AVAHO

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Sickle cell disease (SCD) patients often present with pain and fever, commonly attributed to vaso-occlusive crises (VOC), which can delay the diagnosis of other conditions. This highlights the need for reassessment and bias-aware clinical reasoning.

Case Presentation

A 27-year-old male with SCD, prior hip replacement, and cholecystectomy presented with whole-body pain. Labs supported VOC with anemia, elevated LDH, and reticulocytosis. Despite RUQ tenderness and a positive Murphy sign, the ultrasound was unremarkable, and he was admitted for VOC management. Persistent fever >48 hours prompted further evaluation with MRCP, revealing choledocholithiasis with common bile duct and mild biliary dilatation; later, his pain and fever resolved by ERCP, and he was discharged. However, he returned the following day with whole-body and right upper quadrant pain; lab tests showed normal hemoglobin, LDH, and reticulocyte levels, indicating no active sickling. On follow-ups, the patient started to have fever episodes again. Subsequent fevers prompted a CT scan, revealing pulmonary embolism involving the right interlobar pulmonary artery extending into the segmental and subsegmental vessels and right lower lobe pneumonia. He denied any cough or shortness of breath. Treatment with Eliquis for the embolism and antibiotics for hospital-acquired pneumonia resolved the fever and leukocytosis, but the patient persistently requested high-dose opioids despite normal sickling labs.

Discussion

This case highlights the need for diagnostic flexibility in SCD, as anchoring bias may cause clinicians to overlook other life-threatening conditions when VOC is suspected. The patient’s symptoms, initially suggestive of VOC, were later linked to choledocholithiasis, pulmonary embolism, and pneumonia, highlighting how overlapping complications can be misattributed to a single episode. The delayed diagnosis reflects cognitive and systemic factors, with few reports emphasizing the diagnostic delays when multiple SCD-related complications occur together. The stigma surrounding opioid use may also hinder timely care escalation. This case highlights the need for structured reassessment, red-flag criteria, and multidisciplinary collaboration to improve diagnostic accuracy and prevent fatal delays in complex SCD presentations.

Conclusions

This case emphasizes reassessing persistent symptoms in SCD, avoiding anchoring bias, and recognizing red flags. Multidisciplinary evaluation and bias-aware practices are key to accurate, timely care.

Background

Sickle cell disease (SCD) patients often present with pain and fever, commonly attributed to vaso-occlusive crises (VOC), which can delay the diagnosis of other conditions. This highlights the need for reassessment and bias-aware clinical reasoning.

Case Presentation

A 27-year-old male with SCD, prior hip replacement, and cholecystectomy presented with whole-body pain. Labs supported VOC with anemia, elevated LDH, and reticulocytosis. Despite RUQ tenderness and a positive Murphy sign, the ultrasound was unremarkable, and he was admitted for VOC management. Persistent fever >48 hours prompted further evaluation with MRCP, revealing choledocholithiasis with common bile duct and mild biliary dilatation; later, his pain and fever resolved by ERCP, and he was discharged. However, he returned the following day with whole-body and right upper quadrant pain; lab tests showed normal hemoglobin, LDH, and reticulocyte levels, indicating no active sickling. On follow-ups, the patient started to have fever episodes again. Subsequent fevers prompted a CT scan, revealing pulmonary embolism involving the right interlobar pulmonary artery extending into the segmental and subsegmental vessels and right lower lobe pneumonia. He denied any cough or shortness of breath. Treatment with Eliquis for the embolism and antibiotics for hospital-acquired pneumonia resolved the fever and leukocytosis, but the patient persistently requested high-dose opioids despite normal sickling labs.

Discussion

This case highlights the need for diagnostic flexibility in SCD, as anchoring bias may cause clinicians to overlook other life-threatening conditions when VOC is suspected. The patient’s symptoms, initially suggestive of VOC, were later linked to choledocholithiasis, pulmonary embolism, and pneumonia, highlighting how overlapping complications can be misattributed to a single episode. The delayed diagnosis reflects cognitive and systemic factors, with few reports emphasizing the diagnostic delays when multiple SCD-related complications occur together. The stigma surrounding opioid use may also hinder timely care escalation. This case highlights the need for structured reassessment, red-flag criteria, and multidisciplinary collaboration to improve diagnostic accuracy and prevent fatal delays in complex SCD presentations.

