Oncology

Background

The William S. Middleton Memorial Veterans Hospital (Madison VA) prioritized the goal of ensuring patients with cancer are receiving guideline-based precision oncology care, including comprehensive genomic profiling (CGP) and germline genomics consultation based on evidence-based medicine and the VA Clinical Pathways. A local Precision Oncology Program was created to assist in review of CGP results including documentation in the electronic medical record (EMR) and recommendations for treatment or additional testing as appropriate. The program, which began in February 2024, focused on patients with prostate cancer initially. This was expanded to all genitourinary cancers in April 2024, non-small cell lung cancers (NSCLC) in August 2024, and all cancers in Dec 2024.

Results

Since the implementation of the Madison VA Precision Oncology Program, CGP was reviewed for 73 unique Veterans leading to 281 recommendations including: 25 FDA approved therapies, 2 off-label standard of care treatment options, 11 patients with potential clinical trial eligibility at the Madison VA. Forty-eight patients had no actionable mutations and 44 were recommended for additional germline genetics counseling. For patients with metastatic prostate cancer, after 1 year of program implementation, an increase was seen in the percentage of patients receiving guideline-based CGP, the percentage of actionable alterations identified, and the percentage of patients identified as potentially eligible for a clinical trial open at the Madison VA based on CGP. The percentage of patients with an interfacility consult to the Clinical Cancer Genetics Service was also increased. For patients with metastatic NSCLC, after 6 months of program implementation, an increase was seen in the percentage of patients appropriately receiving CGP, the percentage of actionable alterations identified, and the percentage of patients on targeted therapy. In all cases where an actionable alteration was not being targeted, the treatment option was not yet appropriate for the stage of disease.

Conclusions

The implementation of preemptive review of all CGP results at the Madison VA through the Precision Oncology Program has increased uptake and awareness of CGP results and potential treatment options, improving the access of targeted treatments and clinical trial opportunities for Veterans with cancer.

Background

The William S. Middleton Memorial Veterans Hospital (Madison VA) prioritized the goal of ensuring patients with cancer are receiving guideline-based precision oncology care, including comprehensive genomic profiling (CGP) and germline genomics consultation based on evidence-based medicine and the VA Clinical Pathways. A local Precision Oncology Program was created to assist in review of CGP results including documentation in the electronic medical record (EMR) and recommendations for treatment or additional testing as appropriate. The program, which began in February 2024, focused on patients with prostate cancer initially. This was expanded to all genitourinary cancers in April 2024, non-small cell lung cancers (NSCLC) in August 2024, and all cancers in Dec 2024.

Results

Since the implementation of the Madison VA Precision Oncology Program, CGP was reviewed for 73 unique Veterans leading to 281 recommendations including: 25 FDA approved therapies, 2 off-label standard of care treatment options, 11 patients with potential clinical trial eligibility at the Madison VA. Forty-eight patients had no actionable mutations and 44 were recommended for additional germline genetics counseling. For patients with metastatic prostate cancer, after 1 year of program implementation, an increase was seen in the percentage of patients receiving guideline-based CGP, the percentage of actionable alterations identified, and the percentage of patients identified as potentially eligible for a clinical trial open at the Madison VA based on CGP. The percentage of patients with an interfacility consult to the Clinical Cancer Genetics Service was also increased. For patients with metastatic NSCLC, after 6 months of program implementation, an increase was seen in the percentage of patients appropriately receiving CGP, the percentage of actionable alterations identified, and the percentage of patients on targeted therapy. In all cases where an actionable alteration was not being targeted, the treatment option was not yet appropriate for the stage of disease.

Conclusions

The implementation of preemptive review of all CGP results at the Madison VA through the Precision Oncology Program has increased uptake and awareness of CGP results and potential treatment options, improving the access of targeted treatments and clinical trial opportunities for Veterans with cancer.

Background

The William S. Middleton Memorial Veterans Hospital (Madison VA) prioritized the goal of ensuring patients with cancer are receiving guideline-based precision oncology care, including comprehensive genomic profiling (CGP) and germline genomics consultation based on evidence-based medicine and the VA Clinical Pathways. A local Precision Oncology Program was created to assist in review of CGP results including documentation in the electronic medical record (EMR) and recommendations for treatment or additional testing as appropriate. The program, which began in February 2024, focused on patients with prostate cancer initially. This was expanded to all genitourinary cancers in April 2024, non-small cell lung cancers (NSCLC) in August 2024, and all cancers in Dec 2024.

Results

Since the implementation of the Madison VA Precision Oncology Program, CGP was reviewed for 73 unique Veterans leading to 281 recommendations including: 25 FDA approved therapies, 2 off-label standard of care treatment options, 11 patients with potential clinical trial eligibility at the Madison VA. Forty-eight patients had no actionable mutations and 44 were recommended for additional germline genetics counseling. For patients with metastatic prostate cancer, after 1 year of program implementation, an increase was seen in the percentage of patients receiving guideline-based CGP, the percentage of actionable alterations identified, and the percentage of patients identified as potentially eligible for a clinical trial open at the Madison VA based on CGP. The percentage of patients with an interfacility consult to the Clinical Cancer Genetics Service was also increased. For patients with metastatic NSCLC, after 6 months of program implementation, an increase was seen in the percentage of patients appropriately receiving CGP, the percentage of actionable alterations identified, and the percentage of patients on targeted therapy. In all cases where an actionable alteration was not being targeted, the treatment option was not yet appropriate for the stage of disease.

Conclusions

The implementation of preemptive review of all CGP results at the Madison VA through the Precision Oncology Program has increased uptake and awareness of CGP results and potential treatment options, improving the access of targeted treatments and clinical trial opportunities for Veterans with cancer.

