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Short Story Clubs to Decrease Burnout

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Burnout is common in hematology/oncology practice where work pressure is high, patients are complex, and outcomes are variable. We hypothesized that a short story club could be helpful to improve community, humanism, and transcendence; and thereby to decrease burnout. Most of the potential participants indicated little time for preparation and we, therefore, chose short stories rather than books as reading material. The meetings began in April 2019 and continued until April 2020 when they were suspended for the COVID-19 epidemic. Participants included oncologists (6), oncology fellows (2), psychologist (1), social workers (2), research writer (1) and, student (1). Of these, 7 were females and 6 were males; 4 in senior and 9 in junior positions. Country of origin of participants was USA (6), India (3), Syria (2), Pakistan (1) and, Poland (1). Meetings were held every two months, each time with different stories, focus, themes, and points of view. Readings included classical stories, modern stories, and personal essays, from the eyes of other oncologists, country doctor, patients, nurses, or students. Stories included “The Doctor” by Chekhov, “The Country Doctor” by Kafka, “Three Questions” by Tolstoy, “Elephant Hills” and “Indian Camp” each by Hemingway, “Interpreter of Maladies” by Lahiri, “Get your Own Fatal Disease” by Yalom, “Caves of Lascaux” by Karmel, “The Plagiarist” by Seamon and three essays on “undying,” end-of-life and love. Themes included falling in love with a patient, empathy, loneliness, burnout, communication, helplessness, and end-of-life issues. Discussions lasted two hours and promoted a sense of belonging and community; sharing of feelings and concerns; and transcendence of everyday burdens. Attendance was more than 80% at each meeting and all participants indicated an interest in continuing the club for the foreseeable future. Short story clubs may be one way to overcome or prevent burnout in oncology. Further quantitative and qualitative studies are needed.

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Burnout is common in hematology/oncology practice where work pressure is high, patients are complex, and outcomes are variable. We hypothesized that a short story club could be helpful to improve community, humanism, and transcendence; and thereby to decrease burnout. Most of the potential participants indicated little time for preparation and we, therefore, chose short stories rather than books as reading material. The meetings began in April 2019 and continued until April 2020 when they were suspended for the COVID-19 epidemic. Participants included oncologists (6), oncology fellows (2), psychologist (1), social workers (2), research writer (1) and, student (1). Of these, 7 were females and 6 were males; 4 in senior and 9 in junior positions. Country of origin of participants was USA (6), India (3), Syria (2), Pakistan (1) and, Poland (1). Meetings were held every two months, each time with different stories, focus, themes, and points of view. Readings included classical stories, modern stories, and personal essays, from the eyes of other oncologists, country doctor, patients, nurses, or students. Stories included “The Doctor” by Chekhov, “The Country Doctor” by Kafka, “Three Questions” by Tolstoy, “Elephant Hills” and “Indian Camp” each by Hemingway, “Interpreter of Maladies” by Lahiri, “Get your Own Fatal Disease” by Yalom, “Caves of Lascaux” by Karmel, “The Plagiarist” by Seamon and three essays on “undying,” end-of-life and love. Themes included falling in love with a patient, empathy, loneliness, burnout, communication, helplessness, and end-of-life issues. Discussions lasted two hours and promoted a sense of belonging and community; sharing of feelings and concerns; and transcendence of everyday burdens. Attendance was more than 80% at each meeting and all participants indicated an interest in continuing the club for the foreseeable future. Short story clubs may be one way to overcome or prevent burnout in oncology. Further quantitative and qualitative studies are needed.

Burnout is common in hematology/oncology practice where work pressure is high, patients are complex, and outcomes are variable. We hypothesized that a short story club could be helpful to improve community, humanism, and transcendence; and thereby to decrease burnout. Most of the potential participants indicated little time for preparation and we, therefore, chose short stories rather than books as reading material. The meetings began in April 2019 and continued until April 2020 when they were suspended for the COVID-19 epidemic. Participants included oncologists (6), oncology fellows (2), psychologist (1), social workers (2), research writer (1) and, student (1). Of these, 7 were females and 6 were males; 4 in senior and 9 in junior positions. Country of origin of participants was USA (6), India (3), Syria (2), Pakistan (1) and, Poland (1). Meetings were held every two months, each time with different stories, focus, themes, and points of view. Readings included classical stories, modern stories, and personal essays, from the eyes of other oncologists, country doctor, patients, nurses, or students. Stories included “The Doctor” by Chekhov, “The Country Doctor” by Kafka, “Three Questions” by Tolstoy, “Elephant Hills” and “Indian Camp” each by Hemingway, “Interpreter of Maladies” by Lahiri, “Get your Own Fatal Disease” by Yalom, “Caves of Lascaux” by Karmel, “The Plagiarist” by Seamon and three essays on “undying,” end-of-life and love. Themes included falling in love with a patient, empathy, loneliness, burnout, communication, helplessness, and end-of-life issues. Discussions lasted two hours and promoted a sense of belonging and community; sharing of feelings and concerns; and transcendence of everyday burdens. Attendance was more than 80% at each meeting and all participants indicated an interest in continuing the club for the foreseeable future. Short story clubs may be one way to overcome or prevent burnout in oncology. Further quantitative and qualitative studies are needed.

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Sequential Targeted Treatment of an Elderly Patient With Acute Myeloid Leukemia Harboring Concurrent FLT3-TKD and IDH1 Mutations: A Case Report

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INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.

CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.

CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.

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INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.

CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.

CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.

INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.

CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.

CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.

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Screening Colonoscopy Findings Are Associated With Non-Colorectal Cancer Mortality

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PURPOSE: Examine whether baseline colonoscopy findings are associated with non-Colorectal Cancer (CRC) mortality in a Veteran screening population.

BACKGROUND: Although screening colonoscopy findings are associated with future risk of CRC mortality, whether these findings are also associated with non- CRC mortality remains unknown.

METHODS: The Cooperative Studies Program (CSP) #380 cohort is comprised of 3,121 Veterans age 50-75 who underwent screening colonoscopy from 1994-97. Veterans were followed for 10 years or death, as verified in electronic medical records. Those who died from CRC-specific causes were excluded from this analysis (n=18, 0.6%). Hazard ratios (HR) for risk factors on non-CRC mortality were calculated by Cox Proportional Hazard model, adjusting for demographics, baseline comorbidities, and lifestyle factors. Information on comorbidities, family history, diet, physical activity, and medications were obtained from self-reported questionnaires at baseline.

RESULTS: Of the included 3,103 Veterans, most were male (n=3,021, 96.8%), white (n=2,609, 83.6%), with a mean age of 62.9. During the 10-year follow-up period, 837 (27.0%) Veterans died from non-CRC causes. The risk of non-CRC mortality was higher in Veterans with ≥3 small adenomas (HR 1.45, p=0.02), advanced adenomas (HR 1.34, p=0.04), or CRC (HR 3.00, =0.05) on baseline colonoscopy when compared to Veterans without neoplasia. Additionally, increasing age (HR 1.07, <0.001), modified Charlson score (HR 1.57 for 3-4 points, <0.001, compared to 0-2 points) and current smoking (HR 2.09, <0.001, compared to former and non-smokers) were associated with higher non-CRC mortality. On the other hand, increasing physical activity (HR 0.88, <0.001), family history of CRC (HR 0.75, =0.02), and increased BMI (HR 0.73-0.75, <0.01) were associated with reduced non-CRC mortality. Neither race, NSAID use (including aspirin), or dietary factors impacted non-CRC mortality.

