Inpatient utilization of immune checkpoint inhibitors and clinical outcomes.

INTRODUCTION: Retrospective studies have suggested that patients with poor performance status treated with immune checkpoint inhibitors have shorter overall survival and poorer response rates. This study was undertaken to investigate the possible relationships between inpatient immune checkpoint inhibitor use and clinical outcomes. METHODS: This was a retrospective chart review of cancer patients who received an immune checkpoint inhibitor while hospitalized from 1 January 2016 to 30 December 2020. The primary outcome was 90-day mortality or admission to hospice rate. Secondary outcomes included overall survival, time to death or discharge to hospice, and descriptive summarization of patient characteristics. RESULTS: A total of 52 patients were analyzed. At 90 days, 68.2% of subjects were expired or admitted to hospice (95% CI: 54.7-81%). 90-day overall survival was 47.1%; median survival time was 81 days (95% CI: 28-242 days). The median time to death or hospice was 35 days (95% CI: 24-72 days). The time to death or hospice was shorter for immune checkpoint inhibitor-naive patients compared to those who received immune checkpoint inhibitors prior to admission (29 days, 95% CI: 12-43 days vs. 242 days, 95% CI: 36-1288 days, respectively; HR: 2.74, 95% CI: 1.2-6.25; p = 0.0121). No differences were found when comparing other baseline characteristics. CONCLUSION: A majority of patients who received an immune checkpoint inhibitor while hospitalized were either discharged to hospice or expired by 90 days. An increased rate of death or discharge to hospice was observed for patients who were immune checkpoint inhibitor-naive prior to their admission.

The effect of somatostatin analogs on vitamin D and calcium concentrations in patients with acromegaly.

PURPOSE: The goals of this study were to determine: (1) 25OH vitamin D (25OHD) and calcium levels in patients with acromegaly and their association with insulin-like growth factor (IGF-1) and (2) whether somatostatin analog (SSA) therapy effects calcium and 25OHD levels. METHODS: 125 patients with acromegaly were studied. Serum calcium and 25OHD levels were compared prior to and after vitamin D supplementation between patients receiving versus not receiving SSA in whom medical therapy included pegvisomant and/or dopamine agonists. Calcium and 25OHD levels were also evaluated longitudinally prior to and during short-term (mean 3 months, range 1-5) and long-term (mean 49 months, range 7-180) SSA administration. Vitamin D2 50,000 units weekly were given to 3 patients in the cross sectional and 1 in the longitudinal group; 400-4,000 units/day of D3 were given to 11 and 5 in respective groups. RESULTS: In patients with a comparable mean IGF-1 index and season of testing, mean serum levels of 25OHD prior to vitamin D supplementation did not differ in patients receiving versus not receiving SSA (30 ± 3 vs. 30 ± 1 ng/ml, p = 0.99) and the prevalence of vitamin D sufficiency was similar between SSA and non SSA groups (42 vs. 57%, p = 0.20), prior to vitamin D supplementation. In patients with a comparable mean IGF-1 index and season of testing, mean serum 25OHD levels in patients increased after vitamin D supplementation in both those who were (37 ± 2 ng/ml, N = 23, p = 0.007) and were not receiving SSA (35 ± 1 ng/ml, N = 69, p = 0.005) compared to pre-D supplementation levels but were not different between these groups, p = 0.95) after D supplementation. Calcium and albumin were normal throughout longitudinal follow up. Calcium correlated with IGF-1 index (ρ = 0.29, p = 0.001, N = 125). In the longitudinal subset, serum calcium decreased transiently, in patients receiving short-term SSA (pretreatment 9.9 ± 0.1 mg/dl vs. short-term SSA 9.5 ± 0.1, p = 0.004). After long-term SSA therapy, calcium increased compared to levels on short-term therapy (9.8 ± 0.1 mg/dl vs. 9.5 ± 0.1, p = 0.017) and were unchanged compared to baseline. Mean vitamin D levels were sufficient at baseline prior to SSA therapy (33 ± 5.0 ng/ml), and did not change during short term (29 ± 6 ng/ml, p = 0.85) and long term SSA therapy (35 ± 5 ng/ml, p = 0.43). CONCLUSIONS: Prior to and after vitamin D supplementation, patients with acromegaly receiving long-term SSA had vitamin D levels similar to those receiving other therapies, suggesting that long-term SSA therapy does not affect serum vitamin D. However, given the limitations of this retrospective study, further prospective studies evaluating the impact of SSA on vitamin D levels are necessary to confirm these findings definitively. Calcium levels are positively associated with IGF-1 index in patients with acromegaly. There is a transient decrease in calcium levels with short-term SSA use. The acute effect of SSA on calcium does not appear to be mediated by albumin, 25OHD or PTH and resolves with long-term SSA treatment. The transient decrease in calcium with short-term SSA use resolved with long-term SSA therapy.