Background

There are an estimated 18 million cancer survivors in the US with unique needs including specific surveillance imaging, testing for recurrence, monitoring for and managing late effects of cancer treatments, and for second malignancies. Survivorship care is an unmet need in most VAHC. Purpose: Assess implementation outcomes of a Survivorship Clinic.

Methods

A Survivorship Clinic was initiated comprising of a Survivorship APRN and Nurse Navigator. A referral process and workflow were created. Medical and Radiation Oncology providers were educated regarding availability of survivorship services. We describe the results of the Survivorship Clinic 2021-2025 including demographics, diagnoses and referral patterns.

Results

1,332 visits were completed for 424 patients. 2021 (Oct-Dec): 21, 2022: 219, 2023: 424, 2024: 508, 2025 (Jan-Mar): 160. 364 men and 60 women. Cancer diagnoses seen: lung: 108, lymphoma: 62, colorectal: 52, breast: 45, head and neck: 40, melanoma: 28, NET: 23, testicular: 13, bladder: 13, esophageal: 10, renal: 7, sarcomas: 7, anal: 6, HCC: 6, hepatobiliary: 6, gastric/GIST: 5, leukemia: 5, pancreatic: 5, prostate: 5, Merkel cell: 3, SCC: 3, thymus: 3, uterine: 2, 1 each appendix, anaplastic astrocytoma, periosteal carcinoma, poorly differentiated basaloid chest wall carcinoma, and small intestine. For symptom management the following referrals were placed: Rehab (all departments) : 71, Psychology/Whole Health/THRIVE: 52, Gastroenterology: 43, Nutrition: 24, Dermatology: 20, Urology, ED: 16, Pulmonology: 15, Plastic Surgery: 15, ENT: 12, LIVESTRONG YMCA: 10, Genetics: 9, General Surgery: 4, Neurology: 4, Breast Clinic: 3, Dental: 3, Neurosurgery: 2, Ophthalmology: 2, Pain Management: 2, Radiation Oncology: 2, Wound Care: 2, Pharmacy: 1, and Rheumatology: 1. Survivorship care plans were created and provided to all patients.

Conclusions

Since 2021, the Cancer Survivorship Clinic, operated by an APRN, has successfully served 424 cancer survivors encompassing a wide range of cancers. The disproportionately low number of prostate cancer survivors referred may be reflective of their care being managed by Urology, and presents an opportunity for future growth.

Implications for VA

Having a Survivorship Clinic provides cancer survivors specialized services and meets their unique needs; at the same allowing for improved capacity for new active cancer referrals for the Oncology Clinics.

Background

There are an estimated 18 million cancer survivors in the US with unique needs including specific surveillance imaging, testing for recurrence, monitoring for and managing late effects of cancer treatments, and for second malignancies. Survivorship care is an unmet need in most VAHC. Purpose: Assess implementation outcomes of a Survivorship Clinic.

Methods

A Survivorship Clinic was initiated comprising of a Survivorship APRN and Nurse Navigator. A referral process and workflow were created. Medical and Radiation Oncology providers were educated regarding availability of survivorship services. We describe the results of the Survivorship Clinic 2021-2025 including demographics, diagnoses and referral patterns.

Results

1,332 visits were completed for 424 patients. 2021 (Oct-Dec): 21, 2022: 219, 2023: 424, 2024: 508, 2025 (Jan-Mar): 160. 364 men and 60 women. Cancer diagnoses seen: lung: 108, lymphoma: 62, colorectal: 52, breast: 45, head and neck: 40, melanoma: 28, NET: 23, testicular: 13, bladder: 13, esophageal: 10, renal: 7, sarcomas: 7, anal: 6, HCC: 6, hepatobiliary: 6, gastric/GIST: 5, leukemia: 5, pancreatic: 5, prostate: 5, Merkel cell: 3, SCC: 3, thymus: 3, uterine: 2, 1 each appendix, anaplastic astrocytoma, periosteal carcinoma, poorly differentiated basaloid chest wall carcinoma, and small intestine. For symptom management the following referrals were placed: Rehab (all departments) : 71, Psychology/Whole Health/THRIVE: 52, Gastroenterology: 43, Nutrition: 24, Dermatology: 20, Urology, ED: 16, Pulmonology: 15, Plastic Surgery: 15, ENT: 12, LIVESTRONG YMCA: 10, Genetics: 9, General Surgery: 4, Neurology: 4, Breast Clinic: 3, Dental: 3, Neurosurgery: 2, Ophthalmology: 2, Pain Management: 2, Radiation Oncology: 2, Wound Care: 2, Pharmacy: 1, and Rheumatology: 1. Survivorship care plans were created and provided to all patients.

Conclusions

Since 2021, the Cancer Survivorship Clinic, operated by an APRN, has successfully served 424 cancer survivors encompassing a wide range of cancers. The disproportionately low number of prostate cancer survivors referred may be reflective of their care being managed by Urology, and presents an opportunity for future growth.

Implications for VA

Having a Survivorship Clinic provides cancer survivors specialized services and meets their unique needs; at the same allowing for improved capacity for new active cancer referrals for the Oncology Clinics.

Background

There are an estimated 18 million cancer survivors in the US with unique needs including specific surveillance imaging, testing for recurrence, monitoring for and managing late effects of cancer treatments, and for second malignancies. Survivorship care is an unmet need in most VAHC. Purpose: Assess implementation outcomes of a Survivorship Clinic.

Methods

A Survivorship Clinic was initiated comprising of a Survivorship APRN and Nurse Navigator. A referral process and workflow were created. Medical and Radiation Oncology providers were educated regarding availability of survivorship services. We describe the results of the Survivorship Clinic 2021-2025 including demographics, diagnoses and referral patterns.