Conclusions

This case emphasizes reassessing persistent symptoms in SCD, avoiding anchoring bias, and recognizing red flags. Multidisciplinary evaluation and bias-aware practices are key to accurate, timely care.

Background

Sickle cell disease (SCD) patients often present with pain and fever, commonly attributed to vaso-occlusive crises (VOC), which can delay the diagnosis of other conditions. This highlights the need for reassessment and bias-aware clinical reasoning.

Case Presentation

A 27-year-old male with SCD, prior hip replacement, and cholecystectomy presented with whole-body pain. Labs supported VOC with anemia, elevated LDH, and reticulocytosis. Despite RUQ tenderness and a positive Murphy sign, the ultrasound was unremarkable, and he was admitted for VOC management. Persistent fever >48 hours prompted further evaluation with MRCP, revealing choledocholithiasis with common bile duct and mild biliary dilatation; later, his pain and fever resolved by ERCP, and he was discharged. However, he returned the following day with whole-body and right upper quadrant pain; lab tests showed normal hemoglobin, LDH, and reticulocyte levels, indicating no active sickling. On follow-ups, the patient started to have fever episodes again. Subsequent fevers prompted a CT scan, revealing pulmonary embolism involving the right interlobar pulmonary artery extending into the segmental and subsegmental vessels and right lower lobe pneumonia. He denied any cough or shortness of breath. Treatment with Eliquis for the embolism and antibiotics for hospital-acquired pneumonia resolved the fever and leukocytosis, but the patient persistently requested high-dose opioids despite normal sickling labs.

Discussion

This case highlights the need for diagnostic flexibility in SCD, as anchoring bias may cause clinicians to overlook other life-threatening conditions when VOC is suspected. The patient’s symptoms, initially suggestive of VOC, were later linked to choledocholithiasis, pulmonary embolism, and pneumonia, highlighting how overlapping complications can be misattributed to a single episode. The delayed diagnosis reflects cognitive and systemic factors, with few reports emphasizing the diagnostic delays when multiple SCD-related complications occur together. The stigma surrounding opioid use may also hinder timely care escalation. This case highlights the need for structured reassessment, red-flag criteria, and multidisciplinary collaboration to improve diagnostic accuracy and prevent fatal delays in complex SCD presentations.

Conclusions

This case emphasizes reassessing persistent symptoms in SCD, avoiding anchoring bias, and recognizing red flags. Multidisciplinary evaluation and bias-aware practices are key to accurate, timely care.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.

Case Presentation

A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.

Discussion

The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.

Conclusions

Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.

Background

Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.

Case Presentation

A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.

Discussion

The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.

Conclusions

Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.

Background

Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.

Case Presentation

A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.

Discussion

The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.

Conclusions

Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.

Background

Merkel cell carcinoma (MCC) is a rare and aggressive primary cutaneous neuroendocrine carcinoma. The disease is associated with Merkel cell polyomavirus, immunosuppression, and ultra-violet radiation. Clinical presentation is highly varied and MCC is not suspected in majority of cases initially. It is rapidly growing and has a poor prognosis with a high mortality rate.

Case 1

A 75-year-old male initially presented with a cutaneous left facial lesion which on biopsy was confirmed to be Merkel cell carcinoma. He underwent wide local excision of the lesion with sentinel lymph node biopsy and was monitored. Six months later he was found to have palpable left parotid nodule, and underwent left parotidectomy and left neck lymph node dissection. The parotid nodule itself was of benign etiology; however, one of the cervical lymph nodes was positive for Merkel cell carcinoma with extranodal extension and lymphovascular invasion. Patient received adjuvant radiation to the site. A year after patient was noted to have bone lesions and other lesions concerning for visceral metastasis on surveillance imaging which were also confirmed to be recurrent MCC by biopsy. Patient was started on immunotherapy afterwards.