CONCLUSIONS: In a Veteran CRC screening population, we found that high-risk adenomas or CRC on baseline colonoscopy were independently associated with increased non-CRC mortality within 10 years. Future work will examine the cause-specific factors associated with non-CRC mortality in these groups to 1) identify potential high-yield strategies for tailored non-CRC mortality risk reduction during CRC screening, and 2) better determine when competing risks of non-CRC mortality outweigh the benefit of follow up colonoscopy.

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PURPOSE: Examine whether baseline colonoscopy findings are associated with non-Colorectal Cancer (CRC) mortality in a Veteran screening population.

BACKGROUND: Although screening colonoscopy findings are associated with future risk of CRC mortality, whether these findings are also associated with non- CRC mortality remains unknown.

METHODS: The Cooperative Studies Program (CSP) #380 cohort is comprised of 3,121 Veterans age 50-75 who underwent screening colonoscopy from 1994-97. Veterans were followed for 10 years or death, as verified in electronic medical records. Those who died from CRC-specific causes were excluded from this analysis (n=18, 0.6%). Hazard ratios (HR) for risk factors on non-CRC mortality were calculated by Cox Proportional Hazard model, adjusting for demographics, baseline comorbidities, and lifestyle factors. Information on comorbidities, family history, diet, physical activity, and medications were obtained from self-reported questionnaires at baseline.

RESULTS: Of the included 3,103 Veterans, most were male (n=3,021, 96.8%), white (n=2,609, 83.6%), with a mean age of 62.9. During the 10-year follow-up period, 837 (27.0%) Veterans died from non-CRC causes. The risk of non-CRC mortality was higher in Veterans with ≥3 small adenomas (HR 1.45, p=0.02), advanced adenomas (HR 1.34, p=0.04), or CRC (HR 3.00, =0.05) on baseline colonoscopy when compared to Veterans without neoplasia. Additionally, increasing age (HR 1.07, <0.001), modified Charlson score (HR 1.57 for 3-4 points, <0.001, compared to 0-2 points) and current smoking (HR 2.09, <0.001, compared to former and non-smokers) were associated with higher non-CRC mortality. On the other hand, increasing physical activity (HR 0.88, <0.001), family history of CRC (HR 0.75, =0.02), and increased BMI (HR 0.73-0.75, <0.01) were associated with reduced non-CRC mortality. Neither race, NSAID use (including aspirin), or dietary factors impacted non-CRC mortality.

CONCLUSIONS: In a Veteran CRC screening population, we found that high-risk adenomas or CRC on baseline colonoscopy were independently associated with increased non-CRC mortality within 10 years. Future work will examine the cause-specific factors associated with non-CRC mortality in these groups to 1) identify potential high-yield strategies for tailored non-CRC mortality risk reduction during CRC screening, and 2) better determine when competing risks of non-CRC mortality outweigh the benefit of follow up colonoscopy.

PURPOSE: Examine whether baseline colonoscopy findings are associated with non-Colorectal Cancer (CRC) mortality in a Veteran screening population.

BACKGROUND: Although screening colonoscopy findings are associated with future risk of CRC mortality, whether these findings are also associated with non- CRC mortality remains unknown.

METHODS: The Cooperative Studies Program (CSP) #380 cohort is comprised of 3,121 Veterans age 50-75 who underwent screening colonoscopy from 1994-97. Veterans were followed for 10 years or death, as verified in electronic medical records. Those who died from CRC-specific causes were excluded from this analysis (n=18, 0.6%). Hazard ratios (HR) for risk factors on non-CRC mortality were calculated by Cox Proportional Hazard model, adjusting for demographics, baseline comorbidities, and lifestyle factors. Information on comorbidities, family history, diet, physical activity, and medications were obtained from self-reported questionnaires at baseline.

RESULTS: Of the included 3,103 Veterans, most were male (n=3,021, 96.8%), white (n=2,609, 83.6%), with a mean age of 62.9. During the 10-year follow-up period, 837 (27.0%) Veterans died from non-CRC causes. The risk of non-CRC mortality was higher in Veterans with ≥3 small adenomas (HR 1.45, p=0.02), advanced adenomas (HR 1.34, p=0.04), or CRC (HR 3.00, =0.05) on baseline colonoscopy when compared to Veterans without neoplasia. Additionally, increasing age (HR 1.07, <0.001), modified Charlson score (HR 1.57 for 3-4 points, <0.001, compared to 0-2 points) and current smoking (HR 2.09, <0.001, compared to former and non-smokers) were associated with higher non-CRC mortality. On the other hand, increasing physical activity (HR 0.88, <0.001), family history of CRC (HR 0.75, =0.02), and increased BMI (HR 0.73-0.75, <0.01) were associated with reduced non-CRC mortality. Neither race, NSAID use (including aspirin), or dietary factors impacted non-CRC mortality.

CONCLUSIONS: In a Veteran CRC screening population, we found that high-risk adenomas or CRC on baseline colonoscopy were independently associated with increased non-CRC mortality within 10 years. Future work will examine the cause-specific factors associated with non-CRC mortality in these groups to 1) identify potential high-yield strategies for tailored non-CRC mortality risk reduction during CRC screening, and 2) better determine when competing risks of non-CRC mortality outweigh the benefit of follow up colonoscopy.

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Review of Efficacy and Safety Outcomes of Ibrutinib in a Veteran Population with Chronic Lymphocytic Leukemia

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BACKGROUND/RATIONALE: Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent hematologic malignancies that account for one-quarter of all lymphomas primarily affecting older patients. Survival has improved due to the development of novel oral drugs with 85.1% 5-year survival in 2019. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that interferes with malignant B-cell proliferation and survival. The National Comprehensive Cancer Network recommends ibrutinib as a category one treatment recommendation in all settings of CLL including relapsed/refractory disease and adverse cytogenetics. This study aims to improve clinical knowledge of ibrutinib’s efficacy and safety in a Veteran population.

OBJECTIVES: The primary objective was to determine the efficacy of ibrutinib in the Veteran population as defined by progression-free survival. Secondary objectives included overall survival, overall response, duration of therapy, and prevalence of adverse drug reactions.

METHODS: This was a single center, retrospective study conducted at the Southern Arizona VA Health Care System. A retrospective chart review of patients age 18-89 with CLL or SLL treated with ibrutinib between November 1st, 2013 to August 1st, 2019 was conducted. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Descriptive statistics was used for all other endpoints. RESULTS: Twenty-three patients were included in this study. Progression free survival and overall survival at 63 months (5.25 years) was 68.2% and 72.7%, respectively. The average duration of therapy was 20.3 months with 65.2% achieving partial response, 17.3% with stable disease, and 17.3% with progression of disease. The most common adverse events were gastrointestinal (21.7%) and cardiac (17.4%) including 3 patients who developed atrial fibrillation; 34.7% of patients required a dose reduction due to toxicity.