Results

1,332 visits were completed for 424 patients. 2021 (Oct-Dec): 21, 2022: 219, 2023: 424, 2024: 508, 2025 (Jan-Mar): 160. 364 men and 60 women. Cancer diagnoses seen: lung: 108, lymphoma: 62, colorectal: 52, breast: 45, head and neck: 40, melanoma: 28, NET: 23, testicular: 13, bladder: 13, esophageal: 10, renal: 7, sarcomas: 7, anal: 6, HCC: 6, hepatobiliary: 6, gastric/GIST: 5, leukemia: 5, pancreatic: 5, prostate: 5, Merkel cell: 3, SCC: 3, thymus: 3, uterine: 2, 1 each appendix, anaplastic astrocytoma, periosteal carcinoma, poorly differentiated basaloid chest wall carcinoma, and small intestine. For symptom management the following referrals were placed: Rehab (all departments) : 71, Psychology/Whole Health/THRIVE: 52, Gastroenterology: 43, Nutrition: 24, Dermatology: 20, Urology, ED: 16, Pulmonology: 15, Plastic Surgery: 15, ENT: 12, LIVESTRONG YMCA: 10, Genetics: 9, General Surgery: 4, Neurology: 4, Breast Clinic: 3, Dental: 3, Neurosurgery: 2, Ophthalmology: 2, Pain Management: 2, Radiation Oncology: 2, Wound Care: 2, Pharmacy: 1, and Rheumatology: 1. Survivorship care plans were created and provided to all patients.

Conclusions

Since 2021, the Cancer Survivorship Clinic, operated by an APRN, has successfully served 424 cancer survivors encompassing a wide range of cancers. The disproportionately low number of prostate cancer survivors referred may be reflective of their care being managed by Urology, and presents an opportunity for future growth.

Implications for VA

Having a Survivorship Clinic provides cancer survivors specialized services and meets their unique needs; at the same allowing for improved capacity for new active cancer referrals for the Oncology Clinics.

Background

The rise in the number of T-cell engager therapies highlights their importance in modern cancer treatment paradigms. Having recognized the need for, and complexities of, administering these innovative medications to our patients, our team assessed our institution’s capability to provide these therapies to our patients. We identified that our facility was wellequipped for implementation of T-cell engager therapy due to inpatient administration capabilities, an outpatient infusion center, on-hand supportive care medications (tocilizumab), and access to higher levels of care. Key players included medical oncologists, pharmacists, inpatient and infusion nurses, staff physicians, critical care practitioners, and care coordinators.

Clinical Practice Initiative

Barriers identified: education, toxicity concerns, formulary management, and logistics. To overcome these obstacles, comprehensive plans for procurement, hospital admission, monitoring, and training were developed as a facility-specific standard operating procedure (SOP). All available Tcell engager therapies were presented to the formulary committee and received local approval. Physician and pharmacist champions were registered for the associated risk evaluation and mitigation strategies (REMS) programs. Recorded webinars were done to provide education on REMS requirements, medication logistics, and adverse event management.

An admission plan was formulated to outline admission criteria, medication administration, and safety logistics. Order sets created by pharmacists, encompassed pre, post, and as needed medications for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. To facilitate safe discharge and meet REMS criteria, patients received wallet cards, dexamethasone and acetaminophen PRNs with detailed instructions for use, and direction for seeking emergency care with consideration of local tocilizumab availability.

Conclusions

Our SOP has enabled administration of six T-cell engager therapies for six diseases. The primary limitation for some of these agents is the need for inpatient monitoring at initiation, which may not be available at smaller centers. Facilities that lack these capabilities could utilize community care or partner with a neighboring Veterans Affairs medical center for initial administration, then transition back for continued treatment. Facilities that lack inpatient oncology nursing could administer the drug in the infusion center followed by admission for monitoring and toxicity management. Our implementation plan serves as a scalable model for improving veteran access to novel therapies.

Background

The rise in the number of T-cell engager therapies highlights their importance in modern cancer treatment paradigms. Having recognized the need for, and complexities of, administering these innovative medications to our patients, our team assessed our institution’s capability to provide these therapies to our patients. We identified that our facility was wellequipped for implementation of T-cell engager therapy due to inpatient administration capabilities, an outpatient infusion center, on-hand supportive care medications (tocilizumab), and access to higher levels of care. Key players included medical oncologists, pharmacists, inpatient and infusion nurses, staff physicians, critical care practitioners, and care coordinators.

Clinical Practice Initiative

Barriers identified: education, toxicity concerns, formulary management, and logistics. To overcome these obstacles, comprehensive plans for procurement, hospital admission, monitoring, and training were developed as a facility-specific standard operating procedure (SOP). All available Tcell engager therapies were presented to the formulary committee and received local approval. Physician and pharmacist champions were registered for the associated risk evaluation and mitigation strategies (REMS) programs. Recorded webinars were done to provide education on REMS requirements, medication logistics, and adverse event management.

An admission plan was formulated to outline admission criteria, medication administration, and safety logistics. Order sets created by pharmacists, encompassed pre, post, and as needed medications for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. To facilitate safe discharge and meet REMS criteria, patients received wallet cards, dexamethasone and acetaminophen PRNs with detailed instructions for use, and direction for seeking emergency care with consideration of local tocilizumab availability.

