6539 Background: The impact of insurance status on survival in diffuse large B‐cell lymphoma (DLBCL), the most common aggressive lymphoma, has not been evaluated after the implementation of the Affordable Care Act (ACA). The aim of this study is to compare overall survival (OS) in patients across insurance status groups and in the periods before and after the ACA. Methods: Adult patients with newly diagnosed DLBCL were identified from the National Cancer Database. The analysis was restricted to patients 64 years of age or younger as most patients 65 years or older are eligible for Medicare under the ACA. The 2004-2017 period was chosen to represent the immunochemotherapy era preceding and following the ACA. Logistic regression was used to explore associations between abstracted variables and insurance status groups. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: 93,692 adults (age < 64 years) with newly diagnosed DLBCL and known insurance status were identified (41.3% female, median age 54 years [range: 18 – 64], 81.8% White and 12.1% Black). 7,211 (7.7%) patients were uninsured, 64,744 (69.1%) had private insurance, 11,936 (12.7%) had Medicaid, and 9,801 (10.5%) had Medicare. When compared to insured patients (private insurance, Medicaid or Medicare), uninsured patients were more likely to have a median household outcome of < $38,000 [OR 1.93 (95% CI 1.79-2.07)], less likely to receive chemotherapy [OR 0.69 (0.64-0.77)], more likely to be male [OR 1.14 (1.07-1.21)], more likely to be non-White [OR 1.30 (1.20-1.40], and more likely to present with stage III or IV disease [OR 1.24 (1.16-1.32)]. Uninsured patients had an inferior OS [HR 1.21 (95% CI 1.15-1.27)] when compared to insured patients after adjustment for baseline comorbidity (Charlson-Deyo score ≥2), advanced stage, treatment with chemotherapy, and sociodemographic factors including sex, age, race, household income, facility type (academic/community), and location (urban/rural). With a median follow-up time of 14.8 years (95% CI 14.6-not reached), median OS was lower in uninsured patients [13.4 years (12.3-not reached) vs 14.8 years (14.7-not reached); p < 0.0001]. Despite the lack of major changes in DLBCL therapies, a diagnosis after the implementation of the ACA (in 2010 or later) was associated with a superior OS when compared with the outcomes of patients diagnosed in 2010 or earlier [HR 0.93 (95% CI 0.90-0.95)]. Similarly, five-year OS was superior in the insured group [HR 0.93 (95% CI 0.89-0.96)]. Conclusions: Uninsured patients with DLBCL and < 64 years old had inferior OS when compared with insured patients, and uninsured status emerged as an independent risk factor for inferior OS. Our data highlight the independent effect of insurance disparities - a potential indicator of variations in access to health care - on survival in DLBCL.
Family history of breast and/or ovarian cancer (FHBOC) as an independent prognostic factor in triple negative breast cancer overall survival.
e12579 Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1st, 2nd and/or 3rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1st, 2nd, and 3rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?
Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines. Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance. Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines. Figure Disclosures No relevant conflicts of interest to declare.