HIV Associated Lung Cancer: Unique Clinicopathologic Features and Immune Biomarkers Impacting Lung Cancer Screening and Management.

OBJECTIVES: Lung cancer contributes significantly to morbidity and mortality in people with HIV (PWH). We study the clinicopathologic characteristics and immune microenvironment in HIV associated lung cancer. MATERIAL AND METHODS: Clinicopathological characteristics including immunotherapy outcomes were collected for 174 PWH diagnosed with lung cancer. Immunohistochemical staining for PD-L1, CD4, and CD8 was performed. RESULTS: At diagnosis, patients with HIV associated lung cancer were significantly younger (56.9 vs. 69 years, P < .0001) and more frequently had advanced disease (70% vs. 53%, P = .01). The majority were African American (60% vs. 42%, P < .0001) and were smoking at the time of diagnosis or smoked in the past (98% vs. 86%, P = .0001). Only 10% of HIV associated lung cancer was diagnosed through the screening program. The median CD4+ lymphocyte count was 334 cells/µL, 31% had a CD4 ≤200 cells/µL and 63% of the cohort was virally suppressed. HIV associated non-small-cell lung cancer(NSCLC) was characterized by limited PD-L1 expression compared to the HIV negative cohort, 64% vs. 31% had TPS <1%, and 20% vs. 34% had TPS≥50%, respectively (P = .04). Higher CD8+ TILs were detected in PD-L1-high tumors (P < .0001). 50% of patients achieved disease control in the metastatic setting with the use of immunotherapy, and there were no new safety signals in 19 PWH treated with immunotherapy. CONCLUSION: Lung cancer in PWH demonstrates unique features highlighting the need for a specialized screening program. Despite low PD-L1 expression, immunotherapy is well tolerated with reasonable disease control. Altered immune system in lung cancer pathogenesis in PWH should be further investigated.

Feasibility and safety of targeting the anterior superior iliac spine to perform a bone marrow procedure: a prospective, clinical study.

AIMS: The bone marrow procedure (BMP) has been performed worldwide for years. Nonetheless, no generally accepted standards or guidelines for the performance of the BMP exist. Recent studies suggested that the lateral angulation technique (LAT), targeting the anterior superior iliac spine (ASIS) after penetration of the posterior superior iliac spine, yields longer biopsy cores and is safer for patients. We assessed the feasibility and safety of targeting the ASIS in the prone and lateral decubitus positions. METHODS: We first observed the BMP needle tracks on cadavers. Our cadaver study revealed that the LAT is feasible and safe but requires different operator techniques. Next, we studied 25 adult haematology patients undergoing elective BMP via the LAT approach. Patients returned 5 days after the BMP for a haemoglobin assessment, pain questionnaire and low-dose non-contract CT. RESULTS: 8% of patients reported persistent pain. No fall in haemoglobin and no pelvic haematomas or neurovascular injuries were detected. 88% of BMPs were successfully accomplished by targeting the ASIS. 12% required a back-up traditional angulation technique (TAT), directing the needle straight in, perpendicular to the coronal plane of the back. All three demonstrated inadvertent, but asymptomatic, penetration of the sacrum. Biopsy lengths were compared with a historical TAT control demonstrating that specimens obtained by LAT are significantly longer. Imaging studies showed that a seven-degree change in needle direction can convert a TAT to a LAT. CONCLUSION: The LAT approach is feasible, safe and more productive than the TAT, and may be the preferred standard for training haematologists. TRIAL REGISTRATION NUMBER: NCT02524613.