Case 2

A 60-year-male patient originally presented with a left inguinal mass. Pathology from the initial biopsy was noted to be small cell neuroendocrine carcinoma of unknown primary. Patient received six cycles of cisplatin and etoposide followed by radiation. Four months later patient was found to have local recurrence and underwent surgical resection, followed by five cycles of cyclophosphamide, doxorubicin, and vincristine. Five months later, the patient had a second recurrence in the surgical bed in addition to multiple subcutaneous nodules in the abdominal wall and lower extremity. A repeat biopsy was performed with Merkel cell polyomavirus testing by immunohistochemistry, which resulted as positive. Patient was started on immunotherapy afterwards.

Discussion

The above two cases represent how Merkel cell carcinoma can have varying presentations either on diagnosis or on progression. Thus, it is important to have a low threshold for biopsy or rebiopsy. Additionally, neuroendocrine carcinomas of unknown primary may benefit from additional Merkel cell IHC testing on diagnosis.

Background

Merkel cell carcinoma (MCC) is a rare and aggressive primary cutaneous neuroendocrine carcinoma. The disease is associated with Merkel cell polyomavirus, immunosuppression, and ultra-violet radiation. Clinical presentation is highly varied and MCC is not suspected in majority of cases initially. It is rapidly growing and has a poor prognosis with a high mortality rate.

Case 1

A 75-year-old male initially presented with a cutaneous left facial lesion which on biopsy was confirmed to be Merkel cell carcinoma. He underwent wide local excision of the lesion with sentinel lymph node biopsy and was monitored. Six months later he was found to have palpable left parotid nodule, and underwent left parotidectomy and left neck lymph node dissection. The parotid nodule itself was of benign etiology; however, one of the cervical lymph nodes was positive for Merkel cell carcinoma with extranodal extension and lymphovascular invasion. Patient received adjuvant radiation to the site. A year after patient was noted to have bone lesions and other lesions concerning for visceral metastasis on surveillance imaging which were also confirmed to be recurrent MCC by biopsy. Patient was started on immunotherapy afterwards.

Case 2

A 60-year-male patient originally presented with a left inguinal mass. Pathology from the initial biopsy was noted to be small cell neuroendocrine carcinoma of unknown primary. Patient received six cycles of cisplatin and etoposide followed by radiation. Four months later patient was found to have local recurrence and underwent surgical resection, followed by five cycles of cyclophosphamide, doxorubicin, and vincristine. Five months later, the patient had a second recurrence in the surgical bed in addition to multiple subcutaneous nodules in the abdominal wall and lower extremity. A repeat biopsy was performed with Merkel cell polyomavirus testing by immunohistochemistry, which resulted as positive. Patient was started on immunotherapy afterwards.

Discussion

The above two cases represent how Merkel cell carcinoma can have varying presentations either on diagnosis or on progression. Thus, it is important to have a low threshold for biopsy or rebiopsy. Additionally, neuroendocrine carcinomas of unknown primary may benefit from additional Merkel cell IHC testing on diagnosis.

Background

Merkel cell carcinoma (MCC) is a rare and aggressive primary cutaneous neuroendocrine carcinoma. The disease is associated with Merkel cell polyomavirus, immunosuppression, and ultra-violet radiation. Clinical presentation is highly varied and MCC is not suspected in majority of cases initially. It is rapidly growing and has a poor prognosis with a high mortality rate.

Case 1

A 75-year-old male initially presented with a cutaneous left facial lesion which on biopsy was confirmed to be Merkel cell carcinoma. He underwent wide local excision of the lesion with sentinel lymph node biopsy and was monitored. Six months later he was found to have palpable left parotid nodule, and underwent left parotidectomy and left neck lymph node dissection. The parotid nodule itself was of benign etiology; however, one of the cervical lymph nodes was positive for Merkel cell carcinoma with extranodal extension and lymphovascular invasion. Patient received adjuvant radiation to the site. A year after patient was noted to have bone lesions and other lesions concerning for visceral metastasis on surveillance imaging which were also confirmed to be recurrent MCC by biopsy. Patient was started on immunotherapy afterwards.

Case 2

A 60-year-male patient originally presented with a left inguinal mass. Pathology from the initial biopsy was noted to be small cell neuroendocrine carcinoma of unknown primary. Patient received six cycles of cisplatin and etoposide followed by radiation. Four months later patient was found to have local recurrence and underwent surgical resection, followed by five cycles of cyclophosphamide, doxorubicin, and vincristine. Five months later, the patient had a second recurrence in the surgical bed in addition to multiple subcutaneous nodules in the abdominal wall and lower extremity. A repeat biopsy was performed with Merkel cell polyomavirus testing by immunohistochemistry, which resulted as positive. Patient was started on immunotherapy afterwards.

