Impact of Provider Volume on Outcomes of Patients With Hodgkin Lymphoma.

BACKGROUND: While the provider volume-outcome relationship has been established for many complex surgeries and invasive procedures, the provider volume impact on outcomes for Hodgkin lymphoma (HL) is less certain. We hypothesized that high-volume providers (HVPs) may have superior outcomes compared with low-volume providers (LVPs). METHODS: We performed a chart-based, retrospective review of all patients receiving adriamycin, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for HL at the West Cancer Center from January 2010 to June 2015. Patients were divided into HVP (> 3 inpatient chemotherapy (CT)/month (m)) versus LVP (< 3 CT per m) groups. Of 95 patients identified, 93 received at least one dose of ABVD, 21 treated by HVP and 72 by LVP. Patient characteristics were well balanced between groups. RESULTS: HVPs were less likely to prescribe dose delays (odds ratio (OR): 0.32; confidence interval (CI): 0.16 - 0.65; P = 0.0007) and to hold doses for afebrile neutropenia (OR: 0.05; CI: 0.00 - 0.85; P = 0.0006). HVP delivered significantly fewer prophylactic growth factors (0% of doses vs. 42%, OR: 0.00; CI < 0.00 - 0.06; P < 0.0001). Both event-free survival (EFS) (HR: 6.68; CI: 1.10 - 7.63; P = 0.0321) and overall survival (OS) (HR: 3.68; CI: 1.11 - 12.22; P = 0.032) were significantly inferior in the patients treated by LVP. CONCLUSIONS: In this study, patients with HL treated by LVP had inferior outcomes compared with those treated by HVP. HVPs were less likely to prescribe dose delays, hold doses for afebrile neutropenia or administer growth factor prophylaxis. These observations need to be confirmed in alternative datasets.

Addition of Rituximab to Chemotherapy Reduced the Rate of Surgery for Gastric-DLBCL Without Increasing Early Mortality.

BACKGROUND: We evaluated surgical trends for gastric diffuse large B-cell lymphoma (gDLBCL) before and after the approval of rituximab and whether an association of early mortality existed in patients treated after approval of rituximab. PATIENTS AND METHODS: We utilized the Surveillance Epidemiology and End Results (SEER) 18 database to extract data on patients with gDLBCL diagnosed between 1983-2012. Primary site-specific cancer-directed surgery using SEER site-specific surgical codes and annual trends were analyzed. Patients were analyzed before and after 2006, the year rituximab gained U.S. Food and Drug Administration approval. RESULTS: Joinpoint trend analysis showed the sharpest decline in surgical rates between 2000-2010. Adjusted surgical rates computed using poisson regression declined from 54.4% in 1983 to 6.9% in 2012, with an annual percentage change of -8.9% (95% confidence interval=-9.7% to -8.3%; p-value <0.01). No significant mortality increase at 30 and 60 days was found. CONCLUSION: While rituximab appears to have significantly changed how surgery is utilized for patients with gDLBCL, early mortality was unchanged.

Sweet's syndrome associated with clonal hematopoiesis of indeterminate potential responsive to 5-azacitidine.

Sweet's syndrome (SS) is a rare condition characterized by the abrupt appearance of painful skin lesions due to neutrophilic dermal infiltration. Hematologic neoplasms, particularly acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs), have been commonly reported in association with SS. Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging entity that is a precursor state to myeloid neoplasms. CHIP has not been previously associated with SS. We report the case of a 71-year-old man who presented with recurrent, painful edematous and erythematous papules and nodules for 18 months despite treatment with corticosteroids. He had normal blood counts, but a macrocytosis was noted (110 fl). Alternative causes of macrocytosis were ruled out. A skin biopsy confirmed a diagnosis of SS. Bone marrow biopsy specimen yielded a normal karyotype except for loss of the Y chromosome and equivocal morphologic findings. Polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) of selected genes from the peripheral blood demonstrated a mixed lineage leukemia (MLL) partial tandem duplication (PTD) and sequence variant in CCAAT/enhancer binding protein alpha (CEBPA). These findings were consistent with a diagnosis of CHIP. The patient was treated with 5-azacitidine and achieved a complete remission of his skin lesions and was able to discontinue corticosteroids. To our knowledge, this is the first report of a patient with recurrent SS associated with CHIP. In addition to other myeloid neoplasms like AML and MDS, CHIP should be considered as a potential etiology in cases of recurrent SS. Treatment with a hypomethylating agents such as azacitidine could also serve as an alternative to systemic corticosteroid therapy.

Genomic alterations in neuroendocrine cancers of the ovary.

BACKGROUND: As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. METHODS: Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes. RESULTS: Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12-75] and 26 years [range 8-40], respectively) than patients with NET-O 62 [range 13-76] or SCLC 66 [range 36-86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified. CONCLUSIONS: No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.

