Objectives National palliative care guidelines outline spiritual care as a domain of palliative care, yet patients’ religiousness and/or spirituality (R/S) are underappreciated in the palliative oncology setting. Among patients with advanced cancer receiving palliative radiation therapy (RT), this study aims to characterize patient spirituality, religiousness, and religious coping; examine the relationships of these variables to quality of life (QOL); and assess patients’ perceptions of spiritual care in the cancer care setting. Methods This is a multisite, cross-sectional survey of 69 patients with advanced cancer (response rate = 73%) receiving palliative RT. Scripted interviews assessed patient spirituality, religiousness, religious coping, QOL (McGill QOL Questionnaire), and perceptions of the importance of attention to spiritual needs by health providers. Multivariable models assessed the relationships of patient spirituality and R/S coping to patient QOL, controlling for other significant predictors of QOL. Results Most participants (84%) indicated reliance on R/S beliefs to cope with cancer. Patient spirituality and religious coping were associated with improved QOL in multivariable analyses (β = 10.57, P < .001 and β = 1.28, P = .01, respectively). Most patients considered attention to spiritual concerns an important part of cancer care by physicians (87%) and nurses (85%). Limitations Limitations include a small sample size, a cross-sectional study design, and a limited proportion of nonwhite participants (15%) from one US region. Conclusion Patients receiving palliative RT rely on R/S beliefs to cope with advanced cancer. Furthermore, spirituality and religious coping are contributors to better QOL. These findings highlight the importance of spiritual care in advanced cancer care.

The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2–mutant ( STAG2 -mutant) AML, we identified DNA damage repair and replication as genetic dependencies in cohesin-mutant cells. We demonstrated increased levels of DNA damage and sensitivity of cohesin-mutant cells to poly(ADP-ribose) polymerase (PARP) inhibition. We developed a mouse model of MDS in which Stag2 mutations arose as clonal secondary lesions in the background of clonal hematopoiesis driven by tet methylcytosine dioxygenase 2 ( Tet2 ) mutations and demonstrated selective depletion of cohesin-mutant cells with PARP inhibition in vivo. Finally, we demonstrated a shift from STAG2- to STAG1-containing cohesin complexes in cohesin-mutant cells, which was associated with longer DNA loop extrusion, more intermixing of chromatin compartments, and increased interaction with PARP and replication protein A complex. Our findings inform the biology and therapeutic opportunities for cohesin-mutant malignancies.

Ewing sarcoma is an aggressive bone and soft tissue tumor in children and adolescents, with treatment remaining a clinical challenge. This disease is mediated by somatic chromosomal translocations of the EWS gene and a gene encoding an ETS transcription factor, most commonly, FLI1. While direct targeting of aberrant transcription factors remains a pharmacological challenge, identification of dependencies incurred by EWS/FLI1 expression would offer a new therapeutic avenue. We used a combination of super-enhancer profiling, near-whole genome shRNA-based and small-molecule screening to identify cyclin D1 and CDK4 as Ewing sarcoma-selective dependencies. We revealed that super-enhancers mark Ewing sarcoma specific expression signatures and EWS/FLI1 target genes in human Ewing sarcoma cell lines. Particularly, a super-enhancer regulates cyclin D1 and promotes its expression in Ewing sarcoma. We demonstrated that Ewing sarcoma cells require CDK4 and cyclin D1 for survival and anchorage-independent growth. Additionally, pharmacologic inhibition of CDK4 with selective CDK4/6 inhibitors led to cytostasis and cell death of Ewing sarcoma cell lines in vitro and growth delay in an in vivo Ewing sarcoma xenograft model. These results demonstrated a dependency in Ewing sarcoma on CDK4 and cyclin D1 and support exploration of CDK4/6 inhibitors as a therapeutic approach for patients with this disease.

This Blood Spotlight highlights the background and recent data surrounding the use of the recently approved interferon-γ neutralizing antibody emapalumab, Gamifant, for the treatment of hemophagocytic lymphohistiocytosis.

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Hypothesis Choline transporter-like protein 2 (CTL2), a 68–72 kDa inner ear membrane glycoprotein, is a candidate target antigen in autoimmune hearing loss (AIHL). Objective Test recombinant human CTL2 as a potential target for the detection of human autoantibodies in patients with AIHL. Study Design In vitro assay development. Methods Human inner ear CTL2 mRNA was cloned into baculovirus and used to infect insect cells. Immunofluorescence and western blotting were used to determine optimal expression of recombinant human CTL2 (rHuCTL2) in insect cells. AIHL patient sera of known reactivity with guinea pig inner ear were tested for antibodies to purified rHuCTL2 on western blots. Sera from normal hearing donors were used as controls. Results The rHuCTL2 protein migrated as three bands: a core protein of 62kDa, and two N-glycosylated bands at 66 and 70kDa. Sera from 6/12 (50%) of AIHL patients with antibody to the 68–72 kDa inner ear protein or to supporting cells also have antibody to rHuCTL2. Four/4 patients with antibody to rHuCTL2 responded to corticosteroids whereas 4/8 that lacked antibody to rHuCTL2 did not. Among normal human sera 80% were negative; binding was at the limit of detection in 3/15 (20%). Conclusions rHuCTL2 can be produced efficiently and used as a substrate for testing human sera. Antibodies to rHuCTL2 were detected in 50% of inner ear reactive AIHL sera. Additionally, circulating antibody to rHuCTL2 is associated response to corticosteroids in some AIHL patients.

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Rationale: Hepatic angiosarcoma is a rare endothelial cell tumor that may lead to concurrent consumptive coagulopathies including disseminated intravascular coagulation (DIC). This report details a multifaceted approach to managing DIC in a patient with advanced-stage hepatic angiosarcoma, which continued to progress after a brief response to taxane-based chemotherapy. Patient concerns: A 55-year-old man with a recent history of hemorrhoids and hemarthroses presented with acute rectal bleeding. He was found to have concurrent hepatomegaly, abnormal liver function tests, anemia, thrombocytopenia, and coagulopathy. Diagnoses: DIC in the setting of hepatic angiosarcoma. Interventions: The patient's acute bleeding in the setting of DIC was controlled with a combination of antifibrinolytic agents to prevent clot breakdown, heparin products to prevent deposition of new clot, and romiplostim to increase platelet production. His angiosarcoma was treated with various combinations of chemotherapy, including taxane-based chemotherapy, doxorubicin, and pazopanib. Outcomes: The patient's DIC and acute bleeding on initial presentation improved following treatment with unfractionated heparin and low-molecular weight heparin maintenance therapy. It is unclear if the chemotherapy to treat the hepatic angiosarcoma played a significant role in the improvement of DIC. Lessons: Laboratory measurement of prothrombin fragment 1.2, a byproduct of prothrombin conversion to thrombin, proved to be a useful way to monitor this patient's DIC over time.