Conclusions

Our SOP has enabled administration of six T-cell engager therapies for six diseases. The primary limitation for some of these agents is the need for inpatient monitoring at initiation, which may not be available at smaller centers. Facilities that lack these capabilities could utilize community care or partner with a neighboring Veterans Affairs medical center for initial administration, then transition back for continued treatment. Facilities that lack inpatient oncology nursing could administer the drug in the infusion center followed by admission for monitoring and toxicity management. Our implementation plan serves as a scalable model for improving veteran access to novel therapies.

Background

The rise in the number of T-cell engager therapies highlights their importance in modern cancer treatment paradigms. Having recognized the need for, and complexities of, administering these innovative medications to our patients, our team assessed our institution’s capability to provide these therapies to our patients. We identified that our facility was wellequipped for implementation of T-cell engager therapy due to inpatient administration capabilities, an outpatient infusion center, on-hand supportive care medications (tocilizumab), and access to higher levels of care. Key players included medical oncologists, pharmacists, inpatient and infusion nurses, staff physicians, critical care practitioners, and care coordinators.

Clinical Practice Initiative

Barriers identified: education, toxicity concerns, formulary management, and logistics. To overcome these obstacles, comprehensive plans for procurement, hospital admission, monitoring, and training were developed as a facility-specific standard operating procedure (SOP). All available Tcell engager therapies were presented to the formulary committee and received local approval. Physician and pharmacist champions were registered for the associated risk evaluation and mitigation strategies (REMS) programs. Recorded webinars were done to provide education on REMS requirements, medication logistics, and adverse event management.

An admission plan was formulated to outline admission criteria, medication administration, and safety logistics. Order sets created by pharmacists, encompassed pre, post, and as needed medications for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. To facilitate safe discharge and meet REMS criteria, patients received wallet cards, dexamethasone and acetaminophen PRNs with detailed instructions for use, and direction for seeking emergency care with consideration of local tocilizumab availability.

Conclusions

Our SOP has enabled administration of six T-cell engager therapies for six diseases. The primary limitation for some of these agents is the need for inpatient monitoring at initiation, which may not be available at smaller centers. Facilities that lack these capabilities could utilize community care or partner with a neighboring Veterans Affairs medical center for initial administration, then transition back for continued treatment. Facilities that lack inpatient oncology nursing could administer the drug in the infusion center followed by admission for monitoring and toxicity management. Our implementation plan serves as a scalable model for improving veteran access to novel therapies.

Background

Unmet psychosocial health needs negatively impact cancer care and outcomes. The American College of Surgeons’ Commission on Cancer (CoC) accreditation requirements include Psychosocial Distress Screening (PDS) for all newly diagnosed patients. To enhance cancer care and meet CoC standards, the Tibor Rubin Veterans Affairs Medical Center (TRVAMC) developed and implemented a closed-loop, centralized PDS pathway.

Objectives

Develop processes/methods to: (1) identify all newly diagnosed cancer patients; (2) track initiation of first course of treatment; (3) offer and complete PDS at initiation of first course of treatment; and (4) ensure placement of appropriate referrals.

Methods

All staff members were trained in PDS and competency completed. A standard operating procedure (SOP) was created to identify patients meeting criteria for PDS. Newly diagnosed patients were identified from cancer registry lists, tumor boards, radiology and pathology reports. Patients were placed on a tracking tool by the nurse care coordinator (NCC) and monitored to facilitate timely workup and initiation of treatment. Nurses in the cancer program offered and completed PDS and placed all necessary referrals (to > 11 services). Patients were removed from the tracker only after confirmation of PDS and referrals.

Results

Prior to implementation of PDS, no patients received comprehensive screening and referrals. After implementation, data were collected over a 2 year period. In 2023 and 2024, 277/565 (49%) and 256/526 (48.7%) newly diagnosed patients were eligible for PDS, respectively. All eligible patients were offered PDS (100%). Of patients who underwent PDS, 37% scored their distress at a level of 4/10 or higher, underscoring the severity of distress and unmet need. Referrals to various services were indicated and made in 43.8% patients, most frequently to Social Work, Primary Care or Psychology/Mental Health. More recently, nurses in the Infusion Clinic and Radiation Oncology were trained in and also started conducting PDS on patients coming for treatment.

Conclusions

Implementation of comprehensive and timely PDS resulted in early identification and interventions to address diverse facets of distress that are known to interfere with quality of life, compliance with cancer treatments and outcomes. The program also met the CoC standard for accreditation of TRVAMC in 2024.

Background

Unmet psychosocial health needs negatively impact cancer care and outcomes. The American College of Surgeons’ Commission on Cancer (CoC) accreditation requirements include Psychosocial Distress Screening (PDS) for all newly diagnosed patients. To enhance cancer care and meet CoC standards, the Tibor Rubin Veterans Affairs Medical Center (TRVAMC) developed and implemented a closed-loop, centralized PDS pathway.

Objectives

Develop processes/methods to: (1) identify all newly diagnosed cancer patients; (2) track initiation of first course of treatment; (3) offer and complete PDS at initiation of first course of treatment; and (4) ensure placement of appropriate referrals.

Methods

All staff members were trained in PDS and competency completed. A standard operating procedure (SOP) was created to identify patients meeting criteria for PDS. Newly diagnosed patients were identified from cancer registry lists, tumor boards, radiology and pathology reports. Patients were placed on a tracking tool by the nurse care coordinator (NCC) and monitored to facilitate timely workup and initiation of treatment. Nurses in the cancer program offered and completed PDS and placed all necessary referrals (to > 11 services). Patients were removed from the tracker only after confirmation of PDS and referrals.