CONCLUSION: Use of ibrutinib in the Veteran population had similar progression-free survival as the clinical trials that led to its approval; however, slightly lower overall survival was noted compared to the clinical trials. The rate of atrial fibrillation was higher in the Veteran population compared to clinical trials, whereas the prevalence of gastrointestinal, dermatologic, neurologic, and musculoskeletal adverse events was consistent with published data.

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BACKGROUND/RATIONALE: Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent hematologic malignancies that account for one-quarter of all lymphomas primarily affecting older patients. Survival has improved due to the development of novel oral drugs with 85.1% 5-year survival in 2019. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that interferes with malignant B-cell proliferation and survival. The National Comprehensive Cancer Network recommends ibrutinib as a category one treatment recommendation in all settings of CLL including relapsed/refractory disease and adverse cytogenetics. This study aims to improve clinical knowledge of ibrutinib’s efficacy and safety in a Veteran population.

OBJECTIVES: The primary objective was to determine the efficacy of ibrutinib in the Veteran population as defined by progression-free survival. Secondary objectives included overall survival, overall response, duration of therapy, and prevalence of adverse drug reactions.

METHODS: This was a single center, retrospective study conducted at the Southern Arizona VA Health Care System. A retrospective chart review of patients age 18-89 with CLL or SLL treated with ibrutinib between November 1st, 2013 to August 1st, 2019 was conducted. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Descriptive statistics was used for all other endpoints. RESULTS: Twenty-three patients were included in this study. Progression free survival and overall survival at 63 months (5.25 years) was 68.2% and 72.7%, respectively. The average duration of therapy was 20.3 months with 65.2% achieving partial response, 17.3% with stable disease, and 17.3% with progression of disease. The most common adverse events were gastrointestinal (21.7%) and cardiac (17.4%) including 3 patients who developed atrial fibrillation; 34.7% of patients required a dose reduction due to toxicity.

CONCLUSION: Use of ibrutinib in the Veteran population had similar progression-free survival as the clinical trials that led to its approval; however, slightly lower overall survival was noted compared to the clinical trials. The rate of atrial fibrillation was higher in the Veteran population compared to clinical trials, whereas the prevalence of gastrointestinal, dermatologic, neurologic, and musculoskeletal adverse events was consistent with published data.

BACKGROUND/RATIONALE: Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent hematologic malignancies that account for one-quarter of all lymphomas primarily affecting older patients. Survival has improved due to the development of novel oral drugs with 85.1% 5-year survival in 2019. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that interferes with malignant B-cell proliferation and survival. The National Comprehensive Cancer Network recommends ibrutinib as a category one treatment recommendation in all settings of CLL including relapsed/refractory disease and adverse cytogenetics. This study aims to improve clinical knowledge of ibrutinib’s efficacy and safety in a Veteran population.

OBJECTIVES: The primary objective was to determine the efficacy of ibrutinib in the Veteran population as defined by progression-free survival. Secondary objectives included overall survival, overall response, duration of therapy, and prevalence of adverse drug reactions.

METHODS: This was a single center, retrospective study conducted at the Southern Arizona VA Health Care System. A retrospective chart review of patients age 18-89 with CLL or SLL treated with ibrutinib between November 1st, 2013 to August 1st, 2019 was conducted. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Descriptive statistics was used for all other endpoints. RESULTS: Twenty-three patients were included in this study. Progression free survival and overall survival at 63 months (5.25 years) was 68.2% and 72.7%, respectively. The average duration of therapy was 20.3 months with 65.2% achieving partial response, 17.3% with stable disease, and 17.3% with progression of disease. The most common adverse events were gastrointestinal (21.7%) and cardiac (17.4%) including 3 patients who developed atrial fibrillation; 34.7% of patients required a dose reduction due to toxicity.

CONCLUSION: Use of ibrutinib in the Veteran population had similar progression-free survival as the clinical trials that led to its approval; however, slightly lower overall survival was noted compared to the clinical trials. The rate of atrial fibrillation was higher in the Veteran population compared to clinical trials, whereas the prevalence of gastrointestinal, dermatologic, neurologic, and musculoskeletal adverse events was consistent with published data.

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Recurrent Transient Dysarthria Due to FOLFIRINOX

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INTRODUCTION: FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) has increased survival rates for pancreatic cancer, but has adverse effects of febrile neutropenia, thrombocytopenia, and neuropathy. Transient dysarthria is a rare adverse effect associated with this regimen. We report a case of transient dysarthria as an isolated adverse effect associated with FOLFIRINOX.

CASE REPORT: A 45-year-old woman with stage 3 pancreatic adenocarcinoma was being treated with neoadjuvant FOLFIRINOX. She developed severe dysarthria and generalized weakness after completing Day 1 of her second cycle. Upon ED evaluation, she was given methylprednisolone and diphenhydramine with complete resolution of symptoms. At 3rd cycle, intravenous atropine was given prior to irinotecan infusion. Eight hours after initiation of the infusion, she developed slowed speech and dysarthria. Her vitals remained stable. On physical exam, she was drowsy and had slowed mentation, with slow and slurred speech. No other focal deficits were identified. Her symptoms resolved on follow up evaluation.

DISCUSSION: Acute cholinergic syndrome is a wellknown side effect associated with irinotecan containing chemotherapy regimens such as FOLFIRINOX. Symptoms include diarrhea, flushing, hypersalivation, lacrimation, abdominal cramping, diaphoresis, visual disturbances, bradycardia and shortness of breath. Self-limiting recurrent dysarthria is a rare adverse effect associated with both irinotecan and oxaliplatin. The exact mechanism contributing to dysarthria is unknown. According to Matsuoka et al, irinotecan is thought to bind to the active site of acetylcholinesterase, resulting in an increased cholinergic response. It is known that among the brainstem nuclei, hypoglossal nerve carries the highest density of cholinergic receptors. Hence irinotecan may cause overstimulation of hypoglossal nerve leading to dysarthria. Oxaliplatin is known to potentiate the cholinergic effects of irinotecan by causing neuronal hyperexcitation. Hence infusion of oxaliplatin prior to irinotecan may make dysarthria more prominent. Infusing irinotecan before oxaliplatin is shown to minimize dysarthria. Atropine is known to work well in preventing acute cholinergic syndrome but has shown mixed results in treating dysarthria. It is reassuring that irinotecan-induced dysarthria is self-limiting, but an increased awareness among physicians is needed so that this adverse effect is not misdiagnosed as a stroke.

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INTRODUCTION: FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) has increased survival rates for pancreatic cancer, but has adverse effects of febrile neutropenia, thrombocytopenia, and neuropathy. Transient dysarthria is a rare adverse effect associated with this regimen. We report a case of transient dysarthria as an isolated adverse effect associated with FOLFIRINOX.

CASE REPORT: A 45-year-old woman with stage 3 pancreatic adenocarcinoma was being treated with neoadjuvant FOLFIRINOX. She developed severe dysarthria and generalized weakness after completing Day 1 of her second cycle. Upon ED evaluation, she was given methylprednisolone and diphenhydramine with complete resolution of symptoms. At 3rd cycle, intravenous atropine was given prior to irinotecan infusion. Eight hours after initiation of the infusion, she developed slowed speech and dysarthria. Her vitals remained stable. On physical exam, she was drowsy and had slowed mentation, with slow and slurred speech. No other focal deficits were identified. Her symptoms resolved on follow up evaluation.