Discussion

The above two cases represent how Merkel cell carcinoma can have varying presentations either on diagnosis or on progression. Thus, it is important to have a low threshold for biopsy or rebiopsy. Additionally, neuroendocrine carcinomas of unknown primary may benefit from additional Merkel cell IHC testing on diagnosis.

Background

Anal squamous cell carcinoma is a rare cancer which usually has locoregional spread. We report a case of distant metastasis of primary anal squamous cell carcinoma to the posterior mediastinal lymph node without lung involvement.

Case Presentation

A 63-year-old female presented with a painful anal mass, bleeding, and fluid leakage for around six months. The patient was found to have a near-circumferential fungating anal mass with bilateral inguinal lymphadenopathy. MR imaging revealed an 8.7 x 5.9 cm anal mass extending beyond the mesorectal fascia, with lymphadenopathy involving inguinal, pelvic sidewall, and iliac regions. A biopsy of the mass confirmed anal squamous cell carcinoma (ASCC). Initial treatment included diverting colostomy followed by definitive chemoradiotherapy with Mitomycin and 5-Fluorouracil. Colonoscopy post-treatment revealed tubular adenomas and a hyperplastic polyp, with no malignancy detected. The patient demonstrated a strong therapeutic response, with resolution of the anal mass and improved symptoms. However, one year later, new FDG-avid mediastinal lymph node were detected on the CT/PET scan with no pulmonary involvement. Metastatic ASCC of the Mediastinal lymph node was confirmed by biopsy. Salvage chemotherapy with Carboplatin and Paclitaxel every three weeks for six cycles achieved complete resolution of metastases.

Conclusions

This case underscores the importance of a multidisciplinary approach in managing advanced ASCC and highlights the efficacy of salvage chemotherapy in addressing metastases. Close monitoring of disease progression following surgery and chemotherapy is crucial due to the risk of recurrence.

Background

Anal squamous cell carcinoma is a rare cancer which usually has locoregional spread. We report a case of distant metastasis of primary anal squamous cell carcinoma to the posterior mediastinal lymph node without lung involvement.

Case Presentation

A 63-year-old female presented with a painful anal mass, bleeding, and fluid leakage for around six months. The patient was found to have a near-circumferential fungating anal mass with bilateral inguinal lymphadenopathy. MR imaging revealed an 8.7 x 5.9 cm anal mass extending beyond the mesorectal fascia, with lymphadenopathy involving inguinal, pelvic sidewall, and iliac regions. A biopsy of the mass confirmed anal squamous cell carcinoma (ASCC). Initial treatment included diverting colostomy followed by definitive chemoradiotherapy with Mitomycin and 5-Fluorouracil. Colonoscopy post-treatment revealed tubular adenomas and a hyperplastic polyp, with no malignancy detected. The patient demonstrated a strong therapeutic response, with resolution of the anal mass and improved symptoms. However, one year later, new FDG-avid mediastinal lymph node were detected on the CT/PET scan with no pulmonary involvement. Metastatic ASCC of the Mediastinal lymph node was confirmed by biopsy. Salvage chemotherapy with Carboplatin and Paclitaxel every three weeks for six cycles achieved complete resolution of metastases.

Conclusions

This case underscores the importance of a multidisciplinary approach in managing advanced ASCC and highlights the efficacy of salvage chemotherapy in addressing metastases. Close monitoring of disease progression following surgery and chemotherapy is crucial due to the risk of recurrence.

Background

Anal squamous cell carcinoma is a rare cancer which usually has locoregional spread. We report a case of distant metastasis of primary anal squamous cell carcinoma to the posterior mediastinal lymph node without lung involvement.