Targeting the anterior superior iliac spine yields significantly longer bone marrow cores.

Pathologists and haematologists generally agree that the length of the biopsy core is a good surrogate for the diagnostic quality of the bone marrow. Previous studies suggested that the angulation of the biopsy needle from the posterior superior iliac spine (PSIS) could influence the length of the biopsy cores, targeting the anterior superior iliac spine (ASIS) from the PSIS would yield longer specimens than the traditional angulation technique (TAT), where the biopsy needle is directed straight in, perpendicular to the plane of the back. Twenty five adult haematology patients were prospectively recruited by haematologists-in-training (HITs), who were trained to target the ASIS using a lateral angulationtechnique (LAT). The mean length of biopsy cores was 16 mm and that was significantly longer (p=0.003) than a comparable group of bone marrow biopsies previously obtained by HITs using the TAT approach. These results support the LAT as a new standard of haematology practice. TRIAL REGISTRATION NUMBER: NCT 02524613.

Emerging uses of biomarkers in lung cancer management: molecular mechanisms of resistance.

Management of patients with advanced non-small cell lung cancer (NSCLC) has recently been transformed by molecularly targeted and immunotherapeutic agents. In patients with EGFR/ALK/ROS mutated NSCLC, first line molecular therapy is the standard of care. Moreover, immune checkpoint inhibitors are revolutionary treatment options for advanced NSCLC and are now the standard of care in front-line or later line settings. Both classes of agents have led to improved patient outcomes, however, primary resistance and development of acquired resistance to both targeted and immunotherapeutic agents is commonly observed, limiting the use of these agents in clinical settings. In this review, we will discuss the most recent advances in understanding the mechanisms of primary and acquired resistance, progress in the spectrum of assays detecting causative molecular events and the development of new generations of inhibitors to overcome acquired resistance.

Effects of hemin and hemodialysis in a patient with acute intermittent porphyria and renal failure.

Hemin and hemodialysis had an additive effect in decreasing ALA and PBG in our patient with acute intermittent porphyria and renal failure.The time course of ALA and PBG reaccumulation after hemodialysis is not known.

Alemtuzumab induced ST-segment elevation and acute myocardial dysfunction.

Cardiac toxicity as a side effect of chemotherapeutic agents has been well reported in the literature. Cardiac toxicity secondary to alemtuzumab has been reported, presenting as congestive heart failure and arrhythmias. Here we report a case of acute myocardial dysfunction after administration of a test dose of alemtuzumab. Our patient was a 66-year-old man with a history of small lymphocytic lymphoma/chronic lymphocytic lymphoma who received a test dose of alemtuzumab. Twenty minutes post administration, the patient developed nausea, vomiting, rigors, and tachycardia. Electrocardiography (ECG) showed acute ST-segment elevations in contiguous leads V2-V6, I, and AVL with no associated chest pain. Bedside echocardiogram showed akinesis of the anterior septum, apex, distal anterior wall, and decreased left ventricular ejection fraction. Cardiac catheterization showed non-critical occlusive disease and no intervention was undertaken. Post-catheterization ECG revealed resolution of ST segment elevations, TWI in V4-V6, and prolongation of corrected QT. Repeat echocardiogram 10 days after the event demonstrated no improvement in wall motion or ejection fraction. We discuss the possible mechanisms causing ST-elevations and acute myocardial dysfunction after treatment with alemtuzumab. .

Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report.

INTRODUCTION: Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH)2D3 from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma. CASE PRESENTATION: An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide. CONCLUSION: Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH)2D3 can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.