DISCUSSION: Acute cholinergic syndrome is a wellknown side effect associated with irinotecan containing chemotherapy regimens such as FOLFIRINOX. Symptoms include diarrhea, flushing, hypersalivation, lacrimation, abdominal cramping, diaphoresis, visual disturbances, bradycardia and shortness of breath. Self-limiting recurrent dysarthria is a rare adverse effect associated with both irinotecan and oxaliplatin. The exact mechanism contributing to dysarthria is unknown. According to Matsuoka et al, irinotecan is thought to bind to the active site of acetylcholinesterase, resulting in an increased cholinergic response. It is known that among the brainstem nuclei, hypoglossal nerve carries the highest density of cholinergic receptors. Hence irinotecan may cause overstimulation of hypoglossal nerve leading to dysarthria. Oxaliplatin is known to potentiate the cholinergic effects of irinotecan by causing neuronal hyperexcitation. Hence infusion of oxaliplatin prior to irinotecan may make dysarthria more prominent. Infusing irinotecan before oxaliplatin is shown to minimize dysarthria. Atropine is known to work well in preventing acute cholinergic syndrome but has shown mixed results in treating dysarthria. It is reassuring that irinotecan-induced dysarthria is self-limiting, but an increased awareness among physicians is needed so that this adverse effect is not misdiagnosed as a stroke.

INTRODUCTION: FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) has increased survival rates for pancreatic cancer, but has adverse effects of febrile neutropenia, thrombocytopenia, and neuropathy. Transient dysarthria is a rare adverse effect associated with this regimen. We report a case of transient dysarthria as an isolated adverse effect associated with FOLFIRINOX.

CASE REPORT: A 45-year-old woman with stage 3 pancreatic adenocarcinoma was being treated with neoadjuvant FOLFIRINOX. She developed severe dysarthria and generalized weakness after completing Day 1 of her second cycle. Upon ED evaluation, she was given methylprednisolone and diphenhydramine with complete resolution of symptoms. At 3rd cycle, intravenous atropine was given prior to irinotecan infusion. Eight hours after initiation of the infusion, she developed slowed speech and dysarthria. Her vitals remained stable. On physical exam, she was drowsy and had slowed mentation, with slow and slurred speech. No other focal deficits were identified. Her symptoms resolved on follow up evaluation.

DISCUSSION: Acute cholinergic syndrome is a wellknown side effect associated with irinotecan containing chemotherapy regimens such as FOLFIRINOX. Symptoms include diarrhea, flushing, hypersalivation, lacrimation, abdominal cramping, diaphoresis, visual disturbances, bradycardia and shortness of breath. Self-limiting recurrent dysarthria is a rare adverse effect associated with both irinotecan and oxaliplatin. The exact mechanism contributing to dysarthria is unknown. According to Matsuoka et al, irinotecan is thought to bind to the active site of acetylcholinesterase, resulting in an increased cholinergic response. It is known that among the brainstem nuclei, hypoglossal nerve carries the highest density of cholinergic receptors. Hence irinotecan may cause overstimulation of hypoglossal nerve leading to dysarthria. Oxaliplatin is known to potentiate the cholinergic effects of irinotecan by causing neuronal hyperexcitation. Hence infusion of oxaliplatin prior to irinotecan may make dysarthria more prominent. Infusing irinotecan before oxaliplatin is shown to minimize dysarthria. Atropine is known to work well in preventing acute cholinergic syndrome but has shown mixed results in treating dysarthria. It is reassuring that irinotecan-induced dysarthria is self-limiting, but an increased awareness among physicians is needed so that this adverse effect is not misdiagnosed as a stroke.

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Real-World Evidence on Treatment Patterns, Costs and Healthcare Resource Utilization Associated With Waldenström Macroglobulinemia in the Veterans Health Administration Population

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BACKGROUND: Waldenström macroglobulinemia (WM) is a rare, incurable non-Hodgkin Lymphoma. There is limited real-world evidence on WM treatment among US Veterans.

OBJECTIVE: This retrospective observational study aims to evaluate the real-world treatment patterns and associated outcomes among patients with WM in the Veteran Health Administration (VHA) population.

METHODS: Adults who had ≥2 visits with WM diagnosis codes and ≥1 WM treatment were identified in VHA database (2014-2018). Index date was defined as the first date of WM treatment. Patients included were newly diagnosed, initiating treatment, and enrolled continuously for 6 months prior to and ≥60 days following index date. Treatment regimens were categorized as: rituximab monotherapy, ibrutinib-based, chemotherapybased, proteasome inhibitor-based and other regimens. Healthcare resource utilization examined included hospitalization and length-of-stay (LOS). Total costs were calculated as sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM).

RESULTS: Prevalence and incidence of WM among Veterans ranged from 11.4-12.8 cases, and 0.4-1.6 cases per 100,000 persons, respectively. A total of 255 patients (median age: 72 years, 84% white, mean Charlson comorbidity index score: 1.1) received 1st line (mean duration: 289 days); 96 (38%) patients received 2nd line (mean duration: 267 days); and 34 (13%) received 3rd line therapy (mean duration: 253 days). Treatment pattern for each line of therapy were as follows, 1st line: ibrutinib-based (30%), chemotherapy- based (25%), rituximab monotherapy (25%), proteasome inhibitor-based (14%), and other (5%); 2nd line: chemotherapy-based (27%), ibrutinib-based (24%), rituximab monotherapy (23%), proteasome inhibitor- based (15%), and other (9%); 3rd line: ibrutinib- based (41%), rituximab monotherapy (32%), chemotherapy-based (18%), proteasome inhibitorbased (6%), and other (3%). The overall hospitalization rate was 29% with an average LOS of 12 days. Approximately 21% (LOS: 10.9 days), 18% (LOS: 6.9 days), and 24% (LOS: 7.3 days) of patients had a hospitalization, respectively, during 1st, 2nd, and 3rd line therapy. Average total PPPM costs overall were $13,007, and $13,154, $12,550, and $25,813 during 1st, 2nd, and 3rd line therapy, respectively.

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BACKGROUND: Waldenström macroglobulinemia (WM) is a rare, incurable non-Hodgkin Lymphoma. There is limited real-world evidence on WM treatment among US Veterans.

OBJECTIVE: This retrospective observational study aims to evaluate the real-world treatment patterns and associated outcomes among patients with WM in the Veteran Health Administration (VHA) population.

METHODS: Adults who had ≥2 visits with WM diagnosis codes and ≥1 WM treatment were identified in VHA database (2014-2018). Index date was defined as the first date of WM treatment. Patients included were newly diagnosed, initiating treatment, and enrolled continuously for 6 months prior to and ≥60 days following index date. Treatment regimens were categorized as: rituximab monotherapy, ibrutinib-based, chemotherapybased, proteasome inhibitor-based and other regimens. Healthcare resource utilization examined included hospitalization and length-of-stay (LOS). Total costs were calculated as sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM).