Case Presentation

A 63-year-old female presented with a painful anal mass, bleeding, and fluid leakage for around six months. The patient was found to have a near-circumferential fungating anal mass with bilateral inguinal lymphadenopathy. MR imaging revealed an 8.7 x 5.9 cm anal mass extending beyond the mesorectal fascia, with lymphadenopathy involving inguinal, pelvic sidewall, and iliac regions. A biopsy of the mass confirmed anal squamous cell carcinoma (ASCC). Initial treatment included diverting colostomy followed by definitive chemoradiotherapy with Mitomycin and 5-Fluorouracil. Colonoscopy post-treatment revealed tubular adenomas and a hyperplastic polyp, with no malignancy detected. The patient demonstrated a strong therapeutic response, with resolution of the anal mass and improved symptoms. However, one year later, new FDG-avid mediastinal lymph node were detected on the CT/PET scan with no pulmonary involvement. Metastatic ASCC of the Mediastinal lymph node was confirmed by biopsy. Salvage chemotherapy with Carboplatin and Paclitaxel every three weeks for six cycles achieved complete resolution of metastases.

Conclusions

This case underscores the importance of a multidisciplinary approach in managing advanced ASCC and highlights the efficacy of salvage chemotherapy in addressing metastases. Close monitoring of disease progression following surgery and chemotherapy is crucial due to the risk of recurrence.

Background

The goal of hospice and palliative care is to provide comfort and dignity for individuals by honoring autonomy and patient preferences at endof- life. These standards can be difficult to balance when concerns around decision-making capacity and safety arise. The Veteran’s Health Administration has numerous resources to support interdisciplinary teams. We present a case study highlighting conflict between these ethical principles

Case Presentation

Veteran is a 66-year-old male with metastatic neuroendocrine cancer to brain and co-occurring polysubstance use disorder. Veteran agreed to VA inpatient hospice due to functional decline and limited social support at home. Day passes were initially allowed but later restricted due to multiple safety concerns surrounding mental status, smoking on campus and unauthorized passes. Behaviors escalated and veteran removed secure care monitor, left the unit without notifying staff, and erratically drove off campus prompting local police involvement.

Discussion

Patient demonstrated a preference to attend Alcoholics Anonymous meetings in person, to use his vehicle and to live at home. Given the complexity of this case, we turned to the National Center for Ethics in Health Care for input. This included guidance about legal and ethical limitations and recommendations for ongoing assessment and documentation of decisionmaking capacity and use of a surrogate.

Results

As veteran’s mental status declined, veteran no longer demonstrated the capacity to understand the safety risks of driving or living at home. His sister served as his health care agent and was opposed to home discharge due to safety concerns. The interdisciplinary team attempted to focus on respecting veteran’s dignity and autonomy as veteran approached end-oflife. Conflicts arose between the ethical pillars of autonomy, non-maleficence, community safety, and legal risks to institution. Lessons learned included the importance of daily safety huddles, ensuring secure care system functions properly, performing ongoing capacity assessments, and improving pre-admission screening.

Conclusions

Balancing autonomy and patient prefpreferences in VA hospice care demands continuous evaluation and adjustment of care plans. Legal and institutional ethics can be consulted to assist providers in formulating optimal plans and to guide use of ethical pillars within the VA framework.

Background

The goal of hospice and palliative care is to provide comfort and dignity for individuals by honoring autonomy and patient preferences at endof- life. These standards can be difficult to balance when concerns around decision-making capacity and safety arise. The Veteran’s Health Administration has numerous resources to support interdisciplinary teams. We present a case study highlighting conflict between these ethical principles

Case Presentation

Veteran is a 66-year-old male with metastatic neuroendocrine cancer to brain and co-occurring polysubstance use disorder. Veteran agreed to VA inpatient hospice due to functional decline and limited social support at home. Day passes were initially allowed but later restricted due to multiple safety concerns surrounding mental status, smoking on campus and unauthorized passes. Behaviors escalated and veteran removed secure care monitor, left the unit without notifying staff, and erratically drove off campus prompting local police involvement.

Discussion

Patient demonstrated a preference to attend Alcoholics Anonymous meetings in person, to use his vehicle and to live at home. Given the complexity of this case, we turned to the National Center for Ethics in Health Care for input. This included guidance about legal and ethical limitations and recommendations for ongoing assessment and documentation of decisionmaking capacity and use of a surrogate.