Results

Prior to implementation of PDS, no patients received comprehensive screening and referrals. After implementation, data were collected over a 2 year period. In 2023 and 2024, 277/565 (49%) and 256/526 (48.7%) newly diagnosed patients were eligible for PDS, respectively. All eligible patients were offered PDS (100%). Of patients who underwent PDS, 37% scored their distress at a level of 4/10 or higher, underscoring the severity of distress and unmet need. Referrals to various services were indicated and made in 43.8% patients, most frequently to Social Work, Primary Care or Psychology/Mental Health. More recently, nurses in the Infusion Clinic and Radiation Oncology were trained in and also started conducting PDS on patients coming for treatment.

Conclusions

Implementation of comprehensive and timely PDS resulted in early identification and interventions to address diverse facets of distress that are known to interfere with quality of life, compliance with cancer treatments and outcomes. The program also met the CoC standard for accreditation of TRVAMC in 2024.

Background

Unmet psychosocial health needs negatively impact cancer care and outcomes. The American College of Surgeons’ Commission on Cancer (CoC) accreditation requirements include Psychosocial Distress Screening (PDS) for all newly diagnosed patients. To enhance cancer care and meet CoC standards, the Tibor Rubin Veterans Affairs Medical Center (TRVAMC) developed and implemented a closed-loop, centralized PDS pathway.

Objectives

Develop processes/methods to: (1) identify all newly diagnosed cancer patients; (2) track initiation of first course of treatment; (3) offer and complete PDS at initiation of first course of treatment; and (4) ensure placement of appropriate referrals.

Methods

All staff members were trained in PDS and competency completed. A standard operating procedure (SOP) was created to identify patients meeting criteria for PDS. Newly diagnosed patients were identified from cancer registry lists, tumor boards, radiology and pathology reports. Patients were placed on a tracking tool by the nurse care coordinator (NCC) and monitored to facilitate timely workup and initiation of treatment. Nurses in the cancer program offered and completed PDS and placed all necessary referrals (to > 11 services). Patients were removed from the tracker only after confirmation of PDS and referrals.

Results

Prior to implementation of PDS, no patients received comprehensive screening and referrals. After implementation, data were collected over a 2 year period. In 2023 and 2024, 277/565 (49%) and 256/526 (48.7%) newly diagnosed patients were eligible for PDS, respectively. All eligible patients were offered PDS (100%). Of patients who underwent PDS, 37% scored their distress at a level of 4/10 or higher, underscoring the severity of distress and unmet need. Referrals to various services were indicated and made in 43.8% patients, most frequently to Social Work, Primary Care or Psychology/Mental Health. More recently, nurses in the Infusion Clinic and Radiation Oncology were trained in and also started conducting PDS on patients coming for treatment.

Conclusions

Implementation of comprehensive and timely PDS resulted in early identification and interventions to address diverse facets of distress that are known to interfere with quality of life, compliance with cancer treatments and outcomes. The program also met the CoC standard for accreditation of TRVAMC in 2024.

Case Presentation

A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.

Case Presentation

A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.

Case Presentation

A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.

Background

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract, accounting for approximately 1–2% of GI cancers. Hypoglycemia in patients with GIST is an uncommon and diagnostically challenging presentation, often involving a broad differential diagnosis. This case report explores the diagnostic difficulties encountered in managing persistent hypoglycemia in a patient with a history of advanced GIST.

Case Presentation

An 80-year-old male with a history of stage IV GIST, diagnosed in 2010, presented with persistent symptomatic hypoglycemia. His medical history included extensive abdominal disease, managed with multiple interventions: esophagogastrostomy, left lateral liver resection, a Whipple procedure, and Y-90 radioembolization. He received adjuvant imatinib therapy, which was discontinued in April 2024 due to significant adverse effects, including anasarca. In 2025, the patient developed progressive hypoglycemia, ultimately requiring continuous D10 infusion to maintain euglycemia, prompting an endocrinology evaluation. The initial diagnostic workup included cortisol, insulin, C-peptide levels, and IGF-1/IGF-2 ratio ruling out insulinoma, adrenal insufficiency, and GISTrelated paraneoplastic syndrome. Imaging studies, including PET and CT, showed no radiological evidence of recurrent GIST. Treatment with octreotide infusion resulted in minimal improvement, whereas daily corticosteroid therapy significantly alleviated the patient’s symptoms. The etiology of hypoglycemia remains elusive, with potential causes under consideration including Y-90 radioembolization-induced damage to glucagon-producing cells, immunotherapy-related adverse effects, or radiologically occult GIST. Insulin autoantibody testing is pending, and the case remains under active investigation, highlighting the diagnostic complexity of hypoglycemia in advanced GIST.

Discussion

Hypoglycemia in the context of GIST is a rare and poorly understood phenomenon. Potential mechanisms include paraneoplastic syndromes, such as non-islet cell tumor hypoglycemia (NICTH) mediated by IGF-2, or treatment-related effects, such as radiation-induced pancreatic or hepatic dysfunction. In this case, the absence of detectable IGF-2 abnormalities and negative imaging complicates the diagnosis. The lack of response to octreotide indicates that somatostatin receptor-mediated pathways may not be involved. The discontinuation of imatinib and prior Y-90 radioembolization further broadens the differential, as both could contribute to metabolic dysregulation.

Conclusions

This case illustrates the need for a systematic and multidisciplinary approach to evaluate hypoglycemia in patients with advanced GIST.

Background

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract, accounting for approximately 1–2% of GI cancers. Hypoglycemia in patients with GIST is an uncommon and diagnostically challenging presentation, often involving a broad differential diagnosis. This case report explores the diagnostic difficulties encountered in managing persistent hypoglycemia in a patient with a history of advanced GIST.