RESULTS: Prevalence and incidence of WM among Veterans ranged from 11.4-12.8 cases, and 0.4-1.6 cases per 100,000 persons, respectively. A total of 255 patients (median age: 72 years, 84% white, mean Charlson comorbidity index score: 1.1) received 1st line (mean duration: 289 days); 96 (38%) patients received 2nd line (mean duration: 267 days); and 34 (13%) received 3rd line therapy (mean duration: 253 days). Treatment pattern for each line of therapy were as follows, 1st line: ibrutinib-based (30%), chemotherapy- based (25%), rituximab monotherapy (25%), proteasome inhibitor-based (14%), and other (5%); 2nd line: chemotherapy-based (27%), ibrutinib-based (24%), rituximab monotherapy (23%), proteasome inhibitor- based (15%), and other (9%); 3rd line: ibrutinib- based (41%), rituximab monotherapy (32%), chemotherapy-based (18%), proteasome inhibitorbased (6%), and other (3%). The overall hospitalization rate was 29% with an average LOS of 12 days. Approximately 21% (LOS: 10.9 days), 18% (LOS: 6.9 days), and 24% (LOS: 7.3 days) of patients had a hospitalization, respectively, during 1st, 2nd, and 3rd line therapy. Average total PPPM costs overall were $13,007, and $13,154, $12,550, and $25,813 during 1st, 2nd, and 3rd line therapy, respectively.

BACKGROUND: Waldenström macroglobulinemia (WM) is a rare, incurable non-Hodgkin Lymphoma. There is limited real-world evidence on WM treatment among US Veterans.

OBJECTIVE: This retrospective observational study aims to evaluate the real-world treatment patterns and associated outcomes among patients with WM in the Veteran Health Administration (VHA) population.

METHODS: Adults who had ≥2 visits with WM diagnosis codes and ≥1 WM treatment were identified in VHA database (2014-2018). Index date was defined as the first date of WM treatment. Patients included were newly diagnosed, initiating treatment, and enrolled continuously for 6 months prior to and ≥60 days following index date. Treatment regimens were categorized as: rituximab monotherapy, ibrutinib-based, chemotherapybased, proteasome inhibitor-based and other regimens. Healthcare resource utilization examined included hospitalization and length-of-stay (LOS). Total costs were calculated as sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM).

RESULTS: Prevalence and incidence of WM among Veterans ranged from 11.4-12.8 cases, and 0.4-1.6 cases per 100,000 persons, respectively. A total of 255 patients (median age: 72 years, 84% white, mean Charlson comorbidity index score: 1.1) received 1st line (mean duration: 289 days); 96 (38%) patients received 2nd line (mean duration: 267 days); and 34 (13%) received 3rd line therapy (mean duration: 253 days). Treatment pattern for each line of therapy were as follows, 1st line: ibrutinib-based (30%), chemotherapy- based (25%), rituximab monotherapy (25%), proteasome inhibitor-based (14%), and other (5%); 2nd line: chemotherapy-based (27%), ibrutinib-based (24%), rituximab monotherapy (23%), proteasome inhibitor- based (15%), and other (9%); 3rd line: ibrutinib- based (41%), rituximab monotherapy (32%), chemotherapy-based (18%), proteasome inhibitorbased (6%), and other (3%). The overall hospitalization rate was 29% with an average LOS of 12 days. Approximately 21% (LOS: 10.9 days), 18% (LOS: 6.9 days), and 24% (LOS: 7.3 days) of patients had a hospitalization, respectively, during 1st, 2nd, and 3rd line therapy. Average total PPPM costs overall were $13,007, and $13,154, $12,550, and $25,813 during 1st, 2nd, and 3rd line therapy, respectively.

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Rate of Clinical Trial Enrollment in Patients Treated for DLBCL Within the Veterans Health Administration

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BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is curable in most patients, however this high cure rate is mostly reserved for those who achieve a complete remission with first line treatment. In patients who have relapsed/refractory disease the cure rate is significantly lower. There are limited studies that have previously investigated the rate of clinical trial discussion and enrollment among DLBCL patients. Our aim, as part of a larger study, was to determine the rate of clinical trial enrollment for patients diagnosed with DLBCL at the Veterans Health Administration system (VHA), a population that traditionally experiences poorer outcomes when compared to the community and academic centers.

METHODS: We performed a retrospective chart review of patients diagnosed with DLBCL in the VHA nationwide from 01/01/2011 to 12/31/2017. Patients treated outside of the VHA and patients with primary DLBCL of the CNS were excluded. During our inclusion period, we randomly selected patients and evaluated the number of patients that engaged in discussions with their providers about clinical trials and the number of patients that eventually enrolled in trials.

RESULTS: In total, 721 patients met our inclusion criteria. Median age was 67 and the majority of patients were white (74.5%), male (96.8%), had an ECOG of 2 (83.7%) and presented with advanced stage disease (stage IV: 40.3% and stage III: 26.5%). Of all the patients included in our study 3.7% engaged in discussion about clinical trials and amongst relapsed/ refractory patients (N=182), 12.6% engaged in discussion. The rate of clinical trial enrollment was 1.8% in all patients and 6% in relapsed/refractory patients.

CONCLUSION: Our results show a low rate of 1.8% of DLBCL patients enrolling in clinical trials. These rates are improved but remain low at 6% in relapsed/ refractory patients with only 12.6 % of all relapsed/refractory patients engaging in discussions with their provider about clinical trials, despite NCCN’s recommendation for clinical trial consideration in this subset of DLBCL patients. These results are concerning and show a need to identify and understand the barriers to enrollment in this population in addition to the implementation of mitigation practices.

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BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is curable in most patients, however this high cure rate is mostly reserved for those who achieve a complete remission with first line treatment. In patients who have relapsed/refractory disease the cure rate is significantly lower. There are limited studies that have previously investigated the rate of clinical trial discussion and enrollment among DLBCL patients. Our aim, as part of a larger study, was to determine the rate of clinical trial enrollment for patients diagnosed with DLBCL at the Veterans Health Administration system (VHA), a population that traditionally experiences poorer outcomes when compared to the community and academic centers.

METHODS: We performed a retrospective chart review of patients diagnosed with DLBCL in the VHA nationwide from 01/01/2011 to 12/31/2017. Patients treated outside of the VHA and patients with primary DLBCL of the CNS were excluded. During our inclusion period, we randomly selected patients and evaluated the number of patients that engaged in discussions with their providers about clinical trials and the number of patients that eventually enrolled in trials.

RESULTS: In total, 721 patients met our inclusion criteria. Median age was 67 and the majority of patients were white (74.5%), male (96.8%), had an ECOG of 2 (83.7%) and presented with advanced stage disease (stage IV: 40.3% and stage III: 26.5%). Of all the patients included in our study 3.7% engaged in discussion about clinical trials and amongst relapsed/ refractory patients (N=182), 12.6% engaged in discussion. The rate of clinical trial enrollment was 1.8% in all patients and 6% in relapsed/refractory patients.

CONCLUSION: Our results show a low rate of 1.8% of DLBCL patients enrolling in clinical trials. These rates are improved but remain low at 6% in relapsed/ refractory patients with only 12.6 % of all relapsed/refractory patients engaging in discussions with their provider about clinical trials, despite NCCN’s recommendation for clinical trial consideration in this subset of DLBCL patients. These results are concerning and show a need to identify and understand the barriers to enrollment in this population in addition to the implementation of mitigation practices.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is curable in most patients, however this high cure rate is mostly reserved for those who achieve a complete remission with first line treatment. In patients who have relapsed/refractory disease the cure rate is significantly lower. There are limited studies that have previously investigated the rate of clinical trial discussion and enrollment among DLBCL patients. Our aim, as part of a larger study, was to determine the rate of clinical trial enrollment for patients diagnosed with DLBCL at the Veterans Health Administration system (VHA), a population that traditionally experiences poorer outcomes when compared to the community and academic centers.

METHODS: We performed a retrospective chart review of patients diagnosed with DLBCL in the VHA nationwide from 01/01/2011 to 12/31/2017. Patients treated outside of the VHA and patients with primary DLBCL of the CNS were excluded. During our inclusion period, we randomly selected patients and evaluated the number of patients that engaged in discussions with their providers about clinical trials and the number of patients that eventually enrolled in trials.

RESULTS: In total, 721 patients met our inclusion criteria. Median age was 67 and the majority of patients were white (74.5%), male (96.8%), had an ECOG of 2 (83.7%) and presented with advanced stage disease (stage IV: 40.3% and stage III: 26.5%). Of all the patients included in our study 3.7% engaged in discussion about clinical trials and amongst relapsed/ refractory patients (N=182), 12.6% engaged in discussion. The rate of clinical trial enrollment was 1.8% in all patients and 6% in relapsed/refractory patients.

CONCLUSION: Our results show a low rate of 1.8% of DLBCL patients enrolling in clinical trials. These rates are improved but remain low at 6% in relapsed/ refractory patients with only 12.6 % of all relapsed/refractory patients engaging in discussions with their provider about clinical trials, despite NCCN’s recommendation for clinical trial consideration in this subset of DLBCL patients. These results are concerning and show a need to identify and understand the barriers to enrollment in this population in addition to the implementation of mitigation practices.

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Prostate-Specific Antigen Decline >50% After 4 Weeks of Treatment Is an Indicator of Better Progression Free and Overall Survival Both With Abiraterone and Enzalutamide in Metastatic Castrate Resistant Prostate Cancer

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BACKGROUND: Abiraterone (ABI) and Enzalutamide (ENZA) are the most common medications used for metastatic castrate resistant prostate cancer (mCRPC). Post treatment prostate specific antigen (PSA) changes correlate with prognosis (1). Early PSA decline defined as PSA decline by >50 % at 4 weeks after starting treatment compared to baseline has been demonstrated to corresponds with improved PSA progression-free survival (PSA PFS) and overall survival (OS) (2). Based on our literature review, this relation has not been elucidated previously in the Veteran population.

METHODS: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA from 2011 to 2019 at VA Fresno. Subjects must have received at least 3 months of each drug. The primary outcomes were to document PSAPFS and OS between patients with >50% and <50% decline in PSA at 4 weeks after starting treatment with either ABI or ENZA.

RESULTS: 50 patients were identified who were treated with Abiraterone. 30 (60%) patients had a PSA decrease of 50% or greater in the first 4 weeks. A 50% or greater decrease in PSA at 4 weeks after starting was associated with a better PSA PFS (15 vs 5 months) and better median OS (20.5 vs 12 months). 20 patients were identified treated with Enzalutamide. 13(65%) of patients had a PSA decrease of 50% or greater in the first 4 weeks. A 50% or greater decrease in PSA at 4 weeks was associated with a better PSA PFS (14.5 vs 5 months) and better median OS (20 vs 12 months). 50% of patients in the whole group were diagnosed with metastatic disease at initial diagnosis while the rest were previously treated for localized prostate cancer before being diagnosed as metastatic disease. Most baseline characteristics including, baseline PSA, the modality of initial localized treatment, Gleason score, previous treatment with chemotherapy were similar between the two comparison cohorts (>50% and <50% decrease in PSA after starting treatment with ABI or ENZA).

CONCLUSIONS: Early decrease in PSA is an independent marker for the efficacy of antiandrogen treatment with enzalutamide and abiraterone in metastatic hormone- resistant prostate cancer in the veteran population.

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BACKGROUND: Abiraterone (ABI) and Enzalutamide (ENZA) are the most common medications used for metastatic castrate resistant prostate cancer (mCRPC). Post treatment prostate specific antigen (PSA) changes correlate with prognosis (1). Early PSA decline defined as PSA decline by >50 % at 4 weeks after starting treatment compared to baseline has been demonstrated to corresponds with improved PSA progression-free survival (PSA PFS) and overall survival (OS) (2). Based on our literature review, this relation has not been elucidated previously in the Veteran population.

METHODS: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA from 2011 to 2019 at VA Fresno. Subjects must have received at least 3 months of each drug. The primary outcomes were to document PSAPFS and OS between patients with >50% and <50% decline in PSA at 4 weeks after starting treatment with either ABI or ENZA.

RESULTS: 50 patients were identified who were treated with Abiraterone. 30 (60%) patients had a PSA decrease of 50% or greater in the first 4 weeks. A 50% or greater decrease in PSA at 4 weeks after starting was associated with a better PSA PFS (15 vs 5 months) and better median OS (20.5 vs 12 months). 20 patients were identified treated with Enzalutamide. 13(65%) of patients had a PSA decrease of 50% or greater in the first 4 weeks. A 50% or greater decrease in PSA at 4 weeks was associated with a better PSA PFS (14.5 vs 5 months) and better median OS (20 vs 12 months). 50% of patients in the whole group were diagnosed with metastatic disease at initial diagnosis while the rest were previously treated for localized prostate cancer before being diagnosed as metastatic disease. Most baseline characteristics including, baseline PSA, the modality of initial localized treatment, Gleason score, previous treatment with chemotherapy were similar between the two comparison cohorts (>50% and <50% decrease in PSA after starting treatment with ABI or ENZA).

CONCLUSIONS: Early decrease in PSA is an independent marker for the efficacy of antiandrogen treatment with enzalutamide and abiraterone in metastatic hormone- resistant prostate cancer in the veteran population.

BACKGROUND: Abiraterone (ABI) and Enzalutamide (ENZA) are the most common medications used for metastatic castrate resistant prostate cancer (mCRPC). Post treatment prostate specific antigen (PSA) changes correlate with prognosis (1). Early PSA decline defined as PSA decline by >50 % at 4 weeks after starting treatment compared to baseline has been demonstrated to corresponds with improved PSA progression-free survival (PSA PFS) and overall survival (OS) (2). Based on our literature review, this relation has not been elucidated previously in the Veteran population.

METHODS: A retrospective chart review was conducted in subjects with mCRPC who had received ABI and ENZA from 2011 to 2019 at VA Fresno. Subjects must have received at least 3 months of each drug. The primary outcomes were to document PSAPFS and OS between patients with >50% and <50% decline in PSA at 4 weeks after starting treatment with either ABI or ENZA.