Results

As veteran’s mental status declined, veteran no longer demonstrated the capacity to understand the safety risks of driving or living at home. His sister served as his health care agent and was opposed to home discharge due to safety concerns. The interdisciplinary team attempted to focus on respecting veteran’s dignity and autonomy as veteran approached end-oflife. Conflicts arose between the ethical pillars of autonomy, non-maleficence, community safety, and legal risks to institution. Lessons learned included the importance of daily safety huddles, ensuring secure care system functions properly, performing ongoing capacity assessments, and improving pre-admission screening.

Conclusions

Balancing autonomy and patient prefpreferences in VA hospice care demands continuous evaluation and adjustment of care plans. Legal and institutional ethics can be consulted to assist providers in formulating optimal plans and to guide use of ethical pillars within the VA framework.

Background

The goal of hospice and palliative care is to provide comfort and dignity for individuals by honoring autonomy and patient preferences at endof- life. These standards can be difficult to balance when concerns around decision-making capacity and safety arise. The Veteran’s Health Administration has numerous resources to support interdisciplinary teams. We present a case study highlighting conflict between these ethical principles

Case Presentation

Veteran is a 66-year-old male with metastatic neuroendocrine cancer to brain and co-occurring polysubstance use disorder. Veteran agreed to VA inpatient hospice due to functional decline and limited social support at home. Day passes were initially allowed but later restricted due to multiple safety concerns surrounding mental status, smoking on campus and unauthorized passes. Behaviors escalated and veteran removed secure care monitor, left the unit without notifying staff, and erratically drove off campus prompting local police involvement.

Discussion

Patient demonstrated a preference to attend Alcoholics Anonymous meetings in person, to use his vehicle and to live at home. Given the complexity of this case, we turned to the National Center for Ethics in Health Care for input. This included guidance about legal and ethical limitations and recommendations for ongoing assessment and documentation of decisionmaking capacity and use of a surrogate.

Results

As veteran’s mental status declined, veteran no longer demonstrated the capacity to understand the safety risks of driving or living at home. His sister served as his health care agent and was opposed to home discharge due to safety concerns. The interdisciplinary team attempted to focus on respecting veteran’s dignity and autonomy as veteran approached end-oflife. Conflicts arose between the ethical pillars of autonomy, non-maleficence, community safety, and legal risks to institution. Lessons learned included the importance of daily safety huddles, ensuring secure care system functions properly, performing ongoing capacity assessments, and improving pre-admission screening.

Conclusions

Balancing autonomy and patient prefpreferences in VA hospice care demands continuous evaluation and adjustment of care plans. Legal and institutional ethics can be consulted to assist providers in formulating optimal plans and to guide use of ethical pillars within the VA framework.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.

Methods

This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.

Results

NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.

Conclusions

Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.

Background

The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.

Methods

This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.

Results

NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.

Conclusions

Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.

Background

The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.

Methods

This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.

Results

NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.

Conclusions

Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.

Background

Germline genetic testing (GGT) is essential in prostate cancer care, informing clinical decisions. The Veterans Affairs National Oncology Program (VA NOP) recommends GGT for patients with specific risk factors in non-metastatic prostate cancer and all patients with metastatic disease. Understanding GGT access helps evaluate care quality and guide improvements. Since 2021, VA NOP has implemented pathway health factor (HF) templates to standardize cancer care documentation, including GGT status, enabling data extraction from the Corporate Data Warehouse (CDW) rather than requiring manual review of clinical notes. This work aims to evaluate Veterans’ access to GGT in prostate cancer care by leveraging pathway HF templates, and to assess the feasibility of using structured electronic health record (EHR) data to monitor adherence to GGT recommendations.

Methods

Process delivery diagrams (PDDs) were used to map data flow from prostate cancer clinical pathways to the VA CDW. We identified and categorized HFs related to prostate cancer GGT through the computerized patient record system (CPRS). Descriptive statistics were used to summarize access, ordering, and consent rates.

Results

We identified 5,744 Veterans with at least one prostate cancer GGT-relevant HF entered between 02/01/2021 and 12/31/2024. Of these, 5,125 (89.2%) had access to GGT, with 4,569 (89.2%) consenting to or having GGT ordered, while 556 (10.8%) declined testing. Among the 619 (10.8%) Veterans without GGT access, providers reported plans to discuss GGT in the future for 528 (85.3%) patients, while 91 (14.7%) were off pathway.

