drug interactions (n=15), followed by prevention of adverse events (n=5). Other interventions included drug not indicated (n=3), alternative therapy suggested (n=2), limited-quantity dispensed (n=1), and unnecessary consultation prevented (n=1). Total cost avoidance and savings in three months were estimated at $52,013.

IMPLICATIONS: A CPS-driven medication management program for Veterans receiving OATs through the MISSION/CHOICE Act is associated with clinical and economic benefits.

BACKGROUND: Oral antineoplastic therapy (OAT) use among Veterans is rising significantly. Through the MISSION/CHOICE Act, Veterans can receive Veterans Affairs (VA)-funded hematology/oncology care from non-VA community providers. These providers can prescribe high-risk, high-cost OATs which the VA then dispenses. However, Veterans receiving hematology/ oncology treatment in rural and community settings often lack access to comprehensive medication management, increasing their risk for suboptimal care.

SYNTHESIS OF RELEVANT LITERATURE: A survey performed within VISN 19 revealed Veterans on OATs prescribed by community providers receive inadequate monitoring and follow-up. Clinical pharmacist- driven medication management programs are established in a variety of clinical settings, including for patients taking OATs for hematologic and oncologic malignancies. Additionally, the American Society of Clinical Oncology (ASCO) considers medically integrated dispensing of OATs, often through hematology/ oncology pharmacist-driven medication management programs, a quality standard.

INTERVENTION(S) PROVIDED: The VA CARES program provides a dedicated clinical pharmacy specialist (CPS) for all phases of OAT treatment prescribed by community providers. During the OAT initiation phase, the CPS ensures appropriate indication and dosing, reviews baseline laboratory results, and performs a thorough drug-drug interaction analysis. The CPS also performs baseline patient assessment and education through a telephone encounter. During the OAT maintenance phase, the CPS ensures necessary monitoring occurs (e.g., labs are drawn and results are within appropriate limits), and schedules regular follow-up encounters with the patient to assess knowledge, adherence, toxicities, and need for OAT refills.

OUTCOME OF THE INTERVENTION/SITUATION: In the first three months, VA CARES enrolled sixteen patients with a total of nineteen community care prescriptions (sixteen for OATs, three for broad-spectrum antifungals). The CPS performed thirty-eight encounters and twenty-nine interventions. The majority of interventions included detection and/or prevention of drug-drug interactions (n=15), followed by prevention of adverse events (n=5). Other interventions included drug not indicated (n=3), alternative therapy suggested (n=2), limited-quantity dispensed (n=1), and unnecessary consultation prevented (n=1). Total cost avoidance and savings in three months were estimated at $52,013.

IMPLICATIONS: A CPS-driven medication management program for Veterans receiving OATs through the MISSION/CHOICE Act is associated with clinical and economic benefits.

PURPOSE/BACKGROUND: Long term androgen deprivation therapy (ADT) forms the backbone of treatment of locally advanced and metastatic prostate cancer. Bone modifying agents, such as bisphosphonates and denosumab, may be indicated in osteoporosis dosing in the castration-sensitive setting, and more intense dosing for bone metastases in the castration-resistant setting only. Dental evaluation and care prior to bone modifying agent use in osteoporosis or bone metastases has safety benefit. Historical lack of clinical practice guidelines for bone health in men with prostate cancer have limited evidence-based practice. A retrospective review of patients on active bone remodeling therapies for prostate cancer, Revealed that several patients with castration-sensitive disease received treatment at dosing supported only in the setting of castration resistance with bone metastases. Some patients had not completed dental evaluation prior to initiation of bone modifying agents.

METHODS: Following evidence-based expert consensus recommendations from multiple sources regarding bone health in prostate cancer, we created an algorithm- based clinical practice tool. This decision tool is activated within the electronic medical record order set when starting therapy with a bone remodeling agent in patients with prostate cancer. The tool supports treatment with appropriate dosing for the indication, and ensures pretreatment supportive care, such as dental evaluation, is performed.

DATA ANALYSIS/RESULTS: Since implementation of the algorithm-based decision tool, 0/10 (0%) patients were placed on inappropriate bone modifying agent dosing and dental care was addressed on every patient 10/10 (100%) initiating treatment. When evaluating the effect of the decision tool on the desired outcomes, we note that the fraction of patients getting overly intensive treatment before and after implementation of the tool was 24/41 vs 0/10 (p = 0.0008); lack of pretreatment dental assessment before and after implementation of the tool was noted to be 12/41 vs 0/10): ( =0.09). Fisher’s Exact Test was used for both comparisons.