Role of Genomic Instability in Immunotherapy with Checkpoint Inhibitors.

AIM: We evaluated whether tumor genome sequencing to detect the number and type of alterations could be used as a valuable biomarker for judging the potential utility of immune checkpoint inhibitors in patients with advanced cancers. MATERIALS AND METHODS: We identified patients with solid tumors who were treated with checkpoint inibitors and had received commercially available next generation sequencing (NGS). Tumors profiled by Caris Life Sciences, Foundation Medicine and Guardant360 between 2013 and 2015. Patients were divided into 5 quintiles based on mutational load (pathogenic mutations plus variants of undetermined significance). RESULTS: Fifty patients with solid tumors on immunotherapy that had NGS reports available were identified. Top quintile patients had more genomic alterations (median=16.5) than the others (median=2) and had more pathogenic mutations in cell-cycle regulatory genes (100% versus 48%). The overall survival (OS) was significantly superior for patients in the top quintile (722 days) versus the others (432 days). We found no significant difference in progression-free survival (PFS) between the two groups. The objective response rate was numerically higher for the top quintile (50%) vs. others (20%). Programmed cell death protein 1 (PD1) and programmed death-ligand 1 (PDL1) status by immunohistochemistry was not associated with outcomes. CONCLUSION: The use of immune checkpoint blockade in tumors with higher mutational load was associated with improved OS. Our results suggest that the evaluation of tumor genomes may be predictive of immunotherapy benefit.

Comorbidities Drive Outcomes for Both Malignancy-Associated and Non-Malignancy-Associated Hemophagocytic Syndrome.

BACKGROUND: Secondary hemophagocytic syndrome (SHPS) is a syndrome that develops as a result of infection, autoimmunity, or underlying malignancy. We studied novel predictors of mortality among adults with SHPS. PATIENTS AND METHODS: SHPS were identified from the Nationwide Inpatient Sample for 2009 to 2011 using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), codes. Charlson comorbidity index (CCI) was used for comorbidity assessment, excluding malignancy. Patient- and hospital-related factors on mortality were assessed by chi-square test or analysis of variance. P values were 2 sided, and the level of significance was .05. RESULTS: A total of 276 patient hospitalizations with SHPS were identified. Forty-four had an associated malignancy, 38 (86%) of which were hematologic. Median age was 42 years (range, 18-89 years). A total of 66% (n = 182) had a CCI of 0, 13% (n = 27) had a CCI of 1, and 21% (n = 57) had a CCI of 2 or more. On bivariate analysis, inpatient mortality rate was significantly higher in malignancy-associated hemophagocytic syndrome (HPS) (odds ratio [OR], 2.07; P = .04), age ≥ 50 years (OR, 3.46; P < .01), CCI ≥ 2 (OR, 3.04; P < .01), and Medicare patients (OR, 2.32; P < .01). In multivariate analysis, CCI ≥ 2 remained an independent predictor of survival in the overall study cohort (OR, 3.52; 95% confidence interval, 1.51-8.18; P < .01). CONCLUSION: Malignancy-associated HPS, CCI ≥ 2, age > 50 years, and Medicare patients were associated with a worse in-hospital mortality. In multivariate analysis, greater comorbidity burden appeared to be the single most important predictor of mortality. This suggests that outcomes for adults with HPS are predicated by the extent of organ dysfunction at diagnosis.

Induction of Acute Myeloid Leukemia with Idarubicin, Cytarabine and Cladribine.

BACKGROUND: Daunorubicin and cytarabine has been the standard-of-care for induction therapy for acute myeloid leukemia (AML). Adding cladribine to daunorubicin (60 mg/m(2)) and cytarabine has increased complete remission (CR) rates and median overall survival (OS). However, the efficacy of adding cladribine to 7+3 with other anthracyclines is unknown. PATIENTS AND METHODS: We retrospectively evaluated patients with AML receiving induction with idarubicin, cytarabine and cladribine (ICC) between 1/1/2010 and 06/30/2015 at the Methodist University Hospital in Memphis, Tennessee. Institutional Review Board approval was obtained for the study. Patient, disease characteristics and outcomes were analyzed with GraphPad Prism, Microsoft Excel and SPSSv19.0 software. RESULTS: Twenty-four patients induced with ICC for AML were identified. Thirteen (54.2%) had at least one high-risk feature. Hypoplastic marrow was achieved in all by day 14; 19 (79.2%) achieved CR. Thirty-day mortality was 8.3%; 33-month OS and disease-free survival were 56% and 36%, respectively. CONCLUSION: Induction of AML with ICC was associated with a high CR rate and OS in our high-risk population.