Characterizing after-hours hematology/oncology clinic calls.

BACKGROUND: After-hour calls can be resource intensive and remain a significant challenge to medical practices, though they have historically been poorly or non-reimbursable services. This study reviews after-hour calls from hematology/oncology patients at a cancer center to characterize after-hour care needs, identify care gaps, and look for opportunities to improve outpatient healthcare delivery. METHODS: This descriptive, retrospective Institutional Review Board-approved study analyzed patient calls between June 2015 to February 2021 in an academic hematology/oncology practice. Data from 500 calls were reviewed and cataloged into a database including patient demographics, clinical history, and information surrounding the call (e.g., primary reason for the call, outcome of the call). Calls were also categorized as being urgent or not from a patient or provider's perspective. RESULTS: Among 500 calls, representing 398 unique patients, the average patient was 62 years old and 52% of calls were from females. Most calls were made to report symptoms (65%), followed by calls to follow-up on labs, tests, or imaging (13%), and clarifying treatment plans (10%). Oncology patients represented 67% of calls and hematology (malignant and benign) patients represented 33%. More specifically, patients with gastrointestinal cancer (25%), hematologic malignancies (24%), and thoracic cancer (13%) represented the diagnoses with the highest call volume. CONCLUSIONS: This study explores the complexity and variety of after-hour cancer patient calls. By systematically exploring patient calls, this data can provide insight into patients' needs outside of regular clinic times and help practices develop strategies to anticipate these needs, reduce after-hour call burden, and improve overall quality of care.

Hodgkin Lymphoma: A disease shaped by the tumor micro- and macroenvironment.

The tumor microenvironment (TMicroE) and tumor macroenvironment (TMacroE) are defining features of classical Hodgkin lymphoma (cHL). They are of critical importance to clinicians since they explain the common signs and symptoms, allow us to classify these neoplasms, develop prognostic and predictive biomarkers, bioimaging and novel treatments. The TMicroE is defined by effects of cancer cells to their immediate surrounding and within the tumor. Effects of cancer cells at a distance or outside of the tumor define the TMacroE. Paraneoplastic syndromes are signs and symptoms due to effects of cancer at a distance or the TMacroE, which are not due to direct cancer cell infiltration. The most common paraneoplastic symptoms are B-symptoms, which manifest as fevers, chills, drenching night sweats, and/or weight loss. Less common paraneoplastic syndromes include those that affect the central nervous system, skin, kidney, and hematological autoimmune phenomena including hemophagocytic lymphohistiocytosis (HLH). Paraneoplastic signs such as leukocytosis, lymphopenia, anemia, and hypoalbuminemia are prognostic biomarkers. The neoplastic cells in cHL are the Hodgkin and Reed Sternberg (HRS) cells, which are preapoptotic germinal center B cells with a high mutational burden and almost universal genetic alterations at the 9p24.1 locus primarily through copy gain and amplification with strong activation of signaling via PD-L1, JAK-STAT, NFkB, and c-MYC. In the majority of cases of cHL over 95% of the tumor cells are non-neoplastic. In the TMicroE, HRS cells recruit and mold non-neoplastic cells vigorously via extracellular vesicles, chemokines, cytokines and growth factors such as CCL5, CCL17, IL6, and TGF-ß to promote a feed-forward inflammatory loop, which drives cancer aggressiveness and anti-cancer immune evasion. Novel single cell profiling techniques provide critical information on the role in cHL of monocytes-macrophages, neutrophils, T helper, Tregs, cytotoxic CD8+ T cells, eosinophils, mast cells and fibroblasts. Here, we summarize the effects of EBV on the TMicroE and TMacroE. In addition, how the metabolism of the TMicroE of cHL affects bioimaging and contributes to cancer aggressiveness is reviewed. Finally, we discuss how the TMicroE is being leveraged for risk adapted treatment strategies based on bioimaging results and novel immune therapies. In sum, it is clear that we cannot effectively manage patients with cHL without understanding the TMicroE and TMacroE and its clinical importance is expected to continue to grow rapidly.

Predictors of Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation Followed by Consolidative Durvalumab.