IMPLICATIONS: Through implementation of an evidence- based algorithm and clinical practice tool while prescribing bone remodeling agents to patients with prostate cancer, we were able to improve our institutional practice to a high quality evidenced-based approach to prostate cancer bone health care.

PURPOSE/BACKGROUND: Long term androgen deprivation therapy (ADT) forms the backbone of treatment of locally advanced and metastatic prostate cancer. Bone modifying agents, such as bisphosphonates and denosumab, may be indicated in osteoporosis dosing in the castration-sensitive setting, and more intense dosing for bone metastases in the castration-resistant setting only. Dental evaluation and care prior to bone modifying agent use in osteoporosis or bone metastases has safety benefit. Historical lack of clinical practice guidelines for bone health in men with prostate cancer have limited evidence-based practice. A retrospective review of patients on active bone remodeling therapies for prostate cancer, Revealed that several patients with castration-sensitive disease received treatment at dosing supported only in the setting of castration resistance with bone metastases. Some patients had not completed dental evaluation prior to initiation of bone modifying agents.

METHODS: Following evidence-based expert consensus recommendations from multiple sources regarding bone health in prostate cancer, we created an algorithm- based clinical practice tool. This decision tool is activated within the electronic medical record order set when starting therapy with a bone remodeling agent in patients with prostate cancer. The tool supports treatment with appropriate dosing for the indication, and ensures pretreatment supportive care, such as dental evaluation, is performed.

DATA ANALYSIS/RESULTS: Since implementation of the algorithm-based decision tool, 0/10 (0%) patients were placed on inappropriate bone modifying agent dosing and dental care was addressed on every patient 10/10 (100%) initiating treatment. When evaluating the effect of the decision tool on the desired outcomes, we note that the fraction of patients getting overly intensive treatment before and after implementation of the tool was 24/41 vs 0/10 (p = 0.0008); lack of pretreatment dental assessment before and after implementation of the tool was noted to be 12/41 vs 0/10): ( =0.09). Fisher’s Exact Test was used for both comparisons.

IMPLICATIONS: Through implementation of an evidence- based algorithm and clinical practice tool while prescribing bone remodeling agents to patients with prostate cancer, we were able to improve our institutional practice to a high quality evidenced-based approach to prostate cancer bone health care.

PURPOSE/BACKGROUND: Long term androgen deprivation therapy (ADT) forms the backbone of treatment of locally advanced and metastatic prostate cancer. Bone modifying agents, such as bisphosphonates and denosumab, may be indicated in osteoporosis dosing in the castration-sensitive setting, and more intense dosing for bone metastases in the castration-resistant setting only. Dental evaluation and care prior to bone modifying agent use in osteoporosis or bone metastases has safety benefit. Historical lack of clinical practice guidelines for bone health in men with prostate cancer have limited evidence-based practice. A retrospective review of patients on active bone remodeling therapies for prostate cancer, Revealed that several patients with castration-sensitive disease received treatment at dosing supported only in the setting of castration resistance with bone metastases. Some patients had not completed dental evaluation prior to initiation of bone modifying agents.

METHODS: Following evidence-based expert consensus recommendations from multiple sources regarding bone health in prostate cancer, we created an algorithm- based clinical practice tool. This decision tool is activated within the electronic medical record order set when starting therapy with a bone remodeling agent in patients with prostate cancer. The tool supports treatment with appropriate dosing for the indication, and ensures pretreatment supportive care, such as dental evaluation, is performed.

DATA ANALYSIS/RESULTS: Since implementation of the algorithm-based decision tool, 0/10 (0%) patients were placed on inappropriate bone modifying agent dosing and dental care was addressed on every patient 10/10 (100%) initiating treatment. When evaluating the effect of the decision tool on the desired outcomes, we note that the fraction of patients getting overly intensive treatment before and after implementation of the tool was 24/41 vs 0/10 (p = 0.0008); lack of pretreatment dental assessment before and after implementation of the tool was noted to be 12/41 vs 0/10): ( =0.09). Fisher’s Exact Test was used for both comparisons.