Immune-Related Hematologic Adverse Events in the Context of Checkpoint Inhibitors
Introduction Immune-mediated hematologic disorders are relatively rare but potentially life-threatening immune-related adverse events (irAE) with immune checkpoint inhibitor (ICI) therapy (Shiuan, Beckermann et al 2017). The management strategy often relies on systemic corticosteroids and other immunosuppressant agents in steroid-refractory cases (Brahmer, Lacchetti et al 2018). We hereby describe our institution's experience in diagnosing and managing immune-related hematologic adverse events (ir-h-AE). Methods We retrospectively searched the electronic health record for all ir-h-AE diagnosed by treating providers and confirmed by study authors between 2015 and 2020. The search included patients on ICI and the following conditions: immune-related neutropenia (IRN), autoimmune hemolytic anemia (AIHA), cold agglutinin disease (CAD), immune thrombocytopenia (ITP), immune-related pancytopenia, aplastic anemia (AA), and pure red cell aplasia (PRCA). For AIHA, PRCA, and CAD, partial response (PR) was defined as hemoglobin greater than 10 g/dL but < 12 g/dL and 2 g/dL above the nadir without blood product transfusion. Complete response (CR) was defined as hemoglobin of ≥ 12 g/dL and 2 g/dL above the nadir without blood product transfusion (Peñalver, Alvarez-Larrán et al. 2010). For ITP, CR was defined as platelet count ≥ 100 × 109/L and absence of bleeding. PR was defined as platelet count ≥ 30 × 109/L and ≥ two-fold increase from the baseline count and absence of bleeding (Gómez-Almaguer, Tarín-Arzaga et al. 2013). For IRN, CR was defined as absolute neutrophil count (ANC) ≥ 1500/ mm3 on 2 consecutive measurements separated by 7 days; PR was defined as ANC ≥ 500/ mm3 sustained over 7 days. JMP® 14.1 was used for data analysis. Results Seventeen patients were identified, 9 (52.9%) of whom were female (table 1). Median age was 68 years (range 26-78). The most common pre-existing malignancies were melanoma (6 patients, 35.3%), non-small cell lung cancer (4 patients, 23.5%), and gastrointestinal cancer (3 patients, 17.6%). The ir-h-AE included 7 patients (41.2%) with warm AIHA, 4 (23.5%) with ITP (1 had immune-related pancytopenia that resolved with ITP persisting), 3 (17.6%) with IRN, 1 with AA, 1 with CAD, and 1 with PRCA and mild ITP. All patients had received an ICI dose within 60 days of diagnosis (range 3-52 days, median 18 days). Only 1 patient had a concomitant chronic autoimmune disorder (antinuclear antibody-positive arthritis). Four patients (23.5%) were receiving chemotherapy. Sixteen patients (94.1%) required treatment and received corticosteroids. Eight out of 15 evaluable patients (53.3%) responded to corticosteroids only. Another 4 responders (26.7%) required additional therapies including intravenous immunoglobulins (IVIG) (4, 23.5%) and/or rituximab (4, 23.5%). Overall response rate was 71.4% for AIHA and 100% for IRN. ITP was likely underrepresented in our cohort, and the response rate of 66.7% is likely lower than the response rate in clinical practice. This could be related to the fact that many mild thrombocytopenia cases are not further evaluated in clinical practice. None of our patients died from the sequelae of an ir-h-AE. Two patients (11.8%) died within 30 days of ir-h-AE diagnosis (disseminated intravascular coagulation likely due to the underlying malignancy and sepsis from bacterial pneumonia). At the time of ir-h-AE diagnosis, the malignancy was showing evidence of response in 9 patients (52.9%), progression in 6 patients (35.3%), and stability in 2 patients (11.8%). ICI therapy was permanently discontinued in 9 patients (52.9%) and temporarily held in 6 patients (35.3%). Three of the 5 patients (60%), who were rechallenged with ICI therapy, had recurrence of the same ir-h-AE (AIHA) with adequate response to therapy. Non-hematologic irAE (7 patients, 41.2%) included 3 patients with hepatitis, 2 with thyroiditis, 2 with pneumonitis, 1 with colitis, and 1 with dermatitis. Conclusion Our clinical experience with ir-h-AE highlights the importance of exercising vigilance in assessing the hematologic parameters of patients receiving ICI therapy. While relatively rare, ir-h-AE may impact the clinical course of patients with cancer and their eligibility for therapies that have the potential of offering durable control of the underlying malignancy. ir-h-AE respond to classical therapies including corticosteroids, IVIG, and rituximab. Disclosures Block: Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Marker Therapeutics: Research Funding; Transgene: Research Funding; Immune Design: Research Funding. Kottschade:Bristol-Myers Squibb: Consultancy, Research Funding.
Safety and Efficacy of Ultrasound-Guided Tube Thoracostomy for Pneumothorax Management
e21575 Background: The clinical significance of brain metastases in patients with bronchopulmonary neuroendocrine (NE) tumors is unknown; we therefore conducted a population based analysis to evaluate the implications of brain metastases in these patients. Methods: The NCDB database was queried to identify patients with stage IV bronchopulmonary NE tumors treated between the years of 2004-2012. Patients were split into two groups based on the presence of brain metastases at diagnosis and survival probabilities with multivariate models were performed. Results: A total of 7,725 patients with Stage IV bronchopulmonary NE tumors were identified. The histological subtypes studied in this cohort were NE carcinoma (65.4%), large cell NE carcinoma (30.5%), typical carcinoid (2.8%) and atypical carcinoid (1.3%) . The patients included in this study were mainly white (86.4%) men (56.8%) with a median age of 67 years who had liver (9.5%), bone (6.2%) and brain (5.9%) metastases at diagnosis. The median overall survival (OS) of the cohort was 5.59 (95% CI: 5.4-5.8) months, but when OS was stratified by histological subtype it was significantly better in patients with typical carcinoid (table). In the whole cohort, the median OS did not differ between patients with and without brain metastases (5.55 vs. 5.68; p = 0.24). However, a sensitivity analysis by histology showed that the presence of brain metastases worsen the median OS of patients with typical carcinoid only (15.1 vs 4.6, p = 0.04). An adjusted multivariate analysis restricted to patients with brain metastases showed that administration of systemic chemotherapy (HR:0.5; 95% CI:0.35-0.72, p < 0.001) and resection of distant metastases (HR:0.5; 95% CI:0.29-0.88, p = 0.017) were the two most powerful independent prognostic factors. Conclusions: The presence of brain metastases negatively impact survival of patients with typical carcinoids but not in those with the other histological subtypes included in this study. Staging MRI should be strongly considered at diagnosis in patients with bronchopulmonary NE tumors, due to the sizable proportion of these patients presenting with brain metastases and also due to its prognostic value in a subset of this population. [Table: see text]
Management of bronchopulmonary carcinoid: NCDB database analysis.
e21007 Background: There is a lack of data to guide the management of resectable bronchopulmonary carcinoid tumors (BCTs). Methods: The NCDB database was retrospectively reviewed to analyze the roles of surgery, chemotherapy and radiation. Patients with a diagnosis of clinically staged T1-2/N0-1 typical carcinoid (TC) and atypical carcinoid (AC) between 2004-2012 were included. Kaplan-Meier methods and multivariable analysis were performed. Results: A total of 2148 patients (TC 1874 & AC 274; T1/1648 & T2/500) were identified. The median age was 59 (range 18-89). There was a female (69.7%) and right lung (56.9%) predominance. Fifty-three patients received pneumonectomy, 68 chemotherapy, and 84 radiation therapy. The impact of age, histology (TC vs. AC), medical comorbidities (Charlson/Deyo score 0 vs. ≥1) and type of surgery [sublobar resection (SR) vs. lobectomy vs. lobectomy with mediastinal lymph node dissection (L/MLND)] were subsequently examined. AC, older age, and comorbidities were associated with shorter overall survival (OS) by both univariate and multivariable analysis. Patients who underwent lobectomy had longer OS (119 months) than those with SR (109 months) or L/MLND (115 months). However, this association was not significant by multivariable analysis with age incorporated as either a categorical ( < 60 vs. ≥60) or a continuous variable (Table). In the subgroup analysis of patients with T1, T2, TC and AC respectively, type of surgical resection was not significantly associated with OS by multivariable analysis. Conclusions: Patients with resectable BCTs have excellent OS. Atypical histology, older age, and comorbidities predicted inferior OS. There were insufficient data to support the use of perioperative chemotherapy or radiation therapy. Lobectomy was associated with prolonged OS by univariate analysis but this was not significant in the multivariable model, suggesting that SR is a reasonable approach for patients who cannot tolerate lobectomy. MLND did not seem to provide additional survival benefits. [Table: see text]
How Accurate Is Clinical Staging for Malignant Pleural Mesothelioma?