RESULTS: 50 patients were identified who were treated with Abiraterone. 30 (60%) patients had a PSA decrease of 50% or greater in the first 4 weeks. A 50% or greater decrease in PSA at 4 weeks after starting was associated with a better PSA PFS (15 vs 5 months) and better median OS (20.5 vs 12 months). 20 patients were identified treated with Enzalutamide. 13(65%) of patients had a PSA decrease of 50% or greater in the first 4 weeks. A 50% or greater decrease in PSA at 4 weeks was associated with a better PSA PFS (14.5 vs 5 months) and better median OS (20 vs 12 months). 50% of patients in the whole group were diagnosed with metastatic disease at initial diagnosis while the rest were previously treated for localized prostate cancer before being diagnosed as metastatic disease. Most baseline characteristics including, baseline PSA, the modality of initial localized treatment, Gleason score, previous treatment with chemotherapy were similar between the two comparison cohorts (>50% and <50% decrease in PSA after starting treatment with ABI or ENZA).

CONCLUSIONS: Early decrease in PSA is an independent marker for the efficacy of antiandrogen treatment with enzalutamide and abiraterone in metastatic hormone- resistant prostate cancer in the veteran population.

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Prostate Cancer in a Transgender Woman

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INTRODUCTION: As a neoplasm specific to male reproductive anatomy, prostate cancer represents a complex disease experience for transgender women. We present a patient who initiated her male-to-female (MTF) transition amidst a new prostate cancer diagnosis.

CASE REPORT: A 58-year-old male presented with urinary retention and a PSA of 21.53 ng/ml. Prostate biopsy showed a Gleason 4+5 adenocarcinoma with no evidence of metastasis on imaging. The patient underwent radical prostatectomy, which showed seminal vesicle invasion. After surgery, the PSA nadired to 2.5 ng/ml. Salvage radiation and androgen deprivation therapy (ADT) with leuprolide was initiated. ADT-induced physical feminization prompted the patient to begin discussing lifelong gender dysphoria in group therapy. After completing radiation therapy, she opted for bilateral orchiectomy. Shortly thereafter, she started an estradiol patch. Five months later, the PSA level began to rise. Estradiol-induced carcinogenesis due to tumor estrogen receptor (ER) expression versus natural tumor progression was considered, so she underwent a 6-week trial without estradiol. PSA levels continued increasing, and the tumor was found to be ER-negative. Furthermore, the patient suffered psychological and physical side effects from pausing hormonal therapy, so estradiol was restarted. Abiraterone and prednisone were initiated with PSA response (<0.01 ng/ml).

DISCUSSION: To date, there have been ten reported cases of prostate cancer in MTF transgender patients. Prostate cancer management in this population carries unique considerations, such as the possible carcinogenic effect of estrogen. Estradiol, a commonly used hormone in trans female patients, is a ligand for ER-alpha and ER-beta, both of which are implicated in oncogenesis and progression of prostate cancer. ER-alpha expression is associated with higher Gleason score, more advanced disease, and shorter survival. Orchiectomy as an alternative to long-term ADT should be discussed. These patients may also face significant psycho-social challenges such as exacerbation of gender dysphoria by prostate cancer, difficulty engaging with health care providers, and issues with changing gender status in electronic health record. Mental health support, sensitivity to transgender pronouns, and goals-of-care discussions are critical. As gender fluidity becomes more prevalent, physicians need to tailor biopsychosocial cancer care for transgender patients.

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INTRODUCTION: As a neoplasm specific to male reproductive anatomy, prostate cancer represents a complex disease experience for transgender women. We present a patient who initiated her male-to-female (MTF) transition amidst a new prostate cancer diagnosis.

CASE REPORT: A 58-year-old male presented with urinary retention and a PSA of 21.53 ng/ml. Prostate biopsy showed a Gleason 4+5 adenocarcinoma with no evidence of metastasis on imaging. The patient underwent radical prostatectomy, which showed seminal vesicle invasion. After surgery, the PSA nadired to 2.5 ng/ml. Salvage radiation and androgen deprivation therapy (ADT) with leuprolide was initiated. ADT-induced physical feminization prompted the patient to begin discussing lifelong gender dysphoria in group therapy. After completing radiation therapy, she opted for bilateral orchiectomy. Shortly thereafter, she started an estradiol patch. Five months later, the PSA level began to rise. Estradiol-induced carcinogenesis due to tumor estrogen receptor (ER) expression versus natural tumor progression was considered, so she underwent a 6-week trial without estradiol. PSA levels continued increasing, and the tumor was found to be ER-negative. Furthermore, the patient suffered psychological and physical side effects from pausing hormonal therapy, so estradiol was restarted. Abiraterone and prednisone were initiated with PSA response (<0.01 ng/ml).

DISCUSSION: To date, there have been ten reported cases of prostate cancer in MTF transgender patients. Prostate cancer management in this population carries unique considerations, such as the possible carcinogenic effect of estrogen. Estradiol, a commonly used hormone in trans female patients, is a ligand for ER-alpha and ER-beta, both of which are implicated in oncogenesis and progression of prostate cancer. ER-alpha expression is associated with higher Gleason score, more advanced disease, and shorter survival. Orchiectomy as an alternative to long-term ADT should be discussed. These patients may also face significant psycho-social challenges such as exacerbation of gender dysphoria by prostate cancer, difficulty engaging with health care providers, and issues with changing gender status in electronic health record. Mental health support, sensitivity to transgender pronouns, and goals-of-care discussions are critical. As gender fluidity becomes more prevalent, physicians need to tailor biopsychosocial cancer care for transgender patients.

INTRODUCTION: As a neoplasm specific to male reproductive anatomy, prostate cancer represents a complex disease experience for transgender women. We present a patient who initiated her male-to-female (MTF) transition amidst a new prostate cancer diagnosis.

CASE REPORT: A 58-year-old male presented with urinary retention and a PSA of 21.53 ng/ml. Prostate biopsy showed a Gleason 4+5 adenocarcinoma with no evidence of metastasis on imaging. The patient underwent radical prostatectomy, which showed seminal vesicle invasion. After surgery, the PSA nadired to 2.5 ng/ml. Salvage radiation and androgen deprivation therapy (ADT) with leuprolide was initiated. ADT-induced physical feminization prompted the patient to begin discussing lifelong gender dysphoria in group therapy. After completing radiation therapy, she opted for bilateral orchiectomy. Shortly thereafter, she started an estradiol patch. Five months later, the PSA level began to rise. Estradiol-induced carcinogenesis due to tumor estrogen receptor (ER) expression versus natural tumor progression was considered, so she underwent a 6-week trial without estradiol. PSA levels continued increasing, and the tumor was found to be ER-negative. Furthermore, the patient suffered psychological and physical side effects from pausing hormonal therapy, so estradiol was restarted. Abiraterone and prednisone were initiated with PSA response (<0.01 ng/ml).

DISCUSSION: To date, there have been ten reported cases of prostate cancer in MTF transgender patients. Prostate cancer management in this population carries unique considerations, such as the possible carcinogenic effect of estrogen. Estradiol, a commonly used hormone in trans female patients, is a ligand for ER-alpha and ER-beta, both of which are implicated in oncogenesis and progression of prostate cancer. ER-alpha expression is associated with higher Gleason score, more advanced disease, and shorter survival. Orchiectomy as an alternative to long-term ADT should be discussed. These patients may also face significant psycho-social challenges such as exacerbation of gender dysphoria by prostate cancer, difficulty engaging with health care providers, and issues with changing gender status in electronic health record. Mental health support, sensitivity to transgender pronouns, and goals-of-care discussions are critical. As gender fluidity becomes more prevalent, physicians need to tailor biopsychosocial cancer care for transgender patients.