Case Presentation

An 80-year-old male with a history of stage IV GIST, diagnosed in 2010, presented with persistent symptomatic hypoglycemia. His medical history included extensive abdominal disease, managed with multiple interventions: esophagogastrostomy, left lateral liver resection, a Whipple procedure, and Y-90 radioembolization. He received adjuvant imatinib therapy, which was discontinued in April 2024 due to significant adverse effects, including anasarca. In 2025, the patient developed progressive hypoglycemia, ultimately requiring continuous D10 infusion to maintain euglycemia, prompting an endocrinology evaluation. The initial diagnostic workup included cortisol, insulin, C-peptide levels, and IGF-1/IGF-2 ratio ruling out insulinoma, adrenal insufficiency, and GISTrelated paraneoplastic syndrome. Imaging studies, including PET and CT, showed no radiological evidence of recurrent GIST. Treatment with octreotide infusion resulted in minimal improvement, whereas daily corticosteroid therapy significantly alleviated the patient’s symptoms. The etiology of hypoglycemia remains elusive, with potential causes under consideration including Y-90 radioembolization-induced damage to glucagon-producing cells, immunotherapy-related adverse effects, or radiologically occult GIST. Insulin autoantibody testing is pending, and the case remains under active investigation, highlighting the diagnostic complexity of hypoglycemia in advanced GIST.

Discussion

Hypoglycemia in the context of GIST is a rare and poorly understood phenomenon. Potential mechanisms include paraneoplastic syndromes, such as non-islet cell tumor hypoglycemia (NICTH) mediated by IGF-2, or treatment-related effects, such as radiation-induced pancreatic or hepatic dysfunction. In this case, the absence of detectable IGF-2 abnormalities and negative imaging complicates the diagnosis. The lack of response to octreotide indicates that somatostatin receptor-mediated pathways may not be involved. The discontinuation of imatinib and prior Y-90 radioembolization further broadens the differential, as both could contribute to metabolic dysregulation.

Conclusions

This case illustrates the need for a systematic and multidisciplinary approach to evaluate hypoglycemia in patients with advanced GIST.

Background

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract, accounting for approximately 1–2% of GI cancers. Hypoglycemia in patients with GIST is an uncommon and diagnostically challenging presentation, often involving a broad differential diagnosis. This case report explores the diagnostic difficulties encountered in managing persistent hypoglycemia in a patient with a history of advanced GIST.

Case Presentation

An 80-year-old male with a history of stage IV GIST, diagnosed in 2010, presented with persistent symptomatic hypoglycemia. His medical history included extensive abdominal disease, managed with multiple interventions: esophagogastrostomy, left lateral liver resection, a Whipple procedure, and Y-90 radioembolization. He received adjuvant imatinib therapy, which was discontinued in April 2024 due to significant adverse effects, including anasarca. In 2025, the patient developed progressive hypoglycemia, ultimately requiring continuous D10 infusion to maintain euglycemia, prompting an endocrinology evaluation. The initial diagnostic workup included cortisol, insulin, C-peptide levels, and IGF-1/IGF-2 ratio ruling out insulinoma, adrenal insufficiency, and GISTrelated paraneoplastic syndrome. Imaging studies, including PET and CT, showed no radiological evidence of recurrent GIST. Treatment with octreotide infusion resulted in minimal improvement, whereas daily corticosteroid therapy significantly alleviated the patient’s symptoms. The etiology of hypoglycemia remains elusive, with potential causes under consideration including Y-90 radioembolization-induced damage to glucagon-producing cells, immunotherapy-related adverse effects, or radiologically occult GIST. Insulin autoantibody testing is pending, and the case remains under active investigation, highlighting the diagnostic complexity of hypoglycemia in advanced GIST.

Discussion

Hypoglycemia in the context of GIST is a rare and poorly understood phenomenon. Potential mechanisms include paraneoplastic syndromes, such as non-islet cell tumor hypoglycemia (NICTH) mediated by IGF-2, or treatment-related effects, such as radiation-induced pancreatic or hepatic dysfunction. In this case, the absence of detectable IGF-2 abnormalities and negative imaging complicates the diagnosis. The lack of response to octreotide indicates that somatostatin receptor-mediated pathways may not be involved. The discontinuation of imatinib and prior Y-90 radioembolization further broadens the differential, as both could contribute to metabolic dysregulation.

Conclusions

This case illustrates the need for a systematic and multidisciplinary approach to evaluate hypoglycemia in patients with advanced GIST.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma most commonly arising in mucosal, nodal, or splenic tissues. While extranodal presentations are recognized, involvement of the sciatic foramen is exceedingly rare. We present a unique case of stage IV MZL with primary involvement of the left sciatic foramen, identified incidentally during urologic evaluation.

Case Presentation

A 74-year-old male patient was referred for hematologic evaluation after imaging revealed a left sciatic foraminal mass during work-up for elevated PSA. CT abdomen/pelvis revealed a 4.7 cm mass in the left sciatic foramen. Follow-up PET-CT confirmed hypermetabolic activity in the mass, with additional areas of uptake in the right ilium and pleural- pericardial regions. The patient was asymptomatic and denied B-symptoms. CT-guided biopsy of the sciatic mass revealed low-grade B-cell lymphoma. Flow cytometry showed a CD20-positive, CD5-negative, CD10-negative, lambda light chain–restricted population consistent with marginal zone lymphoma. Laboratory studies demonstrated iron deficiency anemia, with otherwise unremarkable counts and chemistries. He was started on monotherapy with rituximab for four cycles. He tolerated treatment well. Interval PET imaging in April 2025 showed stable disease in the sciatic foramen and mild improvement in pleural- pericardial uptake. He is planned to start obinutuzumab in the upcoming month.