Conclusions

NOP-developed HF templates enabled extraction of GGT information from structured EHR data, eliminating manual extraction from clinical notes. We observed high GGT utilization among Veterans with pathway-entered HFs. However, low overall HF utilization may introduce selection bias. Future work includes developing a Natural Language Processing pipeline using large language models to automatically extract GGT information from clinical notes, with HF data serving as ground truth.

Background

Germline genetic testing (GGT) is essential in prostate cancer care, informing clinical decisions. The Veterans Affairs National Oncology Program (VA NOP) recommends GGT for patients with specific risk factors in non-metastatic prostate cancer and all patients with metastatic disease. Understanding GGT access helps evaluate care quality and guide improvements. Since 2021, VA NOP has implemented pathway health factor (HF) templates to standardize cancer care documentation, including GGT status, enabling data extraction from the Corporate Data Warehouse (CDW) rather than requiring manual review of clinical notes. This work aims to evaluate Veterans’ access to GGT in prostate cancer care by leveraging pathway HF templates, and to assess the feasibility of using structured electronic health record (EHR) data to monitor adherence to GGT recommendations.

Methods

Process delivery diagrams (PDDs) were used to map data flow from prostate cancer clinical pathways to the VA CDW. We identified and categorized HFs related to prostate cancer GGT through the computerized patient record system (CPRS). Descriptive statistics were used to summarize access, ordering, and consent rates.

Results

We identified 5,744 Veterans with at least one prostate cancer GGT-relevant HF entered between 02/01/2021 and 12/31/2024. Of these, 5,125 (89.2%) had access to GGT, with 4,569 (89.2%) consenting to or having GGT ordered, while 556 (10.8%) declined testing. Among the 619 (10.8%) Veterans without GGT access, providers reported plans to discuss GGT in the future for 528 (85.3%) patients, while 91 (14.7%) were off pathway.

Conclusions

NOP-developed HF templates enabled extraction of GGT information from structured EHR data, eliminating manual extraction from clinical notes. We observed high GGT utilization among Veterans with pathway-entered HFs. However, low overall HF utilization may introduce selection bias. Future work includes developing a Natural Language Processing pipeline using large language models to automatically extract GGT information from clinical notes, with HF data serving as ground truth.

Background

Germline genetic testing (GGT) is essential in prostate cancer care, informing clinical decisions. The Veterans Affairs National Oncology Program (VA NOP) recommends GGT for patients with specific risk factors in non-metastatic prostate cancer and all patients with metastatic disease. Understanding GGT access helps evaluate care quality and guide improvements. Since 2021, VA NOP has implemented pathway health factor (HF) templates to standardize cancer care documentation, including GGT status, enabling data extraction from the Corporate Data Warehouse (CDW) rather than requiring manual review of clinical notes. This work aims to evaluate Veterans’ access to GGT in prostate cancer care by leveraging pathway HF templates, and to assess the feasibility of using structured electronic health record (EHR) data to monitor adherence to GGT recommendations.

Methods

Process delivery diagrams (PDDs) were used to map data flow from prostate cancer clinical pathways to the VA CDW. We identified and categorized HFs related to prostate cancer GGT through the computerized patient record system (CPRS). Descriptive statistics were used to summarize access, ordering, and consent rates.

Results

We identified 5,744 Veterans with at least one prostate cancer GGT-relevant HF entered between 02/01/2021 and 12/31/2024. Of these, 5,125 (89.2%) had access to GGT, with 4,569 (89.2%) consenting to or having GGT ordered, while 556 (10.8%) declined testing. Among the 619 (10.8%) Veterans without GGT access, providers reported plans to discuss GGT in the future for 528 (85.3%) patients, while 91 (14.7%) were off pathway.

Conclusions

NOP-developed HF templates enabled extraction of GGT information from structured EHR data, eliminating manual extraction from clinical notes. We observed high GGT utilization among Veterans with pathway-entered HFs. However, low overall HF utilization may introduce selection bias. Future work includes developing a Natural Language Processing pipeline using large language models to automatically extract GGT information from clinical notes, with HF data serving as ground truth.