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Primitive Neuroectodermal Tumor of the Pancreas in Adults; A Rare and Aggressive Malignancy

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INTRODUCTION: Primitive neuroectodermal tumors (PNET) are highly aggressive malignancies composed of small round cells that are neuroectodermal in origin similar to Ewings Sarcoma. PNET of the pancreas is extremely rare with around 20 cases reported in literature.

CASE REPORT: A 60-year-old male experienced abdominal pain, appetite loss and weight loss of around 40 pounds for several months. Abdominal CT revealed a pancreatic head mass with a pseudocyst causing gastric outlet obstruction. He underwent an endoscopic ultrasound guided FNA which did not show any evidence of malignancy. An attempted endoscopic drainage of the pseudocyst was unsuccessful. An exploratory laparotomy with en bloc resection of multiple abdominal organs did not provide much benefit as the pseudocyt recurred, leading way for a second limited laparotomy. Pathology was consistent with PNET demonstrating Immunohistochemistry (IHI) positivity for FL1, CD99, Vimentin and synaptophysin and a Ki 67 index of 90%. 6 months into his course, he was hospitalized with sepsis which was believed to be secondary to peritonitis. CT abdomen showed multiple hepatic masses and extensive omental carcinomatosis with free fluid in the abdomen. The infection failed to improve with antibiotics and supportive care. His poor performance status meant systemic therapy or repeat surgery was not an option. It was believed that his worsening clinical status was due to his enormous intra-abdominal tumor burden. He eventually decided to become comfort care and proceed with hospice.

DISCUSSION: Histopathology, IHI and genetic analysis are essential in the diagnosis of PNET of the pancreas, as other pancreatic mesenchymal and neuroendocrine tumors, pancreatoblastomas and lymphomas are differentials. PNET generally express the MIC2 protein (CD99), vimentin and 85-95% of the times, have the translocation resulting in the EWS-FLI1 fusion product. Abdominal pain, jaundice, dyspepsia and vomiting are the usual presenting symptoms with the head of the pancreas being the most common location. Multi-agent regimes like cyclophosphamide, adriamycin, and vincristine or neoadjuvant vincristine, dactinomycin, adriamycin, cyclophosphamide, ifosfamide and etoposide have been used with limited success This can be combined with surgery and radiation, but the prognosis remains to be poor. Thus, more research is needed to better manage this morbid malignancy.

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Correspondence: Ashok Kumar ([email protected])

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Correspondence: Ashok Kumar ([email protected])

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Correspondence: Ashok Kumar ([email protected])

INTRODUCTION: Primitive neuroectodermal tumors (PNET) are highly aggressive malignancies composed of small round cells that are neuroectodermal in origin similar to Ewings Sarcoma. PNET of the pancreas is extremely rare with around 20 cases reported in literature.

CASE REPORT: A 60-year-old male experienced abdominal pain, appetite loss and weight loss of around 40 pounds for several months. Abdominal CT revealed a pancreatic head mass with a pseudocyst causing gastric outlet obstruction. He underwent an endoscopic ultrasound guided FNA which did not show any evidence of malignancy. An attempted endoscopic drainage of the pseudocyst was unsuccessful. An exploratory laparotomy with en bloc resection of multiple abdominal organs did not provide much benefit as the pseudocyt recurred, leading way for a second limited laparotomy. Pathology was consistent with PNET demonstrating Immunohistochemistry (IHI) positivity for FL1, CD99, Vimentin and synaptophysin and a Ki 67 index of 90%. 6 months into his course, he was hospitalized with sepsis which was believed to be secondary to peritonitis. CT abdomen showed multiple hepatic masses and extensive omental carcinomatosis with free fluid in the abdomen. The infection failed to improve with antibiotics and supportive care. His poor performance status meant systemic therapy or repeat surgery was not an option. It was believed that his worsening clinical status was due to his enormous intra-abdominal tumor burden. He eventually decided to become comfort care and proceed with hospice.

DISCUSSION: Histopathology, IHI and genetic analysis are essential in the diagnosis of PNET of the pancreas, as other pancreatic mesenchymal and neuroendocrine tumors, pancreatoblastomas and lymphomas are differentials. PNET generally express the MIC2 protein (CD99), vimentin and 85-95% of the times, have the translocation resulting in the EWS-FLI1 fusion product. Abdominal pain, jaundice, dyspepsia and vomiting are the usual presenting symptoms with the head of the pancreas being the most common location. Multi-agent regimes like cyclophosphamide, adriamycin, and vincristine or neoadjuvant vincristine, dactinomycin, adriamycin, cyclophosphamide, ifosfamide and etoposide have been used with limited success This can be combined with surgery and radiation, but the prognosis remains to be poor. Thus, more research is needed to better manage this morbid malignancy.

INTRODUCTION: Primitive neuroectodermal tumors (PNET) are highly aggressive malignancies composed of small round cells that are neuroectodermal in origin similar to Ewings Sarcoma. PNET of the pancreas is extremely rare with around 20 cases reported in literature.

CASE REPORT: A 60-year-old male experienced abdominal pain, appetite loss and weight loss of around 40 pounds for several months. Abdominal CT revealed a pancreatic head mass with a pseudocyst causing gastric outlet obstruction. He underwent an endoscopic ultrasound guided FNA which did not show any evidence of malignancy. An attempted endoscopic drainage of the pseudocyst was unsuccessful. An exploratory laparotomy with en bloc resection of multiple abdominal organs did not provide much benefit as the pseudocyt recurred, leading way for a second limited laparotomy. Pathology was consistent with PNET demonstrating Immunohistochemistry (IHI) positivity for FL1, CD99, Vimentin and synaptophysin and a Ki 67 index of 90%. 6 months into his course, he was hospitalized with sepsis which was believed to be secondary to peritonitis. CT abdomen showed multiple hepatic masses and extensive omental carcinomatosis with free fluid in the abdomen. The infection failed to improve with antibiotics and supportive care. His poor performance status meant systemic therapy or repeat surgery was not an option. It was believed that his worsening clinical status was due to his enormous intra-abdominal tumor burden. He eventually decided to become comfort care and proceed with hospice.

DISCUSSION: Histopathology, IHI and genetic analysis are essential in the diagnosis of PNET of the pancreas, as other pancreatic mesenchymal and neuroendocrine tumors, pancreatoblastomas and lymphomas are differentials. PNET generally express the MIC2 protein (CD99), vimentin and 85-95% of the times, have the translocation resulting in the EWS-FLI1 fusion product. Abdominal pain, jaundice, dyspepsia and vomiting are the usual presenting symptoms with the head of the pancreas being the most common location. Multi-agent regimes like cyclophosphamide, adriamycin, and vincristine or neoadjuvant vincristine, dactinomycin, adriamycin, cyclophosphamide, ifosfamide and etoposide have been used with limited success This can be combined with surgery and radiation, but the prognosis remains to be poor. Thus, more research is needed to better manage this morbid malignancy.

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