Discussion

This case illustrates a rare anatomic presentation of MZL, likely representing primary sciatic foramen involvement. The presence of additional PETavid lesions complicates staging, raising consideration of stage I vs. III/IV disease. Biopsy was limited to the sciatic lesion, and no bone marrow sampling was performed. Given the patient’s excellent performance status, absence of symptoms, and low tumor burden, single-agent rituximab was chosen initially in accordance with NCCN guidelines.

Conclusions

Sciatic foramen involvement by MZL is an extremely rare occurrence and may mimic more common soft tissue or neurogenic tumors radiographically. This case underscores the importance of biopsy for diagnosis and the value of multidisciplinary care. In the veteran population, such incidental findings on imaging warrant comprehensive evaluation, particularly in atypical anatomical sites.

Background

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma most commonly arising in mucosal, nodal, or splenic tissues. While extranodal presentations are recognized, involvement of the sciatic foramen is exceedingly rare. We present a unique case of stage IV MZL with primary involvement of the left sciatic foramen, identified incidentally during urologic evaluation.

Case Presentation

A 74-year-old male patient was referred for hematologic evaluation after imaging revealed a left sciatic foraminal mass during work-up for elevated PSA. CT abdomen/pelvis revealed a 4.7 cm mass in the left sciatic foramen. Follow-up PET-CT confirmed hypermetabolic activity in the mass, with additional areas of uptake in the right ilium and pleural- pericardial regions. The patient was asymptomatic and denied B-symptoms. CT-guided biopsy of the sciatic mass revealed low-grade B-cell lymphoma. Flow cytometry showed a CD20-positive, CD5-negative, CD10-negative, lambda light chain–restricted population consistent with marginal zone lymphoma. Laboratory studies demonstrated iron deficiency anemia, with otherwise unremarkable counts and chemistries. He was started on monotherapy with rituximab for four cycles. He tolerated treatment well. Interval PET imaging in April 2025 showed stable disease in the sciatic foramen and mild improvement in pleural- pericardial uptake. He is planned to start obinutuzumab in the upcoming month.

Discussion

This case illustrates a rare anatomic presentation of MZL, likely representing primary sciatic foramen involvement. The presence of additional PETavid lesions complicates staging, raising consideration of stage I vs. III/IV disease. Biopsy was limited to the sciatic lesion, and no bone marrow sampling was performed. Given the patient’s excellent performance status, absence of symptoms, and low tumor burden, single-agent rituximab was chosen initially in accordance with NCCN guidelines.

Conclusions

Sciatic foramen involvement by MZL is an extremely rare occurrence and may mimic more common soft tissue or neurogenic tumors radiographically. This case underscores the importance of biopsy for diagnosis and the value of multidisciplinary care. In the veteran population, such incidental findings on imaging warrant comprehensive evaluation, particularly in atypical anatomical sites.

Background

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma most commonly arising in mucosal, nodal, or splenic tissues. While extranodal presentations are recognized, involvement of the sciatic foramen is exceedingly rare. We present a unique case of stage IV MZL with primary involvement of the left sciatic foramen, identified incidentally during urologic evaluation.

Case Presentation

A 74-year-old male patient was referred for hematologic evaluation after imaging revealed a left sciatic foraminal mass during work-up for elevated PSA. CT abdomen/pelvis revealed a 4.7 cm mass in the left sciatic foramen. Follow-up PET-CT confirmed hypermetabolic activity in the mass, with additional areas of uptake in the right ilium and pleural- pericardial regions. The patient was asymptomatic and denied B-symptoms. CT-guided biopsy of the sciatic mass revealed low-grade B-cell lymphoma. Flow cytometry showed a CD20-positive, CD5-negative, CD10-negative, lambda light chain–restricted population consistent with marginal zone lymphoma. Laboratory studies demonstrated iron deficiency anemia, with otherwise unremarkable counts and chemistries. He was started on monotherapy with rituximab for four cycles. He tolerated treatment well. Interval PET imaging in April 2025 showed stable disease in the sciatic foramen and mild improvement in pleural- pericardial uptake. He is planned to start obinutuzumab in the upcoming month.

Discussion

This case illustrates a rare anatomic presentation of MZL, likely representing primary sciatic foramen involvement. The presence of additional PETavid lesions complicates staging, raising consideration of stage I vs. III/IV disease. Biopsy was limited to the sciatic lesion, and no bone marrow sampling was performed. Given the patient’s excellent performance status, absence of symptoms, and low tumor burden, single-agent rituximab was chosen initially in accordance with NCCN guidelines.

Conclusions

Sciatic foramen involvement by MZL is an extremely rare occurrence and may mimic more common soft tissue or neurogenic tumors radiographically. This case underscores the importance of biopsy for diagnosis and the value of multidisciplinary care. In the veteran population, such incidental findings on imaging warrant comprehensive evaluation, particularly in atypical anatomical sites.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Hypereosinophilic syndrome (HES) is a rare condition caused by an overproduction of eosinophils leading to tissue infiltration and end-organ damage. HES can infiltrate the heart and lead to rare but severe cases of eosinophilic endomyocarditis, potentially causing heart failure, restrictive cardiomyopathy, and thromboembolic events.

Case Presentation

A 53-year-old female presented for abdominal pain but was found to have significant leukocytosis and eosinophilia with an absolute eosinophil count of 15.50×109/L. Further imaging with cardiac MRI showed early nodular subendocardial enhancement suggestive of eosinophilic endomyocarditis. Bone marrow biopsy was negative for clonal disorders and gastric biopsy was negative for eosinophils and H. pylori. Treatment with high-dose prednisone caused reduction in eosinophils and repeat cardiac MRI showed significant improvement in endomyocarditis.