Purpose: In patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), the standard of care is concurrent chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab. Pneumonitis is a known adverse event of both radiation therapy and immune checkpoint inhibitors such as durvalumab. We sought to characterize pneumonitis rates and dosimetric predictors of pneumonitis in a real-world population of patients with NSCLC treated with definitive CRT followed by consolidative durvalumab. Methods and Materials: Patients with NSCLC from a single institution who were treated with definitive CRT followed by consolidative durvalumab were identified. Outcomes of interest included pneumonitis incidence, type of pneumonitis, progression-free survival, and overall survival. Results: Sixty-two patients were included in our data set treated from 2018 to 2021 with a median follow-up of 17 months. The rate of grade 2+ pneumonitis in our cohort was 32.3%, and the rate of grade 3+ pneumonitis was 9.7%. Lung dosimetry parameters including V20 ≥30% and mean lung dose (MLD) >18 Gy were found to be correlated with increased rates of grade 2+ and grade 3+ pneumonitis. Patients with a lung V20 ≥30% had a grade 2+ pneumonitis rate at 1 year of 49.8% compared with 17.8% in patients with a lung V20 <30% (P = .015). Similarly, patients with an MLD >18 Gy had a grade 2+ pneumonitis rate at 1 year of 52.4% compared with 25.8% in patients with an MLD ≤18 Gy (P = .01). Moreover, heart dosimetry parameters including mean heart dose ≥10 Gy were found to be correlated with increased rates of grade 2+ pneumonitis. The estimated 1-year overall survival and progression-free survival of our cohort were 86.8% and 64.1%, respectively. Conclusions: The modern management of locally advanced, unresectable NSCLC involves definitive chemoradiation followed by consolidative durvalumab. Pneumonitis rates were higher than expected in this cohort, particularly for patients with a lung V20 ≥30%, MLD >18 Gy, and mean heart dose ≥10 Gy, suggesting that more stringent radiation planning dose constraints may be needed.

Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.

Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.

Seroconversion and outcomes after initial and booster COVID-19 vaccination in adults with hematologic malignancies.

BACKGROUND: Patients with hematologic malignancies have impaired humoral immunity secondary to their malignancy and its treatment, placing them at risk of severe coronavirus disease-19 (COVID-19) infection and reduced response to vaccination. METHODS: The authors retrospectively analyzed serologic responses to initial and booster COVID-19 vaccination in 378 patients with hematologic malignancy and subsequently tracked COVID-19-related outcomes. RESULTS: Seroconversion occurred in 181 patients (48%) after initial vaccination; patients who had active malignancy or those who were recently treated with a B-cell-depleting monoclonal antibody had the lowest rates of seroconversion. For initial nonresponders to vaccination, seroconversion after a booster dose occurred in 48 of 85 patients (56%). The seroconversion rate after the booster was similar for patients on (53%) and off (58%) active therapy (p = .82). Thirty-three patients (8.8%) developed a COVID-19 infection, and there were three COVID-19-related deaths (0.8%). Although no significant association was observed between postvaccination seroconversion and the incidence of COVID-19 infection, no patient with seroconversion died from COVID-19, and no patient who received tixagevimab/cilgavimab (N = 25) was diagnosed with a COVID-19 infection. CONCLUSIONS: Booster vaccinations can promote seroconversion in a significant proportion of patients who are seronegative after the initial vaccination course regardless of the specific vaccine or on/off treatment status at the time of revaccination. Although postvaccination seroconversion may not be associated with a decrease in any (including asymptomatic) COVID-19 infection, the authors' experience suggested that effective vaccination (including a booster), supplemented by passive immunization using tixagevimab/cilgavimab in case of lack of seroconversion, effectively eliminated the risk of COVID-19 death in the otherwise high-risk population. LAY SUMMARY: Patients with hematologic malignancy, especially lymphoma, have an impaired response to coronavirus disease 2019 (COVID-19) vaccination. In this single-institution review, less than one half of the patients studied made detectable antibodies. For those who did not make detectable antibodies after initial vaccination, over one half (65%) were able to produce antibodies after booster vaccination. By the end of February 2022, 33 of the original 378 patients had a documented COVID-19 infection. The only deaths from COVID-19 were in those who had undetectable antibodies, and no patient who received prophylactic antibody therapy developed a COVID-19 infection.

Treatment-induced sarcoidosis in a patient with metastatic clear cell ovarian cancer.

Sarcoidosis is a granulomatous disease that commonly presents with lung or lymphatic system manifestations. Diagnosis is often delayed due to variable clinical presentation. This is a case of a patient with metastatic clear cell ovarian cancer who developed disease reoccurence after definitive treatment with surgery and adjuvant chemotherapy. She was treated with multiple lines of therapy, including investigational agents. During this time, she developed mediastinal lymphadenopathy and hypercalcaemia. Due to suspicion that her presentation was not a manifestation of her malignancy, she underwent two lymph node biopsies revealing granulomatous disease. She was initiated on prednisone for management of sarcoidosis, which led to radiologic, laboratory and symptomatic improvement. Although the precipitating factor for this patient's sarcoidosis cannot be definitively determined, nivolumab is a possible culprit. This case highlights the importance of a broad differential diagnosis when a patient undergoing antineoplastic treatment develops mediastinal lymphadenopathy or hypercalcaemia.

A 34-Year-Old Woman with Third-Degree Heart Block and Atrial Flutter Associated with Lyme Carditis: A Case Report.

BACKGROUND Lyme disease is a tick-borne illness caused by bacteria of the Borrelia genus, endemic to the northeastern region of the United States. It typically presents with fevers, myalgias, and erythema migrans, but it can result in disseminated symptoms if left untreated. Lyme carditis is a rare, but potentially fatal complication of Lyme disease, occurring in up to 4-10% of untreated cases. Typically, it presents with atrioventricular conduction abnormalities, which resolve with intravenous antibiotics and temporary pacing if indicated. Diverse cardiac pathology, however, has been associated with Lyme carditis, which may be underrecognized in practice. CASE REPORT A 34-year-old woman with no significant medical history presented with fatigue, dizziness, and shortness of breath, 2 weeks after camping in Rhode Island. Her presenting electrocardiogram demonstrated third-degree heart block. She was noted to have targetoid rashes on her left shoulder and breast on physical examination. On laboratory work-up, she was found to have positive Lyme total antibody enzyme immunoassay and positive Lyme western immunoblot. The findings were diagnostic for Lyme carditis. The patient's cardiac rhythm subsequently converted to slow atrial flutter with variable ventricular response unresponsive to antibiotic therapy. Given evidence suggesting that atrioventricular conduction was preserved, synchronized electrical cardioversion was pursued and was ultimately successful in rhythm conversion to normal sinus rhythm. CONCLUSIONS Although Lyme carditis is rare, this diagnosis should be of high clinical consideration in presentations of cardiac conduction abnormalities with acute onset and without other obvious cause, particularly in Lyme-endemic regions such as the northeastern United States.

A Case of Multiple Organ Disseminated Cryptococcosis.

Cryptococcus neoformans is an encapsulated yeast found worldwide.1 Patients with immunosuppression, including individuals with HIV/AIDS, transplant recipients and/or individuals with other T-cell mediated immunosuppression are more susceptible to becoming infected with Cryptococcus neoformans than immunocompetent individuals.2 This is a case report of a 66-year-old woman who presented to the emergency department with an unsteady gait and urinary incontinence. Magnetic resonance imaging (MRI) on presentation showed a large C5-C6 central disc protrusion. The patient underwent surgical repair and was treated with five days of IV steroids. Later in the course of her hospitalization, she had an unexplained increasing leukocytosis and tachycardia with witnessed episodes of unresponsiveness. She subsequently had a pulseless electrical activity cardiac arrest and succumbed despite resuscitative efforts. A post-mortem diagnosis revealed Cryptococcus neoformans fungemia and disseminated cryptococcosis involving multiple organs. Disseminated cryptococcosis primarily affects the central nervous system3, and thus this report presents a rare case of disseminated cryptococcosis involving multiple organs.