Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.

Factors Associated With Delay in Lung Cancer Diagnosis and Surgery in a Lung Cancer Screening Program.

PURPOSE: Delays to biopsy and surgery after lung nodule detection can impact survival from lung cancer. The aim of this study was to identify factors associated with delay in a lung cancer screening (LCS) program. MATERIALS AND METHODS: We evaluated patients in an LCS program from May 2015 through October 2021 with a malignant lung nodule classified as lung CT screening reporting and data system (Lung-RADS) 4B/4X. A cutoff of more than 30 days between screening computed tomography (CT) and first tissue sampling and a cutoff of more than 60 days between screening CT and surgery were considered delayed. We evaluated the relationship between delays to first tissue sampling and surgery and patient sex, age, race, smoking status, median income by zip code, language, Lung-RADS category, and site of surgery (academic vs community hospital). RESULTS: A total of 185 lung cancers met the inclusion criteria, of which 150 underwent surgical resection. The median time from LCS CT to first tissue sampling was 42 days, and the median time from CT to surgery was 52 days. 127 (69%) patients experienced a first tissue sampling delay and 60 (40%) had a surgical delay. In multivariable analysis, active smoking status was associated with delay to first tissue sampling (odds ratio: 3.0, CI: 1.4-6.6, P = 0.005). Only performing enhanced diagnostic CT of the chest before surgery was associated with delayed lung cancer surgery (odds ratio: 30, CI: 3.6-252, P = 0.02). There was no statistically significant difference in delays with patients' sex, age, race, language, or Lung-RADS category. CONCLUSION: Delays to first tissue sampling and surgery in a LCS program were associated with current smoking and performing diagnostic CT before surgery.

RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer.

PURPOSE: ERBB2-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known. EXPERIMENTAL DESIGN: Dana-Farber and Foundation Medicine Inc. Colorectal cancer cohorts with genomic profiling were used to identify ERBB2-amplified cases [Dana-Farber, n = 47/2,729 (1.7%); FMI, n = 1857/49,839 (3.7%)]. Outcomes of patients receiving HER2-directed therapies are reported (Dana-Farber, n = 9; Flatiron Health-Foundation Medicine clinicogenomic database, FH-FMI CGDB, n = 38). Multisite HER2 IHC and genomic profiling were performed to understand HER2 intratumoral and interlesional heterogeneity. The impact of concurrent RAS comutations on the effectiveness of HER2-directed therapies were studied in isogenic colorectal cancer cell lines and xenografts. RESULTS: ERBB2 amplifications are enriched in left-sided colorectal cancer. Twenty percent of ERBB2-amplified colorectal cancers have co-occurring oncogenic RAS/RAF alterations. While RAS/RAF WT colorectal cancers typically have clonal ERBB2 amplification, colorectal cancers with co-occurring RAS/RAF alterations have lower level ERRB2 amplification, higher intratumoral heterogeneity, and interlesional ERBB2 discordance. These distinct genomic patterns lead to differential responsiveness and patterns of resistance to HER2-directed therapy. ERBB2-amplified colorectal cancer with RAS/RAF alterations are resistant to trastuzumab-based combinations, such as trastuzumab/tucatinib, but retain sensitivity to trastuzumab deruxtecan in in vitro and murine models. Trastuzumab deruxtecan shows clinical efficacy in cases with high-level ERBB2-amplified RAS/RAF coaltered colorectal cancer. CONCLUSIONS: Co-occurring RAS/RAF alterations define a unique subtype of ERBB2-amplified colorectal cancer that has increased intratumoral heterogeneity, interlesional discordance, and resistance to trastuzumab-based combinations. Further examination of trastuzumab deruxtecan in this previously understudied cohort of ERBB2-amplified colorectal cancer is warranted.

Rate of benign nodule resection in a lung cancer screening program.