Discussion

HES is a rare condition characterized by persistently elevated eosinophilia that can cause end organ damage, mainly affecting the heart, lungs, skin and GI system. It can be caused by primary, secondary, or idiopathic mechanisms. Primary HES often involves genetic mutations, whereas secondary HES arises due to infections or malignancies. Idiopathic HES is mainly a diagnosis of exclusion. Workup includes bone marrow biopsies and molecular testing to help differentiate between different causes and guide treatment. Eosinophilic endomyocarditis (EM) is a rare and severe complication of HES caused by eosinophilic infiltration of the myocardium. It is characterized by myocardial inflammation, fibrosis, edema, arrhythmias and heart failure if left untreated. EM is a major cause of mortality and morbidity among patients with HES. Cardiac MRI is helpful for early detection but endomyocardial biopsy is the gold standard for definitive diagnosis. Early treatment with corticosteroids can significantly reduce eosinophilic infiltration and improve outcomes. Given the severity of this rare manifestation of HES, further research is needed to help improve diagnostic and treatment strategies for EM.

Conclusions

HES is a rare condition that can cause damage affecting multiple organs with one such complication being eosinophilic endomyocarditis, a condition known to increase mortality and morbidity in those with HES. Early but accurate diagnosis and timely intervention with corticosteroids is necessary for improving the overall outcomes of those affected with this.

Background

Hypereosinophilic syndrome (HES) is a rare condition caused by an overproduction of eosinophils leading to tissue infiltration and end-organ damage. HES can infiltrate the heart and lead to rare but severe cases of eosinophilic endomyocarditis, potentially causing heart failure, restrictive cardiomyopathy, and thromboembolic events.

Case Presentation

A 53-year-old female presented for abdominal pain but was found to have significant leukocytosis and eosinophilia with an absolute eosinophil count of 15.50×109/L. Further imaging with cardiac MRI showed early nodular subendocardial enhancement suggestive of eosinophilic endomyocarditis. Bone marrow biopsy was negative for clonal disorders and gastric biopsy was negative for eosinophils and H. pylori. Treatment with high-dose prednisone caused reduction in eosinophils and repeat cardiac MRI showed significant improvement in endomyocarditis.

Discussion

HES is a rare condition characterized by persistently elevated eosinophilia that can cause end organ damage, mainly affecting the heart, lungs, skin and GI system. It can be caused by primary, secondary, or idiopathic mechanisms. Primary HES often involves genetic mutations, whereas secondary HES arises due to infections or malignancies. Idiopathic HES is mainly a diagnosis of exclusion. Workup includes bone marrow biopsies and molecular testing to help differentiate between different causes and guide treatment. Eosinophilic endomyocarditis (EM) is a rare and severe complication of HES caused by eosinophilic infiltration of the myocardium. It is characterized by myocardial inflammation, fibrosis, edema, arrhythmias and heart failure if left untreated. EM is a major cause of mortality and morbidity among patients with HES. Cardiac MRI is helpful for early detection but endomyocardial biopsy is the gold standard for definitive diagnosis. Early treatment with corticosteroids can significantly reduce eosinophilic infiltration and improve outcomes. Given the severity of this rare manifestation of HES, further research is needed to help improve diagnostic and treatment strategies for EM.

Conclusions

HES is a rare condition that can cause damage affecting multiple organs with one such complication being eosinophilic endomyocarditis, a condition known to increase mortality and morbidity in those with HES. Early but accurate diagnosis and timely intervention with corticosteroids is necessary for improving the overall outcomes of those affected with this.

Background

Hypereosinophilic syndrome (HES) is a rare condition caused by an overproduction of eosinophils leading to tissue infiltration and end-organ damage. HES can infiltrate the heart and lead to rare but severe cases of eosinophilic endomyocarditis, potentially causing heart failure, restrictive cardiomyopathy, and thromboembolic events.

Case Presentation

A 53-year-old female presented for abdominal pain but was found to have significant leukocytosis and eosinophilia with an absolute eosinophil count of 15.50×109/L. Further imaging with cardiac MRI showed early nodular subendocardial enhancement suggestive of eosinophilic endomyocarditis. Bone marrow biopsy was negative for clonal disorders and gastric biopsy was negative for eosinophils and H. pylori. Treatment with high-dose prednisone caused reduction in eosinophils and repeat cardiac MRI showed significant improvement in endomyocarditis.

Discussion

HES is a rare condition characterized by persistently elevated eosinophilia that can cause end organ damage, mainly affecting the heart, lungs, skin and GI system. It can be caused by primary, secondary, or idiopathic mechanisms. Primary HES often involves genetic mutations, whereas secondary HES arises due to infections or malignancies. Idiopathic HES is mainly a diagnosis of exclusion. Workup includes bone marrow biopsies and molecular testing to help differentiate between different causes and guide treatment. Eosinophilic endomyocarditis (EM) is a rare and severe complication of HES caused by eosinophilic infiltration of the myocardium. It is characterized by myocardial inflammation, fibrosis, edema, arrhythmias and heart failure if left untreated. EM is a major cause of mortality and morbidity among patients with HES. Cardiac MRI is helpful for early detection but endomyocardial biopsy is the gold standard for definitive diagnosis. Early treatment with corticosteroids can significantly reduce eosinophilic infiltration and improve outcomes. Given the severity of this rare manifestation of HES, further research is needed to help improve diagnostic and treatment strategies for EM.

Conclusions

HES is a rare condition that can cause damage affecting multiple organs with one such complication being eosinophilic endomyocarditis, a condition known to increase mortality and morbidity in those with HES. Early but accurate diagnosis and timely intervention with corticosteroids is necessary for improving the overall outcomes of those affected with this.