IMPLICATIONS: Through implementation of an evidence- based algorithm and clinical practice tool while prescribing bone remodeling agents to patients with prostate cancer, we were able to improve our institutional practice to a high quality evidenced-based approach to prostate cancer bone health care.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy has become a mainstay in cancer treatment and even has first-line indications for malignancies such as melanoma, non-small cell lung cancer, and many others. Recent data has demonstrated that patients who received either antimicrobial therapy prior to or within the first 60 days of ICI initiation tend to have worse outcomes as measured by time to progression and overall survival. It has been theorized that this may be caused by the influence of the antibiotics on the intestinal microbiota. This study evaluates the effect of antimicrobial therapy on outcomes in veteran patients initiated on ICI therapy.

METHODS: A retrospective chart review was conducted on all patients initiated on ICIs from 1/1/2015 through 12/31/2017. Patients were evaluated as to whether they received any antibiotics within 30 days of ICI initiation or 60 days after ICI initiation or if they received no antibiotics during this time. Data was gathered using the Veterans Health Administration electronic health record. Primary endpoints evaluated were progression free survival (PFS) and overall survival (OS), using Wilcoxon signed-rank test. Descriptive statistics were utilized for patient demographics and antibiotic characteristic comparisons.

RESULTS: A total of 55 patients were identified as having been initiated on an ICI. Twenty-two patients (40%) had received antibiotic treatment prior to or concurrently with their ICI therapy and 33 patients (60%) did not. Median overall survival was numerically longer in patients who did not receive antibiotics at 10 months (95% confidence interval [CI], 4-17 mo.) versus 4 months in patients who received antibiotics (95% CI, 2-9 mo.). However, no significant benefit was observed in median PFS among patients who did not receive antibiotics compared to those who received antibiotics (5 mo. versus 11 mo.).

CONCLUSIONS: No association was observed between antibiotic use and ICI patient outcomes. Although this correlation has been suggested by several recent publications, the cause is not fully understood. This study has several limitations, which could explain why this association was not reproduced. Future investigation and monitoring will be helpful to elucidate any true relationship between ICI and antimicrobial therapies.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy has become a mainstay in cancer treatment and even has first-line indications for malignancies such as melanoma, non-small cell lung cancer, and many others. Recent data has demonstrated that patients who received either antimicrobial therapy prior to or within the first 60 days of ICI initiation tend to have worse outcomes as measured by time to progression and overall survival. It has been theorized that this may be caused by the influence of the antibiotics on the intestinal microbiota. This study evaluates the effect of antimicrobial therapy on outcomes in veteran patients initiated on ICI therapy.

METHODS: A retrospective chart review was conducted on all patients initiated on ICIs from 1/1/2015 through 12/31/2017. Patients were evaluated as to whether they received any antibiotics within 30 days of ICI initiation or 60 days after ICI initiation or if they received no antibiotics during this time. Data was gathered using the Veterans Health Administration electronic health record. Primary endpoints evaluated were progression free survival (PFS) and overall survival (OS), using Wilcoxon signed-rank test. Descriptive statistics were utilized for patient demographics and antibiotic characteristic comparisons.

RESULTS: A total of 55 patients were identified as having been initiated on an ICI. Twenty-two patients (40%) had received antibiotic treatment prior to or concurrently with their ICI therapy and 33 patients (60%) did not. Median overall survival was numerically longer in patients who did not receive antibiotics at 10 months (95% confidence interval [CI], 4-17 mo.) versus 4 months in patients who received antibiotics (95% CI, 2-9 mo.). However, no significant benefit was observed in median PFS among patients who did not receive antibiotics compared to those who received antibiotics (5 mo. versus 11 mo.).

CONCLUSIONS: No association was observed between antibiotic use and ICI patient outcomes. Although this correlation has been suggested by several recent publications, the cause is not fully understood. This study has several limitations, which could explain why this association was not reproduced. Future investigation and monitoring will be helpful to elucidate any true relationship between ICI and antimicrobial therapies.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy has become a mainstay in cancer treatment and even has first-line indications for malignancies such as melanoma, non-small cell lung cancer, and many others. Recent data has demonstrated that patients who received either antimicrobial therapy prior to or within the first 60 days of ICI initiation tend to have worse outcomes as measured by time to progression and overall survival. It has been theorized that this may be caused by the influence of the antibiotics on the intestinal microbiota. This study evaluates the effect of antimicrobial therapy on outcomes in veteran patients initiated on ICI therapy.

METHODS: A retrospective chart review was conducted on all patients initiated on ICIs from 1/1/2015 through 12/31/2017. Patients were evaluated as to whether they received any antibiotics within 30 days of ICI initiation or 60 days after ICI initiation or if they received no antibiotics during this time. Data was gathered using the Veterans Health Administration electronic health record. Primary endpoints evaluated were progression free survival (PFS) and overall survival (OS), using Wilcoxon signed-rank test. Descriptive statistics were utilized for patient demographics and antibiotic characteristic comparisons.

RESULTS: A total of 55 patients were identified as having been initiated on an ICI. Twenty-two patients (40%) had received antibiotic treatment prior to or concurrently with their ICI therapy and 33 patients (60%) did not. Median overall survival was numerically longer in patients who did not receive antibiotics at 10 months (95% confidence interval [CI], 4-17 mo.) versus 4 months in patients who received antibiotics (95% CI, 2-9 mo.). However, no significant benefit was observed in median PFS among patients who did not receive antibiotics compared to those who received antibiotics (5 mo. versus 11 mo.).

CONCLUSIONS: No association was observed between antibiotic use and ICI patient outcomes. Although this correlation has been suggested by several recent publications, the cause is not fully understood. This study has several limitations, which could explain why this association was not reproduced. Future investigation and monitoring will be helpful to elucidate any true relationship between ICI and antimicrobial therapies.

BACKGROUND: Osteolytic lesions are present in 75% of multiple myeloma (MM) patients and frequently require palliation with radiation therapy (RT). Case series of MM patients with bone pain undergoing palliative RT suggest doses > 12 Gy (EQD2) provide excellent bone pain relief. However, recent advances in novel biologic agents have significantly improved overall survival and quality of life for MM patients. We hypothesized that lower-dose RT (LDRT, EQD2 < 12 Gy) offers an effective alternative to higher-dose RT (HDRT, EQD2 > 12 Gy) for palliation of painful MM bone lesions.

METHODS: We retrospectively identified MM patients treated with RT for painful bone lesions and stratified by EQD2 < 12Gy versus ≥12Gy. Clinical pain response (CPR) rates, acute and late toxicity, pain response duration, and retreatment rates between LDRT and HDRT groups were analyzed. RESULTS: Thirty-five patients with 71 treated lesions were included: 24 patients (49 lesions) treated with HDRT and 11 patients (22 lesions) with LDRT. Median follow up was 16.8 months. The median dose of HDRT treatment was 20 Gy (range 8-30 Gy, EQD2 12- 32.5 Gy) versus 4 Gy in the LDRT group (range = 4-8 Gy, EQD2 4.67-9.3 Gy). The CPR rate was 98% for HDRT and 95% for LDRT. There was no significant difference in any grade acute toxicity between the HDRT cohort and LDRT cohort (24.5% vs. 9.1%, χ² P=0.20). Pain recurred in 10% of lesions (12% HDRT versus 9.5% LDRT). Median duration of pain response did not significantly differ between cohorts (p=0.91). Five lesions were retreated, 2 (9.5%) in the LDRT cohort and 3 (6.3%) in the HDRT cohort.

CONCLUSIONS: In this study, LDRT effectively palliated painful MM bony lesions with acceptable CPR and duration of palliation. These data support prospective comparisons of LDRT versus HDRT for palliation of painful MM bony lesions.

BACKGROUND: Osteolytic lesions are present in 75% of multiple myeloma (MM) patients and frequently require palliation with radiation therapy (RT). Case series of MM patients with bone pain undergoing palliative RT suggest doses > 12 Gy (EQD2) provide excellent bone pain relief. However, recent advances in novel biologic agents have significantly improved overall survival and quality of life for MM patients. We hypothesized that lower-dose RT (LDRT, EQD2 < 12 Gy) offers an effective alternative to higher-dose RT (HDRT, EQD2 > 12 Gy) for palliation of painful MM bone lesions.

METHODS: We retrospectively identified MM patients treated with RT for painful bone lesions and stratified by EQD2 < 12Gy versus ≥12Gy. Clinical pain response (CPR) rates, acute and late toxicity, pain response duration, and retreatment rates between LDRT and HDRT groups were analyzed. RESULTS: Thirty-five patients with 71 treated lesions were included: 24 patients (49 lesions) treated with HDRT and 11 patients (22 lesions) with LDRT. Median follow up was 16.8 months. The median dose of HDRT treatment was 20 Gy (range 8-30 Gy, EQD2 12- 32.5 Gy) versus 4 Gy in the LDRT group (range = 4-8 Gy, EQD2 4.67-9.3 Gy). The CPR rate was 98% for HDRT and 95% for LDRT. There was no significant difference in any grade acute toxicity between the HDRT cohort and LDRT cohort (24.5% vs. 9.1%, χ² P=0.20). Pain recurred in 10% of lesions (12% HDRT versus 9.5% LDRT). Median duration of pain response did not significantly differ between cohorts (p=0.91). Five lesions were retreated, 2 (9.5%) in the LDRT cohort and 3 (6.3%) in the HDRT cohort.

CONCLUSIONS: In this study, LDRT effectively palliated painful MM bony lesions with acceptable CPR and duration of palliation. These data support prospective comparisons of LDRT versus HDRT for palliation of painful MM bony lesions.

BACKGROUND: Osteolytic lesions are present in 75% of multiple myeloma (MM) patients and frequently require palliation with radiation therapy (RT). Case series of MM patients with bone pain undergoing palliative RT suggest doses > 12 Gy (EQD2) provide excellent bone pain relief. However, recent advances in novel biologic agents have significantly improved overall survival and quality of life for MM patients. We hypothesized that lower-dose RT (LDRT, EQD2 < 12 Gy) offers an effective alternative to higher-dose RT (HDRT, EQD2 > 12 Gy) for palliation of painful MM bone lesions.

METHODS: We retrospectively identified MM patients treated with RT for painful bone lesions and stratified by EQD2 < 12Gy versus ≥12Gy. Clinical pain response (CPR) rates, acute and late toxicity, pain response duration, and retreatment rates between LDRT and HDRT groups were analyzed. RESULTS: Thirty-five patients with 71 treated lesions were included: 24 patients (49 lesions) treated with HDRT and 11 patients (22 lesions) with LDRT. Median follow up was 16.8 months. The median dose of HDRT treatment was 20 Gy (range 8-30 Gy, EQD2 12- 32.5 Gy) versus 4 Gy in the LDRT group (range = 4-8 Gy, EQD2 4.67-9.3 Gy). The CPR rate was 98% for HDRT and 95% for LDRT. There was no significant difference in any grade acute toxicity between the HDRT cohort and LDRT cohort (24.5% vs. 9.1%, χ² P=0.20). Pain recurred in 10% of lesions (12% HDRT versus 9.5% LDRT). Median duration of pain response did not significantly differ between cohorts (p=0.91). Five lesions were retreated, 2 (9.5%) in the LDRT cohort and 3 (6.3%) in the HDRT cohort.

CONCLUSIONS: In this study, LDRT effectively palliated painful MM bony lesions with acceptable CPR and duration of palliation. These data support prospective comparisons of LDRT versus HDRT for palliation of painful MM bony lesions.

BACKGROUND: PARP inhibitors (PARPi’s) were recently approved for the treatment of metastatic prostate cancer among patients harboring mutations in an array of genes responsible for DNA repair. We sought to identify whether a subset of these genes correlates with response to treatment more frequently than others. Consequently, an evaluation of the specific DNA repair genotypes associated with durable clinical benefit (DCB) using real-world patient data was undertaken.

METHODS: The U.S. Department of Veterans Affairs (VA) National Precision Oncology Program’s (NPOP) database and Corporate Data Warehouse (CDW) were reviewed to select patients who (1) carried a diagnosis of prostate cancer, (2) successfully underwent tumor DNA sequencing through NPOP, (3) were prescribed olaparib, rucaparib, nirapib, and/or talazaporib for their prostate cancer between July 2016 and February 2020, and (4) and achieved DCB, defined as no progression in prostate-specific antigen (PSA) for at least 6 months following PARPi initiation without concurrent systemic or non-systemic therapies other than androgen-deprivation. The DNA repair gene variants and orders placed for NPOP consultative support were reviewed.

RESULTS: Of the 44 prostate cancer patients treated with a PARPi, 6 (13.6%) had tumor DNA sequencing through NPOP and had achieved DCB. Five patients were treated with olaparib and 1 with rucaparib. The median PSA progression-free survival was 8.9 (interquartile range = 8.5 – 11.2) months among these selected patients. Regarding gene variants, 5 patients had 7 BRCA2 mutations, including 4 frameshift, 1 nonsense, 1 single nucleotide variant, and 1 splice site. One patient had frameshift and missense ATM mutations. Referrals to the NPOP consult service were ordered for 2 out of the 5 patients with BRCA2 mutations achieving DCB.

CONCLUSIONS: Within the VA’s NPOP, the presence of BRCA2 gene variants was the most common finding from tumor DNA sequencing among patients with prostate cancer achieving DCB with a PARPi. Further analysis of the genotypes of all patients treated with PARPi in NPOP to assess the differential impact of BRCA2 mutations is needed to confirm the clinical implication of this finding.

BACKGROUND: PARP inhibitors (PARPi’s) were recently approved for the treatment of metastatic prostate cancer among patients harboring mutations in an array of genes responsible for DNA repair. We sought to identify whether a subset of these genes correlates with response to treatment more frequently than others. Consequently, an evaluation of the specific DNA repair genotypes associated with durable clinical benefit (DCB) using real-world patient data was undertaken.

METHODS: The U.S. Department of Veterans Affairs (VA) National Precision Oncology Program’s (NPOP) database and Corporate Data Warehouse (CDW) were reviewed to select patients who (1) carried a diagnosis of prostate cancer, (2) successfully underwent tumor DNA sequencing through NPOP, (3) were prescribed olaparib, rucaparib, nirapib, and/or talazaporib for their prostate cancer between July 2016 and February 2020, and (4) and achieved DCB, defined as no progression in prostate-specific antigen (PSA) for at least 6 months following PARPi initiation without concurrent systemic or non-systemic therapies other than androgen-deprivation. The DNA repair gene variants and orders placed for NPOP consultative support were reviewed.

RESULTS: Of the 44 prostate cancer patients treated with a PARPi, 6 (13.6%) had tumor DNA sequencing through NPOP and had achieved DCB. Five patients were treated with olaparib and 1 with rucaparib. The median PSA progression-free survival was 8.9 (interquartile range = 8.5 – 11.2) months among these selected patients. Regarding gene variants, 5 patients had 7 BRCA2 mutations, including 4 frameshift, 1 nonsense, 1 single nucleotide variant, and 1 splice site. One patient had frameshift and missense ATM mutations. Referrals to the NPOP consult service were ordered for 2 out of the 5 patients with BRCA2 mutations achieving DCB.

CONCLUSIONS: Within the VA’s NPOP, the presence of BRCA2 gene variants was the most common finding from tumor DNA sequencing among patients with prostate cancer achieving DCB with a PARPi. Further analysis of the genotypes of all patients treated with PARPi in NPOP to assess the differential impact of BRCA2 mutations is needed to confirm the clinical implication of this finding.

BACKGROUND: PARP inhibitors (PARPi’s) were recently approved for the treatment of metastatic prostate cancer among patients harboring mutations in an array of genes responsible for DNA repair. We sought to identify whether a subset of these genes correlates with response to treatment more frequently than others. Consequently, an evaluation of the specific DNA repair genotypes associated with durable clinical benefit (DCB) using real-world patient data was undertaken.

METHODS: The U.S. Department of Veterans Affairs (VA) National Precision Oncology Program’s (NPOP) database and Corporate Data Warehouse (CDW) were reviewed to select patients who (1) carried a diagnosis of prostate cancer, (2) successfully underwent tumor DNA sequencing through NPOP, (3) were prescribed olaparib, rucaparib, nirapib, and/or talazaporib for their prostate cancer between July 2016 and February 2020, and (4) and achieved DCB, defined as no progression in prostate-specific antigen (PSA) for at least 6 months following PARPi initiation without concurrent systemic or non-systemic therapies other than androgen-deprivation. The DNA repair gene variants and orders placed for NPOP consultative support were reviewed.

RESULTS: Of the 44 prostate cancer patients treated with a PARPi, 6 (13.6%) had tumor DNA sequencing through NPOP and had achieved DCB. Five patients were treated with olaparib and 1 with rucaparib. The median PSA progression-free survival was 8.9 (interquartile range = 8.5 – 11.2) months among these selected patients. Regarding gene variants, 5 patients had 7 BRCA2 mutations, including 4 frameshift, 1 nonsense, 1 single nucleotide variant, and 1 splice site. One patient had frameshift and missense ATM mutations. Referrals to the NPOP consult service were ordered for 2 out of the 5 patients with BRCA2 mutations achieving DCB.

CONCLUSIONS: Within the VA’s NPOP, the presence of BRCA2 gene variants was the most common finding from tumor DNA sequencing among patients with prostate cancer achieving DCB with a PARPi. Further analysis of the genotypes of all patients treated with PARPi in NPOP to assess the differential impact of BRCA2 mutations is needed to confirm the clinical implication of this finding.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.

CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.

CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.

CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.

CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.

CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.

CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.