PURPOSE: Screening with low dose computed tomography (CT) can reduce lung cancer related death at the expense of unavoidable false positive results. The purpose of this study is to measure the rate of surgery for benign nodules, and evaluate characteristics of those nodules. MATERIALS AND METHODS: In this study, we evaluated patients in the Lung Cancer Screening (LCS) program across a large tertiary healthcare network from 5/2015 through 10/2021 who underwent surgical resection for a lung nodule. We reviewed the pathology reports and subsequent follow-up to establish whether the nodule was benign or malignant. Imaging characteristics of the nodules were evaluated by a radiology fellow, and we recorded Lung-RADS category, nodule status (baseline, stable, new, growing), FDG uptake on PET/CT, and calculated the risk from the Brock model. RESULTS: During this time period, a total of 21,366 LCS CT was performed in 9050 patients, and 260 patients underwent a following surgical resection. Review of the pathology results revealed: 220 lung cancer (85%), 2 other malignancies (1%), and 38 benign findings (15%). Pathology of the benign nodules was as follows: 12 with scarring/fibrosis, 5 with benign neoplasms, 14 with infection/inflammation, and 7 with other diagnoses. Lung-RADS category was as follows: 4 (11%) Lung-RADS 2, 2 (5%) Lung-Rad 3, 11 (29%) Lung-RADS 4A, 13 (34%) Lung-RADS 4B, and 8 (21%) Lung-RADS 4X. The size of the nodules ranged from 4 to 41 mm with a median of 13 mm. 2 (5%) were ground glass, 10 (26%) were part-solid, and 26 (68%) were solid. FDG-PET/CT was performed in 19 out of 38 cases, of which: 2 (11%) had no uptake, 10 (53%) had mild uptake, 3 (16%) had moderate uptake, and 4 (21%) had intense uptake. Risk assessment by Brock calculator revealed that 9 (24) had <5% (very low) risk; 27 (71%) had 5-65% (low-intermediate) risk, and 2 (5%) had >65% (high) risk. CONCLUSION: Surgical resection of benign nodules is unavoidable despite application of Lung-RADS guidelines in a modern screening program, with approximately 15% of surgeries being done for benign lesions.

Complications associated with improper palpation-guided iliac bone marrow biopsy tracts identified on follow-up imaging.

OBJECTIVE: Bone marrow biopsy complications are rare. Our aim is to study the association of improper palpation-guided iliac biopsy tract with complications. MATERIALS AND METHODS: This is a retrospective study of adult patients who underwent iliac bone marrow biopsy without image guidance at our hospital from January 2019 to January 2021, and have cross-sectional radiologic imaging of the pelvis within 30 days following the procedure. Electronic health records were reviewed for clinical data. Two radiologists reviewed images of the pelvis for assessment of biopsy tract and complications. RESULTS: A total of 443 procedures were included in 309 patients, mean age 53.4 ± 18.1 years, 112 females (36.2%). In addition, 332 tracts were proper (75%), 97 improper (22%), and 14 unidentified (3%). All 11 complications occurred in procedures with improper tracts; nine bleeding, one fracture, and one facet joint injury. Improper tract was significantly associated with complications (p < .001). There was no statistically significant association between platelet count, international normalized ratio, antiplatelet use and anticoagulant use, and presence of complications (p > .05). Body mass index and subcutaneous fat thickness overlying posterior superior iliac spine were not associated with improper tract (p > .05). Procedures performed by providers with ≤ 12 months' experience were significantly associated with improper tract (p < .001) and hence associated with complications (p = .007). CONCLUSION: Improper tracts were common in palpation-guided iliac bone marrow biopsy and significantly associated with complications. No complications were encountered in proper tract procedures. Procedures performed by providers with ≤ 12 months' experience were significantly associated with improper tract and complications.

The Use of Voriconazole as Primary Prophylaxis for Invasive Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation: A Single Center's Experience.

BACKGROUND: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. METHODS: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. RESULTS: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. CONCLUSION: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting.